A case of cryopyrin‐associated periodic fever syndrome due to Q703K mutation in the NLRP3 gene

Dear Editor, Cryopyrin-associated periodic syndrome (CAPS) is a rare entity (with estimated prevalence of 1/360 000 people) that encompasses a spectrum of three phenotypes of increasing severity, namely, familial cold urticaria (FCUS), Muckle-Wells syndrome (MWS) and chronic infantile neurological, cutaneous, and articular syndrome/neonatal onset multisystem inflammatory disorder (CINCA/NOMID). The syndrome is due to dominant gain-of-function mutations in NLRP3 gene, which encodes a sensing element of inflammasome, a key component of the innate immunity that regulates the secretion of interleukin (IL)-1b. CAPS manifests as systemic inflammation, with hallmarks of fever, urticarial rash, arthralgia or frank arthritis. CAPS compromises quality of life and leads to serious complications and handicaps. The diagnosis of CAPS is difficult, is based on identification of pattern of febrile episodes with urticarial rash, arthralgia/arthritis (provoked by exposure to cold in FCUS), sensorineural hearing loss (in MWS) or, in CINCA/NOMID, as neonatal onset of severe inflammatory disease with recurrent aseptic meningitis. Other etiologies (infections, malignancies) should be excluded. Genetic test for mutations of NLRP3 gene is not required for the diagnosis due to high rate of negative results. We describe herein a case of a child with CAPS that presented with clinical and laboratory features of systemic juvenile idiopathic arthritis (JIA), and discuss the course of the disease and approach to treatment.