A 34-year-old man with a history of ulcerative colitis was admitted to Aoyama Hospital, Tokyo Women's Medical University on July 12, 2000 with complaints of arthralgia in his right knee, erythema nodosum on his right leg, oral aphthous ulcers and bloody stools. Two months before his first visit, he had arthralgia in his right knee and bloody stools. After an episode of pharyngitis at the end of June 2000, his arthralgia and bloody stools worsened and he developed oral aphthous ulcers and erythema on his right leg.
At 18 years of age, the patient had bloody diarrhea and at 19 years of age, after an episode of pharyngitis, his bloody diarrhea worsened. He visited another hospital where a sigmoidscopy was performed. The sigmoidscopy showed an ulcerative lesion in his rectum. He was diagnosed with ulcerative colitis and treated with sulfasalazine (1.5 g/d kg). Shortly after, his symptoms disappeared.
Upon hospital admission (July 2000), the patient was 161 cm tall and weighed 55 kg. Erythema nodosum was noted on his lower, right leg and arthritis was noted in his right knee joint. An aphthous ulcer was present on his upper lip but no genital ulcers were present. Neurological findings were unremarkable. An eye examination revealed no evidence of uveitis.
The patient's complete blood count showed a normal red blood cell count, mild leukocytosis (8,400/μl) and mild thrombocytosis (56.9×104/μl). Blood chemistry data were within the normal range. Elevations in the erythrocyte sedimentation rate (ESR) (48.5 mm/h) and C-reactive protein level (2.5 mg/dl) were observed. He had no detectable antinuclear antibodies. Elevation of immunoglobulin D (21.0 mg/dl) was observed. The pathergy test was positive. HLA typing revealed that he is HLA-B51 positive. Multiple fresh stool specimens were negative for pathogens, however, these specimens were positive for occult blood (3+). Cerebrospinal fluid revealed no abnormalities including levels of cytokines (i.e., IFN-γ, IL-6 and IL-8). Roentgenograms of his fingers, sacroiliac joints, knee joints and ankle joints showed no abnormalities.
A barium enema (Fig. 1)
was obtained. It was consistent with a diagnosis of ulcerative colitis as it showed multiple simple ulcers and the disappearance of haustral markings, resembling a "lead-pipe appearance". Colonoscopy revealed multiple aphthous ulcers on the cecum, ascending colon, transverse colon, descending colon and sigmoid colon and also revealed a transmural ulcer on the rectum (Fig. 2)
. Biopsies of the sigmoid colon and rectum showed erosions and marked inflammatory cell infiltration in the lamina propria mucosae (Fig. 3A)
. The inflammatory infiltrate was composed of neutrophils, lymphocytes and plasma cells. Slight cryptitis (Fig. 3B)
and moderate goblet cell depletion were apparent, but Paneth cell metaplasia was absent. Neither granulomatous lesions nor vasculitis lesions were observed. From these findings, a diagnosis of ulcerative colitis in a mildly active phase was made.
A rectal biopsy revealed moderate inflammatory cell infiltration consisting of lymphocytes and plasma cells and a moderate loss of mucosa tubules. Hyperplastic lymph follicles were prominent (Fig. 4)
. Neither cryptitis, crypt abscesses nor Paneth cell metaplasia were present. Thus from these findings a diagnosis of chronic, non-specific proctitis with lymphoid hyperplasia was made.
An HE staining and microscopic study revealed no cytomegalovirus inclusion bodies or amoeba. Ziehl-Nielsen staining was negative for acid-fast bacilli. The pathological characteristics of colitis in Behçet's disease are the lack of transmural inflammation, submucosal fibrosis and granulomas. On the other hand, these pathological characteristics are markers of Crohn's disease. Therefore, these pathological findings indicated the presence of entero-Behçet's disease or Crohn's disease. Multiple fresh stool specimens failed to reveal any pathogens including C. difficile, Escherichia coli, Campylobacter, M. tuberculosis, Salmonella and Schistosomiasis.
Based on the following clinical evidence from this patient such as: 1) recurrent oral ulcers; 2) skin lesions (erythema nodosum); 3) positive for pathergy test; the patient was diagnosed as having Behçet's disease with gastrointestinal involvement by international criteria for diagnosis of Behcet's disease (6). However this case does not meet the standard criteria proposed by the Japan Behçet's Disease Research Committee (1987), as the case has two major symptoms (recurrent oral ulcers and skin lesions ) but only one minor symptom (arthritis without joint destruction) (7). A regimen of 5-aminosalicylate (Pentasa 1.5 g/day; Nisshin-Kyorin Pharma Co. Ltd., Tokyo, Japan) was started. The abdominal symptoms and genital ulcers improved after 1 month. A repeated colonoscopy revealed that the lesions including the multiple ulcers had also resolved. The patient was subsequently discharged 2 months after admission. 5-aminosalicylate (1.5 g/day) was continued as maintenance therapy.