Background/Purpose: Muckle-Wells syndrome (MWS) is a rare autoinflammatory disease, which is categorized as one of the three cryopyrin-associated periodic syndromes (CAPS). MWS is characterized by recurrent episodes of fever, rash and joint pain, and may lead to renal amyloidosis and severe neurological involvements such as hydrocephalus and progressive hearing loss. Here we describe the first cohort of MWS patients in Chinese population, with emphasis on clinical features and gene variations.

Methods: Four Han Chinese patients were diagnosed as MWS from the year 2013 to 2016 at our adult clinic for autoinflammatory diseases. All the diagnoses were confirmed by mutations in the NLRP3 gene. All relevant clinical and genetic data were collected retrospectively and followed up prospectively.

Results: All the four patients were male. The median age at disease onset was 4.5 (ranging from 2 to 46) years and the mean disease duration before diagnosis was 14.25¡À12.63 (ranging from 1 to 29) years. One patient had adult onset disease at the age of 46, and the remaining patients experienced delayed diagnosis into adulthood because of physicians’ unfamiliarity with this syndrome in China. All patients denied positive family history. All patients had intermittent febrile episodes with moderate to high temperature. One patient’s attacks could be triggered by cold exposure. The mean duration of fever attacks was 3.81¡À2.51 (ranging from 0.25 to 6) days and the interval between attacks ranged from several weeks to several months. Skin rashes were present in all patients, which could be erythematous macular or papular, urticarial, erythema nodosa-like and Sweet disease-like. Two out of 4 suffered from frequent oral ulcers, 2/4 conjunctivitis, 2/4 myalgia, 2/4 headache, 2/4 arthralgia, 1/4 prominent polyarthritis, 1/4 pharingitis, 1/4 abdominal pain, 1/4 severe sensorineural hearing loss, 1/4 epilepsy, 1/4 chronic meningitis with communicating hydrocephalus. All patients had moderately elevated peripheral leukocyte count and systemic inflammatory markers during attacks, which return to normal during intervals. Each patient carried a novel heterozygous mutation in NLRP3 gene, including Q705K, V72M, D31V, T350M, respectively. Three patients had good response to the combination of moderate to high dose of prednisone and conventional DMARDs. Due to economic constraints and unavailability of anti-interleukin 1 therapies in China, only one patient received an anti-TNF¦Áagent. None showed evidence of renal amyloidosis.

Conclusion: Our observational study suggests for the first time that MWS could be identified among adult Chinese patients with intermittent fever of unknown cause, but with unique features compared with previously reported patient cohorts. Our patients are exclusively male without positive family history, with fewer presentations of urticarial rash and hearing loss, and responded better to conventional oral treatments. Considering the lack of amyloidosis, whether our patients had better outcome remains to be seen. The more accurate characterization of Chinese patients suffering from MWS and CAPS needs further studies. Figure 1. A1& A2: erythematous macular and oral ulcer of one patient. B1& B2: resolution of transient arthritis in 1st TMP within one day. C1& C2: new maculopapular rash in the neck and pigmentation after rash disappearance in the forearm.