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128 Jornal de Pediatria - Vol. 78, Nº2, 2002
0021-7557/02/78-02/128
Jornal de Pediatria
Copyright © 2002 by Sociedade Brasileira de Pediatria

ORIGINAL ARTICLE

Behcet’s disease in childhood

Patrícia R. de Albuquerque,1 Maria Teresa R.A. Terreri,2
Cláudio Len,3 Maria Odete E. Hilário4

Abstract
Objective: to make Pediatricians aware of the fact that they must investigate Behcet’s disease while
performing differential diagnosis of recurrent aphthous stomatitis, even though it is a vasculitis of rare
occurrence in early life.
Methods: between June 1996 and December 2000, we retrospectively evaluated seven patients of our
Pediatric Rheumatology Unit. Demographic, clinical, and laboratory data as well as data regarding
treatment and follow-up were presented.
Results: five out of seven patients were female (71.4%), four were non-Caucasian (57.1%), the mean
age at onset was 8 years and 11 months (variation of 6 months to 13 years and 8 months), the mean period
until diagnosis was 2 years and 3 months (variation of 2 months to 8 years) and the mean follow-up period
was 4 years and 2 months (three patients without follow-up). The major criteria of diagnosis were: oral
ulcers in seven patients (100%), genital ulcers in three patients (42.8%), ophthalmic alterations in four
patients (57.1%) cutaneous vasculitis in one patient (14.2%) and positive pathergy test in one patient
(14.2%). The minor criteria were: arthralgia/arthritis in five patients (71.4%), family history in two patients
(28.5%), and sagittal sinus thrombosis in one patient (14.2%). The initial symptoms included recurrent
aphthous stomatitis (more than three painful aphthous ulcers episodes in the period of 1 year), genital
ulcers, arthralgia, fever and weight loss. The laboratory findings were: mild anemia in 1/6 patients, ESR>25
in 3/6 patients, increased serum gammaglobulin level in 2/4 patients, B5 histocompatibility antigen in 2/
7 patients. The treatment included corticosteroids for 5/7 patients (4 oral, 1 intravenous and one local use),
thalidomide for 4/7 patients, colchicine for 2/7 patients and dapsone for 1/7 patient. The outcome was
favorable in 4/6, and 3/6 patients presented relapse.
Conclusion: our results confirm the importance of considering the diagnosis of Behcet’s disease in
patients with recurrent oral and genital ulcers.

J Pediatr (Rio J) 2002; 78 (2): 128-32: Behcet’s disease, recurrent ulcers.

1. Medical student, Department of Pediatrics, Escola Paulista de Medicina.

2. Associate professor, Department of Pediatrics, Escola Paulista de
Medicina.
3. Visiting professor, Pediatric Rheumatology, Department of Pediatrics,
Universidade Federal de São Paulo (UNIFESP-EPM).
4. Associate professor; Department of Pediatrics, Universidade Federal de
São Paulo (UNIFESP-EPM)..
Manuscript received July 18 2001. Accepted for publication Jan 30 2002.
Introduction
Hulusi Behcet described a triple-symptom complex of
recurrent aphthous ulcers, genital ulcers, and iritis in 1937.1
Behcet’s disease is a rare, chronic, recurrent, and
multisystemic vasculitis in children.2

