Clinical aspects and treatment of systemic lupus erythematosus (SLE)
O1 JSLE and the NLRP3 inflammasome – a novel therapeutic target
Jo Gamble1, Michael W. Beresford2,3
1Child Health, Translational Medicine, University of Liverpool, Liverpool UK; 2Child
Health, University of Liverpool, Liverpool, UK; 3Alder Hey Children's Hospital, Liverpool,
UK
Correspondence: Jo Gamble
Introduction: Juvenile-onset Systemic Lupus Erythematosus (JSLE) is a severe autoimmune
disease causing organ damage and long-term morbidity. Impaired clearance of nuclear
debris from cells and upregulated circulating damage-associated molecular patterns
(DAMPs) and cytokines are thought to trigger cell death and thus, further increase
release of pro-inflammatory molecules following the cytosolic assembly of inflammasomes.
Objectives: To investigate the role of pyroptotic cell death in JSLE, which occurs
following the assembly and activation of the NLRP3 inflammasome, which may be a promising
target in the treatment of JSLE and other inflammatory diseases.
Methods: THP-1 cell line-derived macrophages (Mφs) were primed using lipopolysaccharide
(LPS; 10 ng/ml) and interferon (IFN) γ (20 ng/ml) in complete media at 37 °C for 24 hours,
and subsequently treated with 10 mM Adenosine triphosphate (ATP) for 30 min. Primed
Mφs not treated with ATP were used as a negative control. Some Mφs were incubated
with 10% JSLE patient sera or NETosis-derived material (10 ng/ml) from PMA-treated
neutrophils. Primed Mφs were tested for cell surface markers, HLA-DR, CD282 (TLR2),
and CD68 using flow cytometry. ATP-treated Mφs were collected and either assayed for
pyroptosis marker, lactate dehydrogenase (LDH) activity, cleaved caspase-1 with immunofluorescence
(IF), or lysed for cleaved caspase-1 using western blotting.
Results: Primed Mφs showed an M1 phenotype with geometric means ± SEM of HLA-DR, TLR2
and CD68 expression respectively of: 1177 ± 1.15, 613 ± 0.9, and 1549 ± 0.9 gMFI,
respectively compared with un-primed Mφs of 597 ± 1.0, 122 ± 0.88, and 1225 ± 0.9
gMFI, respectively (n = 3; p < 0.05). ATP-treated Mφs showed increased LDH activity
compared to controls (3.4x10-3 ± 0.12x10-3) compared to 0.00 milliunits/mL, respectively;
n = 3; p < 0.05). Furthermore, a greater increase in LDH activity was observed in
Mφs that were incubated with JSLE serum and NET material (3.7x10-3 ± 0.5x10-3 and
7.6x10-3 ± 0.5x10-3, respectively, compared to 0.00 milliunits/mL; n = 3-6; p < 0.05).
IF was positive for cleaved caspase-1 in ATP treated Mφs; and this was confirmed in
lysed cells, using western blotting.
Conclusion: Overall, the results indicate that Mφs undergo pyroptosis via the NLRP3
inflammasome when challenged with a two-signal approach of priming and ATP, and that
cytokines, nuclear debris and DAMPs may not only trigger, but amplify the inflammatory
response of this pathway. The NLRP3 inflammasome is thought to be an important mediator
in the pathogenesis of certain inflammatory diseases, and flare episodes associated
with JSLE. Further work is planned to investigate the role of the inflammasome in
JSLE, using pharmacological interventions with specific known and novel inhibitors
of the NLRP3 inflammasome. This work could prove the NLRP3 inflammasome to be a promising
target for future therapy for JSLE.
Disclosure of Interest: None Declared
Big data analytics
O2 Persistence of CD4 memory pathogenic subsets in polyarticular juvenile idiopathic
arthritis patients who relapse upon withdrawal of biologic therapy
Jing Yao Leong1, Joo Guan Yeo1,2, Phyllis Chen1, Liyun Lai1, Loshinidevi D/O Thana
Bathi1, Justin Tan2, Thaschawee Arkachaisri2, 3, Daniel J. Lovell4,5, Salvatore Albani1,3
1Singhealth Translational Immunology and Inflammation Centre (STIIC), Singapore Health
Services Pte Ltd, Singhealth, Singapore, Singapore; 2KK Women's and Children's Hospital,
Singapore, Singapore; 3Duke-NUS Graduate Medical School, Singapore, Singapore; 4Division
of Rheumatology, Cincinnati Children's Hospital Medical Centre, Cincinnati, OH, United
States; 5Department of Paediatrics, University of Cincinnati College of Medicine,
Cincinnati, OH, United States
Correspondence: Jing Yao Leong
Introduction: Clinical management of polyarticular JIA with anti-TNF-alpha biologics
has been met with significant success, with up to 80% of patients demonstrating clinically
meaningful efficacy. Concerns about medium/long term drug toxicities and costs have
driven the clinical need to find predictors for successful drug discontinuation. Emerging
evidence from previous published data indicate that T cells play a crucial role in
the disease progression. Defining the pathogenic subsets and mechanisms within the
T cell immunome will likely help stratify patients in terms of therapeutic outcomes.
Objectives: We seek to distill this pathogenic signal hidden within the T cell compartment
through the utilisation of a high dimensional platform, CyToF, that is capable of
phenotyping up to 41 markers at a single cell resolution. JIA patients treated with
anti-TNF-alpha biologics were recruited in the Understanding TNF-alpha trial and segregated
into flare, active and inactive arms after drug discontinuation. The central aim of
this project is to identify pathogenic immune mechanisms of clinical relapse and signatures
capable of distinguishing clinical fates.
Methods: Patients treated with anti-TNF-alpha biologics were recruited into the study
(Improved Understanding of the Biology and Use of TNF inhibition in Children with
JIA Trial) with clinically inactive disease on treatment (Wallace criteria) and initiated
with therapy discontinuation. The patients were followed and evaluated as flare, inactive
and active based on 6 JIA core set parameters; number of joints with active arthritis
and/or loss of motion, MD global assessment of current disease activity, patient/parent
global assessment of overall disease severity in prior week, a validated measure of
physical function and ESR. Healthy paediatric controls without any inflammatory diseases
were recruited from the day surgery during intravenous plug setting pre-operatively
after informed consent.
Results: PBMCs from n = 47 JIA patients (Flare n = 18, Active = 11, Inactive n = 18)
and n = 10 healthy controls were stained with 37 markers/4 barcodes T cell CyToF Panel
after 6 hours stimulation with PMA/Ionmycin. Dimensional reduction cluster analysis
was performed with Marvis and unique nodes representing immune subsets enriched in
flare or active disease was statistically filtered (Mann Whitney Test, p < 0.05) and
manually verified through conventional bivariate gating (FlowJo). In patients destined
to flare (vs inactive/healthy) prior to therapy withdrawal, the CD4 memory compartment
was strongly dysregulated (p < 0.05), enriched particularly in (a) CD4 CD45RA- TNF-alpha+,
(b) CD4 CD45RA- CXCR5+ (TfH), and were skewed towards (c) CD152-/PD1-.When contrasting
against only healthy non-disease controls, patients destined to flare additionally
were up-regulated for CD4 CD45RA- TNF-alpha+ IL-6+, possibly representing as a sub-clinical
disease subset. Intriguingly we noted a migratory subset, that was not evident in
earlier flare cohort comparisons, CD4 CD45RA- CXCR3+ CCR6+ that was present in patients
destined to develop active disease (vs inactive/healthy). Upon flaring, the sub-clinical
subset CD4 CD45RA- TNF-alpha+ IL-6+ surfaces and CD4 memory subsets are now upregulating
expression of CD152/PD1 (vs inactive) in response to ongoing inflammation, but when
compared to healthy controls are still inadequate.
Conclusion: There exists a group of patients (flare) for which biologic therapy with
anti-TNF-alpha is merely controlling the disease activity but not curative. The persistence
of CD4 memory cells are likely to play a pivotal role in disease relapse, that may
be partially explained by a weaker control through immune checkpoints (CD152/PD1)
or interaction with B cells. These results suggest that clinical fate is immunologically
predetermined and patients who will develop different clinical fates can be identified
from prior biologic sampling.
Disclosure of Interest: None Declared.
O3 A multi-dimensional immunomics approach reveals distinct regulatory and antigen
presenting B cell changes associated with childhood onset systemic lupus erythematosus
Joo Guan Yeo1,2, Jingyao Leong1, Thaschawee Arkachaisri2,3, Angela Yun June Tan2,
Loshinidevi D/O Thana Bathi1, Xuesi Sim1, Phyllis Zi Xuan Chen1, Liyun Lai1, Lena
Das2, Justin Hung Tiong Tan2, Elene Seck Choon Lee2, Yun Xin Book2, Salvatore Albani1,2,3
1Singhealth Translational Immunology and Inflammation Centre (STIIC), Singapore Health
Services Pte Ltd, Singapore, Singapore; 2KK Women's and Children's Hospital, Singapore,
Singapore; 3Duke-NUS Graduate Medical School, Singapore, Singapore
Correspondence: Joo Guan Yeo
Introduction: Systemic Lupus Erythematosus (SLE) is a multi-factorial autoimmune disease
and the conventional oligo-dimensional investigative approach involving one or a few
cell types or analyses at a time is inadequate for its study. We hypothesize that
abnormalities within multiple components of the immune system contribute to lupus
pathogenesis and hence, there is a need for a comprehensive interrogative analysis.
Objectives: We aim to employ a multi-dimensional holistic approach using mass cytometry
to study the immunome of childhood onset SLE (cSLE) patients and unravel the immune
derangements involved in its pathogenesis. This will address the critical unmet need
for a simultaneous and holistic interrogation of the different immune cell subsets
in cSLE.
Methods: Peripheral blood mononuclear cells (PBMC) from 14 cSLE patients and 14 healthy
paediatric controls, were stained for 37 immune phenotypic markers after 72 hours
of culturing with and without Class B CpG oligodeoxynucleotide stimulation followed
by interrogation with mass cytometry. Blood from healthy paediatric subjects without
any inflammatory diseases were obtained prior to their elective day surgical procedures
during intravenous plug setting after informed consent. Subsequent analysis of the
data was done using a machine learning approach with dimensional reductions followed
by automated cell classification, clustering and visualization. Unique nodes representing
immune subsets enriched in cSLE patients were statistically evaluated with reference
to the healthy cohort and its clinical and mechanistic significance inferred from
their phenotypes (Wilcoxon rank-sum test, p < 0.05).
Results: A statistically significant enrichment of a class-switched memory B cell
subset (CD19+CD27+IgG+) with CD11c+CD25+HLA-DR+CD40hiCD86hi was found in the SLE cohort,
suggesting its pathologic mechanistic role in lupus. Intriguingly, CD25 (IL-2α chain)
expression was found in this population, indicative of its potential responsiveness
to IL-2 secreted T cells. This observation was coupled with a reciprocal increase
in the transitional/naive B cell population that was negative for CD11c, CD25, CD40
and CD86 in the healthy cohort. Next, a significant enrichment of the memory regulatory
T cell population (CD4+CD45RO+CD25+Foxp3+) was present in the diseased cohort with
a small population of these cells expressing CXCR5. CXCR5 is a homing chemokine receptor
to the lymph node germinal centre, an important lupus related microenvironment, and
its presence may signify a potential regulatory role of these cells. In the healthy
cohort, a reciprocal enrichment in the naive regulatory T cell population was found
instead. Lastly, the B regulatory compartment of the PBMC was interrogated after CpG
stimulation demonstrating an enrichment of IL10 secreting B regulatory cells with
the naive and transitional B cell phenotypes (IgM+IgD+/-CD27-) in the cSLE patients.
These populations of T and B regulatory cells may be involved in the amelioration
of the lupus disease activity during different phases of the illness.
Conclusion: A holistic multi-dimensional approach was able to distill multiple derangements
in the cSLE immunome with clinical and mechanistic significance. The identification
of a B cell subset with phenotypic markers indicative of its ability for antigen presentation
(HLA-DR, CD86) and T-B cell interaction (CD25, CD40) in the cSLE cohort highlights
that the immunopathogenic role of B cell in SLE goes beyond antibodies production
and immune regulation. Additionally, the concurrent demonstration of an increase in
memory CD4 regulatory cells and B regulatory cells in the diseased cohort is consistent
with our hypothesis that multiple immune abnormalities are involved in SLE pathogenesis.
These findings have the translational potential to unravel the pathogenesis of lupus
and identify the cellular subsets for further in-depth mechanistic and functional
studies for the eventual goal of developing novel therapeutics.
Disclosure of Interest: None Declared.
O4 Using blood transcriptomic data for disease etiology discovery in pediatric ANCA-associated
vasculitis
Erin Gill1, Kelly Brown2, Kim Morishita2, David A. Cabral2, Robert E. W. Hancock1
1University of British Columbia, Vancouver, Canada; 2BC Children's Hospital, Vancouver,
Canada
Correspondence: Erin Gill
Introduction: Primary vasculitis encompasses a number of life threatening diseases.
The different clinical manifestations and classification framework is partly determined
by the size (small, medium, large) of the predominantly inflamed blood vessels. Among
small vessel vasculitis (SVV) the Anti-Neutrophil Cytoplasmic Antibody (ANCA) -associated
vasculitis (AAV) subtype includes, Microscopic Polyangiitis (MPA) and Granulomatosis
with Polyangiitis (GPA) that are difficult for physicians to differentiate because
of their many overlapping clinical features1. In the absence of biomarkers, classification
algorithms (European League Against Rheumatism (EULAR2) and European Medicines Agency
(EMA3) algorithms) exist to distinguish these diseases in adults and have been adapted
for use in children. Although rare in childhood, the study of AAV in pediatric patients
provides opportunity for biomarker discovery in individuals with a relatively naïve
immune system and limited comorbidities.
Objectives: Our group has collected blood for RNA-Seq analysis from children diagnosed
with AAV from centres around the world. Transcriptome analyses were conducted in an
attempt to detect biomarkers for MPA and GPA that will help determine disease etiology
and assist physicians in patient classification.
Methods: Briefly, blood was collected in Tempus tubes, RNA was extracted, enriched
for mRNA and RNA-Seq libraries were prepared using standard methods. Sequencing was
performed on an Illumina HiSeq 2500. fastq reads were mapped to the human genome using
STAR4. DESeq25 was used for differential expression analysis while pathway overrepresentation
analysis was conducted via innateDB6 using the Reactome7 pathway annotation system.
Samples from 32 patients at the point of diagnosis or flare-up at blood draw were
included in the analysis. All 32 patients were classified using the EMA algorithm,
although the EMA classification was not used in the analysis.
Results: Hierarchical clustering based on Euclidean distances between samples placed
samples into three clusters. Cluster one is composed of only three samples, while
clusters two and three are composed of 14 and 15 samples, respectively. Cluster two
contains primarily samples from individuals who were classified (via the EMA algorithm)
as having MPA or unclassifiable SVV (10/14 samples), while cluster three contains
primarily samples from individuals who were classified as having GPA or unclassifiable
SVV (14/15 samples). DE analysis between clusters two and three showed 3,198 differentially
expressed genes. The MPA cluster is enriched for pathways including interferon signaling,
the ISG15 antiviral mechanism, TCR signaling and adaptive immunity. Conversely, the
GPA cluster is enriched for pathways including interleukin signaling, TLR4 signaling,
and phagosomal maturation. These enriched pathways suggest a viral and adaptive immunity
signature for MPA and a bacterial and innate immunity signature for GPA.
Conclusion: The identification of preliminary etiologies for GPA and MPA is the first
step toward assisting clinicians in developing improved molecular diagnostics for
disease classification, and suggest an opportunity for seeking different treatment
paradigms for the management of these two diseases.
Disclosure of Interest: None Declared.
References 1. Barut, K. et al. 2016. Curr Opin Rheumatol 28:29.
2. Luqmani, R.A. et al. 2011. Clin Exp Immunol 164:11.
3. Abdulkader, R. et al. 2012. Ann Rheum Dis 72:1888.
4. Dobin, A. et al. 2013. Bioinformatics 29:15.
5. Love, M.I. et al. 2014. Genome Biol. 15:550.
6. Breuer, K. et al. 2013. Nucl Acids Res. 41:D1.
7. Fabregat, A. et al. 2016. Nucl Acids Res. 44:D481.
Remission and outcome of systemic lupus erythematosus (SLE)
O5 Impact of fatigue, depressive symptoms and skin symptoms in adults with childhood-onset
sle and the relation with HRQoL – the CHILL-NL study
Ayse Kaynak1, Noortje Groot1,2, Santusja Ramnath1, Marc Bijl3, Radboud Dolhain4, Onno
Teng5, Els Zirkzee6, Karina de Leeuw7, Ruth Fritsch-Stork8, Irene Bultink9, Sylvia
Kamphuis1 and on behalf of the CHILL-NL study group
1Department of Pediatric Rheumatology, Sophia Children's Hospital – Erasmus University
Medical Centre, Rotterdam, Netherlands; 2Department of Pediatric Immunology, Wilhemina
Children’s Hospital – University Medical Centre Utrecht, Utrecht, Netherlands; 3Department
of Internal Medicine and Rheumatology, Martini Hospital, Groningen, Netherlands; 4Department
of Rheumatology, Erasmus University Medical Centre, Rotterdam, Netherlands; 5Department
of Rheumatology, Leiden University Medical Center, Leiden, Netherlands; 6Department
of Rheumatology, Maasstad Hospital, Rotterdam, Netherlands; 7Department of Rheumatology
and Clinical Immunology, University Medical Center Groningen, Groningen, Netherlands;
8Department of Rheumatology and Clinical Immunology, University Medical Center Utrecht,
Utrecht, Netherlands; 9Amsterdam Rheumatology and Immunology Center, Location VUmc,
Amsterdam, Netherlands
Correspondence: Ayse Kaynak
Introduction: Childhood onset SLE is a lifelong heterogeneous autoimmune disease that
follows a more severe clinical course than adult-onset SLE. Previous studies have
shown that HRQoL is impaired in cSLE, little is known which factors influence HRQoL.
Fatigue, depressive symptoms and skin/mucosal symptoms (leading to changed physical
appearance and potential lower self-esteem) may play an important role for a patient’s
HRQoL.
Objectives: To determine the prevalence of fatigue, depressive symptoms and skin/mucosal
symptoms in adults with cSLE and examine the relation with HRQoL
Methods: 106 adults with cSLE were included in the CHILL-NL (CHILdhood Lupus-NetherLands)
study including a single study visit for structured history, physical examination
and SLEDAI-2 k. HRQoL was assessed with SF-36. Fatigue was assessed with Fatigue Severity
Scale (FSS) with scores range from 1 to 7. FSS score ≥4 defines abnormal fatigue.
Beck Depression Inventory (BDI) was used for depressive symptoms. BDI score ≥14 is
indicative for major depressive symptoms.
Results: 92% of cSLE patients were female and white (73%). The median age at study
visit was 33 yrs, median disease duration was 20 years, 61% had developed damage (SDI
≥1). HRQoL of cSLE patients was impaired (7/8 domains SF36), remarkably mental health
was similar between patients and Dutch norm data. Patients with damage (SDI ≥1) scored
remarkably similar on all HRQoL domains, except for the domain ‘physical functioning’.
68% of cSLE patients were abnormal fatigued (FSS score ≥4). 15% were depressive (BDI-score ≥ 14).
HRQoL (6/8 domains SF36) was lower in all patients with fatigue but also in those
with major depressive symptoms. The median SLEDAI-2 k score was 4, 31% of cSLE patients
had ≥ 1 skin/alopecia/mucosal ulcers and its presence was associated with lower HRQoL.
BDI: Exel E, Lupus 2013;22(14):1462-FSS::ad hoc committee on SLE response criteria,
ArthrRheum2007;57(8):1348
Conclusion: HRQoL in this large cohort of adults with cSLE was not associated with
disease damage, but self-reported fatigue- and major depressive symptoms were. Additionally
physical appearance (skin/alopecia) and mucosal symptoms had a clear impact on HRQoL.
Disclosure of Interest: None Declared.
O6 Clinical predictors of developing lupus nephritis in children
Eve M. Smith1, Peng Yin2, Andrea L. Jorgensen2, Michael W. Beresford1
1Department of Women and Children’s Health, Institute of Translational Medicine, Liverpool,
United Kingdom; 2Department of Biostatistics, Institute of Translational Medicine,
University of Liverpool, Liverpool, United Kingdom
Correspondence: Eve M. Smith
Introduction: A proportion of patients with Juvenile-onset Systemic Lupus Erythematosus
(JSLE) will have lupus nephritis (LN) as part of their initial presentation, but others
will go on to develop this manifestation later [1, 2]. Early recognition and appropriate
management of LN is important as early response to treatment is known to be associated
with better renal outcomes [3]. Identifying those with or at risk of developing LN
is important, so that clinicians can be extra vigilant in monitoring for LN development.
Objectives: (1) To characterise patients with LN at baseline, and how they differ
from patients without LN in terms of clinical and demographic factors. (2) For those
without LN at baseline, who develop it at a later stage, to determine (a) when they
develop LN and (b) whether there are clinical and demographic predictors at baseline
which can predict subsequent development of LN.
Methods: Participants of the UK JSLE Cohort Study, between 2006-2016, were included
if they had active LN at the time of their initial presentation to paediatric rheumatology
care (referred to as ‘baseline’ throughout), or subsequently developed LN. Univariate
logistic regression modelling compared clinical/demographic factors of patients with/without
active LN at baseline. Those without LN at baseline were followed longitudinally,
monitoring for LN development. The association between outcome (time from baseline
visit to the development of LN) and clinical/demographic variables at baseline was
tested univariately using Cox Proportional hazard modelling. Covariates with a p < 0.2
on univariate analysis were included in a multiple regression model and backward stepwise
model selection applied. HRs, 95% CIs and p-values were summarised for covariates
present in the final model and the results were displayed graphically with Kaplan-Meier
curves and risk tables.
Results: 331 JSLE patients were included in the study. A total of 121/331 (37%) of
UK JSLE Cohort Study patients were found to have active LN at baseline. Of the 210/331
patients without LN at baseline, 13 only had a single study visit and were therefore
excluded from further analyses. A further 34/197 (17%) patients were found to develop
LN after a median of 2.04 years [IQR 0.8-3.7]. Six clinical/demographic factors were
found to differ significantly between those with/without LN at baseline. These included
the patient’s first ACR score (p = 3.6 x10-6), presence of severe hypertension (p = 0.0006),
level of proteinuria (p = 5.7x10-12), serum creatinine (p = 0.00024), ESR (p = 0.00075)
and C3 (p = 1.3x10-7). Within the multiple regression model, both ACR score (p = 0.014)
and C3 levels (p = 0.0082) at baseline were also significant predictors for subsequent
LN development. Patients with a higher ACR score and a lower C3 value at baseline
were at greater risk of developing LN at any point in time (ACR score: HR 1.45, 95%
CI 1.08-1.95 and C3: HR 0.27, 95% CI 0.10-0.68).
Conclusion: Using clinical data from the UK JSLE Cohort Study, this study has explored
the ability of basic clinical and demographic factors at baseline for stratifying
JSLE patients as ‘high or low risk’ for LN development at baseline or during their
subsequent disease course. Consideration of such factors may help the clinician when
considering the individual patients LN risk.
Disclosure of Interest: None Declared.
Immunometabolomics
O7 NRF2 enhances metabolic turnover in myeloid cells resulting in expansion of CD11b+Gr-1+MDSCs
Kim Ohl, Patricia Klemm, Klaus Tenbrock
Dept Of Pediatrics, RWTH University of Aachen, Aachen, Germany
Correspondence: Kim Ohl
Introduction: Reactive oxygen species (ROS) were primarily considered as harmful mediators
of inflammation due to their ability to damage proteins, lipids, nucleic acids and
matrix components. However, accumulating evidence point towards an immune-regulatory
role of ROS with inflammation-limiting effects and the ability to prevent autoimmune
diseases. Thus, a deeper analysis of ROS induced pathways in different immune cells
is crucial to understand the ambivalent role of ROS molecules.
Objectives: The aim of our study was to analyse the effects of ROS and oxidative stress
on the immune response by deciphering the role of Nrf2 – the key transcription factor
of the oxidative stress response – in immune cells.
Methods: We generated mice with a constitutive activation of Nrf2 in immune cells.
Emerging CD11b+Gr-1+ cells were analysed by flow cytometry, whole transcriptome analysis
and metabolic assays and compared to wildtype and LPS induced MDSCs. Finally functionality
of CD11b+Gr-1+ cells was tested in vivo by means of a transfer colitis model and in
an acute lung injury model.
Results: Activation of Nrf2 in immune cells induced a massive expansion of splenic
CD11b+Gr-1+ cells, which exhibited characteristics of myeloid derived suppressor cells
(MDSCs) such as suppression of T cell proliferation in vitro and amelioration of T-cell
mediated colitis in vivo. Whole transcriptome analysis revealed Nrf2 dependent activation
of cell cycle and pentose phosphate pathway, which closely resembled pathways in MDSCs
induced by the TLR4 ligand LPS resulting in higher metabolic turnover and cell proliferation.
In addition constitutive activation of Nrf2 was protective in LPS induced acute lung
injury.
Conclusion: Thus Nrf2 is a critical transcriptional regulator for a myeloid cell population
that plays a major regulatory role in inflammation and infections. Modulation of MDSCs
via targeting of Nrf2-dependent metabolism provides ample opportunities for therapeutic
manipulation of MDSCs depending on clinical necessities.
Disclosure of Interest: None Declared
O8 Novel serum broad-based proteomic discovery analysis identifies proteins and pathways
dysregulated in juvenile dermatomyositis (JDM)
Hanna Kim1, Angélique Biancotto2, Foo Cheung2, Terrance O’Hanlon3, Ira Targoff 4,
Yan Huang5, Frederick W. Miller3, Raphaela Goldbach-Mansky5, Lisa Rider3
1NIAMS, National Institutes of Health, Bethesda, MD, United States; 2CHI, NHLBI; 3EAG,
NIEHS, National Institutes of Health, Bethesda, MD, United States; 4Oklahoma University
(OUHSC) and Oklahoma Medical Research Foundation (OMRF), Oklahoma City, OK, United
States; 5TADS, NIAID, National Institutes of Health, Bethesda, MD, United States
Correspondence: Hanna Kim
Introduction: Juvenile dermatomyositis (JDM) is a complex heterogeneous autoimmune
disease. Clinical markers are imperfect to correlate with disease activity. Broad
proteomic analysis with high sensitivity and reproducibility may be used biomarker
discovery. Novel biomarkers from peripheral blood may help characterize pathogenesis
and improve disease monitoring and treatment.
Objectives: To define protein biomarkers dysregulated in JDM and better understand
JDM pathogenesis using novel aptamer-based proteomic technology proteome in a well-characterized
JDM cohort.
Methods: Unbiased internal discovery and validation analysis was done using broad
proteomic analysis of 1306 protein targets using SOMAscan assay of slow off-rate modified
aptamers (SomaLogic, CO) which generates simultaneous quantitative results with high
sensitivity and reproducibility. In a discovery cohort, 27 JDM patient sera (prevalent
cases on variable treatment, average physician global activity or PGA mean 3.9/10
visual analog scale, with 14 anti-p155/140 or TIF1, 6 NXP2, and 7MDA5 myositis specific
autoantibodies or MSAs) was compared versus 19 age and gender-matched healthy controls
or HC sera using Mann Whitney U FDR <0.10 cutoff. Resulting protein targets were subsequently
analyzed in validation cohort sera (14 prevalent JDM cases with similar characteristics
including MSA distribution vs 9 HC) using the same cutoff. Resulting proteins with
expression ratio of >1.3 were analyzed using Ingeunity Analysis or IPA (Qiagen, CA).
The top 10 pathways were then manually clustered to minimize protein overlap with
at least 1 unique protein per pathway cluster. Exploratory analysis of the same set
of significant upregulated proteins in JDM were analyzed for correlation with PGA
by Spearman rank test.
Results: 311 protein targets met above criteria from the discovery cohort; 166 unique
proteins met criteria after analysis in the validation cohort. 80 of these proteins
were upregulated in JDM versus HC and 59 had expression ratio of >1.3. From IPA analysis,
28 proteins fit into 6 pathway clusters: type I IFN notably including IFN beta, granulocyte/agranulocyte
adhesion and diapedesis, remodeling/damage, acute phase response, Th1 pathway, and
adipokines. There were between 1-7 unique proteins per pathway cluster but many proteins
fit into more than 1 pathway cluster. Among the 10 most highly expressed proteins,
the most common associated pathway cluster is type I IFN with granulocyte/agranulocyte
adhesion as the second most common. 13 proteins had significant moderate correlation
with PGA in JDM from varied pathway clusters with Spearman r values of 0.32-0.41.
Further analysis by MSA group is ongoing.
Conclusion: Broad quantitative proteomic analysis in a well-characterized JDM cohort
identifies key differentiating pathway clusters as above in JDM versus HC including
many novel proteins, 13 of which have moderate correlation with PGA. Top upregulated
proteins are most commonly associated with type I IFN pathway cluster, with granulocyte-agranulocyte
adhesion and diapedesis as the second most common pathway cluster. Further analysis
by MSA group is ongoing. While in need of confirmation in other cohorts, these proteins
identified through a high-throughput screen bring to light new pathways that may be
important in JDM.
This research was supported by the Cure JM Foundation and the Intramural Research
Program of the NIH, NIAMS, NIEHS, NHLBI, NIAID, and the CC.
Disclosure of Interest: H. Kim Grant/Research Support from: Cure JM Foundation, A.
Biancotto: None Declared, F. Cheung: None Declared, T. O’Hanlon: None Declared, I.
Targoff: None Declared, Y. Huang: None Declared, F. Miller: None Declared, R. Goldbach-Mansky:
None Declared, L. Rider: None Declared.
Autoinflammatory diseases in practice
O9 A web-based collection of genotype-phenotype correlations in hereditary periodic
fevers from the Eurofever registry
Riccardo Papa1, Matteo Doglio1, Helen J. Lachmann2, Seza Ozen3, Joost Frenkel4, Anna
Simon5, Benedicte Neven6, Jasmin Kuemmerle-Deschner7, Huri Ozdogan8, Roberta Caorsi1,
Silvia Federici1, Martina Finetti1, Nicolino Ruperto1, Isabella Ceccherini9, Marco
Gattorno1 and the Paediatric Rheumatology International Trials Organisation (PRINTO)
and the Eurofever Project
1UO Pediatria II-Reumatologia, Istituto Giannina Gaslini, Genoa, Italy; 2National
Amyloidosis Centre, Royal Free Campus, University College Medical School, London,
United Kingdom; 3Department of Pediatric Nephrology and Rheumatology, Hacettepe University,
Ankara, Turkey; 4Department of Paediatrics, University Medical Center Utrecht, Utrecht,
Netherlands; 5Department of General Internal Medicine, Radboud University Nijmegen
Medical Center, Nijmegen, Netherlands; 6Unité d'immuno-hématologie pédiatrique, Hôpital
Necker Enfants Malades, Paris, France; 7Paediatric Rheumatology, University Hospital
Tübingen, Tübingen, Germany; 8Ic Hastaliklari ABD, Romatoloji BD, Cerrahpasa Tip Fakultesi,
Istanbul, Turkey; 9Laboratory of Molecular Genetics, Istituto Giannina Gaslini, Genoa,
Italy
Correspondence: Riccardo Papa
Introduction: Because of the large number of common variants or polymorphisms in genes
related to hereditary periodic fevers (HPF), genetic results often require an high
clinical discrimination. The Infevers database is a large international registry of
the different variants described for genes associated to autoinflammatory diseases.
Due to the nature of this registry no genotype-phenotype correlation are provided,
except for the clinical phenotype of the first patient(s) described for each mutation.
Objectives: Aim of this study was to elaborate a registry of genotype-phenotype correlations
derived from the patients with HPF enrolled and validated in the Eurofever registry.
Methods: We created a table for each HPF describing the genotype-phenotype correlations
observed in all the patients enrolled in the Eurofever registry. For autosomal dominant
diseases (CAPS, TRAPS), all mutations were analyzed individually. For autosomal recessive
diseases (FMF, MKD), homozygous and all combinations of compound heterozygous are
described. For each mutation or combination, the following items are shown: number
of patients, mean age of onset, disease course (recurrent or chronic), mean duration
of fever episodes, clinical manifestations associated with fever episodes, atypical
manifestations, complications and response to treatment.
Results: We analyzed the genotype-phenotype correlations of 718 patients (313 FMF,
133 CAPS, 114 MKD, 158 TRAPS) already reported in specific papers and validated by
at least two experts for each disease. A total of 152 variants were described: 48
variants of TNFRSF1A, 30 NLRP3, 57 different combinations of MVK and 42 MEFV for compound
heterozygous are available. For each HPF, a table with all the variables described
has been established.
Conclusion: We provide a useful tool for all the physicians, creating a registry of
genotype-phenotype correlation of HPF based on the patients enrolled in the Eurofever
registry. This tool is complementary to the Infevers database and will be available
at the Eurofever and Infevers websites.
Disclosure of Interest: None Declared.
Genetic aspects of pediatric rheumatic diseases
O10 IKZF1 mutation underlines the B cell landscape heterogeneity in mendelian lupus
Cécile Frachette1, Sulliman O. Omarjee1, Anne Laure Mathieu1, Thibault Andrieu2, Paul
Mondier3, Gillian Rice4, Heloïse Reumaux5, David Launay6, Marc Lambert7, Guillaume
Lefevre8, Nicole Fabien9, Christophe Malcus10, Isabelle Rouvet11, Emilie Chopin11,
Anne-Sophie Michallet3, Thierry Defrance3, Thierry Walzer1, Yanick Crow12, Alexandre
Belot1
1Inserm U1111, Centre International de Recherche en Infectiologie- International Center
for Infectiology Research, LYON, France; 2Inserm SFR Biosciences Gerland, LYON, France;
3Centre International de Recherche en Infectiologie- International Center for Infectiology
Research, LYON, France; 4Division of Evolution and Genomic Sciences, Faculty of Biology,
Medicine and Health, University of Manchester, Manchester, United Kingdom; 5Rhumatologie
médecine interne pédiatrique, Urgences, Pédiatrie générale et maladies infectieuses
Hôpital Salengro, Lille, France; 6Department of Internal medicine and Clinical Immunology,
UMR 995 Inserm, University of Lille, Lille, France; 7Service de médecine interne,
Hôpital Huriez, Lille, France; 8Lille Inflammation Research International center,
Lille, France; 9Service d'immunologie, CHU de Lyon HCL-Groupement Hospitalier Sud,
Lyon, France; 10Laboratoire d'immunologie cellulaire, Groupement hospitalier Edouard
herriot, Lyon, France; 11Biotechnology Department, Hospices civils de Lyon, Lyon,
France; 12Inserm UMR 1163, Laboratory of Neurogenetics and Neuroinflammation, Paris,
France
Correspondence: Cécile Frachette
Introduction: Next generation sequencing (NGS) represents a revolution in the field
of molecular medicine, and offers a new approach to deciphering the pathogenesis of
complex diseases. Paediatric-onset SLE (pSLE) is a very rare and more severe phenotype
than its adult-onset counterpart, and is possibly associated with a greater contribution
of genetic aetiological factors. We have in the past described a B cell-related Mendelian
form of lupus due to a deficiency of PKCδ. Here, we identified and characterized a
new B cell-related Mendelian lupus secondary to IKZF1 mutation and compared this novel
monogenic disease with PKCδ deficiency.
Objectives: The aims of the study were to characterize the molecular impact of a new
B cell related variant in IKZF1 encoding the protein IKAROS, and to study the B cell
landscape of two distinct monogenic forms of SLE using mass cytometry (Cytof®).
Methods: We designed an NGS panel comprising 200 genes including proven disease-associated
as well as prospective candidate genes, and analysed 132 patients. We identified a
family with three affected individuals carrying a previously unreported mutation in
IKZF1. We set up functional assays including oligonucleotide pulldown, B cell phosphorylation
and deep B cell immunophenotyping by mass cytometry.
Results: We identified a heterozygous missense mutation in IKZF1 c.359A > T (p. D120V)
in three affected patients in a single family. IKZF1 encodes IKAROS, a key transcriptional
factor in B cell development. Functional assays showed that protein stability was
not impaired, but DNA-binding was partially impacted. We performed mass cytometry
comparing SLE patients carrying a homozygous loss-of-function mutation in PRKCD and
our newly identified IKZF1 mutation. We identified B cell clusters, and unsupervised
analysis underlined the wide differences between two monogenic diseases leading to
SLE.
Conclusion: Ikaros and PKCδ dysfunction demonstrate that monogenic lupus can occur
as a consequence of distinct anomalies of B cell development underlining the fact
that SLE should be considered as a syndrome rather than a single homogenous disease.
Disclosure of Interest: None Declared.
Remission in chronic arthritis
O11 Development of New JADAS and cJADAS cut-offs for disease activity states in oligoarthritis
and rf-negative polyarthritis from a large multinational cohort of children with juvenile
idiopathic arthritis
Alessandro Consolaro1,2, E.H. Pieter van Dijkhuizen3, Graciela Espada4, Boriana Varbanova4,
Sheila K. Oliveira4, Paivi Miettunen4, Gaelle Chédeville4, Michael Hofer4, Pavla Dolezalova4,
Ivan Foeldvari4, Gerd Horneff4, Anne Estmann4, Chris Pruunsild4, Rosa Merino4, Inmaculada
Calvo Penades4, Pablo Mesa-del-Castillo4, Pekka Lahdenne4, Maka Ioseliani4, Maria
Trachana4, Olga Vougiouka4, Miroslav Harjacek4, Ilonka Orban4, Tamàs Constantin4,
Nahid Shafaie4, Violeta Panaviene4, Marite Rygg4, Elzbieta Smolewska4, Jose Antonio
Melo-Gomes4, Jelena Vojinovic4, Ekaterina Alekseeva4, Tadej Avcin4, Veronika Vargova4,
Nuray Aktay Ayaz4, Ozgur Kasapcopur4, Yaryna Boyko4, Sarah Ringold4, Marco Garrone1,4,
Nicolino Ruperto1,4, Angelo Ravelli1,2 on behalf of PRINTO and EPOCA Study Group
1Istituto Giannina Gaslini, Genova, Italy; 2University of Genova, Genova, Italy; 3Wilhelmina
Children's Hospital, Utrecht, Netherlands; 4PRINTO, Genova, Italy
Correspondence: Alessandro Consolaro
Introduction: The measurement of the level of disease activity plays a pivotal role
in the care of patients with ju-venile idiopathic arthritis (JIA). To serve this purpose,
the Juvenile Arthritis Disease Activity Score (JADAS) was developed in 2009. More
recently, a version excluding the acute phase reactant was tested (cJADAS). Cutoff
values for the state of remission, low disease activity (LDA), moderate disease activity
(MDA) and high disease activity (HDA) were recently developed for the original JADAS
score and for the clinical version. These cutoff values are ideally suited for pursuing
tight disease control in a treat-to-target strategy, with treatment escalation if
the desired JADAS score is not reached. However, although cut-offs were validated
in a large and multinational cohort of patients, they were developed in a dataset
of patients from a single pediatric rheumatology center an partly before the advent
of the so-called biologic era.
Objectives: To develop the JADAS and cJADAS cut-off values of remission, LDA, MDA,
and HDA for oligoarthritis and RF-negative polyarthritis in a large multinational
cohort of JIA patients.
Methods: The EPidemiology, treatment and Outcome of Childhood Arthritis (EPOCA) study
is aimed to obtain information on the frequency of JIA subtypes in different geographic
areas, the therapeutic approaches adopted by pediatric rheumatologists practicing
in diverse countries or continents, and the disease and health status of children
with JIA currently followed worldwide. More than 9.000 patients with JIA from 118
pediatric rheumatology centres in 49 countries were collected so far. For the development
of cut-offs, patients with oligoarthritis and polyarthritis followed in the 20 Centres
with the highest frequency of these 2 subtypes were retained. In each centre, the
75th centile of JADAS and cJADAS distribution in patients who were subjectively rated
by the attending physician as being in remission and LDA, and the 25th centile of
JADAS and cJADAS in patients rated as in HDA, were calculated. The obtained values
at each centre were then averaged to obtain the prelimary cut-offs for each disease
activity state.
Results: The cut-offs validation cohorts were made of 930 patients with oligoarthritis
from 20 pediatric rheumatology Centres and 1.004 patients with RF-neg polyarthritis
from 20 pediatric rheumatology Centres. Preliminary cut offs values for each versions
of JADAS and cJADAS are presented in Table 1.
Table 1
(Abstract O11). See text for description
JADAS10
JADAS27
JADAS71
cJADAS10
cJADAS27
cJADAS71
Oligoarthritis
Remission
1.5
1.5
1.5
1.2
1.2
1.2
LDA
3.9
3.7
3.9
3.4
3.3
3.4
HDA
16.4
16.2
16.4
14.3
14.1
14.3
Polyarthritis
Remission
2.6
2.6
2.6
2.4
2.3
2.4
LDA
5.1
4.9
5.1
5.1
4.9
5.1
HDA
18.9
18.9
22.7
19.0
20.0
25.3
Conclusion: New JADAS and cJADAS temptative cut-offs for remission, LDA, and HDA were
calculated. Obtained values will be tested in the validation analysis. The preliminary
values are higher than currently available cut-offs.
Disclosure of Interest: None Declared.
New insights into the pathogenesis of systemic lupus erythematosus (SLE)
O12 Interferon-γ plays a role in the pathogenesis of pediatric systemic lupus erythematosus
and its activity correlates with disease activity
Gian Marco Moneta1, Claudia Bracaglia1, Ivan Caiello1, Luisa Bracci-Laudiero1,2, Rita
Carsetti3, Fabrizio De Benedetti1, Emiliano Marasco1
1Division of Rheumatology, IRCCS Bambino Gesù Children’s Hospital, Rome, Italy; 2Institute
of Translational Pharmacology, CNR, Rome, Italy; 3B Cell Physiopathology Unit, Immunology
Research Area, IRCCS Bambino Gesù Children’s Hospital, Rome, Italy
Correspondence: Marco Moneta
Introduction: Pediatric systemic lupus erythematosus (pSLE) is a rare autoimmune disorder
with onset before 18 years of age and characterized by heterogeneous clinical manifestations,
unpredictable courses and a substantial risk of morbidity. There is no targeted treatment
available for pSLE. In the last decade, several gene expression profiling and protein
studies showed an up-regulation of genes typicallyinduced by type I interferons (IFNα/β)
in the peripheral blood and tissue samples of pSLE patients. Although blood expression
levels of IFNα/β-related genes were also correlated with disease activity of pSLE
patients, the mechanism by which type I IFN contribute to pathogenesis has not yet
been elucidated.
Objectives: In this study, we aim to investigate the role of type II IFN, IFNγ, in
the pathogenesis of pSLE evaluating: 1) the expression levels of IFNγ-related genes
in the peripheral blood of pSLE patients; 2) the relationship between type II and
type I IFNs; 3) the correlations between the expression levels of IFNγ-related genes
in peripheral blood and the clinical features of pSLE patients.
Methods: We analysed the expression levels of IFNα/β induced genes (IFI27, IFI44L,
IFIT1, RSAD2, ISG15, SIGLEC1) and IFNγ induced genes (CXCL9, CXCL10, IDO1) in the
peripheral blood of pSLE patients (n = 19) by real time PCR. For each patient, SLEDAI
score was calculated. Human peripheral blood mononuclear cells (PBMCs) obtained by
healthy donors (HD) (n = 3) were stimulated in vitro with recombinant human IFNγ and
IFNα2b, expression levels of IFN-regulated genes were evaluated by real time PCR.
We used non-parametric Mann-Whitney U test and Spearman r for statistical analysis.
Results: Expression levels of both IFNα/β-induced genes and IFNγ-induced genes were
increased in the peripheral blood of pSLE patients with active disease (n = 9) compared
to HD (n = 10) and pSLE patients with inactive disease (n = 10). We developed a type
II IFN score similarly to the type I IFN score described by Crow et al. We calculated
the type I IFN score and the type II IFN score for each pSLE patient. As previously
reported, the type I IFN score was significantly correlated with the SLEDAI of pSLE
patients (r = 0.67, p < 0.01). We found that the type II score was also significantly
correlated with the SLEDAI score of pSLE patients (r = 0.64, p < 0.01).
As it is known that some IFN-induced genes can be upregulated by both types of interferons,
we asked if IFNγ was able to affect, in human PBMCs, the expression of IFNα/β induced
genes (IFI27, IFI44L, IFIT1, RSAD2, ISG15, SIGLEC1) assessed to calculate the type
I score: we found that IFNγ treatment induced the expression of type I IFN-related
genes in human PBMCs in dose-dependent manner. Interestingly, human PBMC stimulated
with recombinant IFNα2b strongly up-regulated the expression of IFNγ.
Conclusion: Taken together, these data indicate a possible role of IFNγ in the pathogenesis
of pSLE. Both types of IFNs potentiate each other effect on tissues by affecting their
reciprocal biological activity. IFNγ correlates with disease activity in pSLE, IFNγ-induced
gene expression may represents a promising biomarker in this autoimmune disease. The
potential pathogenic role of IFNγ in SLE remains to be elucidated.
Disclosure of Interest: None Declared.
Scleroderma and related disorders
O13 Reliability and performance of the loscat clinical score for the assessment of
activity and tissue damage in a large cohort of patients with juvenile localized scleroderma
Anna Agazzi, Gloria Fadanelli, Fabio Vittadello, Francesco Zulian, Giorgia Martini
Department of Woman and Child Health, University of Padua, Padova, Italy
Correspondence: Anna Agazzi
Introduction: One of the open issues for Juvenile Localized Scleroderma (JLS) is the
assessment and monitoring over time of the extent of inflammation and tissue damage.
The lack of reliable and standardized outcome measures has represented, over the years,
a significant limitation for both clinical monitoring of the disease and development
of therapeutic trials.
Objectives: We assessed the reliability of Localized Scleroderma Cutaneous Assessment
Tool (LoSCAT) clinical score in comparison with contemporary thermographic analysis.
Secondary aim was to evaluate and compare the sensitivity to change of LoSCAT and
thermography over time.
Methods: A longitudinal observational analysis of patients with JLS, consecutively
evaluated at our Paediatric Rheumatology Unit, has been performed by using the LoSCAT
clinical score and infrared thermography.
LoSCAT score is composed of two indexes: the modified Localized Scleroderma Skin Severity
Index (mLoSSI) which measures disease activity considering any new/enlarged lesion,
erythema and thickening, and the Localized Scleroderma Skin Damage Index (LoSDI) which
measures tissue damage as dermal atrophy, subcutaneous atrophy and depigmentation.
Infrared thermography is a non-invasive imaging technique detecting the thermal energy
emitted from the skin providing a graphical representation of its distribution on
the body surface.
Three examiners with different experience in Paediatric Rheumatology blindly evaluated
all patients twice, at baseline and at least three months later. At each visit, thermographic
analysis and LoSCAT score were performed by each examiner. The inter-rater reliability
was assessed by the Intraclass Correlation Coefficient (ICC) and interpreted as follows:
ICC values range 0.75-1 excellent reliability, 0.4-0.74 good reliability, <0.4 poor
reliability. All statistical analyses, including the analysis of variance (ANOVA),
were performed by using IBM SPSS (Vers. 18.0).
Results: Forty-seven patients (129 lesions) entered the study, and 26 (79 lesions)
were reassessed by same examiners with the same modality after 4.5 (+1.5) months.
As for LoSCAT, mLoSSI showed excellent inter-rater reliability expressed by ICC 0.895
(95% CI 0.846-0.931); the analysis of variance (ANOVA) confirmed that values indicated
by the 3 examiners, were not different from each other (test F = 1.275 and p = 0.283).
The inter-rater reliability for LoSDI was excellent too with ICC = 0.880 (95% CI 0.825-0.921),
ANOVA test F = 3.030 (p = 0.052).
In the group of 79 lesions examined twice an improvement for all anatomic sites for
both evaluations of the three examiners and thermographic detection was observed.
Moreover, thermographic analysis showed statistically significant correlation in different
anatomic sites with domains of erythema, dermal atrophy and subcutaneous atrophy of
LoSCAT.
Conclusion: LoSCAT appears as a promising outcome measure in JLS, distinguishing the
different aspects of activity and damage. LoSCAT is not influenced by the experience
of the examiner. Infrared thermography confirms to be a very helpful tool for detecting
disease activity and reliable in monitoring lesions over time.
Disclosure of Interest: None Declared.
O14 Tocilizumab is a promising treatment option for therapy resistent juvenile localised
scleroderma patients
Ivan Foeldvari1, Jordi Anton2, Mark Friswell3, Blanca Bica4, Jaime de Inocencio5,
Angela Aquilani6, Nicola Helmus1
1Hamburg Center for Pediatric and Adolescent Rheumatology, AM Schöen Klinik Eilbek,
Hamburg, Germany; 2Sant Joan de Déu Hospital, Barcelona, Spain; 3Great North Children’s
Hospital, Newcastle, United Kingdom; 4Universidade Federal do Rio de Janeiro, Rio
de Janeiro, Brazil; 5University Hospital 12 de Octubre, Madrid, Spain; 6Ospedale Bambino
Gesù, Rome, Italy
Correspondence: Ivan Foeldvari
Introduction: Juvenile localised scleroderma (jlSc) is an orphan disease. Most patient
respond to treatment ot methotrexate or mycophenolate. In case of nonresponse or partial
response, based on the promising tocilizumab (TOC) data of adult systemic sclerosis
studies, TOC seems to be a promising option. There is no publication regarding the
effectiveness of tocilizumab in jLS.
Objectives: To assess the effectivity of TOC in jlSC patients, who had nonresponse
or partial response on conventional therapy.
Methods: Participants of the pediatric rheumatology email board were asked, if they
follow patients with jlSc, who are treated with TOC. Clinical characteristics and
the response to TOC was assessed.
Results: Six centers responded to the survey from the email board, with around 800
participants, and reported 11 patients. The mean age of the patients at disease onset
was 5.5 years. Disease duration at time of the initiation of TOC was 53.5. months
(range 9 to 109). 5 patients had linear subtype, 3 of them with facial involvement,
2 of them Parry Romberg and one of them coup de sabre. Three had generalized subtype,
2 mixed subtype and 1 limited subtype/morphea. Before starting TOC patients received
10/11 Methotrexate, 7/11 Mycophenolate, 1 abatacept and 1 anti-TNF therapy. Reason
to start TOC was in 9 patients increase in Localised Scleroderma Activity Index[1]
(mLoSSI). In two patients increased extracutaneous activity was the indication, in
one increased activity of arthritis and in the other increased activity of the central
nervous system involvement.
The mean duration of tocilizumab therapy was 14.75 months. 2 patients received s.c.
according the poly JIA dosing and all other i.v.. There were different i.v doses applied,
5 of them 8 mg/kg every 4 weeks, one of them 8 mg/kg every three weeks, 1 every two
weeks and 1 patients received 10 mg/kg every 3 weeks. 3/11 received TOC as monotherapy.
8/11 as combination therapy, 6 of them with Methotrexate and one of each with Mycophenolate
or Tacrolimus. Therapy success was reflected by a decreased mLoSSI in 8/11 patients
and in 6 patients by a decrease in the Localosed Scleroderma Skin Damage Index[1]
(LoSDI). No new lesion occurred during the treatment and in the patients with Parry
Romerg subtype(n = 2) no increase in the facial atrophy occurred. In 8/8 patients
physician global (VAS 0-100) decreased and in 8/8 the patients global disease activity
(VAS 0-100) decreased. In 3/3 patients, were it was applicable, the number of active
joints decreased, in one patients the limb discrepancy decreased. The mean modified
Rodnan skin score assessed in 8 patients decreased from the mean value of 9.6 to 5.5.
Conclusion: Conclusion:
In this small cohort of patients TOC seems to be a promising rescue medication in
methotrexate/mycophenolate nonresponsive patients. A prospective controlled study
would be important to prove the seen effect in a controlled way.
1. Arkachaisri T, Vilaiyuk S, Torok KS, Medsger TA, Jr.: Development and initial validation
of the localized scleroderma skin damage index and physician global assessment of
disease damage: a proof-of-concept study. Rheumatology (Oxford) 2010, 49(2):373-381.
Disclosure of Interest: None Declared.
Pathogenesis of juvenile idiopathic arthritis (JIA)
O15 P75NTR/PRONGF up regulation in synovial tissues activates inflammatory responses
in chronic arthritis patients
gaetana minnone1, Melissa Noack2, Pierre Miossec3, Ivan Caiello1, Marzia Soligo4,
Luigi Manni4, Antonio Manzo5, Fabrizio De Benedetti1, Luisa Bracci-Laudiero4
1Division of Rheumatology and Immuno-Rheumatology Research Laboratories, Bambino Gesù
Children’s Hospital, Rome, Italy; 23 Immunogenomics and Inflammation Research Unit,
EA 4130, Edouard Herriot Hospital, Hospices Civils de Lyon and University Claude Bernard
Lyon 1, Lyon, France; 3Immunogenomics and Inflammation Research Unit, EA 4130, Edouard
Herriot Hospital, Hospices Civils de Lyon and University Claude Bernard Lyon 1,, Lyon,
France; 4Institute of Translational Pharmacology, CNR, Rome, Italy; 5Rheumatology
and Translational Immunology Research Laboratories (LaRIT), Division of Rheumatology,,
IRCCS Policlinico S. Matteo Foundation/University of Pavia, Pavia, Italy
Correspondence: gaetana minnone
Introduction: We have recently demonstrated that synovial fluids of JIA patients contain
elevated levels of proNGF, the immature form of the Nerve Growth Factor (NGF), and
not mature NGF as believed in the past. Moreover, mononuclear cells of JIA patients
show a reduced expression of TrkA, the specific receptor of mature NGF, and an enhanced
expression of p75NTR, the specific receptor for proNGF. This results in an inverted
ratio of TrkA and p75NTR in JIA patients compared to healthy donors. How this altered
proNGF/p75NTR axis can influence the inflammatory response is at present unknown.
Objectives: In this study, we focused on the involvement of p75NTR and its ligand
proNGF in regulating inflammatory responses in the inflamed synovia and in synoviocytes
of arthritis patients.
Methods: Fibroblast-like synoviocytes (FLS) were obtained by synovial tissue of rheumatoid
arthritis patients (RA FLS) after enzymatic digestion. Osteoarthritis fibroblasts
(OF) and skin fibroblasts (SF) were used as control. Using Realtime-PCR and western
blot, we evaluated TrkA, p75NTR, sortilin, NGF mRNA expression and protein levels.
Realtime-PCR and ELISA were used to evaluate cytokine production.
Results: Our preliminary data show that, similarly to JIA SFMC, p75NTR is significantly
upregulated in FLS of RA patients, while TrkA is much less expressed than p75NTR.
Instead, OF and SF showed a higher expression of TrkA than p75NTR. Moreover, FLS express
NGF mRNA and release high amounts of proNGF, but not of mature NGF, in the conditioned
media. Inflammatory stimuli, such as IL-1b, further upregulate p75NTR expression in
FLS and induce the expression of p75NTR in control fibroblasts. In vitro, the addition
of proNGF to FLS induces the expression of pro-inflammatory cytokines. This effect
is abolished when p75NTR activity was inhibited using LM11A-31, a non-peptide ligand
that blocks the binding site of p75NTR for proNGF.
Conclusion: These preliminary data suggest that the proNGF found in synovial fluids
of chronic arthritis patients is produced and released principally by FLS. The accumulated
proNGF binds to its specific receptor p75NTR, which is highly expressed by both FLS
and SFMC, inducing pro-inflammatory cytokine expression. Inflammatory stimuli further
enhances the expression of p75NTR in FLS, creating a vicious circle that amplify the
inflammatory response. The use of p75NTR inhibitors might represent a new therapeutic
approach for the treatment of JIA and RA.
Disclosure of Interest: None Declared.
Oral Presentations 1
O16 Three treatment strategies in recent onset dmard naive juvenile idiopathic arthritis:
first results of clinical outcome after 24 months
Petra Hissink Muller1,2, Danielle Brinkman1,3, Dieneke Schonenberg4, Wytse van den
Bosch1, Yvonne Koopman-Keemink5, Isabel Brederije1, Peter Bekkering6, Taco Kuijpers4,
Marion van Rossum7, Lisette W. van Suijlekom-Smit8, J M. van den Berg4, Stefan Boehringer9,
C F. Allaart10, Rebecca ten Cate1
1Pediatric Rheumatology, LUMC, Leiden, Netherlands 2Pediatric Rheumatology, Erasmus
MC Sophia, Rotterdam, 3Pediatrics, Alrijne Hospital, Leiderdorp, Netherlands 4Department
of Pediatric Hematology, Immunology, Rheumatology and Infectious Diseases, Emma Children’s
Hospital AMC, University of Amsterdam, Amsterdam, Netherlands 5Pediatrics, Juliana
Children's Hospital, The Hague, Netherlands 6Pediatric Oncology, Princess Máxima Center
of Pediatric Oncology, Utrecht, Netherlands 7Pediatric Rheumatology, Amsterdam Rheumatology
and Immunology Center location Reade, Amsterdam, Netherlands 8Pediatric Rheumatology,
Erasmus MC Sophia Children's Hospital, Rotterdam, Netherlands 9Medical Statistics
and Bioinformatics, LUMC, Leiden, Netherlands 10Rheumatology, LUMC, Leiden, Netherlands
Correspondence: Petra Hissink Muller
Introduction
The BeSt treatment strategy for children with juvenile idiopathic arthritis (JIA)
has not been determined as of today.
Objectives
The aim of the BeSt for Kids study was to investigate, which of three treatment strategies
is most effective and safe, by comparing them directly. The therapeutic target in
all arms was inactive disease by rapid reduction of disease activity and repeated
monitoring and revision of therapy in case of insufficient response. We hypothesized
that early treatment with etanercept and methotrexate (arm 3), compared to initial
monotherapy (arm 1) or initial combination therapy with methotrexate and prednisone
(arm 2), would lead to significantly earlier clinical inactive disease.
Methods
We conducted a randomized, single blinded, multicenter, treatment strategy study with
24 months of follow up. Disease modifying anti rheumatic drug (DMARD)-naive JIA patients
were randomized to 1. sequential DMARD-monotherapy (sulfasalazine (SSZ) or methotrexate
(MTX), 2. combination therapy: MTX and prednisolone-bridging, 3. Combination-therapy
MTX with etanercept. For all arms, the treatment protocol described a number of subsequent
treatment steps in case medication failed. After reaching remission for 3 (oligoarticular)
or 6 months (polyarticular) medication was tapered and stopped as dictated per protocol
and flare frequency was observed. Missing data were imputed. Primary outcome was time
to inactive disease and time to flare after tapering and stopping DMARD therapy, both
calculated using Kaplan Meier method with log rank test. Secondary outcomes are adjusted
ACRPedi 30/50/70 scores, toxicity, functional ability and quality of life. Generalised
Estimating Equations were used for longitudinal data analyses. In this abstract we
share the first 24 months results.
Results: Ninety-four patients were randomised, 32 in arm 1, 32 in arm 2 and 30 in
arm 3. Two patients received a different diagnosis during follow-up and were left
out of all analysis. Two patient were lost to follow up but were analysed due to intention
to treat principle. Overall baseline median (InterQuartileRange IQR) age was 9.1 (4.6-12.9)
years. 37% were ANA positive, 11 patients had oligo-articular disease, 66 patients
polyarticular JIA and 15 patients juvenile psoriatic (polyarticular) arthritis. Baseline
median (IQR) ACRpedi-scores: VAS physician 50 (39-58) mm, VAS patient 54 (37-70) mm,
ESR 6(2-14) mm/hr, active joint count 8 (5-12), limited joint count 2.5 (1-5), CHAQ
score 0.9 (0.6-1.5). Inactive disease occurred overall after mean 9.8 months (8.5-11.1).
Time to inactive disease was not significantly different in all three arms (log rank
test p = 0.23). Outcome measures after 24 months of therapy are summarised in the
Table 2.
Table 2
(abstract O16). See text for description
Arm 1 n = 31
Arm 2 n = 32
Arm 3 n = 29
3 vs 1 p OR (CI)
2 vs 1 p OR (CI)
3 vs 2 p OR (CI)
ACRPEdi30(%)(CI)
92.2 (82,1-102.4)
84.4 (71.2-97.5)
96.6 (89.8-103.3)
0.1 1.7 (0.8-3.4)
0.8 0.9(0.5-1.7)
0.1 0.9-3.7
ACRPedi50 (%)(CI)
85.5 (72.4-98.6)
83.8 (70.1-97.4)
93.1 (83.7-102.4)
0.3 1.4(0.7-2.8)
0.9 1.1(0.6-2.0)
0.4 1.3(0.7-2.7)
ACRPedi70 (%)(CI)
69.0 (52.1-85.9)
68.8 (51.6-85.9)
82.8 (68.8-96.8)
0.07 1.8(1.0-3.3)
0.7 0.9(0.4-1.7)
0.03 2.1(1.1-4.0)
Inactive disease (%)
61.0 (39.7-82.3)
63.1 (43.6-82.7)
61.0 (40.9-81.2)
0.9 1.0(0.7-1.7)
0.1 0.7(0.4-1.1)
0.09 1.5(0.9-2.5)
JADAS-10 (CI)
2.6(1.4-3.8)
4.0(2.2-5.8)
3.0(1.6-4.4)
0.6 0.6(0.1-3.5)
0.2 3.1(0.5-20.3)
0.09 0.2(0.03-1.3)
Conclusion: Although our study did not meet its primary end point, treat-to-target
treatment in this cohort of children with recent-onset JIA resulted in high frequencies
of clinical inactive disease and adjusted ACRpedi30/50/70 scores in all three arms.
In clinical trials inactive disease seems a feasible goal in juvenile idiopathic arthritis
patients.
Trial registration identifying number: NTR1574
Disclosure of Interest: None Declared.
O17 Predictive value of magnetic resonance imaging in patients with juvenile idiopathic
arthritis in clinical remission
Marta Mazzoni1, Angela Pistorio2, Stefania Viola3, Alessia Urru1, Emanuela Sacco3,
Eleonora Zaccheddu3, Francesca Magnaguagno4, Angelo Ravelli1, Alberto Martini1, Clara
Malattia1
1Università degli studi di Genova, Pediatria II-Reumatologia, Genoa, Italy; 2Epidemiologia,
Biostatistica e Comitati, Genoa, Italy; 3Pediatria II-Reumatologia, Genoa, Italy;
4Radiologia, G. Gaslini, Genoa, Italy
Correspondence: Marta Mazzoni
Introduction: MRI studies on RA patients showed that subclinical synovitis is often
present in patients in clinical remission and is responsible for progression of joint
damage. A high frequency of MRI-detected inflammation in JIA patients with clinically
inactive disease was also reported. Due to the lack of longitudinal studies in JIA,
it is unclear whether this phenomenon entails a risk of progression of joint damage
and whether it should affect the therapeutic decisions.
Objectives: To assess the prevalence of subclinical synovitis as detected by MRI in
a cohort of JIA patients in clinical remission and to evaluate its association with
disease flare and structural damage progression.
Methods: All JIA patients who met the Wallace criteria for clinical remission and
underwent contrast-enhanced MRI at the Study Unit between 2007 and 2015 were included.
MRIs were scored by two independent readers according to the Outcome Measure in Arthritis
Clinical Trials (OMERACT) Rheumatoid Arthritis Scoring System (RAMRIS). Joint damage
progression was assessed by conventional radiography (CR) according to the adapted
versions of the Sharp/van der Heijde score and to the Childhood Arthritis Radiographic
Score of the Hip. The concordance between the readers was assessed using kappa statistics.
Categorical data were analyzed using chi-squared test and Fisher’s exact test. Comparison
of quantitative variables was performed by the non-parametric Mann–Whitney U-test.
A logistic regression model was applied to perform multivariate analysis of the radiographic
damage risk factors.
Results: A total of 90 patients (15 M, 75 F; mean age 13.8 years; mean disease duration
8.5 years; mean follow-up duration 2.9 years) were included. Fourteen out of 90 patients
(15.6%) were in remission off medication, while 76/90 patients (84.4%) were in remission
on medication. Forty-five patients were assessed by MRI in the wrist, 30 in the hips,
13 in the ankle and 2 in the knee. Fifty-seven patients (63.3%) had evidence of subclinical
synovitis on MRI. The inter-observer agreement for presence/absence of synovitis was
good (k = 0.74; 95% CI: 0.5-0.9). Forty-three out of 57 patients (75,4%) with subclinical
synovitis experienced a disease flare versus 11 out of 33 patients (33.3%) who hadn't
any synovial inflammation (P < 0.0001). Radiographic damage progression was assessed
in 54/90 patients for whom follow-up CRs were available and was detected in 19/54
patients (35.2%). A significant association between systemic JIA subtype and deterioration
of joint damage was found (P = 0.027, Fisher’s exact test). MRI-detected bone marrow
oedema (BMO) score and the baseline radiographic damage score were also significantly
related to structural progression (P = 0.002, Mann–Whitney U-test). The multivariable
logistic regression analysis showed that only baseline BMO score ≥3 independently
contributed to explain radiographic damage progression (OR 4.82; 95% CI: 1.0-23.2;
P = 0.035).
Conclusion: A sizeable proportion of patients in clinical remission had MRI evidence
of persistent joint inflammation. Subclinical synovitis was significantly associated
with disease flare, while BMO showed remarkable promise in predicting joint destruction.
These findings support the utility of MRI for the assessment of JIA patients in clinical
remission and may have important clinical implications for their management.
Disclosure of Interest: None Declared
O18 Baseline predictors of functional disability eight years after disease onset in
the nordic juvenile idiopathic arthritis population-based cohort
Veronika Rypdal1, Ellen D Arnstad2, Lillemor Berntson3, Marek Zak4, Kristiina Aalto5,
Suvi Peltoniemi5, Susan Nielsen4, Mia Glerup6, Troels Herlin6, Anders Fasth7, Maria
Ekelund8, Marite Rygg2, Ellen Nordal1 and Nordic Study Group of Pediatric Rheumatology
(NoSPeR)
1Dep of Pediatrics, University Hospital of North Norway, UiT The Arctic University
of Norway, Tromsø; 2Dep of Laboratory Medicine, Children’s and Women’s Health, NTNU,
Dep of Pediatrics, St.Olavs Hospital, Trondheim, Norway; 3Dep of Women’s and Children’s
Health, Uppsala University, Uppsala, Sweden; 4Pediatric Clinic II, Rigshospitalet,
Copenhagen, Denmark; 5Dep of Pediatrics, Helsinki University Hospital, Helsinki, Finland;
6Dep of Pediatrics, Århus University Hospital, Århus, Denmark; 7Dep of Pediatrics,
University of Gothenburg, Gothenburg, Sweden; 8Dep of Pediatrics, Ryhov County Hospital,
Dep of Women’s and Children’s Health, Uppsala University, Uppsala, Sweden
Correspondence: Veronika Rypdal
Introduction: Baseline clinical predictors on long-term outcome, not only regarding
remission but also on functional ability, may enable assessment of prognosis and guide
early treatment decisions in juvenile idiopathic arthritis (JIA).
Objectives: To evaluate potential baseline clinical predictors of functional ability
assessed by the Childhood Health Assessment Questionnaire (CHAQ) eight years after
disease onset.
Methods: Consecutive cases with newly diagnosed JIA from defined geographical areas
in Denmark, Finland, Sweden and Norway were included and followed over eight years.
Logistic regression was performed to assess potential baseline predictors of disability
in terms of CHAQ (or HAQ for participants ≥18 years of age) score >0 at the final
study visit.
Results: At follow-up 98 months (median, IQR 95-102) after disease onset, CHAQ/HAQ
was available in 352 (80%) of the total 440 participants. A CHAQ/HAQ score of 0 was
found in 239 (68%) of these. The following characteristics at the first study visit
7 months (median, IQR 6-8) predicted CHAQ/HAQ > 0 eight years after disease onset:
higher cumulative joint count, symmetric arthritis in wrists, fingers, or ankles,
higher score on physician and patient/parent global assessment of disease activity,
pain, CHAQ and morning stiffness (Table 3).
Table 3
(abstract O18). Baseline characteristics analysed as predictors of disability eight
years after disease onset
Clinical Characteristics
N
CHAQ/HAQ =0
CHAQ/HAQ >0
OR (95%CI)
p
Cumulative active joint count
352
3 (1-6)
5 (2-9)
1.1 (1.0-1.1)
0.001
Physician GA, VAS
210
1.0 (0.3-2.0)
2.0 (0.7-4.3)
2.5 (1.5-4.0)
< 0.001
Symmetric wrist arthritis, n (%)
351
28 (50.0)
28 (50.0)
2.5 (1.4-4.5)
0.002
Symmetric finger arthritis, n (%)*
351
20 (39.2)
31 (60.8)
4.2 (2.3-7.8)
< 0.001
Symmetric ankle arthritis, n (%)
351
50 (57.5)
37 (42.5)
1.9 (1.1-3.1)
0.02
CHAQ- score at baseline
239
0.1 (0.0-0.9)
0.6 (0.0-1.4)
2.0 (1.4-3.0)
0.001
Patient/parent GA, VAS
234
0.7 (0.0-2.3)
2.0 (1.0-4.0)
2.3 (1.5-3.6)
< 0.001
Pain VAS
231
0.7 (0.0-2.3)
2.7 (1.0-5.0)
3.2 (2.0-5.0)
< 0.001
Morning stiffness > 15 min, n (%)
276
41 (41.4)
58 (58.6)
5.2 (3.0-8.9)
<0.001
Values are the median (IQR) unless otherwise indicated; OR, odds ratio; CI, confidence
interval. * Symmetric finger arthritis: bilateral arthritis in 1 or more of the 14
finger joints; GA, global assessment; VAS, visual analogue scale range 0-10
Conclusion: A higher cumulative joint count, and specifically symmetric arthritis
in finger joints, morning stiffness and higher pain score, higher patient/parent and
physician global VAS score at baseline, predicts functional disability eight years
after disease onset in a population-based Nordic JIA cohort.
Disclosure of Interest: None Declared.
O19 What is the outcome of juvenile idiopathic arthritis in adulthood? The monocentric
experience of 414 patients followed in a transition tertiary clinic of rheumatology
Irene Pontikaki1,2,3, Lorenza Maria Argolini4, Tania Ubiali4, Maria Gerosa2,3, Carolina
Artusi4, Marcello Truzzi5, Roberto Viganò6, Antonella Murgo2,3, Orazio De Lucia2,3,
Pierluigi Meroni2,3
1Center of Pediatric Rheumatology, Milan, Italy; 2Rheumatology, ASST Pini/CTO, Milan,
Italy; 3Chair of Rheumatology, Milan, Italy; 4Rheumatology, University of Milan, Milan,
Italy; 5Rheuma Surgery, Milan, Italy; 6Division of Rheumatoid Arthritis Surgery, ASST
Pini/CTO, Milan, Italy
Correspondence: Irene Pontikaki
Introduction: Juvenile Idiopathic Arthritis (JIA) is a chronic inflammatory disease
that affects children and adolescents and shows many differences in clinical manifestations,
assessment and management compared to adult-onset arthritis. The transition from the
child-centered to the adult-oriented care is a challenging multidimensional process
that emphasizes a lot of aspects that need to be addressed.
Objectives: To describe the long-term outcome of JIA.
Methods: Four-hundred and fifteen patients affected by JIA and referred to a transition
care rheumatology tertiary centre were considered between 1999 and 2016. The outcome
assessment included disease activity, mean disease duration, medications, number of
prosthesis implantation, pregnancies, mortality, social integration (mobility, employment
status and educational level).
Results: A hundred and twenty (28.9%) males and 294 (71%) females were included; 58
(14%) patients were lost to follow up. The median age of the patients was 25 (18-57)
years, the median age at onset was 9 years and the average disease duration was 17 years.
Subtypes of JIA at disease onset included oligoarthritis 212 (51.2%), polyarthritis
98 (23.6%), systemic arthritis 51 (12.3%), psoriatic arthritis 11 (2.7%), enthesitis
related arthritis 41 (9.9%) and undifferentiated arthritis 1 (0.2%). Seventy-one (17.1%)
patients had persistent uveitis. Eighty-five implant prosthesis and 15 arthrodesis
were recorded. Sixty-eight patients (16.4%) were also referred to the ultrasonography-guided
infiltration clinic, to receive either intrarticular steroids or hyaluronic acid.
At follow up 180 (43.5%) had low active disease activity, 84 (20.3%) had moderate
disease activity, 14 (3.4%) had a high disease activity, 72 (17.4%) were on remission
on medication and 64 (15.5%) off medication. Among the 350 patients still on medication,
75 (21.4%) were under treatment with oral steroids, 200 (57.1%) with sDMARDs and 225
(64.3%) with bDMARDs. Five deaths (1.2%) occurred in this cohort. A hundred and eighty-one
(43.7%) subjects had a higher educational level (university), 294 (71%) had an employment,
243 (58.7%) obtained a driving license. Twenty-one (5.1%) pregnancies were registered.
The transition age was considered after the age of sixteen years old. Particular attention
was brought to the multidisciplinary approach towards each patient, that was realized
with the collaboration of other specialists (ophthalmologist, orthopedic, dermatologist,
gastroenterologist, obstetric and psychologist).
Conclusion: In the era of biologic therapy the long-term outcome of JIA underwent
an outstanding improvement regarding a lot of variables. Two hundred and twenty-five
(54.3%) patients were still on tight control, not only because of the continuation
of the biological therapy, but also owing to the multidisciplinary care carried out
even during remission. JIA often persists over the adulthood, therefore the long term
follow-up and care of these patients needs to be conducted by a rheumatologist expertized
in JIA in collaboration with other specialists.
Disclosure of Interest: None Declared.
O20 Identification of novel antibodies predictive of the development of uveitis in
jia using high-density nucleic acid programmable protein arrays
Madeleine Rooney1, David Gibson2, Ji Qui3, Sorcha Finnegan1, Joshua Labaer3
1Center Experimental Medicine, Queens University Belfast, Belfast, United Kingdom;
2NI Centre of Stratified Medicine, Ulster University, Londonderry, United Kingdom;
3Center for Personalized Diagnostics, Arizona State University, Tempe, AZ United States
Correspondence: David Gibson
Introduction: Currently all children with oligo and polyarticular JIA have to be screened
by ophthalmologists for years in order to ensure that this completely asymptomatic
disease is not missed. If missed or inadequately treated, some 50% of these children
can go functionally blind. The only useful biological marker currently available is
ANA status. However this is neither sensitive nor specific enough to significantly
alter regular clinical screening. It does however suggest that autoantibodies, as
yet undiscovered, may be important in the pathophysiology of this disease.
We undertook this proof of concept study to see whether a novel technique capable
of producing multiple proteins could be used to screen for autoantibodies that are
associated with uveitis development in JIA patients. This could enable us to identify
children, at the time of diagnosis of arthritis, who are highly likely to develop
uveitis.
Objectives: To Identify novel antibodies that predict the development of uveitis in
children with JIA.
Methods: Nucleic Acid Programmable Protein Arrays (NAPPA) enable the in situ production
of multiple proteins from DNA templates which are immobilised on a solid phase. Methodology
is described in detail elsewhere [1]. NAPPA slides with 2200 genes were produced.
Pubmed search identified ~60 genes associated with uveitis pathology and ~30 genes
associated with arthritis development. The remaining ~2100 genes were randomly identified
from a ~12000 human gene collection (http://dnasu.asu.edu). The arrays were then probed
using plasma from JIA patients with (n = 20) and without uveitis (n = 20) and from
healthy age and sex matched controls (n = 20). Proteins with higher levels of antibody
detected were confirmed by ELISA.
Results: NAPPA image analysis revealed distinct signals from plasma antibodies of
JIA patients with Uveitis which had reacted with specific array proteins. Hierarchical
clustering heat maps were used to visualize clusters of proteins with higher array
reactivity for JIA or Uveitis samples, realtive to controls. ELISA's were developed
for nine highly reactive proteins including BATF, FO5, PROSAPIP1, CCND1, NOUFV3 and
SSB. Antibodies specific for single-stranded DNA-binding proteins (SSB) were confirmed
to be at significantly higher concentrations in the plasma of JIA patients with uveitis,
relative to JIA patients without eye disease.
Conclusion: These results indicate that the NAPPA technique is a sensitive tool for
screening antigens including specific nuclear antigens which distinguish JIA patients
with uveitis. We plan on developing a nuclear antigen array with over 2000 features
to determine further uveitis patient reactivity. Prospective studies are also required
to establish if these immunoglubulins are present at detectable levels in JIA patients
prior to development of uveitis and to assess their predictive utility.
Reference
[1]: Bian, X., Wiktor, P., Kahn, P., Brunner, A., Khela, A., Karthikeyan, K., Barker,
K., Yu, X., Magee, M., Wasserfall, C. H., Gibson, D., Rooney, M. E., Qiu, J., and
LaBaer, J. (2015) Antiviral antibody profiling by high-density protein arrays. Proteomics
15, 2136–2145
Disclosure of Interest: None Declared.
O21 New onset uveitis in patients with juvenile idiopathic arthritis under biological
therapy
Irina Nikishina1, Olga Kostareva1, Maria Kaleda1, Svetlana Rodionovskaya1, Svetlana
Arsenyeva1, Anna Shapovalenko1, Ekaterina Denisova2
1Pediatric, V.A. Nasonova Research Institute of Rheumatology, Moscow, Russian Federation;
2Pediatric, Helmgoltz Moscow Research Institute of Eye Diseases, Moscow, Russian Federation
Correspondence: Irina Nikishina
Introduction: Biological agents (BA), especially TNF inhibitors, are high efficacy
options for current therapy for patients (pts) with juvenile idiopathic arthritis
(JIA). They are successfully used not only for the arthritis but also for JIA-associated
uveitis, however, development of uveitis de novo in pts treated with BA is a well-established
paradoxical adverse event.
Objectives: to evaluate the frequency of new onset (no-) uveitis, occurring under
BA therapy in JIA pts, to establish clinical features, which may be associated with
development of such phenomenone.
Methods: retrospective cohort study involved all JIA pts (760) who were treated with
BA in our clinic from 2004 to 2017. All cases of no-uveitis were collected for the
describing of their clinical features in disease onset and course, activity level,
JIA category, exposure to Methotrexate (MTX) and BA, presence of ANA, HLA B27.
Results: among of 760 pts treated with different BA we identified 22 (2.9%) pts (12
female/10 male) with no-uveitis under BA, mostly during etanercept (ETA) therapy (22
cases from 302 ETA courses, 6.6%), 1/120 - in abatacept (ABA) and 1/249 - in adalimumab
(ADA). There are no cases of no-uveitis under other BA Frequency of no-uveitis is
much higher in ETA group (2.46 events per 100 patient-year (PY) vs 0.31 in ABA, and
0.15 in ADA. ETA exposure was 14.7 ± 9.7 months (mo).. A case of no-uveitis under
ABA was observed after 5 mo of therapy in a girl previously treated with infliximab.
1 boy with early JIA onset (in age of 18 mo) developed no-uveitis after 71 mo of ADA
71 mo simultaneously with general response decreasing and successfully switched to
ABA. JIA subtypes were as follows: RF-neg polyarthritis 6 (27%), persistent oligoarthritis
3 (14%), extended oligoarthritis 11 (50%), enthesitis-related arthritis (ERA) - 2
(9%). Average age at JIA onset was 4.5 ± 3.9 yrs. 19/22 patients had high laboratory
activity (CRP 54 ± 23 mg/l; ESR 41 ± 19 mm/h) and severe arthritis before BA initiation.
However most of pts (18/22) achieved 90-100% ACRpedi-response by the uveitis development.
14/22 pts were ANA-positive, 11/22 pts had HLAB27, including 3 pts who had the both
features. Uveitis was occurred earlier in ANA plus HLAB27 positive pts (mean exposure
- 10.7 mo) than in only ANA-positive or HLAB27-positive pts (27.4 mo and 21.6 mo accordingly).
19/22 (86%) of pts received methotrexate (MTX) in mean dosage 11.5 mg/m2/week. There
are no differences in time of uveitis development depending of MTX. In all cases of
no-uveitis BA was switched.
Conclusion: Our study suggested that new onset of uveitis is rare adverse event during
BA therapy in JIA without any known predisposing risk factors.. Such paradoxical effects
may reflect not so much therapy complications, but the delayed implication of natural
character of disease. Development of no- uveitis is more often observed in pts receiving
ETA, especially in pts with early age of JIA onset. High activity aggressive manifestations
at the disease onset and good initial response to BA are typical features for all
pts, who developed this paradoxical effect under BA therapy.
Disclosure of Interest: None Declared
O22 Microparticles as potential biomarkers of disease activity in anti-neutrophil
cytoplasmic antibody – associated vasculitis
Milena Kostić1, Fariborz Mobarrez2, Jelena Vojinović1, Iva Gunnarsson2, Aleksandra
Antović2
1Department of Pediatrics, Clinical Center, Nis, Serbia; 2Department of Medicine,
Rheumatology Unit, Karolinska Institutet, Stockholm, Sweden
Correspondence: Milena Kostić
Introduction: Microparticles (MPs) are irregularly shaped submicron vesicles, which
are released from plasma membrane upon cell activation and during the early phase
of apoptosis. Increased levels of circulating MPs (mainly of endothelial cell origin,
but also platelet derived) correlates with autoinflammatory disease activity, such
as anti-neutrophil cytoplasm antibody (ANCA) – associated vasculitis (AAV).
Objectives: To evaluate levels of activity markers expressed on surface of MPs, during
active disease and remission, compared to healthy control subjects.
