Patient 3 was a 24-year-old woman. She had suffered from athetoid cerebral palsy due to cardiopulmonary arrest of unknown cause on postnatal day 1. She had developed epilepsy at the age of 4 years and type 1 diabetes with positive anti-glutamic acid decarboxylase antibody at the age of 12 years. At the age of 24 years, she had a fever, facial erythema, and proteinuria. She was diagnosed with systemic lupus erythematosus (SLE) with the following findings: positive antinuclear antibodies, anti-dsDNA antibodies, anti-Sm antibodies, anti-cardiolipin antibodies, hypocomplementemia, and positive direct Coombs test. She had a heterozygous c.2126A>G (p.Gln709Arg) variant of TNFAIP3. Her father had the same variant but lacked any symptoms.\nThe variant Glu192Lys was identified among 55 patients suspected of having autoinflammatory diseases analyzed at Gifu University Hospital from October 2017 to September 2020. The patients with variants Ile310Thr and Gln709Arg were recruited by personal communication with the collaborators (Nagasaki University and Tokyo Medical and Dental University).\nWritten informed consent to participate in this study was obtained from each of the patients or their parents. This study was conducted in accordance with the Declaration of Helsinki and approved by the ethics boards of Gifu University and Tokyo Medical and Dental University.
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.