Monoclonal gammopathy–associated autoinflammation: A systematic review and meta-analysis of Schnitzler syndrome.

Abstract

e19579 Background: Schnitzler syndrome is a rare, underdiagnosed disorder that usually presents with late-onset systemic inflammation and monoclonal gammopathy. Key clinical findings include chronic urticarial rash, fever, bone pain, and lymphadenopathy. Given that most data regarding this rare disease are derived from small observational studies, this study aims to systematically characterize the demographic, clinical, laboratory, and treatment outcomes of patients with Schnitzler syndrome. Methods: A thorough literature search of the PubMed, Scopus, and Web of Science databases was performed in September 2025. Data on medical history, presentations, complications, diagnostics, treatment patterns, and outcomes were obtained. Results: This pooled analysis includes 187 articles reporting 243 individual cases of Schnitzler syndrome over the years 1989–2025. The mean patient age was 57.4 years ±12.2 with a male-to-female ratio of 1.32:1, indicating a slight male predominance. The most frequently reported manifestations were chronic urticarial rash (226/243, 93.0%), fever (194/243, 79.8%), and arthralgia (145/243, 59.7%), with lymphoid involvement mainly manifesting as lymphadenopathy (63/243, 25.9%); progression to lymphoproliferative disorders was rare (15/243, 6.2%). Most patients presented with an IgM gammopathy (193/243, 79.4%), confirming IgM as the predominant class. In a smaller subset, IgG (26/243, 10.7%) and IgA (3/243, 1.2%) gammopathy was present. Regarding light chain type, kappa predominated (162/243, 66.7%), with fewer cases of lambda (22/243, 9.1%). When stratified by immunoglobulin class, age differed significantly between patients with IgM and IgG gammopathy (58.5 vs 50.8 years, p = 0.015). IL-1 inhibitors were frequently used, with 124/243 patients receiving this therapy (51.0%). Corticosteroids of various formulations were administered in 154/243 patients (63.4%). Treatment response was favorable in most patients, with 126/243 achieving a complete clinical response (51.9%) and 47/243 a partial response (19.3%). Sixteen patients showed no response (6.6%). On multivariate analysis, IL-1 inhibitor use was independently associated with higher odds of complete response (OR 7.89; 95% CI 1.70–36.65). In the minority of patients who relapsed after an initial response to IL-1 inhibitors due to treatment discontinuation or tapering, the addition of corticosteroids restored the response. Conclusions: Schnitzler syndrome is a rare autoinflammatory condition predominantly affecting older males, characterized by chronic urticaria, fever, and IgM kappa gammopathy. While IL-1 inhibitors and corticosteroids offer high rates of clinical response, the frequent relapse upon tapering underscores the need for long-term maintenance. Studies are needed to explore if anti-plasma cell therapy would decrease relapse and induce long-term remission.