Methods: Our study included 48 AAV patients (24 with active and 24 with inactive disease)
and 23 healthy control subjects (age and gender matched). We analyzed the number and
phenotype of MPs in plasma identified by flow cytometry, via labeling with following
monoclonal antibodies: CD142 (tissue factor-TF), anti-H3cit (citrulinated H3 directed
against neutrophil extracellular traps-NETs), anti-pentraxin3 (pentraxin3), HMGB1
(high mobility group box 1 protein-HMGB1), anti-TWEAK (tumor necrosis factor-like
weak inducer of apoptosis-TWEAK), anti-plasminogen (plasminogen), anti-C3a (C3a) and
anti-C5a (C5a). The assessment of vasculitis disease activity was performed using
the Birmingham Vasculitis Activity Score (BVAS), while active disease was defined
as BVAS ≥1 and inactive (remission) as BVAS = 0. Statistical analysis was performed
using GraphPed software.
Results: Half of the patients group (24) had active vasculitis (mean BVAS 6,69 ± 8,76)
and 24 had inactive disease. Plasma levels of MPs expressing TF, NETs, pentraxin3
and HMGB1 in active patients were significantly higher than in those in remission
and healthy controls (p < 0.01, p < 0.0001, respectively). MPs expressing C5a and
C3a were significantly higher in both patients groups compared to controls (p < 0.001).
Additionally, levels of MPs expressing C5a strongly correlated with BVAS (r = 0.78,
p < 0.0001), while there was no significant correlation between other explored markers
and BVAS. Data presented in Table 4.
Table 4
(Abstract O22). Microparticles (MPs) levels in AAV patients with active or inactive
disease and healthy controls
Active AAV
Inactive AAV
Healthy controls
p-value (respectively)
median
IQR
median
IQR
median
IQR
Tissue factor
265
247
174
107
105
84,5
p < 0.01* p < 0.001**
NETs
112
24
103
18
44
35
p < 0.05* p < 0.0001** p < 0.001***
Pentraxin3
1332
1810
347
294,5
184
146,5
p < 0.01* p < 0.0001** ns***
HMGB1
684
452,5
380
258
77
61,5
p < 0.01* p < 0.001** p < 0.001***
TWEAK
131
83
141
102,5
67
53
ns* p < 0.0001** p < 0.05***
Plasminogen
86
23
89
23
44
33,5
ns* p < 0.001** p < 0.01***
C3a
201
91
147
87
89
72
ns* p < 0.001** p < 0.05***
C5a
131
86,5
111
65
51
30
ns* p < 0.001** p < 0.01***
*between active and inactive, ** between active and controls, ***between inactive
and controls
Conclusion: Our results support recently postulated potential role of complement system
in AAV pathogenesis and disease activity. Evaluated proteins expressed on MPs, especially
C5a, could be used as potential biomarkers which might reflect inflammation and disease
activity in AAV patients. Further investigations are necessary to confirm our preliminary
results and to validate the most promising biomarker in AAV.
Disclosure of Interest: None Declared.
O23 Plasmalemma vesicle-associated protein 1 (pv-1) as a marker of active disease
in childhood vasculitis.
Andrea Taddio1, Sarah Abu Rumeileh2, Claudia Bracaglia3, Luigina De Leo4, Rebecca
Nicolai3, Fabrizio De Benedetti3, Alberto Tommasini4, Samuele Naviglio4, Serena Pastore4,
Alessandro Ventura1, Tarcisio Not1
1Institute for Maternal and Child Health - IRCCS "Burlo Garofolo" - and University
of Trieste, Trieste, Italy; 2University of Trieste, Trieste, Italy; 3Division of Rheumatology,
IRCCS Ospedale Pediatrico Bambino Gesù, Rome, Italy; 4Institute for Maternal and Child
Health - IRCCS "Burlo Garofolo" -, Trieste, Italy
Correspondence: Andrea Taddio
Introduction: The endothelial protein Plasmalemma Vesicle-associated protein 1 (PV-1)
is the main component of stomatal and fenestral diaphragms of blood vessels. It regulates
permeability, leukocyte migration and angiogenesis [1]. Considering the central role
of the endothelium in vasculitis pathogenesis and the lack ofspecific biomarkersfor
the clinical diagnosis and management of this group of complex disorders, we have
investigated the levels of PV-1 among children with vasculitis and their association
with disease activity or remission.
Objectives: To determine, for the first time, serum levels of endothelial protein
PV-1 in a population of patients with vasculitis and healthy controls and possibly
to assess the role of PV-1 to serve as a diagnostic biomarker in vasculitis disorders
in childhood and/or to monitor disease activity and severity.
Methods: A case-control matched for age study was conducted including 62 healthy young
people and 35 children with active vasculitis and other inflammatory diseases with
vascular involvement: 18 patients with Pediatric Systemic Lupus Erythematosus (pSLE),
9 with Juvenile Dermatomyositis (JDM), 2 with Kawasaki Disease, 2 with leukocytoclastic
vasculitis, 2 glomerulonephritis, 1 Central Nervous System Vasculitis, 1 Henoch-Schönlein
Purpura (HSP). PV-1 serum levels were also measured in 9 children in clinical remission
(2 SLE, 2 JDM, 3 HSP, 1 Kawasaki disease, 1 Hughes-Stovin Syndrome). Measurement of
PV-1in blood serum (expressed in ng/ml) was performed using ELISA assay following
the manufacturer’s (Biomatik) instructions.
Results: Patients with active disease showed significantly higher concentrations of
PV-1 than healthy controls (p < 0.001) and patients with inactive disease (p < 0.001)
(Table 5). Optimal serum PV-1 cut-off to identify patients with active vasculitis
was found to be 0.78 ng/ml, which achieved on receiver operating characteristic (ROC)
curve analyses an accuracy of 0.90, with 74% sensitivity and 92% specificity. Different
diseases did not show significant differences regarding levels of PV-1.
Table 5
(abstract O23). See text for description
Patients
Controls N = 62
Acute Vasculitis N = 35
Remission vasculitis N = 9
PV – 1 (ng/ml) Median (interquartile range)
0.221 (0.082 – 0.436)
1.818 (0.746– 3.970)
0.316 (0.203 – 0.606)
p value
< 0.001
< 0.001
Conclusion: PV-1 could represent a specific marker of disease activity in vasculitis
disorders in childhood.
1. Guo L, Zhang H, Hou Y, et al. Plasmalemma vesicle–associated protein: A crucial
component of vascular homeostasis (Review). Exp Ther Med 2016; 12:1639–44.
Disclosure of Interest: None Declared.
O24 Takayasu arteritis in childhood: retrospective experience from a tertiary referral
center in South India
Sathish Kumar1, Ruchika Goel2, Debashish Danda2
1Pediatric Rheumatology, Department of Pediatrics, Christian Medical College, Vellore,
India; 2Department of Clinical Immunology and Rheumatology, Christian Medical College,
Vellore, India
Correspondence: Sathish Kumar
Introduction: Takayasu arteritis (TAK) is an idiopathic large-vessel vasculitis affecting
the aorta and its major branches. Although the disease rarely affects children, it
does occur, even in infants. The untreated inflammation often leads to narrowing or
ectasias of aorta and its direct branches with or without pulmonary and coronary involvement.
It’s a rare medical condition but we in our tertiary care center have collected the
second largest single center series of patients over the past 16 years.
Objectives: To evaluate the clinical features, disease activity, treatment and outcome
of childhood TAK in a tertiary center in South India
Methods: We analyzed a retrospective case series of children fulfilling the TAK classification
criteria of the European League against Rheumatism and the Paediatric Rheumatology
European Society. Data has been collected in a retrospective manner from our institute’s
electronic medical records (EMR) for childhood onset TAK. Data regarding demographics,
clinical features, treatments, and outcomes were recorded. Baseline data including
age, gender, disease duration, angiographic type, the extent of clinical disease using
DEI.Tak, CRP, and ESR were collected. Disease activity was assessed by a composite
clinical score namely ITAS-A (CRP). At each visit, active disease was defined as
1. Clinical activity by the presence of any one of the following:
1a. ITAS ≥ 2 (not attributable by in-stent restenosis) or
1b. ITAS-A (CRP) ≥ 3, but at least one point should be contributed by clinical criteria
as in ITAS proforma
2. Activity by imaging by presence of de Novo lesion on follow-up angiography or stenosis
of the same vessel extending beyond stent margins
3. Laboratory criteria of activity were defined by persistently raised CRP as well
as ESR on 2 consecutive visits without any alternative explanation like infection
Results: 100 children with juvenile-onset TAK were included in this study over the
past 16 years. Out of 100 children with TAK, 30 were male and 70 were female. Median
age at onset was 14 years and mean duration of delay in diagnosis was 7 months (4-24
months). The most common clinical features at presentation were pulse abnormality
(67%) followed by arterial hypertension (62%), claudication (40%) and systemic symptoms
like fever and fatigue (36%).
Past, present history of tuberculosis or tuberculosis after treatment was seen in
6 patients while 2 patients had been treated empirically for TB. At presentation,
median ITAS 2010 score was 9 (4-15), DEI. Tak was 9 (6-13) and TADS was 7 (4-11).
The full angiographic profile was performed for 97 patients. Rest of the patients
had limited area imaging. Type 5 was the commonest followed by type 4 and type 1.
Aneurysms or ectasias with or without stenosis seen in 7 patients
Treatment included corticosteroids (85%), combined with MMF in most cases (51), azathioprine(15),
methotrexate (9) and tocilizumab (5) were reserved for severe and/or refractory cases.
Mean follow-up duration was 33 months (12-61). Delta TADS calculated in 75 patients
was 0 (0-1) and last visit ITAS and ITAS-A CRP was 0 (0-1). Disease course was persistently
stable in 39, relapsing in 16, persistent active in 5 children. 1 child expired during
follow-up.
Conclusion: Improved awareness of TAK is essential to secure a timely diagnosis. The
initial symptoms and signs are non-specific, and a high index of suspicion is needed
if the diagnosis is to be made. The investigation and management of Takayasu’s disease
can prove difficult.
Disclosure of Interest: None Declared.
Oral Presentations 2
O25 Single cell RNA-sequencing of bone marrow macrophages identifies a distinct subpopulation
in systemic JIA with features of interferon response, endocytic vesicles and phagocytosis
Grant Schulert1, Nathan Salomonis2, Sherry Thornton1, Alexei Grom1
1Pediatric Rheumatology, Cincinnati Children's Hospital Medical Center, Cincinnati,
OH, United States; 2Biomedical Informatics, Cincinnati Children's Hospital Medical
Center, Cincinnati, OH, United States
Correspondence: Grant Schulert
Introduction: Macrophage activation syndrome (MAS) is a life-threatening complication
of systemic juvenile idiopathic arthritis (SJIA), characterized by activation and
expansion of cytolytic lymphocytes and macrophages with hemophagocytic properties.
Recent work by us and others has shown that emergence of MAS is associated with a
surge in IFN-gamma and IFN-induced chemokines; however, previous gene expression studies
failed to demonstrate this IFN-induced signature in peripheral blood cells. However,
prior studies in SJIA and MAS have been limited by a failure to examine key myeloid
effector cells, specifically activated macrophages or histiocytes which traffic to
tissue including bone marrow during MAS.
Objectives: Utilize single-cell RNA-sequencing to identify specific gene expression
signatures of bone marrow macrophage populations in SJIA and MAS.
Methods: Cell sources include unused portions of bone marrow aspirates obtained as
part of a diagnostic workup and interpreted as normal were obtained from the Cincinnati
Children’s Hospital Immunopathology lab, as well as cells obtained from a bone marrow
biopsy from a newly diagnosed SJIA patient. Macrophage single cell suspensions were
obtained using cell sorting for populations expressing the monocyte and macrophage
surface markers CD14 and CD163 while excluding cells expression the granulocyte/monocyte
marker CD15, prior to loading onto the Fluidigm C1 Single-Cell Auto Prep System. Extracted
RNA was converted into cDNA and sequenced as a pooled library, and aligned to the
human Ensembl transcriptome using Kallisto through AltAnalyze version 2.1.1.
Results: Three independent control samples yielded 180 single cells which passed quality-control
filtering. While there was substantial inter-individual variability, using principle
component analysis and Iterative Clustering and Guide-gene Selection, a core set of
approximately 1400 genes were identified that contributed to the heterogeneity of
normal bone marrow macrophage population. Control macrophages formed at least three
primary cellular clusters, which were distinguished based on expression of genes associated
with inflammatory responses, GM-CSF signaling, and aurora B signaling. 61 single bone
marrow macrophages were captured from a patient with newly diagnosed SJIA with active
systemic features, arthritis, marked anemia and relative thrombocytopenia, but lacking
other overt signs of MAS, who underwent bone marrow biopsy as part of the diagnostic
evaluation. Expression profiles were broadly similar to control macrophages by PCA,
and all macrophage clusters were represented. However, a distinct subpopulation of
bone marrow macrophages from the SJIA patient was identified that exhibited markedly
altered transcriptional profiles. Compared to other macrophages within the cluster,
this SJIA macrophage population showed alterations in gene pathways including cellular
response to interferon gamma (adjusted p = 1.35e-14), endocytic vesicle membranes
(p = 8.44E-14), phagosome (p = 2.98e-9) and vesicle-mediated transport (p = 1.05E-07).
These cells showed a proinflammatory gene expression signature, including significant
enrichment for genes regulated by NF-kB and STAT1. This included S100A12, which is
highly expressed in patients with SJIA and MAS and was markedly elevated in serum
from this patient.
Conclusion: We identify a distinct subpopulation of bone marrow macrophages in an
SJIA patient with features associated with emergence of MAS, including interferon
response, phagocytosis and vesicular transport. This demonstrates the importance of
studying these effector cells at the sites of inflammation, and suggests that tissue
macrophages may be a key source of IFN-induced products during MAS. Together, these
data show that single cell gene expression profiling of bone marrow macrophages can
identify reproducible cellular clusters as well as potential biologically relevant
subpopulations and pathways perturbed during inflammatory disorders.
Disclosure of Interest: G. Schulert Consultant for: Novartis, N. Salomonis: None Declared,
S. Thornton: None Declared, A. Grom Grant/Research Support from: NovImmune, AB2Bio,
Consultant for: Novartis, Juno.
O26 Adjudication of infections from the pharmacovigilance in juvenile idiopathic arthritis
patients (pharmachild) treated with biologic agents and/or methotrexate with a focus
on opportunistic infections
Gabriella Giancane, Joost Swart, Elio Castagnola, Andreas Groll, Gerd Horneff, Hans-Iko
Huppertz, Dan Lovell, Tom Wolfs, Michael Hofer, Ekaterina Alexeeva, Violeta Panaviene,
Susan Nielsen, Jordi Anton, Florence Uettwiller, Valda Stanevicha, Maria Trachana,
Fabrizio De Benedetti, Constantin Ailioaie, Elena Tsitsami, Sylvia Kamphuis, Troels
Herlin, Pavla Dolezalova, Gordana Susic, Berit Flato, Flavio Sztajnbok, Elena Fueri,
Francesca Bovis, Francesca Bagnasco, Angela Pistorio, Alberto Martini, Nico Wulffraat,
Nicolino Ruperto
Pediatria II, Reumatologia; PRINTO, Istituto Giannina Gaslini, GENOA, Italy
Correspondence: Gabriella Giancane
Introduction: Pharmachild is a pharmacovigilance registry on children with JIA treated
mainly with biologics ± methotrexate (MTX). Little evidence exists in literature about
the role of JIA or its immunosuppressive therapy in determining infections, especially
caused by opportunistic pathogens.
Objectives: To provide an update on opportunistic infections (OI) revised by an independent
Safety Adjudication Committee (SAC) (3 pediatric rheumatologists and 2 pediatric infectious
disease specialists).
Methods: The participating centres were asked to report all infections encountered
by their JIA patients. PRINTO and the medical monitor (MM) classified events based
on MedDRA dictionary. Moderate/serious/severe/very severe infections were then revised
blindly by the SAC, who were asked to answer 6 questions. The events with consensus
of at least 3/5 experts on the first 3 questions (‘Is this an infection?’, ‘Is it
common?’, ’Is it opportunistic?’) were retained for the analysis. With referral to
the recommendations by Withrop et al.
1, for the first time a list of opportunistic infections in children with JIA on immunosuppressive
therapy was elaborated and approved by consensus, through three Delphi steps.
Results: A total of 772 safety events related to 634 patients were submitted to the
Safety Adjudication Committee. 689 (89.2%) events received consensus among the experts
on the 3 questions and, of these, 682 (99.0%) were considered as infections, corresponding
to 53 High Level Term (HLT) including 153 different Preferred Terms (PT), according
to MedDRA dictionary. Among the 682 infections, 603 (88.4%) were defined by the experts
as common and 119 (17.4%) as opportunistic. For 92 (60%) of the 153 PT, the MM and
SAC used the same PT, while the remaining 40% was adjudicated by a third examiner,
who analyzed again the case reports and assigned the PT which was the most appropriate
taking into account the experts’ opinion. A final number of 52 HLT emerged and, among
them, herpes viral infections, tract respiratory infections and EBV were the most
frequent (Table 6). Analyzing the infections by PT, 151 different PT resulted. Of
them, the experts adjudicated: 22 as OI, 117 as not OI, 8 discordant and 4 not evaluable.
Comparing the experts’ adjudication with the approved list of OI by PT, there was
full agreement for the 22 PT classified as OI, while 26/117 (22.2%) PT resulted in
the list, but were not classified as OI by the experts.
Table 6
(Abstract O26). The most frequent HLT for the 682 infections with agreement of at
least 3/5 experts on the first 3 questions. (N: number of infections)
HLT
N
%
Herpes viral infections
265
38.9
Lower and upper respiratory tract and lung infections
93
13.6
Epstein-Barr viral infections
38
5.6
Abdominal and gastrointestinal infections
32
4.7
Tuberculous infections
29
4.3
Candida infections
17
2.5
Influenza viral infections
14
2.1
Streptococcal infections
14
2.1
Salmonella infections
9
1.3
Conclusion: Our preliminary analysis showed a significant number of opportunistic
infections in JIA patients on immunosuppressive therapy, which was mostly confirmed
in the list of opportunistic infections approved by the experts. Further analysis
on the correlation with medications is ongoing.
Disclosure of Interest: G. Giancane: None Declared, J. Swart: None Declared, E. Castagnola:
None Declared, A. Groll: None Declared, G. Horneff: None Declared, H.-I. Huppertz:
None Declared, D. Lovell: None Declared, T. Wolfs: None Declared, M. Hofer: None Declared,
E. Alexeeva: None Declared, V. Panaviene: None Declared, S. Nielsen: None Declared,
J. Anton: None Declared, F. Uettwiller: None Declared, V. Stanevicha: None Declared,
M. Trachana: None Declared, F. De Benedetti: None Declared, C. Ailioaie: None Declared,
E. Tsitsami: None Declared, S. Kamphuis: None Declared, T. Herlin: None Declared,
P. Dolezalova: None Declared, G. Susic: None Declared, B. Flato: None Declared, F.
Sztajnbok: None Declared, E. Fueri: None Declared, F. Bovis: None Declared, F. Bagnasco:
None Declared, A. Pistorio: None Declared, A. Martini Grant/Research Support from:
Starting from 1 march 2016 I became the Scientific Director of the G. Gaslini Hospital,
therefore my role does not allow me to render private consultancies resulting in personal
income. I perform consultancy activities on behalf of the Gaslini Institute for the
following companies: Abbvie, Boehringer, Novartis, R-Pharm The money received for
these activities are directly transferred to the Gaslini Institute's bank account.,
N. Wulffraat: None Declared, N. Ruperto Grant/Research Support from: The G. Gaslini
Hospital, which is the public Hospital where I work as full time public employee,
has received contributions from BMS, Hoffman-La Roche, Janssen, Novartis, Pfizer and
Sobi for the coordination activity of the PRINTO network. This money has been reinvested
for the research activities of the hospital in fully independent manners besides any
commitment with third parties., Speaker Bureau of: Abbvie, Ablynx, AstraZeneca, Baxalta
Biosimilars, Biogen Idec, Boehringer, Bristol Myers Squibb,, Eli-Lilly, EMD Serono,
Gilead Sciences, Janssen, Medimmune, Novartis, Pfizer, Rpharm, Roche, Sanofi.
O27 Use of whole-body magnetic resonance to identify potential diagnostic clues in
children with fever of unknown origin (FUO)
Sara Signa1, Giorgio Stagnaro2, Roberta Caorsi1, Francesca Minoia1, Paolo Picco1,
Angelo Ravelli1, Gian Michele Magnano2, Maria Beatrice Damasio2, Marco Gattorno1
1U.O. Pediatria II, Instituto Giannina Gaslini, Genova, Italy; 2U.O. Radiologia, Instituto
Giannina Gaslini, Genova, Italy
Correspondence: Sara Signa
Introduction: Whole-body magnetic resonance imaging (WBMRI) is a fast and accurate
method to detect diseases throughout the entire body without exposure to ionizing
radiation. Possible emerging applications for this technique include rheumatologic
field and evaluation of fever of unknown origin (FUO).
Objectives: To evaluate the ability of WBMRI to identify significant potential diagnostic
clue(PDC) in patients presenting a non specific inflammatory clinical picture.
Methods: We retrospectively collected cases of pediatric patients followed in a single
pediatric rheumatology center who underwent WBMRI between January 2010 and December
2015 for the following indications: i) FUO(temperature greater than 38.3 °C for more
than three weeks or failure to reach diagnosis after one week of investigations),
iii) recurrent fever, iii) persistent low grade fever with evidence of elevation of
acute phase reactants and/or other clinical symptoms.WBMRI studies were acquired with
coronal and sagittal planes (slice thickness 5 mm) with acquisition of several image
sets with automatic direct image realignment after acquisition creating a whole-body
scan.Sequences include short τ inversion recovery (STIR) and T1-weighted. All studies
have been evaluated twice, the second time according to a predefined checklist, defined
by an experienced radiologist, considering systematically single/multifocal bone lesion,
bone marrow, joint effusion, soft tissues, adenopathies, parenchymal and vessels looking
for PDC.
Results: We collected 105 patients who underwent WBMRI; 24 (23%) of them presenting
FUO, 29 (28%) presenting recurrent fever and 52 (49%) presenting persistent low grade
fever.The mean age of onset symptoms was 7 years and seven months (range: 2 weeks
old- 17 years and 6 months). The mean age of execution of WBMRI was 9 years (range:
5 months old- 19 years and one month). After the whole diagnostic work-out a final
diagnosis was achieved in 34 patients (32%).
PDCs were identified at the first evaluation in 72/105 cases (68.5%) and in 29/105
cases (39%)the identified PDC was useful to the achievement of the diagnosis (7 JIA,
8 systemic infections, 4 monogenic inflammatory diseases, 3 ALPS, 2 Goldbloom’s Syndrome,2
Vasculitis,1 eosinophilic fasciitis, 1 hystiocytosis, 1 neuroblastoma).
Blind re-evaluation of WBMRI allowed the identification of additional PDCs in 51 patients
(14 of them previously negative).In 8 cases the PDC found after re-evaluation were
consistent with the final diagnosis (2 JIA, 2 infectious diseases,,1 neuroblastoma,
1 ALPS, 1 monogenic inflammatory disease, 1Takayasu arteritis).
Conclusion: WBMRI can be a powerful diagnostic tool in patients with FUO. A predefined
checklist increase sensitivity of WBMRI in the identification of PDC.
Disclosure of Interest: None Declared.
O28 Usefulness of magnetic resonance imaging in early assesment of low back pain with
possible inflammatory cause in children
Lovro Lamot1,2, Mandica Vidovic1, Matej Mustapic1, Mirta Lamot1, Ivana Rados1, Karla
Rubelj1, Miroslav Harjacek1,2
1Clinical Hospital center Sestre Milosrdnice, Zagreb, Croatia; 2Univeristy of Zagreb
School of Medicine, Zagreb, Croatia
Correspondence: Lovro Lamot
Introduction: Low back pain (LBP) is a common complaint in adults that often begins
in childhood. Despite the increasing frequency, it is estimated only 24% of children
with LBP visit a doctor. Nevertheless, those patients are often seen in pediatric
rheumatology clinic. Although most of the LBP cases after exclusion of trauma are
caused by benign musculoskeletal disease, a history of sacroiliac (SI) joint tenderness
and/or inflammatory lumbosacral (LS) pain is one of the ILAR classification criteria
for enthesitis related arthritis (ErA), a form of juvenile idiopathic arthritis (JIA)
that includes most of the patients with juvenile spondyloarthritis (jSpA). Recognition
of jSpA particularly early in the course of the disease represents a unique set of
challenges and therefore all of the patients with inflammatory back pain (IBP) and
arthritis or enthesitis should be suspected for jSpA with possible involvement of
SI and other vertebral joints. Since magnetic resonance imaging (MRI) is the preferred
method of assessment both for axial inflammation and other possible musculoskeletal,
infectious and malignant causes of LBP in children, it might be advisable to use it
in the initial assessment of suspected IBP in children.
Objectives: To evaluate the usefulness of early MRI in discovering inflammation of
spinal joints and other possible causes of LBP in children with suspected IBP not
fulfilling ILAR classification criteria for ErA at the time of investigation.
Methods: Thirty five children referred to our pediatric rheumatology clinic due to
LBP lasting for more than three months, who meet ASAS criteria for IBP and had SI
joint tenderness and positive FABRE test on physical examination, participated in
the study. Their average age was 14.2 years (6-18) and 11 (31.4%) of them were boys.
Five study participants (14.3%) had arthritis and 19 (54.3%) had enthesitis confirmed
by physical examination and ultrasound, but none of them meet ILAR criteria for ErA
at the time. Twelve (out of 15) were HLA-B27 positive and 13 (37.1%) had a history
of SpA related disease in a first degree relative. One of the patients had a diagnosis
of ulcerative colitis (UC), and one of psoriasis. All of the participants had normal
CBC and CRP values, with negative ANA and RF. None had neurological symptoms. Contrast
enhanced MRI of SI joints and thoracolumbar spine was performed according to recommended
protocols for the assesment of inflammatory changes within one week after initial
visit on a 1.5 T machine and interpreted by experienced musculoskeletal radiologist.
Results: Nineteen (54,3%) patients had various pathological findings detected by MRI.
Four (11,4%) had signs of inflammation with one having an active sacroiliitis according
to ASAS criteria. Schmorl nodes were discovered in six patients and three of them,
including one with the signs of inflammation, had Scheuermann disease. Two patients
had stress reaction in LS region. Five patients had incipient degeneration of intervertebral
discs. Three patients had disc protrusion without and one with radial nerve compression.
After three months of follow up, 19 patients (54.3%) meet ILAR criteria for ErA, one
for psoriatic arthritis and one, who also had UC, meet criteria for undifferentiated
arthritis.
Conclusion: Differential diagnosis of LBP in children is very wide and it is difficult
to distinguish inflammatory and other causes upon the first encounter with pediatric
rheumatologist based on history and physical examination alone. In our study, all
of the patients with LBP had some characteristics of IBP and ErA, while definite diagnosis
of jSpA was subsequently established in almost 60% of the patients. Interestingly,
20% of them already had inflammatory changes of LS and SI joints discovered by MRI,
while many others had signs of other LBP causes. Therefore, MRI performed early after
referral to pediatric rheumatologist, in all children with suspected IBP, can be very
useful in elucidating the cause of LBP and differentiation of those who need only
symptomatic relief, orthopedic consultation or further follow up in pediatric rheumatology
clinic. High cost of this approach can be justified with the benefit of early therapeutic
intervention in those with established axial inflammation and the avoidance of unnecessary
treatment in those with other causes.
Disclosure of Interest: None Declared.
O29 Efficacy and safety of Canakinumab in patients with HIDS/MKD: results from the
pivotal phase 3 cluster trial
Joost Frenkel1, Jordi Anton2, Philip Hashkes3, Marco Cattalini4, Tamas Constantin5,
Avi Livneh6, Bernard Lauwerys7, Susanne Bensler8, Paivi Miettunen9, Tillman Kallinich10,
Jasmin Kummerle-Deschner11, Yankun Gong12, Eleni Vritzali13, Guido Junge13, Fabrizio
De Benedetti14, Anna Simon15
1University Medical Center Utrecht, Utrect, Netherlands; 2Hospital Sant Joan de Déu,
Barcelona, Spain; 3Shaare Zedek Medical Center, Jerusalem, Israel; 4Pediatric Clinic,
University of Brescia and Spedali Civili di Brescia, Brescia, Italy; 5Department of
Pediatrics, Semmelweis Egyetem, Budapest, Hungary; 6Department of Medicine, Sheba
Medical Centre, Tel-Hashomer, Ramat-Gan, Israel; 7Cliniques Universitaires Saint-Luc
and Université Catholique de Louvain, Brussels, Belgium; 8Department of Paediatrics,
Alberta Children's Hospital, University of Calgary, Alberta, Canada; 9Alberta Children’s
Hospital Research Institute Calgary, Calgary, Canada; 10Charité, Humboldt University,
Berlin, Germany; 11University Hospital Tuebingen, Tuebingen, Germany; 12Novartis Pharma,
Shanghai, China; 13Novartis Pharma AG, Basel, Switzerland; 14IRCCS Ospedale Pediatrico
Bambino Gesú, Rome, Italy; 15Radboud University Medical Centre, Nijmegen, Netherlands
Correspondence: Joost Frenkel
Introduction: Canakinumab (CAN), a fully human, specific, anti-interleukin-1β monoclonal
antibody, has been shown to be efficacious in reducing the frequency of flares and
improving clinical symptoms in patients (pts) with hyper immunoglobulin D syndrome/mevalonate
kinase deficiency (HIDS/MKD)1.
Objectives: Primary objective was to demonstrate that CAN 150 mg every 4 weeks (q4w)
was superior to placebo (PBO) in resolving flare by Day 15 with no new flares over
16 weeks (wks). Secondary objectives included: proportion of pts who maintained optimal
control of disease activity (absence of new flares) between Wk 16 and Wk 40 after
dose prolongation; evaluation of pharmacokinetics (PK), pharmacodynamics (PD) and
safety of CAN in the HIDS/MKD pts.
Methods: The study comprised 4 epochs (E1-4): The study design has been reported earlier2.
In E2, HIDS/MKD pts were randomised (1:1) to CAN 150 mg every 4 wks (q4w) or PBO.
Pts who did not flare in E2 in the CAN group were rerandomised to CAN 150 mg q8w or
PBO/CAN withdrawal in E3. In E3, dose could be escalated up to 300 mg q4w for pts
with a flare. For PK/PD assessments, CAN concentrations and total IL1β at baseline
(Day 1), and trough concentrations at Wk 16 were assessed. Safety assessments included
adverse events (AEs) and serious AEs (SAEs).
Results: Of the 72 HIDS/MKD pts randomised to CAN 150 mg q4w (n = 37) or PBO (n = 35)
in E2, 3 discontinued the study (2 PBO, 1 CAN). The proportion of responders at Wk
16 was significantly higher with CAN vs PBO (`). In E3, 13 (CAN E2 responders) were
re-randomised to CAN 150 mg q8w or PBO while 53 pts completing E2 received open-label
CAN treatment. In E3, the proportion of pts who did not present new flares was numerically
higher in the CAN vs PBO group (Table 7). 22.7% of the HIDS/MKD pts, including pts
treated in open-label maintained disease control with a prolonged dosing interval
(q8w) till Wk 40. 22.7% required uptitration back to original dose 150 mg q4w while
28.8% pts required uptitration to 300 mg q4w. No new safety findings or deaths were
reported in CAN treated pts through E3 (Table 7). The serum clearance and steady state
volume of distribution of CAN (liquid in vial) varied according to body weight, and
were estimated to be 0.14 ± 0.04 L/day and 4.96 ± 1.35 L, respectively. The estimated
half-life of CAN was 25 ± 6.4 days. Total IL-1β serum concentrations showed dose proportional
increase.
Table 7
(Abstract O29). Efficacy results and summary of safety
PBO N = 35
CAN 150 mg q4w N = 37
p-value
Proportion of responders at Wk 16 (E2), n (%)
2 (5.7)
13 (35.1)
<0.002*
Proportion of patients with no new flare at Wk 40 (E3), n (%)
PBO N = 7
CAN 150 mg q8w N = 6
p-value
1 (14.3)
3 (50.0)
0.2168
Safety
PBO N = 35
Any CAN*, E2 N = 68
Any CAN*, E2 + E3 N = 71
Exposure to CAN, pyr
3.2
19.1
51.0
Number of AEs (AE rate/100 pyr)
59 (1818.5)
251 (1313.6)
613 (1201.2)
Number of SAEs (SAE rate/100 pyr)
4 (123.3)
11 (57.6)
20 (39.2)
*Indicates statistical significance (one-sided) at the 0.025 level. #Any patient who
received a dose of CAN during E2 or E3
n = number of patients who responded; N = number of patients evaluated for response.
AE, adverse event; CAN, canakinumab; E, epoch; PBO, placebo; q4w, every 4 weeks pyr,
patient-years; SAE, serious AE ; Wk, week
Conclusion: CAN (150 mg q4w) was efficacious in resolving flare by Day 15 and preventing
new flares in HIDS/MKD patients over 16 weeks. Approximately 23% pts did not flare
with a prolonged dose interval (q8w) at the end of E3 compared to 14% pts who did
not flare when CAN was completely withdrawn. No new safety issues were reported over
40 weeks of treatment; the safety profile was not distinct from previous controlled
studies. The PK/PD results observed with the liquid-in-vial form of CAN were similar
to those observed in CAPS and SJIA.
1. Arostegui JI, et al Arthritis Rheumatol. 2015;67(S10). 2. De Benedetti F, et al.
Ann Rheum Dis. 2016;75(Suppl2):615.
Trial registration identifying number: NCT02059291
Disclosure of Interest: J. Frenkel Grant/Research Support from: Novartis and SOBI,
J. Anton: None Declared, P. Hashkes Grant/Research Support from: Novartis, M. Cattalini:
None Declared, T. Constantin: None Declared, A. Livneh: None Declared, B. Lauwerys:
None Declared, S. Bensler Consultant for: Novartis, SOBI, AbbVie, P. Miettunen: None
Declared, T. Kallinich: None Declared, J. Kummerle-Deschner Grant/Research Support
from: Novartis, Consultant for: Novartis, SOBI, Baxalta, Y. Gong Employee of: Novartis,
E. Vritzali Employee of: Novartis, G. Junge Employee of: Novartis, F. De Benedetti
Grant/Research Support from: Pfizer, AbbVie, Roche, Novartis, Novimmune and BMS, A.
Simon Grant/Research Support from: Novartis, Xoma/Servier, CSL Behring, Consultant
for: Novartis, Takeda, SOBI, Xoma.
O30 Efficacy, safety, pharmacokinetics and pharmacodynamics of Canakinumab in patients
with traps: results from the pivotal phase 3 cluster trial
Marco Gattorno1, Ryoki Hara2, Anna Shcherbina3, Laura Obici4, Segundo Bujan5, Gerd
Hoerneff6, Anette Jansson7, Riva Brik8, Itzhak Rosner9, Alberto Tomassini10, Yankun
Gong11, Eleni Vritzali12, Guido Junge12, Fabrizio De Benedetti13, Helen Lachmann14
1Pediatric Rheumatology, G. Gaslini Institute, Genoa, Italy; 2Yokohama City University,
Yokohama, Japan; 3Clinical immunology Department, Center of Children's Hematology
n.a. D. Rogachev, Moscow, Russian Federation; 4Amyloidosis Research and Treatment
Centre, Biotechnology Research Laboratories, Fondazione IRCCS Policlinico San Matteo,
Pavia, Italy; 5Vall d'Hebron Hospital, Barcelona, Spain; 6Asklepios Clinic, Sankt
Augustin, Munich, Germany; 7Department of Rheumatology & Immunology, Dr. von Hauner
Childrens Hospital, Ludwig-Maximilians-University, Munich, Germany; 8Meyer Children's
Hospital, Rambam Medical Center, Haifa, Israel; 9Rheumatology, Bnai-Zion Medical Center,
Rappaport Faculty of Medicine. Technion, Haifa, Israel; 10Institute for Maternal and
Child Health- IRCCS “Burlo Garofolo”, Trieste, Italy; 11Novartis Pharma, Shanghai,
China; 12Novartis Pharma AG, Basel, Switzerland; 13IRCCS Ospedale Pediatrico Bambino
Gesú, Rome, Italy; 14UK National Amyloidosis Centre, University College London, London,
United Kingdom
Correspondence: Marco Gattorno
Introduction: Interleukin (IL)–1β is known to be a key cytokine in the pathogenesis
of tumour necrosis factor receptor associated periodic syndrome (TRAPS).1 Canakinumab
(CAN) is a fully human monoclonal antibody that specifically neutralises the activity
of IL–1β.
Objectives: The primary objective was to demonstrate that canakinumab (CAN)150 mg
every 4 weeks (q4w) is superior to placebo (PBO) in achieving a clinically meaningful
response [resolution of flare at Day 15 and no new disease flares over 16 weeks (wks)
of treatment] in TRAPS patients (pts). Secondary objectives included: the proportion
of pts who maintained optimal control of disease activity (absence of new flares)
between Wk 16 and Wk 40 after dose reduction; evaluation of pharmacokinetics (PK),
pharmacodynamics (PD) and safety of CAN in TRAPS pts.
Methods: The study comprised 4 epochs: a 12-wk screening epoch (E1), a 16-wk randomised
treatment epoch (E2), a 24-wk randomised withdrawal epoch (E3) and a 72-wk open-label
treatment epoch (E4). TRAPS pts with a flare during E1 were randomised in E2 to receive
CAN 150 mg q4w or PBO. Pts who did not flare in E2 in the CAN group were re-randomised
to CAN 150 mg q8w or PBO/CAN withdrawal in E3. In E3, for pts with a flare, dose could
be escalated up to 300 mg q4w. For PK/PD assessments, CAN concentrations and total
IL-1β at baseline (Day 1), and trough concentrations at Wk 16 were assessed. Safety
assessments included adverse events (AEs) and serious AEs (SAEs).
Results: Of the 46 TRAPS pts randomised to CAN 150 mg q4w (n = 22) or PBO (n = 24)
in E2, 2 pts in the PBO group discontinued the study. The proportion of responders
at Wk 16 was statistically higher with CAN vs. PBO (Table 8). In E3, 9 (CAN E2 responders)
were re-randomised to CAN 150 mg q8w or PBO while remaining pts completing E2 received
open-label treatment. In E3, the proportion of pts with no new flare was numerically
higher in the CAN vs PBO group (Table 8). 53.3% of the TRAPS pts, including pts treated
in open-label maintained disease control with a prolonged dosing interval (q8w) till
Wk 40. While 8.3% pts were up-titrated to 300 mg q4w. No new safety findings or death
were reported in CAN treated pts through E3 (Table 8). The serum clearance and steady-state
volume of distribution of CAN varied according to body weight, and were estimated
to be 0.14 ± 0.04 L/day and 4.96 ± 1.35 L, respectively. The estimated half-life of
CAN was 25 ± 6.4 days. Total IL-1β serum concentrations showed dose proportional increase.
Table 8
(Abstract O30). Efficacy and summary of safety
CAN 150 mg q4w N = 22
PBO N = 24
p-value
Proportion of responders at Wk 16 (E2), n(%)
10 (45.5)
2 (8.3)
0.005*
Proportion of patients with no new flare at Wk 40 (E3), n(%)
CAN 150 mg q8w N = 4
PBO N = 5
p-value
3 (75.0)
2 (40.0)
0.3571
Safety
PBO (N = 24)
Any CAN*, E2 (N = 43)
Any CAN*, E2 + E3 (N = 61)
Exposure to CAN, pyr
2.0
12.1
39.2
Number of AEs (AE rate/100 pyr)
34 (1698.8)
112 (925.7)
265 (676.2)
Number of SAEs (SAE rate/100 pyr)
1 (50.0)
3 (24.8)
5 (12.8)
*Indicates statistical significance (one-sided) at the 0.025 level. #Any patient who
received a dose of CAN during E2 or 3.
n = number of patients who responded; N = number of patients evaluated for response.
AE, adverse event; CAN, canakinumab; E, epoch; PBO, placebo; q4w, every 4 weeks pyr,
patient-years; SAE, serious adverse event; W, week
Conclusion: CAN (150 mg q4w) was efficacious in resolving flare by Day 15 and preventing
new flares in TRAPS patients over 16 weeks. The prolonged dose interval (150 mg q8w)
was sufficient to maintain disease control in approximately 50% TRAPS patients at
the end of epoch 3. No new safety issues were reported over 40 weeks of treatment;
the safety profile was not distinct from previous controlled studies. The PK/PD results
observed with the liquid-in-vial form of CAN were similar to those observed in CAPS
and SJIA.
1.Gattorno M, et al. Ann Rheum Dis. 2016;76(1):1738
Trial registration identifying number: NCT02059291
Disclosure of Interest: M. Gattorno Grant/Research Support from: Novartis and SOBI,
Consultant for: Novartis and SOBI, R. Hara: None Declared, A. Shcherbina: None Declared,
L. Obici: None Declared, S. Bujan: None Declared, G. Hoerneff Grant/Research Support
from: AbbVie, Chugai, Novartis, Pfizer, Roche, A. Jansson: None Declared, R. Brik:
None Declared, I. Rosner: None Declared, A. Tomassini: None Declared, Y. Gong Employee
of: Novartis, E. Vritzali Employee of: Novartis, G. Junge Employee of: Novartis, F.
De Benedetti Grant/Research Support from: Pfizer, AbbVie, Roche, Novartis, Novimmune
and BMS, H. Lachmann Consultant for: Novartis, SOBI, Takeda, GSK, Speaker Bureau of:
Novartis, SOBI.
O31 Evidence based recommendations for corticosteroid tapering/discontinuation in
new onset juvenile dermatomyositis patients from the PRINTO trial
Gabriella Giancane, Claudio Lavarello, Angela Pistorio, Francesco Zulian, Bo Magnusson,
Tadej Avcin, Fabrizia Corona, Valeria Gerloni, Serena Pastore, Roberto Marini, Silvana
Martino, Anne Pagnier, Michel Rodiere, Christine Soler, Valda Stanevicha, Rebecca
Ten Cate, Yosef Uziel, Jelena Vojinovic, Elena Fueri, Angelo Ravelli, Alberto Martini,
Nicolino Ruperto
Pediatria II, Reumatologia; PRINTO, Istituto Giannina Gaslini, GENOA, Italy
Correspondence: Gabriella Giancane
Introduction: At present no clear evidence based guidelines exist to standardize the
tapering and discontinuation of corticosteroids (CS) in juvenile dermatomyositis (JDM).
Objectives: To provide evidence-based recommendations for CS tapering/discontinuation
through the analysis of the patients in the PRINTO new onset JDM trial. Secondary
objective of the study was to identify predictors of clinical remission and CS discontinuation.
Methods: New onset JDM children were randomized to receive either prednisone (PDN)
alone or in combination with MTX or CSA. All children were given initially intravenous
methylprednisolone, and then PDN starting with 2 mg/kg/day. Gradual tapering according
to a specific protocol could lead to the safe dose of 0.2 mg/kg/day by month 6, then
discontinued at month 24. Major therapeutic changes (MTC) were defined as the addition
or major increase in the dose of MTX/CSA/other drugs or any other reasons for which
patients were dropped from the trial. Patients were divided according to clinical
remission (CMAS = 52 and MD global = 0 for 6 continuous months) into two major groups.
Group 1 included those on clinical remission, who could discontinue PDN, with no MTC,
and represented the reference standard for the best clinical outcome. Group 1 was
compared with those who did not achieve clinical remission, without or with MTC (group
2 and 3, respectively). JDM core set measures (CSM) were compared in the 3 groups.
We also calculated the gold standard group (group 1) median change in the CSM in the
first 6 and over 24 months and applied a logistic regression model to identify the
predictors of clinical remission with PDN discontinuation.
Results: 139 children were enrolled in the trial: 47 on PDN, 46 on PDN + CSA and 46
on PDN + MTX. We identified 30 (21.6%) patients for group 1, 43 (30.9%) for group
2 and 66 (47.5%) for group 3. At baseline all 3 groups had a high level of disease
activity with no differences in the CSM. Already in the first 2 months a clear differential
trend in disease activity measures, according to clinical remission status and PDN
discontinuation, could be identified. From the observation of the median change in
the CSM of group 1 in the first 6 months, the following recommendations could be extrapolated:
decrease corticosteroids from 2 to 1 mg/kg/day in 2 months if the MD-global, parent-global,
CHAQ, DAS, CMAS, MMT or Phs measures have a change of at least 50%; from 1 to 0.5 mg/kg/day
in the following 2 months if the MD-global, CHAQ, DAS, CMAS have a change of at least
20%; in the following 2 months (month 4-6) corticosteroids can be tapered up to the
safe dose of 0.2 mg/kg/day, if the disease activity measures remain at low/normal
values. We finally ran a logistic regression model that showed that the achievement
of PRINTO criteria 50-70-90 at 2 months from disease onset, an age at onset >9 years
and the combination therapy PDN + MTX, increase the probability of clinical remission
from 4 to 7 times. (Table 9).
Table 9
(Abstract O31). Logistic regression model for the outcome: achievement of remission
(n/tot: 28/130; 21.5%)
OR (95% CI)
P#
Responder at 2 months:Printo-50 (vs. not responder/Printo-20)
5.41 (1.37 - 21.32)
0.0076
Printo-70 (vs. not responder/Printo-20)
6.90 (1.91 - 24.99)
Printo-90 (vs. not responder/Printo-20)
4.46 (1.08 - 18.38)
Age at onset > 8.53 years (£ 8.53 years)
4.64 (1.69 - 12.71)
0.0017
Treatment group: PDN + MTX (vs. PDN/PDN + CSA)
3.63 (1.30 - 10.09)
0.0116
AUC of the model: 0.80
OR: Odds Ratio; 95% CI: 95% Confidence Interval; P#: Likelihood Ratio test
Conclusion: We propose evidence based specific cut-offs for corticosteroid tapering/discontinuation
based on the change in JDM CSM of disease activity, and to identify the best predictors
for clinical remission and corticosteroid discontinuation.
Trial registration identifying number: NCT00323960
Disclosure of Interest: G. Giancane: None Declared, C. Lavarello: None Declared, A.
Pistorio: None Declared, F. Zulian: None Declared, B. Magnusson: None Declared, T.
Avcin: None Declared, F. Corona: None Declared, V. Gerloni: None Declared, S. Pastore:
None Declared, R. Marini: None Declared, S. Martino: None Declared, A. Pagnier: None
Declared, M. Rodiere: None Declared, C. Soler: None Declared, V. Stanevicha: None
Declared, R. Ten Cate: None Declared, Y. Uziel: None Declared, J. Vojinovic: None
Declared, E. Fueri: None Declared, A. Ravelli Grant/Research Support from: BMS, Hoffman-La
Roche, Janssen, Novartis, Pfizer, Sobi, Speaker Bureau of: AbbVie, BMS, Pfizer, Hoffman
LaRoche, Novartis, Centocor., A. Martini Grant/Research Support from: Starting from
1 march 2016 I became the Scientific Director of the G. Gaslini Hospital, therefore
my role does not allow me to render private consultancies resulting in personal income.
I perform consultancy activities on behalf of the Gaslini Institute for the following
companies: Abbvie, Boehringer, Novartis, R-Pharm The money received for these activities
are directly transferred to the Gaslini Institute's bank account., N. Ruperto Grant/Research
Support from: The G. Gaslini Hospital, which is the public Hospital where I work as
full time public employee, has received contributions from BMS, Hoffman-La Roche,
Janssen, Novartis, Pfizer and Sobi for the coordination activity of the PRINTO network.
This money has been reinvested for the research activities of the hospital in fully
independent manners besides any commitment with third parties., Speaker Bureau of:
Abbvie, Ablynx, AstraZeneca, Baxalta Biosimilars, Biogen Idec, Boehringer, Bristol
Myers Squibb,, Eli-Lilly, EMD Serono, Gilead Sciences, Janssen, Medimmune, Novartis,
Pfizer, Rpharm, Roche, Sanofi.
O32 Evaluation of varicella zoster immune status in children with rheumatic diseases
treated with biologic agents
Elena Moraitis1,2, Lucy Backhouse1, Ian Macdonald1, Jennifer Crooks1, Muthana Al-Obaidi1
1Rheumatology, Great Ormond Street Hospital NHS Foundation Trust, London, United Kingdom;
2Infection, Inflammation, Rheumatology, UCL GOS Institute of child Health, London,
United Kingdom
Correspondence: Elena Moraitis
Introduction: In immunocompromised patients, varicella zoster virus (VZV) infection
can have a very severe clinical course. There is scarce evidence that in adult and
paediatric population with rheumatoid or juvenile idiopathic arthritis and other rheumatic
diseases the treatment with biologic agents may impair the antibody response to vaccines.
However, there is no evidence on whether the use of biologic agents affects in children
the VZV IgG levels acquired after natural infection.
Objectives: The aim of the study is to investigate whether children with a rheumatic
condition treated with biologic agents have a change in their VZV immune status.
Methods: We performed retrospective case notes review of children presenting with
any rheumatic diagnosis requiring treatment with a biologic agent to the Paediatric
Rheumatology services at Great Ormond Street Hospital NHS Foundation Trust between
2009 and 2017, identified from the biologic database. We included in the study the
children with positive VZV IgG prior to the treatment with a biologic agent and with
a minimum of one repeat VZV IgG measurement post initiation of the treatment. A sensitive
VaccZyme
VZV glycoprotein IgG Low Level Enzyme Immunoassay Kit (Binding Site) was used to measure
VZV IgG.
Results: Sixty four patients treated with biologic agents and with two measurements
of VZV IgG prior and post biologic were identified. Forty three patients had positive
VZV IgG acquired prior to treatment and were included in the study. None had received
the VZV vaccine, which is not part of the routine childhood vaccination schedule in
the United Kingdom. After initiation of treatment with biologics, 10/43 (23%, 2 males
and 8 females) had a change in VZV IgG, of which 5/43 (11.6%) had negative VZV IgG,
and 5/43 (11.6%) equivocal. Four had a diagnosis of JIA, 2 systemic vasculitides,
and 4 other rheumatic conditions. Seven patients were treated with anti-TNF agents,
2 patients with Tocilizumab and 1 received Abatacept. Nine patients received concomitant
treatment with other disease-modifying anti-rheumatic drugs (7/9 Methotrexate, 2/9
Azathioprine). For the 10 patients, the median age at the measurement of a positive
VZV IgG pre-biologic was 7 years (range 1-12), median time between the two assessments
was 40.5 months (range 9-105), and the median time between the initiation of the biologic
agent and the post-biologic measurement of VZV IgG was 24 months (range 11-68).
Conclusion: We describe the changes in the VZV immune status post treatment with biologics
in the first cohort of paediatric patients with initial seroconversion following natural
infection. Although limited by the size of the study population, observational nature
and other concomitant medications, our results indicate that biologic agents can affect
the VZV immune status of patients with rheumatic conditions, making them susceptible
to re-infection. Therefore we suggest that all patients on biologic agents should
have the VZV IgG levels re-tested regularly to identify whether the VZV IgG levels
are protective and give prophylaxis as required in the event of varicella contact.
Disclosure of Interest: None Declared.
O33 Prolonged reduced aerobic fitness in adolescents and young adults with juvenile
idiopathic arthritis
Philomine Van Pelt1,2, Tim Takken3, Marco V. Brussel3, Radboud Dolhain4, Johannes
Bijlsma5, Aike Kruize5, Nico Wulffraat1
1rheumatology and pediatric rheumatology, Wilhelmina Children’s Hospital, University
Medical Center Utrecht, Utrecht, Netherlands; 2rheumatology and pediatric rheumatology,
ErasmusMC University Rotterdam, Rotterdam, Netherlands; 3Child Development and Exercise
Center, Wilhelmina Children’s Hospital, University Medical Center Utrecht, Utrecht,
Netherlands; 4rheumatology, ErasmusMC University Rotterdam, Rotterdam, Netherlands;
5rheumatology and immunology, University Medical Center Utrecht, Utrecht, Netherlands
Correspondence: Philomine Van Pelt
Introduction: Aerobic fitness may serve as an important health-related outcome measure
in Juvenile Idiopathic Arthritis (JIA). Reduced aerobic fitness is associated with
cardiovascular morbidity, mortality and osteoporosis in adult patients with chronic
diseases. However, in adolescents and young adults, long-term outcome of aerobic fitness
is unknown. Reduced aerobic fitness was described previously in cross-sectional studies
in children and adolescents with JIA and was more impaired in active disease.
Objectives: Our objectives are to describe the course of aerobic fitness in a longitudinal
cohort of adolescents and young adult JIA-patients who are intensively treated and
to identify the association of clinical variables.
Methods: In a longitudinal cohort, all consecutive patients aged 10-24 years were
included after informed consent. Annual examinations were obtained from demographic
and disease-related items. At baseline and at study-end, aerobic fitness (VO2peak)
was assessed using a graded cardiopulmonary exercise test (CPET) to volitional exhaustion
performed on a cycle ergometer. Absolute and relative VO2peak values were measured
and related to reference values of healthy controls (Z-scores), using one-sample T-tests.
Non-parametric tests were used to evaluate results.
Results: Paired Z-scores were available from 35 patients. 40% were male, median age
at baseline was 13,0 yrs (IQR 4,1), disease duration 7,8 yrs (6,4), JADAS27 3,7 (6,4),
DAS28 1,8 (1,0). 79% of the patients were in DAS28-remission. 17% had systemic JIA,
6% persistent oligoarticular and 74% had a polyarticular course. Baseline and end
Z-scores were reduced compared to healthy controls (ZAbs_base -0,68, IQR2,3 p = 0,01;
Zrel_base -1,33, IQR 2,0, p < 0,01; Zabs_end -1,33, IQR 1,7, p < 0,01; Zrel_end -0,70,
IQR 1,8, p = 0,01) and did not change significantly over time (change Zabs_change
0,65, p = 0,34; Zrel_change 0,63, p = 0,31). At baseline, a higher DAS28 (p = 0,01),
higher JADAS27 (p < 0.01), ESR (p < 0,01), higher thrombocytes (p < 0.01) and the
use of MTX (p = 0.01) were associated with a worse outcome of aerobic fitness. The
greatest improvement of aerobic fitness over time was seen in male patients (p < 0.01)
at baseline. Multivariate analysis showed that a higher DAS28 and male gender were
the most important variables for worse aerobic fitness at baseline, a higher ESR at
baseline was the most important predictor for improving aerobic fitness over time.
Conclusion: Aerobic fitness is significantly reduced in adolescents and young adults
with JIA and does not improve over time, despite intensive treatment. Be aware of
a reduced health outcome into adulthood due to a persistent reduced aerobic fitness
during disease course of JIA, despite low disease activity.
Disclosure of Interest: None Declared.
Autoinflammatory diseases
P1 PFAPA syndrome in large pediatric population: a single center experience
Esra Pehllivan, Amra Adrovic, Sezgin Sahin, Kenan Barut, Ovgu Kul, Ozgur Kasapcopur
Pediatric Rheumatology, Istanbul University, Cerrahpasa Medical School, Istanbul,
Turkey
Correspondence: Amra Adrovic
Introduction: Periodic fever, aphthosis, pharyngitis, and adenitis (PFAPA) syndrome
is an auto-inflammatory condition of unknown etiology. It is the second most common
auto-inflammatory disease in our country, following familial Mediterranean fever.
The strong familial clustering suggest a potential genetic origin of the syndrome
but none of single genetic variants seem to be relevant for the disease etiology.
Previous studies showed that tonsillectomy represents efficient treatment options.
Objectives: Our aim was to explore the main clinical features, response to tonsillectomy
and long–term outcome of PFAPA pediatric patients in a single cohort. We assessed
association of MEFV gene mutation with disease characteristics and treatment response.
Methods: We reviewed medical records of patients who were diagnosed with PFAPA syndrome
between the January 2010 and June 2016. All of the recorded 562 patients were called
by the telephone and 359 (64%) of them were reached. Demographic, clinical and therapeutically
features were taken from the patients’ medical records. Data on clinical course and
the disease outcome were collected by using a structured questionnaire, which was
fulfilled during the phone conversation between investigator and patient’s parents.
Results: A total of 359 patients with PFAPA were examined: 155 (43%) of them were
female. The mean age at disease onset, at diagnosis and at the investigation was 22.79 ± 18.8,
41.7 ± 21.7 and 77.14 ± 31.35 months, respectively. The most common disease feature
at the disease onset was: recurrent fever in 359 (100%), cryptic tonsillitis in 359
(100%) and aphtous stomatitis in 317 (88%). Sixty-three (17%) patients met the criteria
for both PFAPA and FMF. MEFV gene mutation analysis was performed in 93 (25%) patients
and 51 of them (54%) had a heterozygous mutation in exon 10. Surgical treatment was
performed in 158 (43%) patients. Complete clinical remission was achieved in 127 (80.3%)
patients. Six (3%) showed no response to surgical treatment while 25 (15.8%) patients
had a partial response. In patients with partial clinical response, frequency of fever
attacks decreased significantly from 17.5 to 7.3 attack per year (p < 0.05). Among
patients who did not respond to tonsillectomy, 11 (52.4%) were carrier of MEFV heterozygous
mutation in exon 10. There was a statistically significant difference between patients
with and without coexistence of FMF features, according to surgical treatment response
(p < 0.05). The mean age of resolution of PFAPA symptoms in patients who underwent
tonsillectomy was 52 ± 22.4 months and in patients without tonsillectomy 66 ± 22.6 months
(Table 10).
Table 10
(Abstract P1). Clinical characteristics of patients according to coexistence of FMF
Patients with coexistence of FMF (n = 63)
Patients without coexistence of FMF(n = 296)
p
Mean age at disease onset (months ± SD)
27 ± 23
22 ± 16.6
0.562
Mean age at diagnosis (months ± SD)
44 ± 23
43 ± 21
0.274
Male/Female ratio
36/27
168/128
1.0
Mean time interval between fever episodes (weeks ± SD)
3 ± 0.9
3.2 ± 1.4
0.61
Mean duration of fever (days ± SD)
3.6 ± 1.4
3.9 ± 3.6
0.94
Cryptic tonsillitis
63 (100%)
296 (100%)
1.0
Abdominal pain
20 (31.7%)
83 (28%)
0.54
Response to colchicum treatment
18/27 (66%)
6/18 (33%)
0.03
Clinical response to surgical treatment
18/36 (50%)
113/146 (77.4%)
0.002
Conclusion: Although PFAPA symptoms usually resolve before age of eight, some patients’
complaints persist. FMF should be considered in tonsilloadenoidectomy unresponsive
PFAPA patients, especially in endemic regions like Turkey. Tonsilloadenoidectomy seems
to be an effective treatment option for pediatric PFAPA patients.
References:
1. Marshall GS, Edwards KM, Butler J, Lawton AR (1987) Syndrome of periodic fever,
pharyngitis, and aphthous stomatitis. J Pediatr 110:43–46
2. Vanoni F, Theodoropoulou K, Hofer M. PFAPA syndrome: a review on treatment and
outcome. Pediatr Rheumatol Online J 2016;14:38.
3. Batu ED, Kara Eroğlu F, Tsoukas P, et al. Periodic Fever, Aphthosis, Pharyngitis,
and Adenitis Syndrome: Analysis of Patients From Two Geographic Areas. Arthritis Care
Res (Hoboken) 2016;68:1859-1865.
4. Celiksoy MH, Ogur G, Yaman E, et al. Could familial Mediterranean fever gene mutations
be related to PFAPA syndrome? Pediatr Allergy Immunol. 2016;27:78-82.
Disclosure of Interest: None Declared.
P2 through new classification criteria for inherited periodic fevers and PFAPA. An
integrated approach among clinicians and geneticists.
Silvia Federici1, Federica Vanoni2, Francesca Bovis3, Maria Pia Sormani3, Nicola Ruperto4,
Marco Gattorno4 and on behalf of the Expert Committee for the Classification Criteria
in periodic fever
12° Division of Pediatric, Gaslini Institute, Genova, Italy; 2Pediatric Rheumatology
Unit, CHUV, University of Lausanne, Lausanne, Switzerland; 3Biostatistics Unit, Department
of Health Sciences, University of Genoa, Genoa, Italy; 42° Division of Pediatric,
Gaslini Institute, Genoa, Italy
Correspondence: Silvia Federici
Introduction: Provisional Eurofever evidence-based classification criteria for inherited
periodic fever (TRAPS, FMF, MKD and CAPS) have been recently developed and other diagnostic
criteria are available for FMF, CAPS and PFAPA. However, no consensus on how to combine
clinical criteria and results of molecular analysis has been reached so far. We have
recently identified, through a process based on the Delphi techniques (2 subsequent
Delphi surveys), those variables the expert, clinicians and geneticists, consider
as important for the diagnosis of each monogenic periodic fever syndrome and PFAPA.
We also obtained, trough a web-based evaluation a consensus >80% among clinicians
and geneticists on the diagnosis for 269 over 360 patients with monogenic periodic
fever, PFAPA and undefined periodic fever (UPF) randomly selected from the Eurofever
Registry.
Objectives: To identify candidate set of classification criteria for monogenic periodic
fever and PFAPA and to test their sensibility and specificity on the subset of patients
having reached a consensus among experts. To select the best sets of criteria for
each disease to be discussed in a Consensus Conference
Methods: We selected for each disease the clinical variables corresponding to the
3rd quartile considering the total score obtained after the second Delphi survey.
Performing univariate statistical analysis, we subsequently assess the ability of
these variables to classify individual patients as having or not FMF, MKD, TRAPS,
CAPS, PFAPA or UPF according to consensus classification of experts. These variables
could be associated both in a positive or negative way to each disease. At the same
time we assigned to each genotype presented by our patients a score from 5 to 1 on
the basis of the evaluation done by the experts to be able to include the results
of genetic testing in the statistical analysis. In a second step, multivariate statistical
analysis has been performed to obtain different sets of criteria including only positively
associated or positively and negatively associated clinical variables with and without
genetic data. For each criteria the sensitivity, specificity, positive predictive
value (PPV), negative predictive value (NPV) and area under the curve (AUC) were calculated.
The best performing criteria for each disease have been selected and presented to
the expert for voting in a consensus Conference held in Genova in march 2017.
Results: A total of 98 clinical variables derived from the second Delphi survey has
been tested. The univariate analysis identified 15 variables significantly associated
with FMF (6 positively and 9 negatively), 20 with CAPS (12 positively and 8 negatively),
9 with TRAPS (6 positively and 3 negatively), 13 with MKD (11 positively and 2 negatively)
and 15 with PFAPA (5 positively and 10 negatively). 193 criteria derived from the
statistical analysis have been selected (45 for FMF, 50 for CAPS, 44 for TRAPS, 32
for MKD and 22 for PFAPA) to be discussed and voted at the consensus. In addition
criteria already published in the literature and criteria directly proposed by experts
were included for discussion.
Conclusion: Our process led to the identification of the best variables to be included
in the multivariate analysis for the identification of the candidate criteria for
monogenic periodic fever and PFAPA. Next, the ability of candidate criteria to classify
individual patients as having FMF, MKD, TRAPS CAPS or PFAPA have been assessed by
evaluating the agreement between the classification yielded using the criteria and
the consensus classification of the experts. The best classification criteria for
each disease in term of sensibility and specificity have been shown and voted by a
panel of Experts during the Consensus Conference held in Genoa. For CAPS, FMF and
MKD a consensus >80% has been reached for the best genetic/clinical criteria and for
the best clinical criteria while for TRAPS the consensus has been reached only for
the best clinical/genetic criteria. A new round of web-based evaluation is now ongoing
to try to reach a consensus on the clinical criteria for TRAPS as well. Moreover a
consensus has been reached for PFAPA clinical criteria.
Disclosure of Interest: None Declared.
P3 Chronic recurrent multifocal osteomyelitis: case report
Maria Francesca Gicchino1, Mario Diplomatico1, Daniela Capalbo1, Carmela Granato1,
Alma Nunzia Olivieri1
1Department of Women, Child and General and Specialistic Surgery, Università della
Campania Luigi Vanvitelli, Naples, Italy
Correspondence: Maria Francesca Gicchino
Introduction: Chronic recurrent multifocal osteomyelitis (CRMO), also known as chronic
nonbacterial osteomyelitis, is a rare, noninfectious inflammatory disorder that causes
multifocal lytic bone lesions with swelling and pain characterized by periodic exacerbations
and remissions of unclear/unknown pathogenesis.
Objectives: To describe a case of CRMO in a 10 years old girl.
Methods: A 10 years old girl came to our department because of pain in her right shoulder
since the age of 9 years. She did not recall a precipitating event or a trauma, reported
no fever or weakness. There was no relevant personal or family history. Before coming
to our observation an X-ray of her right shoulder revealing an osteolytic lesion and
a PET-CT showing the presence of a pathological high-uptake of the lesion were performed,
and a biopsy of the lesion of the right shoulder was done to exclude a neoplastic
lesion, a bone infection, or a Langerhans cells histiocytosis (LCH). Patient’s bone
biopsy showed infiltration by lymphocytes and neutrophils. No neoplastic cells were
identified. All cultures were negative. LCH was excluded since immunohistochemical
evaluation of bone marrow for CD1a and S100 expression was negative. When she was
admitted to our department she had pain in her right arm and shoulder. Laboratory
results showed a modest increase of inflammation parameters (ESR 34 mm/h, CRP 0,88 mg/dL)
with normal complete blood count, liver and renal function. The abdominal ultrasound
and the chest X-ray were normal so we performed an MRI. On MRI the lesion was hypointense
in T1 and hyperintense in T2 and STIR, suggesting an inflammatory process.Suspecting
a CRMO, anti-inflammatory treatment with naproxen was prescribed and the symptomatology
disappeared. Five months later the patient came back to our department because of
pain and swelling in her right clavicle. The physical examination showed a painful
swelling of the sternal end of the right clavicle. Laboratory results indicated a
modest increase of inflammation parameters (ESR 29 mm/h, CRP 0,98 mg/dL). Clavicle
X-ray showed an osteolytic lesion, ultrasound of sternoclavicular joint revealed articular
effusion. On MRI this lesion was hyperintense in T2 and STIR.
Results: Clinical history, physical signs, instrumental investigations and histopathological
pattern were highly suggestive of CRMO. Anti-inflammatory treatment with naproxen
was started again and the symptoms disappeared. After six months was performed a whole-body
MRI to evaluate the status of disease. The MRI did not show new lesions and previous
bone lesions disappeared.
Conclusion: In a patient with recurrent bone pain CRMO should be considered. The diagnosis
is of exclusion and it is based on the clinical and radiological data. Biopsy is needed
to exclude infectious osteomyelitis, malignancy, LCH. Some authors suggest that biopsy
is not necessary if a patient has classical radiological findings of CRMO, or comorbidities,
such as Crohn's disease. Skeletal manifestations are unifocal or multifocal, and the
involvement of clavicle, sternum or mandible suggest a CRMO diagnosis. Extra-articular
manifestation are gastrointestinal and skin involvement (acne, pustolsis, psoriasis).The
SAPHO syndrome seems to be an advanced state of CRMO. The treatment of CRMO has been
mostly empiric; NSAIDs are the first choice for CRMO treatment. When disease activity
is high or there are complications therapy with bisphosphonates or biologic drugs
such as TNF antagonists (etanercept) or inhibitors of IL-1 (anakinra) should be considered.
Disclosure of Interest: None Declared.
P4 Pluripotent stem cell models of Blau syndrome reveal an IFN-γ-dependent inflammatory
response in macrophages
Yuri Kawasaki1, Sanami Takada2, Naotomo Kambe3, Ryuta Nishikomori4, Tatsutoshi Nakahata1,
Megumu K. Saito1
1Department of Clinical Application, Center for iPS Cell Research and Application,
Kyoto University, Kyoto, Japan; 2Department of Dermatology, Chiba University Graduate
School of Medicine, Chiba, Japan; 3Department of Dermatology, Kansai Medical University,
Hirakata, Japan 4Department of Pediatrics, Kyoto University Graduate School of Medicine,
Kyoto, Japan
Correspondence: Yuri Kawasaki
Introduction: Blau syndrome, or early-onset sarcoidosis, is a juvenile-onset systemic
granulomatosis associated with a mutation in nucleotide-binding oligomerization domain
2 (NOD2). The underlying mechanisms of Blau syndrome leading to autoinflammation are
still unclear, and there is currently no effective specific treatment for Blau syndrome.
Objectives: To elucidate the mechanisms of autoinflammation in Blau syndrome, we sought
to clarify the relation between disease associated-mutant NOD2 and the inflammatory
response in human samples.
Methods: Blau syndrome-specific induced pluripotent stem cells (iPSCs) lines were
established. To precisely evaluate the in vitro phenotype of iPSC-derived cells, the
disease-associated NOD2 mutation of iPSCs was corrected using a CRISPR-Cas9 system.
We also introduced the same NOD2 mutation into a control iPSC line. These isogenic
iPSCs were then differentiated into monocytic cell lineages, and the status of NF-κB
pathway and proinflammatory cytokine secretion were investigated.
Results: IFN-γ acted as a priming signal through the up-regulation of NOD2. In iPSC-derived
macrophages with mutant NOD2, IFN-γ treatment induced ligand-independent, NF-κB activation
and proinflammatory cytokine production. RNA-seq analysis revealed distinct transcriptional
profiles of mutant macrophages both before and after IFN-γ treatment. Patient-derived
macrophages demonstrated a similar IFN-γ-dependent inflammatory response.
Conclusion: Our data support the significance of ligand-independent autoinflammation
in the pathophysiology of Blau syndrome. Our comprehensive isogenic disease-specific
iPSC panel provides a useful platform for probing therapeutic and diagnostic clues
for the treatment of Blau syndrome patients.
Disclosure of Interest: None Declared.
P5 Transcriptional regulatory gene variations could influence expression patterns
and inflammatory propagation in clavicular cortical hyperostosis
Lovro Lamot1,2, Kristina Gotovac Jercic2, Antonela Blazekovic2, Mandica Vidovic1,
Mirta Lamot1, Fran Borovecki2, MIroslav Harjacek1,2
1Clinical Hospital Center Sestre Milosrdnice, Zagreb, Croatia; 2University of Zagreb
School of Medicine, Zagreb, Croatia
Correspondence: Lovro Lamot
Introduction: Clavicular cortical hyperostosis (CCH) is a rare inflammatory bone disorder
of unknown aetiology represented by pain and swelling of the clavicle. Although similar
to chronic nonbacetril/recurrent multifocal osteomyelitis (CNO/CRMO), due to lack
of recurrence and additional inflammatory sites, it can be considered separate disease
in the spectrum. In our previous study microarray gene expression profiling of CCH
patients revealed 974 differentially expressed genes involved in various inflammatory
processes (1). Subsequent qRT-PCR in additional number of patients confirmed significantly
lower expression of ERBB2 gene and higher expression of TRPM3 and TPRM7 transient
receptor potential (TRP) channel genes. Additionally, immunofluorescence microscopy
showed high signal of TRPM3 in blood cells of one CCH patient. Based on described
findings and other studies which showed TRP channels are involved in inflammasome
activation, while ERBB activation promotes protective cellular outcomes during inflammation,
we hypothesized CCH could be autoinflammatory disease, but the mechanisms responsible
for observed expression alterations remained unclear.
Objectives: Identify possible disease causing gene variants in CCH patients using
whole exome sequencing (WES).
Methods: Genomic DNA was extracted from peripheral whole blood samples of three CCH
patients. Targeted exome sequencing was performed using the Nextera Rapid Capture
Exome Kit (Illumina). The sequence library was constructed with 50 ng of genomic DNA
and 100-bp paired-end reads were sequenced on HiSeq 2000 next-generation sequencer
(Illumina). The extracted variants were annotated and filtered using the Variant Studio
software (Illumina) and Variant Interpreter (Illumina).
Results: WES analysis identified 428 shared identical variants among affected individuals.
Thirty of these variants were not associated with a gene, 121 were in ZNF717 gene
and 277 were distributed in 63 other genes. One heterozygous variant in CTBP2 gene,
one in HYDIN gene and six in ZNF717 were classified as likely pathogenic (Table 11).
Table 11
(Abstract P5). Shared identical variants classified as likely pathogenic
Gene
Variant
Coordinate
Transcript
Consequence
dbSNP ID
CTBP2
T > T/A
126727602
rs76555439
HYDIN
GA > GA/G
70896015
NM_032821.2
frameshift_variant, feature_truncation
rs77276171
ZNF717
A > A/T
75786827
NM_001128223.1
stop_gained
rs79635065
ZNF717
C > C/A
75786916
NM_001128223.1
stop_gained
rs78906544
ZNF717
G > G/T
75787127
NM_001128223.1
stop_gained
rs74740396, rs148624740
ZNF717
T > T/TA
75787352
NM_001128223.1
frameshift_variant, feature_elongation
ZNF717
GAA > GAA/G
75787645
NM_001128223.1
frameshift_variant, feature_truncation
rs67117547, rs141065192
ZNF717
G > G/C
75788028
NM_001128223.1
stop_gained
rs77971486, rs150689808
Conclusion: In this comprehensive study “bottom-up” approach was used in order to
elucidate the molecular disease mechanisms of what we believe could be a new disease
entity. Previously performed diligent transcriptome analysis and proof-of-concept
experiment which confirmed the results on a protein level indicated CCH could be induced
by sternoclavicular joint overuse, TRP channel overexpression, inflammasome activation
and reduced protection during inflammation. Interestingly, WES analysis identified
majority of likely pathogenic variants in ZNF717 gene. This gene encodes a Kruppel-associated
box (KRAB) zinc-finger protein, which belongs to a large group of transcriptional
regulators and is therefore involved in the regulation of crucial physiological and
pathological processes (2). Many aspects of these proteins are still essentially unknown,
as is their role in the inflammation, yet it is speculated they increase DNA accessibility
and inflammatory gene transcription (3). Together with possible influence on observed
expression patterns, all of these processes could contribute to CCH evolution.
References
1. Lamot L et al. TRP channels overexpression contributes to inflammasome activation
in clavicular cortical hyperostosis? Ann Rheum Dis 2015;74(Suppl2):146.
2. Lupo A et al. KRAB-Zinc Finger Proteins: A Repressor Family Displaying Multiple
Biological Functions. Current Genomics 2013;14(4):268–278.
3. Chinenov Y et al. Glucocorticoid Receptor Coordinates Transcription Factor-Dominated
Regulatory Network in Macrophages. BMC Genomics 2014;15(1):656.
Disclosure of Interest: None Declared.
P6 A novel phenotype associated with ADAM17 mutations
Sonia Melo Gomes1,2, Ebun Omoyinmi1, Ying Hong1, Glenn Anderson3, William Mufzud3,
William Moore4, Clive Edelsten4, Louise Wilson5, Paul Brogan2
1Rheumatology, GOSH UCL Institute of Child Health, London, United Kingdom; 2Rheumatology,
Great Ormond Street Hospital, London, United Kingdom; 3Pathology, Great Ormond Street
Hospital, London, United Kingdom; 4Ophthalmology, Great Ormond Street Hospital, London,
United Kingdom; 5Genetics, Great Ormond Street Hospital, London, United Kingdom
Correspondence: Sonia Melo Gomes
Introduction: ADAM17 is an important shedding enzyme that regulates the response to
tissue injury and inflammation. Only 2 cases of ADAM17 mutations in humans have been
described thus far: siblings with a homozygous ADAM17 deletion resulting in a severely
truncated protein causing autosomal recessive neonatal inflammatory bowel and skin
disease.
Objectives: The aim of this study was to discover the genetic cause affecting a child
with a novel inflammatory phenotype.
Methods: Whole Exome sequencing was performed using DNA extracted from peripheral
blood for a trio analysis. The Nextera Exome Capture and Hiseq sequencing platforms
were used in this process.
Results: A four-year- old girl presented with extreme photophobia, bloody diarrhoea,
anal fissures from the first weeks of life, and intermittent fevers. Examination revealed
blepharitis, perioral rash and gingival inflammation with hyperthrophy. Feeding difficulties
attributed to gastro-oesophageal reflux led to oral aversion and poor weight gain.
Inflammatory markers were moderately elevated (mean CRP-22 mg/L and ESR-32 mm/h) in
between fevers, and higher (CRP > 150 mg/L) during fevers. Upper gastrointestinal
endoscopy at 10 months of age showed gastritis and duodenitis. Brain MRI showed cerebellar
hypoplasia; corneal biopsy revealed an abnormal cornea and conjunctival epithelium.
Extensive neuro-metabolic investigations performed were normal. Whole exome sequencing
revealed 2 rare heterozygous missense mutations in the ADAM17 gene (p.I50V and p.R215V).
Sanger sequencing confirmed these results, and carrier status in the parents. Both
these mutations were absent from our in-house exome database of 120 exomes; were not
seen in homozygous state in population databases; and were predicted damaging in silico.
Biopsies of oral mucosa, tonsillar and skin tissue were then assessed by electron
microscopy showing patchy structural changes in hemidesmosomes.
Conclusion: We describe the third case of human disease associated to ADAM17, but
with a novel phenotype, similar to conditional knock-out mouse models with severely
reduced ADAM17 sheddase activity, which develop opaque eyes, skin and heart defects
as well as increased susceptibility to dextran sulfate induced colitis. This is in-keeping
with the mutations found in our proband, since they are unlikely to result in the
complete absence of the protein described in the other human cases.
Ongoing functional work will provide further information on how these mutations affect
ADAM17 activity and impact on hemidesmosome structure.
Disclosure of Interest: None Declared.
P7 The impact of gastrointestinal clinical manifestations in autoinflammatory diseases
(AID): lessons from the international Eurofever registry
Alessia Omenetti1, Francesca Bovis2, Joost Frenkel3, Helen J. Lachmann4, Seza Ozen5,
Nicolino Ruperto6, Marco Gattorno6 on behalf of PRINTO and Eurofever Registry
1DINOGMI, Genoa, Italy; 2Biostatistics Unit, Department of Health Sciences,, University
of Genoa, Genoa, Italy; 3University Medical Center Utrecht, Utrecht, Netherlands;
4Division of Medicine, University College London, London, United Kingdom; 5Department
of Paediatric Rheumatology, Hacettepe University, Ankara, Turkey; 6Pediatria II, Gaslini
IRCCS, Genoa, Italy
Correspondence: Alessia Omenetti
Introduction: The spectrum of autoinflammatory diseases (AID) is continuosly expanding
and significant delay in diagnosis may occur if those rare entities are not promptly
identified.
Objectives: To assess the impact and significance of gastrointestinal (GI) clinical
manifestations in a broad cohort of AID patients.
Methods: The web-based international Eurofever registry containing data retrospectively
collected about patients enrolled by 108 partecipating centres from November 2009
to June 2016 was evaluated. When present, each GI manifestation was ranked as occasionally
or persistently present during flares. Development of severe GI complications was
also assessed. To then identify subsets of patients featured by homogeneous patterns
of clinical features, the unsupervised Latent Class (LC) analysis was applied to the
cohort featured by GI manifestations (GI cohort) in the attempt to assign mutually
exclusive class membership based on latent patterns among the observed variables.
Results: The cohort included 1655 patients with confirmed diagnosis of AID. At least
1 GI manifestation was reported in 52.32%. Interestingly, the latter had earlier onset
compared to cohort that did not show GI involvement (5.18 ± 8.18 vs 9.11 ± 10.25,
mean years ± SD). As expected, the majority of FMF, MVK and TRAPS were affected by
GI symptoms whereas CAPS and CRMO were mainly represented in the subset lacking GI
involvement. In the GI cohort (Table 12), during flares LC1 (13%) displayed persistent
abdominal pain together with prolonged diarrhea, and it mainly included majority of
MVK. LC2 (7%) was affected by occasional abdominal pain together with occasional vomiting,
diarrhea and hepatosplenomegaly. LC3 represented the majority of GI cohort (72%) and
presented only occasional abdominal pain while LC4 (8%) was characterized by persistent
abdominal pain occasionally associated with vomiting, diarrhea, and sometime developing
complications such as septic peritonitis and peritoneal adhesions. As expected, the
latter was mostly represented by FMF.
Table 12
(abstract P7). See text for description
n=
LC1
LC2
LC3
LC4
Tot GI Cohort
Total not GI Cohort
Total AID
Total
87
52
666
61
866
789
1655
CAPS
4
7
31
2
44
134
179
CRMO
0
0
28
1
29
323
352
FMF
17
15
274
43
349
28
378
MVK
39
15
56
8
118
4
122
PFAPA
11
2
99
0
112
158
271
TRAPS
7
7
101
5
120
37
158
Undefined
9
5
57
1
72
63
135
Others
0
1
20
2
23
38
60
Conclusion: These data unveiled the unforeseen significance of GI involvement in AID
with implications in the daily clinical management. GI specialists should be aware
of these rare diseases in order to avoid delayed diagnosis and joined work-up protocols
should be developed in order to monitor these signs and prevent potential complications.
A prospective analysis is needed in order to delineate the disease history and potential
evolutions (if any) into more defined GI diseases in the contest of autoinflammation.
Disclosure of Interest: None Declared.
P8 Next generation sequencing-based panel screening in patients with undifferentiated
autoinflammatory diseases: friend or foe?
Abstract withdrawn
P9 Monogenic diseases masquerading as Behçet’s disease in the young
Charalampia Papadopoulou1, Ebun Omoyinmi1, Ariane Standing1, Jessica Macwilliam2,
Clare Pain2, Despina Eleftheriou1,3, Paul Brogan1
1Infection, Inflammation and Rheumatology Section, UCL Great Ormond Street Institute
of Child Health, London, United Kingdom; 2Department of Paediatric Rheumatology, Alder
Hey Children's NHS Foundation Trust, Liverpool, United Kingdom; 3 Centre for Adolescent
Rheumatology, Arthritis Research UK, London, United Kingdom
Correspondence: Charalampia Papadopoulou
Introduction: Monogenic autoinflammatory disorders (AID) and some primary immunodeficiencies
can present early in life with Behçet-like symptoms, and may be mistaken for Behçet’s
disease (BD). Most of these monogenic conditions require alternative treatments than
typically required for BD, and are associated with high morbidity and mortality if
diagnosis and appropriate treatment are delayed. Next generation sequencing (NGS)
undoubtedly offers the opportunity to screen for these diseases more efficiently,
and greatly facilitates diagnosis in this context.
