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.
The patient was a 29-year-old female who had suffered from recurrent oral ulcers, abdominal pain and diarrhea since the age of 15 years. Recurrent ascending colonic ulcers and anastomotic ulcers along with intestinal obstruction were observed prior to and for 8 years after right hemicolectomy surgery (), accompanied by vasculitis in extremities (). Laboratory data showed elevated C-reactive protein (19.6 mg/L; normal range (NR) <5 mg/L) and erythrocyte sedimentation rate (25 mm/h; NR<20 mm/h), along with a low titer of the antinuclear antibody (1:100). Serum IgG and IgM were within the normal range but IgA levels were low (IgG 19.3–25.8g/L, IgM 0.73–0.92 g/L, IgA <0.07g/L). The patient responded to a glucocorticoid and thalidomide in 3 months with reduced frequency of diarrhea and less severe abdominal pain. The patient's IgA increased but did not reach normal levels after treatment. Subsequent inquiries into the patient's family history revealed that her father suffered from recurrent oral ulcers when he was young, and her brother had suffered from recurrent fever, oral ulcers and erythema nodosum-like lesions in the skin since he was 4 years old. The level of serum immunoglobulins in the father and brother were in the normal ranges. Because of the mild and non-specific symptoms, they accepted treatment of only antimicrobial mouthwash and dental ulcer paste instead of immunomodulators.