128
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Behcet’s disease in childhood - Albuquerque PR et alii
Some studies report an incidence of 1/20,000 in
children.3. The mean age at diagnosis is ±10 years, regardless
of gender.3,4 The etiology is unknown; however, some
causes are suggested: viral infection and exposure to
organophosphorated compounds. 1,5 Immunological
alterations, such as cellular immunity disorders, presence
of immunocomplexes and complement activation have been
described.6
More specific diagnostic criteria were proposed by the
International Study Group for Behcet’s Disease in 1989.7
Major criteria include: oral ulcers, genital ulcers, ocular
injuries, skin lesions, and pathergy test. Minor criteria
consisted of arthritis, cardiovascular injury,
thrombophlebitis, neurological disorders, gastrointestinal
injury, and family history. The diagnosis should include 3
major criteria or 2 major criteria plus 2 minor criteria.
Oral ulcers are the most frequent symptom, affecting
between 88 and 100% of patients.8-10 Genital ulcers usually
appear at the pubertal stage and can be seen on the penis,
scrotum, vulva and vagina. Skin involvement occurs during
the progression of the disease in 70 to 93% of patients.3,9,11,12
The pathognomonic skin lesion resulting from Behcet’s
disease is the intracutaneous response to the trauma, which
is called pathergy test, and occurs in 22 to 84% of
patients.2,4,10,12 Both the anterior eye segment (iridocyclitis)
and the posterior eye segment (chorioretinitis, optic papillitis,
retinal thrombophlebitis, arteritis) are involved. Ophthalmic
involvement is not common in children; according to the
literature, it is present in 28 to 68% of the children, and is
associated with the presence of HLA- B5.3,4,12,13-18
The involvement of the joints is characterized by arthritis/
arthralgia (usually on the knees), which may be oligoarticular
or polyarticular. Normally, there are no sequelae. Vascular
involvement includes arteries and veins, and is present in
35% of the cases.19 The involvement of the central nervous
system has been described in approximately 18% of the
patients, and is considered the most severe manifestation of
the disease.16 Gastrointestinal involvement is characterized
by esophageal ulcers and anal lesions, abdominal pain,
gastritis, diarrhea, hepatomegaly, and splenomegaly. Other
complications include: nephrotic syndrome, amyloidosis,
focal segmental glomerulonephritis, epididymitis, urethritis,
recurrent cystitis, myocarditis, pericarditis, and myocardial
infarction.
Lab exams may be useful for following up the activity of
the disease and establishing the differential diagnosis. The
increased level of gammaglobulin is a predictor of better
ocular prognosis.18 The assay for autoantibodies is negative.
The HLA-B5 is present in 50 to 84% of the cases.2,17
Several forms of treatment have been proved effective.
Systemic corticosteroids and, occasionally, topic ointments
and eyewash, immunosuppressive therapy, nonhormonal
anti-inflammatory drugs, colchicine and thalidomide are
among the therapeutic options. The disease evolves in
outbreaks and remission at intervals that may comprise
Jornal de Pediatria - Vol. 78, Nº2, 2002 129
months or even years. Mortality occurs in 3% of the children
due to vascular complications.4
Our objective was to assess the clinical and
epidemiological characteristics, the treatment and the
development of children and adolescents with Behcet’s
disease who were assisted at our department .
Patients and methods
The medical records of seven patients assisted at the
Outpatient Clinic of Pediatric Rheumatology (UNIFESP-
EPM) were retrospectively evaluated between June 1996
and December 2000. The inclusion criteria were: 1) children
and adolescents diagnosed with Behcet’s disease by two
independent pediatric rheumatologists; 2) patients with
complete medical records available for data collection. All
patients were submitted to a structured interview and in-
depth physical examination at the time of the study. The
following subsidiary exams were carried out: hemogram,
inflammatory activity tests, protein electrophoresis, renal
function, antinuclear antibodies by indirect immunoflu-
orescence, HLA-B5 by microlymphocytotoxicity, and urine
sedimentation. The medical records were revised by two
investigators who analyzed the epidemiological, clinical,
laboratory, evolution, and treatment data. The present study
was approved by the Ethics Committee.
Results
Table 1 shows the epidemiological characteristics of
patients with Behcet’s disease. Five of seven patients were
female (71.4%), four were non-Caucasian (57.1%), with
mean age at onset of the disease of 8 years and 11 months,
mean time before diagnosis of 2 years and 3 months and
mean evolution time of 4 years and 2 months (3 patients
were not followed up).
Table 2 shows the clinical characteristics, family history,
laboratory results, treatment and evolution of patients. The
major diagnostic criteria were: oral ulcers in 7 patients
(100%), genital ulcers in 3 patients (42.8%), ophthalmologic
alterations in 4 patients (57.1%), cutaneous vasculitis in 1
patient (14.2%) and positive pathergy test in 1 patient
(14.2%). The minor diagnostic criteria were arthralgia/
arthritis in 5 patients (71.4%) and family history in 2
patients (28.5%). We observed saggital sinus thrombosis in
1 patient (14.2%). All patients had oral ulcers at the initial
phase of the disease.
Anemia was present in 1/6 patients (16.6%), ESR>25 in
3/6 patients (50%) and hypergammaglobulinemia in 2/4
patients (50%). The HLA-B5 was positive in only 2/7
patients (28.5%). Leukocyte and platelet count results were
normal. Renal function was normal in all patients. No
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130 Jornal de Pediatria - Vol. 78, Nº2, 2002 Behcet’s disease in childhood - Albuquerque PR et alii

Table 1 - Epidemiological characteristics of patients with Behcet’s disease (n=7)

Patients 1 2 3 4 5 6 7

Gender M F F F F F M
Race NC NC C NC C C NC
Onset age 4y 7m 4y 12y 10m 9y 6m 13y 8m 12y 5m
Time before diagnosis 4m 8y 2m 3y 3y 2m 11m
Evolution time 2y 10m 8y 8m 1y 4y 9m 9y 8m 8m 1y 4m

M = male; F = female; NC = non-Caucasian; C = Caucasian; y = years; m = months

patient had hematuria and/or proteinuria. None of the
patients was positive for antinuclear antibodies.
The treatment consisted of corticosteroids in 5/7 patients
(71.4%), (oral administration in 4, IV in 1, and topic in 1),
thalidomide in 4/7 patients (57.1%), colchicine in 2/7
patients (28,5%) and dapsone in 1/7 patients (14.2%).
Treatment response was satisfactory in 4/6 (66.6%) patients.
The disease was recurrent in 3/6 (50%) patients.
One child (patient 6) had glaucoma as a result of
ophthalmic involvement and muscle weakness as
neurological sequela. No patient died.
Discussion
Behcet’s disease is not a familial entity to pediatricians,
due to its low incidence and nonrecognition, since specific
symptoms/signs sometimes appear at a later time. This

