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The objectives of the study were to present the experience of diagnosis, management, and therapy with IL-1 inhibitors in patients with Schnitzler's syndrome (SchS) according to a multicenter Russian cohort. An observational retrospective study for a 10-year period (2012–2022) involved 17 patients with SchS who were admitted to the hospital or were observed on an outpatient basis (eight women and nine men). The diagnosis of all of them corresponded to the Strasbourg diagnostic criteria. The age of patients ranged from 25 to 81 years (Me 53[46; 56]). The age at the time of the onset of the disease ranged from 20 to 72 years (Me 46[39; 54]), the duration of the disease before diagnosis ranged from 1 to 35 years (Me 6.5[3; 6]), in three patients it exceeded 10 years, in the rest it ranged from 1 to 8 years. Infectious and lymphoproliferative diseases, monogenic AIDs (CAPS, TRAPS, and HIDS) were excluded from all patients at the prehospital stage. The referral diagnosis for all of them was Still 's disease in adults. Clinical manifestations of the disease in all patients included fatigue, lethargy, fatigue, rash, and fever. In all patients, skin elements were urticular and were accompanied by itching in 6 (37.5%) patients. Bone pain was observed in 12 (70.6%) patients; arthralgias, in 16 (94.1%); arthritis, in 9 (52.9%); myalgia, in 7 (41.2%); and weight loss, in 4 (23.5%). Lymphadenopathy was detected in 6 (35.3%) patients; enlarged liver, in 6 (35.3%); pericarditis, in 4 (23.5%); angioedema, in 6 (35.3); redness and dryness in the eyes, in 3 (17.6%); sore throat, in 2 (11.8%); abdominal pain, in 1 (5.9%), distal polyneuropathy, in 2 (11.8%); paraesthesia, in 1 (5.9%); and chondritis of the auricles, in 1 (5.9%). Monoclonal gammopathy was detected in all patients with a secretion level of 2.9–15.1 g/L: IgMk (n = 10, 64.7%), less often IgMλ (n = 2), IgGk (n = 2), IgGλ (n = 1), and IgAλ (n = 1). Ben-Jones protein was not detected in any of them. All patients had an increased level of ESR and CRP. Before inclusion in the study, 16 patients received GCs (94.1%) with a temporary effect that disappeared with dose reduction or cancellation. Seven patients received cDMARDs, including methotrexate (5), hydroxychloroquine (2), and cyclophosphamide (1). All patients received NSAIDs and antihistamines, as well as biologics, including the anti-B-cell drug rituximab (1), monoclonal ABs to IgE omalizumab (2, 1 without effect and 1 with partial effect), IL-1i canakinumab (n = 10, 58.8%) subcutaneously once every 8 weeks, and anakinra (n = 4, 23.5%) subcutaneously daily. The duration of taking anakinra, which was prescribed in the test mode, ranged from 1 week to 2.5 months with a further switch to canakinumab in 3 patients. The duration of taking canakinumab at the time of analysis ranged from 7 months to 8 years. Against the background of treatment with IL-1i, 10 out of 11 (90.9%) patients received a complete response in terms of the clinical manifestations of the disease and a decrease in the level of ESR and CRP within a few days. In one patient, a partial response to the administration of anakinra was detected; however, after switching to canakinumab, the effect of treatment was finally lost. One patient received IL-6i for 8 months with an incomplete effect and a positive dynamics after switching to anakinra. Thus, anakinra was initially prescribed to four patients and changed to canakinumab in two of them; canakinumab was started as the first drug in seven patients. Treatment with anakinra was continued in two patients; with canakinumab, in nine patients. In one patient, due to the persistent absence of relapses, the interval between canakinumab injections was increased to 5 months without signs of reactivation; however, subsequently, against the background of stress and relapses of the disease, the intervals were reduced to 4 months. A healthy child was born by the same patient on the background of treatment. The tolerability of therapy was satisfactory in all patients, no SAEs were noted. SchS is a rare multifactorial/non-monogenic AID that should be differentiated from a number of rheumatic diseases and other AIDs. The onset in adulthood, the presence of recurrent urticarial rashes in combination with fever and other manifestations of a systemic inflammatory response are indications for examination for monoclonal secretion. The use of short- or long-acting IL-1i is a highly effective and safe option in the treatment of such patients. [ABSTRACT FROM AUTHOR]

