Dear Editor,
We report a case of a 38-year-old woman who presented a pustule with erythematous
base in
the right deltoid region after application of lymphocyte active immunotherapy (LAI)
to
treat infertility (reported history of an abortion). Subsequently, a similar, exudative
lesion appeared in the left deltoid region. New lesions appeared bilaterally, forming
hardened erythematoviolaceous plaque (Figure 1).
The same treatment, applied on both arms, was administered four years prior without
complications. Given the clinical picture, the diagnostic hypothesis of sarcoidosis
was
suggested. A biopsy was performed, showing epithelioid cell granulomas without
lymphocyte border ("naked granuloma") and multinucleated histiocytes (giant cells)
in
the dermis, compatible with sarcoidosis (Figure 2).
The patient presented no respiratory symptoms; however, the computed tomography (CT)
of
her thorax showed intrathoracic and bilateral hilar lymphadenopathy. Infiltration
of
intralesional triamcinolone, hydroxychloroquine and subcutaneous methotrexate
(25mg/week) obtained no response. Treatment with infliximab (5mg/kg/infusion) was
then
initiated, with induction at weeks 0, 2, and 6, followed by infusions every eight
weeks
for maintenance. Thus far, induction has been realized, and two maintenance doses
have
been administered (weeks 14 and 22), with significant clinical improvement at week
6 of
induction. Residual cutaneous lesions were noted at week 14 of treatment, and a new
CT
of the thorax did not detect hilar lymphadenopathy (Figure
3). The patient continued with periodic follow-up, using maintenance dosing
of infliximab every eight weeks, without relapse of the lesions.
Figure 1
Erythe matoviolaceous, infiltrated, har dened plaques located in the right
deltoid re gion, before ini tiation of treat ment
Figure 2
Histopathological exam showing epithelioid cell granulo mas without
lymphocyte border ("naked granuloma"), surrounded by fibroplasia
(Hematoxylin & eosin, x100)
Figure 3
Brow nish erythema tous, atrophic and residual pla ques in the right deltoid
region after induction (weeks 0, 2 and 6) and two main tenance doses (weeks
14 and 22) of infliximab
Sarcoidosis is an immune-mediated inflammatory disease characterized by the formation
of
non-caseating granulomas. It can affect different organs, and cutaneous involvement
varies from small lesions to extensive presentations, with impacts on quality of
life.
1
The diagnosis is made
according to clinical, radiological and histopathological data, after exclusion of
differential diagnoses.
2
Although the
cause is yet unknown,
1
,
2
numerous works have proposed to demonstrate substances that may function as triggering
or aggravating factors or may simply be related to its physiopathogeny. It is believed
that a certain agent, infectious or not, must act on an immunogenetically predisposed
individual.
2
In the formation
of sarcoidal granuloma, innumerable cells, interleukins, and intercellular communication
pathways are involved. Among them, the lymphocytes T CD4+ are highlighted.
1
,
2
Interleukin-2, interferon gamma, and tissue necrosis
factor-alpha play important roles.
1
,
2
The disease can appear on areas of damaged skin, such as tattoos, and at previous
intramuscular or intravenous injection sites, for example.
1
Likewise, there are described cases in which the disease
developed after a vaccination.
3
In the
reported case, the injected material was a lymphocyte concentration applied
intradermally. LAI is considered a therapeutic option for patients with recurrent
miscarriages and uses lymphocytes obtained from the patient's male partner or from
a
healthy donor. The objective is to produce blocking antibodies, which act against
the
rejection of the embryo to reduce the risk of miscarriage.
4
According to the literature, after the exclusion of
hepatitis B and C, syphilis and HIV infection, venous blood of the donor is collected
and treated with an anticoagulant (heparin). The lymphocytes are separated, washed
and
diluted in saline solution. The injections are applied at four to six sites on the
patient's upper limb and repeated at 2- or 3-week intervals. However, the therapeutic
scheme and its efficacy remain controversial.
4
It is believed that the immunotherapy functions as an antigen,
with possible activation of reactive T cells, stimulating the onset of an inflammatory
reaction of the damaged skin, and that this reaction is sufficiently intense to persist
until the full development of the disease.
The treatment of sarcoidosis is not curative, and it alters the granulomatous process
and
its clinical consequences.
2
There is no
strict consensus. The use of tetracyclines or hydroxychloroquine is described, though
with a low level of evidence of their efficacy. The use of systemic corticosteroid,
methotrexate and thalidomide is an option for extensive and refractory cases.
1
,
2
Studies on the use of anti-TNF-alpha agents are scarce.
Heidelberger et al.,
5
in an observational multicentric study of 46 patients with cutaneous sarcoidosis,
observed good response to the use of infliximab: significant response in 24% after
three
months; 46% after six months; and 79% after twelve months. However, attention must
be
given to the possibility of recurrence after suspending medication and to the risk
of
adverse effects, such as infections.
The presentation of this case is justified by the rarity of sarcoidosis induced by
the
LAI. The association is currently uncommon; however, new cases may arise as infertile
couples seek this therapeutic option. More studies are needed to clarify the
physiopathogenesis of sarcoidosis resulting from immunotherapy. In addition to
discontinuation of the suspected inducing agent, treatment of this clinical presentation
can be achieved with infliximab, showing satisfactory response. Attention should be
given to possible adverse events and to relapse after suspension of treatment.