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.
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.