Journal of Pediatric Gastroenterology & Nutrition:
Intestinal Behçet's Disease: A Case Report and Review of Japanese Reports in Children
Tabata, Masahiko; Tomomasa, Takeshi; Kaneko, Hiroaki; Morikawa, Akihiro
Department of Pediatrics, Gunma University School of Medicine, Maebashi, Japan
Received June 2, 1998; accepted May 27, 1999.
Address correspondence and reprint requests to Masahiko Tabata, M.D., Department of Pediatrics, Gunma University School of Medicine, 3-39-15 Showa-Machi, Maebashi, Gunma, 371, Japan.
In 1937, Behçet (1) described a syndrome characterized by the triad of aphthous stomatitis, genital ulcers, and iritis. Subsequently, others have recognized that this condition affects many organ systems (2,3), including the gastrointestinal, cardiovascular, neural, and skeletal systems. Although ulcerative lesions in intestinal Behçet's disease may cause severe symptoms and complications, these lesions have been considered very rare in childhood, and few cases have been reported. The prevalence of Behçet's disease is remarkably high in Japan and the Middle East (2-9). Most Japanese cases have not been reported in the English literature or reviewed regarding gastrointestinal involvement in childhood. In this article, we review 21 pediatric cases of intestinal disease reported in the Japanese literature since 1972 (7-25), adding one of our own. The clinical features of these 22 Japanese pediatric cases are compared with the findings in Japanese adults and in Western pediatric reports.
A 5-year-old Japanese boy was admitted to the Gunma University Hospital because of recurrent aphthous stomatitis, abdominal pain, and high fever. Neither the parents nor other family members had features of Behçet's disease or chronic diarrhea. The boy had been born at 33 weeks' gestation, and his birth weight was 1640 g. Between the ages of 3 and 5 years, he had had numerous recurrences of aphthous stomatitis but otherwise remained in good health. A few weeks before his admission, intermittent fever and abdominal pain had developed. Findings in general physical and neurologic examinations were normal. Laboratory test results were as follows: complete blood count with differential count, normal; erythrocyte sedimentation rate, 72 mm/hr; blood chemistry values, normal; and C-reactive protein, 9.5 mg/dl. The following tests produced negative results: serologic tests for rheumatoid factor and antinuclear factor, lupus erythematosus cell test, and antistreptolysin O titer. Nonspecific skin reactivity to needle prick also was normal. A double-contrast barium enema study showed mucosal irregularity and an ulcer in the cecum. A fibercolonoscope study showed a simple ulcer and a dilated terminal ileum. Examination of biopsy specimens obtained from the area of the ulcer showed diffuse infiltrates composed of a mixture of mononuclear cells. No granulocytes, aggregates of lymphocytes, fissure-like ulcerations, or transmural inflammations were found to support the diagnosis of Crohn's disease or Behçet's disease.
We treated the patient with an elemental diet and total parenteral nutrition, as well as steroids and cyclosporine. However, his condition did not improve with any of these treatments. In the 15 months' follow-up since the onset of the disease, episodes of fever, abdominal pain, and aphthous stomatitis recurred. At 6 years of age, subtotal colectomy with ileostomy was performed selectively (Fig. 1). Histopathologic findings in the resected bowel included evidence of vasculitis at the bases of ulcers that were suggestive of Behçet's disease. At 8 years of age, a genital ulcer and erythema nodosum developed. One year later, he underwent emergency surgery for perforation of the terminal ileum adjoining the anastomosis performed at the first operation. He had symptoms including dysarthria, tremor, and gait disturbance of uncertain cause after the second operation. At the age of 12 years and 2 months, edema of the face and arms developed consequent to the superior vena caval syndrome (Fig. 2). He was treated with total parenteral nutrition, steroids, cyclosporine, and anticoagulants. However, no clinical improvement resulted, and viral pneumonia, respiratory distress syndrome, and multiple organ failure occurred. The patient died at the age of 12 years and 8 months, approximately 9 years after the onset of Behçet's disease.
MATERIALS AND METHODS
Case Ascertainment and Analysis
During the 25-year period from 1972 to 1996, 21 pediatric patients with intestinal Behçet's disease have been reported in Japan (10 boys, 11 girls; age range, 8 months to 15 years). The diagnosis of intestinal Behçet's disease was made based on the criteria for Behçet's disease, plus the presence of gastrointestinal ulcers. The diagnosis of Behçet's disease, made according to the Behçet's Disease Research Committee of the Japanese Ministry of Health and Welfare, was based on four major criteria (buccal ulcers, genital ulcers, eye lesions, and skin lesions) and six minor criteria (gastrointestinal lesions, thrombophlebitis, cardiovascular lesions, arthritis, central nervous system lesions, and positive family history). Three major criteria or two major and two minor criteria were needed for diagnosis. We have summarized the clinical symptoms of intestinal Behçet's disease in these 21 pediatric cases and in our case, comparing them with the 11 pediatric cases reported in current Western reviews by Kone-Paut et al. (26,27) and Lang et al., (28) and with 117 Japanese adult cases reported in a current review by the Behçet's Disease Research Committee of the Japanese Ministry of Health and Welfare (7,8,20,22). In the analysis of the prevalence of each symptom, we excluded reports in which the presence or absence of the symptom was not described clearly.
