Schnitzler Syndrome without Monoclonal Gammopathy: A systematic review and case presentation

Background Schnitzler syndrome (SS) is a rare autoinflammatory disorder that presents with chronic urticarial rash, neutrophilic urticarial dermatosis, monoclonal IgG or IgM gammopathy, recurrent fever, joint and/or bone pain and enlarged lymph nodes, spleen, and/or liver. Several cases in the literature have described incomplete variants of SS that lack monoclonal gammopathy. This systematic review aims to analyze the current literature regarding the features of Schnitzler-like Syndrome (SLS) and their treatment outcomes; we also report our own case of SLS. Methods A systematic search of MEDLINE, Embase, Scopus and PubMed was performed (PROSPERO: CRD42024548245). All articles in English or French were included, and no publication date restrictions were applied. All articles with original data, clinical features and treatment outcomes were included. Two reviewers independently conducted screenings and conflicts were resolved by a third reviewer if necessary. Results 15 studies (13 case reports and 2 case series) met inclusion criteria, in addition to one case from our own experience, yielding a total of 18 patients. The majority of our population was male (55.6%) with a median age at diagnosis of 57.5 (IQR=44.8, 62.8). The majority of our patients had absent monoclonal gammopathy (n = 14; 77.8%), and four (22.2%) had delayed-onset monoclonal gammopathy. Antihistamines were the most common treatment (n=17; 94.4%), followed by anakinra (n=14; 77.8%), prednisone (n = 9; 50.0%), unspecified systemic corticosteroids (n=8; 44.4%), omalizumab (n=8; 44.4%), colchicine (n = 5; 27.8%), dapsone (n = 6; 33.3%), cyclosporine (n = 4; 22.2%), canakinumab (n=4; 22.2%), hydroxychloroquine (n=2; 11.1%) and thalidomide (n=1; 5.6%). Of the 14 patients treated with anakinra, 92.9% (n = 13/14) achieved a complete response (CR). Conclusions Our findings raise the hypothesis that monoclonal gammopathy may not be an obligate criterion for Schnitzler syndrome. We propose this as a consideration for future consensus discussions, emphasizing the potential benefits of early recognition and timely IL-1 inhibitor therapy to improve patient outcomes.