The aim – to present the experience of diagnosis, management, and therapy with IL-1 inhibitors in patients with Schnitzler’s syndrome (SchS) according to a multicenter Russian cohort.Materials and methods. In an observational retrospective study for a 10-year period (2012–2022), 17 patients with SchS who were admitted to the hospital or were observed on an outpatient basis, among them 8 women, 9 men, were included in the study. The diagnosis of all corresponded to the Strasbourg diagnostic criteria.Results. The age of patients ranged from 25 to 81 years (Me 53 [46; 56] years). The age at the time of the onset of the disease ranged from 20 to 72 years (Me 46 [39; 54] years), the duration of the disease before diagnosis ranged from 1 to 35 years (Me 6.5 [3; 6] years), in 3 it exceeded 10 years, in the rest it ranged from 1 to 8 years. Infectious and lymphoproliferative diseases, monogenic AIDS (CAPS, TRAPS, HIDS) were excluded from all patients at the prehospital stage. The guiding diagnosis for all was Still’s disease in adults. Clinical manifestations of the disease included: fatigue, lethargy, fatigue, rash and fever in all, skin elements were urticular in all, accompanied by itching in 6 (37.5%). Bone pain had 12 (70.6%), arthralgia – 16 (94.1%), arthritis – 9 (52.9%), myalgia – 7 (41.2%), weight loss in 4 (23.5%). Lymphadenopathy (6), enlarged liver (6), pericarditis (4), angioedema (6), redness and dryness in the eyes (3), sore throat (2), abdominal pain (1), distal polyneuropathy (2), paraesthesia (1), chondritis of the auricles were less common (1). Monoclonal gammopathy was detected in all with a secretion level of 2.9–15.1 g/l: IgMk (n=10 (64.7%)), less often IgMλ (n=2), IgGk (n=2), IgGλ (n=1), IgAλ (n=1). Ben-Jones protein was not detected in any of them. All patients had an increase in the level of ESR, CRP. 16 patients before inclusion in the study received GC (94.1%) with a temporary effect and its escape with dose reduction or cancellation, DMARD – 7, among them methotrexate (5), hydroxychloroquine (2), cyclophosphamide (1), also NSAIDs and antihistamines in all, biological drugs: anti-B-cell the drug rituximab (1), monoclonal AT to IgE – omalizumab in 2 (1 – without effect, 1 – partial effect). 11 patients were prescribed IL-1: canakinumab – 9 (52.9%) subcutaneously once every 8 weeks, anakinra – 4 (23.5%) subcutaneously daily. The duration of taking anakinra, which was prescribed in the test mode, ranged from 1 week to 2.5 months with a further switch to canakinumab in 3. The duration of taking canakinumab at the time of analysis ranged from 7 months to 8 years. Against the background of treatment with IL-1, 10 out of 11 (90.9%) received a complete response from the clinical manifestations of the disease and a decrease in the level of ESR and CRP within a few days. In 1 patient, a partial response was received to the administration of anakinra, and when switching to canakinumab, the effect of treatment was finally lost. 1 patient received IL-6 for 8 months with incomplete effect and transition to IL-1 with positive dynamics. In 1 patient, due to the persistent absence of relapses, the interval between canakinumab injections was increased to 5 months without signs of reactivation, but subsequently, against the background of stress and relapses of the disease, the intervals were reduced to 4 months. A healthy child was born in the same patient on the background of treatment. The tolerability of therapy was satisfactory in all patients, no SAE was noted.Conclusion. SchS is a rare multifactorial/non–monogenic AID that needs to be differentiated from a number of rheumatic diseases and other AIDS. The onset in adulthood, the presence of recurrent urticarial rashes in combination with fever and other manifestations of a systemic inflammatory response are indications for examination for monoclonal secretion. The use of short- or long-acting IL-1 is a highly effective and safe option in the treatment of such patients.