Before the present case, intestinal Behçet's disease had been reported in the Japanese literature in 21 pediatric patients (less than 15 years old). Including our patient, Behçet's disease among Japanese children showed intestinal involvement in 68.8% (22/32) of cases (7,9,11). Table 1 summarizes the clinical features of intestinal Behçet's disease in Japanese children. The male-to-female ratio was 11:11, and ages ranged from 8 months to 15 years. Of the four major diagnostic criteria, all patients (22 cases) had recurrent aphthous stomatitis, 16 of 21 (76.2%) had skin lesions, and 16 of 20 (80%) had genital ulcers. In contrast, eye disease was uncommon in Japanese pediatric patients, occurring in only 6 of 20 cases (30%). Of the five minor criteria apart from family history, arthritis, epididymitis, thrombophlebitis, cardiovascular lesions, and central nervous system lesions were rare in Japanese children. However, the needle-prick test was positive in 8 of 12 patients (66.7%). With respect to abdominal symptoms, all Japanese children with intestinal Behçet's disease had abdominal pain (100%); bloody stool was present in 15 of 16 (93.8%), high fever in 16 of 17 (94.1%), and anal lesions in 10 of 12 (83.3%). Other symptoms (abdominal mass, diarrhea, pain on defecation, anorexia, or emaciation) did not occur in most patients. Twelve of 19 children underwent surgery for indications including perforation (7 patients), covered perforation (5 patients), and stenosis (5 patients).
Table 2 summarizes the clinical symptoms of intestinal Behçet's disease in 22 pediatric cases, comparing them with 117 Japanese adult cases reported in a current review and with 11 pediatric cases reported in current Western reviews.
The diagnosis of Behçet's disease is often difficult to establish because of the absence of pathognomonic symptoms, signs, or laboratory findings at the onset. In Japan, the diagnosis of Behçet's disease is determined according to the Behçet's Disease Research Committee of the Japanese Ministry of Health and Welfare. As noted above, diagnosis is based on four major criteria and six minor criteria. Mason et al. (29) similarly have formulated four major diagnostic criteria (buccal ulcers, genital ulcers, eye lesions, and skin lesions) and six minor criteria (gastrointestinal lesions, thrombophlebitis, cardiovascular lesions, arthritis, central nervous system lesions, and positive family history), again proposing that three major, or two major and two minor criteria are needed to make a diagnosis. Our patient fulfilled three major criteria (recurrent aphthous stomatitis, a genital lesion, and skin lesions) and three minor criteria (gastrointestinal lesions, thrombophlebitis, and central nervous system lesions), satisfying both the Japanese and Western criteria for the diagnosis of Behçcet's disease. The 21 pediatric patients with intestinal Behçet's disease previously reported in Japan from 1972 to 1996 also satisfied both Japanese and Western criteria.
Among Japanese children with Behçet's disease (30), the proportion with intestinal involvement was higher than in Japanese adults (7,8,20,22) or Western children (26-28). It was also higher than that in children of Mediterranean countries (31,32). As for major criteria, all pediatric patients with intestinal Behçet's disease in both Japanese and Western populations had recurrent aphthous stomatitis, and a high frequency of skin lesions and genital ulcers was noted. Eye disease was relatively uncommon in Japanese children compared to Japanese adults and Western children.
Among children with Behçet's disease, a relatively low incidence of ocular disease has been reported by Mori et al., (9) Lang et al., (28) Hamaza (31), Ammann et al., (33) and Hashimoto et al. (34) In contrast, some other reports including adult patients with Behçet's disease have suggested an increased frequency of eye disease in younger patients. Children with Behçet's disease in Iran also frequently have (67%) ophthalmologic lesions (32). These conflicting findings may reflect the small number of pediatric cases in some series. Our review, including a relatively large number of patients, suggests that ocular disease is relatively uncommon in the Japanese pediatric population, at least in the subset with intestinal disease.
Little information is available in the Western literature concerning the symptoms of intestinal Behçet's disease in Western children. Japanese reports indicate that children with intestinal Behçet's disease frequently have abdominal pain, bloody stool, high fever, and anal lesions. The prevalence of abdominal pain is similar in Japanese children and Japanese adults. Bloody stool and abdominal masses occur more frequently in Japanese children than in Japanese adults (7,34). Japanese children appear to have a higher prevalence of stenosis than do Japanese adults, whereas in contrast, the frequency of perforation was 31.8% (7/22) compared with 52.1% (61/117) in Japanese adults.
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