该研究的目的是提供诊断经验,管理,根据俄罗斯多中心队列研究,Schnitzler综合征(SchS)患者使用IL-1抑制剂进行治疗。一项为期10年(2012-2022年)的观察性回顾性研究涉及17名住院或门诊观察的SchS患者(8名女性和9名男性)。所有这些的诊断都符合斯特拉斯堡的诊断标准。患者的年龄范围为25至81岁(Me53[46;56])。发病时的年龄为20至72岁(Me46[39;54]),诊断前的疾病持续时间为1至35年(Me6.5[3;6]),在三名患者中,它超过了10年,其余的时间从1到8年不等。传染性和淋巴增生性疾病,单基因艾滋病(CAPS,陷阱,和HIDS)在院前阶段被排除在所有患者之外。所有这些患者的转诊诊断均为成人Still病。所有患者的临床表现包括疲劳,嗜睡,疲劳,皮疹,和发烧。在所有患者中,6例(37.5%)患者的皮肤成分为荨麻疹,并伴有瘙痒。在12例(70.6%)患者中观察到骨痛;关节痛,16例(94.1%);关节炎,9例(52.9%);肌痛,在7人中(41.2%);和体重减轻,在4(23.5%)。6例(35.3%)患者发现淋巴结肿大;6例(35.3%);心包炎,在4(23.5%);血管性水肿,在6(35.3);眼睛发红和干燥,在3(17.6%);喉咙痛,在2(11.8%);腹痛,在1(5.9%)中,远端多发性神经病,在2中(11.8%);感觉异常,1例(5.9%);耳廓软骨炎,在1(5.9%)。在所有患者中检测到单克隆丙种球蛋白病,分泌水平为2.9-15.1g/L:IgMk(n=10,64.7%),不太常见的是IgMλ(n=2),IgGk(n=2),IgGλ(n=1),和IgAλ(n=1)。在它们中的任何一个中均未检测到Ben-Jones蛋白。所有患者的ESR和CRP水平均升高。在纳入研究之前,16例患者接受了GC(94.1%),其暂时效果随着剂量的减少或取消而消失。七个病人接受了cDMARDs,包括甲氨蝶呤(5),羟氯喹(2),和环磷酰胺(1)。所有患者均接受NSAIDs和抗组胺药,以及生物制品,包括抗B细胞药物利妥昔单抗(1),单克隆ABs对IgE奥马珠单抗(2,1个无作用,1个有部分作用),IL-1icanakinumab(n=10,58.8%)每8周皮下一次,和anakinra(n=4,23.5%)每天皮下。服用阿纳金拉的持续时间,这是在测试模式下规定的,范围为1周至2.5个月,3例患者进一步改用canakinumab.在分析时服用canakinumab的持续时间为7个月至8年。在用IL-1i治疗的背景下,11名患者中有10名(90.9%)在疾病的临床表现方面获得了完全响应,并且在几天内ESR和CRP水平降低。在一个病人中,检测到对anakinra给药的部分反应;然而,改用canakinumab后,治疗的效果终于消失了。一名患者接受IL-6i治疗8个月,但效果不完全,转换为anakinra后动力学呈阳性。因此,最初为4名患者开了anakinra处方,其中2名患者改为canakinumab;7名患者开始使用canakinumab作为第一种药物.两名患者继续使用anakinra进行治疗;使用canakinumab,9名患者在一个病人中,由于持续没有复发,canakinumab注射之间的间隔增加到5个月,没有再激活的迹象;然而,随后,在压力和疾病复发的背景下,间隔减少到4个月.同一患者在治疗背景下出生了一个健康的孩子。所有患者的治疗耐受性均令人满意,没有注意到SAE。SchS是一种罕见的多因素/非单基因AID,应与许多风湿性疾病和其他AID区分开。成年后开始,复发性荨麻疹伴发热和全身炎症反应的其他表现是检查单克隆分泌的适应症。使用短效或长效IL-1i是治疗此类患者的高效且安全的选择。
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.