The index patient is a 12-year-old male, who was born healthy at term to consanguineous parents of Pakistani origin. At 1 year of age, he developed mild, self-limiting oral aphthous ulcers. Neutropenia was first noted on an incidental blood test when he was 3 years old. From the age of 7 years, he suffered progressive, deep oral ulceration severe enough to result in complete dysphagia and several hospital admissions. He also developed transient perianal ulceration associated with episodic diarrhea and intermittent abdominal pain. Other pertinent features included a swinging pyrexia (39°C), oligoarthritis (knees) associated with a joint effusion on at least one occasion, and cervical lymphadenopathy. At the age of 11, he developed a rash on his right shin. The rash was diagnosed as erythema nodosum. He had no eye symptoms, or any other organ involvement. The only notable infections were paronychial nail infections and a conjunctival infection due to herpes simplex virus. The patient had two other siblings, and only the younger brother who initially was asymptomatic, later developed similar but less severe clinical features. There was no other significant family history of inflammatory disorders. The index patient responded well to prednisolone, but he remained dependent on high doses of the steroid. The trial of colchicine was ineffective, but he subsequently responded fully to adalimumab.
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).