Objectives: To retrospectively describe the clinical and laboratory features, and
molecular diagnoses of 11 paediatric cases referred for suspected BD.
Methods: Retrospective, two-centre, case series. A combination of NGS or conventional
candidate gene screening approaches were utilised to ascertain genetic diagnoses,
facilitated in some cases by functional immunological screening assays. NGS approaches
utilised included targeted exome sequencing (the “Vasculitis and Inflammation Panel”,
VIP); or whole exome sequencing (WES).
Results: Eleven children referred with suspected BD underwent further molecular testing
because of incomplete or atypical BD features, and presentation under the age of 5 years.
Seven/11 patients (58%) were Caucasian; the remaining 4/11 were Asian; 64% were female.
Two cases were siblings from a consanguineous kindred with “familial” BD; and another
had a maternal history of BD. The median age of disease onset was 1.0 (range 0.5-3.0)
years. All had systemic inflammation and oral ulceration; 4/11 had genital ulceration;
4/11 had ocular involvement; and 8/11 had cutaneous manifestations. Nine out of 11
were considered to have a monogenic cause: the final genetic diagnoses were: A20 haploinsufficiency
(n = 1); Hyper IgE syndrome (n = 1); LYN associated AID (n = 1); TRAPS (n = 1), Chronic
Granulomatous Disease (n = 2), Periodic Fever Immunodeficiency and thrombocytopenia
Syndrome (PFIT; n = 2), and pustular psoriasis caused by mutation in AP1S3 (n = 1).
The remaining two cases had a suspected atypical AID caused by a novel variant in
MEFV (n = 1); and a STAT1 variant, as the suspected but as yet unproven monogenic
cause (n = 1).
Conclusion: Rare monogenic disorders can mimic BD, particularly when the presentation
is under the age of 5 years. These data are now informing a strategy to begin to explore
screening for genetic mimics of BD in a UK cohort of children and adults to better
understand the proportion of UK BD patients who may in fact have an underlying genetic
diagnosis.
Disclosure of Interest: None Declared.
P10 Proteomic profile of patients with different autoinflammatory diseases: an approach
to identify new biomarkers
Federica Penco1, Andrea Petretto2, Chiara Lavarello2, Elvira Inglese2, Ilaria Gueli3,
Alessia Omenetti3, Martina Finetti3, Federico Tomasi4, Annalisa Barla4, Arinna Bertoni1,
Claudia Pastorino1, Marco Gattorno3
1Laboratorio di Immunologia delle Malattie Reumatiche Pediatria II, Università degli
Studi di Genova, Genova, Italy; 2Core Facilities, Università degli Studi di Genova,
Genova, Italy; 3U.O. Pediatria II, Instituto Giannina Gaslini, Università degli Studi
di Genova, Genova, Italy; 4Dibris, Università degli Studi di Genova, Genova, Italy
Correspondence: Federica Penco
Introduction: Autoinflammatory diseases are a group of inherited diseases characterized
by early onset and systemic inflammation, often manifesting with unexplained fevers.
These pathologies are usually caused by mutations in genes involved in the regulation
of innate immune response with consequent inflammatory phenotype. The mechanism that
lead to the development of this diseases are not still clear and part are however
genetically undefined.
Objectives: Our aim is to evaluate the differences in the expression of proteins or
pathway in monocytes, and plasma metabolites of patients with some of the best-known
autoinflammatory diseases (CAPS, TRAPS, FMF and MKD) and healthy subjects. The purpose
is clusterize the different disorders to better characterize each pathology and try
to distinguish the genetically undefined pathologies.
Methods: Monocytes (purified form peripheral blood and incubated for 4 hours with
or without LPS) and plasma were collected from patients and healthy donors. The samples
were processed and proteins or metabolites expression evaluated by an High Resolution/Mass
Accuracy Liquid Chromatography Tandem Mass Spectrometry (HR/MA LC MS/MS). PCA analysis
and Person’s correlation were used as quality control of experimental design, while
the statistical analysis was performed with the Perseus software.
Results: We analyze the monocytes and plasma of patients with CAPS, TRAPS, FMF and
MKD. We identified about 4000 proteins of each 3500 are quantified by LFQ approach.
PCA analysis and Person’s correlation show a good reproducibility of data and a good
separation between the different groups. In synchronous way using a cluster analysis
and heatmap, based on a machine learning protein selection, we observed a protein
signature specific for each group of pathology and for each condition of monocytes
treatment. Furthermore we used a supervised multivariate analysis to try to identify
a more specific list of proteins for each pathology: at the moment we obtained a list
of about 40 protein per disease, significantly modulated if compared with healthy
controls and comparing each pathology with the other.
Conclusion: Here, we addressed how an high resolution proteomics approach could be
used to better understand the biology of autoinflammatory diseases. The characterization
of a broad spectrum of proteins and metabolites and their interaction network will
allow us to identify new biomarkers for the different pathologies and better comprehend
and recognize the genetically undefined disorders.
Disclosure of Interest: None Declared.
P11 Through new classification criteria for inherited periodic fevers and PFAPA syndrome:
the patient validation phase
Federica Vanoni1,2, Silvia Federici3, Francesca Bovis4, Mariapia Sormani5, Nicola
Ruperto3, Marco Gattorno3, Michaël Hofer2 and on behalf of the Expert Committee for
the Classification Criteria in periodic fever
1Departement of Pediatric of Southern Switzerland, Ospedale San Giovanni, Bellinzona,
Switzerland; 2Pediatric Rheumatology Unit, CHUV, Lausanne, Switzerland; 3Pediatria
II - Reumatologia, Istituto G. Gaslini, University of Genoa, Genoa, Italy; 4Biostatistics
Unit, Department of Health Sciences, University of Genoa, Genoa, Italy; 5Biostatistics
Unit, Department of Health Sciences, University of Genoa, Genoa, Italy
Correspondence: Federica Vanoni
Introduction: Provisional evidence-based classification criteria for inherited periodic
fever (TRAPS, FMF, MKD and CAPS) have been recently developed. However, no consensus
on how to combine clinical criteria, laboratory test and results of molecular analysis
has been reached so far. Moreover, no validated evidence based set of classification
criteria for PFAPA has been established so far. We conducted a multistep process,
based on a combination of expert consensus and analysis of real patient, to develop
new criteria for inherited periodic fevers and PFAPA syndrome.
Objectives: To obtain a consensus > 80% among experts on the diagnosis of a group
of patients with inherited periodic fevers, PFAPA and undefined periodic fevers.
Methods: A panel of experts (25 clinicians and 8 geneticists) was asked to evaluate,
via a web-based system on the basis of clinical and laboratory data, 360 real patients
affected by AIDs (60 FMF, 60 TRAPS, 60 MKD, 60 CAPS, 60 PFAPA and 60 undefined periodic
fever) randomly selected from the EUROFEVER Registry. PFAPA patient were evaluated
only by clinicians. Experts were asked to classify each patient as having FMF, TRAPS,
MKD, CAPS, PFAPA or undefined periodic fever syndrome. The criterion for agreement
used was 80% consensus among raters.
Results: After four round of evaluation, 281 over 360 patients (78%) were classified
with a consensus > 80% for a specific disease: 36 as FMF, 32 as CAPS, 56 as MKD, 39
as TRAPS, 37 as PFAPA and 81 as undefined periodic fever. In 50 cases the diagnosis
changed respect to the diagnosis of the enrolling center. 25 over 36 FMF patients
were homozygous or compound heterozygous for high penetrance variants while 4 over
36 patients were compound heterozygous with one high penetrance mutation associated
with E148Q variant. 6 over 36 were heterozygous for high penetrance mutations and
1over 36 patients carried only the E148Q variant. Over the 32 CAPS patients, 28 had
a genotype consistent with the disease while 4 patients carried a variant of unknown
significance (V198M). None of the patients showing the Q703K variant or with negative
genetic test was classified as CAPS by the experts. Regarding TRAPS only 1 over 15
patients carrying a low penetrance variants (R92Q, P46L) reached the consensus; none
of the 2 patients with negative genetic analysis reached the consensus. Among MKD
patients, 4 carried the V377I variant in heterozygous date and among these 2 reached
the consensus.
Conclusion: Our process led to a consensus on the diagnosis for 281 patients affected
by inherited periodic fevers and PFAPA. In the subsequent phase we had performed statistical
analysis in which variables coming from the EUROFEVER Delphi survey will be tested
on these patients, to identify the best sets of classification criteria (in term of
sensitivity and specificity) for inherited periodic fever and PFAPA that have been
discussed in the consensus conference held in Genoa in March 2017.
Disclosure of Interest: None Declared.
P12 A preliminary study regarding to the levels of vitamin B12 and folate during colchicine
treatment in children with FMF
Özge Kaba1, Mustafa Çakan2, Şerife Gül Karadağ2, Betül Sözeri3, Gonca Keskindemirci1,
Nuray Aktay Ayaz2
1Pediatrics, Kanuni Sultan Süleyman Research And Training Hospital, İstanbul, Turkey;
2Pediatric Rheumatology, Kanuni Sultan Süleyman Research And Training Hospital, İstanbul,
Turkey; 3Pediatric Rheumatology, Ümraniye Research And Training Hospital, İstanbul,
Turkey
Correspondence: Nuray Aktay Ayaz
Introduction: Familial Mediterranean fever (FMF) is an autosomal recessive autoinflammatory
disease characterized by irregular periodic attacks of serosal inflammation. The gold
standard in treatment is colchicine and it is very potent both in preventing attacks
and subsiding inflammation and by that way avoiding emergence of amyloidosis.
Objectives: There is a hypothesis pointing out to the negative influence of colchicine
on the intestinal absorption of vitamin B12. As colchicine treatment should be used
lifelong, vitamin B12 deficiency due to malabsorption may ensue during the course
of treatment. Although there is an adult study, there is no data for children with
FMF under colchicine treatment.
Methods: Forty-six children with newly diagnosed FMF were enrolled to this prospective
study. They were all started colchicine according to their age (0-5 years:0.5 mg,
5-10 years:1 mg, >10 years: 1.5 mg - maximum 2 mg). Vitamin B12 and folic acid levels
were obtained at the first day of colchicine treatment, 3rd month and 6th month of
the treatment. Mutation analysis of the patients and their clinical findings were
also reported.
Results: Of 46 children involved to the study 18 (39.1%) were females and 28 (60.9%)
were males. The mean age of beginning of the symptoms was 65.3 ± 45.5 months, the
mean age of diagnosis was 97.13 ± 50.2 months. There was family history of FMF in
25 patients (54.3%). Fever was present in 40 (86.9%), peritonitis was in 35 (76%),
pleuritis was in 11 (23.9%), arthritis was in 6 (13%) patients. The mean vitamin B12
values and folate values were significantly decreased during colchicine treatment.
Vitamin B12 levels were 436.28 ± 174.43, 411.63 ± 196.70, 361.67 ± 142.58 at the beginning,
on the 3rd and 6th months of the colchicine treatment respectively. Folate levels
were 10.91 ± 3.45, 9.29 ± 4.37, 9.76 ± 5.64 at the beginning, on the 3rd and 6th months
respectively.
Conclusion: There was significant vitamin B12 and folate level decrease on the 6th
month of colchicine therapy in the children with newly diagnosed FMF. This may be
related to ileal malabsorption of vitamin B12 and jejunal malabsorption of folate.
Although the study was performed among a small number of children with FMF and a limited
time period was reported, prolonged periods may show more significant decrements in
the levels of vitamin B12 and folate.
Disclosure of Interest: None Declared
P13 Longitudinal assessment of iron homeostasis in patients with newly diagnosed familial
Mediterranean fever
Özge Kaba1, Nuray Aktay Ayaz2, Şerife Gül Karadağ2, Mustafa Çakan2
1Pediatrics, Kanuni Sultan Süleyman Research and Training Hospital, İstanbul, Turkey;
2Pediatric Rheumatology, Kanuni Sultan Süleyman Research and Training Hospital, İstanbul,
Turkey
Correspondence: Nuray Aktay Ayaz
Introduction: Familial Mediterranean Fever (FMF) is an autosomal recessive autoinflammatory
disease, characterized by recurrent fever and self-limited paroxysmal attacks of serosal
inflammation.
Objectives: The aim of this study was to evaluate whether iron homeostasis parameters
in patients with AAA was improved by treatment with colchicine or not.
Methods: Forty-six pediatric patients with newly diagnosed FMF were included into
the study. All patients were assessed in the attack-free periods for hemoglobin, hematocrit,
platelet, serum amyloid A, iron, total iron binding capacity, and ferritin before
the colchicine treatment, and on the 3rd and 5th months of colchicine treatment.
Results: We have found that there was a significant increase in mean hemoglobin values
when compared the results of hemoglobin levels before the treatment and on the 5th
month of the treatment (p = 0,048; <0,05). Also, we have observed the same increase
in iron levels (p═0,004). We have seen that there was a significant decrease in ferritin
and SAA levels and platelet counts, reflecting the control of ongoing inflammation.
However, no significant difference was found between mean total iron binding capacity
value, mean hematocrit values (Table 13).
Table 13
(abstract P13). See text for description
Before treatment
3th month of treatment
5th month of treatment
p*
HGB
12,11 ± 1,16 (12,08)
12,20 ± 1,03 (12,05)
12,38 ± 1,02 (12,31)
0,027*
HCT
38,05 ± 3,19 (38,02)
38,63 ± 3,45 (38,30)
38,82 ± 2,81 (38,27)
0,135
PLT
350.932 ± 110.096 (334.600)
310.671 ± 85.475 (309.850)
303.202 ± 81.570 (296.700)
<0,001*
SAA
192,19 ± 295,14 (38,95)
20,26 ± 46,58 (3,85)
9,68 ± 25,81 (3,30)
<0,001*
IRON
53,47 ± 29,56 (50,85)
66,76 ± 35,61 (56,50)
67,41 ± 31,15 (64,00)
<0,001*
TIBC
361,09 ± 52,93 (362,50)
364,78 ± 55,12 (365,00)
372,91 ± 48,92 (366,00)
0,163
FERRITIN
56,63 ± 42,46 (45,00)
34,69 ± 21,34 (30,55)
32,74 ± 23,80 (25,55)
0,002*
Conclusion: In conclusion, we think that colchicine may be effective in balancing
the iron homeostasis that is disturbed by chronic inflammation in FMF.
Disclosure of Interest: None Declared
P14 Population based study of frequency of carrying FMF mutation among Armenian females
Artashes Tadevosyan1, Tigran Avagyan1, Gayane Amaryan2,3,4, Hasmik Hayrapetyan5, Anush
Budumyan1
1Public Health, YEREVAN STATE MEDICAL UNIVERSITY, Yerevan, Armenia; 2Pediatrics, YEREVAN
STATE MEDICAL UNIVERSITY, Yerevan, Armenia; 3National Pediatric Centre for Familial
Mediterranean fever, Yerevan, Armenia; 4Arabkir” Joint Medical Centre - Institute
of Child and Adolescent Health, Yerevan, Armenia; 5Centre of Medical Genetics - Primary
Health Care, Yerevan, Armenia,
Correspondence: Tigran Avagyan
Introduction: The Familial Mediterranean fever (FMF; OMIM 249100) is the most common
autoinflammatory syndrome in the group of hereditary periodic fever syndromes, widespread
in Armenia. The existing information on frequency of carrying the mutations of FMF
gene is hospital based data with subsequent recalculations. To our best knowledge
this is first epidemiological population based study in Armenia.
Objectives: The objective is revealing the frequency of MEFV gene mutations and genotypes
in Armenian female population in Republic of Armenia.
Methods: The proportionate random sampling technique was performed to select 173 females
aged 18-19 years from Yerevan and all marzes (regions) of Armenia. Absence of history
or clinical manifestation of FMF or any autoimmune inflammatory disease/syndrome was
the premium inclusion criteria. Venous blood samples were taken in EDTA containing
vials. Genomic DNA was isolated by means of “Puregene kit” (Gentra System, USA). Molecular-genetic
testing performed in the laboratory of auto inflammation diseases of the Center of
Medical Genetics and Primary Health Care that has an international certificate and
is the best in the region. The most common for Armenian ethnicity 12 mutation were
analyzed: M694V, M694I, M680I (G/C), M680I (G/A), V726A, E148Q, K695R, F479L, R761H,
A744S, P369S, 1692del.
Results: 53 (30.6%) of females from total 173 carry at least one mutation of FMF gene.
From tested 12 mutations only 9 were detected: M694V, M680I, V726A, E148Q, K695R,
F479L, R761H, A744S, and P369S. The most frequent finding was M694V: 19 cases (38.8%),
followed by V726A: 11cases (22.4%) and E148Q: 9 cases (18.4%). These three mutations
cumulatively comprised almost 80% of all. Out of 53 carriers 49 were heterozygous
and four carries two mutations. No homozygous were observed. E148Q mutation was presented
in all four compound heterozygote carriers, two in combination with V726A and two
with P369S.
Conclusion: The frequency of carrying of FMF gene mutation in Armenian non-symptomatic
female population is 30.6%. The most common mutations are M694V, V726A, and E148Q.
The M694V reported as the most frequent mutation in hospital settings as well, causing
the most sever course of disease. Asymptomatic carrier of compound heterozygous genotype
is rare, 2.3% only.
Disclosure of Interest: None Declared
P15 Is routine periodic laboratory work-up necessary for paediatric MEFV (mediterranean
fever) carriers
Balahan Balahan, Nesrin Gülez
Behçet Uz Children s Hospital, Izmir, Turkey
Correspondence: Balahan Balahan
Introduction: Familial Mediterranean fever (FMF) is the most common hereditary auto-inflammatory
disease in the world. Although FMF is inherited autosomal recessively, some heterozygotes
may express disease phenotype and require therapy. On the other hand, some of the
patients presenting manifestations evocative of FMF might happen to be heterozygotes
coincidentally due to the high frequency of MEFV variants in at-risk populations.To
date, there is no study in the literature about how to follow-up MEFV heterozygotes
who do not fulfil FMF criteria.
Objectives: To share a single-center experience of the long-term clinical and laboratory
follow-up of paediatric MEFV carriers.
Methods: The hospital charts of 240 children who were heterozygous for MEFV variants
were retrospectively reviewed. Among them, 119 heterozygous patients fulfilled paediatric
FMF diagnostic criteria and were started colchicine in the first 6 months of follow-up.
Ten patients who fulfilled PFAPA syndrome with one MEFV mutation were excluded. 42
patients did not continue to be followed-up at our unit. So, the rest 69 heterozygotes
were included in this study. Families were advised to record an FMF diary; including
presence of fever, abdominal pain, chest pain, arthritis, arthralgia, myalgia, and
erysipelas like erythema and also were asked to record the duration of these symptoms.
Patients were asked to admit to hospital in case of any advocative FMF symptom lasting
at least 6 hours in order to check acute phase reactants. The children were also followed-up
with their routine analysis and serum amyloid A (SAA) levels every 6 months. The data
of the visits in which an infection was reported were not included. The averages of
all laboratory parameters were then calculated.
Results: 39 children had pathogenic mutations and 30 children had MEFV variants of
unknown significance. The most common MEFV variants were M694V (n = 24) and E148Q
(n = 16). The mean age at admission was 7.3 ± 3 years. The mean follow-up was 3.2 ± 1.6 years
(min:2 max:6 years).
The median of average SAA level was 3.5 (3-38) mg/L and the median of average CRP
level was 0.1 (0.01-1.8) mg/dl and mean of average ESR was 11.3 ± 5.4 (5-27) mm/hour.
The children with pathogenic mutations had significantly higher mean SAA levels than
the children with variants of unknown significance (p = 0.018), however; the mean
CRP and ESR were similar. Besides, the children with pathogenic mutations had significantly
more fever episodes than the children with variants of unknown significance (p = 0.04).
None of the children had persistent proteinuria in the follow-up. We started colchicine
in only 2 patients who were M694V heterozygous because of initiation of typical disease
symptoms accompanied by at least one increased acute phase protein during an attack.
Both patients had family history for FMF and fulfilled the disease criteria after
2 years of follow-up. Neither of these patients had persistently elevated acute phase
reactants in their routine follow-up.
Conclusion: The results of this study suggested that routine clinical follow-up is
useful; however, routine periodic laboratory work-up is not necessary among MEFV carriers.
To the best of our knowledge, this is the first study about the long-term periodic
clinical and laboratory follow-up of MEFV carriers in the literature.
Disclosure of Interest: None Declared
P16 Increased psoriasis frequency in patients with familial Mediterranean fever
Ezgi D. Batu1, Abdulsamet Erden2, Emrah Seyhoğlu3, Alper Sarı2, Hafize E. Sönmez1,
Berkan Armagan2, Selcan Demir1, Emre Bilgin3, Levent Kılıç2, Ömer Karadağ2, Ali Akdoğan2,
Yelda Bilginer1, Ihsan Ertenli2, Sedat Kiraz2, Sule A. Bilgen2, Umut Kalyoncu2, Seza
Özen1
1Division of Rheumatology, Department of Pediatrics, HACETTEPE UNIVERSITY FACULTY
OF MEDICINE, Ankara, Turkey; 2Division of Rheumatology, Department of Internal Medicine,
HACETTEPE UNIVERSITY FACULTY OF MEDICINE, Ankara, Turkey; 3Department of Internal
Medicine, HACETTEPE UNIVERSITY FACULTY OF MEDICINE, Ankara, Turkey
Correspondence: Ezgi D. Batu
Introduction: Familial Mediterranean fever (FMF) is a periodic fever syndrome caused
by MEFV mutations. FMF may be associated with psoriasis in some cases. The prevalence
of psoriasis in normal Turkish population is 0.40%.
Objectives: We aimed to investigate the prevalence of psoriasis among FMF patients
and their relatives.
Methods: FMF patients followed at Hacettepe University Adult and Pediatric Rheumatology
Departments between January and August 2016 were included. FMF patients/their relatives
were accepted to have psoriasis if the diagnosis was made by a dermatologist.
Results: 351 FMF patients (177 adults; 174 children) were included. The median (min-max)
age of adult and pediatric patients was 35 (19-63) and 10 (2-18) years, respectively.
Thirteen (3.7%) FMF patients (11 adults, 2 children) had psoriasis. Psoriasis was
more common in adult than pediatric patients (p = 0.02). Psoriasis was present in
22 (12.4%) of adult and 9 (5.2%) of pediatric patients’ relatives (p = 0.023). The
frequency of psoriasis in ≥1 relatives of FMF patients was found to be 8.8%. Abdominal
pain and fever were significantly higher and arthralgia, arthritis, pleural chest
pain, pericarditis, and erysipelas-like erythema were significantly less frequent
in the pediatric group than adults (p < 0.05).
Conclusion: In our study, psoriasis was more common in FMF patients than the normal
population. Thus, FMF patients should be questioned and carefully examined for psoriasis
lesions and psoriasis family history. Prospective multicenter studies may be important
to find the incidence of psoriasis in FMF.
Disclosure of Interest: None Declared
P17 Periodic fever, aphtous stomatitis, pharyngitis and cervical adentitis (PFAPA)
syndrome. A qualitative study of parent's experiences and strategies
Carina Sparud-Lundin1, Stefan Berg2, Anders Fasth3, Anna Karlsson4, Per Wekell5
1Institute of Health and Care Sciences, Sahgrenska Academy, Goteborg, Sweden; 2Pediatric
Immunology and Rheumatology, The Queen Silvia Children's Hospital, Goteborg, Sweden;
3Dept of Pediatrics, Institute of Clinical Sciences, Sahlgrenska Academy, Goteborg,
Sweden; 4Dept of Rheumatology and Inflammation Research, Sahlgrenska Academy, Instutute
of Medicine, Goteborg, Sweden; 5NU-Hospital Organisation, Dept of Pediatrics, Uddevalla,
Sweden
Correspondence: Stefan Berg
Introduction: Periodic fever, aphthous stomatitis, pharyngitis and cervical adenitis
(PFAPA) syndrome is a fairly common autoinflammatory disease. Still, knowledge of
the effects of the recurrent fever episodes on the child and its family situation
are limited.
Objectives: To examine the experiences of parents regarding the impact of the disease
on the child's general well-being, the family's situation and how the family handles
the associated challenges.
Methods: A qualitative approach was used, applying a modified version of Grounded
theory for design, data collection and analysis. Data was collected from two different
sources:
· Face-to face interviews with one of the parents of children diagnosed with PFAPA
(n = 10, 6 mothers and 4 fathers)
· Communication between parents of children with PFAPA in a closed Facebook group
Results: The child´s well-being was highly affected by the symptoms during episodes.
Parents experienced increased stress with constant fatigue, social constraints of
family life and restricted career opportunities. Hope of a recovery was constantly
present. Parents described a lengthy process, depicted in the following Grounded Theory
core category: From uncertainty to gradually managing and awaiting recovery.
Subcategories (below) describes illness trajectory, illness representation and the
experiences/impacts of the periodic condition:
Uncertainty (Harmlessness - severity)
·Worries · Fear · Frustration
Assurance (Establishment of diagnosis)
·Relief · Reassuring · Explaining · Guilt reducing
Gradually managing (Regularity - unpredictability)
·Suffering · Exhaustion · Isolation · Work-related limitations
Recovery
·Outgrowing PFAPA · Surgery (tonsillectomy)
Conclusion: Getting a diagnosis becomes very important for parents since this reduces
uncertainty and feelings of guilt
Disclosure of Interest: None Declared
P18 Aicardi-Goutières syndrome with a novel mutation in the SAMHD1 gene
Sorina Boiu1, Adrianos Nezos2, Isabelle Melki3, Argirios Dinopoulos4, Erato Atsali1,
Clio Mavragani2, Vana Papaevangelou5, Dimitrios Boumpas6
1Pediatric Rheumatology Unit, Third Department of Pediatrics, "Attikon" University
Hospital, National and Kapodistrian University of Athens, Athens, Greece; 2Department
of Physiology, School of Medicine, National and Kapodistrian University of Athens,
Athens, Greece; 3Laboratory of Neurogenetics and Neuroinflammation, INSERM UMR1163,
Institut Imagine, Paris, France; 4Pediatric Neurology Unit, Third Department of Pediatrics,
"Attikon" University Hospital, National and Kapodistrian University of Athens, Athens,
Greece; 5Third Department of Pediatrics, "Attikon" University Hospital, National and
Kapodistrian University of Athens, Athens, Greece; 6Joint Rheumatology Program, Fourth
Department of Medicine, “Attikon” University Hospital, National and Kapodistrian University
of Athens, Athens, Greece
Correspondence: Sorina Boiu
Introduction: Type I interferonopathies are a clinically heterogeneous group of Mendelian
disorders characterized by constitutive upregulation of type I interferon activity.
Aicardi-Goutières syndrome (AGS) manifests as an early-onset encephalopathy and sometimes
mimics a congenital viral infection. Over time, as many as 40% of patients develop
chilblain skin lesions on the fingers, toes, and ears. Classical AGS phenotype was
associated with mutations in seven genes encoding proteins involved in nucleotide
metabolism and/or sensing: TREX1 (AGS1), RNASEH2A (AGS2), RNASEH2B (AGS3), RNASEH2C
(AGS4), SAMHD1 (AGS5), ADAR1 (AGS6), and IFIH1 (AGS7). Mutations in these genes result
in the induction of type I interferon production and upregulation of interferon stimulated
genes. However, the true extent of the phenotype associated with pathogenic variants
in the AGS-related genes is not yet known.
Objectives: To identify the genetic cause for a phenotype associating severe encephalopathy
and chilblain skin lesions in a twenty years old male.
Methods: A twenty years old male presented since early infancy with violaceous, scaling
lesions of the fingers and toes, resorption of distal phalanges, dystrophic nail changes
and, violaceous lesions on the nose that worsened during the cold season. He was diagnosed
at the age of 7 years with Cornelia de Lange syndrome (CdLS) based on the phenotype
associating severe somatic and psychomotor retardation, microcephaly, hypertrichosis,
synophrys, arched palate, strabismus, hearing loss, cryptorchidism and unilateral
vesicoureteral reflux with kidney scarring. Laboratory investigations showed mild
thrombocytopenia and positive anti-thyroid antibodies. No cerebral imaging was ever
performed. The patient consulted in our Clinic because of his severe peripheral vasculopathy.
The interferon type I signature was determined in the peripheral blood of the patient
and four age/sex matched healthy controls by quantitative PCR for 3 interferon-stimulated
genes (ISGs) (MX-1, IFIT-1 and IFI44); a type I interferon score was calculated as
previously described (Nezos et al. J. Autoimmunity, 2015). For disease gene identification,
a next-generation sequencing (NGS) panel followed by Sanger sequencing were performed.
Results: The type I interferon score was markedly higher (98 times higher) in our
patient compared to healthy controls. Using a next-generation sequencing panel, followed
by Sanger confirmation, the patient was found to be homozygous for a novel c.66delC/p.SerGlnfs*43
variant in SAMHD1. Although not seen before, considering that this lesion is predicted
to act as a biallelic nonsense mutation, and in light of the clinical features, this
result confirmed the diagnosis of an Aicardi-Goutières syndrome. A cerebral MRI will
be performed to evaluate the cerebrovascular involvement in this patient, considering
the risk of intracerebral large vessel involvement with catastrophic cerebral vascular
accidents associated with mutations in SAMHD1.
Conclusion: We describe a novel mutation in SAMHD1 in a patient with AGS, previously
diagnosed with CdLS. It is important to consider the diagnosis of AGS in patients
with neurologic symptoms in the presence of chilblain lesions.
Disclosure of Interest: None Declared
P19 The challenges to diagnose and treat a rare patient with candle syndrome
Martin Boyadzhiev1, Veselin Boyadzhiev1, Lachezar Marinov1, Violeta Iotova1, Sophie
Hambleton2, Ivona Aksentijevich3
1Dept. of Pediatrics, Medical University, Varna, Bulgaria; 2Instituste of Cellular
Medicine, Newcastle University, Newcastle Upon Tyne, United Kingdom; 3National Human
Genome Research Institute, National Institutes of Health, Washington D.C., United
States
Correspondence: Martin Boyadzhiev
Introduction: Chronic Atypical Neutrophilic Dermatosis with Lipodystrophy and Elevated
temperature (CANDLE) is a rare recessively inherited autoinflammatory syndrome, characterized
by early-onset recurrent fevers, skin lesions, periorbital swelling, lipodistrophy,
arthritis, myositis, short stature and hepatomegaly. It is caused by defects in assembly
of the proteasome complex. Thus far, mutations have been identified in 5 genes although
most commonly they are found in the PSMB8 gene.
Objectives: We present a 4 year old boy with a genetically confirmed diagnosis of
CANDLE after presenting to our clinic with the typical clinical and laboratory features
of the syndrome.
Methods: The patient was born at full-term and after uneventful pregnancy, to unrelated
parents. At 20 days postnatal age a maculopapular rash appeared, initially confined
to the extremities, and accompanied by fever. Over the next two years the rash spread
to involve the face and body. He developed periorbital swelling, splenomegaly, leucocytosis,
iron-deficiency anemia and thrombocytopenia. Fever, reaching up to 40 °C, was a consistent
features of disease flares. Three skin biopsies were performed and showed evidence
for perivascular and periadnexial infiltrations, consisting mainly of neutrophils.
Bone marrow biopsy and immunologic investigations were unremarkable. Treatments with
Hydroxychloroquine, Methotrexate and short courses of corticosteroid were tried with
little to no effect.
At the age of 2 years and 10 months, the boy presented to our Clinic. Lipodystrophy,
short stature (-4 SDS), typical facial features, longer IV-th and V-th fingers of
both hands and hepatomegaly were noted in addition to the above features and a clinical
diagnosis of CANDLE syndrome was made. Blood samples from the child and both parents
were sent to NIH for genetic testing, revealing compound heterozygous mutations in
the patient’s PSMB8 gene. The two mutations, p.A92V and p.K105Q, were previously associated
with CANDLE. Each parent is heterozygous for one mutation.
Results: The patient has since been on treatment with oral Methylprednisolone that
proved to be effective in controlling his skin rash and systemic inflammation at the
cost of systemic side effects. Regular follow-up during the next two years showed
nephrocalcinosis, which resolved with symptomatic therapy, and arterial hypertension,
controlled by dual antihypertensive therapy. Preliminary reports in the literature
showed that JAK-inhibitors might be very effective in controlling the disease activity
and we hope to obtain this therapy for our patient.
Conclusion: CANDLE should be considered in patients who present with early-onset severe
inflammation, typical skin rash, and lipodystrophy. Genetic testing is already available
and although therapy is currently challenging, treatment with JAK-inhibitors holds
promise for the future.
Disclosure of Interest: None Declared
P20 Complement endorse the pathogenesis in autoinflammation
Juergen Brunner1, Wilfried Posch2, Evelyn Rabensteiner1, Doris Wilflingseder2
1Pediatrics, Medical University Innsbruck, Innsbruck, Austria; 2Division of Hygiene
and Medical Microbiology, Medical University Innsbruck, Innsbruck, Austria
Correspondence: Juergen Brunner
Introduction: The complement system represents a major part of the innate immune system,
consisting of more than 30 different proteins in plasma and on cell surfaces and can
be activated through three different pathways. Inflammasomes are also part of the
innate immune system. A group of disorders in inflammasomes have been associated with
autoinflammatory diseases (AIDs). Familial cold autoinflammatory syndrome (FCAS),
Muckle-Wells syndrome (MWS) and chronic infantile neurological, cutaneous and articular
syndrome/neonatal onset multisystem inflammatory disease (CINCA/NOMID) were originally
described as three distinct diseases. After the identification of their common genetic
origin, i.e. mutations in the NLRP3 gene on chromosome 1q44, they are perceived as
a continuum of one disease entity and labelled cryopyrin-associated periodic syndromes
(CAPS). Aim of this preliminary study in a patient with MWS was to find a correlation
between the complement system and a disorder of autoinflammation.
Objectives: Aim of this preliminary study in a patient with MWS was to find a correlation
between the complement system and a disorder of autoinflammation.
Methods: PBMCs (peripheral blood mononuclear cells) were isolated from blood of a
healthy donor and of an individual suffering from MWS by density gradient centrifugation
using a Ficoll Paque Premium (GE Healthcare). After washing, PBMCs were incubated
with anti-human CD14 Magnetic Beads (BD) to obtain CD14+ monocytes. These were stimulated
by addition of cytokines (IL-4 and GM-CSF) for five days to generate immature moDCs
(iDCs), which were used for cytokine ELISAs and flow cytometric analyses. IL-6 and
IL-1β cytokine ELISAs were performed according to the manufacturer (Biolegend) following
stimulation of cells using either LPS or differentially complement opsonized HIV-1.
Phenotypical characterization of pathogen-exposed DCs was performed by analyzing characteristic
surface markers (CD11c, DC-SIGN (C-type lectin receptor on DCs, characteristic marker
for iDCs), CD86) by multi-color flow cytometry.
Results: IL-1β production of iDCs is higher in the patients cells than in the cells
of the healthy donor. However, the most significant difference was shown in complement
opsonized iDCs. DC-SIGN is higher expressed in complement opsonized iDCs in patient
cells compared to cells of a healthy donor (37,12% v28,64%). DC-SIGN is also higher
expressed in the iDCs of the MWS patient after stimulation with LPS.
Conclusion: The complement system may play an important role in the development of
an proinflammatory milieu in patients with disorders of autoinflammation. The phenomenon
shown in a patient with MWS has to be reproduced in more MWS patients a well as in
patients with other disorder of autoinflammation.
Disclosure of Interest: None Declared
P21 Recurrent pericarditis: clinical course and treatment in pediatric patients
Camilla Celani1, Diala Khraiche2, Pierre Quartier3, Damien Bonnet2, Brigitte Bader-Meunier1
1Unité d'Immunologie-Hématologie et Rhumatologie Pédiatriques, Hopital Necker, Paris,
France2Cardiologie pediatrique, Hopital Necker, Paris, France3Unitè d'Immunologie-Hématologie
et Rhumatologie Pédiatriques, Hopital Necker, Paris, France
Correspondence: Camilla Celani
Introduction: Recurrent pericarditis is a common complication of acute pericarditis
and affects 15-30% of patients after an initial attack. The etiology is poorly understood
and about 80% of these recurrent pericarditis are "idiopathic". However, some data
suggest an autoimmune or autoinflammatory mechanism. Colchicine associated with nonsteroidal
anti-inflammatory drugs (NSAIDs) is the treatment of choice and the use of other treatments
remains exceptional.
Objectives: To analyze the clinical findings, course and treatment of pediatric patients
with recurrent pericarditis.
Methods: Retrospective monocentric study. Inclusion Criteria :1) patients with at
least twice recurrence of recurrent pericarditis (RP) ; 2) followed at Necker hospital
between 2006 and 2016. Exclusion Criteria : 1)Known history of autoimmune or autoinflammatory
disease.
Results: Thirteen patients (10 F and 3 M) with recurrent pericarditis were included.
The median age at disease onset (first episode of pericarditis) was 11.3 years (range
8 - 17). Two groups of patients could be identified: In group 1 (6 patients), the
recurrent pericarditis occurred after surgical correction of cardiac malformations;
in group 2 (7 patients), there was no history of cardiac disease. During the episodes
of pericarditis, all patients showed fever, chest pain, electrocardiographic changes
and increased white blood cell counts and C reactive protein (CRP median 181 mg/l,
polymorphonuclear cells 13619 g/l,) without differences between the two groups. A
family history of recurrent pericarditis was noted in 2 patients from the first group.
Six patients had pleuritis and/or pneumonia with concomitant pleural effusion (3 patients
in each group). Patients in group 1 had more recurrences than in group 2 (median 2.8
vs 1.5) during the same follow-up period (one year). ANA > 1/640 (Anti-nuclear autoantibodies)
and anti-DNA were present in 2 patients of each groups. The pericardial biopsy was
performed in 5 patients and displayed fibrosis and showed[an inflammatory tissue with
predominance of neutrophils. Initial treatments was aspirin with anti-inflammatory
dose, alone (5 patients) or in combination with Colchicine (4 patients), colchicine
alone (1 patients) or in combination with ibuprofen (1 patient) and antibiotic therapy
(2 patients). To prevent recurrence, six of patients were treated with NSAIDs associated
to colchicine or indomethacin alone. Corticotherapy was required in 2 patients in
group 2 . Anakinra was introduced in one of them because of corticodependence. Clinical
remission was obtained in all patients after discontinuation of the treatment (10
patients) or under treatment (3patients). A heterozygous mutation of R92Q for the
TRAPS gene was found in 1 of the 6 patients studied. No mutation in the MEFV gene
was found.
Conclusion: Recurrent pericarditis can develop after cardiac surgery or can be isolated.
The presence of fever, inflammatory syndrome, pericardial neutrophilic infiltrate,
and the efficacy of anti-IL1 in some patients suggests that some recurrent pericarditis
could be considered as auto-inflammatory disease. Furthermore the existence of familial
cases in two patients suggests a genetic susceptibility. In conclusion early anti
inflammatory treatment should be considered in recurrent pericarditis associated with
an inflammatory syndrome, after rulling out an infection.
Disclosure of Interest: None Declared
P22 Sinogenic subdural empyema in two girls treated with Adalimumab for chronic recurrent
multifocal osteomyelitis (CRMO)
Anne Estmann Christensen, Peter Toftedal
Hans Christian Andersen Children's Hospital, Odense University Hospital, Odense, Denmark
Correspondence: Anne Estmann Christensen
Introduction: Sinusitis is a rare cause of intracranial infection in children. The
morbidity and mortality remains high in reported series.
Objectives: We report two cases of sinusitis complicated with intracranial empyema
in patients treated with tumor necrosis factor-alfa monoclonal antibody (Adalimumab)
for CRMO.
Methods: Case report
Results: The two girls were 11 years old when the infectious complication developed.
Patient 1 had been treated with adalimumab for 15 months, as she developed fever,
acute pansinusitis and orbital cellulitis and abscesses during vacation. She was treated
with intravenous antibiotics and drainage. The treatment was continued after returning
home, and clinical improvement and normalisation of C-reactive protein (CRP) was achieved.
Mild and unspecific symptoms of headache, double vision and swelling of the forehead
remained and was initially thought of as sequela after surgery. Upon further investigation
papilloedema was recognised and a CT scan of the brain showed subdural empyema, intra
cerebral oedema located in the frontal lope, abscesses intra orbital and in the forehead,
continued sinusitis and subperiosteal abscess and osteomyelitis (Potts puffy tumor).
An aggressive rhino- and neuro-surgical approach combined with long-term broad-spectrum
antibiotic treatment was initiated. Despite this, osteomyelitis in the frontal bone
reoccurred several times, latest 1½ year after the initial infection. Immunosuppressive
drugs have been discontinued at the beginning of the infectious period.
Patient 2 was treated with methotrexate for a year and received adalimumab for a period
of 3 months. In these months she developed chronic rhinitis and allergy was suspected
but not confirmed. When psoriasis appeared adalimumab was stopped, but the chronic
sinusitis persisted. Two months later she was admitted with high fever and convulsions.
She had discrete increased white cell count in the spinal fluid and a CT scan showed
pansinusitis but no ostitis or intra cerebral changes. Broad-spectrum antibiotic treatment
was started together with drainage of the sinuses. She improved clinically but CRP
remained elevated. A MRI of the head was planned, but before it was performed another
convulsion occurred. MRI showed pansinusitis, osteitis and subdural empyema. Functional
endoscopic sinus surgery (FESS) was performed and the girl is now improving on long-term
antibiotic treatment. Methotrexate treatment was stopped at the initial symptoms of
meningitis.
Conclusion: Tumor necrosis factor-alfa monoclonal antibody is an efficient anti-inflammatory
drug used in treatment of several inflammatory diseases. The increased risk of infections
is well known. Special attention should be drawn towards symptoms of chronic rhinitis/sinusitis,
as severe intra cerebral complications, such as subdural empyema, may develop. Children
with sinusitis and any neurologic finding, signs of complicated sinusitis such as
Pott's puffy tumor or orbital cellulitis, or persistent headache, fever, or nausea
and vomiting should have additional evaluation for sinogenic subdural empyema.
Written consent for publication has been obtained from the parents.
Disclosure of Interest: None Declared
P23 Spectrum of chronic recurrent multifocal osteomyelitis in a Belgian cohort of
25 children: clinical presentation, imaging, treatment and outcome
Lien De Somer1, Sara Kaut2, Ine Van den Wyngaert2, Davy Christiaens3, Carine Wouters1,
Steven Pans3
1Department of Pediatric Rheumatology, UZ Leuven, Leuven, Belgium; 2Pediatrics, UZ
Leuven, Leuven, Belgium; 3Radiology, UZ Leuven, Leuven, Belgium
Correspondence: Lien De Somer
Introduction: Chronic Recurrent Multifocal Osteomyelitis (CRMO) is a rare auto-inflammatory
disorder, characterized by recurrent episodes of bone pain. Diagnosis can be challenging
and is based on exclusion. Laboratory investigations, radiology and histology are
necessary to make a differential diagnosis with malignancy, infectious osteomyelitis
and juvenile idiopathic arthritis.
Objectives: To document clinical characteristics of pediatric patients diagnosed with
CRMO. To collect data on outcome and management of the disease.
Methods: We reviewed clinical characteristics, radiological data and treatment in
pediatric CRMO patients, followed at the pediatric rheumatology department of the
University Hospital of Leuven.
Results: Twenty-five patients were enrolled, with a mean age of 10.1 years at onset
of the disease. The mean age at diagnosis was 11.2 years, with a mean diagnostic delay
of 14 months. Bone pain was the leading symptom (24/25 patients). On imaging, 148
lesions were identified with an average of 5,9 lesions per patient. The most common
sites of involvement were the vertebrae (37%) and lower limbs (31%), followed by the
pelvis (10%) and clavicle (9%). In almost half of patients (12/25) monotherapy with
NSAIDs was sufficient to obtain remission. The remaining 13 patients received bisphosphonates
as 2nd-line therapy. Methotrexate was prescribed in 5 patients. Two patients needed
further therapy with biologicals: etanercept (n = 2) and tocilizumab (n = 1). Disease
was in remission in 15/25 after a mean time of 22.7 months. The prognosis was worse
in patients with spinal involvement, resulting in more long-term sequelae
Conclusion: We present a unique pediatric cohort of 25 CRMO patients. A typical pattern
of bone involvement could be found on MRI. Lesions presented as areas of bone marrow
edema, with an abnormal hyperintensity on STIR images and/or abnormal hypointensity
on T1-weighted images and/or areas of contrast enhancement. NSAIDs were administered
as first-line treatment. Second-line strategies included bisphosphonates, glucocorticosteroids,
methotrexate, etanercept and tocilizumab
Disclosure of Interest: None Declared
P24 Clinical characteristics of familial Mediterranean fever patients according to
their MEFV mutation
Pelin Esmeray1, Zehra S. Arıcı2, Hafize E. Sönmez2, Yelda Bilginer2, Seza Özen2
1Department of Pediatrics, Hacettepe University Faculty of Medicine, Ankara, Turkey;
2Department of Pediatrics, Division of Rheumatology, Hacettepe University Faculty
of Medicine, Ankara, Turkey
Correspondence: Pelin Esmeray
Introduction: Familial Mediterranean fever (FMF) is the most common autoinflammatory
disease in the world. It is an autosomal recessive disease caused by mutations in
MEFV.
Objectives: The aim of this study is to evaluate the clinical characteristics of FMF
patients in relation with their MEFV mutations.
Methods: 378 patients (0-18 years), who were followed up at the Department of Pediatric
Rheumatology in Hacettepe University, Ankara, Turkey, between January 2005 and October
2016, were included in the study. Mutations in MEFV were evaluated in all of the patients.
The clinical characteristics, disease activity, need for additional treatment and
acute phase reactants were compared according to the mutations of the patients. We
have also compared after dividing patients into two groups as patients with high-risk
mutations (M694V/M694V, M680I/M680I, M694V/M680I) and others.
Results: 36.7% of the patients were homozygous for M694V. 14.3% M694V/M680I, 10% M694V/V726A,
9% M694V/-, 6% M694V/E148Q, 3.7% M680I/V726A, and 2.9% were M680I/M680I. The patients
with M69V/M694V were significantly younger at disease onset than other patients (3 years
vs 4 years, respectively; p = 0,021). In addition, the disease duration, disease activity,
acute phase reactants, and AIDAI(auto-ınflammatory disease activity index) values
were higher and need for additional therapy was more frequent among patients with
M694V/M694V compared to others.The disease activity, acute phase reactants were higher
and need for additional therapy was more frequent in patients with high-risk mutations
than others (Table 14).
Table 14
(abstract P24). Clinical characteristics and laboratory findings of M694V homozygote
patients
Others (n = 240)
M694V-Homozygote (n = 138)
p
Age of diagnosis (years),
5 (0-17)
4 (1-15)
0,098*
Disease duration (years),
6 (0-17)
7 (1-17)
0,004*
Attack status in last 6 months, n (%)
72 (30,0)
65 (47,1)
0,001**
Attacks frequency in last 6 months
2 (1-19)
2 (1-15)
0,722*
Disease activity score
0 (0-5)
1 (0-6)
<0,001*
AIDAI,
0 (0-14)
1 (0-9)
<0,001*
Regular drug use (n = 192), n (%)
86 (64,7)
38 (64,4)
0,973**
Need for addditional treatment (n = 192), n (%)
7 (5,3)
13 (22,0)
<0,001**
n: number of patient; %: Column percentage; *Mann-Whitney U Test; **Pearson chi-Square
Test
Conclusion: The disease phenotype is more severe in patients with high-risk mutations.
Therefore, close follow-up is critical for these patients.
Disclosure of Interest: None Declared
P25 Infection status in children with familial Mediterranean fever (FMF) according
to MEFV
Pelin Esmeray1, Ezgi D. Batu2, Zehra S. Arıcı2, Hafize E. Sönmez2, Yelda Bilginer2,
Seza Özen2
1Department of Pediatrics, Hacettepe University Faculty of Medicine, Ankara, Turkey;
2Department of Pediatrics, Division of Rheumatology, Hacettepe University Faculty
of Medicine, Ankara, Turkey
Correspondence: Pelin Esmeray
Introduction: Familial Mediterranean fever (FMF) is the most common auto-inflammatory
disease which is characterized by recurrent, self-limited flares of fever associated
with polyserositis. The association with infectious disease is not clear except for
the association with helicobacter pylori infection.
Objectives: In this study, the aim was to assess whether there was a tendency to infections.
Methods: 197 children with FMF who were followed at the Department of Pediatric Rheumatology
in Hacettepe University, Ankara, Turkey between May 2016 and October 2016 were included
in the study. In immunodeficiencies, the tendency for infections are defined as acute
otitis media, sinusitis and pneumonia frequencies in a year, intravenous antibiotic
requirement, presence of abscess, presence of recurrent urinary tract infections and
acute gastroenteritis. We have assessed these frequencies in our patient groups according
to mutations and attack frequencies.
Results: 30.4% of the patients were in the M694V homozygote group and 42.1% were in
high-risk mutation(M694V/M694V, M680I/M680I, M694V/M680I) group. When examining M694V
homozygous patients; 3% of patients had more than 4 acute otitis media per year, 6.7%
had sinusitis more than 4 per year, and 1.7 had more than 4 per month of upper respiratory
tract infection. All of the patients had less than 2 pneumonia per year. Only 6.7%
of patients needed intravenous antibiotics. Recurrent urinary tract infection was
present in 3.3% and abscess was 1.7% of patients. 13.4% of the patients had a history
of acute gastroenteritis.
When examining high-risk mutations patients; 3.6% of patients had more than 4 acute
otitis media per year, 4.8% had sinusitis more than 4 per year, and 2.4% had more
than 4 per month of upper respiratory tract infection. All of the patients had less
than 2 pneumonia per year. 4.8% of patients needed intravenous antibiotics. Recurrent
urinary tract infection was present in 3.6% and abscess was 1.2% of patients. 14.4%
of the patients had a history of acute gastroenteritis.
There was no statistically significant difference in the incidence of infection between
mutation groups.
When the patients who had an attack in the last 6 months were examined, there was
no significantly difference in infection status.
When the patients, who had increase in any infection frequency, were evaluated according
to the mutation groups and attack status in the last 6 months, there was no significantly
difference between the groups.
Conclusion: FMF patients are not inclined to develop infections as in immunodeficiencies.
It may be speculated that the abnormality in the innate immune system in these patients
does not significantly inpair host defense. More extensive work on this issue may
be needed.
Disclosure of Interest: None Declared
P26 Clinical characteristics of FMF patients according to age groups
Pelin Esmeray1, Ezgi D. Batu2, Hafize E. Sönmez2, Selcan Demir2, Yelda Bilginer2,
Seza Özen2
1Department of Pediatrics, Hacettepe University Faculty of Medicine, Ankara, Turkey;
2Department of Pediatrics, Division of Rheumatology, Hacettepe University Faculty
of Medicine, Ankara, Turkey
Correspondence: Pelin Esmeray
Introduction: Familial Mediterranean fever (FMF) is the most common autoinflammatory
disease in the world. The disease course could be different in different age groups.
Objectives: In this study, we aimed to study the disease characteristics, treatment
compliance and need for additional treatment according to age groups of FMF patients.
Methods: 378 FMF patients (0-18 years) followed at the Department of Pediatric Rheumatology
in Hacettepe University, Ankara, Turkey, between January 2005 and October 2016 were
included in the study. The patients were evaluated in three groups according to their
age at disease onset; 0-5, 6-11, 12-18 years. The treatment compliance was evaluated
in 199 out of 378 patients according to their present ages.
Results: The disease onset was ≤5 years in 69%, 6-11 years in 26%, and ≥12 years in
5% of patients. Fever symptom was significantly less frequent in the ≥12 years group
than the other age groups. The characteristics of patients according to age groups
(at symptom onset) are presented in Table 15. The disease onset was significantly
younger in patients homozygous for M694V mutation than patients who were negative
for M694V (p = 0.021). 64,6% of 199 patients were compliant to colchicine treatment.
When we grouped these patients according to their present age, ≤5 years group was
the most compliant and the adolescent patients (≥12 years of age) was the less compliant
to treatment (p < 0.05).
Table 15
(abstract P26). See text for description
Onset age
p
≤5 yaş (n = 261)
6-11 yaş (n = 98)
≥12 yaş (n = 19)
Age (year), median (min-max)
10 (2-18)
13 (7-18)
17 (14-18)
<0,001*
Sex, n (%) MaleGirl
143 (54,8)118 (45,2)
56 (57,1)42 (42,9)
10 (52,6)9 (47,4)
0,897**
Attack Status in Last 6 Months n (%)
100 (38,3)
29 (29,6)
8 (42,1)
0,237**
Attack frequency in the last 6 months median (min-max)
2 (1-19)
2 (1-6)
1,5 (1-3)
0,226*
ISSF, median (min-max)
1 (0-6)
1 (0-5)
1 (0-4)
0,103*
Treatment compliance (n = 192), n (%)
84 (66,7)
31 (57,4)
9 (75,0)
0,363**
Need for additional treatment (n = 192), n (%)
12 (9,5)
7 (13,0)
1 (8,3)
0,764**
Conclusion: The disease course may be different in different age groups in FMF. FMF
may present with less typical phenotype when the symptoms start at an older age (less
fever symptom in adolescent. Treatment compliance is very critical in FMF patients
and our results have emphasized that poor compliance is an important problem in especially
adolescent patients.
Disclosure of Interest: None Declared
P27 Oral findings in children with familial Mediterranean fever
Pelin Esmeray1, Ezgi D. Batu2, Zehra S. Arıcı2, Tülin I. Keçeli3, Yelda Bilginer2,
Meryem Tekçiçek3, Seza Özen2
1Department of Pediatrics, Hacettepe University Faculty of Medicine, Ankara, Turkey;
2Department of Pediatrics, Division of Rheumatology, Hacettepe University Faculty
of Dentistry, Ankara, Turkey; 3Deparment of Pediatrics Pedodontology, Hacettepe University
Faculty of Dentistry, Ankara, Turkey
Correspondence: Pelin Esmeray
Introduction: Familial Mediterranean fever (FMF) is the most common auto-inflammatory
disease which is characterized by recurrent, self-limited flares of fever associated
with polyserositis. Oral apthosis and periodontitis may be seen in the course of the
disease. However we lack studies on the dental care in pediatric FMF patients.
Objectives: In this study, the aim was to report the oral findings and to check the
effects of tooth decay on disease course in children with FMF.
Methods: 199 children with FMF who were followed at the Department of Pediatric Rheumatology
in Hacettepe University, Ankara, Turkey between May 2016 and October 2016 were included
in the study.
Results: The characteristics of patients are presented in Table 16. The mean age of
patients was 11.24 ± 4.04 years. Tooth decay was observed in 182 (91.5%) patients.
Tongue abnormalities in 65 (32.8%), lip abnormalities in 13 (6.6%), buccal abnormalities
in 6 (3%). Oral aphthosis occured in 21 (10.6%), and recurrent oral aphthosis in 67
(33.8%) patients. The median (min-max) dental plaque index was 1.26 (0-2.25), and
the median gingival index was 0.87 (0-1.81). Erythrocyte sedimentation rate and the
attack frequency at the last six months were both higher in the patients with tooth
decay than patients who did not have decay. Tooth decay was more common away M694V
homozygous patients (98.3% vs 88.6%, p = 0.025; respectively).
Table 16
(Abstract P27). The demographic and laboratory features of the patients
All patients (n = 199)
Patients with tooth decay (n = 182)
Patients who did not have tooth decay (n = 17)
median (minimum-maximum)
The status of attack at the last six months, n (%)
115 (57.7)
75 (97.4)
2 (2.6)
The frequency of attacks at the last six months (n = 115)
0.96 ± 2.08/0 (0-19)
2 (1-19)
2.5 (2-3)
n (%)
Deciduous tooth decay
166 (83,4)
Permanent tooth decay
104 (52,3)
Tooth decay
182 (91,5)
Dental plaque index
1.26/198 (0-2.25)
Gingival index
0.87/198 (0-1.81
Conclusion: The frequency of the tooth decay was higher in our patient group compared
to previously reported Turkish figures(91.5% vs 69.8-73.1%; respectively). The attack
frequency at the last six months was higher away patients with tooth decay. Our results
may suggest that dental problems may be a trigger for inflammatory attack in FMF.
On the other hand, the chronic inflammation itself may be a risk factor for tooth
decay in FMF.
Disclosure of Interest: None Declared
P28 Successful use of tocilizumab, interleukin-6 (IL-6) inhibitor, in a child with
TRAPS
Abstract withdrawn
P29 The Eurofever project: an update on the longitudinal stage
Martina Finetti, Silvia Federici, Joost Frenkel, Seza Ozen, Helen Lachmann, Fabrizio
De Benedetti, Joost Swart, Luca Cantarini, Romina Gallizzi, Marco Cattalini, Rolando
Cimaz, Donato Rigante, Jordi Anton, Maria Alessio, Alma Nunzia Olivieri, Pavla Dolezalova,
Annette Jansson, Giovanna Fabio, Judith Sanchez Manubens, Eric Hachulla, Rita Consolini,
Karoline Krause, Zelal Ekinci, Jurgen Brunner, Isabelle Koné-Paut, Giovanni Filocamo,
Maria del Carmen Pinedo, Efimia Papadopoulou-Alataki, Liliana Bezrodnik, Alberto Martini,
Nicola Ruperto, Marco Gattorno and on behalf of Eurofever Project
Pediatria II - Reumatologia, Istituto Giannina Gaslini on behalf of Eurofever Project,
Genoa, Italy
Correspondence: Martina Finetti
Introduction: In 2008 the Paediatric Rheumathology European Society (PReS) promoted
an International Project (EAHC, Project No2007332) for the study of Autoinflammatory
Diseases (AIDs) named Eurofever, whose main purpose is to create a web-based registry
for the collection of clinical, laboratory, instrumental and response to treatment
information in patients with AIDs.
Objectives: To implement the Registry with the new recently described AIDs and to
increase the collection of longitudinal data, particularly regarding treatment and
safety.
Methods: The data analysed in the study were extracted from the Eurofever registry,
which is hosted in the PRINTO website (http://www.printo.it). From February 2015 we
started the longitudinal collection of follow-up data for the patients already included
in the Registry with particular focus on treatment, modification of the clinical picture,
onset of complication/sequelae/adverse events.
Results: Up to date 3648 patients (M:F = 1799:1849) have been enrolled in the Registry
from 60 different countries (all of them with available baseline demographic information).
In 3183 pts (87%) complete clinical information and response to treatment data from
disease onset to diagnosis are also available. For each disease the number of enrolled
patients is: FMF 1012 pts (877 with complete clinical data); CAPS 289 pts (268 with
complete clinical data); TRAPS 272 pts (254 with complete clinical data); MKD 203
pts (188 with complete clinical data); Blau’s disease 50 pts (26 with complete clinical
data); PAPA 35 pts (all of them with complete clinical data); NLRP-12 mediated periodic
fever 13 pts (10 with complete clinical data); DADA2 10 pts (6 with complete clinical
data); SAVI 3 pts (all of them with complete clinical data); DIRA 3 pts (all of them
with complete clinical data); Majeed 3 pts (all of them with complete clinical data);
CANDLE 1 pt (with complete clinical data). Among multifactorial autoinflammatory diseases:
PFAPA 653 pts (530 with complete clinical data); CRMO 535 pts (513 with complete clinical
data); 340 pts with undefined periodic fever (269 with complete clinical data); Bechet
disease 215 pts (186 with complete clinical data) and Schnitzler syndrome 11 pts (all
of them with complete clinical data).
Longitudinal data are available for 393 pts (11%, M:F = 190:203). For each disease,
the number of patients with at least one follow-up visit is: FMF 72 pts, CAPS 36 pts,
TRAPS 32 pts, MKD 29 pts, PAPA 6 pts, DADA2 3 pts, SAVI 1 pt, DIRA 1 pt. Among multifactorial
diseases: CRMO 99 pts, Bechet disease 67 pts, undefined periodic fever 29 pts, PFAPA
14 pts, Schnitzler syndrome 4 pts.
Conclusion: The enrolment in Eurofever Registry is still ongoing. The longitudinal
collection and analysis of data coming from the Registry will improve our knowledge
both on the natural history of the single disease and on the efficacy/safety of treatment
commonly used in the clinical practice.
Disclosure of Interest: M. Finetti: None Declared, S. Federici: None Declared, J.
Frenkel: None Declared, S. Ozen: None Declared, H. Lachmann: None Declared, F. De
Benedetti: None Declared, J. Swart: None Declared, L. Cantarini: None Declared, R.
Gallizzi: None Declared, M. Cattalini: None Declared, R. Cimaz: None Declared, D.
Rigante: None Declared, J. Anton: None Declared, M. Alessio: None Declared, A. N.
Olivieri: None Declared, P. Dolezalova: None Declared, A. Jansson: None Declared,
G. Fabio: None Declared, J. Sanchez Manubens: None Declared, E. Hachulla: None Declared,
R. Consolini: None Declared, K. Krause: None Declared, Z. Ekinci: None Declared, J.
Brunner: None Declared, I. Koné-Paut: None Declared, G. Filocamo: None Declared, M.
D. C. Pinedo: None Declared, E. Papadopoulou-Alataki : None Declared, L. Bezrodnik:
None Declared, A. Martini Grant/Research Support from: Starting from 1 march 2016
I became the Scientific Director of the G. Gaslini Hospital, therefore my role does
not allow me to render private consultancies resulting in personal income. I perform
consultancy activities on behalf of the Gaslini Institute for the following companies:
Abbvie, Boehringer, Novartis, R-Pharm. The money received for these activities are
directly transferred to the Gaslini Institute's bank account., N. Ruperto Grant/Research
Support from: The G. Gaslini Hospital, which is the public Hospital where I work as
full time public employee, has received contributions from BMS, Hoffman-La Roche,
Janssen, Novartis, Pfizer and Sobi for the coordination activity of the PRINTO network.
This money has been reinvested for the research activities of the hospital in fully
independent manners besides any commitment with third parties., Speaker Bureau of:
Abbvie, Ablynx, AstraZeneca, Baxalta Biosimilars, Biogen Idec, Boehringer, Bristol
Myers Squibb,, Eli-Lilly, EMD Serono, Gilead Sciences, Janssen, Medimmune, Novartis,
Pfizer, Rpharm, Roche, Sanofi., M. Gattorno Grant/Research Support from: Unrestricted
grant from SOBI and NOVARTIS
P30 Mevalonate-kinase deficiency in the Czech Republic
Abstract withdrawn
P31 Eye manifestations of patients with Muckle-Wells syndrome
sukru cekic1, ozgur yalcinbayır2, Sara Sebnem Kilic1
1Pediatric Rheumatology, Uludag University Medical Faculty, Bursa, Turkey; 2ophthalmatology,
Uludag University Medical Faculty, Bursa, Turkey
Correspondence: Sara Sebnem Kilic
Introduction: CAPS is a rare autoinflammatory disease associated with mutations in
the CIAS1 gene, encoding for NLRP3 that result in overactivation of the inflammasome
and systemic inflammation. Muckle-Wells syndrome (MWS) is a rare autosomal dominant
disease which causes episodic fever attacks, sensorineural deafness, recurrent hives,
arthritis and eye involvement.
Objectives: Here we present the findings of eye involvement in a family whose 11 members
have MWS.
Methods: Clinical data was collected during the course of ongoing patient care.
Results: We evaluated the clinical features of 11 patients who were referred to a
tertiary care center. The median age of the patients was 25 years (range: 9-65). The
ratio of females/males was 1.2 (6/5). All patients had arthritis with exacerbation
on exposure to cold and recurrent episodes of pink eye. The median age of onset of
ocular involvement was 8 years (2-45). We observed severe eye involvement in 27% of
our cases, including band keratopathy, severe damage of corneal stroma and neovascularization.
Corneal involvement and clouding was detected in four patient. Two of those had the
diagnosis of keratoconus as well. Patients with keratoconus had corneal scarring due
to corneal hydrops verified with corneal topography. The other two patients with corneal
clouding had bant keratopathy. One of those patient was a 17 year old girl who had
recurrent uveitis with hypopyon which necessiated the use of intravitreal dexamethasone
implant. She also had posterior synechia of the iris to the lens. The other eye of
that patient had signs of phthisis bulbi. The other patient with bant keraopathy was
46 years old male who had optic atrophy and tractional fibrovascular membranes at
the posterior pole of the eye. Anakinra was used for treatment of 5 cases, and canakinumab
of 3 cases. It was observed that the frequency of conjunctivitis decreased after anti
IL-1 therapy. There was no mutation detected in the study of MEFV (all exons), TNFRSF1A
(exons 2 to 7), MVK (all exons), NLRP3 (all exons), NOD2 (exons 4, 8 and 9) and PSTPIP1
(exons 10 and 11) genes.
Conclusion: In this study, it has been shown that eye findings related to MWS can
vary from conjunctivitis to severe uveitis. We want to emphasize that ocular involvement
in MWS should be carefully assessed, since it can lead to visual impairment.
Trial registration identifying number:
Disclosure of Interest: None Declared
P32 Clinical comparison of patients with unifocal and multifocal chronic recurrent
multifocal osteomyelitis in an Irish cohort
Daire O'Leary1, Anthony Gerard Wilson2, Emma-Jane MacDermott3, Orla Killeen3
1Paediatric Department, RCSI, Dublin, Ireland; 2School of Medicine, UCD, Dublin, Ireland;
3National Centre for Paediatric Rheumatology, Our Lady's Children's Hospital, Dublin,
Ireland
Correspondence: Orla Killeen
Introduction: Chronic recurrent multifocal osteomyelitis (CRMO) is an auto-inflammatory
condition primarily affecting children with an estimated prevalence of 1 per 106.
The umbrella term CRMO includes patients unifocal and multifocal disease that meet
the diagnostic criteria.
Objectives: To describe clinical phenotype of an Irish cohort of patients with CRMO
and compare those with unifocal and multifocal disease.
Methods: This study was a retrospective chart review of a prospectively gathered cohort
of patients attending a single paediatric rheumatology centre.
Results: Since 2006, 42 patients have been diagnosed with CRMO at the National Centre
for Paediatric Rheumatology (NCPR) and 5 of these have unifocal disease. Patients
with unifocal disease had a single site involved throughout the disease. Three patients
with unifocal disease had a single symptomatic episode. All patients met the diagnostic
criteria proposed by Jansson et al and are ethnically Irish. Overall the mean age
at diagnosis was 10.4 years, diagnostic delay was 0.78 years and number of physicians
seen prior to referral to paediatric rheumatology was 3.5. All patients with unifocal
disease and 68% of patients with multifocal disease were female (overall F:M = :1).
The distribution of lesions was similar in both groups. In patients with unifocal
disease, all underwent biopsy to confirm the diagnosis, none had systemic symptoms
at presentation, synovitis at any stage or a personal history/first-degree relative
with an associated autoimmune disease. In patients with multifocal disease, 81% underwent
biopsy, 24% had systemic symptoms at presentation, 21% had synovitis and 38% had a
personal history/first-degree relative with autoimmune disease. 1 patient (20%) with
unifocal disease was refractory to NSAID treatment and received methotrexate. 14 patients
(38%) with multifocal disease were refractory to NSAID treatment and received methotrexate,
corticosteroids, anti-TNF, pamidronate or a combination of these.
Conclusion: The clinical phenotype of patients with unifocal CRMO appears to be different
to those with multifocal disease. It may be less frequently associated with other
autoimmune or autoinflammatory conditions and more frequently responsive to NSAID
treatment alone. However, the number of patients with unifocal disease in this cohort
was low.
Disclosure of Interest: None Declared
Bone in rheumatic diseases
P33 Magnetic resonance imaging bone marrow oedema in children: insight to comprehension
and clinical significance
Federico Caldonazzi1, Sara Pieropan2, Maddalena Maschio3, Gloria Dallagiacoma2, Daniela
Degani3, Giorgio Piacentini3, Diego A. Ramaroli3, Domenico Biasi2, Maurizio Rossini2
1UOC di Pediatria, Universita' degli Studi di Verona, Verona, Italy; 2UOC di Reumatologia,
Università degli Studi di Verona, Verona, Italy; 3UOC di Pediatria, Università degli
Studi di Verona, Verona, Italy
Correspondence: Federico Caldonazzi
Introduction: Bone marrow oedema in a child is a rare and uncommon condition associated
with joint and bone pain exacerbated by weight bearing.
Objectives: We re-evaluated in the period of 2015-2016 seven pediatric patients referred
to our Rheumatology Clinic for persistent foot pain with MRI oedema of the feet bones
(interpreted commonly as algodystrophic syndrome manifestation); they had all been
misdiagnosed in other institutions as affected by algodystrophy of the ankle/feet
or complex regional pain syndrome (CRPS).
Methods: All the patients were re-evaluated with clinical examination, blood samples
of bone turnover and vitamin D levels.
Results: Mean age of the 7 patients (F:M 6:1) was 11 years. 3 of the patients (43%)
had a previous diagnosis of oligoarticular juvenile idiopathic arthritis ANA+ with
the disease in complete remission at the moment of the clinical evaluation; 4 patients
did not suffer from any chronic disease.
Physical examination did not reveal any skin color change (rubor) but intense pain
limited to the skeletal sites of feet and ankles; only two patients (28%) had a slight
swelling of the feet.
6 of the patients suffered from joint hypermobility with recall of minor ankle strain
prior to the symptoms onset as precipitating event after meticulous history; 1 was
a football player and reported recurrent feet microtrauma.
1 patient had been treated in another institution with bisphosphonates without any
improvement. Bone turnover markers were normal in the 6 patients not treated previously
with bisphosphonates; vitamin D was below the lower limits in all patients (72% < 20 ng/mL).
All Patients were treated with an adequate daily vitamin D intake and symptomatic
pain relief was achieved with low dose NSAIDs (ibuprofen) or a short course of steroid
treatment (prednisone); rest and physical therapy were recommended; vitamin C was
added when diet intake was too low according to minimal daily diet recommendations.
Clinical improvement appeared within a 2 to 3 month treatment period in all patients;
MRI performed in the 3 patients with over 6 month of treatment documented complete
regression of bone marrow oedema.
Conclusion: Symptoms and disability out of proportion to the clinical findings is
a clinical key feature of MRI bone oedema of painful skeletal sites in children; differential
diagnosis with the multifacet pediatric CRPS is possible when bone oedema is associated
with limited clinical findings; it may be secondary to underestimated articular microtraumatisms
in a bone turnover milieu of vitamin D deficiency; we underline the importance of
supplementing vitamin D until the age of 18 as daily drops, in order to avoid its
deficiency, which, in combination with other environmental and predisposing factors,
could be the cause of invalidating clinical complaints.
Disclosure of Interest: None Declared
P34 Performance of bone scan compared to whole body-MRI in evaluation of chronic non-bacterial
osteomyelitis
Pei Ling Ooi1, Gemma Buckley2, Lorenzo Biassoni2, Marina Easty2, Sandrine Compeyrot-Lacassagne1
1Department of Rheumatology, Great Ormond Street Hospital for Children, London, United
Kingdom;
2Department of Radiology, Great Ormond Street Hospital for Children, London, United
Kingdom
Correspondence: Pei Ling Ooi
Introduction: Chronic non-bacterial osteomyelitis (CNO) is a rare non-infectious inflammatory
bone disorder that affects young children and adolescents. It usually affects multiple
sites and most commonly the metaphyseal regions of long bones in the lower limbs,
pelvis and clavicles.
There is presently no approved guideline for evaluation of bone inflammation in chronic
non-bacterial osteomyelitis (CNO) or chronic recurrent multifocal osteomyelitis (CRMO).
Bone scan (BS) has been the conventional imaging modality used to evaluate this rare
inflammatory bone disease. While recent literature suggests whole body-magnetic resonance
imaging (WB-MRI) as the imaging modality of choice, limited resources and high costs
are often prohibitive.
Objectives: We aimed to compare the diagnostic yield of bone scan to WB-MRI in CRMO
in relation to clinical symptoms and location of lesions on imaging.
Methods: A retrospective review of clinical notes of children with CNO/CRMO was performed.
7 patients with paired BS and WB-MRI performed less than 9 weeks apart between September
2009 and October 2015 were analysed. Patients were excluded if both scans were done
more than 9 weeks apart or if there was treatment change between scans.
Results: Four sets of scans were performed at diagnosis and 3 sets after initiation
of treatment. BS and WB-MRI detected a total of 29 and 40 lesions respectively. 6
out of 7 patients had asymptomatic lesions. 17/29 (58.6%) and 27/40 (67.5%) were found
on BS and WB-MRI respectively.
Symmetrical lesions were detected in 4/7 patients with no significant difference between
both modalities (BS 43% vs MRI 57%). All symmetrical lesions occurred in the pelvis
and lower limbs. BS was superior in detecting lesions in the spine (85.7% vs 57.4%)
and feet (42.8% vs 14.29%), whereas WB-MRI was better for upper limb (0% vs 14.29%)
and lower limb (57.1% vs 71.4%) lesions. Both performed equally in detecting lesions
in the pelvis and clavicles, with an incidence of 85.7% and 28.6% respectively.
None of the differences in results reached statistical significance but our cohort
of patients was small.
Conclusion: Whole body bone scan performs comparably to MRI in detecting inflammatory
bone lesions in CRMO, both symptomatic and asymptomatic. Bone scan remains an appropriate
and accessible imaging modality in the evaluation of CRMO, particularly in institutions
where resources are limited.
Disclosure of Interest: None Declared
P35 The status of bone metabolism in children with juvenile idiopathic arthritis
Yury M. Spivakovskiy1, Anna Spivakovskaja1, Youri Chernenkov1, Natalya Zacharova2
1Department of Hospitality Pediatrics, SARATOV STATE MEDICAL UNIVERSITY, Saratov,
Russian Federation; 2SARATOV STATE MEDICAL UNIVERSITY, Saratov, Russian Federation
Correspondence: Yury M. Spivakovskiy
Introduction: The decrease in mineral bone density (BMD) is one of the main manifestations
of juvenile idiopathic arthritis (JIA).
Objectives: To evaluate indicators of bone metabolism in patients with articular JIA.
Methods: The study included 66 patients with articular variant of JIA (36 oligoarticular
variant of the disease, 30 - with polyarticular), whose average age of 9.74 + 3.56 years,
boys – 28, girls - 38. All patients by ELISA in the serum was assessed level: beta
crosslaps c-terminal telopeptide (CL), osteoprotegerin (OPG), a membrane protein RANKLand
25-hydroxycholecalciferol (25(Oh)D), carried out ultrasonic densitometry. The obtained
data were compared with the results defined in the group of children without signs
of inflammatory diseases (comparison group).
Results: The results of densitometry showed a reduction in BMD in the range Z = -1,1
-2,6 SD up to 40% of cases with oligoarticular the form of JIA and in 57,7% of cases,
polyarticular JIA variant. Deficiency of 25(Oh)D in blood serum of examined children
with oligoarthritis and polyarthritis detected at 23.3% and 50%, respectively, and
the failure is at 76,7% and 50%, respectively. In the control group, these figures
were 10% and 75%, respectively. The ratio of RANKL/OPG in children with oligoarthritis
were 0.17 and polyarthritis - 0,22 in the control group - 0,07. Indicators of CL,
indicating bone resorption in the group of oligoarthritis was increased at 93.3%,
in the group of polyarthritis in 100%.
Conclusion: Thus, in patients with JIA is a decrease in BMD, with changes in biochemical
parameters outstrip the capabilities of the method of instrumental diagnosis (densitometry)
and can be recommended for research on early stages of osteopenia providing for timely
correction of bone metabolism.
Disclosure of Interest: None Declared
P36 Tocilizumab (ANTI-IL6R MOAB) achieves complete and sustained remission in a patient
with refractory CRMO
Abstract withdrawn
Disease outcome
P37 Intraarticular corticosteroid injections (IACI) of temporo-mandibular joints (TMJ)
in juvenile idiopathic arthritis (JIA): the patients’ perspective
Alessia Arduini1, Denise Pires-Marafon2, Rebecca Nicolai2, Aurora Pucacco2, Fabrizio
De Benedetti2, Silvia Magni-Manzoni2
1Pediatrics, Policlinico Umberto I, “La Sapienza” University, Rome, Italy 2Rheumatology,
IRCCS Bambino Gesù Hospital, Rome, Italy
Correspondence: Alessia Arduini
Introduction: Several studies investigated the accuracy and efficacy of IACI for the
treatment of TMJ involvement in JIA. However, the impact on patients’ daily activities
and patients’ acceptance of TMJ IACI has been scarcely studied.
Objectives: To detect variations in daily activities involving TMJs in patients with
JIA, before and after TMJ IACI, through a Juvenile Arthritis TMJ self-reported Assessment
(JATA) questionnaire, developed for the purpose. Second aim: to assess the patients’
acceptance of the TMJ IACI procedure at the study center.
Methods: Patients with JIA and clinical involvement of TMJ consecutively seen at the
study center in September-December 2016, with at least 8 years of age, were asked
to identify the daily activities most affected by TMJ arthritis. From the collected
items, we asked them to select the most relevant and representative of “TMJ well-being/worsening”
in their daily life. We included in the JATA the items most frequently selected and
a patient’s global assessment (GA) of their TMJs (VAS 0-10; 0 = worst; 10 = best).
Then, a subgroup of patients, who underwent to intraarticular corticosteroid injection
(IACI) of one or both TMJ, was asked to complete the questionnaire (VAS 0-10; 0 = totally
unable, 10 = fully able) and TMJ-GA, before and after the therapeutic intervention.
Further, we asked the patients to provide a global assessment of the TMJ IACI procedure
performed at the study center (VAS 0-10; 0 = worst; 10 = best). Statistical analysis
was performed using GraphPad Prism 5 software. Scores of each item and JATA-score
were compared between pre- and post-TMJ IACI (Wilcoxon matched pairs test, statistical
significance: p <0.05).
Results: Twenty (77%) out of the 26 eligible JIA patients identified daily activities
most relevantly affected by TMJ involvement. Thereafter, the items most frequently
selected were included in the JATA: 1.ability to bite a sandwich/an apple/a “bombolone”;
2.ability to eat a pizza or a steak; and 3.ability to accurately wash the teeth. Eight
patients (100% female, 62.5% with persistent oligoarthritis and 12.5% with extended
oligoarthritis, polyarticular RF-negative, and polyarticular RF-positive, respectively)
filled the JATA questionnaire, reporting their abilities and global assessment of
TMJ before and after TMJ IACI. Each questionnaire was completed in about 3-5 minutes.
We observed a statistically significant improvement in the scores, both of the single
items and the TMJ-GA, prior and after TMJ IACI (Table 17). The procedure was evaluated
with a median score of 8 (IQR: 7.8-10).
Table 17
(Abstract P37). Comparison between JATA single-item scores and JATA TMJ-GA before
and after TMJ intraarticular corticosteroid injection (IACI); VAS 0-10 (0 = worst;10 = best).
Values are expressed as median (IQ). Wilcoxon test; statistical significance: p < 0.05.
Pre-TMJ IACI
Post-TMJ IACI
p
Ability to bite a sandwich/an apple/a “bombolone”
5,0 (4,8-6,0)
9,0 (8,0-10,0)
0,022
Ability to eat a pizza or a steak
5,0 (4,0-7,0)
9,0 (8,5-10,0)
0,036
Ability to accurately wash the teeth
4,0 (4,0-7,3)
10,0 (9,5-10,0)
0,035
TMJ global assessment
5,0 (3,0-5,3)
9,0 (8,5-9,5)
0,022
Conclusion: The JATA questionnaire demonstrated to be easily applicable and showed
significant improvement of each item, after TMJ IACI. TMJ IACI procedure at the study
center was well accepted. Further studies are planned to confirm these results and
investigate the applicability of JATA in clinical practice and research.
Disclosure of Interest: None Declared
P38 Early pain report in oligoarticular juvenile idiopathic arthritis is related to
long-term outcome
Ellen D. Arnstad1,2, Veronika G. Rypdal3,4, Suvi Peltoniemi5, Ellen Nordal3,4, Lillemor
Berntson6, Kristiina Aalto5, Anders Fasth7, Troels Herlin8, Susan Nielsen9, Marek
Zak9, Pål R. Romundstad10, Marite Rygg2,11 and Nordic Study Group of Pediatric Rheumatology
(NoSPeR)
1Department of Pediatrics, Levanger Hospital, Levanger, Norway;
2Department of Laboratory Medicine, Children’s and Women’s Health, NTNU - Norwegian
University of Science and Technology, Trondheim, Norway;
3Department of Pediatrics, University Hospital of North Norway, Tromsø, Norway;
4Department of Clinical Medicine, UIT The Arctic University of Norway, Tromsø, Norway;
5Department of Pediatrics, Children’s Hospital, Helsinki University Hospital, Helsinki,
Finland;
6Department of Women`s and Children`s Health, Uppsala University, Uppsala, Sweden;
7Department of Pediatrics, University of Gothenburg, Gothenburg, Sweden;
8Department of Pediatrics, Århus University Hospital, Århus, Denmark;
9Pediatric Rheumatology Department, Pediatric Clinic II, Copenhagen University Hospital,
Rigshospitalet, Copenhagen, Denmark;
10Department of Public Health and General Practice, NTNU - Norwegian University of
Science and Technology;
11Department of Pediatrics, St. Olavs Hospital, Trondheim, Norway
Correspondence: Ellen D. Arnstad
Introduction: Persistent course oligoarticular juvenile idiopathic arthritis (JIA)
has the best prognosis of all JIA categories. One third of children with oligoarticular
onset will, however, develop oligoarticular extended JIA or other JIA categories during
the course of the disease with outcome similar to polyarticular disease (1). Therefore
it is important to look for early predictive factors to define long-term outcome for
these children. Pain is a frequent complaint, and knowledge of pain and its relevance
for disease outcome is limited.