Table 2 - Clinical characteristics, family history, laboratory results, treatment and evolution of patients with
Behcet’s disease (n=7)

Pacientes 1 2 3 4 5 6 7

Oral ulcers yes yes yes yes yes yes yes

Genital ulcers no no yes no yes yes no
Ophtalmological conjunctivitis retinal no uveitis/ no glaucoma no
alterations vasculitis conjunctivitis
Arthralgia/ arthritis no yes no yes yes yes yes
Cutaneous vasculitis no no yes no no no no
Pathergy yes no no no no no no
Saggital sinus thrombosis no no no no no yes no
Other symptoms no no fever / fever no no fever
↓ weight
Family history yes no no no yes no no
Hb < 11.0 yes NR no no no no no
BSR >25 yes NR yes no yes no no
ϒ >1.6 NR NR NR no yes no yes
HLA B5 no no yes no yes no no
Medication CE OA CE OA CE OA CE thalidomide CE OA thalidomide
thalidomide thalidomide CE IA eye drops colchicine
dapsone colchicine
Positive response no NE yes yes no yes yes
Recurrence yes NE no yes yes no no

yes = present; no = absent; - = decrease; Hb = hemoglobin; BSR= blood sedimentation rate; ϒ = gammaglobulin; HLA B5 =
histocompatibility antigen-B5; CE = corticosteroid; OA = oral administration; IA = intravenous administration; NE = nonevaluated
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Behcet’s disease in childhood - Albuquerque PR et alii
should not be forgotten in the case of children who have
recurrent oral ulcers (more than 3 episodes a year), associated
with other nonspecific clinical manifestations. The incidence
of Behcet’s disease is low, except in some Mediterranean
countries, such as Israel and Turkey.2,10,12
Although no gender-specific predominance has been
found in the literature, female patients were predominantly
affected by the disease (5:2) in our study.
The mean age for disease onset in our patients was 8
years and 11 months, which is in agreement with other
studies.2-4,9,17 However, Behcet’s disease was reported in
infants,4 as was the case of our youngest patient (6 months
old at diagnosis). We found out that early diagnosis was
usually made in patients with more intense symptoms at the
beginning of the disease, with bipolar ulcers (patient 3) and
cerebral thrombosis (patient 6). The mean time for the
appearance of symptoms until diagnosis was 2 years and 3
months, which is lower than that described in the literature
(5 years).4,10
All of our patients had recurrent oral ulcers as initial
symptom, with an incidence rate similar to that described in
the literature.8-10 However, genital ulcers occurred at the
onset of the disease in only 3 (42.8%) patients. This type of
ulcer is less frequent than oral ulcers, and is usually present
when Behcet’s disease appears during puberty. This hinders
diagnosis at early ages, since bipolar ulcers are highly
indicative of the disease. Ophthalmologic disorders were
present in 57% of the cases. We know that ophthalmologic
complications are more common in childhood,
predominantly in males, and are associated with HLA.14-16,18
We did not observe that possibly due to our population’s
characteristics. One of our female patients had glaucoma,
but the HLA-B5 was negative.
Skin involvement was present in only one patient; this is
different from the information obtained from other reports
(92%).3,9,11,12 This might result from shorter evolution
time presented by our patients. According to the literature,
the frequency of the pathergy test varies a lot (from 22 to
84%).2,4,10,12 Only one patient had positive pathergy test
results (14.2%).
The only vascular disorder was saggital sinus thrombosis,
although thrombophlebitis is mostly frequent.11
Only 4 patients met the necessary criteria for the diagnosis
of Behcet’s disease during the evolution of the disease
(patients 1, 3, 5 and 6), indicating that the incomplete
presentation of the disease is frequent.3 Patients 2 and 4 had
two major criteria and one minor criterion, while patient 7
had one major and one minor criterion.
Lab exams are not specific and help with the follow-up
of disease evolution in few cases. The presence of
hypergammaglobulinemia was described as the best
prognostic factor for ophthalmic involvement.18 Although
we carried out this exam in only 4 patients, the results we
obtained confirm the findings reported in the literature. In
other words, 2 patients who had hypergammaglobulinemia
Jornal de Pediatria - Vol. 78, Nº2, 2002 131
did not show this kind of involvement, while the 2 patients
with normal gammaglobulin had ophthalmic involvement.
The frequency of HLA B5 occurred in only 2 patients
(28%), a low frequency if compared with other studies (50
to 84%);2,17 this may happen due to the characteristics of
our population.
The treatment with oral corticosteroids is used in the
acute phase of the disease in most patients. In milder cases,
corticosteroids are not necessary, as with 3 of our patients.
Thalidomide and colchicine were used according to patients’
clinical symptoms.
The efficacy of the treatment was assessed in 6/7 patients.
The treatment was efficient in 66% of the cases. The
frequency of recurrence was 50%, which is in agreement
with the literature.3
Since Behcet’s disease is not so frequent and its initial
symptoms are nonspecific, it may not be recognized by
pediatricians. Recurrent oral ulcers at any time during
childhood and adolescence should be regarded as possible
diagnosis of the disease.
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