International consensus on the diagnosis and management of pediatric patients with hereditary angioedema with C1 inhibitor deficiency

There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

Abstract

Background

The consensus documents published to date on hereditary angioedema with C1 inhibitor deficiency (C1‐ INH‐ HAE) have focused on adult patients. Many of the previous recommendations have not been adapted to pediatric patients. We intended to produce consensus recommendations for the diagnosis and management of pediatric patients with C1‐ INH‐ HAE.

Methods

During an expert panel meeting that took place during the 9th C1 Inhibitor Deficiency Workshop in Budapest, 2015 ( www.haenet.hu), pediatric data were presented and discussed and a consensus was developed by voting.

Results

The symptoms of C1‐ INH‐ HAE often present in childhood. Differential diagnosis can be difficult as abdominal pain is common in pediatric C1‐ INH‐ HAE, but also commonly occurs in the general pediatric population. The early onset of symptoms may predict a more severe subsequent course of the disease. Before the age of 1 year, C1‐ INH levels may be lower than in adults; therefore, it is advisable to confirm the diagnosis after the age of one year. All neonates/infants with an affected C1‐ INH‐ HAE family member should be screened for C1‐ INH deficiency. Pediatric patients should always carry a C1‐ INH‐ HAE information card and medicine for emergency use. The regulatory approval status of the drugs for prophylaxis and for acute treatment is different in each country. Plasma‐derived C1‐ INH, recombinant C1‐ INH, and ecallantide are the only agents licensed for the acute treatment of pediatric patients. Clinical trials are underway with additional drugs. It is recommended to follow up patients in an HAE comprehensive care center.

Conclusions

The pediatric‐focused international consensus for the diagnosis and management of C1‐ INH‐ HAE patients was created.

Related collections

Most cited references 102

Record: found
Abstract: found
Article: not found

Hereditary angioedema: new findings concerning symptoms, affected organs, and course.

Jochen Hardt, G. Meng, Petra Staubach … (2006)

Hereditary angioedema (HAE) due to C1 inhibitor deficiency is clinically characterized by relapsing skin swellings, abdominal pain attacks, and life-threatening upper airway obstruction. Our aim was to examine a temporal and spatial pattern of the edema episodes by evaluating the long-term course of hereditary angioedema in order to establish a specific swelling pattern. Data were generated from 221 patients with C1 inhibitor deficiency by asking them about symptoms they experienced during their edema episodes. Documentation was accomplished through the use of standardized questionnaires. A total of 131110 edema episodes were observed. Clinical symptoms started at a mean age of 11.2 (SD 7.7) years. During the following cumulative 5736 years, only 370 (6.5%) symptom-free years occurred. Skin swellings, including extremity, facial, genital, and trunk swellings, and abdominal attacks occurred in 97.4% of all edema episodes of the disease. The other episodes were laryngeal edema (0.9%); edema of the soft palate (0.6%); tongue swellings (0.3%); headache episodes (0.7%); episodes affecting urinary bladder (0.3%), chest (0.2%), muscles (0.4%), joints (0.1%), kidneys (0.1%), and esophagus (0.05%), and were partly combined with other edema episodes. The per-patient analysis and the per-episode analysis revealed markedly discrepant results. On average, women had a more severe course of the disease than men. Patients with early onset of clinical symptoms were affected more severely than those with late onset. The described swelling pattern is specific for HAE and allows a tentative diagnosis based on clinical symptoms and the course of the disease.

0 comments Cited 170 times – based on 0 reviews      Review now

Bookmark

Record: found
Abstract: found
Article: not found

Icatibant, a new bradykinin-receptor antagonist, in hereditary angioedema.

Marco Cicardi, Aleena Banerji, Francisco Bracho … (2010)

Hereditary angioedema is characterized by recurrent attacks of angioedema of the skin, larynx, and gastrointestinal tract. Bradykinin is the key mediator of symptoms. Icatibant is a selective bradykinin B2 receptor antagonist. In two double-blind, randomized, multicenter trials, we evaluated the effect of icatibant in patients with hereditary angioedema presenting with cutaneous or abdominal attacks. In the For Angioedema Subcutaneous Treatment (FAST) 1 trial, patients received either icatibant or placebo; in FAST-2, patients received either icatibant or oral tranexamic acid, at a dose of 3 g daily for 2 days. Icatibant was given once, subcutaneously, at a dose of 30 mg. The primary end point was the median time to clinically significant relief of symptoms. A total of 56 and 74 patients underwent randomization in the FAST-1 and FAST-2 trials, respectively. The primary end point was reached in 2.5 hours with icatibant versus 4.6 hours with placebo in the FAST-1 trial (P=0.14) and in 2.0 hours with icatibant versus 12.0 hours with tranexamic acid in the FAST-2 trial (P<0.001). In the FAST-1 study, 3 recipients of icatibant and 13 recipients of placebo needed treatment with rescue medication. The median time to first improvement of symptoms, as assessed by patients and by investigators, was significantly shorter with icatibant in both trials. No icatibant-related serious adverse events were reported. In patients with hereditary angioedema having acute attacks, we found a significant benefit of icatibant as compared with tranexamic acid in one trial and a nonsignificant benefit of icatibant as compared with placebo in the other trial with regard to the primary end point. The early use of rescue medication may have obscured the benefit of icatibant in the placebo trial. (Funded by Jerini; ClinicalTrials.gov numbers, NCT00097695 and NCT00500656.)