Objectives: To study if self-reported pain early in disease course can predict long-term
disease outcome among children with oligoarticular JIA.
Methods: Consecutive cases of JIA from defined areas of Norway, Denmark, Sweden and
Finland with onset in 1997 to 2000 were prospectively included in a population-based
cohort study (1). Self-reported pain was measured on a 10 cm visual analogue scale
(VASpain). The Finnish participants were excluded due to lack of pain scores. Remission
at 8 years follow-up was defined according to Wallace (2). We used binomial regression
in STATA for multivariable analyses.
Results: The final study population consisted of 243 children, and of these 120 (49%)
had oligoarticular disease 6 months after disease onset. Median age at onset in the
oligoarticular group was 5.0 years, 73% were girls and 67% reported VASpain >0 six
months after disease onset. At 8 years follow-up 43% had developed oligoarticular
extended or other JIA categories, 49% reported VASpain >0 and 53% were not in remission
off medication.
In the oligoarticular onset group, we analyzed associations between early pain reports
and outcome at 8 years follow-up. Children reporting pain 6 months after disease onset
developed oligoarticular extended or other JIA categories more often compared to those
reporting no pain at 6 months (percent point difference 19%, 95% CI [1-37%]). Among
those reporting pain at 6 months, a higher proportion reported pain also at 8 years,
compared to children with no pain at 6 months (percent point difference 35%, 95% CI
[16-53%]. Pain at 6 months was associated with not being in remission off medication
at 8 years compared to no pain at 6 months (percent point difference 36%, 95% CI [19-54%].
After adjustments for age and sex, the results were similar.
Conclusion: Early pain report among children with oligoarticular JIA seems to predict
development into prognostically more unfavourable JIA categories, more pain persistence
and more severe long-term disease outcome.
References:
1. Nordal E, et al. Arthritis Rheum 2011;63:2809-18
2. Wallace CA, et al. J Rheumatol 2004;31:2290-4
Trial registration identifying number:
Disclosure of Interest: None Declared
P39 HLA II class alleles in juvenile idiopathic arthritis patients with and without
chronic arthritis signs in temporomandibular joints evaluated with contrast enhanced
MRI
Zane Davidsone1,2, Elena Eglite3, Aleksandrs Kolesovs4, Ruta Santere1, Valda Stanevica1
1Rheumatology, Childrens university hospital, Riga, Latvia; 2Pediatric, Riga`s Stradins
University, Riga, Latvia; 3Laboratory of clinical immunology and immunogenetics, Riga
Stradins University, Riga, Latvia; 4University of Latvia, Riga, Latvia
Correspondence: Zane Davidsone
Introduction: Temporomandibular joint (TMJ) involvement with both active and chronic
signs of arthritis is seen very often (17-87%) in children with juvenile idiopathic
arthritis. Contrast enhanced MRI is the golden standart for diagnosis of TMJ arthritis.
There are data that specific HLA II class alleles can be asociated with more severe
disease course and radiologic progression in patients with rheumatoid arthritis.
Objectives: To identify HLA II class alleles of risk and protection in JIA patients
with chronic arthritis signs in temporomandibular joints evaluated with contrast enhanced
MRI.
Methods: We performed retrospective study with 72 JIA patients treated at Childrens
university hospital in whom TMJ MRI was performed and acute or chronic or both signs
of arthritis were detected. Patients were genotyped for HLA- DRB1; DQB1; DQA1- using
RT-PCR with sequence-specific primers. Associations of DRB1; DQB1; DQA1 alleles in
patients were examined individually using the Chi-square test and Cochran-Mantel-Haenszel
test.
Results: 72 JIA patients with mean age of 13.9 years (range 6.0-17.9 yr); 48 (77%)
girls and 14 (23%) boys. The mean duration of the disease from the time of diagnosis
till performing TMJ MRI was 1.5 years (range 0.2-8.0 yr). JIA subtypes were as follows:
seronegative polyarthritis 60%, seropositive polyarthritis 8%, peristant olygoarthritis
2%, arthritis with enthesitis 9%, undifferentiated 3% and 2%for systemic arthritis.
Two groups were separated on the basis of presence of chronic arthritis signs (n = 62)
or absence of them (n = 10). Alleles DRB1*14 (OR = 0.19, 95% CI from 0.04 to 0.92,
p = 0.039) and DQA1*05:01 (OR = 0.29, 95% CI from 0.11 to 0.80, p = 0.016) were less
often observed in the group with chronic arthritis signs than in the group without
them. There were no longer duration of disease in the group with chronic arthritis
signs (1,47 ± 1,98) compared with 2nd group (2,71 ± 3,30) (p = 0,173).
Conclusion: Alleles DRB1*14 and DQA1*05:01 are possibly protective for development
of structural damage in temporomandibular joints in JIA patients and is not dependent
on duration of the disease.
Disclosure of Interest: None Declared
P40 The role of antinuclear antibodies positivity in predicting clinical remission
in juvenile idiopathic arthritis
Raquel M. Ferreira, Francisca Aguiar, Mariana Rodrigues, Iva Brito
São João Hospital Centre, Porto, Portugal
Correspondence: Raquel M. Ferreira
Introduction: Juvenile idiopathic arthritis (JIA) consists of an auto-immune condition
with several subgroups with distint clinical, laboratory features and therapy response.
Although antinuclear antibody (ANA) positivity can be found in all subtypes, a higher
prevalence in the oligoarticular form is well known. Recently, its association with
the remission rate has been studied, but few data are available.
Objectives: To evaluate the clinical response based on ANA status in JIA patients.
Methods: We performed an observational retrospective study with all children diagnosed
with JIA followed in our Rheumatology Pediatric Unit until april 2017. Demographic
and clinical data were colleted from medical records. JIA subtypes were categorized
according to the classification of the International League of Associations for Rheumatology
2001. ANA were considered positive when at least 2 titers were ≥ 1/100. Remission
status at follow-up was defined using the Wallace preliminary criteria. Parametric
and non-parametric test were used for statistic analysis (SPSS 20.0). P-values <0.05
were considered statistically significant.
Results: A total of ninety-four patients were enrolled. Sixty-three were female (67%).
The mean age at time of diagnosis was 7.2 years (SD 4.4) and the mean follow-up was
8.9 years (SD 6.6). The most common subgroup was oligoarticular persistent JIA (38.3%),
followed by polyarticular (25.5%), systemic (13.8%), psoriatic (10.6%), enthesitis-related
arthritis (7.4%) and oligoarticular extended JIA (4.3%). Extra-articular manifestation
as uveitis was seen in 14 patients. Both rheumatoid factor and anti-citrullinated
peptide antibody were positive in 37.5% of the polyarticular JIA. ANA positivity was
presented in 41.5% of all patients, in which was found a significant predominance
of the oligoarticular form, female gender, earlier onset of disease and increased
risk of developing chronic anterior uveitis during the course of the disease (p = 0.001,
p = 0.025, p = 0.001, p = 0.015, respectively). The mean joint count at diagnosis
was 3.9 (SD 5.0). At the last follow-up evaluation the mean joint count was 0.32 (SD
0.7), almost 59% of the patients were in remission (25.5% on medication for at least
6 months and 33% off medication for ≥ 12 months) and 41.5% had active disease. 6.4%
of the patients were treated with biologic monotherapy, 37.2% were receiving classic
DMARDs while 14.9% were under combination therapy. In the group of patients in remission
on medication >6 months, 8.3% and 45.8% of the patients were treated with biologic
and classic DMARDs respectively, and combination therapy was observed in 37.5% of
them. In the group with active disease, biologic monotherapy, classic DMARDs or combination
therapy use was seen in 10.3%, 61.5% and 12.8% of the patients, respectively. No significant
diferences were found in what concerns clinical outcome when comparing ANA-positive
and ANA-negative patients (p = 0.091).
Conclusion: Our study demonstrates once again the association between the ANA positivity
and the oligoarticular subtype, female predominance and the presence of uveitis. It
also supports the late literature that didn’t find a relationship between the remission
rate and ANA status.
Disclosure of Interest: None Declared
P41 Evaluation of knee joint Q angle and balance in juvenile idiopathic arthritis
patients with pesplanovalgus deformity
Eylul Pinar Kisa1, Serap Inal2, Ela Tarakci3, Nilay Arman3, Ozgur Kasapcopur4
1Division of Physiotherapy and Rehabilitation, Faculty of Health Science, Yeditepe
University, Istanbul, Turkey; 2Division of Physiotherapy and Rehabilitation, Faculty
of Health Science, Bahcesehir University, Istanbul, Turkey; 3Division of Physiotherapy
and Rehabilitation, Faculty of Health Science, Istanbul, Turkey 4Department of Pediatric
Rheumatology, Medical Faculty of Cerrahpasa, Istanbul University, Istanbul, Turkey
Correspondence: Eylul Pinar Kisa
Introduction: Juvenile idiopathic arthritis (JIA) is the childhood disability from
a musculoskeletal disorder. It generally affects large joints such as the knee and
the ankle. JIA combine with muscle weakness, poor flexibility, atrophy, pain, and
decreased proprioception of the affected joints, abnormal biomechanics, articular
cartilage damage.
Objectives: We aimed to observe the effects of knee Q deformity on postural stability
of children with pes planovalgus having JIA.
Methods: Twenty participants as age range 4-16 years (4 female,16 male) were enrolled
this study. New York Posture Rating Scale were used to evaluate the posture of participants.
Hand held dynamometry was used to assess the strength of the lower extremity muscles.
Their static balance evaluated with Flamingo balance test. Their dynamic balance evaluated
with Prokin balance system. Q angle was calculated by Universal desktop ruler. Universal
Desktop Ruler allows you to measure not only a straight-line distance but any curved
distance on the screen. For statistical analysis SPSS Version 21.0 program was used.
Results: For our statistical evaluations, abduction, adduction, knee flexion and extension
negatively, knee flexion angle and addiction angle positively may affect static balance(p < 0,05).
In addition to that, dynamic balance related to power of plantar flexion positively,
knee extension, inversion, abduction angle positively. The results of this study showed
that knee flexion angle and plantar flexion angle may affect Q angle negatively. There
is statistically significant effect between Q angle and posture deformity (p < 0.05).
Conclusion: In this study, power of hip flexion structure and function of the foot
and ankle, and there is preliminary evidence that foot problems impair balance. Balance
has often been used as a measure of lower extremity function and is defined as the
process of maintaining the center of gravity within the body's base of support. These
results are supported by evaluating more children with juvenile idiopathic arthritis
with pesplanovalgus.
Disclosure of Interest: None Declared
P42 Development of a unique platform for pediatric immuno-rheumatologic diseases (JIRCOHORTE):
inclusion of 3266 patients.
M. Mejbri1, R. Carlomagno1, F. Hofer1, V. Hentgen2, B. Bader-Meunier3, B. Fonjallaz4,
S. Georgin- Lavialle5, Y. Guex-Crosier6, P. Scolozzi7, A. Woerner8, E. Cannizzaro9,
D. Kaiser10, G. Berthet11, W. Baer12, F. Vanoni1, K Theodoropoulou1, A. Belot13, M.
Hofer1
1Consultation Romande d’immuno-rhumatologie pediatrique CHUV, HUG, Lausanne, Geneva,
Switzerland, 2Centre Hospitalier de Versailles, Versailles, France 3Hôpital Universitaire
Necker, Paris, France, 4Ligue Genevoise contre le Rhumatisme, Geneva, Switzerland,
5Hôpital Tenon, Paris, France, 6Hôpital Ophtalmique Jules-Gonin, Lausanne, Switzerland
7HUG, Geneva, Switzerland 8Kinderspital Beider, Basel, Switzerland 9Kinderspital,
Zürich, Switzerland 10Kinderklinik, LUCERNE, Switzerland 11Kinderklinik, Aarau, Switzerland
12Kantonspital, Graubunden, Switzerland, 13Hôpital Femme Mère Enfant, Lyon, France
Correspondence: M. Mejbri
Introduction: Pediatric immune-rheumatologic diseases are rare, characterized by chronic
course and significant impact on patient’s life. Recent developments have significantly
improved the prognosis of these diseases, but a close follow-up of patients’ cohorts
is essential to evaluate the long- term outcome. The JIRcohorte is an international
platform developed to follow pediatric immune- rheumatologic diseases, and evaluate
the long-term tolerance and efficacy of immunosuppressive and biological therapies.
The challenge was to develop a tool with items both common for all patients and specific
for each disease.
Objectives: Describe the multi-module tool implemented in the JIRcohorte platform
and the collective of patients included in the different modules.
Methods: For each of the eCRF, an expert group has defined the items to be collected
for prospective follow-up of patients with a specific disease. A first comparison
was done to highlight the identical items from the different eCRF and the items specific
to each one. For all the items reported in more than one module in a similar but not
identical way, a negotiation between the experts made it possible either to find a
common item or to clearly define the difference between them. We describe the patients
of 45 centers (in Belgium, France, Maroc and Switzerland) included in the JIRcohorte
between 2014 and 2017.
Results: Thanks to the development of a multi-module tool, we were able to reduce
the number of items to insert in the JIRcohorte from 3860 to 2188, by keeping the
same level of information. A total of 3266 patients and 10733 visits were collected.
The number of patients and visits per module are as follows: Juvenile Idiopathic Arthritis
(1371 patients, 4782 visits), Temporomandibular Arthritis (64, 156), Juvenile Dermatomyositis
(18, 61), Juvenile Systemic Lupus (121, 369), Juvenile Periodic Fever Syndrome (450,
803), Still Disease (54, 176), Uveitis (142, 1409) and Vaccination (2251, 6924).
Conclusion: JIRcohorte collects follow-up data on pediatric patients with different
immuno- rheumatologic pathologies. Thanks to its structure, with both common and specific
items in each module, it can be used as a valuable tool to compare pediatric patients
with different inflammatory rheumatic diseases.
Disclosure of Interest: None Declared
Genetics and environment
P43 Progressive pseudorheumatoid dysplasia resolved by whole exome sequencing: a novel
mutation in WISP3 and review of the literature
Aviva Eliyahu1,2, ben pode-shakked3,4,5, Asaf Vivante5,6, Ortal Barel7, Shai Padeh8,9,
Dina Marel-Yagel9,10, Alvit Veber11, Shachar Abudi12, Irit Tirosh2,13, Shiri Shpilman2,14,
Shirlee Shril15, gideon rechavi7,16,17, Friedhelm Hildebrandt18, Mordechai Shohat7,19,
yair anikster3,20,21
1 Metabolic Disease Unit, Edmond and Lily Safra Children's Hospital, Sheba Medical
Center, tel hashomer, Israel; 2Sackler Faculty of Medicine, Tel-Aviv University, Tel
Aviv, Israel; 3Metabolic Disease Unit, Edmond and Lily Safra Children's Hospital,
Sheba Medical Center, Tel Hashomer, Israel; 4Sackler Faculty of Medicine, Tel-Aviv
University, Tel Aviv, Israel; 5The Dr. Pinchas Borenstein Talpiot Medical Leadership
Program, Sheba Medical Center, Tel-Hashomer, Israel; 6Division of Nephrology, Department
of Medicine, Boston Children's Hospital, Harvard Medical School, Boston, MA, United
States; 7Sheba Cancer Research Center, Sheba Medical Center, Tel Hashomer, Israel;
8Pediatric Rheumatology Unit and Department of Pediatrics, Edmond and Lily Safra Children's
Hospital, Sheba Medical Center, Tel-Hashomer, Israel; 9Sackler Faculty of Medicine,
Tel-Aviv University, Tel-Aviv, Israel; 10Metabolic Disease Unit Israel, Edmond and
Lily Safra Children's Hospital, Sheba Medical Center, Tel-Hashomer, Israel; 11Metabolic
Disease Unit, Edmond and Lily Safra Children's Hospital, Sheba Medical Center, Tel-Hashomer,
Israel; 12Metabolic Disease Unit, Edmond and Lily Safra Children's Hospital, Sheba
Medical Center, Tel-Hashomer, Israel; 13Pediatric Rheumatology Unit and Department
of Pediatrics, Edmond and Lily Safra Children's Hospital, Sheba Medical Center, Tel
Hashomer, Israel; 14Pediatric Rheumatology Unit and Department of Pediatrics, Edmond
and Lily Safra Children's Hospital, Tel Hashomer, Israel; 15Division of Nephrology,
Department of Medicine, Boston Children's Hospital, Harvard Medical School, Boston,
MA, United States; 16Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel;
17The Wohl Institute for Translational Medicine, Sheba Medical Center, Tel Hashomer,
Israel; 18 Division of Nephrology, Department of Medicine, Boston Children's Hospital,
Harvard Medical School, Boston MA, United States; 19Sackler Faculty of Medicine, Tel-Aviv
University, Tel-Aviv, Israel; 20Sackler Faculty of Medicine, Tel-Aviv University,
Tel-Aviv, Israel; 21The Wohl Institute for Translational Medicine, Sheba Medical Center,
Tel-Hashomer, Israel
Correspondence: Aviva Eliyahu
Introduction: Progressive pseudorheumatoid dysplasia (PPRD) is a rare autosomal-recessive,
non-inflammatory arthropathy, shown to be caused by mutations in the WNT1-inducible
signaling pathway protein 3 (WISP3) gene. Although several hundred cases were reported
worldwide, the diagnosis remains challenging. Subsequently, the syndrome is often
unrecognized and misdiagnosed, leading to unnecessary procedures and treatments.
Objectives: We present here a multiply affected consanguineous family of Iraqi-Jewish
descent with PPRD. The proband, a 6.5 years old girl, presented with bilateral symmetric
bony enlargements of the 1st interphalangeal joints of the hands, without signs of
synovitis.
Methods: Molecular analysis by Whole Exome Sequencing and homozygosity mapping was
performed on the proband and other affected and non affected relatives.
Results: Molecular analysis by Whole Exome Sequencing and homozygosity mapping identified
a novel homozygous missense mutation (c.257G > T, p.C86F) in the WISP3 gene. Following
this diagnosis, an additional 53 years old affected family member was found to harbor
the mutation. Two other individuals in the family were reported to have had similar
involvement however both had died of unrelated causes.
Conclusion: The reported family underscores the importance of recognition of this
unique skeletal dysplasia by clinicians, and especially by pediatric rheumatologists
and orthopedic surgeons.
Disclosure of Interest: None Declared
P44 Cytokines genes and the severity of juvenile idiopathic arthritis
Liliia S. Nazarova1, Kseniia V. Danilko1, Tatiana V. Viktorova1,2, Viktor A. Malievsky1
1Bashkir State Medical University, Ufa, Russian Federation; 2Institute of Biochemistry
and Genetics, Ufa, Russian Federation
Correspondence: Viktor A. Malievsky
Introduction: Juvenile idiopathic arthritis (JIA) is the most common chronic rheumatic
disease in children and an important cause of short-term and long-term disability
[1]. It is essential to know the prognosis for the individual patient early in the
course of disease and preferentially at the time of diagnosis in order to start the
right treatment immediately [2].
Objectives: The goal of the study was to determine whether the TNFA gene -308A > G,
IL1B gene -511C > T and IL6 gene -174G > C single nucleotide polymorphisms (SNPs)
are associated with the disease severity in patients with JIA.
Methods: The study included 255 patients with JIA who were divided into 4 subgroups
according to the severity of the disease course: mild (N = 33), moderate (N = 58),
severe (N = 68) and very severe (N = 96). The grouping was performed depending on
the number of affected joints, the presence or absence of high laboratory activity,
systemic features, uveitis, early radiologic progression, functional disability and
the need for early "aggressive" therapy. Genotyping was performed using real-time
PCR method. Statistical analysis was performed using two-tailed Fisher's exact test
(p), odds ratio (OR) and 95% confidence interval (CI).
Results: The IL6 -174G allele was significantly more frequent in patients with a very
severe disease course, than in other patients (p = 0.040, OR = 1.498, 95%CI 1.033-2.167).
At the same time, there was a significantly higher proportion of the IL1B -511CT genotype
in a mild disease course subgroup in comparison to other subgroups (p = 0.024, OR = 2.427,
95%CI 1.109-5.160). Then the analysis was performed separately for girls and boys.
The association mentioned above for the IL6 -174G allele was confirmed only for boys
(p = 0.026, OR = 2.108, 95%CI 1.131-3.883) and for the IL1B -511CT genotype – only
for girls (p = 0.0004, OR = 10.079, 95% CI 2.656-44.857). In addition, it was found
that the IL1B -511 T allele marks a very severe JIA course in boys (p = 0.019, OR = 2.231,
95% CI 1.135-4.215) and that the TNFA -308A allele marks a mild JIA course in boys
(p = 0.007, OR = 4.778, 95% CI 1.731-14.256).
Conclusion: In this study we revealed gender-specific associations of the IL6 gene
-174G > C, IL1B gene -511C > T and TNFA gene -308A > G SNPs with an altered risk of
a very severe or mild JIA course.
References. [1] Ravelli A, Martini A. Juvenile idiopathic arthritis. Lancet. 2007
Mar 3;369(9563):767-78.
[2] van Dijkhuizen EH, Wulffraat NM. Early predictors of prognosis in juvenile idiopathic
arthritis: a systematic literature review. Ann Rheum Dis. 2015 Nov;74(11):1996-2005.
Disclosure of Interest: None Declared
P45 Single nucleotide polymorphisms in survivin gene are associated to response to
methotrexate in juvenile idiopathic arthritis
Mojca Zajc Avramovič1, Vita Dolzan2, Natasa Toplak1, Tadej Avcin1
1Department of Allergology, Rheumatology and Clinical Immunology, Children’s Hospital,
University Medical Centre Ljubljana, Slovenia, Ljubljana, Slovenia 2Institute of Biochemistry,
Medical faculty, Ljubljana, Slovenia
Correspondence: Mojca Zajc Avramovič
Introduction: Survivin is an anti-apoptotic protein and its circulating levels were
associated with joint destruction and erosions in rheumatoid arthritis (RA). Recently
it was suggested to be a marker of severe disease course in adult patients with RA
as well as juvenile idiopathic arthritis (JIA). Three single nucleotide polymorphisms
(SNPs) can affect the normal protein and its concentration. Methotrexate (MTX) is
an important drug in treating JIA, but markers to predict its efficacy are needed.
Objectives: To evaluate the effect of SNPs in survivin gene on methotrexate efficacy
in JIA.
Methods: The data of 119 consecutive patients with JIA treated with MTX at the University
Children’s Hospital Ljubljana from June 2011 to January 2015 have been retrospectively
reviewed. The disease activity was measured using JADAS 71 score. Non-responders were
defined as patients not reaching 30% improvement in JADAS 71 score 6 months after
the beginning of treatment with MTX. Genotyping of SNPs in the genes for survivin
was performed using real time PCR methods. The following SNPs were analyzed: BIRC5
G692C rs8073069, BIRC5 T241C rs17878465 and BIRC5 G692C rs8073069. Two-tailed Fisher
exact test was used for statistical analysis.
Results: A total of 119 patients were included in the analysis, 91 (76.5%) girls and
28 (23.5%) boys. Ten (8.4%) patients had systemic arthritis, 41 (34.5%) RF negative
polyarthritis, 5 (4.2%) RF positive polyarthritis, 24 (20.2%) persistent oligoarthritis,
24 (20.2%) extended oligoarthritis, 11 (9.2%) juvenile psoriatic arthritis, 2 (1.7%)
patients suffered from enthesitis related arthritis and 2 (1.7%) had undifferentiated
arthritis. Mean time of disease duration before MTX was started was 13 months in the
whole cohort and 6.9 months in the subgroup of patients with polyarticular disease
(RF positive and RF negative). Mean starting dose of MTX was 10.3 mg/m2 and mean dose
at 6 months was 12.0 mg/m2. Forty-two (35%) patients were switched to subcutaneous
MTX to achieve higher efficacy. At 6 months 30/116 (25.8%) of patients were defined
as non-responders. BIRC5 rs17878465 (p < 0.0001) and BIRC5 rs9904341 (p = 0.0272)
were associated with achieving 30% improvement in JADAS 71 after 6 months. BIRC5 rs9904341
was also associated with 70% improvement in JADAS 71 score (p < 0.0001) after 6 months
of treatment.
Conclusion: Our results suggest that SNPs in survivin gene, BIRC5 rs17878465 and BIRC
rs9904341 could be markers of MTX response in JIA.
Disclosure of Interest: None Declared
Imaging - Vasculitides
P46 Henoch schonlein purpura nephitis: initial risk factor and outcomes in a tertiary
center of Latin America
Izabel M. Buscatti, Beatriz B. Casella, Nadia E. Aikawa, Andrea Watanabe, Sylvia C.
Fahrat, Lucia M. Campos, Clovis A. Silva
Pediatric Rheumatology Division, CHILDREN’S INSTITUTE, HOSPITAL DAS CLINICAS HCFMUSP,
FACULDADE DE MEDICINA, UNIVERSIDADE DE SAO PAULO, São Paulo, Brazil
Correspondence: Izabel M. Buscatti
Introduction: European League Against Rheumatism/Paediatric Rheumatology International
Trials Organisation/Paediatric Rheumatology European Society (EULAR/PRINTO/PRES) proposed
validated classification criteria for Henoch-Schönlein purpura (HSP). However, there
are rare studies reporting initial risk factors to HSP nephritis (HSPN) and outcomes
using these new criteria. In addition, these studies generally included small samples,
and none of them were evaluated in Latin American population.
Objectives: To evaluate risk factors associated with HSPN and outcomes in children
and adolescents of a tertiary center in Latin America.
Methods: Two hundred ninety six patients with HSP were retrospectively assessed by
demographic data, and initial clinical manifestations, laboratory exams and treatments
evaluating in the first three months of disease. All of them fulfilled validated EULAR/PRINTO/PRES
criteria for HSP. They were also divided in two groups: with and without nephritis.
Additional, persistent non-nephrotic proteinuria, nephrotic proteinuria and renal
insufficiency were also evaluated at 1, 5, 10 and 15 years after diagnosis.
Results: Nephritis was detected in 139/296 (47%) at first 3 months. The median of
age at diagnosis was significantly higher in HSPN patients compared to those without
this complication [6.6(1.5-17.7) vs. 5.7(0.9-13.5) years, p = 0.022]. The frequencies
of persistent purpura (31% vs. 10%, p < 0.0001), recurrent abdominal pain (16% vs.
7%, p = 0.011), gastrointestinal bleeding (25% vs. 10%, p < 0.0001) and corticosteroid
use (54% vs. 41%, p = 0.023) were significantly higher in the former group. In the
multivariate analysis, logistic regression demonstrated that the independent variables
that predicted HSNP were persistent purpura (OR = 3.601; 95%CI 1.605-8.079; p = 0.002)
and gastrointestinal bleeding (OR = 2.991; 95%CI 1.245-7.183; p = 0.014). Of 139 HSPN,
further analysis revealed that persistent non-nephrotic proteinuria, nephrotic proteinuria
and renal insufficiency occurred during follow-up: at 1 year [46/88 (52%), 1/88 (1%)
and 2/88 (2%)], at 5 year [25/47 (53%), 1/47 (2%) and 1/47 (2%)], at 10 year [9/20
(45%), 1/20 (5%) and 1/20 (5%)] and at 15 years [1/6 (17%), 0/6 (0%) and 0/6 (0%)].
In addition, in patients without HSPN at disease onset: 29/118 (25%) had persistent
non-nephrotic proteinuria and/or hematuria only at 1 year of follow-up, 19/61 (31%)
at 5 years, 6/17 (35%) at 10 years and 4/6 (67%) at 15 years of follow-up.
Conclusion: Persistent purpura and gastrointestinal bleeding were initial predictors
for HSPN. Persistent non-nephrotic proteinuria and/or hematuria may occur during the
disease follow-up, even in patients without previous HSPN, and rigorous monitoring
of renal involvement should be performed.
Disclosure of Interest: I. Buscatti: None Declared, B. Casella: None Declared, N.
Aikawa: None Declared, A. Watanabe: None Declared, S. Fahrat: None Declared, L. Campos:
None Declared, C. Silva Grant/Research Support from: Conselho Nacional de Desenvolvimento
Científico e Tecnológico (CNPq 472155/2012-1)
P47 Toward the development of a new radiographic score for diagnosis and monitoring
of temporomandibular joint disease in children with juvenile idiopathic arthritis
Gabriella Giancane, Giacomo Chiappe, Fiammetta Sertorio, Veronica Incarbone, Alessandro
Consolaro, Nicola Laffi, Gian Michele Magnano, Angelo Ravelli
Istituto Giannina Gaslini, Genoa, Italy
Correspondence: Gabriella Giancane
Introduction: Arthritis of the temporo-mandibular joint (TMJ) is often responsible
for severe osteo-articular damage in patients with juvenile idiopathic arthritis (JIA).
Early diagnosis of TMJ involvement remains difficult, due to the lack of reliable
clinical or imaging parameters. However, magnetic resonance imaging (MRI) is regarded
as the most sensitive tool for the detection of TMJ involvement in JIA.
Objectives: To develop and validate a MRI score for early detection of TMJ disease
activity and damage in children with JIA.
Methods: After a review of the most recent literature on MRI of the TMJ in JIA and
based on their experience, three specialists in different fields (a rheumatologist,
a dentist and a radiologist) devised the score for the assessment of activity and
damage of TMJ shown in Table 18. The score consists of 3 parameters of arthritis activity
(joint effusion, contrast enhancement (CE) and bone edema), and 4 parameters of joint
damage (erosion/irregularities of the mandibular condyle, disc abnormalities, flattening
of the condyle, mandibular asymmetry). The activity score ranges from 0 to 6 and the
damage score from 0 to 9. After a series of training sessions aimed to reach consensus
on the definition of the score features, each specialist assigned independently the
MRI score to an unselected sample of TMJ MRIs of JIA patients followed at our center.
The inter- and intra-observer reliability were calculated through the weighted kappa.
The CE parameter was also compared with a recently validated score calculated on a
specific region of interest (ROI) of the TMJ MRI in JIA patients1. Agreement was considered
acceptable for a k value > 0.60.
Table 18
(Abstract P47). MRI score (CE: contrast enhancement)
TMJ ACTIVITY PARAMETERS
Right
Left
Total score
Joint effusion
YES □ NO □
YES □ NO □
0-2
Contrast enhancement (CE)
YES □ NO □
YES □ NO □
0-2
Bone edema/bone marrow CE
YES □ NO □
YES □ NO □
0-2
Total activity score
0-3
0-3
0-6
TMJ DAMAGE PARAMETERS
Erosions/irregularities of the condyle
YES □ NO □
YES □ NO □
0-2
Disc abnormalities
YES □ NO □
YES □ NO □
0-2
Flattening of condyle
MODERATE/SEVERE □ MILD□NO□
MODERATE/SEVERE □ MILD□NO□
0-4
Mandibular asimmetry
YES □ NO □IF YES: RIGHT < □ LEFT < □
0-1
Total damage score
0-5
0-9
Results: A total of 35 TMJ MRIs performed between December 2013 and December 2016
were evaluated. The analysis of the absolute agreement in score assignment among specialists
revealed substantial agreement, with greater concordance between the dentist and the
radiologist. The rheumatologist tended to assign lower scores. Among disease activity
parameters, the lowest agreement was seen for bone edema, whereas the most challenging
joint damage parameter was disc abnormalities. There was a moderate agreement between
the CE recorded by the study assessors and that obtained through the ROI calculation,
especially for the rheumatologist and the dentist.
Conclusion: We have developed a new simple and feasible MRI score for the detection
and quantification of disease activity and damage of the TMJ in children with JIA.
Although the overall score proved reliable across different specialists, further work
is needed to increase concordance for assessment of bone edema and disc abnormalities.
Reference: 1. Resnick CM et al. Quantifying Temporomandibular Joint Synovitis in Children
With Juvenile Idiopathic Arthritis. Arthritis Care Res (Hoboken). 2016;68:1795-1802.
Disclosure of Interest: None Declared
P48 Determining disease activity in CIA by optical imaging of phagocyte migration
Sandra Gran1, Lisa Honold2, Olesja Fehler1, Stefanie Zenker1, Sven Hermann2, Michael
Schäfers2, Thomas Vogl1, Johannes Roth1
1Institute of Immunology, Münster, Germany; 2European Institute for Molecular Imaging,
Münster, Germany
Correspondence: Sandra Gran
Introduction: Phagocyte recruitment and migration to the site of inflammation are
key events in the early phase of inflammation. They are indispensable for pathogen
elimination, tissue repair and restoration of tissue homeostasis. However, dysregulated
phagocyte infiltration and a subsequently overwhelming immune response can also cause
severe inflammatory disorders. Therefore, targeting and modulation of phagocyte infiltration
represents a promising new approach to fight inflammatory disorders and diseases,
such as rheumatoid arthritis. Furthermore, non-invasive tracking of phagocyte migration
to the site of inflammation could extend both scientific knowledge as well as the
repertoire of diagnostic strategies in clinical use.
Objectives: Within this study we aimed to establish a Fluorescence reflectance imaging
(FRI) based system to visualize and analyze migration properties of different cell
populations in inflammatory disease models, like experimental arthritis, in vivo.
Methods: Immortalized murine myeloid progenitor ER-HoxB8 cells were differentiated
to neutrophils or monocytes (Wang et al., 2006). Differentiated cells were labeled
in vitro with the membrane-selective fluorescent dyes DIR (Eisenblätter et al., 2009)
or DID, respectively. Viability and functionality of labeled cells were confirmed
by in vitro assays. In several mouse models - particularly in a collagen induced arthritis
(CIA) mouse model - we investigated the ability and specific properties of different
cell populations to migrate to sites of inflammation in vivo via fluorescence reflectance
imaging (FRI). Using CRISPR-Cas9 technology we introduced targeted gene deletions
for main adhesion molecules.
Results: ER-HoxB8 monocytes and neutrophils could effectively be labeled with DIR
or DID. In vitro assays confirmed that viability and functionality of ER-HoxB8 cells
was not affected by cell labeling. Subsequent in vivo imaging experiments allowed
the visualization of migrated labeled phagocytes in different murine disease models,
thereby cells could be detected at sites of inflammation with high sensitivity and
specificity. In a CIA mouse model the amount of immigrated cells could even be associated
closely to disease score and disease severity. Thus, the detection of immigration
of labeled cells might also give hints about new inflammatory spots that are about
to settle up before they can be detected macroscopically. Furthermore, differential
cell labeling allowed direct quantitative comparison of differences in migration rates
of wildtype and CD18 or CD49d knockout cells in vivo.
Conclusion: Specific and distinguishable labeling of diverse cell types allows in
vivo tracking and subsequent quantification of migrated cells within the same animal.
Targeted gene deletion allows analysis of molecular mechanisms relevant for leukocyte
recruitment during different stages of arthritis. Correlation of the amount of immigrated
cells to disease severity offers new opportunities to non-invasively detect and monitor
inflammatory sites in vivo.
Disclosure of Interest: None Declared
P49 Juvenile Sjögrens syndrome (JSS): comparing glandular ultrasound in primary and
secondary JSS
Johannes-Peter Haas, Manuela Krumrey-Langkammerer
German Center for pediatric and adolescent rheumatology, Garmisch-Partenkirchen, Germany
Correspondence: Manuela Krumrey-Langkammerer
Introduction: Diagnosis of juvenile Sjögrens syndrome (jSS) although rare seems to
be underestimated in pediatric patients. Especially in patients with undifferenciated
mixed connective tissue disease (MCTD) secondary jSS is frequently present but missed
in the diagnostic work-up.
Objectives: Our intend was to characterize distinct, ultrasonographic (US) findings
in a cohort of primary- and secondary jSS patients, the latter with a focus on MCTD
and attribute these findings to US scores defined in adult SS.
Methods: A single-center study collected data from clinical charts of jSS-patients
admitted to the GCPAR. According the EULAR/ACR criteria 8 patients with primary jSS,
8 patients with secondary jSS and MCTD and 9 patients with secondary jSS and other
collagenoses were included. All ultrasonographic (US) findings were performed by two
experienced investigators between 5/2014 and 3/2017 using a GE logic 8 system. Different
scoring systems from the literature were compared for accuracy for gland echostructural
abnormalities.
Results: A total of 25 patients (22 females, 3 males) with a mean age of 15,8 years
have been included. All 9 pjSS patients had sicca symptoms, this was present in only
56,3% of sjSS. Swelling or pain in major salivary glands occurred in 7 of 9 pjSS but
only 5 of 16 sjSS (including MCTD). US scoring of salivary glands according to Hocevar
[1] which had been proven to be accurate in jSS as well [2] showed a mean score of
26 in pjSS and 18,28 in sjSS patients. We could not correlate US score (Hocevar) with
the duration of the disease (Pearsons r =0.197) (Table 19).
Table 19
(Abstract P49). Salivary gland US-scores according Hocevar´s classification
pjSS (n = 9)
sjSS other (n = 8)
sjSS in MCTD (n = 8)
All (n = 25)
Decrease in echogenity
3 (33,3%)
3 (37,5%)
2 (25%)
18 (72%)
Inhomogenous parenchyma
9 (100%)
7 (87,5%)
6 (75%)
22 (88%)
Hypoechoic areas
9 (100%)
8 (100%)
7 (87,5%)
24 (96%)
Hyperechoic reflexes
7 (77,7%)
6 (75%)
6 (75%)
19 (76%)
Disturbed border
4 (44,4%)
2 (25%)
0
6 (24%)
Conclusion: In patients with pjSS and sjSS salivary gland ultrasound is a helpful,
first-line tool not only to detect salivary gland involvement but to score the severity
of inflammation as well. As sjSS is supposed to be underestimated in collagenoses
and MCTD, screening of salivary gland by US is usefull even in patients without sicca-symptoms
to identified typical, inhomogeneous parchenchymal appearance with hypoechoic lesions
suggestive for jSS.
References:
1. Hocevar A. et al;. Rheumatology 2005; Vol 44; pp 768
2. Krumrey-Langkammerer M. et al. 2015: Ultraschall in Med 2015; 36 - A349
Disclosure of Interest: None Declared
P50 Toward the achievement of an agreement between clinical and ultrasound assessment
of the ankle region
Stefano Lanni1, Alessandra Alongi1, Adele Civino2, Alessandro Consolaro1,3, Giovanni
Filocamo4, Angelo Ravelli1,3
1IRCCS Istituto Giannina Gaslini, Genova, Italy; 2Pia Fondazione di Culto e Religione
Card. G. Panico, Tricase, Italy; 3Università degli Studi di Genova, Genova, Italy;
4Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milano, Italy
Correspondence: Stefano Lanni
Introduction: The ankle is a complex anatomical structure owing to the multiple joint
recesses and surrounding tendons. The clinical examination of this joint is a challenging
task even for the expert physician. Ultrasound (US) is becoming a useful adjunctive
tool to clinical evaluation for the assessment of children with juvenile idiopathic
arthritis (JIA). Disagreement between clinical and US examinations in the assessment
of the ankle region has been shown in some studies.
Objectives: The aims of the study were: 1) to assess the frequency of clinical signs
of articular and periarticular involvement and of US abnormalities in the different
joint recesses and tendon compartments of the ankle region; 2) to investigate the
correlation between clinical signs of articular involvement and US abnormalities in
the different joint recesses of the ankle region.
Methods: Twenty-seven ankles of 19 patients with JIA with a clinical suspicion of
disease involvement were included in the study. At the same consultation, the ankles
were scanned by a physician with experience in the US assessment of children with
JIA, who was blinded to clinical findings. Clinical and US evaluations focused on
tibiotalar and subtalar joints, the tarsal area and on tendon compartments. For each
of the joint recesses the presence of swelling, pain on motion and restricted motion
and the detection of joint effusion (JE), synovial hypertrophy (SH) and power Doppler
(PD) signal inside the area of SH were recorded on clinical and on US evaluation,
respectively. US abnormalities were graded on a 4-point semiquantitative scale. Correlation
between clinical signs of articular involvement and US abnormalities in the different
joint recesses of the ankle region was estimated using the Kendall’s tau (τ) coefficient.
Results: Overall, on clinical assessment swelling was found more frequently in the
tibiotalar joint (52%), whereas both pain and restricted motion were documented more
commonly in the subtalar joint (44% and 41%, respectively). On US assessment JE and
SH were detected more frequently in the tibiotalar joint (56% and 67%, respectively);
PD signal was displayed more commonly in the subtalar joint (44%). Among tendon compartments,
both clinical and US assessments documented a more frequent involvement of flexor
tendons (11% and 52%, respectively). Correlation was found between presence of pain
or restricted motion on clinical evaluation and detection of PD signal on US in the
tibiotalar joint (τ = 0,58, p = 0,002 and τ = 0,57, p = 0,002, respectively). In the
tarsal area correlation was found between presence of restricted motion on clinical
assessment and detection of PD signal on US (τ = 0,43, p = 0,024) and between presence
of pain on clinical assessment and detection of SH on US (τ = 0,41, p = 0,033). No
correlation was found in the subtalar joint between any clinical sign of articular
involvement and US abnormalities.
Conclusion: Tibiotalar and subtalar joints are more commonly affected than the tarsal
area on both clinical and US assessment in case of ankle involvement in JIA. Flexor
tendons are more frequently inflamed than the anterior and lateral tendon compartments.
On clinical examination, pain or restricted motion, but not swelling, in the tibiotalar
joint and in the tarsal area seem to correlate with the presence of synovitis on US
in these joint recesses of the ankle region. The assessment of the subtalar joint
remains a challenging task for the physician without the use of US.
Disclosure of Interest: None Declared
P51 Kawasaki disease: initial echocardiogram predicts subsequent coronary disease
and immunoglobuline resistance
Dima Chbeir1, Jean Gaschinard1, Ronan Bonnefoy1, Constance Beyler2, Isabelle Melki1,
Albert Faye1, Ulrich Meinzer 1
1Pédiatrie générale, maladies infectieuses et médecine interne, Paris, France 2Service
de cardiologie pédiatrique, Hôpital Robert Debré, Paris, France
Correspondence: Ulrich Meinzer
Introduction: Kawasaki disease (KD) is an acute febrile systemic vasculitis that affects
blood vessels of small and medium calibre. With the availability of intensified treatments
for most severe patients, it is crucial to early identify patients at high risk for
coronary artery aneurysms (CAA). However, the available risk scoring systems from
Japan have not been validated in European populations. There is little data concerning
the link between initial echocardiogram findings and cardiac prognosis.
Objectives: To investigate the first echocardiogram can predict resistance to conventional
therapy and/or subsequent development of CAA
Methods: We retrospectively analysed demographic, clinical, biological, echocardiographic
and therapeutic data from children diagnosed with KD between 2006 and 2016 at the
Robert-Debré University Hospital, Paris, France.
Results: A total of 157 children with KD were included. Initial echocardiogram was
performed after a median of 6 days of fever and was abnormal in 48 cases (31%). The
initial presence of any echocardiographic abnormality was strongly associated with
resistance to intravenous immunoglobulin (p = 0.005) and development of coronary artery
lesions within the first six weeks of disease (p = 0.01). All patients (n = 7) with
persistent coronary abnormalities at one year already had an abnormal initial echocardiogram.
In contrast, severity scores had low sensitivity (24-33%) and low specificity (72-81%)
to predict immunoglobulin resistance or cardiac involvement.
Conclusion: Abnormalities in the initial echocardiogram can be used to early identify
patients with severe Kawasaki disease in populations with mixed ethnic backgrounds.
Disclosure of Interest: None Declared
P52 Childhood-onset Takayasu arteritis: a referral center experience in Turkey
Sezgin Sahin1, Duhan Hopurcuoglu1, Sule Bektas1, Ezgi Belhan1, Amra Adrovic1, Kenan
Barut1, Nur Canpolat2, Salim Calıskan2, Lale Sever2, Ozgur Kasapcopur1
1Pediatric Rheumatology, Istanbul University, Cerrahpasa Medical School, Istanbul,
Turkey 2Pediatric Nephrology, Istanbul University, Cerrahpasa Medical School, Istanbul,
Turkey
Correspondence: Sezgin Sahin
Introduction: Takayasu arteritis is a chronic granulomatous vasculitis that effects
primarily aorta and its main branches and rarely seen before the age of 18. Delay
in diagnosis and treatment is a common feature due to the nonspecific systemic features.
There is limited data on clinical features and long-term outcome of Takayasu arteritis.
Also, there is need to evaluate efficacy of current therapies, since the spectrum
of treatment options have been increased compared to the past.
Objectives: We aimed to report our referral center experience on the clinical features
and treatment options of Takayasu arteritis. In addition, we have evaluated the correlation
of various activity and damage scores with eachother
Methods: We performed a retrospective chart review for Takayasu arteritis between
October 2002 and October 2017 at our tertiary referral pediatric rheumatology center.
In addition to the current cases that are followed-up, we have comprehensively searched
the hospital database for the ICD-9 code 446.7 and ICD-10 code M31.4 to identify Takayasu
arteritis patients.
Results: Overall, 16 patients (12 female) have been diagnosed with Takayasu arteritis
in last 15 years. Mean age of the patients at disease onset and diagnosis were 10.9 ± 4.8 years
and 11.5 ± 4.7 years, respectively. While the median duration from the onset of first
symptom until the diagnosis was 2.4 months (range 0.1-65 months), the mean disease
duration was 6.1 ± 5.9 years. The most frequent manifestation at admission was nonspecific
systemic features (fever, fatigue, anorexia, weight loss) (n = 13, 81.2%) followed
by hypertension (n = 10, 62.5%) and neurologic findings (n = 4, 25%). Tuberculosis
disease was also detected in 4/16 subjects (25%) at disease onset and anti-tuberculosis
therapy initiated concomitantly with immunosuppressive drugs. All patients had met
the ACR 1990 criteria for the classification of Takayasu arteritis. The most common
angiographic type was Numano’s type IV seen in 5 patients, followed by type V in 4,
type III in 4, type IIa in 2, type IIb and type I one patient each. Subjects had extensive
disease at presentation with mean DEI.Tak (±SD) of 13.8 (±6); All of the subjects
had elevated acute-phase reactants, and were active at presentation [mean ITAS2010
score (±SD): 18.7 (±7.1) and mean PVAS score (±SD): 14.0 (±4.4)). These three activity
scores correlated with each other both at disease onset and last visit (p < 0.05).
The most frequently used immunosuppressive drug in therapy was corticosteroids (n = 16/16,
100%), followed by azathioprine (n = 15/16, 93.7%), cyclophosphamide (n = 10/16, 62.5%),
methotrexate (n = 6/16, 37.5%) and tocilizumab (n = 6/16, 37.5%). The rate of angioplasty
and/or bypass was not rare (n = 7/16, 43.7%). Despite the high frequency of surgical
procedure, there was no deceased patient with Takayasu arteritis in the last 15 years.
Conclusion: There is no deceased Takayasu patient in the last 15 years. Fairly good
clinical outcomes compared to the past may be due to new biologic drugs and/or improved
surgical techniques. Three different disease activity scores were in a great concordance
with each other.
References
1. Brunner J, Feldman BM, Tyrrell PN, et al. Takayasu arteritis in children and adolescents.
Rheumatology (Oxford) 2010; 49(10): 1806-14.
2. Eleftheriou D, Varnier G, Dolezalova P. Takayasu arteritis in childhood: retrospective
experience from a tertiary referral centre in the United Kingdom. Arthritis Res Ther
2015; 17: 36.
3. Misra DP, Aggarwal A, Lawrence A, Agarwal V, Misra R. Pediatric-onset Takayasu's
arteritis: clinical features and short-term outcome. Rheumatol Int 2015; 35: 1701-6.
Disclosure of Interest: None Declared
P53 Low dose CT coronary angiography and calcium scoring in patients with Kawasaki
disease in convalescent phase- a preliminary study
Rajkumar Chakraborty1, Surjit Singh2, Manphool Singhal1, Deepti Suri2
1Radiodiagnosis and Imaging, Post Graduate Institute of Medical Education and Research,
Chandigarh, India, Chandigarh, India; 2Allergy immunology Unit, Advanced Pediatrics
Centre, Post Graduate Institute of Medical Education and Research, Chandigarh, India,
Chandigarh, India
Correspondence: Surjit Singh
Introduction: Development of coronary artery abnormalities (CAA) is the hallmark of
Kawasaki disease (KD) and accounts for most of the morbidity and mortality associated
with the disease. Concerns have been raised as to whether patients with KD are really
at risk for premature atherosclerosis later in adulthood. With advancements in technology,
dual-source computerized tomography (DSCT) coronary angiography can be developed as
a low radiation imaging paradigm for patients with KD. Advantages over echocardiography
include the ability to visualize middle and distal coronary segments with little or
no inter-observer variability. Unlike catheter angiography, DSCT angiography is non-invasive
and clearly delineates calcification and intraluminal abnormalities.
Objectives: This study is designed to evaluate whether KD is a risk factor for premature
atherosclerosis by calcium scoring (Agatson’s algorithm) and to detect the CAA (aneurysm/thrombus/stenosis/ectasia)
using DSCT with low radiation protocols.
Methods: In this prospective study, 21 patients (male: female- 15:6) with KD in convalescence
for more than 10 years were enrolled (mean: 15.76 years). Diagnosis of KD was based
on the 2004 American Heart Association (AHA) Criteria for KD. Written informed consent
was taken from all the patients prior to the enrolment. Patients were scanned during
a single breath-hold with a customized protocol designed to minimize the administered
radiation dose. Non-ionic contrast (Omnipaque 350, GE Healthcare, Ireland) 2-4 ml/kg
was injected at a rate of 4-5 ml/s (through 20G cannula), in the right antecubital
vein, followed by a saline push (1-2 mL/kg at a rate of 1.5 mL/second) with a dual
head power injector. An 128 slice SOMATOM Definition flash DSCT scanner (SIEMENS HEALTH
CARE; Germany) was used for coronary angiography. The data acquisition parameters
were 80-100 KVp voltage, tube current (mAs) (care dose 4D), detector configuration
128x0.6 mm, gantry rotation time 0.28 seconds, and the scan length was adjusted from
the scout image to encompass the entire heart. The scan was taken from carina till
the apex of heart. Images were analyzed on dedicated work station using proprietary
soft ware (Syngovia). Coronary arteries was evaluated using the 13 segment model proposed
by the AHA. The calcium score was calculated by determining the density of the highest
density pixel in each plaque taking the threshold of 130 HU and applying a weighting
factor to each plaque, depending upon the peak density in the plaque. Heart rate at
which data was acquired, was recorded along with electrocardiogram tracing.
Results: Mean age of the patients at the time of diagnosis was 3.21 years and mean
time interval time interval between diagnosis and imaging 12.59 yrs. At the time of
data acquisition the mean heart rate of the patients were 80 beat/min, mean tube current
2417.66 mAs, median scan time 2.5 seconds and median effective dose 2.52 mSv. CAAs
are seen in the form of aneurysms and ectasias in two patients (9.52%) in our study.
No patient with significant stenosis was seen. The aneurysms were detected in proximal
segments of RCA (Saccular, medium sized) and LAD (fusiform, small sized). The ectasias
were detected in one patient (4.76%) in LAD and LCx. Raised calcium score is seen
only one (4.76%) patient with abnormal coronary arteries. The calcium deposition is
seen in only in abnormal segments.
Conclusion: Our study suggests that KD itself may not be a cause for premature atherosclerosis
unless the coronary arteries are involved in form of aneurysms. However, the results
of this preliminary study done in a small population size has to be replicated in
larger cohorts to make a firm conclusion.
Disclosure of Interest: None Declared
P54 Low dose dual source CT coronary angiography and calcium scoring in children with
Kawasaki disease not treated with intravenous immunoglobulin– a preliminary study
Santosh Dusad1, Surjit Singh1, Manphool Singhal2, Deepti Suri1
1Allergy immunology Unit, Advanced Pediatrics Centre, Post Graduate Institute of Medical
Education and Research, Chandigarh, India, Chandigarh, India 2Radiodiagnosis and Imaging,
Post Graduate Institute of Medical Education and Research, Chandigarh, India, Chandigarh,
India
Correspondence: Surjit Singh
Introduction: Coronary artery abnormalities (CAA) develop in 20-25% of untreated cases
and 3-5% of treated cases of Kawasaki disease (KD), that accounts for most of the
morbidity and mortality associated with the disease. Although, transthoracic 2-D Echocardiography
(2DE) is the initial preferred modality for imaging coronary arteries, it has several
inherent limitations- unclear views of middle and distal segments of coronaries, chances
of inter-observer variation, and poor acoustic windows in older children to view the
coronaries. Dual source CT (DSCT) coronary angiography has recently emerged as an
non-invasive tool that has low radiation exposure and can accurately demonstrate the
coronary wall anatomy and intraluminal abnormalities like thrombosis, stenosis, calcification.
It has several advantages over echocardiography including the ability to visualize
middle and distal coronary segments with little or no inter-observer variability.
Objectives: To evaluate the role of DSCT coronary angiography in detecting CAAs in
children with KD who were not treated with intravenous immunoglobulin during acute
stage and its comparison with 2DE.
Methods: Nineteen (19) children (M:F = 15:4) with KD who did not receive intravenous
immunoglobulin and are on regular follow up in Pediatric Rheumatology Clinic were
enrolled (median age: 11.03 years; range: 3.7-23 years). Diagnosis was based on diagnostic
criteria given by AHA. All of the patients were the cases of incomplete KD and were
not given IVIg because they either presented late in convalescent phase or when then
presented to us, they were afebrile and ESR, CRP were not raised. Mean duration since
diagnosis of KD to the time when study was conducted was 3.84 ± 2.27 years. The study
was approved by the Ethics Committee of the Institute. A written informed consent
from the parents was obtained prior to enrolment. Children underwent both SOMATOM
128-slice Definition flash DSCT coronary angiography (SIEMENS HEALTH CARE; Germany)
and 2DE on the same day. Diameters of major coronary arteries were measured and presence
of any coronary artery lesions was looked for. Results of 2DE carried out at the time
of diagnosis were also taken into account. Student paired T test was used to compare
the average diameter of coronaries obtained by two imaging modalities.
Results: None of the patients showed any coronary artery abnormalities by both DSCT
and 2DE. All coronary arteries were well visualized by DSCT and even LCX branches
and distal RCA was also well visualized. However, coronary artery could not be visualized
in 7 patients out of 19 by 2DE. In 3 patients, even main arteries were also not seen
due to poor acoustic window. However, in 4 cases, RCA and LMCA were well visualized,
but it was difficult to visualize left circumflex artery clearly. The 2DE and DSCT
had almost the same results of proximal coronary artery especially LMCA, proximal
RCA, and LAD. However, DSCT provided the more accurate visualization of distal coronary
artery than 2DE. The average diameter of coronary artery measured by 2DE and CT angiography
was almost similar. 2DE at the time of diagnosis showed dilatation of coronaries in
3 children (2 LMCA, 1 LAD) which were not seen in current echo and DSCT.
Conclusion: DSCT coronary angiography more accurately delineated the anatomy and lumen
of coronary arteries especially in older children with KD when compared with 2DE.
DSCT is superior to echo for distal coronary artery visualization. It can reveal coronary
artery lesions in patients with KD in timely manner and help with therapeutic decision
making to improve the prognosis.
Disclosure of Interest: None Declared
P55 Flow mediated dilatation of brachial artery during the acute and convalescent
stages of Kawasaki disease-a preliminary study
Santosh Kumar1, Surjit Singh1, Manphool Singhal2, Vivek Kumar3, Deepti Suri1
1Allergy immunology Unit, Advanced Pediatrics Centre, Post Graduate Institute of Medical
Education and Research, Chandigarh, India, 2Radiodiagnosis and Imaging, Post Graduate
Institute of Medical Education and Research, Chandigarh, India, 3Nephrology, Post
Graduate Institute of Medical Education and Research, Chandigarh, India,
Correspondence: Surjit Singh
Introduction: Kawasaki disease (KD) is usually considered as an acute, self-limited
vasculitis of childhood. However, of late, several long-term complications including
development of major coronary events and premature atherosclerosis have been recognized
in patients with KD. The evaluation of vascular endothelial function is important
in predicting several long-term complications in patients with KD. Flow mediated dilatation
(FMD) of the brachial arteries is considered one of the non-invasive ways to study
the vascular endothelial dysfunction.
Objectives: To study the FMD of brachial artery (BA) and evaluate for endothelial
dysfunction in children with KD in both acute and convalescent phases.
Methods: Sixteen (16) children with KD and an equal number of controls were enrolled.
The diagnosis of KD was based on the standard clinical diagnostic criteria enunciated
by the 2004 American Heart Association (AHA). FDA approved automated edge detection
software program (Brachial artery analyserTM) combined with high resolution ultrasound
images were used to study the BA. Ultrasonography (USG) on a standard Philips Medical
system was performed by a trained and expert radiologist. The software provided the
diameter measurement every second. A 10-MHz multifrequency linear array probe attached
to a high-resolution ultrasound machine was used to acquire images of the right BA.
Baseline images of the right brachial artery were obtained for 2 minutes. A forearm
cuff was positioned 1 cm under the antecubital fossa and inflated to 250 mm Hg for
5 minutes to induce forearm-reactive hyperemia. The cuff was then released and images
of BA were recorded continuously for next 5 minutes. The basal diameter was taken
as the average of measures collected during the first minute, and FMD was calculated
as the maximum percentage change in the brachial artery diameter compared with the
basal value. The USG was repeated in convalescent stage, at least three months later
the diagnosis.
Results: Mean age of the study population was 4.8 years in cases (n = 16; M:F- 12:4)
and 5.75 years in control population (n = 16; M:F- 10:6). The baseline BA diameter
in acute phase of KD children is 2.3 ± 0.34 mm and that of convalescent phase is 2.49 ± 0.35 mm.
Healthy control population had a mean baseline BA diameter of 2.35 ± 0.46 mm. Maximum
dilatation was 2.56 ± 0.36 mm in the group of acute KD, 2.93 ± 0.31 mm in the group
of convalescent KD and 2.95 ± 0.56 mm in healthy controls (p- 0.02). Children with
KD had FMD of 12.32 ± 6.2% in acute phase and 17.99 ± 8.13% in convalescent phase,
whereas, the control population had FMD of 26.88 ± 12.76% (p <0.01).
Conclusion: Our results suggest that FMD is significantly reduced in children with
KD in acute phase and convalescent phase as compared to healthy controls. To the best
of our knowledge, ours is the first study done in both phases of KD and suggests that
endothelial dysfunction starts as early as in the acute phase of KD.
Disclosure of Interest: None Declared
P56 Discrepancies between clinical assessment and MR imaging in JIA
E. Charlotte van Gulik1, Robert Hemke1, Mendy M. Welsink-Karssies2, Dieneke Schonenberg1,
Koert M. Dolman3, Anouk M. Barendregt1, Charlotte M. Nusman1, Taco W. Kuijpers1, Mario
Maas1, J. Merlijn van den Berg1
1AMC, Amsterdam, Netherlands; 2OLVG, Amsterdam, Netherlands; 3Reade, Amsterdam, Netherlands
Correspondence: E. Charlotte van Gulik
Introduction: With the increased use of imaging as a supportive tool for starting
or intensifying treatment in JIA patients, discrepancy between the MR imaging and
clinical assessment will pose a dilemma.
Objectives
To evaluate patient characteristics and disease activity parameters in a single tertiary
center cohort of JIA patients, both with and without synovial hypertrophy upon MRI,
in order to explore frequency of mismatching results.
Methods
Clinical, laboratory, and contrast-enhanced MRI data of the knee of prospectively
enrolled JIA patients from 2008-2014 were analyzed. JIA was diagnosed according to
the ILAR criteria. The Wallace criteria for inactive disease were used. The validated
Juvenile Arthritis MRI Scoring (JAMRIS) system for the knee was used to evaluate the
presence of synovial hypertrophy (1). Clinically active and inactive patients were,
as separate groups, divided into two groups based on the JAMRIS (four groups in total):
JAMRIS score ≥1, meaning synovial hypertrophy, or JAMRIS score 0. Patient characteristics
and disease activity parameters were then compared using the Chi-square and Fishers
exact test if data were categorical and with the Mann–Whitney U if continuous.
Results
The MRI showed contradictory findings with reference to the clinical assessment in
43 of 124 patients (34.7%) (Table 20). The clinically active patients with discordant
findings ((i.e. no synovial hypertrophy seen on MRI; n = 25) were significantly older
and had been more often diagnosed with polyarticular JIA, compared to the clinically
active patients with concordant findings (n = 47) (median age 13.2 years vs 10.9;
p = 0.006 and 72% vs 34%; p = 0.003, respectively). The clinically inactive patients
with discordant findings (i.e. synovial hypertrophy seen on MRI; n = 18) were significantly
younger than the clinically inactive patients with concordant findings (median age
10.7 years vs 14.4; p = 0.008). Other clinical parameters, including CHAQ, laboratory
results and medication usage were, however, not significantly different between the
discordant and concordant groups (Table 20).
Table 20
(Abstract P56). See text for description
Clinically Active
Clinically Inactive
Variable
Concordant n = 47
Discordant n = 25
p-value
Concordant n = 34
Discordant n = 18
p-value
Female gender, n(%)
26 (55.3)
18 (72.0)
0.209
23 (44.2)
10 (19.2)
0.389
Age, years
10.9 (8.6-13.7)
13.2 (11.3-15.6)
0.006
14.4 (12.1-16.3)
10.7 (9.3-13.6)
0.008
Oligoarticular JIA, n(%)
21 (44.7)
2 (8.0)
0.001
11 (32.4)
11 (61.1)
0.076
Polyarticular JIA, n(%)
16 (34.0)
18 (72.0)
0.003
19 (55.9)
4 (22.2)
0.038
Other subtypes, n(%)
10 (21.3)
5 (20)
1.000
4 (11.8)
3 (16.7)
0.682
Conclusion
Nearly 35% of the JIA patients showed discordant findings between clinical assessment
and MRI. Clinically active patients without synovial hypertrophy on MRI were significantly
older at the time of MRI than the clinically active patients with synovial hypertrophy
on MRI.
In the clinically inactive JIA patients, the discrepancy between clinical assessment
and MRI was especially seen in younger patients. The meaning of synovial hypertrophy
in the clinically inactive patient is still unknown, but it might indicate an incomplete
disease remission.
References
1. Hemke R, van Rossum MA, van Veenendaal M, Terra MP, Deurloo EE, de Jonge MC, et
al. Reliability and responsiveness of the Juvenile Arthritis MRI Scoring (JAMRIS)
system for the knee. European radiology. 2013;23(4):1075-83.
Disclosure of Interest: None Declared
P57 Flow cytometry based assay of platelet reactivity in children with Kawasaki disease-
a preliminary study
Pandiarajan Vignesh1, Surjit Singh1, Amit Rawat1, Man Updesh S. Sachdeva2, Jasmina
Ahluwalia2
1ALLERGY IMMUNOLOGY UNIT, PEDIATRICS, POSTGRADUATE INSTITUTE OF MEDICAL EDUCATION
AND RESEARCH, Chandigarh, India; 2Hematology, POSTGRADUATE INSTITUTE OF MEDICAL EDUCATION
AND RESEARCH, Chandigarh, India
Correspondence: Pandiarajan Vignesh
Introduction: The acute phase of Kawasaki disease (KD) involve endothelial damage
and activation of platelets. Markers of platelet activation were found to be elevated
in adults with coronary artery disease (CAD) and venous thromboembolism. The actual
evidence for platelet activation in KD, however, is limited to platelet aggregation
studies and few studies on platelet activation markers and circulating microparticles.
Monocyte-platelet aggregates (MPA), one of the most sensitive markers for activated
platelets has not been studied in the acute phase of KD.
Objectives: To assess platelet reactivity by flow cytometry based measurement of MPA
in children with KD.
Methods: Fourteen (14) children with KD, 15 age-matched febrile controls, and 13 age-matched
healthy controls were enrolled in this prospective study. Diagnosis of KD was based
on the American Heart Association (AHA) 2004 criteria. Samples were collected at three
different phases of illness in patients with KD- acute stage prior to administration
of IVIg and aspirin, 24 hours after administration of IVIg, and 3 months after onset
of illness. Immediate fixation of the sample and lysis of red blood cells (RBC) were
carried out at the room temperature with the use of BD FACS lysing solution. The washed
samples were immunolabeled with a saturating concentration of PerCP-conjugated CD14
(lipopolysaccharide-protein receptor, BD PharmingenTM, Catalogue no. 555398) and fluorescein
isothiocyanate (FITC) conjugated GP IIb (CD41, BD PharmingenTM, Catalogue no. 555466).
Following incubation for 20 minutes at room temperature, the cells were acquired on
the flow cytometry (Beckman coulter, Navios). The monocytes were gated from the lymphocyte
side scatter plot and MPAs was identified from the monocyte population that had expressed
both CD14 (monocyte marker) and CD41 (platelet marker) using the Kaluza software.
Results: The median age group (inter-quartile range) in the cases, febrile controls,
and normal controls were 6 (3.0, 7.25), 5 (3.6, 9.0), and 5.5 years (4.15, 6.5), respectively.
Male to female ratio among the groups were 12:2, 13:2, and 11:2 respectively. Echocardiographic
abnormalities were detected in 3 children (2- transient abnormalities such as coronary
wall brightness and coronary ectasia, 1- giant coronary aneurysms). Percentage of
MPA% values were significantly high in children with KD [Median (IQR)- 41.3% (26.6,
52.7)] compared to the febrile [Median (IQR)- 5.98% (2.98, 9.72)] and normal controls
[Median (IQR)- 4.48% (2.57, 5.59)], p < 0.01. A consistent drop in serial MPA% was
observed from the diagnosis of KD to the end of third month follow-up [Table 21].
The MPA% values at 3 months post diagnosis of KD [Mean (SD)- 9.59% (7.65)] were significantly
higher compared to the normal controls [Mean (SD)- 4.3% (2.03)], p-0.004.
Table 21
(Abstract P57). See text for description Median percentage values of MPA (CD14 + CD41+)
in children with KD in follow-up: at diagnosis, 24 hour after completion of IVIg infusion
and 3 months after diagnosis
S no
Category
Median MPA% (IQR)
P value
1
At enrolment (n = 14)
41.31 (26.6, 52.69)
<0.001*
2
24 hours after IVIg (n = 14)
18.55 (9.2, 22.99)
3
Follow-up at 3rd month (n = 11)
7.55 (4.15, 14.6)
*p < 0.05 considered significant
Conclusion: MPA% as an objective measure of platelet activation was significantly
elevated in children with acute stages of KD when compared with age and sex-matched
febrile and normal controls. Elevated levels of MPA% in patients with KD 3 months
post diagnosis suggest that the endothelial inflammation or damage in KD persists
for a longer duration even after control of symptoms and signs of systemic inflammation.
Long-term studies on platelet activation markers in a larger multicentric cohort would
conclusively establish the role of platelets in acute and long-term cardiac morbidity
in KD.
Disclosure of Interest: None Declared
Immunodeficiency and infection related arthritis
P58 Deficiency of CD70 is responsible of a case of chronic active EBV (CAEBV) infection
presenting as periodic fever
Roberta Caorsi1, Marta Rusmini2, Stefano Volpi1, Sabrina Chiesa1, Caludia Pastorino1,
Francesca Minoia1, Alice Grossi2, Sara Signa1,3, Paolo Picco1, Angelo Ravelli1,3,
Isabella Ceccherini2, Marco Gattorno1
1Second division of Pediatrics, G. Gaslini Institute, Genova, Italy; 2Division of
Human Genetics, G. Gaslini Institute, Genova, Italy’; 3DINOMGI, University of Genova,
Genova, Italy
Correspondence: Roberta Caorsi
Introduction: Chronic active EBV (CAEBV) infection is a rare condition associated
to a chronic activation of Epstein Barr virus and therefore to a chronic and potentially
life-threating lymphoproliferation. The prognosis is poor: most of the patients not
treated with bone marrow transplantation die for lymphatic malignancies and the common
immunosuppressive and antiviral therapy are usually not effective. Even if with a
wide heterogeneity, most of the patients with CAEBV present severe clinical manifestations
with early onset and poor prognosis; the presence of an underlying immunodeficiency
causing an unusual EBV replication is therefore reasonable.
Objectives: To describe the clinical course and the genetic characterization of a
patient with CAEBV mimicking PFAPA at disease onset.
Methods: In a patient with CAEBV infection a whole exome sequencing (WES) approach
was undertaken and variants were prioritized with a custom pipeline to identify the
genetic cause of his condition that was validated through Sanger Sequencing in the
trio.
Results: The patient, born of consanguineous parents, at the age of 15 months presented,
in complete wellbeing, a not-complicated infectious mononucleosis; in the following
months he presented recurrent episodes of high fever with exudative tonsillitis, adenitis,
splenomegaly and sweating, lasting 3-5 days and treated with NSAIDS or antibiotics.
Blood examinations revealed neutrophilic leukocytosis and elevation of acute phase
reactants; plasmatic immunoglobulins were within the normal range. An autoinflammatory
condition with periodic fever was suspected and therefore on-demand steroidal treatment
was suggested, with good response. The child continued to present periodic fever,
associated to the occurrence of respiratory infections requiring antibiotics, and
recurrent episodes of cheratitis. Several destructive dental caries were found as
well as hyper sensibility to mosquitoes bite.
Immunologic test revealed then a reduction in the level of plasmatic immunoglobulins.
The detection of EBV DNA with quantitative PCR revealed 21935 copies for 100000 leucocytes
with prevalence of infection in the B cells. Whole body positron emission tomography
revealed a retroperitoneal formation of about 35 mm with an increased metabolism that,
at biopsy, revealed a reactive lymphadenopathy with paracortical involvement associated
with EBV infection.
Genetic conditions associated to chronic EBV infection and immunodeficiency were ruled
out: the genetic tests for SAP, XIAP, BAFF-R and ICOS were negative and the cytofluorimetric
analysis of perforin, CD107 and 2B4 receptor were normal. In light of these findings
a CAEBV was suspected.
Being the patient in good general conditions and in light of the prevalent involvement
of CD20+ lymphocytes, on demand treatment with rituximab was started. The clinical
response to treatment was initially very satisfying; however after two years the child
presented severe infections requiring prolonged hospitalisation; stem cell transplantation
was then performed with a complete normalization of both clinical and immunological
features.
Among variants identified through a WES analysis of the patients and his parents,
a homozygous mutation of the CD70 gene appeared to fit the recessive model of inheritance.
The variantc.163-2A > G affects the exon2AG-acceptor splice site of the CD70 gene
(NM_001252) leading to a deficiency in CD70, the ligand of CD27, a gene involved in
isolated immunodeficiency. In the meantime our analysis was ongoing, CD70 mutations
were reported in a few patients with a similar condition.
At the protein level, the anti-CD70 antibody failed to detect CD70 by flow cytometry
at the cell surface of PHA-stimulated T and EBV-trasformed B cells of the patient.
In contrast, expression of CD70 was detectable on cells from healthy donors.
Conclusion: This case describe a new case of a newly identified genetic cause of CAEVB
presenting with recurrent periodic fever.
Disclosure of Interest: None Declared
P59 Clostridium difficile enterocolitis and reactive arthritis: a case report ad re-view
of the literature
Lorenzo Mambelli1, Michela Cappella2, Martina Mainetti1, Federico Marchetti1
1Pediatrics, S. Maria delle Croci Hospital, Ravenna, Italy; 2Pediatric and Adolescence
Rheumatology, S.Maria Nuova Hospital, Reggio Emilia, Italy
Correspondence: Lorenzo Mambelli
We report the case of a 6-year-old boy with pain in the right knee and both ankles
after a 10-day course of oral amoxicillin-clavulanate completed three weeks earlier;
at the same time he developed diarrhea with positive culture for Clostridium difficile
(CD). Three days later the knee and ankles arthritis resolved spontaneously but appeared
in the right shoulder and homolateral hip with a migratory pattern and with fever.
Synovial fluid and blood cultures, rheumatoid factor, ANA and HLA-B27 antigen were
negative. The improvement of colitis and the negativity of fecal calprotectin at follow-up
allowed to exclude an inflammatory bowel disease. Nonsteroidal anti-inflammatory drugs
(NSAIDs) and metronidazole completely resolved pain, joint swelling and diarrhea.
After 24 months of follow-up there has been no recurrence.
Reactive Arthritis (ReA) is an aseptic acute inflammatory arthritis occurring after
an intercurrent infection in which the causative organism is outside from the joint.
It is typically an asymmetrical oligo/polyarthritis predominantly in the lower limbs
large joints (knee, ankle, hip) and present approximately 2-4 weeks following infection.
Several patients present a migratory pattern and acute arthritis is often characterized
by severe pain and sometimes erythema over the affected joints; enthesitis/tenosynovitis
may occur. Most frequent causes are Salmonella, Shigella, Yersinia, C. jejuni, group
A Streptococcus and C. trachomatis.
CD is the most common cause of diarrhea after antibiotic therapy but CD ReA is rare
and its pediatric epidemiology is poorly known; it was generally migratory and polyarticular,
involving large joint and tipically with a good outcome and self-limiting course.
For the diagnosis of ReaA following CD enterocolitis there are criteria established
by Putterman and Rubinow [1], but basically a history of diarrhoea after a course
of antibiotic with the exclusion of other causes of gastroenteritis or noninfectious
arthritis is essential.
Jacobs et al [2] documented until 2001 35 cases of CD ReA in adults; epidemiology
in child instead is rare and unknown, but incidence of CD infection has increased
among children. We performed a literature search of MEDLINE, Google Scholar, and Cochrane
Reviews computerized databases using the keywords “Clostridium difficile”, “arthritis”,
and “child” to identify all papers reporting CD enterocolitis-associated ReA in childhood.
Six papers met our review's inclusion criteria with a total of 32 pediatrics cases
of CD ReA. The most recent study identified, from 2004 to 2013, 26 cases with acute
arthritis/tenosynovitis after CD infection and authors estimate that CD ReA affected
1.4% of child with CD infection; only 35% of CD ReA were correctly diagnosed, occasionally
misdiagnosed as septic arthritis [3].
Conclusion: CD infection should be suspected in children presenting with an acute
inflammatory arthritis following an episode of diarrhea, especially when culture for
common enteric infection are negative and the patient has received antibiotic therapy
before the onset of diarrhea.
Written informed consent for the publication of patient details was obtained.
Disclosure of Interest: None Declared
References
[1]Putterman et al,Reactive arthritis associated with Clostridium difficile pseudomembranous
colitis.Seminars in Arthritis and Rheumatism;22(6),pp 420-6,1993
[2]Jacobs et al,Extracolonic manifestations of Clostridium difficile infections:Presentation
of 2 cases and review of the literature.Medicine;80(2),pp 88-101,2001
[3]Horton et al,Epidemiology of Clostridium difficile Infection–Associated Reactive
Arthritis in Children.An Underdiagnosed,Potentially Morbid Condition.JAMA Pediatr.
2016;170(7)
Juvenile idiopathic arthritis (JIA) in practice
P60 The effect of task-oriented training with video-based games on activity performance
and participation in children with juvenile idiopathic arthritis
Nilay Arman1, Ela Tarakci1, Devrim Tarakci2, Ozgur Kasapcopur3
1Division of Physiotherapy and Rehabilitation, Faculty of Health Science, Istanbul
University, Istanbul, Turkey; 2Division of Ergotherapy, Istanbul Medipol University,
Istanbul, Turkey; 3Department of Pediatric Rheumatology, Medical Faculty of Cerrahpasa,
Istanbul University, Istanbul, Turkey
Correspondence: Nilay Arman
Introduction: Juvenile idiopathic arthritis (JIA) is most common chronic rheumatic
disease in childhood. The upper extremity involvement in JIA causes muscle imbalance,
joint destruction, pain, stiffness and limitations on activities of daily living (ADL)
in varying degrees. However, the information about prevalence of symptoms, disorders,
ADL limitations, participation restriction and options of treatments for upper extremity
involvement in JIA are limited. It has been reported that improvements of upper extremity
functions were achieved by video-based games (VBG) in various disease groups. However,
in the literature, no study has been found about effectiveness of VBG in children
with arthritis.
Objectives: The aim of the study was to investigate the effects of two different task-oriented
activity training to activity performance and participation in children who have involved
upper limb with JIA.
Methods: 62 patients included in the study were randomized into two groups as group
I (patient-centered task-oriented activity training in daily living conditions) and
group II (patient-centered task-oriented activity training with VBG). The patients’
pain, by “Numeric Rating Scale (NRS)”, range of motion (ROM) by “goniometer”, muscle
and grip strengths by “dynamometer”, activity performance and participation by “Childhood
Health Assessment Questionaire (CHAQ)”, “Duruoz Hand Index (DEI)”, “Jebsen-Taylor
Hand Function Test (JTHFT)” and “Nine Hole Peg Test (NHPT)” were evaluated. In group
I, ADL were trained with real materials used in daily life and various rehabilitation
products. In group II, ADL were trained with VBG. We have created training protocol
with Xbox 360 games for patient-centered task-oriented activity training with VBG.
We prefered ‘Dance Central2’, one of the Xbox 360 games, for warming (macerana dancing,
10 minutes). Other games, ‘Fruit Ninja’, ‘Table Tennis’, ‘Boxing’, ‘Volleyball’, ‘Darts’
and ‘Bowling’ were selected appropriately according to patients performance. All the
patients completed 8 weeks (45 minutes for every session, 3 times in a week) of client-centered
treatment.
Results: After treatment in both groups, significant changes were found in NRS, ROM,
muscle strength, grips strength, CHAQ, DEI, JTHFT and NHPT (p < 0,05). Table 1 shows
comparison between the groups for the activity performance, pain severity, hand grip
and pinch grip strengths. After the treatment, group II was statistically more superior
than group I in changes of wrist extension ROM and DEI (p <0.05). In addition to,
almost all changes of muscles strength in group II were statistically more superior
than changes of group I (p < 0.001).
Conclusion: In our study, two different task-oriented activity training provided significant
changes in pain, ROMs of upper extremity, muscle strength, grip strength, activity
performance and participation and patient-centered task-oriented activity training
with video-based games has been proved as an alternative treatment in children who
have involved upper limb with JIA.
Trial registration identifying number: Clinical Trial Number: NCT02954718
This work was supported by Research Fund of Istanbul University. Project No: 51144
Disclosure of Interest: None Declared
P61 Analysis of activity performance problems in patients with juvenile idiopathic
arthritis
Nilay Arman1, Ela Tarakci1, Ozgur Kasapcopur2
1Faculty of Health Sciences, Division of Physiotherapy and Rehabilitation, Medical
Faculty of Cerrahpasa, Istanbul University, Istanbul, Turkey; 2Department of Pediatric
Rheumatology, Medical Faculty of Cerrahpasa, Istanbul University, Istanbul, Turkey
Correspondence: Nilay Arman
Introduction: Juvenile idiopathic arthritis (JIA) is the most common chronic rheumatic
disease in children and is an important cause of short-term and long-term disability.
Many children appeared to have elbow, hand- and/or wrist-related symptoms and impairments,
with resulting moderate to severe levels of activity limitations and participation
restrictions at daily living. However, in the literature, no study has been found
about variety of activity performance problems in patients with JIA. The Canadian
Occupational Performance Measure (COPM) is a client-centered, patient reported outcome
measure with which clients evaluate their activity performance and satisfaction with
performance in areas of self-care, productivity and leisure. COPM is generally used
for analyzing activity performance problems in many chronic diseases.
Objectives: The aim of the study was to analyze the activity performance problems
of patients with JIA.
Methods: 50 patients with JIA (42 Female, 8 Male) were included in the study. Inclusion
criteria consisted of a diagnosis of JIA according to the International League of
Associations for Rheumatology criteria, being aged between 6–18 years, having at least
one affected joint in upper extremity (shoulder, elbow, wrist, and finger joints).
Activity performance problems as perceived by the individual were measured using face
to face interview by the Canadian Occupational Performance Measure (COPM). During
the interviews, the patients were encouraged to identify any daily activity that they
would like or need to do but found difficult to complete because of their rheumatic
diseases. Patients then identified the five most important daily activities and rated,
first, their current level of performance, and then, how satisfied they were with
this current level of performance. These performance and satisfaction scores were
rated by on a 10-point scale, with higher scores indicating better performance and
satisfaction. The statistical software SPSS 21.0 was used for the analyses.
Results: The mean age was 12,76 ± 3,16 and the mean disease duration was 5,92 ± 3,82 years.
8% of patients had involvement shoulder joint, 74% of them had involvement elbow joint,
88% of them had involvement wrist joint and also 64% of them had involvement finger
joint. The patients with JIA described 36 different types of problematic activities
and identified 30 of them as the five most important daily activities. Table 22 shows
frequencies of five most important daily activities of patients with JIA. The five
most identified problems were “carrying something” (66%), “writing” (50%), “opening
a bottle cap” (48%), “dressing” (38%) and “opening a door with handle/knob” (38%)
according to COPM. The mean of COPM-performance scores was 3,99 ± 1,72 and the mean
disease COPM-satisfaction scores was 2,56 ± 1,70.
