Background: Muckle-Wells syndrome (MWS) is a monogenic autoinflammatory disease caused by a NLRP3 gene mutation. It is the most common variant of cryopyrin-associated periodic syndromes (CAPSs) and can be observed in rheumatology practice. It manifests itself in fever, urticaria-like rash, arthralgias/arthritides, conjunctivitis/uveitis, sensorineural hearing loss, acute-phase markers (ESR, CRP). The disease’s onset usually takes place in infancy. There are examples of family cases. Targeted therapy: interleukin-1 inhibitors (anakinra, canakinumab).

Objectives: to provide characteristics of MWS patients, family cases in the rheumatology practice of the Federal Rheumatology Center in Russia.

Methods: in a 10-year period (2009 to 2019), MWS was diagnosed in 42 outpatient and inpatient patients, among them were 24 children, 18 adults, and 9 family cases. All of them underwent a standard rheumatology examination, including a ECR, CRP, ophthalmologist examination, and an audiogram. A molecular genetic test of the NLRP3 gene was carried out for all patients, the diagnosis was confirmed in all of them.

Results: Out of 18 adult patients aged between 19 and 59 years, women were prevalent (16 to 2), the onset age was 0 to 53 years, in 88,9% cases the onset took place before a patient was 18 years old. When diagnosed, the disease duration varied from 6 to 46 years. Most patients demonstrated fever, urticarial-like rash, arthralgias/arthritides, which were observed in 16 patients (88.9%), conjunctivitides were observed in 15 patients (83,3%), sensorineural hearing loss – in 8 patients (44,4%), abdominal pain, nausea, vomiting – in 4 patients, headache, dizziness – in 6 patients. There also were rare manifestations, such as: recurrent oral ulcers (8), genital ulcers (3), erythema nodosum (3), sore throat and raids on the tonsils (PFAPA-like phenotype) was observed in 2 patients. In 3 patients manifestations were triggered by cold temperature. All patients had an increased ESR and C-reactive protein concentration. Eight family cases of MWS were identified (in total 26 family members aged between 2.5 and 62 years) with a number of affected in one family ranging from 2 to 6 people of different age (8 children, 18 adults, out of which 20 were female, and 6 were male). Most patients had fever (17), urticarial-like rash (18), conjunctivitides (12), oral ulcers (7), articular syndrome (14), sensorineural hearing loss (5), and 2 patients died of renal insufficiency (probably due to amyloidosis of the kidneys). The heterozygous mutations in NLRP3 have been identified in pts: T348M (3 families), R262W (2 families), A439V (1), V198M (1), Pro294Ser (1). Ten patients received canakinumab for a period of 6 months to 6.5 years, and 5 patients received anakinra before canakinumab.

Conclusion: MWS is an orphan autoinflammatory disease, however it sometimes can be observed in rheumatology practice. It is very important to acquire family medical history to identify affected family members and prescribe therapy in a timely manner. IL-1 inhibitors are an effective and safe treatment option for MWS patients.

Disclosure of Interests: None declared