0 comments Cited 124 times – based on 0 reviews      Review now

Bookmark

Record: found
Abstract: found
Article: not found

Hereditary and acquired angioedema: Problems and progress: Proceedings of the third C1 esterase inhibitor deficiency workshop and beyond

Angelo Agostoni, Emel Aygören-Pürsün, Karen E Binkley … (2004)

Hereditary angioedema (HAE), a rare but life-threatening condition, manifests as acute attacks of facial, laryngeal, genital, or peripheral swelling or abdominal pain secondary to intra-abdominal edema. Resulting from mutations affecting C1 esterase inhibitor (C1-INH), inhibitor of the first complement system component, attacks are not histamine-mediated and do not respond to antihistamines or corticosteroids. Low awareness and resemblance to other disorders often delay diagnosis; despite availability of C1-INH replacement in some countries, no approved, safe acute attack therapy exists in the United States. The biennial C1 Esterase Inhibitor Deficiency Workshops resulted from a European initiative for better knowledge and treatment of HAE and related diseases. This supplement contains work presented at the third workshop and expanded content toward a definitive picture of angioedema in the absence of allergy. Most notably, it includes cumulative genetic investigations; multinational laboratory diagnosis recommendations; current pathogenesis hypotheses; suggested prophylaxis and acute attack treatment, including home treatment; future treatment options; and analysis of patient subpopulations, including pediatric patients and patients whose angioedema worsened during pregnancy or hormone administration. Causes and management of acquired angioedema and a new type of angioedema with normal C1-INH are also discussed. Collaborative patient and physician efforts, crucial in rare diseases, are emphasized. This supplement seeks to raise awareness and aid diagnosis of HAE, optimize treatment for all patients, and provide a platform for further research in this rare, partially understood disorder.

0 comments Cited 122 times – based on 0 reviews      Review now

Bookmark

All references

Author and article information

Contributors

H. Farkas: farkas.henriette@med.semmelweis-univ.hu

Journal

Journal ID (nlm-ta): Allergy

Journal ID (iso-abbrev): Allergy

Journal ID (doi): 10.1111/(ISSN)1398-9995

Journal ID (publisher-id): ALL

Title: Allergy

Publisher: John Wiley and Sons Inc. (Hoboken )

ISSN (Print): 0105-4538

ISSN (Electronic): 1398-9995

Publication date (Electronic): 08 September 2016

Publication date (Print): February 2017

Volume: 72

Issue: 2 ( doiID: 10.1111/all.2017.72.issue-2 )

Pages: 300-313

Affiliations

[ ¹ ] 3rd Department of Internal Medicine Hungarian Angioedema CenterSemmelweis University BudapestHungary

[ ² ]Hemophilia Center Rhine Main Moerfelden‐WalldorfGermany

[ ³ ] Department of DermatologyUniversity Medical Center Mainz MainzGermany

[ ⁴ ] Departments of Medicine and PaediatricsUniversity of Calgary Calgary ABCanada

[ ⁵ ] Department of Medicine, Pediatrics and Graduate StudiesPenn State University Hershey PAUSA

[ ⁶ ] Department of PediatricsDuke University Medical Center Durham NCUSA

[ ⁷ ] Department of Immunology and Histocompatibility School of Health Sciences Faculty of MedicineUniversity of Thessaly LarissaGreece

[ ⁸ ] Outpatient Group of Recurrent InfectionsFaculty of Medicine ABC Santo Andre SPBrazil

[ ⁹ ] 1st Department of PediatricsSemmelweis University BudapestHungary

[ ¹⁰ ] Department of Biomedical and Clinical Sciences “Luigi Sacco”University of Milan, ASST Fatebenefratelli Sacco MilanItaly

Author notes

[*] [* ] Correspondence

Henriette Farkas, MD, PhD, DSc, 3rd Department of Internal Medicine, Hungarian Angioedema Center, Semmelweis University, H‐1125 Budapest, Kútvölgyi street 4, Hungary.

Tel.: (+36 1) 325 1481

Fax: (+36 1) 225 3899

E‐mail: farkas.henriette@ 123456med.semmelweis-univ.hu

See Appendix for the members of HAWK.

Article

Publisher ID: ALL13001

DOI: 10.1111/all.13001

PMC ID: 5248622

PubMed ID: 27503784

SO-VID: aca12232-27a1-4728-bcfe-38e1a923accf

License:

This is an open access article under the terms of the Creative Commons Attribution‐NonCommercial License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes.

History

Date accepted : 06 August 2016

Page count

Figures: 1, Tables: 2, Pages: 14, Words: 11670

Funding

Funded by: Biocryst

Funded by: CSL Behring

Funded by: Dyax

Funded by: Pharming NV

Funded by: Shire Pharmaceuticals

Funded by: Swedish Orphan Biovitrum

Custom metadata

source-schema-version-number 2.0

component-id all13001

cover-date February 2017

details-of-publishers-convertor Converter:WILEY_ML3GV2_TO_NLMPMC version:5.0.2 mode:remove_FC converted:20.01.2017

ScienceOpen disciplines: Immunology

Keywords: c1 inhibitor deficiency,diagnosis,hereditary angioedema,management,pediatric

Data availability:

ScienceOpen disciplines: Immunology

Keywords: c1 inhibitor deficiency, diagnosis, hereditary angioedema, management, pediatric

International consensus on the diagnosis and management of pediatric patients with hereditary angioedema with C1 inhibitor deficiency

Read this article at

Abstract

Background

Methods

Results

Conclusions

Related collections

CHAIN Network Collection

Most cited references 102

Hereditary angioedema: new findings concerning symptoms, affected organs, and course.

Icatibant, a new bradykinin-receptor antagonist, in hereditary angioedema.

Hereditary and acquired angioedema: Problems and progress: Proceedings of the third C1 esterase inhibitor deficiency workshop and beyond

Author and article information

Contributors

Journal

Affiliations

Author notes

Article

History

Page count

Funding

Categories

Custom metadata

Comments

Comment on this article

Similar content 216

Cited by 50

Most referenced authors 1,010