Table 22
(Abstract P61). Frequencies of five most important daily activities of patients with
JIA
Activity
%
Activity
%
Activity
%
Activity
%
Carrying something
66
Using a knife
20
Drinking
8
Gripping small objects
4
Writing
50
Buttoning
18
Cutting nail
8
Using a scissors
4
Opening a bottle cap
48
Taking a bath
16
Washing dishes
6
Stirring a soup
2
Dressing
38
Peeling a fruit
14
Pushing something
6
Opening a zipper
2
Opening a door with handle/knob
38
Washing hair
14
Removing a sock
4
Acclaiming
2
Combing
28
Tying a shoelace
12
Reaching to grab something
4
Using a fork
2
Unlocking
28
Brushing teeth
10
Unpacking
4
Tapping
26
Eating
10
Conclusion: Our results showed that patients with JIA, who have at least one affected
joint in upper extremity, reported problems with a wide range of activities. We suppose
that the COPM can be a useful tool for identifying activity performance problems as
a patient-focused outcome measure and also, it could provide information about patient
centered management for patients with JIA.
Disclosure of Interest: None Declared
P62 Vaccination coverage in children with rheumatic diseases
Maša Bizjak1, Tadej Avčin1,2, Nataša Toplak1,2
1Department of Allergology, Rheumatology and Clinical Immunology, University Children's
Hospital, University Medical Centre Ljubljana, Ljubljana, Slovenia; 2Department of
Pediatrics, Faculty of Medicine, University of Ljubljana, Ljubljana, Slovenia
Correspondence: Maša Bizjak
Introduction: The evidence of vaccine safety and efficacy in patients with rheumatic
diseases is increasing. However, the data on vaccination status in children with rheumatic
diseases remain scarce. So far, only few smaller studies were published that found
suboptimal vaccination coverage in patients with rheumatic diseases.
Objectives: To assess vaccination status in a cohort of children with rheumatic diseases
followed at the University Children's Hospital Ljubljana and to evaluate the most
common reasons for vaccination dropout.
Methods: All consecutive patients with rheumatic diseases evaluated at the rheumatology
outpatient clinic between 1 January 2015 and 15 January 2017 received a questionnaire
about their vaccination status and reasons for potential vaccination dropout. Descriptive
statistics were used to analyse the proportion of children with full vaccination status
at 5, 10, 18 years and at their last clinic visit. The study was approved by the national
ethics committee.
Results: By May 2017 the data were received from 125 out of 422 enrolled patients
(29.6%). Among included patients 64.8% were female, median age was 12.3 (1.5-22.9)
years and median age at diagnosis 5.8 (0.7-16.6) years. The majority of included children
had JIA (n = 114), followed by SLE (n = 5), CRMO (n = 2), JDM (n = 2), MCTD (n = 1)
and systemic sclerosis (n = 1). Vaccination coverage was complete in 92.1%, 81.3%,
72.2% and 71.2% of patients at 5, 10, 18 years and at their last clinic visit, respectively.
Most commonly omitted vaccines were Hepatitis B (22.9%) and second dose of Measles,
Mumps and Rubella vaccine (18.3%). Most common additional vaccine was against tick-borne
encephalitis (26.4%), which is an endemic disease in Slovenia. Most common reasons
for vaccination dropout were suggestion of the treating rheumatologist and active
disease.
Conclusion: We experienced a low initial response rate of 30%, which might be due
to increasing parents' vaccine hesitancy. In our sample we found an approximately
10% decrease in complete vaccination coverage between consecutive age cohorts. Overall
vaccination coverage in children with rheumatic diseases is lower than in general
population in Slovenia. Parent and patient education on vaccination remains crucial
and when possible, vaccination catch-up plans and booster vaccinations should be advocated
on an individual basis.
Disclosure of Interest: None Declared
P63 Quality of referral letters to pediatric rheumatology and its impact on access
to care
Abstract withdrawn
P64 Contextualizing guidelines for the management of juvenile idiopathic arthritis
in developing countries: a needs assessment
Mercedes O. Chan1, Ricardo Russo2, Lawrence Okong'o3, Christiaan Scott4
1Pediatrics (Rheumatology), University of Alberta, Edmonton, Canada; 2Immunology and
Rheumatology, Hospital de Pediatría Garrahan, Buenos Aires, Argentina; 3Paediatrics
and Child Health, University of Nairobi, Nairobi, Kenya, 4University of Cape Town,
Cape Town, South Africa
Correspondence: Mercedes O. Chan
Introduction: Juvenile idiopathic arthritis (JIA) is the most common rheumatic disease
of childhood (4/1000 children) and untreated, can lead to significant morbidity including
joint deformities, loss of function and blindness (uveitis). Guidelines for the management
of JIA have been created for use in the developed world. Challenges in diagnosis and
management arise when these guidelines are applied in low-resource settings given
different endemic diseases, access to care, and sociocultural practices.
Objectives: We performed a needs assessment of clinicians managing JIA in low-resource
settings with a view to applying our findings to recommendations for JIA management
in developing countries.
Methods: An anonymous needs assessment regarding the management of JIA in developing
countries was developed based on four areas of attention identified by rheumatologists
in the developing world: patient management (access to care and medications, clinical
work-up, transition); education (to the health professions and the public); advocacy,
networks and policy; and research. The survey (available in English and Spanish) was
tested, validated and electronically circulated to healthcare practitioners who see
children with JIA in developing countries. Contacts were acquired through pediatric
rheumatology professional networks
Results: The survey was distributed to 502 practitioners, with 116 responses from
clinicians in South America (50%), Africa (28%), Asia (12%), the Middle East (1.5%),
Central America (1.5%) and other countries (7%). Respondents were pediatric rheumatologists
(66%), adult rheumatologists (22%), allied health professionals (7%), general pediatricians
(4%) and general practitioners (1%); median age 40-50 years, median 10-15 years in
practice. The percentage of time devoted by these clinicians to pediatric rheumatology
in their practice was: <25% (29%), between 26-50% (19%), between 51-75% (13%), >75%
(17%) and 100% (22%).
Barriers to accessing care for children with JIA identified by respondents were: insufficient
training in JIA among pediatricians (74%), lack of awareness of JIA in the healthcare
community (73%), long referral pathways (67%) and few pediatric rheumatologists (63%).
Endemic diseases that complicate the management of JIA in participants’ settings were:
tuberculosis (84%), HIV (41%), sickle cell anemia (31%), malaria (19%) and diarrheal
disease (19%). Transition planning was not a programmed strategy in >40%; and non-adherence
to uveitis screening guidelines was reported in >40%.
Education on JIA was available to 71% of pediatrics trainees, 50% of adult rheumatology
trainees and <50% of medical students in participants’ settings. Established pediatric
rheumatology training programs were unavailable to 40%; access to educational resources
and educating the public on JIA was available to only one third of respondents.
Policy and advocacy interventions felt to potentially improve access to care for JIA
patients were: increasing the availability of pediatric rheumatologists (79%) and
jobs for them (50%), better training on managing JIA (74%), formulation of clear referral
channels (65%), formation of patient support groups (62%) and availability of management
guidelines (49%).
One third of participants were not involved in research. Epidemiological and clinical
research were felt to be research priorities in JIA by 75% and 62% of participants
to ascertain local burdens of disease. Major barriers to performing research include:
lack of funding (79%), lack of time (58%), lack of support systems, e.g., laboratory
(52%), lack of trained personnel (46%) and lack of experience (26%).
Conclusion: Management of JIA remains a challenge in the developing world; is rooted
in educational gaps in the medical and general community; and complicated by endemic
disease and insufficient access to resources. Guidelines specific to low-resource
settings, and informed by research exploring the local burdens of disease and experiences
of stakeholders, may serve as a powerful educational document to advocate for policy
change and best practices.
Disclosure of Interest: M. Chan Grant/Research Support from: International League
Against Rheumatism Grant, R. Russo Grant/Research Support from: International League
Against Rheumatism Grant, L. Okong'o Grant/Research Support from: International League
Against Rheumatism Grant, C. Scott Grant/Research Support from: International League
Against Rheumatism Grant
P65 Evaluation of the diagnostic delay and access to remission in JIA patients of
the JIR cohorte
Caroline Freychet1, Natalia Cabrera2, Lega Jean Christophe2, Michael Hofer3, Alexandre
Belot4 and JIR cohorte
1Laboratory HESPER (Health Services and Performance Research), University Claude Bernard
Lyon 1, Lyon, France; 2Team Evaluation et Modélisations des Effets Thérapeutiques,
University Claude Bernard Lyon 1, Lyon, France; 3Paediatric Rheumatology, University
hospital of Lausanne, Lausanne, Switzerland; 4Paediatric Rheumatology, University
hospital of Lyon, Lyon, France
Correspondence: Caroline Freychet
Introduction: Many studies in pediatric rheumatology underline the concept of « window
of opportunity », early in the disease course to prevent joint or ocular damage in
the context of juvenile idiopathic arthritis (JIA). In Europe, despite facilitated
access to health care, children with JIA are referred to pediatric rheumatology centres
with significant delay. This delay is closely linked to the organization of the country’s
health care delivery system. In France and Switzerland nothing is known about diagnostic
delay and little about access to remission in JIA.
Objectives: To assess the diagnostic delay and the rate of remission at one year and
2 years in JIA patients of the JIR cohorte.
Methods: The JIRcohorte is an international network dedicated to collect prospective
and retrospective data on juvenile inflammatory rheumatic diseases. Data collection
started in 2013. We included all French and Swiss JIA patients according to the ILAR
classification. We focused on the relationship between (i) diagnostic delay (defined
by the number of weeks between the first symptoms and the diagnosis), (ii) distance
between parent’s home and the place of the diagnosis, and (iii) remission rate at
one year, two years and treatments.
Results: We included 709 JIA patients (50% oligoarthritis, 17% RF– polyarthritis,
15% enthesitis-related arthritis [ERA], 10% systemic JIA [sJIA], 3% RF+ polyarthritis,
3% psoriatic arthritis, and 2% undifferentiated arthritis).
The median diagnostic delay of the whole cohort was 17 weeks (interquartile range
(IQR) 9-48). The patients with ERA had the longest delay: 45 weeks (13-104), whereas
children with sJIA had the shortest delay: 9 weeks (4-21). The median diagnostic delay
was not correlated with parents’ home distance from the diagnostic center. 59% and
57% of the patients were in remission and 57% at 1 and 2 years of follow-up, respectively.
The median delay between diagnosis and treatment onset was 3 weeks (IQR 0-34) for
oral corticosteroids, 8 weeks (IQR 0.3- 30) for intra-articular corticosteroids, 9 weeks
(IQR 0-52) for DMARDS and 52 weeks (IQR 19-147) for biologics.
The diagnostic delays for the whole cohort and for the different JIA subtypes are
in line with the international literature. JIA with indolent symptoms as ERA had the
longest diagnostic delay whereas sJIA associated to overt manifestations including
fever had the shortest delay. In France and Switzerland, there are no guidelines about
diagnostic delay but UK guidelines advocate a diagnostic delay inferior to 10 weeks.
According to these guidelines, 68% of our patients exceed this delay, which is shlighly
lower than previous studies. The absence of correlation with parents’ home distance
from the diagnostic center is also described in other countries. Our remission rate
at 1 year is higher than described in other studies but it decrease at 2 years. The
treatment delay is longer in our cohort than in other studies.
Conclusion: The diagnostic delay and treatment delay in France and Switzerland are
too long. Strong efforts have to be made to understand the underlying factors to suggest
improvements in care pathway organization and practices by the elaboration of care
course management guidelines. The JIR network permit to design a prospective study
to identify these factors and improve the short-term prognosis of JIA, in the context
of national and European rare disease health programs.
Disclosure of Interest: None Declared
P66 Performance of disease activity measures in pediatric patients with enthesitis-related
arthritis
Abstract withdrawn
P67 Teaching adult rheumatology fellows to help young adult patients ‘stick the landing’
when transferring from pediatric to adult rheumatology care
Rebecca E. Sadun1, Gary R. Maslow2, Lisa G. Criscione-Schreiber3
1Internal Medicine and Pediatrics, Duke University, Durham, NC, United States; 2Pediatrics
and Psychiatry, Duke University, Durham, NC, United States; 3Internal Medicine, Duke
University, Durham, NC, United States
Correspondence: Rebecca E. Sadun
Introduction: The transition from pediatric to adult healthcare is a vulnerable time
for adolescents and young adults (AYA) with chronic conditions. Thie year the European
League Against Rheumatism (EULAR) and the Pediatric Rheumatology European Society
(PReS) jointly offered expert-opinions regarding transitional care of AYA with juvenile-onset
rheumatic diseases and the American College of Rheumatology (ACR) developed a toolkit.
For these guidelines to be implemented or for these resoures to be utilized, adult
and pediatric rheumatologists need to understand their application. Nevertheless,
there are no published curricula for teaching transition skills to rheumatologist-in-training.
Objectives: We sought to develop and assess the impact of a workshop designed to help
adult rheumatology fellows learn key skills for providing effective transition care
to transferring young adult patients.
Methods: A 1-hour skills-based workshop on transition and transfer best practices
was developed alongside an objective standardized clinical examination (OSCE) station
in which trainees were given 12 minutes to welcome a young adult with lupus – and
her parent – to a first visit in an adult clinic and perform a full history. The OSCE
evaluation rubric assessed five transition/transfer skills (skills 1-5) and one “control
skill” (skill 6), on a Likert scale of 1-5, with 5 being the best performance. Adult
rheumatology fellows (n = 19) from 5 institutions were evaluated with the OSCE; 12
were tested with the OSCE de novo, whereas 7 were tested with the OSCE after participating
in the workshop. Unpaired, aggregated OSCE scores were complemented with unpaired
pre- & post-survey data in which fellows reported their self-assessed level of preparation
for 12 transition and transfer skills.
Results: Fellows’ self-assessed proficiency with 12 key transition/transfer skills
increased significantly with participation in the workshop and accompanying OSCE,
including fellows’ confidence in their ability to discuss the needs of the transferring
patient with the pediatric rheumatologist (p < 0.01). In addition, OSCE performance
(see Table 23) was greater in the group of fellows that participated in the workshop
prior to the OSCE (“post-workshop” - average score of 4.3) than in the group that
took the OSCE de novo (“pre-workshop” - average score of 3.3, p = 0.01). The skills
demonstrating statistically significantly higher scores post-workshop were: skill
1) highlighting differences between adult and pediatric care and setting expectations
(p < 0.01); skill 2) placing the patient in the primary role and utilizing the parent
for corroboration (p < 0.05); and skill 4) performing a confidential adolescent social
history. There was a trend towards improved performance for skill 3, assessing self-management
skills, whereas there was no significant change in skill 5, assessing barriers to
transition and medication adherence. Performance on skill 6, the control skill of
assessing patient and parent understanding of the disease process, was lower in the
group of fellows’ that participated in the workshop prior to being tested with the
OSCE (p = 0.01).
Table 23
(Abstract P67). See text for description
Skill 1
Skill 2
Skill 3
Skill 4
Skill 5
Total/Avg
Skill 6
Pre-workshop (n = 12)
3.5
4.3
3.8
2.8
2.3
16.7/3.3
3.5
Post-workshop (n = 7)
4.6
5.0
4.4
4.7
2.6
21.3/4.3
2.0
p-value
<0.01
<0.05
0.18
0.01
0.86
0.01
0.01
Conclusion: A brief educational intervention successfully increased adult rheumatology
fellows’ perception of their proficiency with key transition/transfer skills. In addition,
fellows who participated in the educational intervention had significantly higher
scores on their OSCE performance. It is likely that the “control skill” score was
lower in the post-workshop group owing to more time being spent on newly acquired
peri-transfer skills: during the 12-minute OSCE scenario, discussing disease pathogenesis
took a backseat to conversations about expectations in the adult care model, self-management
skills, and goal setting. Making this curriculum available to all rheumatologists-in-training
would likely improve the care young adult rheumatology patients receive when transferring
from pediatric to adult rheumatology. A complementary curriculum for pediatric rheumatology
fellows could further improve the care of AYA rheumatology patients.
Disclosure of Interest: None Declared
P68 No radiographic damage after early aggressive treatment in juvenile idiopathic
arthritis
Dieuwke Schreurs1,2, Willemieke van Braak2, Petra Hissink Muller1, Charlotte Nusman2
1Pediatric Rheumatology, LUMC, Leiden, Netherlands; 2Radiology, AMC, Amsterdam, Netherlands
Correspondence: Dieuwke Schreurs
Introduction: Juvenile idiopathic arthritis (JIA) is characterized by chronic inflammation
of the joints which can lead to structural bone damage.
Objectives: The primary objective of this study was to evaluate response of newly
diagnosed JIA patients to an early aggressive treatment by conventional radiography.
Secondary objective was to compare Poznanski and BoneXpert methods to evaluate presence
and progression of radiological damage in wrists of JIA patients.
Methods: JIA patients participating in the BeSt for Kids study (NTR 1574) were eligible
in case of wrist involvement at inclusion if conventional radiographs were available
at baseline or within 6 months before/after study inclusion. Follow-up radiographs
after 12-36 months were available for comparison. Radiographic bone damage as reflected
by carpal length was assessed using Poznanski score. BoneXpert method was used to
determine bone age and bone mineral density (BMD).
Results: Forty JIA (27 female) patients were evaluated for Poznanski score and BMD
(mean age 7.2 ± 3.4 years), 26 patients (15 female) were evaluated for bone age (mean
age 9.3 ± 2.2). At baseline mean Z-score of RM/M2 was 0.047. At follow-up mean Z-score
changed to 0.055 (p = 0.937). Baseline and follow-up Z-scores were not different from
a healthy population. Bone age did not significantly differ at baseline (Z-score 0.08)
and follow-up (Z-score 0.25). At baseline BMD was significantly diminished compared
to healthy controls (Z-score -0.71) and improved significantly (Z-score -0.44 (p = 0.032)).
Conclusion: In this cohort of JIA patients treated early and aggressively we have
detected no radiographic damage in the wrist at baseline or follow up. BMD was significantly
diminished at baseline but improved significantly after follow-up.
Disclosure of Interest: None Declared
P69 The characteristic of the undifferentiated arthritis in juvenile idiopathic arthritis
Betul Sozeri1, Eylem Topaktas1, Duygu Kurtulus2
1Pediatric Rheumatology, University of Health Sciences, Istanbul, Umraniye Training
and Research Hospital, Istanbul, Turkey; 2Physical Medicine and Rehabilitation, University
of Health Sciences, Istanbul, Umraniye Training and Research Hospital, Istanbul, Turkey
Correspondence: Betul Sozeri
Introduction: Juvenile idiopathic arthritis, JIA, is classified into seven categories;
systemic-onset type, persistent and extended oligoarthritis, polyarthritis with rheumatoid
factor negative, polyarthritis with rheumatoid factor positive, psoriatic arthritis,
enthesitis-related arthritis and undifferentiated arthritis classified by the International
League of Associations for Rheumatology. As each category of JIA has different features
in clinical phenotypes, precise subtyping is required for research and management.
Due to inclusion and exclusion criteria, some patients is ended up in the undifferentiated
category. Undifferentiated arthritis includes patients who do not meet criteria for
any category. Or, they meet the criteria for more than 1 category but with either
a close relative who has psoriasis or the presence of RF. The prevalence of subtypes
of JIA was reported; Oligoarticular JIA occurs most frequently (50% to 60% of cases),
followed by polyarticular JIA. However, there is not enough information in the literature
about the undifferentiated arthritis group.
Objectives: We aimed to analysis the characteristic findings of the undifferentiated
arthritis group in JIA patients.
Methods: This was a retrospective longitudinal cohort study of patients with JIA at
a tertiary care pediatric rheumatology clinic. Subjects were included if they were
evaluated at our pediatric rheumatology clinic between June 2016 and May 2017, had
a diagnosis of JIA according to ILAR criteria.
Demographics (sex, age at diagnosis, ANA, RF, HLA B27 status), clinical disease elements
(active joint count, tender enthesis count) and current medication use at each visit
were identified by querying the electronic medical record. All available visits were
included in the analysis. All analyses were performed using SPSS 16.0
Results: During the study period there were 215 JIA patients evaluated at 640 visits.
180(84%) of patients had newly-diagnosed JIA.
There were 21 (84%) girls and 4 (16%) boys. Mean age at disease onset was 13.4 ± 2.2 years.The
median duration of disease was 8 years.The median duration prior to treatment was
1 months. Among 25 patients with undifferentiated arthritis, 11 (48%) patients had
enthesitis, 15 (60%) had sacroiliitis. Joints mainly affected in the undifferentiated
arthritis group with were knees (16, 64%) and 2 patients were RF-positive and 7patients
had positive ANA had undifferentiated arthritis. 6 patients (24%) of undifferentiated
JIA patients used more than one DMARD.Methotrexate was the mainstay of treatment (52%),
with an initial dose of 10–15 mg/m2/week and a maximum dose of 20– 25 mg/m2/week or
25 mg/week. Sulfasalazine was used in36 % of undifferentiated JIA patients. 2 of the
patients received biologic agents.
Conclusion: Since distribution of the JIA category is different upon ethnicity, this
study showed that percentage of undifferentiated JIA patients in our cohort was found
higher reported from other studies in the literature. This is a single center, referral-based
cohort study. As such, it might not represent the entire population of Turkey. In
our conclusion, to clarify characteristics of undifferentiated JIA patients, need
large cohort and multicenter study.
Disclosure of Interest: None Declared
Juvenile idiopathic arthritis
P70 Time of onset of ocular disease in 336 children with juvenile idiopathic arthritis-associated
uveitis: evidence-based data to refine current ophthalmologic screening guidelines
Serena Calandra1, Valentina Muratore2, Valentina Ravaschio1, Gabriella Giancane1,
Alessandra Alongi1, Angela Pistorio1, Alessandro Consolaro1, Angelo Ravelli1
1Istituto Giannina Gaslini, Genova, Italy; 2Fondazione IRCCS Policlinico San Matteo,
Pavia, Italy
Correspondence: Serena Calandra
Introduction: Uveitis is the most common form of extraarticular organ involvement
in juvenile idiopathic arthritis (JIA). The onset of chronic anterior uveitis in JIA
is insidious and often entirely asymptomatic. Children with JIA must be subjected
to periodic eye examinations with slit lamp according to the different risk of developing
this complication. The decision to undertake a screening program depends on the cost-benefit
balance. To date, however, there is uncertainty about the optimal frequency of eye
examinations. Although guidelines for ophthalmologic surveillance have been proposed,
none of them is universally embraced.
Objectives: To evaluate the time of the occurrence of uveitis after the onset of arthritis
in children with JIA
Methods: The clinical charts of 1425 patients with JIA by ILAR criteria followed at
study centers from January 1987 to October 2016 and with a follow-up of at least 6 months
after disease onset were reviewed to identify those who had uveitis. In all patients,
the diagnosis of chronic anterior uveitis was confirmed by an ophthalmologist and
was defined according to the Standardization of Uveitis Nomenclature Working Group
criteria. Children with systemic arthritis, rheumatoid-factor positive polyarthritis
and enthesitis-related arthritis were excluded. Patients who developed uveitis before
the onset of arthritis were also excluded. Patients who developed uveitis at the same
time of the arthritis onset were included. Through the construction of a cumulative
frequency curve, we defined the risk of developing uveitis for each year of disease,
starting with the onset of arthritis.
Results: A total of 336 patients (23.6%) had uveitis a median of 1.1 years after onset
of arthritis. The cumulative frequency curve showed that 47.6% and 67.3% of patients
developed uveitis in the first 1 and 2 years of illness, respectively, and that less
than 5% of all instances of uveitis occurred after 7 years from the onset of arthritis
(Table 24).
Table 24
(Abstract P70). Cumulative frequency of uveitis
Follow-up (years)
0 to 1
1 to 2
2 to 4
4 to 6
6 to 8
8 to 9
> 9
N.
160
66
51
31
15
6
7
Cumulative %
47.6
67.3
82.4
91.7
96.1
97.9
100
Conclusion: Our study shows that nearly half of JIA patients with uveitis developed
this complication in the first year after onset of arthritis and around two-third
within two years. Less than 5% of patients had uveitis after 7 years from disease
onset. These findings underscore the need for tight ophthalmologic monitoring in the
first 2 years of disease and support the recommendation of current guidelines to lengthen
ophthalmologic screening after 7 years of disease without ocular involvement.
Disclosure of Interest: None Declared
P71 An open-label extension study to assess the long-term safety and clinical benefit
of etanercept in pediatric patients with extended oligo, enthesitis related, and psoriatic
JIA: 6-year data from the clipper studies
Ivan Foeldvari1, Tamas Constantin1, Jelena Vojinovic1, Gerd Horneff1, Joke Dehoorne1,
Gordana Susic1, Katarzyna Kobusinska1, Violeta Panaviene1, Zbigniew Zuber1, Valda
Stanevica1, Vyacheslav Chasnyk1, Ronald Pedersen2, Jack Bukowski2, Tina Hinnershitz2,
Bonnie Vlahos2, Alberto Martini1, Nicolino Ruperto1 on behalf of the Paediatric Rheumatology
International Trials Organisation (PRINTO)
1PRINTO, Genoa, Italy; 2Pfizer, Collegeville, PA, United States
Correspondence: Ivan Foeldvari
Introduction: A Phase 3b, open-label (OL), multicenter study (CLIPPER) has shown efficacy
of etanercept (ETN) in pediatric patients (pts) with extended oligoarticular (eo)
juvenile idiopathic arthritis (JIA), enthesitis-related arthritis (ERA), and psoriatic
arthritis (PsA). CLIPPER2 is an ongoing OL extension study assessing long-term safety
and clinical benefits of ETN in this population.
Objectives: Describe safety and clinical benefit of 6 yr of ETN treatment in CLIPPER
(2 yr) and CLIPPER2 (4 yr) studies.
Methods: 127 pts with eoJIA (2–17 yr), ERA, or PsA (12–17 yr) who received ≥1 ETN
dose (0.8 mg/kg QW [max, 50 mg]) in CLIPPER were eligible to enter CLIPPER2. Efficacy
endpoints included proportions of pts achieving JIA ACR30/50/70/90/100 and Wallace/Juvenile
Arthritis Disease Activity Score (JADAS) inactive disease/clinical remission criteria.
Time to disease flare for pts who met predefined study criteria for withdrawing from
ETN treatment was assessed by Kaplan-Meier (KM) analysis. Safety was assessed from
CLIPPER baseline (BL) to month (m) 72.
Results: 109/127 (86%) pts entered CLIPPER2. At m72, 46/127 (36%) were taking ETN
(39 [31%] ongoing, 7 [6%] restarted treatment), 44 (35%) had stopped ETN treatment,
and 37 (29%) had discontinued the study. Improvements in disease activity seen in
CLIPPER (m0–24) were largely maintained at m72 (Table; observed cases). Proportion
of pts achieving JIA ACR30/50/70 responses at m24 (% = 99/98/93) was maintained to
m72 (% = 96/96/88). Proportion of pts achieving JIA ACR90/100/Wallace inactive disease
at m24 (% = 65/54/34) was maintained to m60 (% = 71/51/31) but afterwards decreased
(% = 50/26/10 at m72). Sustained remission (≥12 continuous months) was achieved by
7/98 (7%) pts. 22/127 (17%) pts withdrew from ETN treatment due to low/inactive disease;
13/22 (59%) experienced disease flare (median time to flare [KM] = 190 days).
Most frequently reported treatment-emergent adverse events (TEAEs) were (no. events
[N], events per 100 pt-yr [EP100PY]), headache (28, 5.34), arthralgia (24, 4.58),
and pyrexia (20, 3.81) (Table 25). Number and frequency (N, EP100PY) of TEAEs (excluding
infections/injection site reactions [ISR]) decreased over the 6-yr study period from
193, 173.81 in yr1 to 37, 61.34 in yr6. Most commonly reported treatment-emergent
(TE) infections were (N, EP100PY) upper respiratory tract infection (66, 52.0), pharyngitis
(58, 45.7), and gastroenteritis (31, 24.4). 1 case of malignancy (Hodgkin’s lymphoma)
and no cases of active tuberculosis, demyelinating disorders, or deaths were reported.
Table 25
(Abstract P71). See text for description
Clinical OutcomesMean (95% CI)
Safety Summary (to m72)N (EP100PY) unless otherwise stated
BL1(n = 127)
m241(n = 109)
m482(n = 64)
m722(n = 47)
eoJIAEXP = 245.607 PY
ERAEXP = 158.888 PY
PsAEXP = 119.945 PY
TotalEXP = 524.441 PY
PtGA
4.96 (4.6,5.4)
0.97 (0.7,1.2)
1.32 (0.9,1.8)
1.29 (0.9,1.7)
TEAEs*
244 (99.35)
151 (95.04)
90 (75.03)
485 (92.48)
PGA
5.02 (4.7,5.3)
n = 108 0.62 (0.5,0.8)
n = 63 0.67 (0.5,0.9)
0.76 (0.5,1.0)
TE infections
351 (142.91)
93 (58.53)
117 (97.54)
561 (106.97)
CRP, mg/L
8.26 (5.7,10.8)
n = 103 2.76 (1.7,3.8)
2.85 (1.6,4.1)
n = 46 1.58 (1.2,2.0)
TEAEs* causing withdrawal, n (%)
5 (2.04)
8 (5.03)
0
13 (2.48)
JADAS 73 joints
n = 119 17.16 (15.9,18.4)
n = 102 2.28 (1.7,2.9)
n = 61 2.48 (1.8,3.1)
n = 29 3.12 (2.2,4.1)
TE infections causing withdrawal, n (%)
2 (0.81)
0
1 (0.83)
3 (0.57)
No. active joints
6.74 (5.9,7.6)
0.61 (0.2,1.0)
n = 63 0.49 (0.3,0.7)
n = 30 0.60 (0.2,1.0)
Serious TEAEs
11 (4.48)
17 (10.70)
4 (3.33)
32 (6.10)
No. active joints (LOM)
5.72 (5.0,6.5)
1.06 (0.5,1.6)
n = 63 1.02 (0.6,1.4)
n = 30 1.10 (0.5,1.8)
Serious TE infections
5 (2.04)
4 (2.52)
4 (3.33)
13 (2.48)
Opportunistic infections†
0
1 (0.63)
1 (0.83)
2 (0.38)
Data from patients taking ETN (full analysis set)
1CLIPPER study
2CLIPPER2 study
*Excluding infections/ISR
†All herpes zoster
CRP, C-reactive protein; EXP, exposure to ETN; LOM, limitation of motion; PGA, physician’s
global assessment; PtGA, patient/parent global assessment; PY, pt-yr
Conclusion: OL ETN treatment to m72 was effective and well tolerated in pts with eoJIA,
ERA, and PsA. Majority of pts who withdrew from ETN treatment experienced disease
flare. TEAE frequency decreased over time.
Trial registration identifying number: NCT00962741/NCT01421069
Disclosure of Interest: I. Foeldvari: None Declared, T. Constantin: None Declared,
J. Vojinovic Speaker Bureau of: Abbvie, G. Horneff Grant/Research Support from: Pfizer,
Abbvie, Roche, Novartis, J. Dehoorne Consultant for: Abbvie, Speaker Bureau of: Abbvie,
G. Susic Grant/Research Support from: Pfizer, K. Kobusinska: None Declared, V. Panaviene:
None Declared, Z. Zuber: None Declared, V. Stanevica Grant/Research Support from:
Pfizer, Consultant for: Abbvie, V. Chasnyk: None Declared, R. Pedersen Shareholder
of: Pfizer, Employee of: Pfizer, J. Bukowski Employee of: Pfizer, T. Hinnershitz Employee
of: Pfizer, B. Vlahos Shareholder of: Pfizer, Employee of: Pfizer, A. Martini Consultant
for: Abbvie, Boehringer, Novartis, R-Pharm, N. Ruperto Grant/Research Support from:
BMS, Hoffman-La Roche, Janssen, Novartis, Pfizer, Sobi, Speaker Bureau of: Abbvie,
Ablynx, AstraZeneca, Baxalta Biosimilars, Biogen Idec, Boehringer, Bristol Myers Squibb,
Eli-Lilly, EMD Serono, Gilead Sciences, Janssen, Medimmune, Novartis, Pfizer, Rpharm,
Roche, Sanofi
P72 Successful treatment of methotrexate intolerance in juvenile idiopathic arthritis
using eye movement desensitization and reprocessing (EMDR)
Lea Höfel1, Bruno Eppler1, Elisabeth Schnöbel-Müller1, Johannes-Peter Haas2, Boris
Hügle2
1Psychology, German Center for Pediatric and Adolescent Rheumatology, Garmisch-Partenkirchen,
Germany; 2Rheumatology, German Center for Pediatric and Adolescent Rheumatology, Garmisch-Partenkirchen,
Germany
Correspondence: Lea Höfel
Introduction: Methotrexate (MTX) is commonly used in the treatment of children with
juvenile idiopathic arthritis (JIA). Frequently it is discontinued due to intolerance
with anticipatory and associative gastrointestinal symptoms. Eye Movement Desensitization
and Reprocessing (EMDR) is a therapy where non-processed and dysfunctional experiences
and memories are reprocessed by intensive recall combined with eye movements. This
leads to selective processing of the negative affect.
Objectives: Objective of this study was to investigate effectiveness of EMDR in the
treatment of MTX intolerance in JIA patients, with the underlying hypothesis that
intolerance occurs due to dysfunctional memories and expectations.
Methods: An open prospective study on consecutive JIA patients with MTX intolerance
was performed. Intolerance was determined using the Methotrexate Intolerance Severity
Score (MISS) questionnaire and health-related quality of live was determined using
the PedsQL, at 3 time points: directly before and after treatment (after treatment:
MISS only), and 4 months after treatment. Patients were treated using a standardized
EMDR protocol with 8 sessions over a time period of 2 weeks. Changes in MISS and PedsQL
were compared using descriptive and non-parametric methods.
Results: 14 patients with MTX intolerance (median MISS at inclusion: 13.5, range:
6-26) were included. Directly after treatment, all patients reported marked improvement
of MTX intolerance symptoms (median MISS: 0.5, range: 0-3, p = 0.001). After 4 months,
lasting reduction of MTX intolerance symptoms was observed (n = 5, median MISS: 5,
range: 0-10, p = 0.068). However, 2/5 patients (40%) showed MISS >6. The health-related
quality of life showed a trend towards improvement 4 months after treatment (n = 5,
median pedsQL prior to treatment 84.4%, 4 months after treatment 92.4%, p = 0.46).
Conclusion: MTX intolerance in children with JIA can effectively be treated using
an EMDR protocol, with lasting effect over 4 months. This intervention could potentially
increase quality of life in affected patients and enable continued treatment with
MTX.
Disclosure of Interest: None Declared
P73 The comparison characteristic between patients with systemic onset of juvenile
idiopathic arthritis with and without lung involvement.
Mikhail M. Kostik1, Eugenia Isupova1, Irina Chikova1, Margarita Dubko1, Vera Masalova1,
Ludmila Snegireva1, Olga Kopchak1,2, Tatyana Kornishina1, Natalia Abramova1, Maria
Rumyantseva1, Daria Dzhilkaidarova1, Maria Kaneva1, Olga Kalashnikova1, Vyacheslav
Chasnyk1
1Saint-Petersburg State Pediatric Medical University, Saint-Petersburg, Russian Federation;
2Kirov’s regional children’s hospital, Kirov, Russian Federation
Correspondence: Mikhail M. Kostik
Introduction: Juvenile idiopathic arthritis with systemic onset (soJIA) is the most
striking form of JIA with combination of arthritis and systemic features. The acute
lung involvement (ALI) is not frequent manifestation of soJIA but often influence
on disease course, outcomes and treatment. The mechanisms of lung involvement are
still unclear.
Objectives: The aim of our study was to compare clinical and laboratorial features
of patients with soJIA with and without ALI.
Methods: In the study were included retrospective data of 82 children with soJIA.
ALI was described if patient had at least one: dyspnoe, shortness of breath, signs
of respiratory distress syndrome, interstitial lung disease, pulmonary arterial hypertension.
Results: ALI was detected in the onset of soJIA in 18 (22.0%) of patients. Patients
with ALI had more severe soJIA disease course (data in Table 26).
Table 26
(Abstract 73). See text for description
Parameter
ALI (n = 18)
W\o ALI (n = 67)
p
Hemoglobin, g/l
86,5 (80,0; 108,0)
105,0 (94,0; 116,0)
0,003
Platelets, x109/l
201,0 (95,0; 492,0)
454,0 (361,0; 588,0)
0,006
CRP, mg/l
104,8 (37,5; 154,0)
47 (18,0; 104,0)
0,07
LDH, U/l
1042,0 (543,0; 1230,0)
516,0 (395,0; 676,0)
0,012
Ferritin, ng/ml
1759,0 (1144,0; 11300,0)
321,0 (139,0; 1278,0)
0,0009
Prothrombin, %
71,1 (63,0; 79,0)
91,0 (79,0; 98,0)
0,0009
Fibrinogen, g/l
1,8 (0,8; 4,0)
4,7 (3,2; 5,7)
0,012
Total protein, g/l
64,6 (55,0; 70,3)
71,2 (67,0; 77,0)
0,002
Albumin, %
24,1 (23,0; 25,6)
39,0 (31,8; 43,2)
0,00001
Patients with ALI more frequently had MAS (p = 0,0006), pericarditis (p = 0,0006),
transient proteiunuria, attributed to MAS (p = 0,015), concomitant sepsis (p = 0,005)
and morphological evidence of hemophagocytosis in bone marrow (p = 0,02).
The main predictors of development ALI were presence of macrophage activation syndrome
(OR = 6.6 [2.1; 21.0], p = 0.0006), bone marrow hemophagocytosis (OR = 13.9 [0.7;
269.2], p = 0.02), heart involvement (OR = 6.4 [2.1; 19.7], p = 0.0006), kidney involvement
(transient proteinuria) (OR = 6.1 [1.2; 30.3], p = 0.0015), evidence of concomitant
sepsis (OR = 21.2 [1.0; 466.0], p = 0.005), albumin ≤ 25.6 g/l (OR = 73.3 [10.9; 495.0],
p = 0.0000001), AST > 37.3 U/l (OR = 5.3 [1.4; 20.2], p = 0.008), CRP > 125.0 g/l
(OR = 5.6 [1.7; 18.6], p = 0.003), ferritin > 690 ng/ml (OR = 22.7 [2.7; 191.4], p = 0.0002),
hemoglobin ≤ 89 g/l (OR = 7.1 [2.3; 22.6], p = 0.0001), LDH > 882 U/l (OR = 4.8 [1.4;
16.4], p = 0.002), platelets ≤ 211x109/l (OR = 10.1 [3.1; 32.9], p = 0.00002), prothrombin ≤ 74.6%
(OR = 12.6 [2.8; 57.3], p = 0.0003), total protein ≤ 65.0 g/l (OR = 8.7 [2.7; 27.8],
p = 0.00008).
Conclusion: The identified predictors of ALI in soJIA have to check to evaluation
of prognosis and choosing treatment plans.
Disclosure of Interest: None Declared
P74 Decreasing prevalence of uveitis in children with juvenile idiopathic arthritis
seen over a 30-year period
Valentina Ravaschio1, Valentina Muratore2, Serena Calandra1, Gabriella Giancane1,
Alessandra Alongi1, Angela Pistorio1, Alessandro Consolaro1, Benedetta Schiappapietra1,
Angelo Ravelli1
1Istituto Giannina Gaslini, Genova, Italy; 2Fondazione IRCCS Policlinico San Matteo,
Pavia, Italy
Correspondence: Valentina Ravaschio
Introduction: Uveitis is the most common extra-articular manifestation of juvenile
idiopathic arthritis (JIA). In recent years, there has been a major advance in the
management of both JIA and of uveitis. Non-controlled studies have suggested that
some medications, particularly methotrexate and anti-TNF antibodies, are potentially
capable to prevent the occurrence of uveitis. However, whether the recent therapeutic
progress had led to a reduction in the prevalence of uveitis is unknown.
Objectives: To investigate the temporal trend in the prevalence of uveitis in JIA
patients seen over a 30-year period.
Methods: A retrospective analysis of the medical records of all children with JIA
by ILAR criteria who were seen at authors’ units between January 1987 to October 2016
was carried out. The prevalence of uveitis in patients with onset of JIA in different
time periods (before 1997, between 1997 and 2005 and after 2005) was evaluated. Patients
without uveitis who had a disease duration of less than 6 months were excluded.
Results: A total of 1.425 patients with JIA, 336 (23.6%) of whom had developed uveitis
were identified. The prevalence of uveitis was 60/211 (28.4%) among patients with
onset before 1997, 149/602 (24.8%) among patients with onset between 1997 and 2005,
and 127/612 (20,8%) among patients with onset after 2005. The follow-up of patients
seen in the three time periods was comparable (Table 27).
Table 27
(Abstract P74). See text for description
Before 1997 (n = 211)
1997-2005 (n = 602)
After 2005 (n = 612)
number of Uveitis
60 (28,4%)
149 (24,8%)
127 (20,8%)
Age at onset <3
96 (45,5%)
273 (45,3%)
302 (49,3%)
Age at onset 3-7
80 (37,9%)
203 (33,7%)
169 (27,6%)
Age at onset >7
35 (16,6%)
126 (20,9)
141 (23,0%)
Extended oligoarthritis
35 (16,6%)
84 (14,0%)
97 (15,8%)
Persistent oligoarthritis
117 (55,5%)
317 (52,7%)
348 (56,9%)
FR-negative poliarthritis
35 (16,6%)
139 (23,1%)
138 (22,5%)
Psoriatic arthritis
11 (5,2%)
21 (3,5%)
10 (1,6%)
Undifferentiated arthritis
13 (6,2%)
41 (6,8%)
19 (3,1%)
Conclusion: Our study shows a decrease in the prevalence of uveitis over time, which
might be, at least partially, related to the increased tendency toward earlier use
of methotrexate and the introduction of biologic agents. This finding should to be
confirmed in patient series seen in other pediatric rheumatology centers.
Disclosure of Interest: None Declared
P75 Comparison of patients with familial Mediterranean fever accompanied with sacroiliitis
and patients with juvenile spondyloarthropathy
Hafize E. Sönmez, Ezgi D. Batu, Selcan Demir, Yelda Bilginer, Seza Özen
Department of Pediatrics, Division of Rheumatology, HACETTEPE UNIVERSITY FACULTY OF
MEDICINE, Ankara, Turkey
Correspondence: Hafize E. Sönmez
Introduction: Familial Mediterranean fever (FMF) is the most common autoinflammatory
disease manifesting with self-limited recurrent febrile attacks and polyserositis.
Acute recurrent monoarthritis is the most common form of musculoskeletal involvement
in FMF; however, up to 5% of FMF patients may develop chronic joint diseases including
sacroileitis. It is difficult to distinguish whether sacroiliitis is a musculoskeletal
finding of FMF or whether this is the coexistence of two diseases; FMF and SpA.
Objectives: In this study, we aimed to evaluate FMF patients with sacroiliitis, and
compare their features with juvenile spondyloarthropathy (SpA) patients all of whom
had sacroiliitis.
Methods: 15 pediatric FMF patients with sacroiliitis and 30 patients with juvenile
SpA followed between 2014-2016 at the Department of Pediatric Rheumatology at Hacettepe
University, Ankara, were included in the study.
Results: The median (min-max) age at diagnosis of sacroiliitis was 11 (7-15) for FMF + sacroiliitis,
and 11.5 (7-16) years for juvenile SpA patients. All patients suffered from hip pain
and morning stiffness. Only two FMF + sacroiliitis patients had enthesitis, while
nearly half of juvenile SpA patients (46.7%) had enthesitis. Four FMF patients suffered
from lower back pain, although none of them had spinal involvement. On the other hand,
approximately one third of juvenile SpA patients had spinal involvement. The median
white blood cell count, erythrocyte sedimentation rate, and C reactive protein values
in FMF + sacroiliitis patients were higher (10.1x103/mm3 vs 7.8x103/mm3, p = 0.002;
41 vs 28 mm/h, p < 0.001; 4.6 vs 1.3 mg/dl, p < 0.001; respectively) than juvenile
SpA patients. HLA B27 positivity was more common in juvenile SpA than FMF + sacroiliitis
patients (86.6% vs 26.7%, respectively, p = 0.001). The most common MEFV (MEditerranean
FeVer) mutation was M694V in FMF patients. All juvenile SpA patients but one were
negative for MEFV mutations. One juvenile SpA patient was heterozygous for E148Q.
Conclusion: We demonstrated that pediatric patients with FMF + sacroiliitis showed
different characteristics (higher inflammatory markers, less frequent spinal and enthesitis
involvement and HLA-B27 positivity) from patients with juvenile SpA. The jury is out
to decide whether FMF is a triggering factor for SpA or whether this is a feature
of FMF per se.
Disclosure of Interest: None Declared
P76 Epidemiology, clinical manifestations and treatment of systemic-onset juvenile
idiopathic arthritis (SOJIA): a multicentric study through the international platform
JIRcohorte.
Katerina Theodoropoulou1, Alexandre Belot2, Véronique Hentgen3, Isabelle Kone-Paut4,
Carine Wouters5, Kenza Bouayed6, Elvira Cannizzaro7, Aurélia Carbasse8, Etienne Merlin9,
Claire Ballot10, Daniela Kaiser11, Pascal Pillet, Andreas Woerner 13, Walter Bär14,
Sylvaine Poignant15, Véronique Despert16, Caroline Freychet17, Gerald Berthet18, Laetitia
Higel19, Tu Tran20, Federica Vanoni21, Sophie Georgin-Lavialle22, Michaël Hofer1
1Pediatric Rheumatology, CHUV, Lausanne, Switzerland; 2Hospices Civils de Lyon, Lyon,
France; 3CH de Versailles - Hôpital André Mignot, Paris, France; 4Centre Hospitalier
Universitaire Kremlin-Bicêtre, Paris, France ; 5UZ Leuven, Leuven, Netherlands ; 6Hôpital
d’Enfants Ebnou Rochd Casablanca, Casablanca, Morocco; 7Kinderspital Zürich, Zürich,
Switzerland; 8CHU Arnaud de Villeneuve Montpellier, Montpelier, France; 9Centre Hospitalier
Universitaire de Clermont-Ferrand, Clermont-Ferrand, France; 10CHRU Besançon, Besançon,
France; 11Luzerner Kantonspital, Lucerne, Switzerland; 12CHU de Bordeaux, Bordeaux,
France; 13Universitäts-Kinderspital beider Basel, Basel, Switzerland; 14Kantonspital
Graubünden, Graubünden, Switzerland; 15CHU Nantes, Nantes, France; 16CHU Rennes, Rennes,
France; 17CHU St-Etienne, St-Etienne, France; 18Kantonspital Aarau, Aarau, Switzerland;
19Hôpital Hautepierre Strasbourg, Strasbourg, France; 20CHU Nîmes, Nîmes, France;
21L’Ospedale Regionale di Bellinzona e Valli, Bellinzona, Switzerland; 22Hôpital TENON,
Paris, France
Correspondence: Katerina Theodoropoulou
Introduction: Systemic-onset juvenile idiopathic arthritis (SoJIA) is a rare paediatric
rheumatic condition with unclear pathogenesis, challenging diagnosis and treatment.
Objectives: The aim of our study is to describe the epidemiology, clinical presentation
and biologic treatment of SoJIA patients registered in the JIRcohorte.
Methods: This is a multicentre, observational, retrospective and inception cohort
study, through an international platform: JIRcohorte. Patients with SoJIA, diagnosed
and followed in one of the participating centres in the JIRcohorte project in Switzerland,
France, Belgium and Morocco are enrolled in the registry.
Results: 212 patients with SoJIA have been included; 119 were girls with a female:
male ratio of 1.3:1. The median age at diagnosis was 5.4 years and the median diagnostic
delay was 40 days. Data for initial systemic manifestations were available in 57 patients:
96% presented with typical fever (55/57), 56% with rash (32/57), 32% with lymphadenopathy
(18/57), 21% with splenomegaly (12/57), 21% with hepatomegaly (12/57), and 16% with
serositis (9/57). Data for joint involvement were available in 46 patients: arthritis
was reported in only 61% of them during the first year of disease evolution, with
a poly-articular predominance (61%). 169 out of 212 patients (80%) had a biologic
treatment at least once during their disease course. Before 2008, anti-TNFa agents
were more frequently used (69%), followed by anti-IL-1 agents (30%), with a very few
patients receiving anti-IL-6 agent (1%). Since 2008, anti-IL-1 agents became the most
common biologic treatment (46%), followed by tocilizumab (36%), with fewer patients
under anti-TNFa agents (18%). Higher rate of infectious adverse effects was reported
with Tocilizumab, while Anakinra was associated with skin and administration site
effects.
Conclusion: We describe here the main epidemiologic and clinical characteristics,
as well as the treatment of patients with SoJIA included in our international JIRcohorte
platform. Biologic therapies, in particular anti-IL1 agents, are widely used in the
treatment of this disease throughout the last years. Further prospective data analysis
is required to evaluate the long-term efficacy and the safety of these treatments.
Disclosure of Interest: None Declared
P77 Autoinflammatory mechanisms via NF-KB and caspase-1/IL-1 inflammasome pathways
in ana negative juvenile idiopathic arthritis
Andrea Zacarias1, Anna Mensa2, Estibaliz Iglesias1, Rosa Bou1, Joan Calzada1, Jordi
Anton1, Juan Ignacio arostegui2, Juan Manuel Mosquera1, Violeta Bittermann1
1Rheumatology, Hospital Sant Joan de Deu, Barcelona, Spain; 2Inmunology, Hospital
Clinic, Barcelona, Spain
Correspondence: Andrea Zacarias
Introduction: Classification criteria of Juvenile Idiopathic Arthritis (JIA) are clinical
and of exclusion. Autoinflammatory Inherited Diseases (AID) are innate immune system
disorders with clinical similarity with JIA that have been considered in differential
diagnosis of this disease. Patients with AID previously wrongly diagnosis as JIA has
been described
Objectives: To evaluate presence of variations on genes implicated in AID in a group
of JIA patients attended at our center between January 2000-2015. To compare clinical
and laboratory data between patients with and without variations on these genes.
Methods: Transversal (January 2000-2014) and prospective (January 2014-2015) study.
Clinical, demographics and laboratory (erythrocyte sedimentation rate (ESR), C reactive
protein (CRP), ANA, blood cell count) data were collected. Next-generation sequencing
test of MEFV, TNFRSF1A, MVK, NLRP3, NOD2 and PSTPIP1 were done.
Results: One hundred and one patients were included (76 girls). 61 oligoarticular
JIA, 20 rheumatoid factor (RF) negative polyarticular JIA, 19 extended oligoarticular
JIA and 1 RF positive polyarticular JIA. Fifty patients were ANA positive. At least
one variation was identified in 26.7% of our patients. Accumulated probability of
having some variation in these genes in our JIA series was statistical significant
greater than healthy Iberian population (20 vs 8.2% respectively, p = 0.01). Table 28
describes identified genetic variations. Variations in all searched genes were detected
except for MVK. Oligoarticular extended JIA was the more affected subtype (47.4%,
p = 0.082). We did not find differences according to ANA.
Table 28
(Abstract P77). See text for description
Genes
MEFV
MEFV
MEFV
TNFRSF1A
NLRP3
NOD2
NOD2
NOD2
PSTPIP1
Mutation
E148Q
I591T
M694I
P46L
V198M
D925G
N289S
E778K
G258a
JIA Patients
7/101 6,9%
4/101 3,9%
3/101 2,9%
1/101 0,9%
4/101 3,9%
1/101 0,9%
4/101 3,9%
1/101 0,9%
1/101 0,9%
Iberian Population
0/107 0%
2/107 1,8%
18/69.706 0,03%
0/107 0%
1/107 1,8%
1/107 1,8%
1/107 1,8%
0/107 0%
1/6498 0,01%
Based on the presence of a genetic variation we did not find differences in age at
onset disease, presence of extra-articular symptoms, laboratory parameters at diagnosis.
Conclusion: Variations on all AID studied genes were detected except for MVK. We found
greater prevalence of genetic variations in JIA patients than described in healthy
Iberian population. We did not find differences according ANA. We did not find clinical
nor laboratory predictors of presence of a genetic variation
Disclosure of Interest: None Declared
Juvenile idiopathic arthritis (JIA) (oligo, poly, psoriatic)
P78 The lull before the TMJ storm: identifying a window of opportunity for early identification
of TMJ arthropathy
Clare Marie Adams1, Clarissa Pilkington2
1Rheumatology, Great Ormond Street Hospital for Children, London, United Kingdom;
2Consultant Paediatric Rheumatologist, Great Ormond Street Hospital, London, United
Kingdom
Correspondence: Clare Marie Adams
Introduction: Temporomandibular joint (TMJ) arthritis is common in children with Juvenile
Idiopathc Arthritis (JIA); it confers significant functional and psychological morbidity
to young people suffering with pain, functional impairment and facial asymmetry, as
a result of TMJ destruction. Gadolinium-enhanced MRI is the gold-standard imaging
modality for detection of synovitis, however early recognition of TMJ arthritis is
challenging: clinical assessment is insensitive and early findings on MRI overlap
with non-inflammatory synovial enhancement of normal children. With the expense and
relative scarcity of MRI, coupled with challenging interpretation of results in early
disease, there is an absence of international consensus with regard to screening in
TMJ arthritis. Reducing the burden of deforming TMJ disease in young people would
undoubtedly be aided by effective early detection of joint involvement.
Objectives: This observational study aims to understand the characteristics of the
JIA patient cohort undergoing TMJ MRI in our centre. It aims to identify opportunities
for improved clinical practice with a view to early detection of TMJ arthritis, and
to contribute to discussion regarding development of consensus based local guidance
for TMJ surveillance in children with JIA.
Methods: The electronic clinical records of 30 consecutive patients undergoing TMJ
MRI between March 2014 and April 2016 were retrospectively reviewed. They were split
into two age groups, 0-4 years (n = 15) and 5-12 years (n = 15). Baseline characteristics
including age, sex, JIA subtype, time lag between JIA diagnosis and MRI-TMJ involvement,
indications for MRI, MRI reports and whether the MRI changed clinical management were
assessed. All TMJ MRIs (n = 56) performed on these 30 patients were assessed.
Results: Children developed TMJ involvement aged 8-10 years old, regardless of age
of onset of JIA. Following diagnosis of JIA, TMJ involvement was identified after
6.75 years (median, range 1.25–9.33 years. Mean 5.92 years) in 0-4 age group, and
1 year (median, range 0-9year. Mean 1.83 years) in 5-12 group. 40% (6 children, aged
7-11years) in 5-12 group had TMJ involvement at diagnosis. Most common indications
for MRI were pain and restriction (0-4 group), with deviation and asymmetry (5-12
group). The 5-12 group had more bony erosions on MRI report (13/15) and more unilateral
disease compared to 0-4 group. The burden of TMJ disease occurs predominantly over
the age of 5 (28/30). MRI changed clinical management (18/30).
Conclusion: Irrespective of age of onset of JIA, children developed TMJ involvement
between 8-10 years of age. This indentifies a group upon which to focus targetted
MRI surveillance with the aim of detecting early TMJ disease. This is a small study,
but it contributes to the ongoing discussions regarding formation of pragmatic consensus
guidance in TMJ surveillance in asymptomatic children with JIA. Further study is required.
Disclosure of Interest: None Declared
P79 Burden of disease in the pediatric rheumatology clinic at Alain Hospital: the
UAE experience
Amal A. Alhosani
child health institute, Alain Hospital, alain, abu dhabi, United Arab Emirates
Introduction: Introduction: The subspeciality of pediatric rheumatology is the newest
discipline established at child health institution in Alain hospital, in 2013. The
service provides tertiary care for children with rheumatic diseases from all over
United Arab Emirates. Currently there are no data that describe the epidemiology of
rheumatic diseases in children.
Objectives: The aim of this study is to describe the demographics and diagnostic classification
of children with rheumatic conditions followed up in the clinic.
Methods: Methods: a retrospective cohort was conducted. All the files from August
2013 to July April 2017 were reviewed. Case description and diagnosis were captured.
Standardized description of diagnosis was used. All patients were screened for uveitis
by ophthalmologist using slit lamp examination
Results: Results: rheumatic conditions were diagnosed in 130 subject. JIA was the
most frequently encountered rheumatic condition 44% (n = 58), followed by FMF 10%
(n = 14) and SLE 9% (n = 12). Among JIA group oligoarticular JIA was the most common
subtype 60% (n = 35), 10% (n = 10) of the cases were complicated by anterior uveitis.
The remaining 37% of patients had a variety of other conditions. MTX was used to treat
38% (n = 51) of the cases. Biologics were started in 20% (n = 25) cases.
Conclusion: Conclusion: this is the first cohort that describes the epidemiology of
rheumatic conditions among UAE children, it highlights the rheumatologist conditions
and their frequencies among pediatric population, however continuos prospective data
is needed to confirm our initial observation.
Disclosure of Interest: None Declared
P80 Investigating longitudinal course of ankle involvement in relation to treatment
in children with JIA using a multistate markov model approach
Alessandra Alongi1,2, Alessandro Consolaro2, Angelo Ravelli2
1Università degli Studi di Genova; 2Instituto Giannina Gaslini, Genova, Italy
Correspondence: Alessandra Alongi
Introduction: The ankle-foot complex (AFC) is a commonly involved joint site in children
with Juvenile Idiopathic Arthritis (JIA) that requires special attention from clinicians
due to the complexity of its anatomical structure and the recognized association with
a more severe disease course. Some patients experience recurrent, treatment refractory
involvement of this region, posing unique challenges for therapeutic management. Little
information concerning the longitudinal course of AFC arthritis in relation to treatment
and its predictors is available to date to guide treatment strategies for JIA patients.
Objectives: To describe trajectories of AFC involvement in a cohort of JIA patients
in relation with received treatments, and identify subgroups of patients at risk of
recurrent or treatment resistant AFC arthritis over time.
Methods: Records of oligoarticular and polyarticular RF-negative JIA patients followed
in a single tertiary center and diagnosed between 2005 and 2012 were retrospectively
evaluated for the occurrence of clinically assessed tibiotalar, subtalar and tarsal
arthritis. 143 patients with at least one episode of AFC involvement in the first
5 years from disease onset and complete records were identified. Data collected during
a total of 2288 visits - at baseline and at intervals of 3-4 months during the first
5 years of follow-up - were included in the analysis. Specifically, time-varying variables
such as disease status, patterns of joint involvement, and current treatments including
intra-articular steroid injections were analyzed. Probabilities of AFC arthritis and
of being treated with methotrexate (MTX), etanercept (ETN), other TNFa inhibitors
or systemic steroids at each evaluation from the second to the fifth year of follow-up
were evaluated through multistate Markov modeling, which allows detecting transitions
among different clinical states. The relationship between the identified states and
clinical-demographical features at onset and in the first year of follow-up was then
assessed through regression modeling.
Results: The model identified 6 latent states, defined by the combination of AFC activity
and treatment status at each time point: absence of AFC involvement in patients currently
off medication (State 1, 906 observations); absence of AFC involvement while receiving
MTX treatment (State 2, 622 observations); low probability of AFC arthritis and during
treatment with both MTX and ETN (State 3, 316 observations); AFC arthritis in patients
currently off medication (State 4, 158 observations); State 5 (197 observations) and
State 6 (89 observations) are associated with AFC arthritis during MTX therapy but
with high and low probability respectively. After adjusting for active joints count,
the number of relapses involving the tibiotalar joint during the first year from onset
predicted the transition from State 1 to State 4 - relapse off therapy - and were
inversely correlated with probability of transition from State 3 to State 1, namely
maintaining remission after therapy withdraw (p = 0.014 and p = 0.035, respectively).
Tarsal joints arthritis in the first year of disease was negatively associated with
transition from State 5 to State 2, namely AFC response to MTX therapy (p = 0.030).
A negative correlation between the occurrence of subtalar involvement in the first
year of disease and State 1 was also observed (p = 0.021).
Conclusion: Analysis of longitudinal data provides insight for the identification
of patients at risk of recurrent AFC involvement and their clinical management. Further
studies are needed to assess the potential value of such information in guiding therapeutic
strategies for JIA patients.
Disclosure of Interest: None Declared
P81 Novel mutations in PRG4 gene in one Greek family with camptodactyly-arthropathy-coxa
vara-pericarditis (CACP) syndrome
Sorina Boiu1, Mouna Barat2, Isabelle Touitou3, David Geneviève4, Vasileios Kontogeorgakos5,
Erato Atsali6, Dimitrios Boumpas7, Vana Papaevangelou8
1Pediatric Rheumatology Unit, Third Department of Pediatrics, "Attikon" University
Hospital, National and Kapodistrian University of Athens, Athens, Greece, 2Laboratoire
de Génétique, Hôpital Arnaud de Villeneuve, CHRU Montpellier Montpellier, France,
3Laboratoire de Génétique, Hôpital Arnaud de Villeneuve, CHRU Montpellier, Montpellier,
France 4Département de Génétique Médicale, Maladies Rares et Médecine Personnalisée,
Unité Inserm U1183, CHU Montpellier, Université Montpellier, Montpellier, France,
5First Department of Orthopedics, “Attikon” University Hospital, National and Kapodistrian
University of Athens, Athens, Greece 6Pediatric Rheumatology Unit, Third Department
of Pediatrics, “Attikon” University Hospital, National and Kapodistrian University
of Athens, Athens, Greece 7Joint Rheumatology Program, Fourth Department of Medicine,
“Attikon” University Hospital, National and Kapodistrian University of Athens, Athens,
Greece 8Third Department of Pediatrics, “Attikon” University Hospital, National and
Kapodistrian University of Athens, Athens, Greece
Correspondence: Sorina Boiu
Introduction: Camptodactyly-Arthropathy-Coxavara-Pericarditis (CACP) syndrome is a
rare autosomal recessive disorder caused by mutations in the PRG4 (proteoglycan 4)
gene located on chromosome 1q31.1 (OMIM:*604283). Hallmarks of the syndrome include
congenital or early-onset camptodactyly and arthropathy with synovial hyperplasia,
progressive coxa vara deformity and non-inflammatory pericarditis. Patients affected
by CACP syndrome lack the glycoprotein lubricin, a major lubricant expressed mainly
in joints and in pericardial and pleural cavities. Features of CACP syndrome mimic
juvenile idiopathic arthritis (JIA) and children with CACP are often misdiagnosed
as JIA. To date, twenty-two homozygous mutations and 1 case of CACP syndrome resulting
from uniparental disomy of chromosome 1 have been reported in different ethnic populations,
none from Greece.
Objectives: To report the mutations in the PRG4 gene in 2 siblings with CACP syndrome
in one family from Greece.
Methods: A 6 years old boy suffered from congenital camptodactyly and progressive
non-inflammatory arthropathy from the age of 2 years (knees, ankles, elbows, wrists,
and cervical spine). Radiographs, ultrasound and MR images revealed features of CACP
syndrome. He was diagnosed with juvenile idiopathic arthritis at the age of 3 years
and received corticosteroids, methotrexate, and anti-TNF treatment without efficacy.
The patient's younger brother, aged 2 years, had a similar history, albeit more severe,
starting at the age of 2 months. The family consulted in our Clinic for a second opinion
at the age of 6 years. Molecular genetic studies were done for all coding exons and
the exon-intron boundaries of the PRG4 gene. NGS was performed on hybridization-captured
region of interest. All variants were confirmed by Sanger sequencing.
Results: The 2 siblings were found to be compound heterozygotes for c.[957del];[3254_3260del]
p.[(Asp320Ilefs*2)];[(Ser1085*)]. These rearrangements lead to a shift of the reading
frame and the appearance of a premature stop codon. This type of mutations is likely
to lead to the synthesis of a non-functional truncated protein.
Conclusion: To our knowledge, this is the first report of PRG4 mutations from Greece
as well as the first case of CACP syndrome phenotype caused by novel heterozygous
mutations. The presence of arthropathy with camptodactyly, especially if familial,
should alert the clinician to the possibility of CACP syndrome and avoid misdiagnosis
of JIA and unnecessary treatment with potentially harmful drugs.
Disclosure of Interest: None Declared
P82 Dental anxiety and oral health in juvenile idiopathic arthritis
Christina Boros1, Jason Armfiled2
1Discipline of Paediatrics, University of Adelaide, Adelaide, Australia; 2Australian
Research Centre for Population Oral Health, University of Adelaide, Adelaide, Australia
Correspondence: Christina Boros
Introduction: Previous studies suggest that children with Juvenile Idiopathic Arthritis
(JIA) have poorer oral health compared to their healthy peers despite adequate knowledge
of appropriate dental care. We hypothesised that this may be due to dental anxiety
and that there may be specific dental and/or disease related factors which predict
dental fear in this population
Objectives: We aimed to determine the prevalence and predictors of dental fear in
a single centre population of JIA patients.
Methods: JIA patients aged 5–18 years attending the rheumatology clinic at the Women’s
and Children’s Hospital in Adelaide, South Australia completed a questionnaire regarding
dental visit frequency, past dental experiences, oral health behaviour, self-rated
dental health, assessment of dental anxiety using the Modified Child Dental Anxiety
Response Scale (MCDASf), their cognitive vulnerability-related perceptions of dental
treatment-related events and the degree of pain and reduced movement in upper limb
and temporo-mandibular joints (TMJs). Clinical data relating to JIA subtype, medications,
arthritis activity in upper limbs and TMJs and JADAS score on the day of questionnaire
completion were also documented.
Results: Ninety four patients, (24 boys, 25.5%) participated. Average age was 12.3 years
(SD = 4.3), average disease duration 5.6 years (SD = 4.3) and median JADAS score 1
(range 0–17.2). Thirty eight (40.4%) had oligoarticular and 33 (35.1%) had polyarticular
onset disease. Nine (9.6%) had examination findings of TMJ involvement and four (4.3%)
had active arthritis in upper limb joints of the dominant hand. Mean MCDASf score
(Cronbach’s alpha = 0.93) was 2.97 with 50.5% of children having a score above the
cut point for classifiable high dental fear. While dental fear was not related to
having received any specific previous dental treatment, those who had not received
any treatment had higher dental fear than those who had experienced at least one treatment
(3.61 cf 2.87, p = 0.002). There was no statistically significant association between
having had a previously unpleasant dental experience and dental fear (F = 2.06, p = 0.112).
However, dental fear was associated with anxiety related to receiving blood tests
(r = 0.32, p = 0.002) and injectable medications (r = 0.34, p = 0.001). Vulnerability-related
cognitions, ie perceptions of the dental visit as dangerous, disgusting, uncontrollable
and unpredictable were significantly correlated with dental fear (r = 0.44, p < 0.001)
and in a multivariable stepwise regression model accounted for a statistically significant
amount of variance in dental fear (adjusted R
2 = 31.1%) after controlling for participant demographics, medically-related fears,
and having received a past dental treatment.
Conclusion: In a single-centre cohort of JIA, approximately 50% reported high levels
of dental fear associated with procedures related to their arthritis care rather than
a previously unpleasant dental experience. Those who had not yet visited a dentist
had higher dental fear with vulnerability-related cognitions of the dental visit contributing
most significantly to dental fear. These results may explain poorer dental health
reported in JIA patients.
Disclosure of Interest: None Declared
P83 Characterization of a Colombian cohort with juvenile idiopathic arthritis: a single
multicenter experience
Miguel Cañola1, Maria A. Alzate2, Deicy Hernandez-Parra2, Diana Echeverry2, Juan C.
Uribe-Salazar3, Javier Alvarez4, Lorena Londoño1, Paula Ortiz-Salazar2, Ricardo Pineda2
1Rheumatology division, Artmedica, IPS, Medellin, Colombia; 2Clinical information
group, Artmedica, IPS, Medellin, Colombia; 3School of Statistics, Faculty of Sciences,
National University of Colombia, Medellin, Colombia; 4Medical student, Universidad
CES, Medellin, Colombia
Correspondence: Miguel Cañola
Introduction: Juvenile idiopathic arthritis (JIA) is the most common chronic rheumatologic
disease in children (1). Artmedica is one of the main medical facilities specialized
in pediatric rheumatology.
Objectives: To describe a large cohort of patients with JIA from several regions of
Colombia that are followed in a specialized private medical center.
Methods: A cross-sectional study was conducted in 366 patients who were enrolled in
the registry between December of 2011 and August of 2016. There were 342 patients
who met the International League of Statistical Associations for Rheumatology criteria
who were included in the analysis. Association was examined by means of Chi-square
tests, Kruskal-wallis test, and logistic regression analyses (to adjust for possible
confounders).
Results: Analysis of clinical characteristics by subtypes showed differences in gender,
rheumatoid factor positivity, bone erosions, axial and peripheral involvement (Table 29).
Hand and/or feet deformities were present in 21,3% of the patients, bone ankylosis
of the wrist in 9,6%, asymmetric extremities in 2,9%, and ankylosis of the hip in
1,2%. Complications such as uveitis, delayed growth and osteoporosis presented in
4,7%, 7,9% and 5,5%, respectively. Three cases of avascular necrosis and one case
of macrophage activation syndrome were registered during follow up. No significant
differences in DMARD and biologic therapy were found among groups, but less use of
steroid therapy in oligoarthritis (OR 0,24 95%CI 0,09-0,91) and enthesitis related
arthritis (OR 0,05 95%CI 0,02-0,16).
Table 29
(Abstract P83). Clinical characteristics of patients with JIA by subtypes
All N = 342
Oligoarthritis N = 91
Polyarthritis N = 120
Systemic N = 28
Enthesitis related – Psoriatic N = 83
Un classified N = 20
p-value
Age at onset (median)
7
8
10
6
10
9
<.0001
Duration of disease (median)
4
3
7
6,5
3
33
<.0001
GenderMale:Female
4:6
4:6
2:8
4:6
7:3
4:6
<.0001
N %
N %
N %
N %
N %
N %
p-value
RF (+)
92/252 36,5
17/63 26,9
62/112 55,3
3/15 20
5/50 10
5/12 41,6
<.0001
HLA-B27
26/126 20,6
7/34 20,5
3/23 13,1
0/4 0
15/61 24,6
1/4 25
0,648
Bone erosions
33/147 22,4
4/38 10,5
17/66 25,7
4/7 57
2/27 7,4
6/9 66,6
0.0002
Axial involvement
60 17,5
10 10,9
14 11,6
4 14,2
30 36,4
2 10
<.0001
Peripheral involvement
285 83,3
80 87,9
103 85,8
22 78,5
72 86,7
8 40
<.0001
Conclusion: Polyarthritis was more common in preadolescent females while enthesitis
related arthritis in preadolescent males. Bone erosivity was particularly conspicuous
in polyarticular and systemic JIA, which implies a great risk of deformities and ankylosis,
and could justify a more agressive and early management. The definition of regional
epidemiological profiles in JIA helps to understand differences in disease patterns,
that allow both the development of personalized interventions and resources optimization.
Disclosure of Interest: None Declared
References
1. Ravelli A, Martini A, Villa L, Al. E, Lenko H, Wulffraat N. Juvenile idiopathic
arthritis. Lancet (London, England). Elsevier Saunders, Philadelphia; 2007;369(9563):767–78.
P84 Effectiveness and safety of tocilizumab in juvenile idiopathic arthritis (JIA)
in clinical practice.
Gisela Díaz-Cordovés1,2, Natalia Mena1, Esmeralda Nuñez-Cuadros2, Sara Manrique1,
Rocio Galindo-Zavala2
1Department of Rheumatology, at the University Regional Hospital of Malaga (HRUM),
MÁLAGA, Spain; 2Pediatric Rheumatology Unit, at the University Regional Hospital of
Malaga (HRUM), MÁLAGA, Spain
Correspondence: Gisela Díaz-Cordovés
Introduction: Tocilizumab, an anti-interleukin 6-receptor, its an effective treatment
in the juvenile idiopathic arthritis, but there is not so much date about the use
in clinical practice in subcuteneous administration and what happens when we optimize
it.
Objectives: To study the effectiveness and safety of tocilizumab (TCZ intravenous
and subcutaneous) in JIA patients in clinical practice
Methods: Design:Case series. Population:Consecutive patients with JIA treated with
TCZ in HRUM. Inclusion criteria: Patients with JIA, infant-juvenile and adult, followed
in the Maternal and Child Hospital and Civil Hospital respectively. Exclusion criteria:
Missing data on primary outcome variable. Protocol: Patients with infant-juvenile
AIJ treated with TCZ. They are reviewed during every infusion of TCZ. Before age of
14 years old, patients are derived to Rheumatology Unit to be reviewed in adult unit
and then they are followed each time they receive an infusion of the drug in day-hospital
or every three months if they are in sc therapy (sc biological therapy clinic). Outcomes:
Mean changes from baseline in DAS28, HAQ and activity level at 3rd month from change
to sc TCZ and at 6 months from the reduction; count and description of serious and
non-serious side effects during the follow-up. Other variables: Demographics, therapeutic
and clinical-analytical data: tenderness joint count (TJC), swollen joint count (SJC),
CRP, ESR, physician VAS, patient VAS, adverse events. Statistical analysis: Paired
t test or Wilcoxon signed rank between the first and last TCZ administration, between
the dose reduction and after 6 months, and between switching to sc administration
and after 3 months
Results: The main baseline characteristics of patients with JIA during last administration
of TCZ are shown in Table. The mean of DAS28 was higher in JIA adults in the last
administration of TCZ (p = 0.028).During the exposure to TCZ three non-severe adverse
events were recorded. Three patients switched to sc. At 3 months after to start sc
TCZ, no differences were observed in effectiveness outcomes and any adverse effect
with sc TCZ was recorded. There was not any switch to sc TCZ in patients with infant-juvenile
JIA, compared to patients older than 14 years where 70% of them changed to sc TCZ
(p = 0.022).Seven patients reduced doses: 6 with iv and 1 sc. Six months after the
reduction, no difference was observed in effectiveness outcomes; only trend to fewer
non-severe adverse effects in patient with reduced doses (3 with full doses versus
none patient in dose reduction;p = 0.07). Only one patient returned to full dose because
inefficiency.
Conclusion: Conclusions: TCZ in JIA patients seem an effective option in daily clinical
practice. The switch from iv to sc TCZ in JIA patients seems effective in clinical
practice. Reduction in TCZ dose in JIA may possible, maintaining good control of the
disease and possibly with fewer side effects
Disclosure of Interest: None Declared
P85 Fat mass in juvenile idiopathic arthritis. Should we think about it?
Gisela Díaz-Cordovés1,2, Esmeralda Nuñez-Cuadros1, Rocio Galindo-Zavala1, Sara Manrique2,
Mena Natalia2
1PEDIATRIC RHEUMATOLOGY UNIT, HOSPITAL REGIONAL UNIVERSITARIO DE MÁLAGA, MÁLAGA, Spain;
2Rheumatology D., HOSPITAL REGIONAL UNIVERSITARIO DE MÁLAGA, MÁLAGA, Spain
Correspondence: Gisela Díaz-Cordovés
Introduction: Various studies have shown that the excess of adiposity is a proinflamatory
state that conditions worse response to treatment. There are few studies on the subject
in arthritis juvenile idiopathic (JIA).
Objectives: OBJECTIVE: To describe the body composition and anthropometric parameters
of patients with JIA, and evaluate the possible relationship with the activity of
the disease.
Methods: PATIENTS and methods: Observational, cross-sectional, in children aged 4-15
years with JIA (excluding forms monoarticular), study in a tertiary hospital pediatric
Rheumatology unit. It collected data anthropometric, clinical and of treatment. Also
held dual absorptiometry of x-rays (DEXA) body total with assessment of body composition.
Define the index of mass fat (MFI) as the mass fat divided by the mass total and (MFFI)
fat-free mass index as lean mass (kg)/height (m2).
The JADAS27 index was used for the evaluation of the activity of the disease.
Results: RESULTS: We analyzed 80 patients, whose characteristics are shown in Table 30.
The most frequent subtype was oligoarticular JIA (16.3% extended, 47.5% persistent)
followed by polyarticular JIA (25.1%). Twenty-five percent had uveitis. Fifty percent
had inactive disease with treatment, 26% had activity and 23% were inactive without
treatment. 52.5% had methotrexate and 30% had a biological drug (22.5% antiTNFα, 5%
antiIL-1, 2.5% antiIL-6), with an average disease duration of 6.6 years (±3.7DE).They
had mean scores of JADAS27 of 2 (± 4DE), PCR of 4.7 mg/l (± 9,5DE), VSG of 8.7 mm
(± 7,2DE) and CHAQ of 0.17 (± 0,38DE). The anthropometric parameters are shown in
Table 30. The mean of JADAS27 in patients with normal BMI, was lower than 1.7 (± 3.6
SD) for those who were overweight or with obesity 3.3 (± 6.0 SD), although not significant
(p = 0.255). In simple linear regression, an increase of 0.3 JADAS27 was observed
for each unit of IMG increase (p = 0.03). This relationship was maintained in the
multivariate analysis (B 0.015; p 0.01) independently of the JIA subtype and the treatment
received during the evolution.
Table 30
(Abstract P85). See text for description
VARIABLE
n = 80
Age in years, median (±DE)
10,7 (3,3)
Sex, female; n (%)
56 (70)
BMI
Median en kg/m2 (±DE)
18,2 (4,2)
Percentile, median (±DE)
42,0 (29,9)
Index waist/hip (±DE)
0,84 (0,06)
Total fat (kg), media (±DE)
11,36 (8,9)
Total Lean (kg), media (±DE)
26,1 (8,9)
Total mass (kg), media (±DE)
38,8 (16,7)
MFI (%) media (±DE)
7,5(5,3)
MFFI (%) media (±DE)
17,8 (3,8)
Conclusion
CONCLUSION: In JIA patients, there is a linear relationship between IMG and disease
activity measured by JADAS, but most patients had a normal BMI. The establishment
of this relationship (fat-inflammatory activity) would be transcendental because of
the need to optimize the recommendations in the JIA approach
Disclosure of Interest: None Declared
P86 Hypovitaminosis D in juvenile idiopathic arthritis: prevalence and involved factors
Rocio Galindo Zavala1, Laura Martín Pedraz2, Esmeralda Núñez Cuadros1, Gisela Díaz-Cordovés
Rego3, Antonio L. Urda Cardona2
1Paediatric Rheumatology, Universitary Regional Malaga Hospital, MALAGA, Spain; 2Paediatrics,
Universitary Regional Malaga Hospital, MALAGA, Spain; 3Rheumatology, Universitary
Regional Malaga Hospital, MALAGA, Spain
Correspondence: Rocio Galindo Zavala
Introduction: 25hydroxi-vitamin D has antiinflammatory and immunomodulatory properties.
Hypovitaminosis D prevalence in Juvenile Idiopathic Arthritis (JIA) patients ranges
from 6% to 30%
Objectives: Evaluate hypovitaminosis D in JIA pediatric patients in Spain and assess
involved factors.
Methods: Observational cross-sectional study in JIA Spanish patients from 4 to 15 years
old, monitored by a Pediatric Rheumatology Unit. Monoarticular forms and patients
with other chronic diseases were excluded.
Anthropometric, clinical and treatment data were recorded. Blood test with bone metabolism
parameters and validated diet (KIDMED- Mediterranean Diet Quality Index) and exercise
(PAQ-C/PAQ-A-Physical Activity Questionnaire for Children) questionnaires were obtained.
Hypovitaminosis D was defined as 25hydroxi-vitamin D plasma levels lower than 30 ng/ml
Results: 76 children were enrolled. Their characteristics are included in Table 31.
Table 31
(Abstract P86). See text for description
PATIENTS` CHARACTERITICS (N = 76)
Gender (Male),
23 (30,3)
Age (years), median (IR) n (%)
10,83 (8,52-13,54)
25OH-Vitamin D (ng/mL), mean (+/-SD)
34,04 ng/mL (8,90 ng/mL)
DISEASE CHARACTERISTICS (N = 76)
JIA subtype, n (%)
Systemic
9 (11,8)
Oligoarticular
47 (61,9)
Polyarticular
20 (26,3)
Inflammatory activity duration (days), median (IR)
385,0(246,75-761,25)
RECEIVED TREATMENTS (N = 76)*
Systemic GC, n (%)
61 (80,2)
Synthetic DMARDs treatment, n (%)
39 (51,3)
Biological DMARDs treatment subtype, n(%)
Anti-TNFα
15 (19,7)
Anti-IL1
4 (5,2)
Anti-IL6
2 (2,6)
JIA: Juvenile idiopathic arthrtis; RF: Rheumatic factor; GC: glucocorticoids;
DMARD: Disease-modifying antirheumatic drug; Anti- TNFα: anti- tumoral necrosis factor
α;
Anti-IL1: anti-interleukin 1; Anti-IL6; anti-interleukin 6
The population's prevalence estimation of hypovitaminosis D was 16 - 35% (CI 95%).
We found no relationship between 25 hydroxi vitamin D levels and sex, JIA subtype
nor duration or dose of systemic glucocorticoids.
In bivariate analysis we found direct association between hypovitaminosis D and Body
Mass Index percentile (BMIp)(p = 0,05), received dose of prednisone (p = 0,03) and
clinical activity duration (p = 0,04); and an inverse relation with physical activity
level (p = 0,04).
In multivariate analysis, relationship between hypovitaminosis D and BMIp (B 0,024;
p 0,016) and with disease activity (B 0,015; p 0,01) were maintained. Moreover, we
found an inverse association with biological disease-modifiying antirheumatic drugs
(B-4,69; p 0,048), specifically with anti tumoral necrosis factor α (antiTNFα) (B
-4,7; p 0,042)
Conclusion: Hypovitaminosis D prevalence in our population is similar to previously
described.
JIA patients with higher BMIp have more hypovitaminosis D, as it has been reported
in other inflammatory diseases.
A direct relationship exists between inflammatory activity and hypovitaminosis D,
but we need more studies to asses if one is cause or consecuence of the other.
Patients treated with antiTNF have higher plasma levels of 25 hydroxi-vitamin D, this
can be explained because these drugs may increase 25 hydroxi-vitamin D levels or due
to a better response to antiTNF of those patient with higher plasma levels of 25 hydroxi-vitamin
D.
