Schnitzler's syndrome (SchS) is a rare, disabling, autoinflammatory disorder characterized by recurrent urticarial rash and monoclonal IgM gammopathy. Interleukin-1 beta (IL-1β) plays an important role in the pathophysiology of SchS. Only anecdotal reports demonstrate the efficiency and safety of human monoclonal anti-human IL-1β antibody (canakinumab) use in SchS therapy. However, there are no generally accepted recommendations concerning the scheme (or frequency) of canakinumab use for this disease. Here, we report the effective long-term treatment of SchS in a 44-year-old male with a standard canakinumab dose (150 mg) but with an increased 4-month injection interval.

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Background:Schnitzler’s syndrome (SchS) and adult onset Still disease (AOSD) are currently considered as multifactorial autoinflammatory diseases (MAIDs) and are classified as systemic inflammation with urticarial rash. Clinical similarities between SchS and AOSD (fever, urticarial rash, arthralgias), increased ESR and CRP and the efficacy of IL-1 inhibitors may lead to the diagnostic delay in SchS pts. Testing for monoclonal gammopathy helps establish the diagnosis in SchS pts but is not routinely used in AOSD pts.Objectives:to examine demographic, clinical and laboratory characteristics, and the therapy of SchS pts in a single rheumatology center.Methods:5 SchS patients (2 females, 3 males), aged 32 to 68, underwent inpatient and outpatient examinations in the rheumatology center. All pts underwent a standard rheumatology examination, including ESR, CRP and M-gradient. 4 pts underwent genetic testing for mutations inNLRP3, TNFRSF1Agenes to exclude MAIDs, such as CAPS and TRAPS.Results:All pts were initially diagnosed with AOSD. The age at onset ranged between 28 and 66 years. Time to diagnosis varied from 2 to 22 years, being within 4 years in 4 of 5 pts. Patients presented with fever (4), urticarial rash (5) and musculoskeletal manifestations (5) (arthralgia in 3, bone pain in 4). Of 2 pts with serositis one presented with pericarditis and another – with pleuritis. Only 1 demonstrated a sore throat and polyneuropathy of the lower extremities. ESR and CRP were increased in all pts, leukocytosis was noted in 4 (Table 1). The monoclonal IgMk secretion was revealed in 5 pts, IgMκ and IgMλ – in 1 and IgGκ and IgGλ - 1. NoNLRP3, TNFRSF1Agene mutations were identified. Prior to the diagnosis, all pts were treated with glucocorticoids with a transient partial clinical response and a disease relapse after reducing the dose or stopping the treatment. 2 pts failed to respond to methotrexate and 1 – to hydroxychloroquine. 4 pts were prescribed with 150 mg canakinumab, a monoclonal antibody targeting IL-1, subcutaneously once every 8 weeks. The treatment duration varied from 6 months to 5 years. 2 pts, who initially received daily 100 mg anakinra subcutaneously for 2 to 3 months with a positive response, were further treated with canakinumab. During the treatment with canakinumab, all pts rapidly responded with a complete resolution of fever, rash, arthralgias and bone pains, an overall health improvement and a normalization in ESR and CRP levels. The therapy was well tolerated. In 1 patient, the intervals between canakinumab injections were prolonged to 5 months without any evidence of relapse. During this period, the male patient became a parent to a healthy child.Conclusion:In rheumatology practice SchS can be misdiagnosed with AOSD. AOSD patients should be tested for monoclonal gammopathy. IL-1 inhibitors are a highly effective and well-tolerated treatment option for SchS. In SchS patients with a complete response to canakinumab, injection intervals can be individualized.Disclosure of Interests:None declared

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