AB1102 SCHNITZLER SYNDROME IN THE CLINICAL PRACTICE OF A RHEUMATOLOGIST

Abstract

Background Schnitzler syndrome (SchS) is a rare autoinflammatory multifactorial disease, manifested by urticaria, monoclonal immunoglobulin (usually IgM) secretion, bone pain, and clinical and laboratory signs of systemic inflammation (fever, leukocytosis, and CRP increase) [1]. SchS is included in the differential diagnosis of the adult Still’s disease, autoinflammatory diseases, and Waldenstrom macroglobulinemia. Interleukin 1 (IL-1) inhibitors (anakinra and canakinumab) have been shown to the efficient pathogenetic therapy of SchS [2,3]. Objectives To provide clinical and laboratory characteristics and the results of IL-1 inhibitors therapy in the SchS patients from 2015 to 2018 observed in the V.A. Nasonova Research Institute of Rheumatology (Moscow, Russia). Methods The study included 4 patients (1 female, 3 males) aged from 32 to 56 years. Patients with suspected SchS were studied with electrophoresis of serum and urine proteins, histological and cytological examination of the bone marrow (in 3 of 4 patients), and testing of mutations in NLRP3 and TNFRSF1A genes (in 3 of 4 patients). Results SchS was diagnosed 3 to 22 years (median 3,5 years) after the onset of clinical manifestations. Three patients had a fever. All patients showed chronic urticaria and musculoskeletal manifestations (arthralgia and leg bone pain). Two patients showed fluid collections in serous cavities. Pericarditis was observed in one patient, and pleurisy in another patient. To our knowledge, serositis was not described in SchS previously. Three patients had leukocytosis from 16.0 to 23.6 x109/L. In all patients, ESR (from 31 to 140 mm/h) and CRP level (from 29 to 192 g/L) increased. In all patients, secretion of monoclonal IgM was detected, not exceeding 7.8 g/L. In three cases, IgM included kappa chain, and in one patient biclonal secretion was found (IgM kappa and IgM lambda). Mutations in NLRP3 and TNFRSF1A genes were not identified. None of the patients showed lymphoplasmacytic infiltration of bone marrow. All patients before the diagnosis were prescribed with glucocorticosteroids with a temporary positive response and relapse of the disease after the dose reduction or withdrawal. Two patients received canakinumab 150 mg subcutaneously once every 8 weeks for 1.5-3.5 years, with a complete response. In one, the interval between injections was increased during the last year to 5 months, with the preservation of clinical and laboratory remission of SchS. Against the background of canakinumab therapy, one patient became a farther of a healthy baby. One patient received anakinra 100 mg subcutaneously of daily, with the complete clinical and laboratory response after 2 weeks of therapy. During the use of the IL-1 inhibitors, we have observed none clinically significant side effects. Conclusion To diagnose SchS in adult patients with chronic urticaria, fever, and acute phase signs of inflammation, one should perform serum proteins electrophoresis. SchS can manifest with serositis. IL-1 inhibitors in SchS patients are the efficient by and safe therapy.