Disclosure of Interest: None Declared
P87 Neuropsychological assessment in juvenile idiopathic arthritis - Part I: cross-sectional
study in a single Hungarian centre
Diana Garan1, Gyurgyinka Gergev1, Wouter Wijker2, Imre Bozi2, Tamás Constantin1
1Rheumatology, 2nd Department of Pediatrics Semmelweis University, Budapest, Hungary;
2Auxiliis-Pharma Kft., Budapest, Hungary
Correspondence: Diana Garan
Introduction: Juvenile idiopathic arthritis (JIA) is one of the most common pediatric
chronic illnesses. A remarkable number of patients need long term or lifelong treatment.
In ‘biological era’ many publications have strengthened the safety and effectiveness
of TNF inhibitors and some of them noticed psychological or neuropsychological (NP)
adverse events (AE). The relationship of these AEs with the treatment is unclear.
There is no evidence available if these skills vary in different therapy and change
during JIA therapy.
Objectives: Our aims are to estimate NP state in JIA treatment groups and specify
NP state influencing factors. The next step was to compare NP state in different treatment
groups.
Methods: Descriptive statistics and exploratory analysis were completed. 120 patients
were examined at the Paediatric Rheumatology Unit (Semmelweis University, Budapest)
between 01.01.2015 - 31.12.2016. 68 patients received combined therapy (TNF inhibitor + methotrexate
(MTX) and/or salazopyrin (SSZ)), 42 patients received DMARD: MTX +/-SSZ, 18 patients
were on only TNF inhibitor therapy. After a formal psychological assessment, all patients
were tested with age specific questionnaires as well: Infant Behaviour Questionnaire,
Children’s Behaviour Questionnaire, Child Behaviour Checklist. Furthermore, by using
Woodcock Johnson III Tests of Achievement, three NP variables were compared in treatment
groups: attention, learning, and working memory. In addition, current and baseline
disease activity, duration of therapy and demographic parameters were assessed in
each group. These parameters were stratified, and NP variables were compared in these
strata. Comparison of NP variables of different treatment groups were age-, age at
diagnosis-, gender-, duration of treatment-, current and baseline JADAS disease activity-matched.
Results: In the analysis of each treatment groups we did not observe any significant
deviation of all NP variables based on age, gender, duration of treatment, current
JADAS disease activity. All NP variables were the highest in patients whose JIA was
diagnosed between 3,1-5,25 years of age. In combined therapy group attention was significantly
(p < 0,05) higher in patients whose baseline disease activity was low. In the analysis
of comparison of treatment groups the following differences were observed: learning
score was significantly lower (p < 0,05) in male patients in MTX group than in the
combined therapy group. Working memory score was significantly (p < 0,05) higher in
patients whose JIA was diagnosed between 3,1-5,25 year of age, and whose treatment
duration was longer than 3 years in combined therapy group. Attention score remained
stable in age-, age at diagnosis-, gender-, JADAS disease activity-matched treatment
groups. There was no significant discrepancy in all three NP variables between disease
activity-matched treatment groups.
Conclusion: We have not observed any clinically significant difference in the neuropsychological
state in different treatment groups assessed only at a definite date. Age, age at
diagnosis, gender, duration of treatment, current and baseline JADAS disease activity
were not clinically influencing factors of NP variables in this study. The analysis
of cognitive function has already been assessed, but has not been analysed yet. In
a prospective study we will follow patient’s psychological changes before and during
therapy in order to observe if different therapies have any effect on psychological
functions in JIA patients.
Disclosure of Interest: None Declared
P88 Characteristics of TNF inhibitor treatment in juvenile idiopathic arthritis -
2-year-follow-up in a Hungarian centre
Diana Garan, Anita P. Juhász, Andrea Ponyi, Tamás Constantin
Rheumatology, 2nd Department of Pediatrics Semmelweis University, Budapest, Hungary
Correspondence: Diana Garan
Introduction: TNF inhibitors have been widely used in the therapy of juvenile idiopathic
arthritis (JIA) since the early 2000s.
Objectives: We assessed the efficacy, change in efficacy, reason for treatment discontinuation,
relapse rate of TNF inhibitor treatments for JIA started between 2012-2016 at the
Unit of Pediatric Rheumatology, Semmelweis University, Budapest.
Methods: 146 treatments were started for 116 patients with polyarticular course JIA.
The following variables were assessed: Giannini improvement and JADAS-71 score every
3 months, the time for achieving at least 90% Giannini improvement, reason for treatment
discontinuation, relapse rate. We estimated the alteration of Giannini improvement
and JADAS-71 disease activity in patients treated for at least 24 months. Finally,
we analysed the features of patients achieved inactive disease. Paired Wilcoxon test,
Kaplan-Meier survival analysis, log rank test, chi square test, Fisher’s test, T test
were used with SPSS statistics program.
Results: Statistically significant (p < 0,05) alteration was detected in achieving
ever higher improvement of the Giannini’s criteria in the first 12 months of treatment,
afterwards this alteration remained in tendency but not statistically. The JADAS-71
disease activity significantly decreased in the first 6 months of the treatment, afterwards
the decline remained in tendency. Giannini 90% improvement was achieved significantly
more frequently in those who received etanercept treatment, first-line TNF inhibitor
treatment and any first-line biological. Among those who achieved inactive disease,
there were significantly more of those, who started treatment with fewer active joints,
lower JADAS score and CHAQ values, and were significantly younger at diagnosis. Biological
therapy was discontinued due to inefficacy in 50,8%, remission 28% and adverse events
10,5% of cases. In addition, 37,5% of patients had relapse whose treatment was discontinued
due to remission, all within the first 3 months on off-medication.
Conclusion: Giannini’s criteria improved significantly over the first 12 months, the
disease activity decreased significantly in the first 6 months, afterwards these observations
remained in tendency in our cohort. Approximately one-third of treatments were discontinued
due to remission almost two-third of these patients have not experienced relapse during
our observation period.
Disclosure of Interest: None Declared
P89 Body composition measured by DEXA in children with juvenile idiopathic arthritis.
do they have sarcopenia?
Pilar Guarnizo1,2,3, Sally Pino2,4, Adriana Diaz-Maldonado2,5,6, Juan Manuel Reyes2
1Fundacion Cardio Infantil, Bogota, Colombia; 2Care for Kids, Bogota, Colombia; 3Cayre,
Bogota, Colombia; 4Hospital Universitario Infantil de San Jose, Bogota, Colombia;
5Hospital de La Misericordia, Bogota, Colombia; 6Instituto Roosevelt, Bogota, Colombia
Correspondence: Pilar Guarnizo
Introduction: Juvenile Idiopathic Arthritis (JIA) is the most frequent disease in
pediatric rheumatology. There are few studies about body composition in these population,
most of them suggest they have excess fat.
Sarcopenia in children and young adults is pathologic and constitute a risk factor
of morbi-mortality due to its association with alteration in immunologic function,
decrease strength muscle and thermoregulation capacity, exercise tolerance and functionality,
all of them affect articular function and preservation. Additionally, bone mass accretion
and bone mineral density are related proportionally direct to muscle mass.
Also patients with sarcopenia could present an increase in the fat mass known as sarcopenic-obesity.
Objectives: To describe body composition alterations in a cohort of children diagnosed
with JIA in Bogota, Colombia.
Methods: Cross-sectional study where a cohort of children with JIA was assessed the
anthropometry and densitometry measured by dual-energy X-ray absorptiometry (LUNAR
iDXA). It was evaluated stature and weight. The fat mass was evaluated through Fat
Mass Index (FMI): Kg/m2, subtotal percentage body fat for age and gender, and subtotal
trunk fat mass. To measure lean mass was used: lean mass index (LMI): Kg/m2, appendicular
lean mass (arm and leg lean): Kg/m2, and total bone mineral density less head (TBLH)
The statistical analysis was only descriptive where it involved measurement of central
tendency and dispersion.
Results: Thirty children were included in the study. Fifty three percentage were female
with average age of 13.8 years (ranked from 5 to 22 years).All subtypes of arthritis
were included, 56% had systemic and polyarticular subtypes.
The average of onset of the disease was 5 year (ranked from 2 to 14 years).
In this cohort 33% of the patients had short stature.
36% patients had compromise in fat mass. FMI median z-score was -0.57 (ranked from
-1.66 to 1.11), 26% of children presented fat deficiency (12.5% of them had severe
fat deficit), and 10% excess fat - obese. In 20% of patients the percentage of fat
was above of expected and trunk fat mass was higher in 16% of the studied children;
the last measure is related to cardiovascular risks.
80% of the patients had low LMI z-score that is considered as low lean mass- sarcopenia.
LMI z score median was -2.17 (ranked from -4.56 to 0.36). 58.6% presented low appendicular
lean mass.
30% of patients had compromise in two compartments (FMI and LMI). 100% of patients
with Fat deficit had low lean mass –sarcopenia, while 33% of patients had sarcopenic-obesity
(fat excess with sarcopenia) which is associated to decrease in life- expectancy.
The median z score for Total bone mineral density less head (TBLH) was -1.25 (ranked
from -3,8 to 1,5 . The TBLH density was low in a 30% of patients, from which 100%
had low lean mass-sarcopenia.
Conclusion: The included children diagnosed with JIA presented high percentage of
disorders of body compositions characterized by sarcopenia 80% followed by fat mass
compromise in 36% (low fat mass 26% and excess fat 10%) and low bone density in 30%.
The abnormalities in the lean mass could be explained due to the increase in metabolic
rate and catabolism which lead to skeletal muscle consumption. It has been described
“rheumatic cachexia” in 67% of adults with rheumatoid arthritis, affecting bone mineralization,
strength muscle loss, and is associated with cardiovascular risk increase, but there
is not any data in children with JIA.
This is the first study which measure sarcopenia by DEXA in this population, additional
studies including more patients are necessary to validated these results and establish
opportune interventions to improve their nutritional status and quality of life.
Disclosure of Interest: None Declared
Reference
1. Evaluacion del estado nutricion en una población mexicana de pacientes adultos
con artritis reumatoide. L. Puentes, G. F. Hurtado, C. Abud, A. Bravo. NutrHosp. 2009:24:233-238
P90 Clinical TMJ involvement in JIA patients according to the ILAR categories : preliminary
study in 137 children.
Severine Guillaume Czitrom, Gianpaolo de Filippo
Service de Medecine des Adolescents, Chu Bicetre, Kremlin-Bicetre, France
Correspondence: Severine Guillaume Czitrom
Introduction: Temporo-manidibular joint (TMJ) involvement in juvenile idiopathic arthritis
(JIA) is the subject of many unanswered questions.
Objectives: We here wonder if the ILAR categories might help identifying JIA patients
at risk of TMJ involvement.
Methods: In single cohort of consecutive JIA patients, TMJs were systematically examined
at each follow-up visit of JIA patients according to the European recommendations.
Clinical involvement of TMJs over time was longitudinally recorded during JIA follow-up.
JIA categories were defined according to ILAR definitions.
Results: There were 137 JIA patient, comprising 89 girls and 44 boys aged 14.13 years
+/- 4.99 at the time of the analysis. Mean age at disease onset was 7.84 years +/-
4.89 and mean follow-up was 4.41 years +/- 3.83 [0.2-23.9 years]. There were 63 ERAs,
33 oligoarticular JIAs with 26 persistent and 7 extended diseases, 27 polyarticular
JIAs, 6 being RF positive, 10 psoriatic arthritis and 4 systemic JIAs.
44 JIA children had clinically detectable TMJ involvement (32%), but the percentages
were rather different across the ILAR sub-groups : TMJs were symptomatic in 12 ERAs
(19%), in 9 oligoarticular JIAs (27.3%), in 18 polyarticular JIAs (66.7%), in 3 psoriatic
arthritis (30%) and in 2 systemics (50%) ; moreover, within the oligoarticular group,
the most affected category was the oligo-extended group with 6 out of 7 patients having
TMJs involved (85.7%).
Interestingly, the clinical manifestations were not the same since half of the oligoextended
JIA patients reported no pain, no chewing difficulty, no evidence of mouth opening
limitation but insidiously developped facial asymetry due to unilateral TMJ inflammation.
In all cases, the spreading of the arthritic process happened before 5 of age. In
contrast, ERA patients manifested pain and reduced mouth opening much more frequently
and at a later age, prompting to a quick therapeutic answer.
Conclusion: In conclusion, TMJ arthritis might have severe consequences in those patients
starting agressive disease early in life, as many extended-oligoarticular as well
as part of polyarticular JIAs and systemics. Detecting the patients at high risk for
structural damage in TMJs should be a major goal in the coming years. This preliminary
study also shows that a significant proportion of ERA patients suffer from TMJ inflammation
during the course of their disease. The limited number of patients is the drawback
of this preliminary study and larger prospective studies are required to validate
these data.
Disclosure of Interest: None Declared
P91 MRP8/14 and conventional inflammatory markers explaining physician’s global assessment
of disease activity in new-onset juvenile idiopathic arthritic patients
Paula Keskitalo1, Salla Kangas2, Paula Vähäsalo1
1Department of Children and Adolescents, University of Oulu, Oulu, Finland; 2Medical
Research Center Oulu, Oulu University Hospital and PEDEGO Research Unit, University
of Oulu, Oulu, Finland
Correspondence: Paula Keskitalo
Introduction: Juvenile idiopathic arthritis (JIA) is a chronic inflammatory joint
disease affecting children. In clinical practice it is occasionally difficult to assess
the real inflammatory activity. Physician’s assessment of global disease activity
(PGA) is a holistic assessment and it is always available. The myeloid-related protein
complex 8/14 (MRP8/14, calprotectin) secreted by infiltrating phagocytes in synovial
inflammation has been suggested to function better than conventional acute-phase reactants
as a marker of low inflammatory activity and to be more sensitive and reliable indicator
of disease activity.
Objectives: The aim of our prospective, observational cohort study was to analyze
whether the MRP8/14 levels in serum (S-MRP8/14) or plasma (P-MRP8/14) and conventional
inflammatory markers, such as erythrocyte sedimentation rate (ESR), C-reactive protein
(CRP), leucocytes (leuc) and neutrophils (neutr), correlate with disease activity
assessed by physician.
Methods: Serum and plasma MRP8/14 concentrations from 88 concecutive new-onset JIA
patients collected before starting DMARDs were measured by human calprotectin ELISA
kit (Hycult biotech). Clinical data of the patients with median age of 6.6 yrs (range
1 – 15.3 yrs) were collected during the visits in the pediatric rheumatology outpatient
clinic in Oulu University Hospital between October 2011 and November 2014. Median
PGA was 21 with the scale 0-100 (range 3 – 85), median patients/parents global assessment
of wellness 31 (range 0 – 88), median patients/parents assessment of pain 31 (range
1 – 45), and median number of joints with active arthritis (AJC) 3 (range 1 – 45).
Correlations were analyzed by Spearman’s coefficient. Multiple linear regression was
used to quantify the strength of the relationship between laboratory inflammatory
markers and to assess which parameter has the most powerfull coefficient of determination
of PGA.
Results: Median P-MRP8/14 concentration was 184.9 ng/ml (range 1.2 – 685.9 ng/ml)
and in S-MRP8/14 255.0 ng/ml (67.4 – 553.5 ng/ml). Median CRP was 1.5 mg/l (1.5 –
193 mg/l), ESR 13 mm/h (2 – 98 mm/h), leuc 7.4 x 10E9/l (3.4 – 15.2 x 10 E9/l) and
neutr 3.9 x 10E9/l (1 – 10.5 x 10E9/l).
We found positive correlations between PGA and the laboratory parameters. PGA weakly
correlated with leuc (Spearman’s Rho 0.281, P = 0.008) and neutr (0.313, P = 0.007).
Association was better with ESR (0.432, P < 0.001), CRP (0.582, p < 0.001), P-MRP8/14
(0.682, P < 0.001) and S-MRP8/14 (0.409, P < 0.001).
PGA has stronger association with P-MRP8/14 than with the other inflammatory parameters
(Table 32.). Multiple linear regression analysis showed leuc, ESR, CRP, neutr, S-MRP8/14
and P-MRP8/14 explaining 55% of PGA. When analyzed the standardized B the strongest
relationship was found between P-MRP8/14 and PGA (B = 0.084 (95% CI: 0.045 – 0.123)
P < 0.001, standardized B = 0.733), but association between S-MRP8/14 and PGA remained
weak (B = -0.032 (95% CI: -0.074 – 0.010), P = 0.14, standardized B = -0.203).
Table 32
(Abstract P91). Relationships between PGA and laboratory parameters analyzed by linear
regression
B
95% CI
P-value
R2
ESR
0.358
0.194 – 0.523
<0.001
18.3%
CRP
0.345
0.227 – 0.463
<0.001
28.7%
Leucocytes
1.387
0.064 – 2.710
0.040
4.9%
Neutrophils
1.849
-0.289 – 3.986
0.089
4%
MRP8/14 in serum
0.056
0.024 – 0.087
0.001
12.9%
MRP8/14 in plasma
0.075
0.056 – 0.094
<0.001
47.8%
R2 coefficient of determination, B regression coefficient
Conclusion: P-MRP8/14 seemed to be much better than the other conventional inflammatory
laboratory markers or MRP8/14 serum concentration when assessing disease activity
in JIA patients. P-MRP8/14 concentration might be useful indicator to be used in clinical
practice when making evalution of disease activity.
Disclosure of Interest: None Declared
P92 Chronic arthritis as the only manifestation of FMF in Armenian children
Gayane Khloyan
ARABKIR JMS ICAH, Yerevan, Armenia
Introduction: Familial Mediterranean Fever (FMF) is the most common inherited auto
inflammatory disease, characterized by recurrent, self–limited attacks of fever and
aseptic polyserositis.FMF is widespread in Armenia and there is a higher than expected
frequency of FMF-associated arthritis in children. Chronic arthritis can be the first,
and sometimes the only manifestation of FMF.
Objectives: To the importance of genetic investigation for MEFV gene mutations in
patients of high-FMF-prevalence ethnicities with chronic arthritis.
Methods: Case reports of two patients with chronic arthritis as their first symptom
of FMF.
Results: 1-st case: A 6 year-old boy was admitted to the hospital with complaints
of weakness and limping during the last 1.5 years. He had also self- limited episodes
of knee and foot pain. The physical examination revealed pain on flexion of the left
knee, painful palpation of both sacroiliac joints, but no visible or palpable changes
of the joints. Initial laboratory examination showed elevation of ESR– 49 mm/h and
CRP-48 mg/l. WBC, RBS, PLT were in normal range. An extensive diagnostic work up including
biochemical examination, serology tests, urine test, chest X-ray, Echo-CG revealed
no changes. Splenomegaly was found on abdominal sonography. MRI of the pelvic bones
and hip joints indicated signs of bilateral sacroiliitis. Chronic arthritis was diagnosed.
Despite of absence of clinical features of FMF, genetic analysis for MEFV gene mutations
was done and homozygous genotype for M694V mutation (M694V/M694V) was found. Treatment
with colchicine and sulfasalazine was started and both his clinical condition and
laboratory findings improved significantly. Only occasionally the patient still has
gait abnormalities.
2-nd case. A 1.8 year-old girl was admitted to the hospital because of pain, swelling
and deformity of the left wrist, which had started 5 months earlier. In her past history
2 episodes of unexplained fever of 1 day duration were noticed. The physical examination
revealed swelling, pain and limitation of motions of the left wrist. ESR was elevated
within 53 mm/h, but CRP was negative. Thorough diagnostic work up (CBC, biochemical
examination, serology tests, urine test, chest X-ray, Echo-CG, abdominal sonography)
revealed no pathologies. MRI of the left wrist indicated signs of arthritis. Chronic
arthritis was diagnosed. But also genetic analysis of MEFV mutations was done and
2 mutations (M694V/R761H) in compound-heterozygous state were found. Intraarticular
injection of triamcinolone acetonide to the left wrist was done and colchicine treatment
was started with significant improvement: during 4 months of follow up the girl had
no complaints and no inflammatory activity with normal level of ESR.
Conclusion: In ethnicities with high prevalence of FMF, screening for MEFV gene mutations
is recommended for patients with chronic arthritis even in the absence of FMF symptoms.
Disclosure of Interest: None Declared
P93 The efficacy of etanercept in non-systemic juvenile idiopathic arthritis in Saint-Petersburg:
the preliminary data of 148 patients from biologic registry.
Mikhail M. Kostik, Irina Chikova, Eugenia Isupova, Margarita Dubko, Vera Masalova,
Ludmila Snegireva, Ekaterina Gaidar, Olga Kalashnikova, Vyacheslav Chasnyk
Saint-Petersburg State Pediatric Medical University, Saint-Petersburg, Russian Federation
Correspondence: Mikhail M. Kostik
Introduction: Etanercept was the first biologic drug approved in children. Russian
rheumatologist received the access to etanercept only in 2009 after infliximab, adalimumab,
abatacept. Currently etanercept reach the first position in the biologics, used in
JIA in Saint-Petersburg.
Objectives: The aim of our study was to evaluate the efficacy of etanercept in the
tertial hospital in Saint-Petersburg using the registry.
Methods: The data about all patient (n = 148) who received etanercept were included
into the registry. We evaluated all routine JIA measures, ESR, CRP, achievement the
remission every 6 months, dynamics of height, weight and side effects. The duration
of study was more than 30 months.
Results: The demographic of study population was: girls were 92/148 (62.2%), onset
age - 4.9 (2.4; 9.6), age of etanercept initiation: 9.8 (5.9; 13.9) time between JIA
onset and etanercept was 2.4 (1.2; 5.8). Duration of etanercept treatment was 3.5
(2.3; 4.3) years. The distribution of JIA categories was: persistent oligoarthritis
6/148 (4.1%), extended oligoarthritis 11/148 (7.4%), RF-negative polyarthritis 84/148
(56.8%), RF-positive polyarthritis - 3/148 (2.0%), enthesitis-related arthritis -
32/148 (21.6%), psoriatic arthritis - 9/148 (6.1%), non-differentiated arthritis 3/148
(2.0%). ANA-positivity was in 33/120 (27.5%), HLA B27 - 24/80 (30%) and RF-positivity
- 5/148 (3.4%).
During the trial the etanercept shows high efficacy in the main JIA measures and laboratorial
tests (Table 33). Also we have observed decreasing of WBC (p = 0.03), PLT (p = 0.000001),
ESR (p = 0.03), increasing the hemoglobin (p = 0. 006), body mass index (p = 0.02).
Frequency of morning stiffness decreased from 62.8% to 4.6% (p = 0.0001). The achievement
of remission (ACRPedi100) reached 69.3% patients.
Table 33
(Abstract P93). See text for description
Parameter
Baseline
End of study
p
Morning stiffness, minutes
60.0 (30.0; 120.0)
20.0 (10.0; 20.0)
0.03
Global disease activity, mm
48.0 (35.0; 68.0)
0.0 (0.0; 28.0)
0.000001
MD VAS, mm
43.5 (30.0; 60.0)
0.0 (0.0; 18.0)
0.000001
Patient’s VAS, mm
20.0 (10.0; 20.0)
0.0 (0.0; 10.0)
0.000001
Painful joints, n
2.0 (1.0; 5.0)
0.0 (0.0; 0.0)
0.000001
Swollen joints, n
4.0 (2.0; 11.0)
0.0 (0.0; 0.0)
0.000001
Joints with LOM, n
4.0 (1.0; 9.0)
0.0 (0.0; 0.0)
0.000001
Active joints, n
7.0 (3.0; 15.0)
0.0 (0.0; 0.0)
0.000001
CRP, mg/l
1.9 (1.0; 5.5)
0.5 (0.2; 1.3)
0.000001
Etanercept was discontinued in 12/148 (8.1%) due to primary or secondary inefficacy
or new onset of uveitis, injection site reactions were rare and lead to discontinuation
of etanercept in 1/148 (0.7%). No serious infections, tuberculosis, malignancy were
observed during the study.
Conclusion: Etanercept show high efficacy in non-systemic JIA patients. Serious side
effects were rare and comparative to literature data. Registry of biologics is a good
tool for collection data about patients. Future investigations required.
Disclosure of Interest: None Declared
P94 The treatment of 40 polyarticular juvenile idiopathic arthritis children with
tocilizumab: single center experience.
Mikhail M. Kostik, Irina Chikova, Eugenia Isupova, Margarita Dubko, Vera Masalova,
Ludmila Snegireva, Ekaterina Gaidar, Olga Kalashnikova, Vyacheslav Chasnyk
Saint-Petersburg State Pediatric Medical University, Saint-Petersburg, Russian Federation
Correspondence: Mikhail M. Kostik
Introduction: Juvenile idiopathic arthritis (JIA) – is a chronic inflammatory joint
diseases, which affects the children under the age 16. Methotrexate (MTX) is a basis
of treatment of patients with polyarticular JIA (pJIA). Patients, who fall or intolerance
MTX required in biologic treatment.
Objectives: The aim of our study was evaluate the efficacy and safety of tocilizumab
(TCZ) in children with pJIA.
Methods: In the present retrospective study with maximal duration 42 months were included
40 children (82,5% girls) with active pJIA, resistant to previous therapy with MTX
alone or combination with others non-biologic DMARDs, whom were treated with TCZ every
4 weeks 8 mg/kg (weight ≥ 30 kg) and 10 mg/kg (weight < 30 kg). Onset JIA age was
4,8 (2,9; 8,1) years, time between JIA onset and start of TCZ was 5,7 (1,8; 8,5) years.
Duration of TCZ treatment was 1109 (452; 1542) days. TCZ monotherapy was in 13,2%
children.
Results: During TCZ course NSAID were discontinued in all studied population, decreased
part of children who were treated with combination of non-biologic DMARDs from 37.5%
to 2.5% and proportion of whom were treated with MTX from 92.5% to 75.0%, and leflunomide
up to 2.5%. The discontinuation of the second DMARD, corticosteroids, cyclosporine
and NSAIDs were due to achievement of remission and rare due to intolerance. In first
6 months of therapy was revealed impressed decreasing of ESR (p = 0.000002), CRP (p = 0.00002),
WBC and (p = 0.001) PLT (p = 0.00002) up to normal ranges during whole TCZ course.
Number of active joints decreased gradually (p = 0,00002), reached the median = 0
to 24th month, 15.3% obtained inactive disease status in 6 months and 80% in 42 months.
During the study inactive disease status was reached totally in 60.5% patients and
in 3 patients TCZ was discontinued due to persistent remission. The main predictors
of achievement inactive disease were WBC < 9.0 x 109/l (HR = 1,92, p = 0.16), absence
of previous biologic treatment (HR = 1.92, p = 0.16). The absence of previous biologic
treatment was also predictor of low disease activity status (HR = 2.4, p = 0.01).
Among adverse effects were transient hypercholesterolemia and hypertriglyceridemia
and single episode of grade II neutropenia which not lead to TCZ discontinuation infection
side effects and antibiotic treatment.
Conclusion: The safety and efficacy of TCZ was demonstrated in children with pJIA.
Serious adverse events were not revealed.
Disclosure of Interest: None Declared
P95 Atypical oligoarticular juvenile arthritis in children: elbow chronic monoarthritis
Aleksey Kozhevnikov1,2, Nina Pozdeeva1, Michael Konev1, Maxim Nikitin1, Anastasia
Bryanskaya1, Evgeniy Prokopovich1, Konstantin Afonichev1, Gennadiy Novik2
1Orthopedic and rheumatology department, Federal state budget institution “The Turner
Scientific and Research Institute for Children's Orthopedics”, Saint-Petersburg, Russian
Federation; 2Pediatric department n.a. prof. I.M. Voroncov, Federal state budget institution
of higher professional education “Saint-Petersburg State Pediatric Medical University”,
Saint-Petersburg, Russian Federation
Correspondence: Aleksey Kozhevnikov
Introduction: Juvenile arthritis is a broad term that describes heterogeneous group
of a chronic inflammatory joint disease which characterized by progressive course
leading reduced mobility and function. Progressive chronic arthritis of an unknown
cause lasting for at least more than three months are the main diagnostic criteria
of JIA. A typical classic variant of oligoarticular JIA (oligo-JIA) is well known.
Monoarthritis of the elbow joint is atypical onset oligo-JIA. It’s difficult to differentiate
of elbow chronic synovitis due to clinically heterogeneous. The instrumental and specific
diagnostic tests are great assistance to determine cause of synovitis.
Objectives: Chronic synovitis in children arises from several causes. There are inflammatory,
infectious, traumatic, reactive, hemorrhagic, neoplastic and undifferent etiologies
of synovial diseases. Usually chronic elbow monoarthritis associated with tumor-like
conditions (pigmented villonodular synovitis, synovial haemangioma and chondromatosis),
osteomyelitis, tuberculosis arthritis, osteochondropathy and rare JIA. The aim of
the present study was to determine diagnostic and treatment strategies of elbow monoarthritis
manifested like oligo-JIA.
Methods: We carried out a retrospective review of sixteen children with chronic undifferentiated
elbow monoarthritis which were hospitalized at Children Orthopedics Institute, Saint-Petersburg
(rheumatology department) between 2011 and 2016. The data of clinical, serological,
x-ray, ultrasound, MRI, arthroscopy and synovial fluid were analyzed. Detected atypical/diffuse
form synovial proliferation or limited to a well-defined single nodule were recommended
for arthroscopy and biopsy. Six children were excluded from study due to verification
of cause elbow monoarthritis: 6-yr-old girl - PVNS, 10-yr-old boy cavernous haemangioma
and 17-yr-old boy - synovial chondromatosis, 2 small girls and 1 boy - osteoid osteoma.
Ten children were study group (median age 5,8 ± 2,5, range 3-11 years; female 90%,
male 10%). Children with post-traumatic elbow joint transient effusion were controls.
Results: Trauma of elbow joint related to onset chronic arthritis, progressive flexure
contracture with dry synovitis, low activity and the long-term period absence of clinical
involvement of other joints were occurred in all children. Asymptomatic early-stage,
progressive flexure/combined contracture less joint effusion and morning stiffness
were cause of late diagnosis of oligo-JIA. Only seven children (all girls) were ANF
positive ≥ 1:160, two HLA-B27 positive. Radiographic finding of early-stage JIA were
accelerated cartilage model ossification of distal humeral epiphysis and trochlear,
osteoporosis with subchondral bone sclerosis and cyst-like deformation. The MR imaging
were non-specific inflamed elbow synovium. Overgrowth of epiphysis and trochlear with
joint space narrowing, deformation articular surfaces with erosive changes were radiographic
findings of late-stage JIA. MR imaging revealed significance multiple erosive synovitis
with bone cyst-like deformation. Ultrasound wasn’t show elbow synovitis at half of
the study children. 70% children were negative effect of monotherapy NSAID. Positive
treated effect was achieved after intra-articular triamcinolone injection (20-40 mgs)
and methotrexate therapy (15 mg/m2/week) > 6 months, splinting and physiotherapy.
After 2-3 years 30% children were persistence oligo-JIA (involved wrist or knee),
40% - extended oligo-JIA, 30% - isolated monoarthritis. Children with post-traumatic
elbow joint deformation haven’t revealed chronic synovitis.
Conclusion: Monoarthritis of elbow joint are rare atypical manifestation of pauciarticular
JIA. Non-specific clinical signs and instrumental imaging may contribute to diagnostic
problems of elbow chronic synovitis. Therapy of elbow chronic idiopathic monoarthritis
must be coincide treat-to-target strategy in juvenile arthritis. Ultrasound can’t
be the decisive diagnostic method of chronic elbow pathology.
Disclosure of Interest: None Declared
P96 Platelet microparticles level in juvenile idiopathic arthritis
Sathish Kumar, Naresh Kumar
Rheumatology, Department of Pediatrics, Christian Medical College, Vellore, India
Correspondence: Sathish Kumar
Introduction: Juvenile idiopathic arthritis (JIA) encompasses a complex group of disorders
comprising several entities in children. Multiple biomarkers have been used to detect
the disease activity. Platelet Microparticles(PMP) are small vesicles released from
plasma membrane upon platelet activation. Several studies stated that PMP has been
associated with the thrombotic event and inflammatory process in adults. This is the
first study in literature to estimate PMP in JIA.
Objectives: To estimate the level of plasma PMP in children with JIA and to study
the relationship with disease activity of JIA.
Methods: Study design: Cross-sectional study
Inclusion criteria: Children with JIA who fulfilled the International League of Associations
for Rheumatology (ILAR) classification criteria for juvenile idiopathic arthritis
were included.They were categorized into active disease group and inactive disease
as assessed by Wallace criteria. Complete Blood count, ESR, CRP, and PMP were estimated
in all children. PMP level was calculated by Flow Cytometry.Blood investigations and
baseline demographics were analyzed
Results: Out of 26 children with JIA, 12 had active disease group and 14 had an inactive
disease as assessed by Wallace criteria. Mean PMP level was 83507 cells/μland 34904
cells/μlin active and inactive disease respectively (p = 0.06). There was no significant
correlation between PMP level in JIA patients with corresponding ESR, CRP, and platelets
Conclusion: Our study states that level of PMP is significantly elevated in disease
activity of JIA and could represent a new biomarker reflecting the state of cell activation
in JIA. PMP role in the inflammatory processes needs to be further elucidated
Disclosure of Interest: None Declared
Miscellaneous rheumatic diseases
P97 The need for dedicated paediatric rheumatology services: retrospective review
of a clinic service at Tygerberg Hospital, South Africa
Deepthi R. Abraham1, Monika M. Esser2
1Dept of Paediatrics and Child Health, Faculty of Medicine and Health Sciences, NHLS
Immunology Unit Tygerberg Hospital, Division Medical Microbiology, Faculty of Medicine
and Health Sciences, Stellenbosch University, Cape Town, South Africa; 2Department
of Pathology, NHLS Immunology Unit Tygerberg Hospital, Division Medical Microbiology,
Faculty of Medicine and Health Sciences, Stellenbosch University, Cape Town, South
Africa
Correspondence: Deepthi R. Abraham
Introduction: Paediatric Rheumatology in South Africa competes with limited health
care resources allocated to epidemic diseases. Data on prevalence, incidence, disease
categories, delay in diagnosis and management are crucial for defining the need for
specialized services. Available literature is limited in South and sub-Saharan Africa.
Major challenges include lack of awareness; lack of trained staff, facilities and
support services.1 Education in Paediatric Rheumatology is neglected at undergraduate
and postgraduate levels with a shortage of paediatric rheumatologists.1 Tygerberg
Hospital offers a dedicated clinical service since 1995 with an accredited subspecialty
training post since 2005.
Objectives: The primary aim is to document demography, disease profile and medical
management of patients attending the Tygerberg Paediatric Rheumatology clinic. The
secondary aim, based on these findings, will address the need of specialized services
and subspecialty training posts.
Methods: Retrospective folder review, electronic data search and use of bivariate
and multivariate statistical tools used for analysis to outline the disease profile
of JIA (Juvenile Idiopathic Arthritis), other autoimmune (AI) or auto-inflammatory
diseases and miscellaneous musculoskeletal conditions and management thereof.
Results: 450 patients were reviewed between March 1995 and March 2017. Referrals were
derived from secondary and tertiary hospitals (68%), general and private practitioners
(13%) and 8.2% by primary healthcare centers. 60% of referred patients resided in
the greater Cape Town region and 40% in rural-country regions, depending on availability
of public health transportation services. Most of the patients (74%) were from a family
income bracket of less than 7700 USD per year.
Gender distribution reflected 56% female and 44% male. The most common age of presentation
was between 10-14 years (46%) with a range of 0 to19 years. Racial distribution was
Mixed Racial 79%, Blacks 16%, Whites 4% and Asians 1%. JIA (38%) was most common rheumatological
condition. Reactive Arthritis (23%), autoimmune and autoinflammatory conditions (11%),
vasculitides (2%) and miscellaneous musculoskeletal conditions (39%) e.g. growing
pains, Raynaud's, infection related arthritis, malignancies etc. comprised the rest.
Common presenting symptoms were tender joints (71%), stiffness after rest (46%) and
swollen joints (44%). Uveitis was present in 9% at initial diagnosis or during follow
up. Delay in diagnosis was up to 9 years.
Ibuprofen (42%) was the most commonly used NSAID. Most frequently used DMARD's were
methotrexate and hydroxychloroquine. Intra articular steroid injections were frequently
indicated and biological therapy accessed by selected patients.
Referral to ancillary services included physiotherapy (51.6%), imaging predominantly
X-rays (41%), ophthalmology (47.1%), orthopedics (37%), occupational therapy (27%)
and dermatology (16.7%).
46.5% were offered social grants. 14.7% recorded, achieved remission. Remission could
not be established in most patients due to high rate of patients lost to follow up
(50%). 3.5% transitioned to adult Rheumatology services.
Conclusion: Patients reviewed were mainly of mixed racial origin from low-income homes.
JIA was the most common paediatric rheumatological condition seen. Delay in diagnosis
and late referrals were frequent. Increased awareness, education and training, early
diagnosis of disease and appropriate funding for these neglected diseases could dramatically
improve outcome. Addressing challenges unique to a developing country and resultant
complexities of management are essential for advocacy and planning of such services.
Disclosure of Interest: None Declared
P98 Raynaud phenomenon secondary to the use of illicit drugs
Abstract withdrawn
P99 Unilateral recurrent ear chondritis in spondylarthritis does not always progress
to polychondritis
Laura Damian1,2, Simona Rednic2,3,4, Cristina Pamfil5,6, Linda Ghib3, Maria-Magdalena
Tamas3, Siao-Pin Simon2,5, Calin Lazar7, Laura Muntean5, Alma Maniu3,8
1Rheumatology, Centre for Rare Musculoskeletal Autoimmune and Autoinflammatory Diseases,
Cluj-Napoca, Romania; 2Emergency Clinical County Hospital, Cluj-Napoca, Romania; 3Iuliu
Hatieganu University of Medicine and Pharmacy, Cluj-Napoca, Romania; 4Centre for Rare
Musculoskeletal Autoimmune and Autoinflammatory Diseases, Cluj-Napoca, Romania; 5Rheumatology,
Iuliu Hatieganu University of Medicine and Pharmacy, Cluj-Napoca, Romania; 6Centre
for Rare Musculoskeletal Autoimmune and Autoinflammatory Diseases, Emergency Clinical
County Hospital, Cluj-Napoca, Romania; 7Pediatrics, Emergency Clinical County Hospital,
Cluj-Napoca, Romania; 8ENT, Emergency Clinical County Hospital, Cluj-Napoca, Romania
Correspondence: Laura Damian
Introduction: Ear perichondritis can be caused by trauma, relapsing polychondritis
(RP), vasculitis, infections etc. Irrespective of etiology, cartilage deformity and
necrosis may occur. Chondrodermatitis nodularis helicis (Winkler’s disease) is a localized
cartilage inflammation, often with crusting, resulting from trauma or bland vascular
impaiment.
Objectives: Long-term assessment of recurrent unilateral perichondritis in patients
with systemic diseases, for the development of RP diagnostic criteria.
Methods: We retrospectively identified the cases of unilateral recurrent ear perichondritis
in the patients with suspected polychondritis in the last 15 years in a tertiary referral
adult Rheumatology department. The patients then fulfilled a questionnaire and were
seen prospectively for two years. All chondritis episodes and the Mc Adam and Damiani-Levine
polychondritis criteria were assessed. Laboratory tests for inflammation, immunology,
uric acid, ENT examination, cartilage biopsy whenever accepted and an extensive search
for infection,vasculitis, hematologic malignancies, as well as complications of other
organs classically involved by polychondritis were recorded, as part of the regular
screening for polychondritis.
Results: We identified 3 cases of recurrent unilateral chondritis, all occuring in
spondylarthritis patients, that were followed up for 3 to 12 years for other polychondritis
features, without development of RP criteria. None of these patients developed ulcerations
or crusting to suggest Winkler’s disease, either.
Case 1: A 26-years female patient with a juvenile extensive oligoarthritis since the
age of 5 and psoriasis since 11, on methotrexate, presented with recurrent episodes
of right ear swelling and inflammation, healing within three days, not altered by
empiric antibiotic short courses, accompanied by transient mild leukocytosis with
neutrophilia. An active follow-up for 12 years did not reveal other chondritis sites.
NSAIDs helped to alleviate the attacks, which became less frequent with time.
Case 2: A 48-year male patient with aseptic abscesses syndromes, Crohn’s disease and
spondylarthritis with bilateral coxitis diagnosed for 3 years had a recurrent left
ear upper lobe inflammation since the first visit. The nodular chondritis, with low-level
local inflammation generally lasting for one week, independent from the joint flares,
responded to the addition of NSAID and sulfasalazine to adalimumab and azathioprine.
No progression to polychondritis was noted in 3 years.
Case 3: A patient with undifferentiated spondylarthritis and a history of treated
medullar thyroid carcinoma presented with recurrent right ear painful inflammation.
No signs of tumoral dissemination or relapse were detected in 6 years. The cartilage
biopsy was normal. The attacks' frequency decreased after leflunomide.
Conclusion: Unilateral recurrent ear perichondritis may not always herald polychondritis,
at least in spondylarthritides. It can be speculated that local triggers (pressure
on the ear, etc) may activate the innate immunity through danger-associated molecular
patterns, however, the progression to polychondritis probably requires activation
of certain Toll-like receptors. An active search for an RP is nevertheless worthed
in the unilateral chondritis, as RP requires a more aggressive therapy. Informed consent
to publish has been obtained from the patient/parent/guardian.
Funding:PN-II-RU-TE-2014-4-2708
Disclosure of Interest: None Declared
P100 Evaluation of the dental and temporomandibular joint status in children with
generalized joint hypermobility
Ferhat Demir1, Tamer Tüzüner2, Özgül Baygın2, Mukaddes Kalyoncu1
1Department of Pediatric Rheumatology, Karadeniz Technical University Faculty of Medicine,
Trabzon, Turkey; 2Department of Pediatric Dentistry, Karadeniz Technical University
Faculty of Dentistry, Trabzon, Turkey
Correspondence: Ferhat Demir
Introduction: Generalized joint hypermobility (GJH) is characterized by deficiency
of collagen and changes in the proportion of collagen subtypes. It is a clinical feature
associated with excessive laxity of joints. Oral mucosa, teeth and temporomandibular
joint (TMJ) can be affected in these condition.
Objectives: It was aimed to evaluate the dental and temporomandibular status in children
with GJH.
Methods: Sixty two children with GJH and age-sex match sixty two healthy children
as a control group were enrolled to the study. The GJH was assessed by the Beighton
Hypermobility Score (BHS). The subjects screened for dental and TMJ status. Assesment
included index for ‘Decayed’, ‘Missing’ and ‘Filled Teeth’ (DMFT), visual plaque index
(VPI) and gingival bleeding index (GBI) scores, tooth mobility and TMJ evaluation.
The Mann–Whitney U and chi-square tests were used to evaluate the data.
Results: Mean BHS score was found 6.3 ± 1.2 in GJH group. VPI and GBI scores were
found significantly higher in children with GJH then control group (p < 0.05). No
differences were found regarding the DMFT scores between GJH and control groups (p > 0.05).
Temporomandibular disease (TMD) frequency was significantly higher in children with
GJH compared to the control group (p < 0.001) (Table 34). The most frequent TMD obtained
as clicking while maximum active mouth opening. By the way, combined TMJ problems
observed in approximately one third of the GJH children.
Table 34
(Abstract P100). Comparison of dental status, MT and TMD between in GJH and control
groups
GJH group
Control group
p
Age (median (min-max))
8 (5-17)
9 (5-17)
0.43*
Gender (M/F)
36/26
36/26
0.57#
VPI positivity (%)
88.7
74.2
0.03#
GBI positivity (%)
64.5
45.2
0.02#
DMFT score (median(min-max))
0.062 (0-0.23)
0.080 (0-0.23)
0.27*
MT positivity (%)
3.2%
1.6%
0.50#
TMD positivity (%)
48.4%
14.5%
<0.001#
*Mann-Whitney U test and #Chi-square test was used for analysis. VPI: Visual plaque
index, GBI: Gingival bleeding index, DMFT: decayed, missing and filled teeth, MT:
Mobility of tooth, TMD: temporomandibular disease.
Conclusion: High frequency of TMD in GJH group may demonstrate that TMJ is also affected
in GJH. The higher VPI and GBI scores indicating the poor oral hygiene in children
with GJH may point out that, this children can not perform properbly toothbrushing.
Trial registration identifying number: Ethical approval was obtained from the Ethics
Committee of Karadeniz Technical University, Faculty of Medicine (Approval number:
2016/102).
Disclosure of Interest: None Declared
P101 Successful treatment of pediatric IGG4 related ophthalmic disease with mycophenolate
mofetil: case report and a review of the pediatric autoimmune dacryoadenitis literature
Talia Diaz, Yuridiana Ramirez, Sofia Osorio, Maria Teresa Braña, Luis Aparicio, Andres
Rodriguez, Enrique Faugier, Rocio Maldonado
Pediatric Rheumatology, Hospital Infantil de Mexico Federico Gomez, Ciudad de Mexico,
Mexico
Correspondence: Talia Diaz
Introduction: IgG4-related disease (IgG4-RD) is relatively a new growing entity of
immune mediated origin, characterized by a unique pathological feature that affect
a wide variety of organs with infiltration of IgG4-positive plasma cells and occasionally
elevated serum IgG4. It is both a systemic inflammation and a sclerosing disease.
The most common manifestations are parotid (14-26%) and lacrimal swelling (4-13%),
lymphadenopathy and autoimmune pancreatitis. Several studies have examined orbital
adnexal IgG4-related disease or IgG4-related orbital inflammation. The diagnosis should
be proven histopathologically but other conditions such as lymphoma should be carefully
excluded. Patients with IgG4-RD respond beneficially to glucocorticoid therapy especially
when administered at early onset stages. In some cases, the combination of immunosuppressive
agents is required.
Objectives: To describe a pediatric clinical case with orbital IgG4 related disease
with an excellent response after immunosuppresive treatment.
Methods: We present a 16-year-old girl with IgG4-RD during one year with left ocular
pain and eye inflammation, diagnosed as bacterial conjunctivitis and trated with ophtlamic
antibioticoteraphy, with no improvement. Weight loss and increased acute phase reactants
(erythrocyte sedimentation rate and C-reactive protein). On ocular computed tomography.
Histopathology clearly defined the mass to be IgG4 related fibrosis with focally arranged
fibrosis in a storiform pattern, and positive CD20 deposit ++++, positive IgG4 +++
in plasmatic cells and lymphocytes, positive CD38 deposit ++. Biopsy report: Autoimmune
Dacryoadenitis Associated with IgG4 Disease. IgG4 serum normal level 9 mg/dl.
Ocular Magnetic resonance imaging was performed in which volume and lacrimal gland
intensity is identified, which displaces the rectus and oblique muscle causing proptosis,
the lacrimal gland presented an increase in it’s dimensions with measures of 23x8x10mm
in its posterior axes, posterior No abnormal reinforcement is identified in the contrast
medium. Infectious serological test were negative (EBV, CMV, HBV, HCV, toxocara and
toxoplasma).
Results: The patient was started on oral corticosteroids and mycophenolate mofetil,
which resulted in significant clinical improvement after 3 months of treatment, the
mass became smaller and the patient was asymptomatic.
Conclusion: IgG4-RD remains a field not yet fully explored or understood. Early and
efficient therapies aiming to achieve a beneficial outcome, and to improve prognosis
are still required.
Disclosure of Interest: None Declared
P102 Rheumatic fever and post-streptococcal arthritis in a tertiary hospital from
Paraguay.
Jorge Garcete1, Luz Galeano1, Carla Montiel2, Dong Chin2, Maria del Carmen Cabrera2,
Milagros Vargas Peña2, Carlos Verón2, María Lezcano3, Alicia Aldana3, Ana Campuzano
de Rolón1, Zoilo Morel Ayala4
1Pediatric Service, Hospital de Clinicas. Facultad de Ciencias Medicas.Universidad
Nacional de Asuncion., San Lorenzo, Paraguay; 2Pediatric Cardiology, Hospital de Clinicas.
Facultad de Ciencias Medicas.Universidad Nacional de Asuncion., San Lorenzo, Paraguay;
3Pediatric Neurology, Hospital de Clinicas. Facultad de Ciencias Medicas.Universidad
Nacional de Asuncion., San Lorenzo, Paraguay; 4Pediatric Rheumatology, Hospital de
Clinicas. Facultad de Ciencias Medicas.Universidad Nacional de Asuncion., San Lorenzo,
Paraguay
Correspondence: Jorge Garcete
Introduction: Rheumatic fever (RF) and post-streptococcal arthritis (PSA) are characterized
by autoantibodies secondary to beta hemolytic streptococcus group A infection. In
our country, the cardiac sequelae acquired by the RF generate substantial costs for
the State and family, becoming a public health problem.
Objectives: To assess the clinical characteristics and outcome of patients with RF
and PSA from a Paraguayan referral hospital.
Methods: Retrospective and descriptive study of patients under the age of 18 years,
diagnosed with RF and PSA between January 2009 and April 2017.
Results: 32 cases of RF and 8 PSA (all misdiagnosed as originally RF) were found.
The population is distributed similarly by all states of the Eastern Region from Paraguay.
The average monthly income per household is 18% with 2 minimum wages, 37% with a minimum
salary, 30% less than 1 minimum wage, and 15% without data. 62% of children with RF
sleeps with 3 or more family members in the same room. Mean age at diagnosis: 10.5
(3-17) years. The female to male ratio is 4:6. Only 5% are Native patients. During
the acute phase, 52% had polyarthritis, 43% had carditis, 13% had chorea, 2% had subcutaneous
nodules, and 2% had erythema marginatum. Jones minor criteria: arthralgia 20%, fever
14%, elevated ESR 21%, CRP positive 16%, EKG altered 13%. The most affected heart
valve is the mitral (45%), followed by mitral and aortic simultaneously (10%), 8%
aortic and 5% tricuspid alone; 32% with no affected heart valves. In 93% of patients
not throat culture was done. ASO + in 21% of cases, performed in all patients. Treatment:
all received benzathine penicillin G, 35% NSAID, 18% corticosteroids, 10% haloperidol,
14% valproic acid. Eleven patients discontinued treatment. Only 10% of patients with
RF has required heart surgery (valve replacement), with one death.
Conclusion: RF remains a major cause of acquired heart disease in our country, perhaps
by inadequate management of streptococcal infections, in addition to late diagnosis
of the disease and household overcrowding.
Disclosure of Interest: None Declared
P103 Immunoglobulin therapy in the treatment of cerebral consequences of neonatal
lupus erythematosus
Abstract withdrawn
P104 Validaty and reliability study for the Korean version of the haemophilia activity
list in pediatric and adult patients with haemophilic arthropathy
Seonghoon Park, Hwajeong Lee, Jung-Yoon Choe
Department of mediciane, Catholic university of Daegu School of medicine, Daegu, Korea,
Republic Of
Correspondence: Seonghoon Park
Introduction: There has been increasing interest in the patient’s perspective on outcome
of treatment. The Haemophilia Activity List (HAL) has been developed as a disease-specific
questionnaire for haemophilia patients and is a validated self-report measure of function
developed according to WHO’s International Classification of Functioning, Disability
and Health.
Objectives: In this study, we performed a cross-cultural adaptation and linguistic
validation of the HAL questionnaire to assess the health-related quality of life in
hemophilia patients in the future.
Methods: To validate HAL in Korean, the English versions of HAL were translated into
Korean using ‘the forward–backward translation’ method and merged into a final Korean
version. Validation was performed against the Korean version of the multidimensional
health assessment questionnaires (MDHAQ) as general tool and Routine Assessment of
Patient Index Data (RAPID3) as similar arthritis-specific tool. All processes were
done with permission of the developer and according to WHO guidelines.
Results: Eighty-six patients with severe and moderate forms of haemophilia A and B
with haemophilic arthropathy were invited to participate in the study. Spearman’s
rank correlation test was used for validation and internal consistency of the HAL
was calculated with Cronbach’s alpha. Seventy-five patients (86.2%) (15–62 years old)
answered the questionnaires. The internal consistency of the Korean version of HAL
was high, with Cronbach’s alpha being 0.80–0.95. Upper extremity function had the
highest consistency and leisure activities and sport had the lowest. The correlation
was good between the HAL overall score and MDHAQ overall (r = 0.78), MDHAQ pain (r = 0.79),
and RAPID3 physical function (r = 0.82).
Conclusion: The Korean version of HAL has both internal consistency and convergent
validity and may complement other functional tests to gather information on the patient’s
self-perceived ability. This questionnaire of Korean version can be useful as a disease-specific
instrument for evaluation of the health-related quality of life in Korean patients
with haemophilic arthropathy.
Disclosure of Interest: None Declared
P105 Inflammatory pseudotumor: T helper cell subtypes and relation to IGG4-related
disease?
Erdal Sag1, Gulsev Kale2, Beril Talim2
1Pediatric Basic Sciences, Pediatric Autoinflammatory Disease Programme, Hacettepe
University Faculty of Medicine, Institution of Child Health, Ankara, Turkey; 2Department
of Pediatrics, Pathology Unit, Hacettepe University Faculty of Medicine, Ankara, Turkey
Correspondence: Erdal Sag
Introduction: IgG4-related disease is a fibroinflammatory condition characterized
by tumefactive lesions, dense lymphoplasmacytic infiltrate rich in IgG4-positive plasma
cells, storiform fibrosis and often elevated serum IgG4 concentration. On microscopic
examination, presence of IgG+ plasma cells (>10-50/HPF), IgG4+/IgG+ plasma cell ratio
(>50%) and typical histopathologic pattern confirm the diagnosis. Inflammatory pseudotumor
(inflammatory myofibroblastic tumor) is a mass lesion composed of myofibroblasts,
plasma cells, lymphocytes and eosinophils.
Objectives: The aim of this study is to analyze the pediatric patients with inflammatory
pseudotumor (inflammatory myofibroblastic tumor) of various organs for the diagnosis
of IgG4 related disease, and to investigate the composition of T helper subsets.
Methods: 20 patients who were diagnosed as inflammatory pseudotumor (inflammatory
myofibroblastic tumor) of various organs at Hacettepe University Faculty of Medicine,
Department of Pediatrics, Pathology Unit were included in the study. Immunohistochemical
expression of IgG, IgG4, CD3, CD20, CD68, IL-10, IL-17, Foxp3, IFN-gamma, IFN-alpha
and IL-4 were studied from archived paraffin blocks.
Results: The mean age of the patients at the time of biopsy was 7,36 ± 3.85 yr. The
biopsies were taken from orbita (2 patients), mediastinum (7 patients; 3 from lungs,
3 from mediastinal wall, 1 from bronchi), and abdomen (10 patients; 2 liver, 1 spleen,
2 intestinal, 4 intraabdominal, 1 retroperitoneal wall). Out of the 20 patients, 3
had more than 50 IgG4+ cells per HPF but none of them did fulfil the diagnostic criteria
for IgG4-related disease. In terms of inflammatory milieu, all the biopsies were positive
for CD3, CD20 and CD68. As for T helper cell subtypes, all of the biopsies were IL-10
positive, 85% of the biopsies were IL-4 positive, 95% were IL-17 positive, 80% were
Foxp3 positive, 50% were IFN-alpha and 35% were IFN-gamma positive.
Conclusion: In our cohort, none of the inflammatory pseudotumors (inflammatory myofibroblastic
tumors) fulfilled the diagnostic criteria for IgG4-related disease. B cells, macrophages
and T cells are present in the inflammatory pseudotumor and all T helper cell subtypes
such as Th1, Th2, Th17 and Treg are included in the inflammatory milieu.
Disclosure of Interest: None Declared
P106 Hyperbaric oxygen therapy in a livedoid vasculopathy: a case report
Nihal Sahin1, Aysenur Pac Kisaarslan1, Sümeyra Ozdemir Cicek1, Betül Sözeri2, Mehmet
E. Akcin3, Zubeyde Gunduz1, Ruhan Dusunsel1, Muammer H. Poyrazoglu1
1Pediatric Rheumatology, Erciyes University Faculty of Medicine, Kayseri, Turkey 2Pediatric
Rheumatology, Umraniye Research and Training Hospital, İstanbul, Turkey 3Underwater
and Hyperbaric Medicine, Kayseri Research and Training Hospital, Kayseri, Turkey
Correspondence: Nihal Sahin
Introduction: Livedoid vasculopathy is characterized disease with recurrent ulceration
and thrombosis. Its pathogenesis has been found to be related to occlusion of the
cutaneous microcirculation leading to thrombosis, ischemia and minimal inflammation
in the vascular wall. There is still no definitive treatment for this disease. Hyperbaric
oxygen therapy (HBO) facilitates wound healing by affecting the fibrinolytic pathway.
We used HBO in a patient resistant to other treatments.
Methods: A girl aged 15 years was admitted to the Erciyes University Faculty of Medicine
Pediatric Rheumatology Department at the first time in May 2016 complaining of painful
ulceration in the ankles and foot.
Results: A fifteen-year old female presented with a one year- old history of recurrent
multiple painful ulcer, purpuric macule and porcelain – white stellate scars on the
ankle and the foot. Patient did not give any history of any other medical illness,
or any systemic complaints. There was no remarkable feature in baseline laboratory
examinations. Doppler ultrasonography of the lower extremities did not find any vascular
insufficiency in the major vessels. Skin biopsy from the lesion site revealed featured
of focal necrosis of the epidermis, subepithelial focal hemorrhage, hyalinization
of the capillary walls and thrombosis in some vessels. The tests containing C3, C4,
RF, ANA, ANCAs, ACA IgM and IgG, lupus anti-coagulant, anti-thrombin III, protein
C, protein S, homocysteine were normal. Factor V Leiden, prothrombin and methylenetetrahydrofolate
reductase (MTHFR) gene mutation analysis were performed. Heterozygous mutation was
detected in nucleotide region 1298 of the MTHFR gene. Anti-platelet, immunosuppressive,
immunomodulatory drugs and systemic steroid were given to the patient with diagnosis
of livedoid vasculopathy. Hyperbaric oxygen therapy was applied on frequent relapses
with these treatments. The patient completely relieved from pain and ulcers showed
marked improvement.
Conclusion: Treatment of livedoid vasculopathy is very challenging due to low incidence
and unclear pathogenesis. Hyperbaric oxygen therapy is well tolerated, with few side-effects
compared with the other treatment regime. We treated resistant livedoid vasculopathy
with hyperbaric oxygen therapy.
Disclosure of Interest: None Declared
P107 Echocardiographic findings in children with osteogenesis imperfecta
Shahrzad Fallah1, Mohammad Reza Alaee2, Reza Shiari3, Saeed Mojtahed zadeh2, Behnam
Sobouti4
1pediatrician, Shahid Beheshti Univesity of Medical Sciences Tehran, Iran, Islamic
Republic Of’; 2Pediatric Cardiologist, Shahid Beheshti Univesity of Medical Sciences
Tehran, Iran, Islamic Republic Of; 3Pediatric Rheumatology, Shahid Beheshti Univesity
of Medical Sciences Tehran, Iran, Islamic Republic Of; 4pediatrician, Iran Medical
Universuty, Tehran, Iran, Islamic Republic Of
Correspondence: Reza Shiari
Introduction: Osteogenesis imperfecta, an inherited connective tissue disorder with
remarkable clinical variability, is caused by a quantitative or qualitative defect
in collagen synthesis. Exact prevalence of cardiac involvement in Osteogenesis imperfecta
is indistinct.
Objectives: The aim of this study was to determine the prevalence of cardiac involvement
in children with Osteogenesis imperfect by Echocardiography.
Methods: During one year, Sixty five patients were referred to Out-patient Clinic
of Musculoskeletal and endocrinology in Mofid Children’s Hospital. All of them were
consulted with our Pediatric Cardiologist and echocardiography was performed.
Results: Among 65 patients (60% male, 40% female), mean age was 6.95 ± 4.36 year-old
(ranging from 2 months to 17 years old). Twenty percent of patients were belong to
subtype one, 47.7% to subtype III, and 32.3% to subtype IV according to silence category.
Prevalence of aortic root dilatation, mitral valve prolapse (MVP), mitral regurgitation
(MR), and tricuspid regurgitation (TR) were 13.8%, 15.38%, 7.6%, and 15.38% respectively.
We found a significant relationship between MVP and female gender, however, no relation
with patient’s subgroups.
Conclusion: Because of the importance of cardiac involvement in our study, we suggest
to perform echocardiography in all children with osteogenesis imperfecta.
Disclosure of Interest: None Declared
P108 Acid ceramidase deficiency (Farber disease) causes symptoms resembling JIA and
is likely underdiagnosed: we present a unique cross-sectional natural history study
design to address the lack of clinical data on this rare disease
Alexander Solyom1, Boris Hügle2, Dustin Tetzl3, Edward H. Schuchman4
1Enzyvant, Basel, Switzerland; 2German Center for Pediatric Rheumatology, Garmisch-Partenkirchen,
Germany; 3Enzyvant, New York, NY, United States; 4Genetic and Genomic Sciences, Icahn
School of Medicine at Mt. Sinai, New York, NY, United States
Correspondence: Alexander Solyom
Introduction: Acid ceramidase deficiency (Farber disease; Farber lipogranulomatosis)
is caused by mutations in both alleles of the ASAH1 gene, resulting in deficiency
of acid ceramidase and accumulation of the pro-apoptotic and pro-inflammatory sphingolipid,
ceramide. It is considered an ultra-rare disease, with only 109 cases reported in
the medical literature since 1952. However, since 2014, we have identified a cohort
of 45 patients (some of whom are since deceased) from 30 countries on 6 continents,
which indicates a much broader phenotypic spectrum and potentially higher incidence
than previously thought. The information collected from this cohort demonstrates that
there are patients diagnosed in late adulthood with attenuated forms, as well as patients
for whom years elapse between the appearance of the three typical Farber symptoms:
joint disease (arthritis and/or contractures), subcutaneous nodules, and hoarseness
(due to laryngeal involvement). Moreover, there is wide intra- and inter-patient variability
of symptom severity.
Objectives: To develop a natural history study structure and design that would enable
systematic collection of information on deceased patients using medical records, as
well as on living patients who have or have not undergone hematopoietic stem cell
transplantation (HSCT). In addition, the study will evaluate clinical assessment tools
used for other diseases with similar symptoms, as well as those developed specifically
for Farber disease.
Methods: We designed a cross-sectional cohort study with a unique data collection
instrument, including sections for the collection of retrospective data on disease-specific
and general medical history, as well as data from clinical assessments to be performed
at prospective visits.
Results: The pre-existing clinical assessment tools include (among others) the Childhood
Health Assessment Questionnaire (CHAQ), and Wong-Baker Faces Pain Rating Scale, 6-minute
Walk Test, Pulmonary Function Testing, and Joint Range of Motion measurements. We
also developed a unique patient reported outcome measure related to Farber disease
symptoms including physical impairment, pain, and emotional distress, and a method
for the assessment of change in size of subcutaneous nodules.
Conclusion: Consideration of the broad spectrum of ages and heterogeneous phenotypes
in a small population of patients available to participate in a study of the natural
history of acid ceramidase deficiency led to the design of a cross-sectional cohort
study with retrospective and prospective components. By including deceased patients
and patients having undergone HSCT in the study design, the amount of data that can
contribute to the understanding of this very rare disease is substantially increased.
Furthermore, the specific prospective assessments will allow us to follow disease
progression over time, and to evaluate the degree to which the assessment tools and
techniques may be appropriate measures to use to register change in certain symptoms.
It is our hope that this unique design will provide data which is sufficiently robust
to serve as the basis for preventing misdiagnosis of acid ceramidase deficiency as
JIA, provide an indication of the most appropriate methods for measuring efficacy
in future therapeutic trials, and serve as a potential point of reference in the design
of similar studies in rare disease populations.
Disclosure of Interest: A. Solyom Employee of: Enzyvant, B. Hügle: None Declared,
D. Tetzl Employee of: Enzyvant, E. Schuchman Shareholder of: Enzyvant
P109 Involving patients, parents and carers in paediatric rheumatology research: best
practices examples from lay representatives of the United Kingdom's clinical studies
group
Simon Robert Stones1,2, Catherine Wright2,3 on behalf of Lay/Consumer CSG Representatives
1School of Healthcare, University of Leeds, Leeds, United Kingdom; 2Paediatric Rheumatology
CSG, NIHR CRN: Children/Arthritis Research UK, Liverpool, United Kingdom; 3Arthritis
Care Northern Ireland, Arthritis Care, Belfast, United Kingdom
Correspondence: Simon Robert Stones
Introduction: The lived experiences and opinions of patients, parents and carers (PPCs)
living with rheumatic and musculoskeletal diseases (RMDs) must inform and influence
all aspects of research, from prioritisation through to dissemination. For example,
contributing to grant applications, designing studies, identifying the most suitable
outcomes to include in a clinical trial, facilitating study recruitment and sharing
findings with the wider community. In turn, it is possible that involving PPCs may
enhance expectations and subsequent levels of satisfaction with research.
Objectives: The aim of the PPC representatives on the clinical studies group is to
provide strategic guidance for the paediatric rheumatology community about the most
effective ways of engaging and involving PPCs in clinical and health services research.
Methods: To effectively represent PPCs living with RMDs, it is critical to have a
means of ensuring that PPC representatives encapsulate the range of views within the
PPC community. The paediatric rheumatology clinical studies group PPC representatives
aim to do this through networking, linking with external rheumatology stakeholder
groups and through hosting consumer research meetings. In addition, PPC representatives
comment on various documents as part of their role, including trial protocols, ethics
applications and and participant information sheets. They have also been involved
in formulating three research questions as part of the clinical studies group research
strategy. The top three research priorities were informed by a patient-led research
study with young people and their families. With much delight, one research priority
has informed the current development of a study to improve treatment tolerability
for young people with RMDs.
Results: Activities of PPC representatives include attendance several face-to-face
and teleconference meetings each year. This is an essential activity that enables
researchers and healthcare professionals to actively interact with PPCs as equal partners,
in order to shape ongoing and future research activities. This approach also emphasises
the importance of physical meetings in fostering collaborative and participatory approaches
to research. In addition, PPC represenatives bridge the gap between the research community,
patient groups and charities, facilitating communication between individuals and teams.
Conclusion: By widely accepting and embracing the PPC voice as a catalyst for high
quality, young person- and family-focused research, it is hoped that the often negative
experiences of living with an RMD can be used positively to shape research, so as
to be able to provide the best possible care, treatment and support for young people
and their families living with RMDs in the future.
Disclosure of Interest: None Declared
P110 Defining the clinical impact of symptoms in a diverse population of patients
with a rare disease: a qualitative research study in acid ceramidase deficiency (Farber
disease)
Alexander Solyom1, Brendan Johnson2, Karoline Ehlert3, Dustin Tetzl4, Karin Coyne5
1Enzyvant, Basel, Switzerland; 2Roivant Sciences, Durham, NC, United States; 3University
Medical Center, Greifswald, Germany; 4Enzyvant, New York, NY, United States; 5Evidera,
Bethesda, MD, United States
Correspondence: Dustin Tetzl
Introduction: Acid ceramidase deficiency (Farber disease; Farber lipogranulomatosis)
is considered an ultra-rare disease. Since 2014, Enzyvant has identified a cohort
of 45 patients from 30 countries on 6 continents, with a much broader phenotypic spectrum
and demonstrating a potentially higher incidence than previously thought. The cardinal
symptoms of Farber disease are: arthritis, subcutaneous nodules, and hoarseness. Over
70% of the moderate and attenuated phenotype patients in the Enzyvant cohort were
initially diagnosed with a form of Juvenile Idiopathic Arthritis.
Objectives: Initiate a qualitative research study to understand the symptoms and impact
of Farber disease from the perspective of patients and caregivers by conducting one-on-one
interviews for concept elicitation, content validity, and patient interpretation of
newly developed patient-reported outcome tools.
Methods: This study consisted of two parts: semi-structured qualitative interviews
to understand Farber disease (FD) symptoms and to evaluate new Farber-specific PRO
measures to capture the impact of FD symptoms on patients including: subcutaneous
nodules, voice, overall pain, arthritis, ability to move joints, ability to perform
daily tasks, and level of fatigue. Participants were asked to rate the symptoms’ impact
on a scale of 0–10, with 0 meaning no impact and 10 meaning greatest impact. Additional
PROs for benchmark assessment were (among others): Childhood Health Assessment Questionnaire
(CHAQ), SF-36 in patients and caregivers.
Results: Eight interviews were conducted with 4 caregivers and 4 patients. Included
were: 2 adult patients (attenuated phenotype); 1 caregiver of deceased child (severe
phenotype); 1 transplanted adult patient (moderate phenotype); 1 caregiver of transplanted
pediatric patient (moderate phenotype); 1 caregiver of a pediatric patient (moderate
phenotype); and 1 caregiver/patient dyad of a non-transplanted pediatric patient (moderate
phenotype). Interviews revealed the symptoms of acid ceramidase deficiency have measurable
clinical impact across a broad spectrum of phenotypes and symptom severity. In general,
all participants found the questionnaires and assessments relevant to their condition.
Feedback was provided by the participants to improve the formulation and scope of
questions. With regard to the relative impact of symptoms, the ability to move joints
had an average impact rating of 6.6 (range 1 to 10), followed by ability to perform
daily activities and subcutaneous nodules with 5.9 (range 1 to 10 for daily activities
and 3 to 9 for nodules), voice impact was rated 5 (range of 3 to 9). The remaining
symptoms (arthritis, overall pain, level of tiredness, and other symptoms) all yielded
lower levels of impact. In the cases where the SF-36 and CHAQ were completed, scores
demonstrated significant impact and disability in the population of patients with
acid ceramidase deficiency.
Conclusion: In spite of the small number of participants, the information gathered
provides a better understanding of methods useful for measuring symptom impact, potentially
in the context of future therapeutic trials, and may allow better discussion of symptom
impact between physicians, patients and caregivers. This type of qualitative study
can be particularly useful in rare disease populations, and may also help interpret
the utility of both new and established patient reported outcomes in cases when the
size and variability of the available population prohibits traditional methods of
validation.
Disclosure of Interest: A. Solyom Employee of: Enzyvant, B. Johnson Employee of: Roivant
Sciences, K. Ehlert: None Declared, D. Tetzl Employee of: Enzyvant, K. Coyne Employee
of: Evidera
P111 A novel homozygous mutation of gene WISP3 in progressive pseudorheumatoid dysplasia
Abstract withdrawn
P112 Association of juvenile-onset primary Sjögren syndrome with type I C2 deficiency
Erika Van Nieuwenhove1,2, Lien De Somer3, Carine Wouters3,4
1Center for Brain and Disease Research, VIB/KULeuven, Leuven, Belgium; 2Pediatrics,
University of Leuven, Leuven, Belgium; 3Pediatric Rheumatology, University of Leuven,
Leuven, Belgium; 4Department of microbiology and immunology, KULeuven, Leuven, Belgium
Correspondence: Erika Van Nieuwenhove
Introduction: Sjögren syndrome (SS) is a systemic autoimmune disease characterized
clinically by sicca syndrome resulting from lymphocytic infiltration of the exocrine
glands.
Objectives: To identify genetic susceptibility factors in juvenile-onset primary Sjögren
syndrome through whole exome sequencing.
Methods: Paired-end sequencing was performed on genomic DNA on an Illumina HiSeq 2500
(Genomics Core Facility). Burrows-Wheeler Aligner software was used for alignment
to Genome Build hg19, GATK Haplotype Caller for base calling and ANNOVAR software
for annotation. Identified variants were confirmed by Sanger sequencing (LGC Genomics
Facility, Berlin, Germany).
Results: A girl (P1) aged 14 years was born the second of four children to consanguineous
parents of Moroccan origin. In the familial history we note beta thalassemia minor
in father and index patient and type 1 diabetes in the father. Immunological screening
was prompted by two occurrences of ethmoiditis with orbital cellulitis and progression
to an orbital abscess in the first episode, before the age of 4 years. However, no
notable infectious episodes recurred. Laboratory analysis revealed isolated IgG2 deficiency
(0.55 g/L; 0.72-3.40), very low memory B cells (1.8%) and a low response to 1/3 pneumococcal
serotypes tested. At the age of 9 years, she presented with recurrent transient episodes
of fever and arthritis in her knees and ankles. Laboratory analysis showed clear immune
activation with hypergammaglobulinemia (IgG 24.40 g/L; 5.30-13.06), mildly elevated
sedimentation (26 mm/h) and positivity for rheumatoid factor (RF) (519 IU/ml; ≤40)
and anti-Ro autoantibodies (>282.0; ≤7.0) (Table 1), suggestive for SS. In addition,
increased CD5+ B cells (31.4%), glutamic acid decarboxylase (GAD) autoantibodies (4.2;
≤0.9), low total complement levels (<20%; 70-140) and undetectable levels of C2 were
found (<7 mg/L; 14 – 25). Symptoms persisted and at the age of 10 years she developed
cutaneous vasculitis of the legs, feet, hands and eyelids. Furthermore, she developed
sicca symptoms of the eyes and mouth, secondary caries, hoarseness and a persistent
elevation of amylase (214U/L; 28-100). Magnetic resonance imaging (MRI) demonstrated
mild enlargement of the right parotid gland, which appeared lightly inhomogeneous
with T2-hyperintesive foci and a limited number of intraglandular lymph nodes, suggestive
for parotitis. Due to persistent disease activity at the age of 12 years, she was
started on treatment with daily administration of 200 mg Plaquenil. While hypergammaglobulinemia
and sicca symptoms persist, sustained remission of vasculitis and arthritis ensued.
Whole exome sequencing revealed P1 is homozygous for the classic deletion in C2 causal
for type I C2 deficiency.
Conclusion: The presentation of primary SS at this age is very rare and P1 displayed
both typical clinical (vasculitis, arthritis, parotitis) and laboratory (hypergammaglobulinemia,
anti-Ro autoantibodies, RF positivitiy, low memory and high circulating CD5+ B cells)
features. To the best of our knowledge C2 deficiency, the most frequent hereditary
deficiency in the classical component pathway, was never reported in association with
SS. One study on adult pSS detected low CH50 in 15% of patients and hypocomplementaemia
correlated with systemic symptoms1. Unlike deficiency for the C1 complex or C4, the
penetrance of C2 deficiency in SLE is merely 10%2. However, since the majority of
C2 deficient patients do not manifest autoimmunity there are likely other genetic
or environmental drivers for disease. C2 deficiency may be a negative modulating factor
on the development and course of autoimmune disease and screening should be considered
in patients with primary SS.
References
1. Ramos-Casals, M. et al. Hypocomplementaemia as an immunological marker of morbidity
and mortality in patients with primary Sjögren’s syndrome. Rheumatology
44, 89–94 (2005).
2. Lintner, K. E. et al. Early components of the complement classical activation pathway
in human systemic autoimmune diseases. Front. Immunol.
7, 1–22 (2016).
Disclosure of Interest: None Declared
Psycho-social aspects and rehabilitation
P113 Introducing RAiISE - raising awareness of invisible illnesses in schools and
education
Sophie Ainsworth1, Jenny Ainsworth1, Jennifer Preston2, Simon Stones1, Robyn Challinor1,
Marie Rowe1
1RAiISE, Liverpool, United Kingdom; 2Patient and Public Involvement, Alder Hey Children's
Foundation Trust, Liverpool, United Kingdom
Correspondence: Sophie Ainsworth
Introduction: RAiISE is a user-led research project inspired by the negative experiences
that young people face while studying and living with an invisible illness. Many young
people who live with chronic illnesses look no different to their healthy peers. The
invisible nature of some illnesses can often lead to an invisible struggle, leading
to misunderstandings, particularly in the case of young people. It can be a huge burden
on the chronically ill to make the invisible, visible to others.
Objectives: The main objective of RAiISE is to improve the standard of care given
to young people with invisible illnesses in school, college and university and to
create a resource to teach education professionals a series of strategies and techniques
to support their students. RAiISE will also offer support to young people with invisible
illnesses and aim to empower them to take control of their own health.
Methods: A young patient of Alder Hey NHS Children's Foundation Trust decided to raise
awareness of living with an invisible illness. A network of young people, parents,
education and health professionals was created and a series of workshop and focus
groups allowed each stakeholder to share their experiences and expertise as they inspired
and advised the production of the RAiISE information pack. It is important that young
people are able to shape research based on their lived experiences. Several international
charities and organisations have offered support and knowledge in advising the process.
Results: At early workshop meetings, young people with invisible illnesses and their
parents were able to offer personal accounts and experiences which highlighted that
the most common themes were problems with communication and trust, as well as difficulty
in understanding the erratic nature of many chronic illnesses. From this research,
a draft information pack was written by the RAiISE committee, which was later presented
to young people, parents, health and education professionals and charity representatives.
All stakeholders were able to offer their expertise from their respective fields.
Feedback was overwhelmingly positive and any adjustments are to be made in the coming
weeks. The final pack will be completed and ready for distribution by the end of summer
2017.
Conclusion: The project has been a successful example of young patient led research
and highlights the importance of self-management in young people living with invisible
chronic illnesses. The collaboration between young people, parents, and education
and health professionals has highlighted the necessity for cooperation between all
stakeholders for the benefit of the young person.
Disclosure of Interest: None Declared
P114 Development and feasability of a shared management tool for school children with
juvenile idiopathic arthritis
Jeannette H. Cappon1, Bianca Knoester1, Marion A. van Rossum2
1Paediatric Rehabilitation, Reade, center for Rheumatology and Rehabilitation, Amsterdam,
Netherlands 2Paediatric Rheumatology, Amsterdam Rheumatology and Immunology Center
|Reade, Amsterdam, Netherlands
Correspondence: Jeannette H. Cappon
Introduction: Health related quality of life (HRQOL) can be severely affected in children
with juvenile idiopathic arthritis (JIA). Earlier studies have shown that, amongst
other factors, school absence is one of the main predictors of HRQOL in children with
JIA[i]. HRQOL is also related to pain intensity and coping strategies.[ii] In young
JIA patients (aged 4–9 years) school functioning can be impaired due to pain, fatigue
and limited joint function. Adequately coping with these symptoms of JIA during schooldays
demands a shared management approach between the young child, parent(s), teacher and
health professionals. An instrument supporting young children with JIA in managing
their symptoms during schooldays in a structured way was lacking.
Objectives: 1. To develop an instrument to support a young child with JIA managing
symptoms during schooldays.
2. Implementation and evaluation of the feasability of the developed shared management
tool in the rehabilitation program.
Methods: 1. Elements necessary in the instrument are elected after consulting parents
of young children with JIA and health professionals of Reade multidisciplinary team
for children with JIA. With help of a professional designer an instrument is developed
to provide a shared management tool for managing symptoms during schooldays.
2. Children with JIA (aged 4–9 years) with problems in school attendance and their
parents are informed about the instrument and invited to use it during their rehabilitation
program in Reade. Parents, children and health professionals evaluate the feasability
after using the instrument by filling in a questionnaire.
3. Results of questionnaires are discussed in the multidisciplinary team for evaluation.
4. Improvement points for the instrument are proposed.
Results: 1. A personal diary called “Back and Forth Booklet” is designed which contains
(1) education pages for the child, parents and the teacher about JIA, pain and energy
levels and how to manage these, (2) a daily pain measure instrument for location and
amount of pain for the child (colour-in pain puppet), (3) a level of energy instrument
for expressing fatigue (image of full/half full/empty glass) (4) space for registration
of appropriate alternatives for limited activities by the health professionals or
parents, (5) daily feedback spaces for the teacher and (6) a visual analogue (VAS)
Likert smiley scale for daily self-evaluation by the child.
2. 9 children and their parent(s), 3 occupational therapists, 3 physical therapists,
1 social worker, 1 psychologist and 9 teachers have used the Back and Forth Booklet.
Two parents, two children, one teacher and seven health professionals completed a
questionnaire.
3. Evaluation of the questionnaires so far showed that the use of the Back and Forth
Booklet contributes in communication about the child’s pain and fatigue among the
child, parents, teachers and health professionals. The Back and Forth Booklet facilitates
schoolteachers in supporting a child with tailored pain and fatigue coping strategies.
All users were satisfied with the design. Children appreciated the colour-in pain
puppet for not having to explain verbally the teacher about their pain.
4. Items for improvement were: (1) Parents need open space for sharing daily information
with the teacher (2) Occupational therapists suggest extra space for documentation
of appropriate alternatives for limited activities.
Conclusion: The “Back and Forth Booklet” is a promising shared management tool, supporting
young children to cope with JIA symptoms in school. Small adjustments can improve
the feasability.
[i] Haverman et al A&R 2012; 64(5)694-703
[ii] Sawyer et al Rheumatology 2004;43:325-330
Disclosure of Interest: None Declared
P115 A smiling childhood: a social window for families with children affected by chronic
rheumatics and rare pathologies
antonella celano, on behalf of apmar onlus, raffaella arnesano, annalisa sticchi,
on behalf of apmar onlus and apmar onlus
Italian national Association people with rheumatic and rare diseases, Lecce, Italy
Correspondence: antonella celano
Introduction: The Smiling Childhood project was launched by APMAR Onlus, supported
by the Valdese Church and their generous 8x1000 funds donation.
The project comes from a long journey undertaken by our association in order to be
closer to people affected by chronic pathologies during their daily lives, defining
strategies of inclusion in order to create an understanding atmosphere about Rheumatic
Pathologies, who unfortunately are still not very well known nowadays.
Some of these pathologies are diagnosed at a later stage, resulting in a late treatment
and in some cases in a great degrade in self-sufficiency.
Objectives: The aim of our project is to offer support for families and develop empowerment
over chronic and rare Rheumatic Pathologies in children; giving easier access to information,
promoting actions in order to offer an early diagnosis, helping families face the
new challenges they will be inevitably exposed to
Methods
The method is to create a partecipative process by involving all possible factors
in an active process regarding chronic and rare rheumatic pathologies in children.
