Schnitzler syndrome without monoclonal gammopathy: a systematic review and case presentation

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 patients with incomplete variants of SS that lack monoclonal gammopathy. This systematic review aims to analyse the current literature regarding the features of Schnitzler-like syndrome (SLS; i.e. patients with clinical features of SS but without the obligate Strasbourg criterion of monoclonal gammopathy) and their treatment outcomes; we also report our own case of a patient with SLS. 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. In total, 15 studies (13 case reports and 2 case series) met inclusion criteria, in addition to 1 patient's case from our own experience, resulting in a total of 18 patients. The majority of our population were male patients (56%) with a median age at diagnosis of 57.5 years (interquartile range 44.8-62.8). Most of the patients had absent monoclonal gammopathy (n = 14; 78%), and four (22%) had delayed-onset monoclonal gammopathy. Antihistamines were the most common treatment (n = 18; 100%), followed by anakinra (n = 14; 78%), prednisone (n = 9; 50%), unspecified systemic corticosteroids (n = 8; 44%), omalizumab (n = 8; 44%), colchicine (n = 5; 28%), dapsone (n = 6; 33%), ciclosporin (n = 4; 22%), canakinumab (n = 4; 22%), hydroxychloroquine (n = 2; 11%) and thalidomide (n = 1; 6%). Of the 14 patients treated with anakinra, 93% (n = 13/14) achieved a complete response. Our findings raise the hypothesis that monoclonal gammopathy may not be an obligate criterion for SS. We propose this as a consideration for future consensus discussions, emphasizing the potential benefits of early recognition and timely interleukin-1 inhibitor therapy to improve patient outcomes.