Patient 1 was a 4-year-old boy. At 11 months old, he had been hospitalized for cervical lymphadenitis and then suffered from repeated tonsillitis, cervical lymphadenitis, and bronchitis with elevated serum C-reactive protein (CRP). He was initially suspected of having an immunodeficiency disease but had no abnormalities in neutrophil function, lymphocyte fraction, or immunoglobulin levels. During the fever episodes, no significant pathogens were detected and his fever often improved without antibiotics. Because a single dose of prednisolone (PSL) was effective for the fever, he was diagnosed with periodic fever, aphthous stomatitis, pharyngitis, and adenitis (PFAPA) syndrome based on Thomas’s criteria []. At the age of 4 years and 2 months, fever with pharyngeal redness persisted for 9 days, with PSL not being effective for it. The patient also had temporary nonbacterial coxitis. He had a heterozygous c.574G>A (p.Glu192Lys) variant of TNFAIP3. After undergoing tonsillectomy, the frequency of the fever episodes decreased. His father also suffered from recurrent stomatitis, folliculitis, and hemorrhoids and possessed the same variant of TNFAIP3.
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).