We have involved, over the course of the years and through the help of educational
and informational workshops, various family members, journalists and paediatricians.
Results: We have therefore been able to build a social window, in collaboration with
professional staff, that works overall to make the journey that these families will
have to face easier. With the use of this social window, the family nucleus can find
information as well as a place to be heard and guided.
Moreover, available to them is also a psychotherapist psychologist, both over the
phone or in the form of a private meeting. The clinical instrument used here is the
meeting with our staff (both hearing and empathy), and with the use of monitoring
sheets, drawings and illustrations according to the age of the child. At the end of
this formative journey, the family will be asked to fill out a survey in order to
rate our project.
Our social window is also available online in the form of a blog. Other communication
and participation activities take place in local doctor’s surgeries, schools, and
with the collaboration of Rheumatology Paediatricians. We have also developed a comic,
‘A new challenge together’, in order to inform young adults and children on these
issues.
Conclusion: The presence of a Rheumatic Pathology can result in heavy effect on the
life of a child and its family. These impacts vary depending on the resources that
they might have available. May these be ‘external’ (financial and economical, available
treatments, network support) or ‘internal’ (the possession of medical and bureaucratic
information useful to the management of the problem, the relationship between the
members of each family and their degree of flexibility).
Our project, ‘A Smiling Childhood’ has kept many families informed, emotionally supported
and aware of their internal resources.
Disclosure of Interest: None Declared
P116 Anxiety, depression, and parental perception of uncertainty among parents of
children with juvenile idiopathic arthritis in Bogota, Colombia.
Adriana Diaz-Maldonado1,2,3, Sally Pino2,4, Pilar Guarnizo2,5,6, Juan Manuel Reyes2,
Leonardo Ariza2
1Hospital de la Misericordia, Bogota, Colombia; 2Care for Kids, Bogota, Colombia;
3Instituto Roosevelt, Bogota, Colombia; 4Hospital San Jose Infantil, Bogota, Colombia;
5Fundacion Cardio Infantil, Bogota, Colombia; 6Cayre, Bogota, Colombia
Correspondence: Adriana Diaz-Maldonado
Introduction: Juvenile idiopathic arthritis (JIA) is a chronic illness which affects
among 2 – 150 children for 100.000 in Europe and North America, most of them are cared
by their parents (1). It has been estimated that parents of a child with chronic illness
can present mood problems, cognitive problems, anxiety, high level of distress and
lower levels of quality of life (2).
Objectives: Describe the anxiety, depression, familiar functionality and parental
perceptions among parents of a child with JIA in Bogotá, Colombia.
Methods: A cohort of parents of children with JIA were approached for this study in
Bogota, Colombia. The questionnaires Hamilton rating scale for anxiety (HAM-A), Beck
depression inventory (BDI), family APGAR scale, parental perception of uncertainty
scale (PPUS), and parental coping strategy inventory (PCSI) were self-administrated.
Descriptive analysis was performed according to the nature of the variables.
Results: Twenty two parents participated in the study characterized by 16 women and
6 men. The average age of the parents was 43.86 years (ranged from 33 to 62 years).
Most of them with mild to high income and the 55% of the parents had graduate degrees.
Age of children with JIA was 14.95 years (8 to 20 years), 55% were female. The most
frequent type of JIA was polyarticular and enthesitis-related arthritis (64%), followed
by systemic (16%), oligoarticular (16%) and psoriatic arthritis (5%).
In terms of anxiety, 46% of parents reported having moderate anxiety. Similar results
related to stress were observed. Mild depression symptoms were found in 18% of parents
and moderate in 9%. Severe and moderate familiar dysfunctionality were reported by
the parents in 14% and 36%, respectively. There was not association of familiar dysfunctionality
and the number of years living with the disease. However, those parents of children
with more than two years of disease present an increase in moderate symptoms of depression.
Perception of uncertainty was moderate with mean score of PPUS of 83.85 (SD 15.66).
Parents of children with recent diagnosis(less than 2 years) presented higher scores
than parents of children which had been diagnosed longer than two years (mean score
88.5 (SD 8.70) vs 80.75 (SD 18.68), respectively). Among parents with higher PPUS
score: 89% reported severe or moderate anxiety, 66% reported moderate symptoms of
depression, and 44% informed moderate or severe familiar dysfunctionality.
Being optimistic, learning about the diseases and treatment, and interactions with
their ill child were the most frequent coping strategies used by the parents. However,
parents of children with recent diagnosis are more optimistic and interact more with
their ill child compared with parents of children which had been diagnosed longer
than two years.
Conclusion: This study shows that anxiety and stress in parents of children with JIA
is present frequently. Perception of uncertainty, anxiety, and familiar dysfunctionality
were observed more frequent and severe in parents of children with recent diagnosis(less
than two years). Considering the limitations of the study, in order to alleviate anxiety
and depression symptoms on parents, and prevent family dysfunctionality, psychological
intervention and participation in group support are recommended strategies for parents
of children with recent JIA diagnosis.
References
1. Ravelli A, Martini A. Juvenile idiopathic arthritis.. Lancet. 2007;369:767–778.
doi: 10.1016/S0140-6736(07)60363-8
2.Murphy NA, Christian B, Caplin DA, Young PC: The health of caregivers for children
with disabilities: caregiver perspectives. Child Care Health Dev 2007, 33:180 – 187.
Disclosure of Interest: None Declared
P117 Rehabilitation games for juvenile idiopathic arthritis. Focus on hand and wrist.
Michaela Foà1, Rocco M. Chiuri2, Antonella Petaccia1, Fabrizia Corona1, Pier L. Lanzi2,
Giovanni Filocamo1
1Dipartimento della Donna, del Bambino e del Neonato, Fondazione Irccs Cà Granda Ospedale
Maggiore Policlinico, Milano, Italy; 2Dipartimento di Elettronica, Informazione e
Bioingegneria, Politecnico di Milano, Milano, Italy
Correspondence: Michaela Foà
Introduction: Juvenile idiopathic arthritis (JIA) is the most common chronic rheumatic
disease in children and an important cause of short-term and long-term disability.
Physiotherapy and occupational therapy, with the aim to keep or restore joint function
and to achieve a normal pattern of mobility, are important components of the therapeutic
approach. In standard physical therapy patients tend to lose interest in the treatment,
due to the monotony of the exercises, and as a consequence, patients either perform
their exercises irregularly or quit the physical therapy. In recent years, the introduction
of new gaming input devices, such as Nintendo’s Wii Remote™ and Microsoft’s Kinect,
and the development of games that involve physical activity, induced the researchers
to consider the possibility of using videogames to perform physical therapy.
Objectives: To design a set of rehabilitation games that could help patients affected
with Juvenile Idiopathic Arthritis performing their physical therapy.
Methods: A multidisciplinary study group involving paediatric rheumatologists, physiotherapists
and engineers of the Department of Electronics, Information and Bioengineering of
the Politecnico of Milan was created.
During the first meeting, the rheumatologists explained the basic aspects of disease
and the principal physical problem observed in patients with JIA; the therapists introduced
how the physical therapy for JIA works.
In order to improve the final outcome, engineers used an iterative design approach,
that is, they designed the games, and then they followed a cyclic process of prototyping,
testing and analyzing designs. The key points on which engineers focused were: the
ability of the game to adapt to the capabilities of the patient, the possibility for
the therapists to create custom game levels, the need to save every information about
how the patient performs during the exercises and the possibility to see again the
exercise carried out by the patient.
For this study, the attention was focused on hand and wrist.
Four different games to play were developed. For each game was defined a rewarding
system that increases the score when the player does something good, but does not
decrease it when he/she makes a mistake. The scoring system was also a useful first
qualitative feedback for the therapist about the patient’s performance.
The therapists were asked to create a custom level for the flight simulator game,
so she could simulate an exercise performed in a typical training session.
Results: Three poliarticular JIA patients took part to the first experimental session.
Ten, fifteen and twenty-one years old respectively. The first patient had ankle involvement,
while the last two had wrist and small joints of the hand involvement.
Two games were tested on the 3 patients; a flight simulator and a Flappy Bird-like
game. The flight simulator, in particular, was tested both with the hands and with
the feet.
The feedback from the subjects was quite good; The therapists’ feedbacks were also
good. The patients enjoyed the exercises much more and “it did not look like they
were doing exercises”. The subjects were doing without complaint the same exercises
that they found to be boring and difficult during standard physical therapy.
Conclusion: The feedbacks received during the experimental sessions validated the
work. The patients liked the games and suggested some additional changes to make them
more appealing. The therapists also were satisfied with the study design. They were
glad to see how easily the patients performed their exercises by playing the games.
In future work it should be possible t dynamically adapt the difficulty during the
game in relation to the patients’ performances. It would be consider also the possibility
to use a webcam to see live the patients while they are playing and to record the
patient’s performance, giving the therapist a second visual feedback in addition to
the replay.
Disclosure of Interest: None Declared
P118 Rehabilitation games for juvenile idiopathic arthritis. Focus on knee and ankle.
Amalia Lopopolo1, Mattia Giannotti2, Antonella Petaccia1, Fabrizia Corona1, Pier L.
Lanzi2, Giovanni Filocamo1
1Dipartimento della Donna, del Bambino o del Neonato, Fondazione Irccs Cà Granda Ospedale
Maggiore Policlinico, Milano, Italy; 2Dipartimento di Elettronica, Informazione e
Bioingegneria, Politecnico di Milano, Milano, Italy
Correspondence: Amalia Lopopolo
Introduction: Juvenile idiopathic arthritis (JIA) is the most common chronic rheumatic
disease in children and a cause of short-term and long-term disability.
Physiotherapy is an important component of the therapeutic approach. The rehabilitation
process is developed through a series of simple, repetitive exercises to be performed
frequently and for a long time. Often patients lose interest and stop performing them
before the results have been accomplished.
Recently a new frontier in the design of videogames has been explored: the games for
rehabilitation. The development of this research field has been limited by the cost,
technical limitations and technical expertise needed to use the products and the sensors
needed.
The introduction of new gaming input devices and the development of games that involve
physical activity, induced the researchers to consider the possibility of using videogames
to perform physical therapy.
Objectives: To design a set of rehabilitation games for children with JIA, that would
be considered amusing by the largest part of players, while helping them in performing
their rehabilitation exercises for the mobility of knee and ankle.
Methods: The project was conducted in collaboration between pediatric rheumatologists,
physiotherapists and engineers researchers of the Politecnico of Milan.
The specific rehabilitation principles were applied to the ones of the common game
design, to obtain games both medical relevant and fun to play. The iterative design
approach, a methodology based on a cyclic process of prototyping, testing, analysing,
and refining of the games was applied by the researchers.
Four different games were designed, one for the ankle, three for the knee. The third
and the fourth games were redesigned to perform two types of exercises.
The first exercise prescribe the use of a wobble board, a board mainly used to perform
equilibrium exercises. During the exercise the patient had to tilt on all four different
directions the board by performing the deflection of the extension of the ankles,
if the patient is seated on a chair, or by changing the position of the whole body.
The second exercise prescribed to perform the extension-deflection movement of the
knee while the patient was seated from the rest position to the maximum angle reachable
by the patient.
For each of this games the therapist could completely personalize the parameters of
the game in order to personalize the experience of the patient and make it suitable
for his/her clinical condition.
Experimental sessions were performed to validate the result of the system.
The interaction of the patient with the games were tested, and it was verified how
they react to the different type of experience.
Results
Tuning session.
Tuning session was completed by testing the games with 2 JIA patients, 15 and 12 years
of age respectively, with predominant involvement of ankles (patient 1) and ankles
and right knee (patient 2).
Therapeutic sessions.
Two therapeutic sessions were performed on 4 (3 female and 1 male) and 3 (female)
patients respectively. Median age 7 years (5-15 years)
Feedbacks received from patients and therapists were good, and all the patients completed
easily their sessions.
Conclusion: Four rehabilitation games for the mobility of knee and ankle were developed.
The feedbacks received from the patients and therapists were very good. The rehabilitative
sessions were easily controlled, the patients enjoied the sessions and the therapists
appreciated also the possibility to monitor the patient even in remote.
Disclosure of Interest: None Declared
P119 Recurrent arthralgia or functional pain? Evaluation of psychological distress
in Italian school students
margherita Lo Curto, Maria Cristina Maggio, Fabio Campisi, Giovanni Corsello
University Department Pro.Sa.M.I. “G. D’Alessandro”, University of Palermo, Palermo,
Italy
Correspondence: Maria Cristina Maggio
Introduction: Requests of rheumatologic visits for lims arthralgia are more frequent
in these last years, expecially in adolescents. Functional Pain (without demonstrable
organic cause), is often associated with psychological problems.
Objectives: to differentiate organic articular pain from functional pain;
to evaluate the real incidence of functional pain in healthy school students;
to investigate the correlation between functional pain and psychological disagreement,
in a series of school students.
Methods: A questionnaire was given to a group of students of primary school; the following
data were collected: a) sex, age; b) functional pain; c) relation with relatives,
teachers and schoolfellows; d) failure in school-studies.
Results: 809 students, 354 females, 455 males, median age 14 years, participated to
the study.
Functional Pain was referred from 537/809 students: 265 Females, 272 males: p = 0,155.
Pain episodes showed a different incidence between females and males (p = 0,511).
Pain intensity vs. number of episodes in females showed a statistically significant
correlation (p = -0,001). Most frequently abdominal pain was recorded in females and
limbs pain was selectively described in males.
Psychological disagreement was referred from 513/809 students: 260 females, 253 males
(p = 0,150).
Psychological disagreement was reported with: parents in 15; with siblings in 59;
with other relatives in 45; with teachers in 42, with schoolfellows in 356.
The correlation disagreement vs. functional pain in all the students included in the
study was statistically significant (p < 0,001).
Conclusion: Most students reported psychological disagreement and pain. The most frequent
cause of disagreement was schoolfellows’ behaviors. Limbs pain is a frequent record,
especially in adolescent males.
Functional pain correlates significantly with psychological disagreements: according
to literature, it can lead to severe manifestations. Psychological approach, supported
by several studies, demonstrated that it is mandatory to recognize such pain; to talk
with the students concerning the cause of their psychological disagreements, to know
their problems and to reassure them with the aim of gaining their confidence. A confidence
with parents and/or teachers and/or their peers, may be useful for adolescents.
Disclosure of Interest: None Declared
P120 Posture and balance deficit in children with JIA: a pilot study
Antonino Patti1, Giovanni Corsello2, Antonino Bianco1, Giuseppe Messina1, Angelo Iovane1,
Antonio Palma1, Jessica Brusa3, Maria Cristina Maggio2
1Department of Psychology and Educational Science, University of Palermo, Palermo,
Italy; 2University Department Pro.Sa.M.I. “G. D’Alessandro”, University of Palermo,
Palermo, Italy; 3Posturalab Italia, Palermo, Posturalab Italia, Palermo, Palermo,
Italy
Correspondence: Maria Cristina Maggio
Introduction: Juvenile Idiopathic Arthritis (JIA) is the more frequent rheumatologic
disease in paediatric age with a possible worsening on posture in a vulnerable period
of life. This condition can show a negative impact on balance and on activities of
daily life.
Objectives: The aim of the study is to evaluate the efficacy of regular physical activity
on posture and balance deficit in children and adolescents affected by JIA.
Methods: We enrolled 56 patients (17 patients affected by JIA: JIA group; and 39 healthy
control subjects, of comparable age: CG). Furthermore, JIA group was stratiphied in
two subgroups: inactive (AIG-SED) and active (AIG-ACT). All the patients were tested
by a computerized analysis of posturography, by a new-generation stabilometric platform
(Sensor Medica; Guidonia Montecelio, Roma).
Results: The group AIG-SED showed statistically significant differences vs. the group
CG on the following indexes: ellipse surface (p < 0,05), ball length (p < 0,0001)
e Y mean (p < 0,05). At the opposite, no statistically significant difference was
relieved between the AIG-ACT and the CG, with the exception of the ball length (p < 0,05),
which is reduced respect the CG.
Conclusion: This pilot study confirms the relieve of regular physical activity on
the motor deficit, on balance and posture secondary to JIA, especially in evolutive
age.
Disclosure of Interest: None Declared
P121 Improved transitional process by nurse guided transition program
Karina Mördrup, Anna Vermé
Pediatric Rheumatology Unit, Karolinska University Hospital, Stockholm, Sweden
Correspondence: Karina Mördrup
Introduction: Children’s experience of moving from children’s hospital department
to adult department in hospital care are often related to increased stress and anxiety.
The transition period could also be very demanding for the parents. Studies show that
preparing the children from early age could prevent most of the stress and anxiety.
By starting the transition process several years before the child’s move to adult
care we presume the parents gets educated and supported for letting their child take
more responsibility for its own illness. At the pediatric reumatology department,
Astrid Lindgrens Childrens hospital we are working with a transition program inspired
by Janet McDonagh. The program consists three meetings with the rheumatology nurse.
Objectives: To prepare and facilitate the child and its parents for the child’s transition
to adult care.
Methods: The children and their parents are called to three meetings over a period
of 5 years. The first meeting are placed when the child is 14 years old. Before the
meeting the child and its parents filled in different transition formula. To evaluate
the child’s knowledge about its disease and treatment we used the questionnaire MEPS
abbreviation for medical issues, exercise, pain and social support.
Results: To evaluate if the child and its parents found it valuable to participate
in the transition program, we did a pilot study. After the visit to the nurse the
child got a evaluation formula. The results showed that 86% of the participants should
totally recommend this to other children with rheumatic disease and the remaining
14% recommended it. Neither of the children found it embarrassing or hard to fulfilled
the transition formula.
Conclusion: Both the children and their parents found the first transition meeting
with the nurse very educational and valuable. The meeting with the nurse seems to
facilitate the transition process for the child and its parents. By offering a structured
transition program to the children and their parents the fear of moving to adult care
can be reduced.
Disclosure of Interest: None Declared
P122 Transition in rheumatology- 5 year experience
Marija Šenjug Perica1, Miroslav Mayer2, Mandica Vidović3, Lovro Lamot3,4, Miroslav
Harjaček3,4, Lana Tambić Bukovac1
1Department of Pediatric and Adolescent Rheumatology, Children’s Hospital Srebrnjak,
Zagreb, Croatia; 2Department of Internal Medicine, Division of Clinical Immunology
and Rheumatology, University Hospital Centre Zagreb, Zagreb, Croatia; 3Department
of Pediatric and Adolescent Rheumatology, Clinical Hospital Centre Sisters of Charity,
Zagreb, Croatia; 4University of Zagreb, School of Medicine, Zagreb, Croatia
Correspondence: Marija Šenjug Perica
Introduction: Transition for patients with chronic diseases is defined as the purposeful,
planned movement of adolescents and young adults from child-centered to adult oriented
health care system.1 Rheumatic diseases of childhood extend to adulthood as active
diseases in 30-70%, which is the reason for requiring rheumatologic care into adulthood.
First coordinated transition of pediatric rheumatologic patients in Croatia was organized
in 2012 as developmental type of transition, where patient is gradually prepared for
the transition by a pediatrician rheumatologist throughout years preceding transfer.
The moment of final transfer to adult care is organized in the pediatric rheumatology
clinic, where patients and their parents are meeting adult rheumatologist in known
environment (pediatric rheumatology ambulance). At the transfer, patient's history
is being presented to the adult rheumatologist and afterwards patient is examined
by both of the specialists. At the end of the examination, patient is given next checkup
date at adult rheumatologist clinic, where the patient will continue with regular
follow up visits.
Objectives: Our objective is to verify successfulness of organized transition of pediatric
rheumatologic patients to adult care.
Methods: We have conducted a retrospective research of patients’ databases at Departments
of Pediatric Rheumatology and correlated them with data from adult Clinical Immunology
and Rheumatology Department in order to verify number of pediatric patients that have
continued with regular follow up in adult care after coordinated transition.
Results: During 5 year period (2012.-2017.) 78 patients have been transferred to adult
rheumatologist. There were 50 JIA patients, 18 SLE patients, and 10 patients with
other rheumatic diseases (8 patients with mixed connective tissue disease, 1 with
Wegener's granulomatosis, 1 with fever of unknown origin). Median age at the time
of transfer was 19,6 years (14,6-26,6). Patients with SLE were older at the time of
transfer than two other groups of patients (SLE 21,29 ± 2,99 vs. JIA 18,83 ± 1,22
vs. other diagnosis 19,42 ± 2,8, p < 0,01). Total of 63 patients (80,8%) have continued
with regular follow up at adult rheumatologist and 15 patients never showed up at
adult rheumatologist clinic, probably due to remission of the disease or possible
follow up by other chosen adult rheumatologist.
Conclusion: Young adults with rheumatic diseases have complex medical and psychological
needs and transition to adult care is a critical component of care. In order to maintain
adequate level of follow up and prevent additional flares in turbulent adolescent
period, continuity of rheumatologic care is essential. By organizing coordinated transition
to adult rheumatologist, a most of the pediatric patients with rheumatic disease (80,8%)
are continuing with regular follow up in the adult care. Each transition should be
an individually tailored process according to needs and psychological maturity of
patients.
1Blum RW et al. Transition from child-centered to adult health-care systems for adolescents
with chronic conditions. A position paper of the Society for Adolescent Medicine.
J Adolesc Health. 1993.
Disclosure of Interest: None Declared
P123 The psychomotor effect of an organized summer camp program on children with rheumatic
diseases: a 5 year evaluation
Maria Stavrakidou, Kyriaki Spanidou, Polyxeni Pratsidou-Gertsi, Artemis Koutsonikoli,
Florence Kanakoudi-Tsakalidou
First Dept of Pediatrics,Pediatric Immunology and Rheumatology Referral Center, Hippokration
Hospital, Thessaloniki, Greece 2Asklepeio Physiotherapy Clinic, Thessaloniki, Greece
Correspondence: Maria Stavrakidou
Introduction: According to the Referral Center’s policy regarding the patients’ psychomotor
rehabilitation, a summer camp program is annually offered to children with Chronic
Rheumatic Diseases (CRD) in clinical remission and ability for self-care.They attend
a sport camp addressed to healthy children, where the CRD group participates in various
camp activities (handicrafts, arts, games, sports and swimming), accompanied by a
specialized physiotherapist and a pediatric rheumatologist. During their 2-week camp
life, they additionally receive education and practice on maintaining group and personalized
physiotherapy.
Objectives: To evaluate the psychomotor impact of organized summer rehabilitation
program on children with CRD, in a setting away from the caregiver protection, for
5 consecutive years.
Methods: A 28-item questionnaire was created pertaining 5 domains: physical activity,
self-care, pain, socialization and psychology and a score range 1-4 (4 the best).
The questionnaire was annually completed by the children after the end of the camp
and the responses were evaluated in respect to the participants’ age and their experience
in the camp setting.
Results: Replies of 69 campers with a mean age of 11 yrs were analyzed. A mean total
score of 54/65 was found, which was positively correlated with the participants age
(p < 0.001). Campers with no previous experience had a significantly median lower
score (48), after age adjustment (p = 0.05). The domains of physical activity and
psychology had the worst scores for the naive campers (p = 0.018, and p = 0.027, respectively).
Socialization was positively correlated with age (p = 0.008) and especially among
the naïve young participants (p = 0.005). There was no correlation between pain and
activities’ restriction. Home sickness regarding either the family, or peers or TV
watching was reported by 82%, 74% and 37.5%, respectively. Noteworthy, 88% expressed
the desire to become future camp team-leaders.
Conclusion: These findings indicate that the aforementioned kind of camp life offering
a rehabilitation program for children with CRD has a beneficial impact on their quality
of life. The valuable effect was found to be correlated with the campers’ age and
was more prominent, in those with the least experience. The reported home sickness
by the majority of children did not affect their active participation in the program.
Moreover, they expressed the wish to gain more camp experiences and take future camp
responsibilities as leaders.
Disclosure of Interest: None Declared
Systemic lupus erythematosus
P124 Emerging role for the renal glomerular endothelial cells as potent inflammatory
contributors in juvenile-onset lupus nephritis
Paraskevi Dimou1, Matthew Peak1,2, Angela Midgley1, Simon C. Satchell3, Rachael D.
Wright1, Michael W. Beresford1,2
1Department of Women's and Children's Health, University of Liverpool, Liverpool,
United Kingdom; 2Department of Paediatric Rheumatology, Alder Hey Children’s NHS Foundation
Trust, Liverpool, United Kingdom; 3Academic Renal Unit, University of Bristol, Bristol,
United Kingdom
Correspondence: Paraskevi Dimou
Introduction: Lupus nephritis (LN) is one of the most frequent complications of juvenile-onset
systemic lupus erythematosus (JSLE). LN can cause serious renal damage due to formation
of a highly inflammatory environment inside the kidneys, eventually leading to glomerular
destruction, proteinuria and end-stage renal failure. The specific role of the resident
renal cells in LN is still largely unknown.
Objectives: To investigate the role of the human glomerular endothelial cells (GEnCs)
in renal inflammation, by measuring the production of pro-inflammatory factors under
various stimuli.
Methods: Human conditionally immortalized GEnCs (ciGEnCs) were treated for 24 hours
with 10 ng/ml of human recombinant cytokines previously identified to play a prominent
role in juvenile-onset LN; Interferon (IFN) -alpha and -gamma (IFN-α, IFN-γ), interleukin
(IL) -1β, IL-6 and IL-13, tumour necrosis factor-alpha (TNF-α) and vascular endothelial
growth factor (VEGF). The effect of bacterial endotoxin inflammation was tested via
lipopolysaccharide (LPS) treatment (1 μg/ml).
Real-time PCR, ELISA and Luminex multiplex assays were performed to assess changes
in expression and secretion of pro-inflammatory cytokines and chemokines: TNF-α, IFN-γ,
IL-6, IL-8, IL-10, soluble vascular cell adhesion molecule-1(sVCAM-1), monocyte chemoattractant
protein-1 (MCP-1), monocyte inducible protein-1α (MIP-1α), IFN-γ induced protein-10
(IP-10), macrophage- and granulocyte macrophage- colony stimulating factors (M-CSF,
GM-CSF). Flow cytometry was used to assess surface expression of intercellular adhesion
molecule-1 (ICAM-1) and VCAM-1. Data were analysed by Kruskal-Wallis test with Dunn’s
post-hoc test. All measurements were compared to untreated ciGEnCs.
Results: At 24 hours, TNF-α and IL-1β upregulated MCP-1, MIP-1α and GM-CSF protein
secretion. IL-1β stimulated IL-6 and TNF-α secretion whereas IFN-γ promoted IP-10,
IL-10 and TNF-α secretion. The combined cytokine treatment enhanced M-CSF secretion.
IL-13 upregulated sVCAM-1 secretion whereas IL-13 and TNF-α increased surface expression
of VCAM-1. TNF-α upregulated surface ICAM-1. LPS stimulated IL-6, IL-10, MIP-1α, IP-10,
GM-CSF, IFN-γ and TNF-α secretion. The outcome of the real-time PCR assays reflected
the protein assay results.
ELISA, Luminex and flow cytometry results of protein secretion and surface expression
are presented in the table below.
Conclusion: This study provides evidence for a prominent role of GEnCs in the propagation
of inflammation in LN. Four pro-inflammatory cytokines (TNF-α, IL-1β, IFN-γ and IL-13)
and LPS were identified as key players in GEnC activation in vitro.
During a renal flare in LN, these cytokines together with LPS could stimulate inflamed
GEnCs to produce other pro-inflammatory cytokines, chemokines and adhesion molecules
which, in turn, would further enhance the glomerular inflammatory microenvironment
by increasing the recruitment of immune cells inside the glomerulus.
Disclosure of Interest: None Declared
Table 35
(Abstract P124). See text for description
ciGEnC treatment
Pro-inflammatory factors
Protein concentration (pg/ml)/surface expressionMedian/GeoMean Fluoresecence; IQR,
n = 6)Untreated Stimulated
TNF-α
· GM-CSF
(0; 0-0)
(197.7; 189.7-272.3, P = 0.049)
· MIP-1α
(208.5; 207-209)
(222.3; 221-223.3, P = 0.048)
· ICAM-1
(247.5; 211.5-279)
(443; 353.3-472.3, P = 0.009)
IL-1β
· IL-6
(30.55; 16.9-108.5)
(3479; 1815-5243, P = 0.0004)
· GM-CSF
(0; 0-0)
(950.5; 464.9-1128, P = 0.0004)
· TNF-α
(4.484; 3.717-4.383)
(10.60; 7.048-12.71, P = 0.011)
· MIP-1α
(208.5; 207-209)
(221.5; 215.8-225.8, P = 0.049)
IFN-γ
· IL-10
(0.514; 0.370-0.610)
(18.19; 15.69-19.77, P = 0.004)
· TNF-α
(4.484; 3.717-4.383)
(8.381; 7.270-8.825, P = 0.029)
· IP-10
(2.387; 2.279-3.688)
(3015; 2642-3114, P = 0.008)
IL-13
· sVCAM-1
(191.8; 88.54-559.1)
(1539; 1033-1646, P = 0.022)
Combined cytokine treatment
· MCP-1
(800.1; 446-1705)
(3755; 3359-3911, P = 0.008)
· M-CSF
(192.4; 85.19-1427)
(3461; 2093-5098, P = 0.021)
· VCAM-1
(59.60; 49.65-69.58)
(119; 85.13-163.3, P = 0.005)
LPS
· IL-6
(30.55; 16.9-108.5)
(3323; 2083-4886, P = 0.0007)
· IL-10
(0.514; 0.370-0.610)
(17.32; 9.014-20.25, P = 0.009)
· GM-CSF
(0; 0-0)
(312.2; 125.5-576.5, P = 0.017)
· IFN-γ
(0; 0-0)
(28.47; 12.14-40.44, P = 0.003)
· TNF-α
(4.484; 3.717-4.383)
(14.60; 10.38-20.15, P = 0.0005)
· IP-10
(2.387; 2.279-3.688)
(2870; 1042-3147, P = 0.013)
P125 Comparison of clinical and serological features of juvenile and adult-onset neuropsychiatric
lupus in Spanish patients
Sandra Garrote Corral, Antía García Fernández, Walter A. Sifuentes Giraldo, Alina
L. Boteanu, María L. Gámir Gámir, Antonio Zea Mendoza
Rheumatology, Ramon Y Cajal University Hospital, Madrid, Spain
Correspondence: Sandra Garrote Corral
Introduction: Neuropsychiatric (NP) manifestations are a main cause of morbidity and
mortality in juvenile-onset systemic lupus erythematosus (jSLE). Some studies suggest
that they are more frequent and severe in jSLE than in adult-onset SLE (aSLE).
Objectives: To compare the clinical and serological profile of pediatric and adult
patients with neuropsychiatric lupus (NPSLE) treated in a Spanish tertiary center.
Methods: A retrospective study of patients with jSLE (age of onset: 0-18y) and aSLE
(age of onset: >18y) seen in our center during the period 1988-2016 was performed.
Case definitions of the American College of Rheumatology were used to identify NPSLE
manifestations. Demographics, clinical and serological data were obtained through
a review of their medical records.
Results: A total of 69 patients with NPSLE were included, aSLE 41 (59%) and jSLE 28
(41%), the comparison of groups is presented in the table. Most of them were Caucasian
(92%), mean age at diagnosis in adults was 36.4 years (range: 19-68) and 13.9 years
(range: 8-18) in children. The proportion of males was higher in the latter group.
The mean duration of the disease was significantly greater in adults, as well as the
time from SLE diagnosis to NP manifestation onset, although without significant difference.
Central NP manifestations were the most frequent in both groups (aSLE 93%, jSLE 96%)
regarding to the peripheral manifestations (aSLE 12%, jSLE 11%). The most frequent
manifestations in aSLE were headache (29%), cerebrovascular disease (27%), seizures
(17%) and myelopathy (15%), whereas in jSLE were seizures (46%), headache (29%), mood
disorder/depression (25%), psychosis (18%) and autonomic disorders (18%). A significant
group of patients presented ≥ 2 central manifestation during their evolution (aSLE
32%, jSLE 41%), with the mean number of manifestations in adults being 1.36 (range:
1-3) and in children 1.44 (range: 1-4). Patients with jSLE developed lupus nephritis
with a significantly higher frequency, as well as higher titres of anti-DNA antibodies,
erythrocyte sedimentation rate (ESR) and hypocomplementemia. During the study period
there was mortality in 2 cases of aSLE and 2 jSLE (5% and 7%, respectively).
Conclusion: Our results corroborate that juvenile patients with NPSLE present higher
disease activity compared to adults. There was no significant diference in the time
from SLE diagnosis to NP manifestation onset, but tended to be shorter in jSLE. The
spectrum of NPSLE was varied both groups and an important proportion of them developed ≥ 2
manifestation. Mortality continues to be important in NPSLE in both age groups.
Disclosure of Interest: None Declared
Table 36
(Abstract P125). See text for description
Juvenile NPSLE
Adult NPSLE
p-value
N° of patients
28 (41%)
41 (59%)
-
Women:men
20:8
39:2
0.0060*
Time of disease (months)
19.8
232.5
0.0001*
NP manifestations at onset
7 (25%)
11 (27%)
0.8651
Lupus nephritis
16 (57%)
9 (22%)
0.0028*
Anti-DNA ab (IU/ml)
178.9
39.4
0.0005*
ESR (mm/h)
53.8
35.7
0.0199*
C3 low (< 80 mg/dl)
22 (79%)
16 (39%)
0.0012*
C4 low (< 16 mg/dl)
22 (79%)
13 (32%)
0.0001*
P126 Cytokine profile and expression of STAT1 and STAT5 in peripheral blood in patients
with childhood-onset systemic lupus erythematosus
Marija Holcar1, Aleš Goropevšek2, Tadej Avčin3
1Unit for Special Laboratory Diagnostics, University Children's Hospital, University
Medical Centre Ljubljana, Ljubljana, Slovenia ; 2Department for Laboratory Diagnostics,
University Medical Centre Maribor, Maribor, Slovenia ; 3Department of Allergology,
Rheumatology and Clinical Immunology, University Children's Hospital, University Medical
Centre Ljubljana, Ljubljana, Slovenia
Correspondence: Marija Holcar
Introduction: Systemic lupus erythematosus (SLE) is a multisystemic chronic autoimmune
disease with variable clinical and laboratory manifestations. Characteristic hyperactivity
of the immune system in patients with SLE is reflected in dysregulation of proteins
of various signaling pathways as well as in aberrant concentrations of pro- and anti-inflammatory
plasma cytokines.
Objectives: In this study, we focused on STAT1 and STAT5 basal expression and phosphorylation
as well as cytokine profile in peripheral blood of patients with cSLE.
Methods: Whole peripheral blood of 20 healthy donors (HD, mean age 17.2 years), 10
JIA patients (disease control, mean age 11.1 years), and 17 patients with cSLE (mean
age 18.0 years) was analysed using the Phosflow flow cytometry. Cells were analyzed
using FACSCantoII Flow Cytometer (BD Biosciences) and subsequent analysis using FlowJo
software (Tree Star). We measured concentrations of IL-1α, IL-1β, IL-2, IL-4, IL-6,
IL-8, IL-10, MCP1, VEGF, TNF-α and IFN-γ in the peripheral blood of 10 healthy donors
(mean age 18.9 years), 5 JIA patients (mean age 15.0 years) and 10 patients with cSLE
(mean age 18.2 years) using the multiplex immunoassay on a biochip. Two-tailed Kruskal-Wallis
test was used to evaluate differences between the groups.
Results: Our results demonstrate a significant increase in basal expression of protein
STAT1 (cSLE:JIA p < 0.05; cSLE: HD p < 0,0001) and protein STAT5 (cSLE:HD p < 0,001)
in Th lymphocytes of cSLE patients compared to control groups. Basal phosphorylation
of STAT1 was also elevated (cSLE:JIA p < 0.05; cSLE: HD p < 0,001), but we found no
difference in basal phosphorylation of protein STAT5 between groups.This indicates
strong IFN signature and suggests a mechanism of inflammation self-maintenance utilizing
the JAK-STAT signaling pathway in cSLE patients. No significant differences were found
in the peripheral blood concentrations of IL-1α, IL-1β, IL-2, IL-4, IL-6, IL-8, IL-10,
MCP1, VEGF, TNF-α and IFN-γ between groups, which suggests a limited role of these
cytokines in the pathogenesis of cSLE.
Conclusion: Many IFN regulated genes are dependent o STAT1 for optimal transcription,
and STAT1 protein expression is under control of IFNs. Our findings support the role
of aberrant expression and phosphorylation of STAT proteins, especially STAT1, but
show normal physiological concentrations of many cytokines, including IFN-γ. This
finding suggests that other cytokines, such as IFN-α and IL-17, may contribute to
the pathogenesis of the disease.
Disclosure of Interest: None Declared
P127 The expression of IFN receptor chains on naïve and primed neutrophils
Sophie Irwin1, Angela Midgley1, Matthew Peak2, Michael Beresford1,2
1Women's and Children's Health, University of Liverpool, Liverpool, United Kingdom;
2NIHR, Alder Hey Clinical Research Facility, Alder Hey Children’s NHS Foundation Trust,
Liverpool, United Kingdom
Correspondence: Sophie Irwin
Introduction: Juvenile-onset Systemic Lupus Erythematosus (JSLE) is a multi-organ
autoimmune disease, characterised by autoantibodies directed against nuclear antigens
caused in part by increased dysregulated apoptotic neutrophils. Type 1 (α and β) and
2 (γ) interferon (IFN) expression is increased in both adult-onset and JSLE. An associated
granulocyte and IFN gene signature present in JSLE. IFNs have both anti- and pro-apoptotic
effects, through the activation of anti-apoptotic STAT3 and pro-apoptotic STAT1 respectively.
Previous studies demonstrated high concentrations of IFN induced apoptosis in primed
neutrophils. Physiological levels of IFNs induced an increase in pSTAT1 and a decrease
in pSTAT3 in primed neutrophils compared to naïve neutrophils. IFN signalling is dependent
on IFN receptor chains, which may contribute to apoptosis. However, expression of
IFN receptors that may contribute to this differential signalling is yet to be established.
Objectives: To investigate the effect of neutrophil activation on the expression of
the type 1 and 2 IFN receptors.
Methods: Neutrophils were isolated from healthy adult control donor blood, and stimulated
with 1 μg/mL each of: TNFα, IFNα, IFNγ, and IFNβ for 30 mins. Type 1 IFN receptor
(IFNAR) and type 2 IFN receptor (IFNGR) were analysed using flow cytometry. Neutrophils
were stained with IFNAR1-PE, IFNAR2-APC, IFNGR1-PE and IFNGR2-APC, and analysed on
the flow cytometer. Neutrophil activation markers CD11b and CD62L were also assessed
to confirm TNFα-associated priming.
Results: Activation of neutrophils following TNFα treatment was confirmed by: (1)
the significant increase in CD11b (geometric mean ± SEM; 2135 ± 289 [IFNAR analysed
cells], n = 5, p < 0.05; 2227 ± 310 [IFNGR analysed cells], n = 5, p < 0.05) compared
to unstimulated cells (1259 ± 152 [IFNAR analysed cells]; 1242 ± 107 [IFNGR analysed
cells]) and (2) the decrease in CD62L (90 ± 15 [IFNAR analysed cells], n = 5, p < 0.05;
68 ± 6 [IFNGR analysed cells] n = 5, p < 0.05) compared to unstimulated cells (377 ± 53
[IFNAR analysed cells]; 375 ± 51 [IFNGR analysed cells]). IFNα and IFNγ significantly
increased CD11b (IFNα = 1334 ± 139 vs 1259 ± 152, n = 5, p < 0.05; IFNγ = 1325 ± 120
vs 1242 ± 107, n = 5, p < 0.05). There was no overall observed change in activation
markers upon IFNβ stimulation. IFNAR1 was significantly decreased (53 ± 11 vs 123 ± 36,
n = 5, p < 0.05) and IFNGR2 was significantly increased (58 ± 7 vs 47 ± 3, n = 5,
p < 0.05) in TNFα activated neutrophils compared to unstimulated neutrophils. IFNγ
induced a small increase in IFNGR2 (59 ± 10, n = 5, p = 0.345) compared to unstimulated
neutrophils (47 ± 3), although this was not statistically significant. Overall, IFNs
had little effect on receptor expression.
Conclusion: Here we show that in an in vitro model, neutrophils from healthy adults
can be activated using TNFα, determined by the expression of established activation
markers. IFNα and IFNγ have some activating effect on neutrophils; however IFNβ was
shown to have no overall activating effect. There was a significant increase in the
IFNAR1 expression and a significant decrease in IFNGR2 expression in activated neutrophils
compared to unstimulated neutrophils.
Previous studies have shown an IFN induced increase in apoptosis in primed neutrophils,
which may be due to the increase in pSTAT1 and decrease in pSTAT3 also seen in primed
neutrophils. This increase in pSTAT1 and subsequent increase in apoptosis may be due
to the differential expression of the receptors in IFN signalling. These observations
may be important factors in the increase in JSLE neutrophil apoptosis, and create
a potential therapeutic target.
Disclosure of Interest: None Declared
P128 C1Q-deficiency lupus treated successfully with fresh frozen plasma in a sibling
pair: first description of this novel therapy in paediatric patients
Rebecca A. James1, Yvonne Glackin1, Clarissa A. Pilkington1,2
1Department of Rheumatology, Great Ormond Street Hospital, London, United Kingdom
2UCL Institute of Child Health, University College London, London, United Kingdom
Correspondence: Rebecca A. James
Introduction: We present the case of a paediatric male and female sibling pair with
severe monogenic lupus due to C1q deficiency, refractory to prior treatments, who
experienced substantial clinical and laboratory improvement following treatment with
fresh frozen plasma (FFP). FFP has previously been described in the treatment of adult
and adolescent patients with C1q deficiency, with good results. To our knowledge this
is the first description of its use in paediatric patients.
Objectives: To describe fresh frozen plasma as a novel therapy for the treatment of
children with lupus due to C1q-deficiency, and to describe the clinical and laboratory
improvement experienced by a sibling pair who received this treatment.
Methods: A seven year old girl and her three year old brother were well known to our
paediatric rheumatology service with severe lupus due to C1q deficiency. The pair
were born of consanguineous parents of Pakistani background. The female patient is
known to be homozygous Q208X in the C1QA gene; both children had unrecordable C1q
levels and severely reduced classical complement pathway functioning (0-1% normal
levels).
The female patient presented at 7 months with fever, rash and myositis. She has had
persistent disease activity since, and has failed to respond adequately to multiple
prior therapies including ciclosporin, methotrexate, azathioprine, hydroxychloroquine,
mycophenolate and rituximab. Her disease was characterised by ongoing severe facial
rashes, scarring alopecia and cytopenias. She was also under neurology follow-up for
spastic dystonic motor disorder in her lower limbs which had been extensively investigated
with no alternate cause found. Her disease was complicated by an episode of meningococcal
sepsis with acute renal failure aged 13 months.
Her brother was diagnosed with C1q deficiency on sibling screening at three months
of age, and developed malar rashes aged 10 months. His phenotype is similar to that
of his sister but somewhat milder, with photosensitive rashes, scarring alopecia and
cytopenias, as well as increased lower limb tone. He had previously failed to respond
adequately to azathioprine, methotrexate, rituximab and mycophenolate.
Both patients were steroid dependent and showed signs of profound steroid toxicity
including cushingoid habitus, growth restriction, hirsuitism and hypertension.
In light of ongoing steroid dependence, and limited treatment options, the pair were
commenced on regular infusions of intravenous fresh frozen plasma. Dosing regimen
was: 10 ml/kg given weekly for 4 infusions, and fortnightly thereafter. Complement
function and C1q levels were monitored.
Results: Both siblings experienced a significant improvement in their skin disease
and alopecia, with improved rashes, return of hair growth and a reduction in their
steroid requirements. After prolonged periods of steroid dependence, the male sibling
came off steroid therapy 3 months after commencing FFP infusions; his sister came
off steroid therapy 6 months after commencing infusions, by which point she was seven
years old and had been on steroids since 8 months of age. Classical pathway complement
function testing normalised in both patients, although measured C1q levels remain
unrecordably low. To date, neither patient has experienced adverse effects from the
FFP infusions.
Conclusion: To our knowledge, this is the first description of the use of FFP for
the treatment of paediatric patients with C1q deficiency, and proposes FFP as a potentially
safe and effective treatment for this rare condition. Further studies are warranted
to explore its safety and efficacy profile, and its role as an adjuvant treatment
option in C1q-deficiency lupus. (Consent for publication was obtained from the children’s
mother.)
Disclosure of Interest: None Declared
P129 Childhood lupus glomerulonephritis outcome is associated with low C3 levels and
anti-DNA antibodies at disease onset
Claudia S. Magalhaes1, Daniele F. Miguel1, Luciana G. Portasio1, Jose E. Corrente1,
Glaucia F. Novak2, Beatriz Molinari2, Ana P. Sakamoto3, Rosa R. Pereira4, Teresa Terreri3,
Eloisa Bonfa4, Lucia A. Campos2, Simone Appenzeller5, Claudio A. Len3, Clovis A. Silva2
1Sao Paulo State University (UNESP), Botucatu, Brazil 2University of Sao Paulo (ICr-USP),
Sao Paulo, Brazil 3Sao Paulo Federal University (UNIFESP), Sao Paulo, Brazil 4University
of Sao Paulo (USP), Sao Paulo, Brazil 5Campinas State University (UNICAMP), Campinas,
Brazil
Correspondence: Claudia S. Magalhaes
Introduction: Complement activation can damage the kidneys by attracting leukocytes,
which in turn causes inflammation, contributing to the pathogenesis of lupus glomerulonephritis
(LN). Immunodeficiency of early classical pathway of Complement components can also
induce tissue damage with low complement levels. Anti-DNA antibodies and Complement
C3, C4, CH50, reflecting complement activation, are currently used parameters to assess
SLE disease activity, in daily practice. Nevertheless, their utility remains controversial
as C3 and C4 may not accurately reflect complement activation, due to increased levels
during acute phase reaction.
Objectives: Evaluate serum levels of C3, C4, CH50 and anti-DNA antibodies at disease
onset and its association with lupus glomerulonephritis (LN) occurrence and outcome,
related to the multifactorial pathogenesis of complement activation in LN.
Methods: We combined a cumulative historical database of childhood- Systemic Lupus
Erythematosus (c-SLE) (Gomes RC et al. Arthritis Care Res 2016 10.1002/acr.22881)
to assess clinical and laboratory features and their relationship with onset age and
kidney involvement. It is a retrospective multicenter cohort started in 2013 enrolling
up to 2016, 846 pediatric subjects diagnosed with c-SLE by ACR-1997 criteria, in 10
Pediatric Rheumatology centers. Parameters of c-SLE activity were SLEDAI-2 K scores
at onset and the last follow up assessment, major organ involvement and disease damage
scored by SLICC-DI, during the last visit. Laboratory data, including antibody tests,
renal function and Complement tests, were obtained using standard methods in clinical
laboratory according to each center standard practice. Renal biopsy was performed
and classified according to WHO and ISN/RPS in each of the centers. Subjects were
classified in 3 age groups, <6, 6-12 and >12 years of onset age, and according to
the presence or absence of LN, during the disease course, estimated by clinical and
biopsy findings, during the first and last assessments.Data analyzes was performed
by descriptive and parametric statistics.
Results: Of the 846 subjects enrolled, mean age 11.6 (SD 3.6) years with 5 (SD 3.6)
years of disease duration; 427 (50.5%) had LN, of those 228 were diagnosed with renal
biopsy in addition to renal function parameters, and 419 (49,5%) did not have LN.
Median SLEDAI-2 K scores at the first and last visits were 15 and 2, respectively.
SLICC-DI scores varied from 0-9, median 0. There was no significant difference (NS)
of LN proportion, in the three age groups, <6, 6-12, >12 years onset age. Low C3,
but not C3 levels, associated significantly with LN at any time of disease course
(chi-square test, p = 0.03). Low C4, C4 levels, low CH50 and CH50 levels had no significant
association (NS). In the same line, onset hematuria (p < 0.001), proteinuria (p < 0.001)
urine casts (p = 0.02), but not urine leukocytes (NS), arterial hypertension (p = 0.0005),
neuropsychiatric events at any time (p = 0.02), high ESR (p = 0.008) but not CRP levels,
had significant association with LN outcome. High anti-DNA antibody test associated
significantly with LN (p < 0.00001), but anti-Sm, anti-RNP, anti-Ro, anti-La antibodies
had no significant association (NS). LN at any time associated significantly with
higher SLICC-DI scores (p = 0.003).
Conclusion: We confirmed in this population of c-SLE with a wide range of manifestations
and organ involvement, the role of C3 and anti-DNA antibodies association with the
occurrence and outcome of LN. In the same extent, the urine parameters and ESR at
disease onset may be reliable and cost-effective tests for identifying early childhood
LN flare or remission, and optimize clinical management and treatment in daily practice.
Acknowledgement: Ms. Daniele F. Miguel1§ is undergraduate FAPESP scholar (2016/09092-3)
Disclosure of Interest: None Declared
P130 Decreased antibodies against rubella in previously vaccinated treatment naïve-JSLE
patients: a prospective case control study
Despoina Maritsi1, Olga Vougiouka1, Margarita Onoufriou2, Susan Coffin3, Maria Tsolia1
1Second Department of Paediatrics, Medical Faculty, University of Athens, Athens,
Greece, 2Pediatrics, "Archbishop MAkarios III" Children' Hospital, Nicosia, Cyprus,
3Infectious Diseases Department, Children's Hospital of Philadelphia, Philadelphia,
PA, United States
Correspondence: Despoina Maritsi
Introduction: Systemic lupus erythematosus(SLE) is a multisystem autoimmune disease
primarily affecting young females. SLE patients are susceptible to infections due
to their defective immune system and the immunosuppressive treatment they receive.
However we lack data regarding response to specific vaccines. Rubella infection in
pregnant women is associated with serious neonatal consequences, including miscarriage,
fetal death and congenital rubella syndrome. Thus it is critical that we understand
the impact of SLE on young women’s immunity to rubella.
Objectives: In this study we determined the immune status against rubella in previously
vaccinated juvenile SLE (jSLE) patients, prior to commencement of treatment and at
one and three years, and compare this to healthy controls.
Methods: This was a prospective controlled study including 21 newly diagnosed jSLE
patients and 76 healthy controls. The control group consisted of randomly selected
healthy adolescents matched for ethnic origin, age and gender to the jSLE group, attending
the Pediatric Outpatients Department for routine checks; the same exclusion criteria
were applied. All participants had two doses of the live attenuated MMR vaccine in
early childhood. Exclusion criteria were underlying immunodeficiency, recent blood
transfusion (<6 months) and previous treatment with immunomodulating agents. Demographic,
clinical and laboratory data as well as data regarding immunization status, vaccine
history and mean time between the doses of the vaccine were collected. Seroprotection
rates and rubella-IgG titers were measured at enrollment and at specific intervals
afterwards(0,12,36 months). Total IgG levels were measured simultaneously. Rubella-IgG
antibodies were assessed by ELISA. The cutoff value for seroprotection was deemed
at 200mIU/ml. The Hospital’s Research and Ethics’ Committee approved the study; written
informed consent was obtained. Statistical significance was set at p < 0.05 and analyses
were conducted using SPSS.
Results: The two groups had similar demographic characteristics, vaccination history
and immunization status. No significant differences were detected in terms of vaccine
type, time interval between the two groups as well as mean time from last vaccination
to blood sampling. Seroprotection rates were adequate for both groups. Nonetheless,
the jSLE group had consistently inferior (but not statistically meaningful) seroprotection
rates at all time-points. Mean rubella-IgG antibodies were significantly lower in
the jSLE compared to the control group(p < 0.01). Similar results were found at one
and three years’ follow up(Table 37). None of the participants had hypogammaglobulinaemia
at the time of blood sampling. During the follow up period, the jSLE group had greater
decrease in antibody levels as indicated from the significant interaction effect of
analysis. There was no association detected between the degree of antibody loss and
type of jSLE treatment received or jSLE disease activity.
Table 37
(Abstract P130). Demographic characteristics, seroprotection rates and mean rubella-IgG
titers for the SLE and the control group
Parameters
SLE group
Control group
P value
Study sample, n
21
76
0.9*
Age, years, mean (SD)
13.3 (2.3)
13 (2.7)
0.8*
Gender n (%)
female
20 (95%)
72 (95%)
0.83+
male
1 (5%)
4 (5%)
Steroids (21/21)
-
- · mean dose
10 mg
NA
- · mean duration of treatment
17 months
HCQ (21/21)
- · mean dose
200 mg
- · mean duration of treatment
36 months
Azathioprine (9/21)
- · mean dose
75 mg
- · mean duration of treatment
18 months
SLEDAI score
- · Enrolment
7
- · 1 year
1
- · 3 years
0
Seroprotection rate at diagnosis (%)
95
98
0.4+
Seroprotection rate at 1 year (%)
92
97
0.1+
Seroprotection rate at 3 years (%)
89
96
0.04+
Mean IgG titers at diagnosis, mIU/ml
432
590
< 0.01*
Mean IgG titers at 1 year, mIU/ml
340
554
< 0.01*
Mean IgG titers at 3 years, mIU/ml
298
468
< 0.01*
Conclusion: Although seroprotection rates were similar between the two groups, mean
rubella-IgG titers were significantly lower in the jSLE group at all time-points.
Further studies are required to address the question of long-term immunity conveyed
by immunizations given at an early stage in children with rheumatic diseases. However,
evaluation of immunization status against all vaccine preventable diseases in such
patients may be beneficiary.
Disclosure of Interest: None Declared
P131 Features of 1,555 childhood-onset lupus in three groups based on distinct time
intervals to disease diagnosis: a Brazilian multicenter study
Glaucia V. Novak1, Beatriz C. Molinari1, Ana P. Sakamoto2, Maria T. Terreri2, Rosa
M. Pereira3, Claudia Saad-Magalhães4, Nadia E. Aikawa3, Lucia M. Campos1, Claudio
A. Len2, Simone Appenzeller5, Virgínia P. Ferriani6, Marco F. Silva7, Sheila K. Oliveira8,
Aline G. Islabão9, Flávio R. Sztajnbok10, Luciana B. Paim11, Cássia M. Barbosa12,
Maria C. Santos13, Blanca E. Bica14, Evaldo G. Sena15, Ana J. Moraes16, Ana M. Rolim17,
Paulo F. Spelling18, Iloite M. Scheibel19, André S. Cavalcanti20, Erica N. Matos21,
Teresa C. Robazzi22, Luciano J. Guimarães23, Flávia P. Santos24, Cynthia T. Silva25,
Eloisa Bonfá3, Clovis A. Silva1
1Pediatric Rheumatology Division, CHILDREN’S INSTITUTE, HOSPITAL DAS CLINICAS HCFMUSP,
FACULDADE DE MEDICINA, UNIVERSIDADE DE SAO PAULO, São Paulo, Brazil 2Pediatric Rheumatology
Division, Federal University of São Paulo (UNIFESP), São Paulo, Brazil 3Rheumatology
Division, HOSPITAL DAS CLINICAS HCFMUSP, FACULDADE DE MEDICINA, UNIVERSIDADE DE SAO
PAULO, São Paulo, Brazil 4Pediatric Rheumatology Division, Sao Paulo State University
(UNESP), Botucatu, Brazil 5Pediatric Rheumatology Division, State University of Campinas
(UNICAMP), Campinas, Brazil 6Pediatric Rheumatology Division, University of São Paulo
(FMUSP-Ribeirão Preto), Ribeirão Preto, Brazil 7Pediatric Rheumatology Division, Hospital
Geral de Fortaleza, Fortaleza, Brazil 8Pediatric Rheumatology Division, Rio de Janeiro
Federal University (IPPMG-UFRJ), Rio de Janeiro, Brazil 9Pediatric Rheumatology Division,
Hospital Jose Alencar, Brasilia, Brazil 10Pediatric Rheumatology Division, Pedro Ernesto
University Hospital, Rio de Janeiro, Brazil 11Pediatric Rheumatology Division, Albert
Sabin Hospital, Fortaleza, Brazil 12Pediatric Rheumatology Division, Hospital Darcy
Vargas, São Paulo, Brazil 13Pediatric Rheumatology Division, Santa Casa de São Paulo,
São Paulo, Brazil 14Rheumatology Division, Federal University of Rio de Janeiro, Rio
de Janeiro, Brazil 15Pediatric Rheumatology Division, Lauro Vanderley University Hospital,
João Pessoa, Brazil 16Pediatric Rheumatology Division, Federal University of Pará,
Pará, Brazil 17Pediatric Rheumatology Division, Obras Sociais Irmã Dulce, Salvador,
Brazil 18Pediatric Rheumatology Division, Hospital Evangélico de Curitiba, Curitiba,
Brazil 19Pediatric Rheumatology Division, Hospital Conceição, Porto Alegre, Brazil
20Pediatric Rheumatology Division, Federal University of Pernambuco, Recife, Brazil
21Pediatric Rheumatology Division, Federal University of Mato Grosso do Sul, Campo
Grande, Brazil 22Pediatric Rheumatology Division, Federal University of Bahia, Salvador,
Brazil 23Pediatric Rheumatology Division, University of Brasilia, Brasilia, Brazil
24Pediatric Rheumatology Division, Federal University of Minas Gerais, Belo Horizonte,
Brazil 25Pediatric Rheumatology Division, Hospital Municipal Piedade, Rio de Janeiro,
Brazil
Correspondence: Glaucia V. Novak
Introduction: Longer or shorter interval between the first manifestation attributable
to SLE and the clinical diagnosis may influence disease expression in terms of initial
clinical and laboratorial presentation and disease activity in childhood systemic
lupus erythematosus (cSLE) patients.
Objectives: The objective of the present large multicenter study was to compare demographic
data, Systemic Lupus International Collaborating Clinics Classification Criteria for
Systemic Lupus Erythematosus (SLICC) parameters, neuropsychiatric involvement and
SLEDAI-2 K at diagnosis in three different groups with distinct time intervals between
onset of signs/symptoms and disease diagnosis.
Methods: A retrospective multicenter study was performed in 1,555 cSLE (ACR criteria)
patients from 27 Pediatric Rheumatology services of 5 regions of Brazil: North (n = 34),
Northeast (n = 259), Central-West (n = 124), Southeast (n = 1075) and South (n = 63).
Patients were divided in three cSLE groups: A: short time interval to diagnosis (<1 month),
B: intermediate time interval (≥1 and <3 months) and C: long time interval (≥3 months).
An investigator meeting was held to define the protocol and to harmonize clinical
parameters definition in Brasilia, at the time of Brazilian Congress of Rheumatology
in 2016. Demographic data, SLICC, neuropsychiatric involvement according to ACR classification
criteria and disease activity (SLEDAI-2 K) were systematically evaluated.
Results: The number of patients in each group was: A = 60 (4%), B = 522 (33.5%) and
C = 973 (62.5%). The median age at diagnosis [11.1 (4.2-17) vs. 12 (1.9-17.7) vs.
12.5 (3-18) years, p = 0.025] was significantly lower in the group A compared to B
and C. The median number of diagnostic criteria according to SLICC [7 (4-12) vs. 6
(4-13) vs. 6 (4-12), p < 0.0001] and SLEDAI-2 K score [18 (6-57) vs. 16 (2-63) vs.
13 (1-49), p < 0.0001] were significantly higher in the group A than the other two
groups. cSLE groups were distinct with regard to: SLEDAI-2 K ≥ 8 (90% vs. 89% vs.
82%, p = 0.002), serositis (37% vs. 33% vs. 25%, p = 0.002), renal disorder (52% vs.
47% vs. 40%, p = 0.009), neuropsychiatric disorder (22% vs. 13% vs. 10%, p = 0.008),
leucopenia/lymphopenia (65% vs. 46% vs. 40%, p < 0.0001) and thrombocytopenia (32%
vs. 18% vs. 19%, p = 0.037); as well as synovitis (61% vs. 66% vs. 71%, p = 0.032)
and headache (5% vs. 7% vs. 11%, p = 0.043).
Conclusion: Our large Brazilian multicenter study identified distinct features of
cSLE patients suggesting that a shorter time interval to diagnosis was associated
with a more active disease and multisystem severe presentation.
Disclosure of Interest: G. Novak: None Declared, B. Molinari: None Declared, A. Sakamoto
: None Declared, M. Terreri : None Declared, R. Pereira : None Declared, C. Saad-Magalhães
: None Declared, N. Aikawa : None Declared, L. Campos : None Declared, C. Len : None
Declared, S. Appenzeller : None Declared, V. Ferriani : None Declared, M. Silva :
None Declared, S. Oliveira : None Declared, A. Islabão : None Declared, F. Sztajnbok
: None Declared, L. Paim : None Declared, C. Barbosa : None Declared, M. Santos :
None Declared, B. Bica : None Declared, E. Sena : None Declared, A. Moraes : None
Declared, A. Rolim: None Declared, P. Spelling : None Declared, I. Scheibel : None
Declared, A. Cavalcanti : None Declared, E. Matos : None Declared, T. Robazzi : None
Declared, L. Guimarães : None Declared, F. Santos : None Declared, C. Silva : None
Declared, E. Bonfá : None Declared, C. Silva Grant/Research Support from: Conselho
Nacional de Desenvolvimento Científico e Tecnológico (CNPq 302724/2011-7)
P132 Adult outcomes in a large cohort of childhood-onset SLE patients: coping and
resilience in relation to health-related quality of life - the CHILL-NL study
Radhevi A. S. Ramnath1, Noortje Groot1, 2, Ayse Kaynak1, Marc Bijl3, Radboud J.E.
M. Dolhain4, Y.K. O. Teng5, Els Zirkzee6, Karina de Leeuw7, Ruth Fritsch-Stork8, Irene
Bultink9, Sylvia S. M. Kamphuis1 on behalf of the CHILL-NL study group
1Department of Pediatric Rheumatology, Sophia Children's Hospital - Erasmus University
Medical Center, Rotterdam, Netherlands 2Department of Pediatric Immunology, Wilhelmina
Children's Hospital - University Medical Center Utrecht, Utrecht, Netherlands 3Department
of Internal Medicine and Rheumatology, Martini Hospital, Groningen, Netherlands 4Department
of Rheumatology, Erasmus University Medical Center, Rotterdam, Netherlands 5Department
of Rheumatology, Leiden University Medical Center, Leiden, Netherlands 6Department
of Rheumatology, Maasstad Hospital, Rotterdam, Netherlands 7Department of Rheumatology
and Clinical Immunology, University Medical Center, Groningen, Netherlands 8Department
of Rheumatology and Clinical Immunology, University Medical Center Utrecht, Utrecht,
Netherlands 9Amsterdam Rheumatology and Immunology Center, Location VUmc, Amsterdam,
Netherlands
Correspondence: Radhevi A. S. Ramnath
Introduction: Childhood-onset SLE is a lifelong severe disease and results in significant
disease/therapy-related damage. This chronic disease has a clear impact on HRQoL,
requesting adequate resilience and coping mechanisms. Not much is known regarding
coping/resilience capacities in patients with cSLE.
Objectives: To investigate individual resilience capacities and coping strategies
in a large cohort (n = 106) of adults with childhood-onset SLE and the relation with
HRQoL
Methods: Adults with cSLE were included in the CHILL-NL (CHILdhood Lupus-NetherLands)
study via Dutch medical specialists and patient organizations. The study consisted
of a single study visit containing a structured history and physical examination.
Individual resilience capacities were assessed using the Brief Resilience Coping Scale
(BRCS). This is a 4-item self-reported questionnaire that aims to assess the ability
to handle stress in an adaptive manner, score range from 4 to 20: low-resilience ≤ 13,
medium-resilience 14-16, high-resilience: ≥17. Coping strategies were assessed by
the Assimilation-Accommodation Coping Scale (AACS). The AACS was utilized to measure
coping methods, it consists of two subscales: tenacious goal pursuit (TGP) and flexible
goal adjustment (FGA). Higher scores on one of the subscales indicate more use of
that strategy. HRQoL was assessed with SF-36. Outcomes were compared to Dutch norm
data.
Results: 106 cSLE patients (92% female, 73% white) were included, median age at study
visit was 33 years and median disease duration 20 years. 61% had disease damage (SDI ≥ 1).
HRQoL of cSLE patients was impaired (7/8 domains SF36): remarkably mental health was
similar between patients and Dutch norm data. Surprisingly, HRQoL was not related
to disease damage(7/8 domains SF36).
Low-resilient copers (BRCS) had impaired HRQoL in 2/8 domains of SF36 (general health
and vitality), when compared to medium and high-resilient copers. Preference for a
coping strategy (AACS) also influenced HRQoL: patients who applied tenacious goal
pursuit (TGP) appeared to have impaired HRQoL (5/8 domains SF36) compared to patients
preferring flexible goal adjustment. The extent to which the coping strategies were
scored by patients on a scale from 0 to 60 seemed to relate to their resilience capacities
with low-resilient patients having lower scores on the coping list.
Resilience measured by BRCS: Sinclair, V.G. & Wallston, 2004, Assessment. Individual
coping measured by AACS: Brandtstädter & Renner, 1990, Psychology and Aging.
Conclusion: In this large cohort of adults with cSLE, self-reported resilience and
coping capacities have an impact on HRQoL. This opens perspective to improve HRQoL
with cognitive training methods focused on improving resilience and coping strategies
in individual patients.
Disclosure of Interest: None Declared
P133 Understanding the immunopathogenesis of juvenile-onset SLE using immune and metabolic
phenotyping
George Robinson1,2, Marsilio Adriani1, Ines Pineda Torra3, Yiannis Ioannou2, Elizabeth
Jury1 and Jury Group
1Rheumatology, University college london, London, United Kingdom 2Centre for Adolescent
Rheumatology, University college london, London, United Kingdom 3Clinical Pharmacology,
University college london, London, United Kingdom
Correspondence: George Robinson
Introduction: Juvenile-onset systemic lupus erythematosus (JSLE) is an autoimmune
disorder characterized by immune cell dysregulation, chronic inflammation and increased
cardiovascular risk. Disease onset dominates mid-puberty and the female to male ratio
is 4.5:1, suggesting a hormonal importance in disease pathogenesis. JSLE patients
have more aggressive disease, more major organ involvement and increased standardised
mortality ratios compared to patients with adult-onset SLE yet research into JSLE
is uncommon. Our previous findings show that defects in immune cell lipid metabolism
contribute to disease pathogenesis in adult-onset SLE. However, in JSLE little is
known about the immune profile or whether abnormal lipid metabolism also contributes
to pathogenesis.
Objectives: Since altered metabolism plays a role in adult-onset SLE our objective
was to explore this in JSLE through in depth immune and metabolic phenotyping of a
cohort of JSLE patients and age and gender matched healthy donors (HCs).
Methods: Flow cytometry was carried out using two 15-colour panels to immune-phenotype
peripheral blood mononuclear cells from 39 healthy donors (HCs, 17 male, 22 female,
mean age 18) and 35 JSLE patients (12 male, 23 female, mean age 19). Data was analysed
by cluster and phenotype–phenotype correlation. Flow cytometry was also used to measure
functional and metabolic marker expression on immune cell subsets. Data was correlated
with clinical assessments of disease.
Results: Patients with JSLE were characterised by increased naïve and decreased memory
B-cell and T-cell subsets and increased monocyte frequency (p = 0.0013) compared to
HCs. Furthermore, phenotype-phenotype correlation analysis identified differential
associations between naïve and memory immune cell subtypes when comparing the HC and
JSLE cohorts.
CD4+ and CD8+ T-cells from JSLE patients had elevated membrane lipid raft (p = 0.0185,
p = 0.0087) and glucose transport receptor (GLUT-1) (p = 0.0205, p = 0.0017) expression
suggesting that they were more metabolically active. Metabolic defects were also found
in monocytes and plasmacytoid dendritic cells. The expression of these metabolic markers
on different subsets correlated with cell frequency suggesting a role of cell metabolism
in driving the JSLE phenotype. Furthermore the metabolic immune-phenotype in JSLE
correlated positively with disease activity, erythrocyte sedimentation rate and dsDNA
titre and negatively with complement protein C3 supporting the hypothesis that altered
metabolism is associated with JSLE development and severity.
Unsupervised hierarchical cluster analysis of patient clinical data revealed that
JSLE patients in this cohort could be stratified into 5 groups each with a unique
clinical identity mainly associated with disease activity markers and the presence
of anti-cardiolipin antibodies. Each group had a unique immune-phenotype and metabolic
profile.
Conclusion: Differences in the metabolic profiles of immune cell subsets in JSLE contribute
to disease pathogenesis and severity. Cellular metabolic regulators may therefore
have therapeutic benefit for JSLE patients. Defining these patient groups further
may help to determine the therapeutic benefit of these and other therapeutics and
allow for the treatment patients in a more effective and personalised manner.
Disclosure of Interest: None Declared
P134 Hepatitis a virus vaccination in juvenile-onset systemic lupus erythematosus
Sevinc Mertoglu1, Sezgin Sahin1, Omer F. Beser2, Amra Adrovic1, Pelin Yuksel3, Soner
Sazak4, Bekir S. Kocazeybek3, Ozgur Kasapcopur1
1Pediatric Rheumatology, Istanbul University, Cerrahpasa Medical School, Istanbul,
Turkey 2Pediatric gastroenterology, Okmeydani Education and Training Hospital, Istanbul,
Turkey 3Microbiology, Istanbul University, Cerrahpasa Medical School, Istanbul, Turkey
4Pediatrics, Okmeydani Education and Training Hospital, Istanbul, Turkey
Correspondence: Sezgin Sahin
Introduction: Systemic lupus erythematosus (SLE) is an autoimmune disease and various
infections play significant roles in flares of this chronic remitting-relapsing disease.
Hepatitis A virus is one of these infectious agents that has high endemicity particularly
in developing countries and countries with poor sanitary conditions. Hence, immunization
via vaccination against this infectious agent would provide a better management of
the disease. However, both immunosuppressive drugs and the disease itself are believed
to impair the normal functioning of immune system. Little is known regarding the safety
and immunogenicity of vaccinations in SLE patients. Moreover, to the best of our knowledge
safety and efficacy of hepatitis A vaccination were not studied in children with SLE.
Objectives: In the present study, we aimed to compare the antibody titers and seropositivity
in juvenile SLE and healthy subjects after hepatitis A vaccination. Besides, we examined
the effect of immunosuppressive drugs and disease activity on antibody responses.
Methods: Sixty-nine juvenile SLE patients were enrolled in the study. Initially, we
evaluated anti-HAV IgM and anti-HAV IgG titers in juvenile SLE patients. Of the 69
subjects, 37 patients were seronegative and eligible for hepatitis A vaccination.
However, 7 juvenile SLE patients refused to participate to the study. Finally, anti-HAV
Ig G negative 30 patients and 39 healthy subjects were vaccinated with two doses of
hepatitis A vaccine (at 0 months and at sixth months). After vaccinations, anti-HAV
Ig G titers were measured and compared between two groups.
Results: Anti-HAV Ig G concentrations were measured after vaccination in 30 patients
with juvenile SLE and 39 control subjects. Anti-HAV Ig G titer of the juvenile SLE
patients was significantly lower than that of the healthy controls (median 4.6 versus
11.9 IU/L, p = 0.02). Although the rate of seropositivity was lower in juvenile SLE
patients (n = 24/30, 80%) compared to healthy controls (n = 33/39, 84.6%); this was
not statistically significant (p = 0.6). No adverse reaction was reported after vaccination.
Conclusion: Although anti-HAV Ig G antibody titers after vaccination have found to
be somewhat lower than that of the healthy subjects, significant portion of juvenile
SLE patients were seropositive. According to these results, we conclude that hepatitis
A vaccine is adequately immunogenic and quite safe in juvenile SLE patients.
References:
1. Borgia RE, Silverman ED. Childhood-onset systemic lupus erythematosus: an update.
Curr Opin Rheumatol 2015; 27: 483-92.
2. Zandman-Goddard G, Shoenfeld Y. Infections and SLE. Autoimmunity 2005; 38: 473–85.
3. Wucherpfennig KW. Mechanisms for the induction of autoimmunity by infectious agents.
J Clin Invest 2001; 108:1097–104.
4. Melhem NM, Talhouk R, Rachidi H, Ramia S. Hepatitis A virus in the Middle East
and North Africa region: a new challenge. Journal of viral hepatitis 2014; 21(9):
605-615.
5. Aytac MB, Kasapcopur O, Aslan M, Erener-Ercan T, Cullu-Cokugras F, Arisoy N. Hepatitis
B vaccination in juvenile systemic lupus erythematosus. Clin Exp Rheumatol 2011; 29:
882-6.
Disclosure of Interest: None Declared
P135 Microangiopathy in childhood-onset systemic lupus erythematosus, a detailed further
quantitative analysis of capillaroscopy abnormalities
Dieneke Schonenberg-Meinema1,2, J.M. vd Berg1, Amara Nassar-Sheikh-Rashid1, Godelieve
de Bree3, A.E. Hak4, Marieke van Onna4, Karin Melsens5, Maurizio Cutolo6, T.W. Kuijpers1,
Vanessa Smith5,7 and EULAR study group on microcirculation in rheumatic diseases
1Department of Pediatric Hematology, Immunology, Rheumatology and Infectious Diseases,
Emma Children’s Hospital, Academical Medical Center, Amsterdam, Netherlands 2Department
of Pediatric Hematology, Immunology, Rheumatology and Infectious Diseases, Emma Children’s
Hospital, Academical Medical Center (AMC), Amsterdam, Netherlands, 3Department of
Infectious Diseases, 4Department of Clinical Immunology and Rheumatology, Academical
medical center, Amsterdam, Netherlands, 5Department of Rheumatology, Ghent University
Hospital, Ghent, Belgium, 6Research Laboratory and Academic Unit of Clinical Rheumatology,
University of Genova, Genova, Italy, 7Faculty of Internal Medicine, Ghent University,
Ghent, Belgium
Correspondence: Dieneke Schonenberg-Meinema
Introduction: Capillaroscopy findings can be qualitatively described as: normal, microangiopathy
(non-specific abnormalities) or scleroderma pattern. Capillary abnormalities, described
in varying prevalence in patients with systemic lupus erythematosus (SLE), are mainly
described as microangiopathy with nonspecific capillary morphologic changes
Objectives: To describe the capillary morphologic abnormalities in a cross-sectional
tertiary cohort of patients with childhood-onset SLE (cSLE) by a detailed quantitative
assessment
Methods: Nailfold videocapillaroscopy (NVC) was performed in cSLE-patients (onset < 18 years)
with a x200 magnification lens (Optilia). All fingers except the thumb were examined
with four images per finger. The following capillaroscopic characteristics were evaluated
per millimeter: density (compared to mean density known for age, sex and ethnicity),
number of abnormal shapes (as defined by the EULAR study group on microcirculation
in Rheumatic Diseases), giant capillaries (defined as apical diameter >50 mcm), maximum
apical diameter (dilatations defined as apical diameter 20-50mcm) and microbleedings
(categorized by large hemorrhages and small multiple point-shaped hemorrhages surrounding
the capillary loop)
Results: This cohort of cSLE-patients was predominantly female (n = 19/22, 86.4%),
with a median age of 14 years at onset of disease. At time of capillaroscopy, the
median age was 17 years with a median disease duration of 29.3 months (IQR* 25-75:
12.7-56.5 months). Thirteen patients (59.1%) had an African/Afro-Caribbean ethnic
background and seven (31.8%) a Caucasian. Median SLEDAI-score** at diagnosis was 11,
and median SLEDAI-score at moment of capillaroscopy was 4.
In total, 4607 capillaries from 22 patients were analyzed. By qualitative analysis,
81.8% (n = 18) showed a pattern of microangiopathy. Quantitatively, all of these patients
showed a specific combination (observed per finger) of three specific morphological
capillary abnormalities: apical dilatations, small point-shaped hemorrhages and abnormal
shapes. Looking at frequency and localization of these combined capillary abnormalities,
three patients (3/22, 13.6%) showed them in all eight examined fingers, 54.5% (12/22)
in four or more fingers and 72.7% (16/22) in three or more fingers. The fingers that
were most affected were fourth finger left (n = 14), fourth finger right (n = 13)
and fifth finger left (n = 13 patients).
*IQR = InterQuartile Range
**SLEDAI = Systemic Lupus Erythematosus Disease Activity Index
Conclusion: In this pilot (n = 22) of cSLE patients, 81.8% (n = 18) showed a combination
of specific capillary morphological abnormalities: apical dilatations, small point-shaped
hemorrhages and abnormal shapes. Up to 72.7% showed this combination in three or more
fingers and 13.6% in all eight examined fingers. More studies in (c)SLE-patients are
needed to assess if these capillary abnormalities are specific for SLE
Disclosure of Interest: None Declared
P136 Timing of intravenous cyclophosphamide and long-term outcome in children with
proliferative lupus nephritis
Tetsuya Tsuchida1, Asami Ohara1, Kenichi Nishimura1, Tomo Nozawa1, Ryoki Hara1, Shuichi
Ito1
1Department of Pediatrics, Yokohama City University Hospital, Yokohama, Japan
Correspondence: Tetsuya Tsuchida
Introduction: Induction therapy combined with corticosteroid and immunosuppressant
from the acute phase improves long-term outcome in people with systemic lupus erythematosus
(SLE). The prognosis of SLE is significantly improved by intravenous cyclophosphamide
(IVCY) and mycophenolate mofetil (MMF). According to major guidelines for lupus nephritis
(LN), IVCY and MMF are recommended as the first line remission induction therapy for
adult proliferative LN (type III or IV), but the use of this strategy in childhood
LN is not well established.
Objectives: To investigate if early remission induction therapy using IVCY can improve
long-term outcome in childhood proliferative LN (type III or IV), by comparing patients
treated with IVCY at onset versus later at disease flare.
Methods: Thirty-four children with SLE who were admitted to our institute from April
1997 to April 2016 were enrolled. Diagnosis of SLE was based on 1987 ACR criteria
and diagnosis of LN was based on WHO classification or 2003 ISN/RPS classification.
Patients were divided into two groups; group A: IVCY was used at the time of onset
(n = 22), and group B: IVCY was used at the first recurrence (serological and/or clinical
flare of SLE/LN) (n = 12). All patients successfully achieved remission once. We retrospectively
evaluated parameters before and after IVCY including renal pathology, period to the
first recurrence after IVCY, dose of prednisolone at the last observation, SLE disease
activity index (SLEDAI), anti-double-strand DNA antibody (anti-dsDNAab), complement,
urinary protein, estimated glomerular filtration rate (eGFR) and immunosuppressant
as remission maintenance therapy.
Results: There was no significant difference in patient’s characteristics between
the two groups. Type IV LN was more common than type III in both groups. The median
number of IVCY was 8.5 (6–12) in group A and 8.5 (6–9) in group B (p = 0.83). Eleven
of 22 patients had recurrence in group A (50%) and 8 of 12 patients had recurrence
in group B (67%) after IVCY. The median period to the first recurrence after IVCY
was 74 months in group A and 47.5 months in group B (p = 0.34, log-rank test). At
the last observation, daily dose of prednisolone did not differ between groups A and
B (0.100 vs. 0.155 mg/kg, p = 0.15). Additionally, there was no significant difference
in titer of anti-dsDNAab, complement, SLEDAI, urinary protein, or eGFR. Regarding
remission maintenance therapy after IVCY, 26 patients were treated with MMF (16 group
A, 10 group B), and 8 patients were treated with other immunosuppressants such as
azathioprine and mizoribine (6 group A, 2 group B). Of note, 12 of 26 patients treated
with MMF (46%) and 7 of 8 patients on non-MMF immunosuppressants (88%) experienced
recurrence (p = 0.039, log-rank test). Six of 16 patients on MMF in group A and 6
of 10 on MMF in group B experienced recurrence (p = 0.47). There were no deaths during
the observation period.
Conclusion: In this study, timing of IVCY did not affect either prevention of recurrence
or recurrence-free survival. Despite IVCY as induction therapy at onset, half the
patients later had recurrence. Surprisingly, choice of MMF as maintenance therapy
after IVCY is one factor to achieve longer remission. A recent meta-analysis showed
that MMF was the most favorable maintenance therapy for adult SLE/LN1). Our results
were consistent with this finding and IVCY followed by MMF could be a favorable treatment
for childhood proliferative LN. However, to avoid gonadal toxicity and malignancy
due to IVCY, remission induction therapy with MMF for childhood proliferative LN should
be evaluated by a prospective randomized-control trial in the future.
Reference
1)Palmer SC, Tunnicliffe DJ, Singh-Grewal D, Mavridis D, Tonelli M, Johnson DW, et
al. Induction and Maintenance Immunosuppression Treatment of Proliferative Lupus Nephritis
: A Network Meta-analysis of Randomized Trials. Am J Kidney Dis. 2017 Feb 20. pii:
Cited in PubMed ; S0272-6386(17)30036-7. doi: 10.1053/j.ajkd.2016.12.008. [Epub ahead
of print]
Disclosure of Interest: None Declared
P137 Sexual differences in TLR7 driven interferon alpha production may explain the
increased prevalence of JSLE in females after puberty
Kate Webb1, Gary Butler2, Madhvi Menon3, Hannah Peckham1, Ania Radziszewska1, Lucy
R. Wedderburn1, Yiannis Ioannou1
1Centre for Adolescent Rheumatology, UCL, London, United Kingdom 2Paediatric endocrinology,
UCL, London, United Kingdom 3Medicine, UCL, London, United Kingdom
Correspondence: Kate Webb
Introduction: Juvenile onset systemic lupus erythematosus (jSLE) is an interferon
alpha (IFNα) driven disease with a higher prevalence in females after puberty. The
median ages of onset for puberty and jSLE are very similar, implying that puberty
acts as a biological switch in the development of jSLE.
