A CIAS1 mutation in a Japanese girl with familial cold autoinflammatory syndrome

Abstract

Abbreviations ACU acquired cold urticaria CIAS1 cold-induced autoinflammatory syndrome 1 CINCA chronic infantile neurologic cutaneous and articular FCAS familial cold autoinflammatory syndrome MWS Muckle-Wells syndrome NOMID neonatal-onset multisystem inflammatory disease Here we describe a Japanese girl with familial cold autoinflammatory syndrome (FCAS) and identify the mutation in the CIAS1 gene, encoding a cryopyrin protein expressed mainly in phagocytic cells. A 14-year-old girl was referred to our hospital because of a rash, fever, and arthralgia. From 4 months of age, she had suffered from intermittent episodes of pruritic rash. At the age of 13 years, she had developed severe pain in the right hip joint and a gait disturbance and had been admitted to a local hospital. The patient then experienced intermittent right arthralgia and lumbago and was treated with nonsteroidal anti-inflammatory drugs. Physical examination revealed discrete urticarial plaques 2–10 mm in diameter surrounded by macular erythema distributed across the cheeks and lower and upper extremities (Fig. 1a). After exposure to cold air, the urticarial rash worsened and conjunctivitis appeared. The ice cube test result was negative. The patient’s father and paternal grandmother seemed to also have a similar urticarial rash and conjunctivitis after cold exposure. Laboratory tests showed an elevated white blood cell count of 13,500/μl with 79% neutrophils, an elevated erythrocyte sedimentation rate of 44 mm/h, and an elevated C-reactive protein concentration of 4.4 mg/dl. Skin biopsy revealed moderate superficial and minimal deep perivascular inflammation with interstitial neutrophils and mononuclear cells (Fig. 1b). Patients have long been diagnosed as having acquired cold urticaria (ACU) because FCAS has not been reported in Japan. However, in this case, an ice cube test was negative, and the patient was suspected Eur J Pediatr (2008) 167:245–247 DOI 10.1007/s00431-007-0451-x