Background/Purpose: Schnitzler’s syndrome is a rare late onset auto-inflammatory disease which associates a chronic/recurrent urticarial skin rash, a monoclonal gammopathy (mostly IgM kappa), and a variable combination of intermittent fever, osteoarticular pain, sclerotic bone lesions, lymphadenopathy and/or hepatosplenomegaly. This chronic disease can significantly alter patients’ quality of life through intermittent fever, rash, pain and sometimes profound weight loss or anaemia. Patients can also develop a hematologic malignancy (mainly Waldenström’s macroglobulinemia). In recent years several case reports have underscored the efficacy of Anakinra but long-term follow-up data are scare. Further, a few patients who did not respond to IL1 blockade have been reported recently.

Methods: Retrospective analysis of a French multicenter cohort of 40 patients with Schnitzler’s syndrome.

Results: In this cohort mean age at disease onset was 61y (53-74). Mean diagnostic delay was 3 years. Disease manifestations included urticarial rash (100%), intermittent fever (81%), weight loss (62%), bone and/or articular pain (86%) and anaemia (Hb<10g/dL ; 46%). All patients had systemic inflammation and 80% had bone lesions. Monoclonal gammopathy was IgM kappa in 85% of cases. Mean follow-up was 9 years (2-35). Twenty eight patients (70%) received Anakinra. Thirteen of those were corticodependant (mean dose : 15mg/d) when Anakinra was introduced. All 28 patients experienced a dramatic improvement of all clinico-biological signs of disease activity. Mean hemoglobin level rose from 11,2 to 13,4 g/dL  (p<0.001). At last follow-up, all patients remained on anti-IL1 therapy. A single patient was switched to Canakinumab, due to injection site reactions to anakinra. Eighty percent of patients were in complete remission under anti-IL1 monotherapy, 11% were in complete remission under anakinra plus low dose corticosteroids and 4% were in partial remission under anakinra monotherapy. Mean follow-up under anakinra was 40 months (2-73). No loss of effectiveness was observed. In case of treatment interruption most patients experienced disease flare within 24-48 h. Alternate day injections were sufficient to maintain remission in only 4 cases. Three cases of uncomplicated neutropenia were recorded. Six patients developed severe infections including pneumonia in 5 cases, with local predisposing factor in 4 (severe COPD in 3, enteral feeding in 1). Anakinra had no obvious effect on the monoclonal component. No lymphoproliferative disease occured. When last seen, all 12 patients without anakinra had an active disease with variable impact on quality of life. Their mean corticosteroids dosage was 7mg/d.

Conclusion: Anakinra is dramatically effective in Schnitzler’s syndrome. Treatment failure should lead to reconsider the diagnosis. Long-term follow-up reveals no loss of effectiveness and a favourable safety and tolerance profile. Alternate day injections are rarely sufficient to maintain remission. The effects regarding the risk of malignant transformation remain undertermined.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/long-term-efficacy-and-safety-of-il1-receptor-antagonist-in-schnitzlers-syndrome-a-french-multicenter-study/