Objectives: 1.To investigate whether transition through puberty is associated with
increased production of IFNα by plasmacytoid dendritic cells (pDC) in females compared
to males. 2.To investigate whether interferon regulatory factor 5 (IRF5) and interferon
stimulated gene expression (as measured by tetherin expression) change with puberty
or sex.
Methods: Blood from heathy volunteers pre, during and post puberty, was collected
and peripheral blood monocytes separated by ficoll gradient centrifugation. Ex vivo
phenotype including cell type percentage, IRF5 expression and tetherin expression
was assessed by flow cytometry. Cells were also separately stimulated with toll like
receptor (TLR) 7 agonist R848 or TLR 9 agonist CPGODN2216, before assessing for the
production of IFNα by pDC by flow cytometry.
Results: 60 young healthy volunteers between ages 6-18 years were recruited. pDCs
from female volunteers produced significantly more IFNα than males upon TLR7 stimulation,
overall (p = 0.01) and after puberty (p = 0.03) but not before puberty (p = 0.47).There
was no difference in TLR9 stimulated pDCs between sexes across the age groups. In
females, IRF5 expression after puberty was significantly reduced in pDCs (p = 0.02),
monocytes (p = 0.04) and B cells (p = 0.03) when compared to males. After puberty,
female pDCs (p = 0.04) and monocytes (p = 0.04) expressed significantly more tetherin
(an interferon inducible gene protein product) than males.
Conclusion: Females produce more IFNα than males upon TLR7 stimulation after puberty,
but not before. In addition, females express less IRF5 and may have a higher IFNα
signature after puberty. These unique IFNα-related changes that occur in the immune
system between sexes over puberty may account for the increased incidence of jSLE
in females after sexual maturity and provide insights into the pathogenesis of jSLE.
Disclosure of Interest: None Declared
Systemic lupus erythematosus and antiphospholipid syndrome
P138 Similarities and differences between childhood-onset and adult-onset systemic
lupus erythematosus in sultanate of Oman
Asma Al Rasbi1, Rabab Sultan2, Nisreen Abdallah3, Juma Al Kaabi3, Reem Abdwani2
1SQU, Muscat, Oman 2Child Health, SQUH, Muscat, Oman 3Medicine, SQU, Muscat, Oman
Correspondence: Reem Abdwani
Introduction: SLE is a disease that mainly affects women of childbearing age, however,
its prevalence is not confined within this population. A total of 15–20% of cases
present in children under 16 years of age. Although adult onset SLE (aSLE) and childhood
onset SLE (cSLE) share the same clinical features and diagnostic criteria, differences
between the two groups have been identified.
Objectives: The aim of this study is to compare the similarities and differences in
demographics, clinical presentation, serology, outcomes, treatment, disease severity
and damage between aSLE and cSLE in an Omani cohort. This will be first study of this
nature to be conducted from an Arab population from the Middle East region.
Methods: We evaluated 225 SLE patients, 139 adults and 86 children, followed at the
pediatric and adult rheumatology department from January 2006 to July 2016 in Sultan
Qaboos University Hospital, a tertiary and academic center in Oman. We included all
patients with available clinical data at the disease onset in the hospital information
system. cSLE was defined as children diagnosed at the age of 16 or below, while those
diagnosed above the age of 16 were classified aSLE. All patients that were included
in the study satisfied the 1997 American College of Rheumatology (ACR) Revised Criteria.
Results: The mean age at diagnosis of aSLE 28.1 years (SD ± 8.8 yrs) and cSLE 9,4 years
(SD ± 4.2 yrs.). While the mean disease duration in aSLE 5.9 years (SD ±4.4) and cSLE
8.9 years (SD ± 5.7). There was greater female predominance of the disease with increasing
age in cSLE. The F:M ratio in different age groups; less than 5 yrs, 5-12 year and
13-16 year were 2.5:1, 3.5:1, 6.7:1 respectively. While the female predominance in
aSLE decreased with increasing age. The F:M ratio in different age groups; 17-25 years,
25-50 year and greater than 50 years were 11.1:1, 6.5:1 and 3:1 respectively. The
distribution of SLE from various regions in the sultanate was proportionate to population
density in aSLE as would be expected. However, there was higher prevalence of cSLE
in A’Sharqiya, a region in the Sultanate of Oman with a relatively low population
density. The clinical features in cSLE showed higher frequency of renal, musculoskeletal
and pulmonary involvement; while aSLE showed higher frequency of hematological and
mucocuatnous involvement as shown in Table 38. Serological differences demonstrated
significantly higher frequency of antidsDNA antibody in cSLE, with higher frequency
of anti-smith antibody in aSLE. The mean disease activity sindex (SLEDAI) at disease
onset and over disease course was also higher in cSLE than aSLE (Table 38). cSLE were
more likely to be treated with immunosuppressants such as cyclophosphamide and MMF
than aSLE (54%, 21.5% vs 69.8%, 51.2%).
Table 38
(Abstract P138). Demographics clinical and laboratory characteristics of 225 SLE patients
included in analysis
aSLE 139(62%)
cSLE 86 (38%)
P Value
Cutanous
17 (12.2%)
0 (0.0%)
0.004
Arthritis
74 (53.2%)
58 (67.4%)
0.050
Renal
27 (19.4%)
42 (48.8%)
P < 0.0005
Hematologic
62 (44.6%)
19 (22.1%)
0.001
Neurologic
12 (8.6%)
15 (17.4%)
0.078
Pulmonary
4 (2.9%)
11 (12.8%)
0.009
SLEDAI at disease onset (Mean ± SD)
8.47
13.27
P < 0.05
SLEDAI over disease course (Mean ± SD)
11.77
16.34
P < 0.05
Conclusion: Differences between aSLE and cSLE in an Arabic cohort from Oman were different
than the difference noted in other Caucasian cohort. It appears that individual races
and ethnicities may exhibit differences in disease susceptibility and disease manifestations
Disclosure of Interest: None Declared
P139 Neonatal lupus erythematosus: a 12-year retrospective study in Korea
Jong Gyun Ahn1, Dong Soo Kim1, Young Dae Kim2, Kwang Nam Kim3
1Department of Pediatrics, Severance Children's Hospital, Yonsei University College
of Medicine, Seoul, Korea, Republic Of 2Department of Pediatrics, Inje University
School of Medicine, Seoul, Korea, Republic Of 3Department of Pediatrics, Hallym University
Sacred Heart Hospital, Hallym University College of Medicine, Anyang, Korea, Republic
Of
Correspondence: Jong Gyun Ahn
Introduction: Neonatal lupus erythematosus (NLE) is a rare autoimmune disease manifested
commonly by cutaneous erythema and congenital heart block. NLE is presumed to result
from transplacental passage of maternal autoantibodies of the Ro/La family.
Objectives: The aim of this study is to investigate clinical manifestations, treatment
and outcomes of NLE.
Methods: Medical records of patients with NLE and their mothers from Severance children’s
hospital in Korea between January 2015 and April 2017 were reviewed. A diagnosis of
NLE was made if the infant had the presence of clinical symptoms plus positive anti-Ro/SSA
or anti-La/SSB or both.
Results: There were 20 cases (male:female ratio of 8:12). Age of onset of clinical
features was from birth to 68 days (median age of 7 days). Cutaneous lesions were
seen in more than 90% of patients, while hepatobiliary, hematologogic, and cardiac
abnormalities were present in 45%, 20% and 10% of cases, respectively. Anti-Ro/SSA
and anti-La/SSB were positive in 100% and 65% of cases. There was no mortality during
the study period. Most neonatal lupus erythematosus mothers (16 cases, 74.2%) had
underlying autoimmune diseases (systemic lupus erythematosus in 11 cases and other
autoimmune diseases in 5 cases). However, two of the mothers without pre-pregnancy
autoimmune disease were found to have autoimmune antibodies in tests after the baby’s
diagnosis.
Conclusion: NLE should be screened if infant have congenital heart block or skin rash
with multi-system involvement despite the absence of history of maternal autoimmune
disease. Most NLE patients without congenital heart block have relatively excellent
outcome.
Disclosure of Interest: None Declared
P140 Analysis of MEFV gene sequence variants and association with clinical features
and disease activity in juvenile systemic lupus erythematosus patients
Ayşe Zopçuk1, Nuray Aktay Ayaz1, Betül Sözeri2, Mustafa Çakan1, Şerife Gül Karadağ1,
Ayşenur Paç Kısaarslan3, Zübeyde Gündüz3
1Pediatric Rheumatology, Kanuni Sultan Süleyman Research And Training Hospital, İstanbul,
Turkey 2Pediatric Rheumatology, Ümraniye Research And Training Hospital, İstanbul,
Turkey 3Pediatric Rheumatology, Erciyes University, Kayseri, Turkey
Correspondence: Nuray Aktay Ayaz
Introduction: FMF is a hereditary autoinflammatory periodic fever syndrome that is
caused by mutations in the MEFV gene. It is common in Mediterranean countries and
the carrier rate in MEFV gene in Turkey is reported to be around 20%. It has also
been reported that in many chronic inflammatory diseases, the frequency of MEFV mutations
is increased and the course of the disease may be altered.
Objectives: The aim of this study was to assess the frequency of MEFV gene sequence
variants in patients with juvenile SLE and compare the clinical features, disease
severity and course of the patients with or without MEFV sequence variants.
Methods: MEFV gene analysis was studied in 40 jSLE patients that were being followed
in 2 pediatric rheumatology centers in Istanbul and Kayseri. None of the patients
in the cohort had diagnosis of FMF.
Results: The frequency of MEFV polymorphisms and mutations in juvenile SLE patients
was found to be 35% (Table 39). The most common of these was R202Q polymorphism (50%).
The significance of the R202Q and E148Q sequence variants is controversial. After
the exclusion of these variants, re-analysis revealed that the carrier rate was 12.5%.
Table 39
(Abstract P140). MEFV mutation analysis of SLE patients
Mutation
n
Min
Max
Mean ± SD
Median
p
Age of Diagnosis (Year)
No
26
3
17
12,6 ± 3
13
0,79
Yes
14
8
17
12,9 ± 2,8
13,5
Duration of disease (month)
No
26
10
100
34,9 ± 19,8
31
0,69
Yes
14
11
71
37,4 ± 16,8
42
SLICC
No
26
0
3
0,4 ± 0,8
0
0,59
Yes
14
0
2
0,5 ± 0,7
0
SLEDAI
No
26
0
10
3,1 ± 3,2
2
0,62
Yes
14
0
8
1,8 ± 2,5
1
Age at onset of the disease, duration of the disease, SLICC and SLEDAI scores did
not differ between the carrier and non-carrier groups. Hepatic involvement was found
to be more frequent in MEFV mutation carriers (p = 0.037). There was no difference
regarding fever, hematologic involvement, renal involvement, serositis, neuropsychiatric
involvement, mucocutaneous findings, and vascular involvement in between the two groups.
Conclusion: In conclusion, we have seen that MEFV carrier rate was high in SLE patients.
But we did not observe any differences in both clinical findings and disease damage
in SLE patients with MEFV variant carriers except for hepatic involvement.
Disclosure of Interest: None Declared
P141 Epidemiology, clinical characteristics and therapy approaches of a retrospective
cohort of pediatric systemic lupus erythematosus in a tertiary centre
Rosa M. Alcobendas, Sara Murias, Agustin Remesal, Amelia Munoz Calongue
Pediatric Rheumatology, university hospital La Paz, Madrid, Spain
Correspondence: Rosa M. Alcobendas
Introduction: Systemic lupus erythematosus (SLE) is a chronic autoimmune disease,
potentially severe, with broad clinical spectrum, which can affect multiple organs
and systems.
Objectives: To analyze the initial manifestations, laboratory examinations and therapeutic
approaches of patients diagnosed with childhood onset systemic lupus erythematosus
(c-SLE) followed in a tertiary hospital in the last 14 years.
Methods: Retrospective chart review. Inclusion criteria were: children under 18 years
diagnosed with c-SLE between January 2003 and January 2017.
Results: During the study period, 38 patients were identified (ratio female/male:
3/1). The mean age at the onset of disease was 11.5 years (range 6-17). All had caucasic
origin, except 5 coming from South America, 2 from India and 1 from Africa. Onset
of the disease took place in spring in 22 (58%) patients, while in 10 (26%) patients
onset was in summer, 5 (13%) in autumn and only one (3%) in winter season.
The most frequently clinical manifestations found at the debut were cutaneous involvement
(66%, predominantly in the form of a malar rash), renal (65%) and joint (60%, 48%
arthralgia and 52% polyarthritis). Other manifestations were fever (50%), cytopenias
(39%), asthenia (36%), serositis and neurological clinic (both 26%) and oral aphthosis
(23%). Among the neurological manifestations, 4 patients showed bradypsychia, 3 headache,
2 seizures and 1 manifested a paralysis of the sixth cranial nerve. Only 1 patient
presented macrophage activation syndrome after primoinfection by Ebstein Barr Virus.
During the study period, no deaths ocurred.
Ten patients also had some other associated autoimmune disease: 6 hypothyroidisms,
2 IgA deficiency, 1 vitiligo and 1 celiac disease. No case of diabetes mellitus was
identified.
Regarding immunology, in all cases, positive antinuclear antibodies (ANA) were detected,
although with variable titers (1/80 - 1/5120). Of the 25 patients who presented renal
disease at the onset, 19 associated Anti-dsDNA antibodies positive at the initial
time of the determination. Although antibodies related to antiphospholipid syndrome
(APS) (anticardiolipin, anti-2glycoprotein and lupus anticoagulant) were detected
in 12 patients (32%), only two developed associated clinical manifestations (both
deep vein thrombosis in the lower limbs).
Regarding treatment, all patients required corticosteroids. Therapy with acetylsalicylic
acid was indicated in all patients with APS-associated immunology. Only 6 patients
received treatment with corticosteroids and hydroxychloroquine exclusively. Nineteen
(50%) patients initially received azathioprine therapy, being necessary to switch
to mycophenolate mofetil for lack of response in eleven, receiving the last treatment
20 patients finally (52%). Eighteen patients (47%) received cyclophosphamide therapy,
16 of them as a consequence of their renal involvement. In addition, biologic therapy
(rituximab and belimumab, respectively) was used in two multirefractory patients.
Conclusion: As widely already reported, SLE is a disease that affects predominantly
women. Moreover, as it has been previously described in the literature the most frequently
initial manifestations found in c-SLE are cutaneous, renal and articular. However,
a large variability of onset symptoms exists, thus c-SLE should be ruled out in patients
with multisystemic involvement.
Disclosure of Interest: None Declared
P142 Histological grading of lupus nephritis is related to early change in growth
parameters.
Yuri A. Arguello1, Giovanni Filocamo1, Sofia Torreggiani1, Valentina Litta Modigliani1,
Giani Marisa1, Giovanni Montini1
1Medicine and Surgery Faculty, Università degli Studi di Milano, Milan, Italy
Correspondence: Yuri A. Arguello
Introduction: Childhood Systemic Lupus Erythematosus (cSLE) is a multisystemic chronic
autoimmune disease characterized by a wide spectrum of clinical manifestations. Renal
involvement is one of the most common manifestations of cSLE, reported in 40-80% of
patients. Growth failure and delayed puberty are features of cSLE, caused by long
term disease activity, and side effects of drugs, especially corticosteroids.
Objectives:
To assess the early influence of SLE Lupus Nephritis disease and treatment on growth
parameters in children.
Methods: Patients diagnosed with cSLE in a tertiary care center in the past 22 years,
with kidney biopsy-proven Lupus Nephritis were included in our study. Patients were
excluded if incomplete data were available. The WHO classification was considered
to evaluate histological findings. Patients were divided by histological class in
two groups: the mild group (Class II-III) and the severe group (Class IV-V).
Height (cm) and Weight (kg) were measured with type of stadiometer specified (Harpenden,
wall-mounted). BMI (Body Mass Index) was calculated as weight (kg) divided by height
(meter) squared. We assessed the anthropometric parameters using Atlanta 2000 curves.
Student t test has been calculated for continuous variables to compare the two groups.
In all analyses, P < 0.05 was taken to indicate statistical significance.
Results: From 1994 to 2016, 45 children with lupus nephritis (LN) were biopsied. 15
of them presented incomplete clinical data and were excluded. Female-to-male ratio
was 3:1., the mean age at onset was 11.5 ± 3.1 years. The most common class of Lupus
Nephritis was considering WHO classification class IV (40%), followed by class III
(36.7%), II (16.7%) and V (6.7%). We compared all parameters (height, weight, BMI
percentiles) when first renal biopsy was performed and after 12 months.
Conclusion: This study compared patients with mild and severe histological assessed
LN in the first year of disease. Considering height percentile, mild LN patients didn’t
have a substantial growth speed deflexion, while severe LN patients had a mild decrease
even in the first year of disease. Comparing weight percentiles, we observed in both
groups an increase of weight, more accentuated in severe LN patients.
The BMI percentile of patients with mild LN didn’t register a significant mean gain,
whereas severe LN patients had a statistical relevant gain of BMI percentile after
1 year (p value 0.027)
A higher kidney-biopsy grade seems to be related to early change in growth parameters,
even if statistical significativity was reached only for BMI.
Data collection is still ongoing in order to define the influence of the treatment
performed and to define if early change in growth parameters is a related to the long
term growth disturbance.
Trial registration identifying number:
Disclosure of Interest: None Declared
P143 Is abnormality of lipid profile associated with more severe histological findings
at renal biopsy in children with lupus nephritis ?
Francesco Baldo1, Valentina Litta-Modignani1, Sofia Torreggiani1, Carlo Virginio Agostoni1,
Marisa Giani1, Giovanni Montini1, Giovanni Filocamo1
1Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy
Correspondence: Francesco Baldo
Introduction: Childhood Systemic Erythematosus Lupus (cSLE) is a severe multisystem
autoimmune disease. Renal involvement is a major cause of morbidity and mortality
in cSLE. Serum triglyceride, total cholesterol, low density lipoprotein (LDL) and
apolipoprotein B (apoB) concentrations were reported significantly higher in patients
with lupus nephritis (LN). It is unclear if abnormality in lipid profile is related
to the severity of renal function, the steroid therapy or both.
Objectives: To evaluate the lipid profile in children with Lupus Nephritis (LN) at
onset and after one year of treatment and to investigate if different lipid profile
can be related to the severity of renal involvement.
Methods: We performed a retrospective analysis of children with cSLE and nephritis
confirmed at renal biopsy, followed since 1994 to 2016 in a single tertiary care center.
Lipid profile (total cholesterol, LDL, HDL and triglycerides), serum albumin level
and proteinuria were researched at disease onset (T1) and after one year of disease
duration (T2).
Proteinuria was measured as the quantity of protein in a 24-hour urine collection
test, alternatively, the concentration of protein in the urine was reported as protein/creatinine
ratio.
The WHO classification of LN was used to grade histological findings.
Renal biopsy findings were grouped into two categories: mild (for class I-III) and
severe (class IV-VI).
Dependent T test was performed to evaluate the differences between the disease onset
and the second evaluation. Independent T test was used to compare the results between
mild and severe bioptic classes. P < 0.05 was taken to indicate statistical significance.
Results: From 1994 to 2016, 45 children with lupus nephritis (LN) were biopsied. 15
of them presented incomplete clinical data and were excluded. In the 30 patients enrolled
in the study, the female-to-male ratio was 3:1, the mean age at onset was 11.5 ± 3.1 years.
The mean disease duration since cSLE onset until renal biopsy was 10 and 19 months
for mild and severe involvement respectively.
Patients were distributed among the histological classes as follows: Class II: 5 patients
(16.7%), Class III: 11 patients (36.7%), Class IV: 12 patients (40%) and Class V:
2 patients (6.7%).
Daily proteinuria resulted 672 ± 550 mg/die for mild class and 2475 ± 3737,5 g/die
for severe class. The urine protein/creatinine ratio resulted 1,08 ± 1,39 and 1,34 ± 1,19
for mild and severe class respectively, the difference was not significant.
Results are displayed in Table 40.
Table 40
(Abstract P143). See text for description
T1
T2
Mean ± (standard deviation)
Mild
Severe
Mild
Severe
Albumin (mg/dl)
3,4 (± 0,8)
3,7 ± (0,5)
4 ± (0,9)
3,7 ± (0,6)
Total cholesterol (mg/dl)
203,5 (± 68,5)
187,7 ± (55,5)
197,2 ± (51,4)
222,5 ± (52)
HDL-cholesterol (mg/dl)
57,4 (± 37,4)
39,9 ± (16,2)
69 ± (28,3)
52,5 ± (11,4)
LDL-cholesterol (mg/dl)
102,6 (± 30,1)
130,2 ± (32,5)
127,5 ± (40,3)
124,8 ± (33,5)
Triglycerides (mg/dl)
164,7 (± 116,2)
178,5 ± (163,4)
129 ± (39,3)
172,1 ± (99)
Conclusion: Total cholesterol level at onset resulted higher in patients with milder
renal disease, even if dyslipoproteinemia resulted more significant in the severe
group because of an higher level of LDL and triglycerides. After one year of disease
duration the differences in lipid profile between the two groups became less relevant.
Disclosure of Interest: None Declared
P144 Clinical and immunological characteristics of childhood-onset systemic lupus
erythematosus patients treated with rituximab
Alina Lucica Boteanu, Maria Angeles Blazquez Cañamero, Adela Alia Jimenez, Sandra
Garrote Corral, Maria Jesus García Villanueva, Mariluz Gamir Gamir
Rheumatology, University Hospital Ramon Y Cajal, Madrid, Spain
Correspondence: Alina Lucica Boteanu
Introduction: Systemic lupus erythematosus (SLE) is an autoimmune disease that is
more severe in pediatric population than in adults. Biological therapy with anti-CD20
(rituximab) is an option in patient that do not respond to conventional therapy.
Objectives: The aim of this study is to determine the clinical and immunological response
in 9 patients with childhood-onset systemic lupus erythematosus (cSLE) that received
treatment with rituximab in a third level hospital.
Methods: This is a retrospective observational study. 9 patients treated with Rituximab
between November 2007 and October 2016 were included and their medical records were
reviewed. The response to treatment at 6 months and one year after the first infusion
of Rituximab were assessed. Patients with overlap syndromes were excluded. All patients
fulfilled four or more of the 1982 revised American College of Rheumatology criteria
for the diagnosis of SLE (< 16 years).
Results: Nine pediatric patients with SLE treated with rituximab were included, all
of them were female. The age at diagnosis of SLE was a mean of 15,22 years. The mean
time duration of disease was 87,55 months (5-255 m). 7 patients were caucasians. Rituximab
was indicated in 6 patients with class IV of lupus nephritis (LN) 1/9 with class III
LN, 1/9 with severe cutaneous lupus, and with severe hematological manifestations
in 1 case (haemolytic anemia). In addition, 6/9 patients had mucocutaneous and articular
manifestations. The disease activity of all patients was assessed using SELENA-SLEDAI
index pre rituximab infusion, the mean was 17,11 (8-33). All patients had low level
of complement C3 and C4 and 8/9 increased anti-DNA. In 8/9 patients Rituximab was
used as a rescue treatment and in a single case as a first line. 3/6 patients with
renal involvement were previously treated with cyclophosphamide (CF) iv and mycophenolate,
2/6 CF. In case of cutaneous involvement the previous treatment was methotrexate,
azathioprine (AZA) and dapsone and in case of hemolytic anemia was AZA.The treatment
protocol was 1 gram x 2 (1 cycle) in 7/9 patients, 375 mg/m2x 4 in 1/9 cases and 600 mg
monthly for 5 months in the case of hemolytic anemia. Five patients received more
than 1 cycle. After the administration of Rituximab, the SELENA-SLEDAI activity index
was 4.5 points. At 6 months a complete response was obtained in the case of hematological
and cutaneous manifestations, in 2 cases of lupus nephritis (proteinuria <0.5 g/day)
and partial response was obtained in 2 cases. Data were not analyzed in 2 patients
(death and less than 6 months of the first dose of rituximab). Patients with partial
response and lack of response achieved complete response at 12 months. 2/9 patients
had side effects (Rituximab pneumonitis in 1 case and infections in 2 cases). Mortality
was 11.11% (1/9 patients, per infection and lupus activity, SLEDAI pre rituximab = 33)
Conclusion: In our study, although it consisted of few patients, it was objected that
Rituximab therapy in patients with cSLE is effective, reduces lupus activity index,
especially in cases of renal, cutaneous and hematologic involvement, that don’t respond
to conventional therapy. It may be consider in the future as an effective alternative
treatment at first line treatment.
Disclosure of Interest: None Declared
P145 Panniculitis in childhood-onset systemic lupus erythematosus: a multicentric
cohort study
Lucia M. Campos1, Mônica Verdier 2, Pedro Anuardo 2, Natali Gormezano 1, Ricardo Romiti
3, Nadia Aikawa 2, Rosa Pereira 2, Maria T. Terreri 4, Claudia Magalhães 5, Juliana
Ferreira 1, Marco Silva 1, Mariana Ferriani 1, Ana P. Sakamoto 4, Virginia Ferriani
6, Maraísa Centeville 7, Juliana Sato 5, Maria C. Santos 8, Eloisa Bonfá 2, Clovis
Silva 1
1Paediatric Rheumatology Unit, Children’s Institute, University of São Paulo, São
Paulo, Brazil 2Rheumatology Department, University of São Paulo, São Paulo, Brazil
3Dermatology Department, University of São Paulo, São Paulo, Brazil 4Paediatric Rheumatology
Unit, Universidade Federal de São Paulo, São Paulo, Brazil 5Paediatric Rheumatology
Unit, Faculdade de Medicina de Botucatu, Botucatu, Brazil 6Paediatric Rheumatology
Unit, Ribeirão Preto Medical School – University of São Paulo, São Paulo, Brazil 7Paediatric
Rheumatology Unit, University of Campinas, Campinas, Brazil 8Paediatric Rheumatology
Unit, Santa Casa de Misericórdia de São Paulo, São Paulo, Brazil
Correspondence: Lucia M. Campos
Introduction: Lupus erythematosus panniculitis (LEP) is a rare form of chronic cutaneous
lupus erythematosus described from 2% to 5% of adult SLE. In cSLE, LEP data are limited
to few case reports
Objectives: To evaluate prevalence, clinical manifestations, laboratory abnormalities,
treatment and outcome in a multicenter cohort of childhood-onset systemic lupus erythematosus(cSLE)
patients with and without panniculitis.
Methods: Panniculitis was diagnosed due to painful subcutaneous nodules and/or plaques
in deep dermis/subcutaneous tissues and lobular/mixed panniculitis with lymphocytic
lobular inflammatory infiltrate in skin biopsy. Statistical analysis was performed
using Bonferroni correction(p < 0.004).
Results: Panniculitis was observed in 6/847(0.7%) cSLE. Painful subcutaneous erythematosus
and indurated nodules were observed in 6/6 panniculitis patients and painful subcutaneous
plaques in 4/6. Generalized distribution was evidenced in 3/6 and localized in upper
limbs in 2/6 and face in 1/6. Histopathology features showed lobular panniculitis
without vasculitis in 5/6(one of them had concomitant obliterative vasculopathy due
to antiphospholipid syndrome) and panniculitis with vasculitis in 1/6. Comparison
between cSLE with panniculitis and 60 cSLE without panniculitis with same disease
duration [2.75(0-11.4) vs. 2.83(0-11.8) years,p = 0.297], showed higher frequencies
of constitutional involvement (67% vs. 10%,p = 0.003), leukopenia (67% vs. 7%,p = 0.002)
and median C-reactive protein (10.5 vs. 0.5 mg/L,p = 0.001). Cutaneous atrophy and
hyperpigmentation occurred in 83% of patients.
Conclusion: Panniculitis is a rare skin manifestation of cSLE occurring in the first
three years of disease with considerable sequelae. The majority of patients have concomitant
mild lupus manifestations.
Disclosure of Interest: None Declared
P146 Prevalence of ena and anti cardiolipin antibodies in different classes of lupus
nephritis.
Giancarla Di Landro, Francesco Baldo, Valentina Litta Modignani, Marisa Giani, Giovanni
Montini, Carlo Virginio Agostoni, Giovanni Filocamo
Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy
Correspondence: Giancarla Di Landro
Introduction: Childhood Systemic Lupus Erythematosus (cSLE) is a rare autoimmune disease.
Lupus nephritis (LN) is one of the most serious manifestations of cSLE, associated
with poor prognosis and reported in 40-80% of patients at onset disease. Extractable
nuclear antigen (ENA) antibody can be detected in SLE and some of them are related
to a distinct clinical subset of disease, independently of their frequency. Autoantibodies
against Smith antigen (Sm) are reported in high prevalence in patients with active
LN. It is unclear if the prevalence of ENA autoantibodies is related to the severity
of renal involvement.
Objectives: To evaluate if ENA antibodies positivity in early stage of SLE disease
is associated with the development of more severe disease, assessed by histological
finding.
Methods: We performed a retrospective analysis of children with cSLE and nephritis
confirmed by renal biopsy, followed since 1994 to 2016 in a single tertiary care center.
Clinical features, renal involvement and biopsy findings were collected from patients
files as well as the positivity of ENA antibodies (Anti-RNP, Anti-Sm, anti-Ro/SS-A,
anti-La/SS-B, anti-Scl-70, anti-Jo1, anti-nucleosome, anti-histone), Lupus Anti Coagulant
(LAC) test and Anti- cardiolipin antibodies (ACL).
The WHO classification of LN was used to grade histological findings.
Renal biopsy findings were grouped into two categories: mild (for class I-III) and
severe (class IV-VI).
Chi-Squared Test was used to to determine significant relationship between categorical
variables. P < 0.05 was taken to indicate statistical significance.
Results: From 1994 to 2016, 45 children with LN were biopsied. In 22 of them ENA screening
was not reported in clinical records and they were excluded from the analysis. Between
the 23 remaining patients, 12 were included in the mild group, the remaining patients
in the severe group; 1 from the severe class had record of ENA positivity, but not
of the specif pattern.
In the 23 patients enrolled, the female-to-male ratio was 2,6:1, the mean age at onset
was 11.75 ± 3.2 years. The mean disease duration up to renal biopsy was 15 and 19 months
for mild and severe involvement respectively.
ACL and LAC screening record were found for 21 and 20 patients respectively. LAC was
present in 19,1% of patients and IgM and IgG anti-cardiolipin were present in 40%
of patients. ENA were positive in 13 out 23 patients (56.5%). Overall the patients
enrolled, the most common positive ENA subtypes were, anti-Ro/SS-A (38%), followed
by anti-Sm and anti-RNP(22,7%). The prevalence of ENA in patients with mild and severe
renal involvement are reported in Table 41.
Table 41
(Abstract P146). See text for description
AUTOANTIBODIES
MILD
SEVERE
p value
ENA:
7
63,63%
6
50,00%
0,509
anti-RNP
3
27,27%
2
18,18%
0,611
anti-Sm
2
18,18%
3
27,27%
0,611
anti-Ro/SS-A
5
45,45%
4
36,36%
0,665
anti-La/SS-B
1
9,09%
3
27,27%
0,269
Scl-70
1
9,09%
1
9,09%
1
Anti-nucleosome and anti-histone
1
9,09%
0
0
NS
LAC
2
20,00%
2
18,18%
0,91
IgM and IgG aCL > 10
4
40,00%
4
40,00%
1
Conclusion: ENA autoantibodies are present in about half of the patients with LN.
The prevalence of ENA, ACL and LAC does not differ significantly in patients with
different grade of renal involvement.
Disclosure of Interest: None Declared
P147 Juvenile systemic lupus erythematosus: clinical and immunological patterns of
disease expression in a cohort of Mexican children.
Sofia Osorio, Andrés Rodríguez, Rocio Maldonado, Enrique Faugier, Talia Diaz, Yuridiana
Ramirez, Luis Aparicio, Maria Braña
Pediatric Rheumatology, Hospital Infantil de Mexico Federico Gomez, Ciudad de mexico,
Mexico
Correspondence: Talia Diaz
Introduction: Juvenile systemic lupus erythematosus is a chronic multisystem autoimmune
disease of unpredictable course and prognosis. It manifests with a wide spectrum of
clinical and immunological abnormalities. To date, no literature has been described
about the most frequent clinical manifestations in mexican children with this disease.
Objectives: To define the pattern of disease expression in subjects with juvenile
systemic lupus erythematosus in Mexico and compare it with what has been reported
in other series, in addition to gain a better understanding of juvenile systemic lupus
erythematosus in mexican children.
Methods: The features of 150 patients with juvenile systemic lupus erythematosus who
had disease onset before the age of 18 years in the Children’s Hospital of Mexico < <Federico
Gómez>>, were retrospectively analysed. Demographic, clinical and laboratory manifestations,
therapy were assessed.
Results: A cohort of 150 patients with a mean age at diagnosis of 11.3 ± 3.13 years
and a mean period of follow-up of 3.34 ± 2.14 years were analyzed. One hundred thirty-one
(87.3%) patients were female. The most common manifestations were mucocutaneous (74.7%),
hematological (56%) and musculoskeletal (39.3%) abnormalities. Upon diagnosis, renal
damage was found in 56 patients (37.3%), of which 28 (18.3%) were diagnosed with lupus
nephritis. Antinuclear and double-stranded anti-DNA antibodies were positive in most
patients, 96.7% and 77.3%, respectively; antiphospholipid antibody positivity was
observed in 40.7%. During follow-up, immunosuppressive management consisted of azathioprine
in 54%, cyclophosphamide in 66.6%, mycophenolate mofetil in 31%, a combination of
more than one of the above in 56.7%, being the most frequent azathioprine and cyclophosphamide;
22 individuals (14%) were only treated with hydroxychloroquine as an immunomodulator.
Conclusion: This study suggests that in our patients the clinical and laboratory features
observed were similar to juvenile systemic lupus erythematosus patients from other
series.
Disclosure of Interest: None Declared
P148 Neonatal lupus - case series of a tertiary hospital
Ana R. Teixeira 1, Raquel Ferreira1, 2, Mariana Rodrigues 3, 4, Francisca Aguiar 1,
2, Iva Brito 2, 5
1Faculty of Medicine, University of Porto, Porto, Portugal 2Rheumatology, Centro Hospitalar
de São João, Porto, Portugal 3Pediatrics, Centro Hospitalar de São João, Porto, Portugal
4Pediatrics, Faculty of Medicine, University of Porto, Porto, Portugal 5Medicine,
Faculty of Medicine, University of Porto, Porto, Portugal
Correspondence: Raquel Ferreira
Introduction: Neonatal Lupus (NL) is a rare condition caused by the transplacental
passage of autoantibodies anti-Ro/SSA, anti-Sa/SSB and/or anti-U1 RNP antibodies into
the fetal circulation which affects newborns. The mother may be asymptomatic or have
a known autoimmune disorder, like Sjögren syndrome or Systemic Lupus Erythematosus.
Clinical manifestations are diverse and have varying severity, the most common being
cutaneous and cardiac.
Objectives: Identify NL cases, describe the clinical manifestations and its course,
evaluate the presence of the most important antibodies and the history of mother’s
disease.
Methods: Retrospective review of case files of all patients diagnosed with NL in the
last eight years, admitted to the Neonatal Unit and/or followed at the outpatients
department of a tertiary teaching hospital.
Results
The authors present a case series which includes eight cases diagnosed with NL and
a brief review of the literature (Table 42).
Table 42
(Abstract P148). Clinical and Laboratory Characteristics; F, Female; M, Male; SS,
Sjögren Syndrome; SLE, Systemic Lupus Erythematosus; NE, Not Evaluated
Case 1
Case 2
Case 3
Case 4
Case 5
Case 6
Case 7
Case 8
Gender
F
F
M
F
F
F
M
M
Maternal history
SS
LES
LES
LES
SS
SS
SS, LES
SS
Dermatological involvement
No
No
No
No
No
No
Yes
Yes
Cardiac involvement
Yes
Yes
Yes
Yes
Yes
Yes
Yes
No
Other organs involvement
No
Yes
Yes
No
No
No
No
No
Child's autoantibodies
NE
Anti-SSA and SSB
Anti-SSA
NE
NE
Anti-SSB
Anti-SSA and SSB
NE
Maternal autoantibodies
Anti-SSA
Anti-SSA and SSB
Anti-SSA and SSB
Anti-SSA
Anti-SSA and SSB
Anti-SSA and SSB
Anti-SSA and SSB
Anti-SSA and SSB
Conclusion: Underdiagnosis might explain the reduced number of patients identified.
The positivity of anti-Ro/SSA and anti-Sa/SSB seems to be associated with higher prevalence
of neonatal cardiac manifestations. Early detection of this condition is paramount
since treatment may reverse lower grade HB. Also, adequate maternal treatment can
reduce the likelihood of NL.
Disclosure of Interest: None Declared
P149 Gender differences in systemic lupus erythematosus presentation and treatment
at paediatric rheumatology department, Sofia, Bulgaria for a period of 4 years (2013-2017)
Margarita Ganeva, Stefan Stefanov, Albena Telcharova, Dimitrina Mihaylova, Vanya Kostova,
Katya Temelkova, Tanya Andreeva
Paediatric Rheumatology, University Children's Hospital, Medical University Sofia,
Sofia, Bulgaria
Correspondence: Margarita Ganeva
Introduction: The prevalence of systemic lupus erythematosus (SLE) is known to be
lower in boys than in girls. The female-to-male ratio of paediatric SLE (pSLE) is
4.5-5:1. Much controversy surrounds the differences in disease manifestation in both
sexes.
Objectives: The aim of this retrospective study is to compare the gender differences
in the age of onset, time to diagnosis, clinical and laboratory manifestations and
medication use in pSLE at presentation.
Methods: Seventeen patients (11 boys and 6 girls) with newly diagnosed pSLE admitted
to the Paediatric Rheumatology Department, Sofia, Bulgaria for a period of 4 years
(2013-2017) were included in the study. The medical records of all patients were retrospectively
reviewed. Patients fulfilled the American College of Rheumatology (ACR) SLE classification
criteria.
Results: The female-to-male ratio in the described cohort of patients is reversed
- 3.6:6.4. The mean age of onset in male pSLE patients was 12.59 yrs (5.83-17.83 yrs)
with mean time to diagnosis of 2 ± 1.3 months. The mean age of onset in female patients
was 14.06 yrs (7.5-16.33 yrs) with mean time to diagnosis – 3.5 ± 3.99 months. No
statistically significant differences were found between boys and girls with regard
to mean age of onset, mean time to diagnosis and clinical and laboratory manifestations
of pSLE. The most common clinical sign at presentation in boys was arthritis (9/11;
81.8%), followed by renal involvement (7/11; 63.6%). Girls presented most frequently
with malar rash (5/6; 83.3%), followed by arthritis (3/6; 50%). Renal involvement
at presentation was detected in only one of the girls (1/6; 16.6%). Serositis was
noted as presenting manifestation in one girl (1/6; 16.6%) and was not observed in
any of the boys. Vascular thrombosis was seen in one boy (1/11; 9.1%). No neurological
manifestation was observed in both groups. The most frequently detected hematological
manifestation in the male group was lymphopenia (7/11; 63.6%) with leucopenia being
the most common presenting laboratory sign in the female group (5/6; 83.3%). The least
commonly observed laboratory sign in both groups was Coombs-positive autoimmune hemolytic
anemia. Positive anti-dsDNA antibodies were detected in 90.9% of the boys and 100%
of the girls. Antinuclear antibodies were positive in 100% of the boys and 83.8% of
the girls. Low complement levels were seen in 81.8% of the males and 83.8% of the
girls. All patients received corticosteroid therapy with intravenous pulse therapy
performed in one girl and three boys. Cyclophosphamide for the initial 6-month induction
period was used in 50% of the girls and 63.6% of the boys. Azathioprine was given
to one girl and two boys. Chloroquine was used in 33.3% of the girls and 18.1% of
the boys.
Conclusion: A male predominance of SLE has been observed. The mean age at disease
onset and mean time interval from disease onset to diagnosis did not differ in male
and female patients. The observed clinical and laboratory manifestations were also
comparable between the two groups. Arthritis and renal involvement were found to be
the commonest clinical manifestation among boys. Renal involvement favored males,
however the result was not statistically significant.
Disclosure of Interest: None Declared
P150 Differences of the metabolome of autoimmune diseases
Anna E. A. Glaser1, Angela Midgley1, Helen L. Wright2, Marie M. Phelan3,4, Matthew
Peak5, Michael W. Beresford1,5
1Department of Women’s and Children’s Health, University of Liverpool, Liverpool,
United Kingdom 2Department of Biochemistry, University of Liverpool, Liverpool, United
Kingdom 3Institute of Integrative Biology, University of Liverpool, Liverpool, United
Kingdom 4HLS Technology Directorate, University of Liverpool, Liverpool, United Kingdom
5Department of Paediatric Rheumatology, Alder Hey Children's NHS Foundation Trust,
Liverpool, United Kingdom
Correspondence: Anna E. A. Glaser
Introduction: Both juvenile-onset systemic lupus erythematosus (JSLE) and juvenile
idiopathic arthritis (JIA) are autoimmune diseases which can affect multiple targets
in different organs of the body. Metabolomics studies are a comprehensive way to investigate
reactions and interactions of different, potentially important cells contributing
to the immunopathogenesis of these disorders.
Objectives: To compare the metabolite profiles of serum and urine of patients with
JIA and JSLE as well as non-inflammatory paediatric control patients.
Methods: Serum and urine samples were obtained from children (diagnosed <17 years
of age) with JIA (n = 5 for serum, n = 4 for urine), with JSLE (n = 10, n = 8) and
from paediatric healthy controls (n = 9, n = 4). The samples were run at 310 K for
serum and at 300 K for urine on a Bruker 600 MHz AvanceIII with CryoProbe. Resulting
1H NMR spectra were analysed with Topspin, Chenomx NMR Suite and R.
Results: In serum global changes in spectra analysed via Partial Least Squares Discriminant
Analysis (PLSDA) revealed variation between JIA, JSLE and control patients. While
JSLE and control patients were separated, the JIA patients fell in-between and a clear
clustering was therefore not possible.
Cross-validation accuracy for this PLSDA was 0.67 with a robustness (R2) 0.88 and
a prediction (Q2) of 0.25 with optimal model using four linear discriminants. Univariate
analysis using ANOVA showed that Acetoacetate was significantly higher (p < 0.05)
in JIA patients compared to healthy controls (1.8-fold) and JSLE patients (1.8-fold).
Alanine on the other hand was significantly lower (p < 0.05) with a 0.8-fold change
in JIA patients compared to healthy controls and JSLE patients. Pyruvate on the other
hand was significantly increased (p < 0.05) in JSLE patients compared to JIA patients
(1.4-fold) and healthy controls (1.3-fold).
These differences in the serum indicate that these diseases utilize different pathways
to generate energy.
In urine, PLSDA of the spectra resulted in a clear separation of the three groups
with a cross-validation accuracy of 0.75 an R2-value of 0.95 and Q2–value of 0.38
with the optimal model using three linear discriminants. Metabolites contributing
to this separation included hippurate, taurine, citrate and 4-hydroxybenzoate.
Conclusion: Variation in metabolic profiles was observed in JIA and JSLE patients
compared to paediatric healthy controls. Analysis of serum and urine indicate urine
to be a better biofluid sample to distinguish between diseases. Investigating changes
of metabolites in serum samples gave us indications of which pathways are differentially
regulated between the three conditions. Further analyses are being undertaken to investigate
which pathways are regulated differently between the two diseases.
Disclosure of Interest: None Declared
P151 Primary antiphospholipid syndrome in children – case series from Chennai, South
India
Abstract withdrawn
P152 Novel urine biomarkers for the assessment of pediatric systemic lupus erythematosus
nephritis
Artemis Koutsonikoli1, Maria Trachana1, Evangelia Farmaki1, Vasiliki Tzimouli1, Polyxeni
Pratsidou-Gertsi1, Nikoleta Printza1, Alexandros Garyphallos2, Vasiliki Galanopoulou3,
Florence Kanakoudi-Tsakalidou1, Fotios Papachristou1
1First Department of Pediatrics, Aristotle University of Thessaloniki, Hippokration
Hospital, Thessaloniki, Greece 2Fourth Department of Internal Medicine, Aristotle
University of Thessaloniki, Hippokration Hospital, Thessaloniki, Greece 3Department
of Rheumatology, Papageorgiou Hospital, Thessaloniki, Greece
Correspondence: Artemis Koutsonikoli
Introduction: Novel urine biomarkers, with a proven specificity for pediatric Lupus
Nephritis (pLN), will facilitate the non-invasive and reliable assessment of the disease
course and the subsequent choice of targeted treatment.
Objectives: To explore the relation of urine Neutrophil Gelatinase-Associated Lipocalin
(NGAL) and High-Mobility Group Box 1 (HMGB1) protein to: (a) the presence of pLN and
(b) the pLN activity, in a homogeneous Caucasian pediatric Systemic Lupus Erythematosus
(pSLE) population from Northern Greece.
Methods: Thirty-three urine samples were collected from 17 pLN patients and 12 urine
samples from 12 pSLE patients without pLN. The pLN activity was assessed using the
renal domain of the Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2 K).
The biomarkers’ levels were determined by ELISA.
Results: The levels of the urine NGAL were higher in the pLN patients [median (IQR):
33.46 (19.37-84.7) pg/ml] as compared to the pSLE patients without pLN [14.1 (10.24-21.45)
pg/ml] (p = 0.001) and were correlated with the pLN activity (rho = 0.457, p = 0.008).
The levels of the urine HMGB1 were higher in the pLN patients [5.55 (4.17- 6.54) ng/ml]
as compared to the pSLE patients without pLN [3.81 (2.46-5.1) ng/ml] (p = 0.034) and
were correlated with the pLN activity (rho = 0.685, p < 0.001).
Conclusion: These preliminary findings indicate that the combination of the urine
NGAL and HMGB1 levels may serve as biomarkers of pLN presence in pSLE patients, and
may be considered as another non-invasive tool for the assessment of pLN activity.
Further studies in Caucasian patients are needed to verify these results.
Disclosure of Interest: None Declared
Treatment
P153 Smart technologies to improve health outcomes in juvenile idiopathic arthritis
Andrea Coda1, Dean Sculley1, Derek Santos2, Xavier Girones3, Derek Smith4, Joshua
Burns5, Keith Rome6, Jane Munro7, Davinder Singh-Grewal8
1School of Health Sciences, The University of Newcastle, Ourimbah, Australia, 2School
of Health Sciences, Queen Margaret University, Edinburgh, United Kingdom, 3Faculty
of Health Sciences, Manresa University, University of Vic-Central University of Catalonia,
University of Barcelona), Manresa, Spain, 4School of Health Sciences, James Cook University,
Townsville, Australia 5 Allied Health (Paediatrics), The Children’s Hospital at Westmead
& the University of Sydney, Sydney, Australia, 6 Acting Director of Health & Research
Rehabilitation Institute, AUT University, Auckland, New Zealand, 7 Head of Rheumatology
Unit, Dept of General Medicine, Royal Children’s Hospital, Parkville - Victoria, Australia
8Paediatric Rheumatologists & Paediatrician Consultant, Sydney Children Hospitals
Network & Clinical A/Prof- The University of Sydney, Sydney, Australia
Correspondence: Andrea Coda
Introduction: Children and adolescents diagnosed with Juvenile Idiopathic Arthritis
(JIA) often exhibit lower physical activity level and poorer aerobic and anaerobic
exercise capacity when compared to their non-JIA counterparts. Mild intensity exercise
regimen has been proven to be safe in children with JIA and may produce significant
improvements in overall physical function. Inadequate adherence to the treatment prescribed
by paediatric rheumatologists, could also have a detrimental impact towards different
clinical outcomes and possibly increased disease activity. This includes symptoms
such as pain, fatigue, quality of life, longer term outcomes including joint damage,
as well as increase of healthcare associated costs. Low adherence to medications such
as methotrexate and biological-drugs remains a significant issue in paediatric rheumatology,
with evidence that less than half of the children with JIA are actually compliant
to their drug-therapy. The recent advances in smart technology resulting in a variety
of wearable user-friendly interactive devices may become a key solution to tackle
important challenges in JIA clinical management.
Objectives: The aim of this review was to explore the current use of modern interactive
technologies in the provision of health care
Methods: A litterature review was performed using MEDLINE, PUBMED and CINAHL. This
review focused in 4 main topics: monitoring symptoms and disease progression using
interactive technologies, adherence to prescribed medications using smart devices,
available app to encourage physical activity and data protection.
Results: The recent advances in smart technology resulting in a variety of wearable
user-friendly interactive devices may become a key solution to tackle important challenges
in JIA clinical management. Fully understanding the impact that JIA and treatment
complications have upon patients and their families has long been a challenge for
clinicians. Modern interactive technologies can be adapted to the individual requirements
and accessed directly in the hands or wrists of children with JIA. These secured networks
could be accessible 'live' at anytime and anywhere by the child, parents and clinicians.
Multidisciplinary teams in paediatric rheumatology may benefit from adopting these
smart devices to enhance the understanding in different aspects, such as: patient’s
biological parameters, symptoms progression, and adherence to drug-therapy, quality
of life, and participation in physical activities. Most importantly the use of interactive
technologies may also promote more timely clinical decisions, improve self-management
and parents active involvement with their child's disease. Paediatric rheumatology
research could also further advance from the use of these smart devices, as they would
enable real-time access to meaningful data to thoroughly analyse the disease-patterns
of JIA, such as pain and physical activity outcomes. Data collection that typically
occurs once every 1 or 3 months in the clinical setting could instead be gathered
every week, day, minute or virtually live online. Many limitations in wearing such
interactive technologies still exist and require further developments and investments.
Conclusion: Further studies in paediatric rheumatology are required to critically
evaluate the effectiveness and acceptability of already available apps in large number
of patients and to develop new devices utilizing valuable input and feedback from
patients, carers and clinicians. Finally, by embracing and adapting these new and
now highly accessible interactive technologies, clinical management and research progress
in paediatric rheumatology could be greatly advanced.
Trial registration identifying number: NA
Disclosure of Interest: None Declared
P154 Reduced-dose rituximab in treatment of pediatric rheumatic diseases
Nadina E. Rubio-Perez, Fernando Garcia-Rodriguez, Marcia D. Torres-Made, Manuel E.
de la O-Cavazos
Pediatric Rheumatology, Departamento de Pediatría, Hospital Universitario "Dr. José
E. González", UANL, Monterrey, Mexico
Correspondence: Fernando Garcia-Rodriguez
Introduction: Rituximab (RTX) response does not depend on its serum concentration,
so reduced doses (miniRTX) could be an alternative treatment in pediatric rheumatic
diseases (PRD), especially in low-income countries.
Objectives: To describe the outcome of a longitudinal series of PRD patients treated
with miniRTX.
Methods: A longitudinal, open-label, non-controlled, case series was conducted. We
enrolled all consecutive patients diagnosed with PRD in whom failure to standard therapy
was stablished. Treatment with miniRTX, defined as either 500 mg in a single dose
infusion or 100 mg a week during 4 weeks, were added to patients’ therapy. A 200 mg
dose were administered as maintenance treatment at 6 and 12 months after first dose
to those patients whom achieved a significant clinical response. Clinical outcome
were registered in every patient during a follow up of at least 18 months.
Results: Eight patients were included in this series, seven female, median age 14
(2 – 17) years old at the time of diagnosis and 18 (11 – 82) months of disease duration.
Most of the patients (seven) has juvenile systemic lupus erythematosus (JSLE) and
one patient presented with juvenile dermatomyositis (JDM).
Among JSLE patients, previous used treatments were azathioprine (3 patients), mofetil
mycophenolate (7 patients), and cyclophosphamide (5 patients) in different periods.
All those patients received corticosteroids (both orally and/or IV) and hydroxychloroquine.
Patient with JDM received corticosteroids, methotrexate, azathioprine, cyclosporine
A, and hydroxychloroquine prior to miniRTX.
Clinical manifestations presented in JSLE patients at the time of miniRTX administration
were hematological (5 patients), arthritis (4 patients), nephritis (4 patients), vasculitis
(2 patients), serositis (1 patient), secondary antiphospholipid syndrome (APL) and
neuropsychiatric (1 patient).
Most of the patients received 100 mg/week miniRTX scheme, while two received a single
dose (500 mg).
Two patients presented primary failure to therapy (one JSLE and JDM patient) so no
maintenance doses were administered. One patient with JSLE and APL presented initial
good response but a relapse were evident 12 months after initial administration. Five
patients completed the 18 months follow up with absence of JSLE signs and symptoms;
however, none of the patients completed an off-treatment remission criterion.
One patient presented recurrent ear infections and secondary immunodeficiency were
diagnosed attributable to miniRTX administration. Patient received complementary IVIG
with resolution and no other complications were presented in this series.
Conclusion: Comparative studies are needed to establish the usefulness of miniRTX
in PRD; however, the response in most of the patients of this small series was favorable.
Disclosure of Interest: None Declared
P155 Etanercept (ENBREL®) treatment retention in the sub-population of pediatric patients
from a retrospective cohort study using Canadian claims-level data
Majed Khraishi1, Brad Millson2, John Woolcott3, Heather Jones4, Lisa Marshall4
1Faculty of Medicine, Memorial University of Newfoundland, St. Johns, Canada; 2Health
Access and Outcomes, QuintilesIMS, Kanata, Canada; 3Inflammation and Immunology, Global
Outcomes and Evidence, Pfizer, Collegeville, PA, United States; 4Inflammation and
Immunology, Global Medical Affairs, Pfizer, Collegeville, PA, United States
Correspondence: Majed Khraishi
Introduction: Since its initial approval for the treatment of patients with moderate
to severe refractory rheumatoid arthritis (RA), etanercept (ETN; Enbrel®), a recombinant
fusion protein, has led the expansion of therapeutic options available for patients
with other inflammatory diseases.1 ETN was the first biologic approved for use in
the treatment of patients with polyarticular-course juvenile idiopathic arthritis
(JIA),2 and is now indicated in the JIA categories, extended oligoarthritis, enthesitis-related
arthritis, and psoriatic arthritis.3 Use of ETN in patients with JIA has seen significant
benefit in reducing disease symptoms4 and radiographic progression.5 There is evidence
from registry studies and real-world data sources that ETN is favored as a first-line
biologic therapy in clinical practice in patients with JIA;6,7 however, the factors
associated with long-term retention of ETN in this patient population have been little
explored.
Objectives: To evaluate retention rates up to 6 years in ETN-treated pediatric patients
in Canada.
Methods: A retrospective cohort study was conducted using longitudinal prescription
drug claims data from QuintilesIMS Private Drug Plan database (PDP), Ontario Public
Drug Plan database (OPDP), and Quebec Public Drug Plan database (RAMQ). Between 07/2008
and 06/2010, biologic-naïve patients (ie, patients with no biologic treatment in the
preceding 12 months) who initiated ETN, were identified and followed for 72 months.
Disease indications were inferred through patient drug history. 12-month retention
rates were evaluated in 1-year increments for all patients retained on therapy at
years 1, 2, 3, 4, 5, and 6 post initiation, and comparisons made to retention rates
in the first year with P-values reported. Two-proportion z-tests were made with reference
to year-1 retention; the Bonferroni method was used to counteract the problem of multiple
comparisons.
Results: The study identified 4528 ETN-treated patients (61% female, 85% rheumatic
diseases, and 15% psoriasis) across Canada, who initiated therapy during the selection
period. 65 (1.4%) were identified as pediatric patients (ie, age 2-12 years; 94% with
JIA) at the time of therapy initiation. The majority of patients were from Ontario
(48%) and insured by private drug plan. 12-month ETN retention rates for the pediatric
patients increased following their first year on therapy. 68% of patients were retained
at year 1; 12-month retention rates through years 2-6 are shown in the Table. Retention
rates for the corresponding periods in the adult population (>18 years) were: 66%,
79%, 82%, 84%, 83%, and 79%. A total of 23.1% (n = 15) of pediatric patients remained
on ETN treatment for the entire 72 months of the study.
Conclusion: Pediatric patients who were treated with ETN demonstrated higher retention
rates after the first year, particularly if they were maintained on ETN for more than
2 years. The sample size of pediatric patients in this study is relatively small.
Further analysis of the reasons for ETN treatment discontinuation in a larger sample
of pediatric patients may assist in identifying measures to support patients in maintaining
treatment to achieve sustained clinical benefit4 and quality of life.8
References: 1. Scott LJ. Drugs 2014;74:1379-1410; 2. Hinze C, et al. Nat Rev Rheumatol
2015;11:290-300; 3. Windschall D, et al. Clin Rheumatol 2015;34:61-9; 4. Giannini
EH, et al. Arthritis Rheum 2009;60:2794-804; 5. Nielsen S, et al. Clin Exp Rheumatol
2008;26:688-92; 6. Horneff G, et al. Arthritis Res Ther 2016;18:272; 7. Verazza S,
et al. Pediatr Rheumatol Online J 2016;14:68; 8. Klotsche J, et al. Arthritis Care
Res (Hoboken) 2014;66:253-62.
Disclosure of Interest: M. Khraishi Consultant for: Pfizer, Canada and Amgen, Canada,
B. Millson Employee of: Quintiles, J. Woolcott Shareholder of: Pfizer, Employee of:
Pfizer, H. Jones Shareholder of: Pfizer, Employee of: Pfizer, L. Marshall Shareholder
of: Pfizer, Employee of: Pfizer
Table 43
(Abstract P155). ETN treatment retention in pediatric patients (aged 2-12 years)
Year
Tracked Patients, n
Retained Patients, n
Retention Rate, %
P-Value
1
65
44
68
2
41
33
80
0.1501
3
31
28
90
0.0166
4
28
25
89
0.0290
5
25
19
76
0.4411
6
18
15
83
0.1952
P156 A case report of a pediatric patient with orbital IGG4-related disease
Anna Kozlova, Vasiliy Burlakov, Dmitriy Abramov, Garik Sagoyan, Anna Shcherbina
Immunology, Federal State Budgetary Institution "National Scientific and Practical
Center of Pediatric Hematology, Oncology and Immunology named after Dmitry Rogachev"
of the Ministry of Healthcare of the Russian Federation, Moscow, Russian Federation
Correspondence: Anna Kozlova
Introduction: IgG4-related disease (IgG4-RD) is a fibroinflammatory condition that
can affect essentially any organ.
Objectives: The disease shows similar histopathological findings across organs and
systems, and consist of a lymphoplasmacytic infiltrate enriched in IgG4-positive plasma
cells. Most patients with IgG4-RD respond at least partially to glucocorticoids, but
is it toxic therapy. Treatment protocols of IgG4-RD in children are not established.
Methods: We report a case of pediatric patient with orbital IgG4-related disease and
successful treatment JAK inhibitor – ruxolitinib.
Results: Thirteen years old boy has been suffering from hyperemia of the left eye
and edema of the eyelid. The MRI showed a lesion adjacent to the orbita. The child
underwent biopsy of the tumor, and the histologic examination revealed lymphoplasmacytic
iniltrates with fibrosis and vasculitis correlating with IgG4-related disease. Serum
IgG4 level was not elevated. Blood tests and acute phase reactants were normal. He
was started on JAK inhibitor therapy (ruxolitinib) with good effect. His tumor mass
of eyes changed from 25 to10mm for 2 months. The condition and quality of life of
the child became better. Adverse events were not noted.
Conclusion: In our case of IgG4-RD patient JAK inhibitor – ruxolitinib therapy was
highly effective and is a safe treatment modality but indications for therapy require
further investigation.
Disclosure of Interest: None Declared
P157 Optimum serum adalimumab levels in juvenile idiopathic arthritis according to
the response criteria
Berta Lopez1, M. Isabel Gonzalez1, Miguel Marti1, Lorena Martinez2, Silvia Gabriela
Ceberio2, Inmaculada Calvo1
1Pediatric Rheumatology, Huip La Fe, Valencia, Spain; 2Pharmacology, Huip La Fe, Valencia,
Spain
Correspondence: BERTA LOPEZ
Introduction: Serum adalimumab (ADA) levels have been related to treatment response
in juvenile idiopathic arthritis (JIA).
Objectives: The aim of this study is to determine the optimal cutoff point of adalimumab
in our cohort of JIA patients in function of the variable chosen for remission: inactive
JIA.
Methods: Retrospective observational study. Patients with JIA and pharmacokinetic
monitoring of adalimumab, between September 2014 and February 2017, were included.
The JIA improvement criteria were used: visual analogue physician scale (EVA physician),
visual analogue patient scale (EVAp), number of active joints, number of limited joints,
CHAQ (quality of life questionnaire) and ESR. Inactive JIA was defined according to
Wallace criteria as the absence of active joints, systemic symptoms and uveitis; normal
ESR or PCR values; EVA medical negative and duration of stiffness less than 15 minutes.
The 7 subtypes of JIA were oligorticular, polyarticular, psoriatic and enthesitis
related arthritis.
Results: Thirty-four patients (58.82% female) were included in the study, with a total
of 50 determinations. The mean age was 12.35 years (95% CI: 10.45-14.26). The forms
of JIA were: oligoarticular 35.29% (n = 12), polyarticular 29.41% (n = 10), enthesitis
related arthritis 23.53% (n = 8) and psoriatic arthritis 11.77% (n = 4). All of patients
were given methotrexate concomitantly. The mean ADA levels according JIA forms were:
oligoarticular 9.21 mcg/mL, polyarticular 8.36 mcg/mL, enthesitis related arthritis
7.73 mcg/mL and psoriatic arthritis 13.44 mcg/mL. In the group with uveítis, ten of
them had active uveitis, predominantly oligoarticular and polyarticular (90%). The
mean ADA levels were 9.80 and 5.88 mcg/mL (p = 0.019) inactive and active uveitis
respectively. Mean levels were higher in patients with inactive JIA compared to patients
with active JIA (10.76 mcg/mL vs. 7.33 mcg/mL, p = 0.024). AUC (IC95%) according to
the ROC curve was 0.70 (0.53-0.86) with an optimal cutoff of 11 mcg/mL (Sensitivity
(Se) = 52.6%; Specificity (Ep) = 85.5%).
Conclusion: In our cohort of patients, it has been observed that inactive JIA requires
ADA levels higher than those of active JIA. On the other hand, despite the predominance
of oligoarticular and polyarticular forms in active uveitis, psoriatic arthritis requires
higher levels of ADA. Finally, the optimal ADA cut-off point indicates that the levels
of ADA for JIA are higher than those generally established for adult rheumatology
patients.
Disclosure of Interest: None Declared
P158 Efficacy of omalizumab treatment in a girl with autoinflammatory desease and
chronic urticaria
Maria Cristina Maggio1, Anna Lucania2, Giovanni Corsello1
1University Department Pro.Sa.M.I. “G. D’Alessandro”, University of Palermo, Palermo,
Italy; 2II Pediatric Unit,, “G. Di Cristina” Children Hospital, ARNAS, Palermo, Palermo,
Italy
Correspondence: Maria Cristina Maggio
Introduction: Chronic Idiopathic Urticaria (CIU) is associated to angioedema in 40%
of patients, with a prevalence of 0.1-0.3%, a medium age at the diagnosis of 6-11
years. Furthermore, the 25-85% of cases remain with a diagnosis of an “idiopathic”
disease, for the negativity of all the diagnostic tests. 30-50% of patients have an
autoimmune origin, although confirmation of the diagnosis in these cases is not easy.
Some patients, in fact, have autoantibodies against the high-affinity IgE receptor
FcεR1 or the IgE. These patients, show an increased incidence of anti-thyroid autoantibodies,
and represent 30-50% of the patients designated as having CIU.
CAPS are Autoinflammatory diseases (AID) classically characterized by recurrent episodes
of fever, rash, significant increase of inflammatory markers (SAA, CRP, ESR, neutrophil
leukocytes), arthralgia, myalgia, abdominal and chest pain; these patients can have
severe clinical manifestations, which require to be treated with biological drugs
anti-IL-1.
Objectives: However, in some patients genetic analysis of the candidate genes (NLRP3,
NLRP12…) are negative and the best treatment is hard to decide.
Methods: We describe the clinical case of a 9-year-olf-female with recurrent monthly
episodes of fever (> 38,5 ° C for about 5 days), arthralgia, abdominal pain, urticaria-angioedema,
without itch, significant increase of SAA, CRP, ESR, leucocytosis. ANA, ENA, ASCA,
ANCA, LAC, RAST, IgE, thyroiditis and coeliac disease markers, C3 and C4 anti-C1q
inhibitor e C1q inhibitor gene mutations were negative. The genetic study of AID (FMF,
TRAPS, MVK, NLRP3, NLRP12) was negative.
Results: The attacks only partially responded to high doses of steroids and antihistaminic
drugs. She was tested with omalizumab, a monoclonal humanized murine antibody direct
against IgE. The treatment, off-label for age, induced a prompt and persistent resolution
of the clinical manifestations and the normalization of inflammatory markers. Fever
and arthralgia resolved and- after 5 months of treatment- she did not present more
attacks.
Conclusion: Omalizumab induced an on-going positive response and was well tolerated
without side effects. The omalizumab effect was extended on inflammatory markers and
symptoms, suggesting the possible employ of the drug in severely symptomatic patients
in whom urticaria is the dominant sign and genetic analysis does not support the diagnosis
of CAPS.
Disclosure of Interest: None Declared
P159 The use of consequential biologic DMARDs in paediatric rheumatology
Joseph Mcallister1, Adam Clough2, Phil Riley1, Alice Chieng1
1Paediatric Rheumatology, Royal Manchester Childrens Hospital, Central Manchester
University Hospitals, Manchester, United Kingdom; 2Pharmacy, Royal Manchester Childrens
Hospital, Central Manchester University Hospitals, Manchester, United Kingdom
Correspondence: Joseph Mcallister
Introduction: Biologic DMARDs (bDMARDs) are integral to the management of paediatric
rheumatological disease. There is an increasing cohort of patients who have tried
more than one bDMARD and the indications and side effects are not well studied. In
our department some have received up to four different bDMARDs. Despite their widespread
use, there is limited evidence about the consequential use of different bDMARDs in
paediatric rheumatology.
Objectives: The aim of this study was to investigate the consequential use of bDMARDs
in the paediatric rheumatology. The outcomes were to define local practice and the
group of patients who clinically need multiple bDMARDs. We also wanted to look at
the adverse effects of receiving consequential bDMARDs.
Methods: Using hospital pharmacy records, a database of paediatric rheumatology patients
who received two or more bDMARDs was created. Patient records were scrutinised for
demographics and diagnoses. Data collection was completed by documenting bDMARDs,
and recording information pertinent to each course of treatment including the duration,
side effects, reported infections and reason for changing to another bDMARD.
Results: From February 2015 to March 2017 there were 34 patients who received consequential
bDMARDs who collectively underwent 48 medication changes. Their diagnoses included
juvenile idiopathic arthritis (JIA) (poly-JIA - 14%; oligo-JIA alone – 8.2%; systemic
JIA – 4.1%; oligo JIA and uveitis - 18.8%). Enthesitis-related arthritis, uveitis
and sarcoidosis accounted for the remainder. 25 patients received two bDMARDs, 10
patients received three bDMARDs and 4 patients received four bDMARDs. The mean duration
of treatment was 49.4 months (range 15 - 132 months).
Etanercept was prescribed 22 times, usually first line (90%). Adalimumab was prescribed
31 times, mostly second line (77%). Infliximab was prescribed 16 times mostly first
line (56%). Tocilizumab was prescribed for 13 patients mostly as third (46%) and fourth
line (23%) therapy and never as first line. Abatacept was prescribed once as fourth
line. Anakinra was used twice. Practice was mostly in keeping with BSPAR guidance
for bDMARD usage.
Many factors contributed to switching. Most common were poor control of JIA (41.6%),
uveitis (18.8%), and infections (5%). Intolerance to administration for adalimumab
and etanercept was common (22%). Adverse reactions to infliximab accounted for 8%.
Patients requiring three or more bDMARDs had diagnoses of antibody negative oligo-JIA
(7/10) six of whom also had active uveitis. The three remaining patients had poly-JIA
and two of these were Rheumatoid Factor positive (RF+).
158 infections were reported, most of which were mild. Eight infections required hospitalisation.
The most common infections were upper respiratory tract infections (40.5%), urinary
tract infections (12%), ear infections, cellulitis and pneumonia (7% each). Other
serious infections reported were appendicitis, central line sepsis and sialitis. Minor
infections includeded thrush, gastroenteritis, threadworms, tinea, dental infections,
herpes simplex, varicella zoster, paronychia and infected ingrown toenails (Table 44).
Table 44
(Abstract P159). See text for description
Results table
bDMARD
No. patients
No. treatment years
Observed no. infections
Infections per 100 patient years
Observed no. adverse events
Adverse events per 100 patient years
% changed for ongoing JIA or uveitis
1st agent
34
51.1
64
3.68
23
3.68
58.8%
2nd agent
34
77.8
76
2.87
12
0.45
70%
3rd agent
10
5.8
10
17.39
2
3.48
25%
4th agent
4
5.3
8
37.5
0
0
-
Total
1680
158
Conclusion: This investigation highlights practice at a tertiary centre in which bDMARD
use is frequent. The results show factors contributing to bDMARD switching and this
can aid decision making when commencing therapy. This needs further studying as 41.6%
reported poor efficacy with their first bDMARD. It appears that patients with antibody
negative oligo-JIA and uveitis, and possibly RF + ve poly-JIA are at risk of poor
response. Infection rates increased during 3rd and 4th bDMARD courses, and although
reducing patient numbers are confounding, this is an interesting area for future research
given the impact on quality of life. Future research should follow patients into adulthood
to demonstrate long term effects of these medications.
Disclosure of Interest: None Declared
Uveitis
P160 The persistence of ana positive in JIA patients and the risk of developing chronic
anterior uveitis: a retrospective study
Alina Lucica Boteanu, Maria Llop Vilaltella, Maria Andreina Terán Tinedo, Maria Angeles
Blazquez Cañamero, Mariluz Gamir Gamir
Rheumatology, University Hospital Ramon Y Cajal, Madrid, Spain
Correspondence: Alina Lucica Boteanu
Introduction: Juvenile idiopathic arthritis (JIA) is one of the most frequent rheumathologic
conditions in childhood. The most common extra-articular manifestation of JIA is chronic
anterior uveitis (CAU). It usually has an insidious, asymptomatic onset, with a chronic
and recurrent course, being blindness its major complication. Several risk factors
to develop CAU has been reported, including early age at the onset of arthritis (before
6 years), short disease duration and some JIA subtypes (oligoarticular-persistent
and extended-oligoarticular JIA, psoriatic arthritis, undifferentiated arthritis).
The presence of positive antinuclear antibodies (ANA) tests is one of the most important
risk factors. In some cases ANA are present at the onset of the disease, subsequently
becoming negative.
Objectives: To determine if the presence of steadily ANA positivity (>2 determinations)
throughout disease course is associated with an increased risk of developing chronic
anterior uveitis
Methods: We performed a retrospective study including JIA patients with high-risk
to develop CAU and at least one positive ANA determination during the follow-up at
the Pediatric Rheumatology Unit of our center. A cut-off point titer of 1/80 was considered
for ANA positivity. The χ2 test was performed with Fisher's adjustment. The level
of significance was set by the 95% confidence interval (CI) and p <0.05.
Results: A total of 53 JIA patients were included, 48 (90.5%) of them are girls, with
a mean age at diagnosis of 3 years. 16 patients developed CAU (31.3% of the girls
and 20% of the boys), without a statistically significant difference in the percentage
of patients who developed CAU between the genders or age. When dividing into groups,
52% of the girls had 1or 2 positive ANA determinations and 48% had ≥3 positive determinations;
40% of the boys had 1or 2 positive ANA determinations and 60% had ≥3 positive determinations.
Analysing by groups, patients with 3 or more determinations an OR: 4.93 (95% CI: 1.32-18.31)
to develop CAU compared to those with 1or 2 positive determinations.
Conclusion: Our results are similar to others studies previously published regarding
the absence of association of chronic anterior uveitis with the female sex, based
on the frequency difference in the largest number of girls with JIA who debut at an
early age. Traditionally, 2 positive ANA determinations are considered to be associated
with a high risk of CAU. In addition, the results of our study suggest that the persistence
of ANA is associated with an even higher risk of developing chronic anterior uveitis.
Further studies with a larger cohort are needed to confirm these findings.
Disclosure of Interest: None Declared
P161 Uveitis associated with juvenile idiopathic arthritis: lower prevalence and unique
clinical characteristics in Asian patients
Pauline Chan Ng, Lee Kean Lim, Elizabeth Youning Ang, Pei Ling Ooi
Khoo Teck Puat-National University Children’s Medical Institute, National University
Hospital, Singapore, Singapore
Correspondence: Pauline Chan Ng
Introduction: Uveitis is the most frequent extra-articular manifestation in Juvenile
Idiopathic Arthritis (JIA) and results in significant morbidities including vision
loss. Paucity of data on JIA-associated uveitis (JIA-U) in Asia makes it challenging
to develop well-informed clinical practice guidelines for screening of JIA-U in this
population.
Objectives: We aim to describe the prevalence, clinical characteristics and risk factors
of JIA-U in patients treated in a Paediatric tertiary centre in Singapore.
Methods: 103 patients were diagnosed with JIA in our hospital from Jan 2007 to Feb
2017. We analysed the electronic medical records (EMRs) of 83 of these patients. Twenty
patients were excluded from our study: 15 did not have available EMRs and 5 made only
one visit to the Paediatric Rheumatology clinic.
Results: Among 83 patients with JIA, 29 (34.9%) were girls and 54 (65.1%) were boys.
Most of the patients were Chinese (n = 39, 47.0%), 22 (26.5%) Indonesian, 10 (12.0%)
Indian and 2 (2.4%) Malays. Ten patients were from Bangladesh, Cambodia, Korea, Vietnam,
Sri Lanka and East Timor. The subtypes of JIA were: enthesitis related arthritis (ERA)
(35.7%), oligoarthritis (22.6%), systemic JIA (15.5%), seronegative polyarthritis
(15.5%), seropositive polyarthritis (7.1%), psoriatic arthritis (2.4%) and undifferentiated
(1.2%). Twenty five of 72 patients (34.7%) were positive for ANA.
Four children (4.8%) were diagnosed with uveitis: 3 had ERA and developed anterior
uveitis, while 1 had oligoarticular JIA and had panuveitis. All 4 affected patients
were negative for ANA and Rheumatoid factor. All 3 patients with ERA were symptomatic
for uveitis and had bilateral involvement. The patient with oligoarticular JIA presented
with unilateral ptosis only. Mean age at diagnosis of uveitis was 10.3 years (CI 2.34–18.26).
Clinical characteristics of the 4 patients with JIA-U are shown in Table 45.
Table 45
(Abstract P161). Clinical characteristics of patients with JIA-U. (Abbreviations:
MTX, methotrexate)
Patient
JIA subtype
Gender; Ethnicity
Age of uveitis diagnosis (years)
Uveitis diagnosis from JIA diagnosis (years)
Symptom onset to diagnosis (months)
Symptoms
Disease extent
Complication
Treatment
1
ERA
Male; Indonesian
9.2
– 3.8
0.6
Pain and redness
Bilateral; anterior
–
Topical steroids, Adalimumab
2
ERA
Male; Indonesian
13.8
1.3
1.1
Redness, blurring of vision, photophobia
Bilateral; anterior
Macular oedema
Topical and systemic steroids, MTX, Adalimumab
3
ERA
Male; Indian
13.0
0
1.6
Redness
Bilateral; anterior
–
Topical and systemic steroids, MTX, Adalimumab
4
Oligoarticular-extended
Male; Indian
5.1
1.5
5.2
Left eye ptosis
Left; panuveitis
Macular oedema, glaucoma, cataract
Topical and systemic steroids, MTX, Infliximab; cataract surgery; YAG laser
Conclusion: Our Asian population demonstrates distinct differences to our Western
counterparts:
Our patients have a much lower prevalence at 4.8%. Literature from Western populations
cite prevalence of JIA-U between 11 and 30%. Even though our Asian patient population
is fairly heterogeneous, our prevalence is consistent with the 4.7% prevalence demonstrated
in a study done in Taiwan, a more homogeneous Asian population.
Our Asian population did not demonstrate the same risk factors for JIA-U as in previous
studies. There was a much higher association of uveitis with ERA in both our and the
Taiwanese study. Frequently reported risk factors of ANA-positivity, young age of
disease onset, female gender were not evident in our population.
Lastly, majority (3 of 4) of our patients were symptomatic for uveitis.
These preliminary findings have implications for screening guidelines for uveitis
in Asian patients with JIA. Larger population studies are required to characterize
the risk factors for JIA-U to guide development of such guidelines.
Disclosure of Interest: None Declared
P162 Our modest experience with adalimumab in the treatment of juvenile idiopathic
arthritis associated uveitis
Almira Ćosićkić1, Fahrija Skokić2, Sanimir Suljendić3, Meliha Halilbašić4, Amela Selimović5
1Department of Allergy, Rheumatology and Immunology, Children's Hospital, Tuzla, Bosnia
and Herzegovina; 2Department of Neonatology, Children's Hospital, Tuzla, Bosnia and
Herzegovina; 3Department of Children's Surgery, Children's Hospital, Tuzla, Bosnia
and Herzegovina; 4Ophthalmology Clinic, Tuzla, Bosnia and Herzegovina; 5Department
of Intensive Care and Therapy, University Clinical Center, Tuzla, Bosnia and Herzegovina
Correspondence: Almira Ćosićkić
Introduction: Juvenile idiopathic arthritis (JIA) is commonly complicated by chronic
uveitis. Therapy of JIA-associated uveitis is guided by the severity of inflammation
and complications. When the standard anthireumatic drugs and the local eye therapy
are insufficient we need to consider immunosuppressive or biological agents.
Objectives: Observation was aimed at assessing the effectiveness of adalimumab (ADA)
in the treatment of juvenile idiopathic arthritis associated uveitis in children with
disease resistance to standard antirheumatic therapy.
Methods: 7 patients with JIA (5 oligoarticular, 2 polyarticular) and who experienced
eye problems were included in the study, 6 girls and 1 boy. Mean age was 6.3 years;
the age of disease onset was 4.4 ± 1.2 years. Prior to ADA administration all children
received the topical treatment of uveitis and methotrexate and 4/7 children received
oral corticosteroids. 4 children had bilateral eye involvement and 3 children had
unilateral; 5 children had active uveitis; most children had the moderate activity
of arthritis; mean ESR was 23.4 ± 15.3 mm/h; CRP 72 ± 18.1 mg/dl (ref <3.0 mg/dl).
Results: After 6 months of ADA administration, uveitis remission was achived in 27.3%
eyes, 18.2% eyes showed a reduction in inflammatory activity, flares was observed
in 2/7 children; after 12 months of ADA 42.8% eyes had uveitis remission, 14.3% eyes
had sub active uveitis. Monitoring arthritis for 6 months of ADA administration, 95%
children achieved ACR ped-30, 57.1% ACR ped 50 with substantially decreased ESR, CRP
also; after 12 months of ADA, ACR ped-30 and ACR ped-50 was achieved in all children,
while ACR ped-70 in 4 children; mean ESR decreased to 11.4 ± 2.3 mm/h and also CRP
from 72 ± 18.1 mg/dl to 25.2 ± 2.1 mg/dl.
Conclusion: Our modest experience has confirmed that adalimumab in the treatment of
JIA associated with uveitis has the significant efficacy in the majority of children.
Disclosure of Interest: None Declared
P163 A rare case of recurrent bilateral optic disc edema in tubulointerstitial nephritis
and uveitis syndrome treated with infliximab
Siska E. Dhaese1, Joke Dehoorne2, Jean-Baptiste Willemot3, Johan Vande Walle2, Ilse
De Schryver3
1Medical School, Ghent University, Ghent, Belgium; 2Pediatric Nephrology and Rheumatology
Unit, Ghent University Hospital, Ghent, Belgium; 3Ophthalmology, Ghent University
Hospital, Ghent, Belgium
Correspondence: Siska E. Dhaese
Introduction: Tubulointerstitial Nephritis and Uveitis syndrome (TINU) is a rare disorder
characterized by inflammation of the tubulointerstitium associated with recurrent
unilateral or bilateral uveitis. Since TINU syndrome may not be obvious at initial
presentation, it remains often underdiagnosed.
Objectives: To report a case of recurrent bilateral optic disc edema in a definite
TINU syndrome with limited responsiveness to corticosteroid therapy and immunosuppressants.
An anti-TNF-α blocking agent was added in order to control the inflammation.
Methods: Observational report about a 13-year-old Caucasian boy diagnosed with TINU
syndrome and bilateral papilledema. An extensive general and ophthalmological workup
confirmed the diagnosis of TINU.
Results: A 13-year-old boy diagnosed with TINU syndrome, was referred to our department
with a bilateral papilledema. In a 25-months follow-up 4 episodes of bilateral anterior
uveitis were observed. At the 2nd episode the anterior chamber inflammation was accompanied
by bilateral optic disc edema. The ocular inflammation responded initially well to
systemic corticosteroids but after a recurrence-free period of 1-year, bilateral papilledema
recurred. At referral ocular examination showed mild anterior chamber reaction with
bilateral optic disc edema. Visual field testing was normal and optical coherence
tomography showed a thicker peripapillary retinal nerve fiber layer (PPRNFL). Immunosuppressive
therapy with mycophenolate mofetil and methotrexate failed to control the inflammation.
A treatment with infliximab, an anti-TNF-α blocking agent, was initiated. Initially
remission with a recurrence-free period of 7 months was achieved but papilledema recurred.
Conclusion: TINU syndrome may rarely manifest with optic disc edema. To our knowledge,
this is the first case of TINU syndrome with bilateral papilledema treated with infliximab.
Despite a recurrence-free period of 7 months, the anti-TNF-α blocking agent failed
to control the papilledema. Since the limited responsiveness to anti-TNF-α blocking
agents, alternative treatment options need to be explored.
Disclosure of Interest: None Declared