Patient 3 (III-1 in Fig. b) is a 12-year-old girl who is the first child of non-consanguineous Japanese parents. At 2 months of age, she presented with 38–39 °C fever accompanied by abdominal pain, diarrhea, ankle arthralgia, oral ulcers, pharyngalgia, and an enlarged tonsil. Febrile attacks were recurrent every 1–2 weeks and resolved within 4 days. She presented with perianal ulcers (at 4 years old), bloody stool, and weight loss (at 5 years old), but colonoscopy did not identify any abnormality. At 9 years of age, she was prescribed with naproxen and methotrexate (MTX) because of left ankle arthritis, but MTX was stopped because of abdominal pain. She was treated with colchicine and mesalazine for abdominal pain, but they were not effective. At 10 years of age, she was suspected of having a periodic fever, aphthous stomatitis, pharyngitis, and adenitis (PFAPA) syndrome and was treated with cimetidine, which contributed to a reduction in the number of febrile attacks. Gastrointestinal and capsule endoscopy revealed multiple ulcers throughout the intestinal tract (Fig. ), and mesalazine was re-administered. Histopathology of ulcer biopsies showed infiltration of lymphocytes and plasma cells. There was no evidence of granuloma, cryptitis, or crypt abscess, and the findings were thought to indicate nonspecific chronic inflammation. At 11 years of age, bilateral non-granulomatous acute anterior uveitis was revealed by ophthalmologic examination and diagnosed as BD. She did not show any neurodevelopmental delay. Currently, she experiences genital ulcers and has been treated with colchicine (400 mg/day), cimetidine (1.0 mg/day), and corticosteroid eye drops. The severity of abdominal pain is milder than before and fever is less frequent.
Patient 1 (III-2 in Fig. a) is a 35-year-old male who is the second child of non-consanguineous Japanese parents. He presented with fever and lymphadenopathy at the age of 6. He was diagnosed with BD at 7 years of age because of recurrent oral and perianal ulcers and was prescribed with oral prednisolone (PSL). He had recurrent episodes of high-grade fever (up to 39 °C) associated with lymphadenopathy, pharyngalgia, and nausea. PSL dosage was adjusted according to the patient’s condition, and the withdrawal of PSL was difficult. He did not show any ophthalmological or neurological symptoms. He is currently treated with PSL (12.5 mg/day) and colchicine (1.0 mg/day).