Patient 2 was a 20-year-old woman. From around the age of 12, she had occasionally suffered from severe abdominal pain of unknown cause. Around 13 years of age, she had suffered from a recurrent fever that persisted for 3–7 days and abdominal pain with a high level of serum CRP approximately every 2 months. Serum inflammatory reactants were negative during the intermittent episodes of fever. Lower gastrointestinal endoscopy showed erosion in Peyer’s patch of the ileum. Histopathologically, this lesion showed ulcers and granulation tissue with inflammatory cell infiltration. This case was initially considered to possibly involve familial Mediterranean fever (FMF) related to the heterozygous c.329T>C (p.Leu110Pro; rs11466018) and c.442G>C (p.Glu148Gln; rs3743930) variants of MEFV. However, colchicine given for diagnostic and therapeutic purposes failed to reduce the fever attacks, while NSAIDs and PSL were also ineffective for the fever and abdominal pain. When infliximab treatment was started with methotrexate as secondary prevention, the episodes of fever and abdominal pain completely disappeared. Finally, the heterozygous c.929T>C (p.Ile310Thr; rs530310566) variant of TNFAIP3 was identified in this patient. Her mother had the same variant but lacked any symptoms.
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).