Paediatric Rheumatology and Autoinflammatory Diseases Unit, Department of Paediatrics and Adolescent Medicine, First Faculty of Medicine, General University Hospital in Prague, Charles University, Prague, Czechia.
Department of Paediatric Rheumatology, University Hospital Brno, Brno, Czechia.
Front Immunol. 2019 Apr 16;10:802. doi: 10.3389/fimmu.2019.00802. eCollection 2019.
Muckle-Wells syndrome (MWS) represents a moderate phenotype of cryopyrinopathies. Sensorineural hearing loss and AA amyloidosis belong to the most severe manifestations of uncontrolled disease. Simultaneous discovery of MWS in four generations of one large kindred has enabled us to document natural evolution of untreated disease and their response to targeted therapy. A retrospective case study, clinical assessment at the time of diagnosis and 2-year prospective follow-up using standardized disease assessments were combined. Collaborative effort of primary care physicians and pediatric and adult specialists led to identification of 11 individuals with MWS within one family. Presence of p.Ala441Val mutation was confirmed. The mildest phenotype of young children suffering with recurrent rash surprised by normal blood tests and absence of fevers. Young adults all presented with fevers, rash, conjunctivitis, and arthralgia/arthritis with raised inflammatory markers. Two patients aged over 50 years suffered with hearing loss and AA amyloidosis. IL-1 blockade induced disease remission in all individuals while hearing mildly improved or remained stable in affected patients as did renal function in one surviving individual with amyloidosis. We have shown that severity of MWS symptoms gradually increased with age toward distinct generation-specific phenotypes. A uniform trajectory of disease evolution has encouraged us to postpone institution of IL-1 blockade in affected oligosymptomatic children. This report illustrates importance of close interdisciplinary collaboration.
Muckle-Wells 综合征（MWS）代表一种中等严重程度的冷吡啉相关周期性综合征。感觉神经性耳聋和 AA 淀粉样变性是疾病失控的最严重表现。在一个大家庭的四代人同时发现 MWS，使我们能够记录未治疗疾病的自然演变及其对靶向治疗的反应。这是一项回顾性病例研究，结合了诊断时的临床评估和使用标准化疾病评估的 2 年前瞻性随访。初级保健医生以及儿科和成人专家的协作努力，在一个家庭中发现了 11 名患有 MWS 的个体。证实存在 p.Ala441Val 突变。患有反复发作皮疹的儿童表现出最轻微的表型，令他们惊讶的是，血液检查正常且无发热。年轻的成年人都有发热、皮疹、结膜炎、关节痛/关节炎和炎症标志物升高。两名 50 岁以上的患者患有听力损失和 AA 淀粉样变性。所有个体的 IL-1 阻断都诱导疾病缓解，而受影响的患者的听力仅略有改善或保持稳定，一名患有淀粉样变性的个体的肾功能也保持稳定。我们已经表明，MWS 症状的严重程度随着年龄的增长逐渐增加，呈现出特定于特定世代的明显表型。疾病演变的统一轨迹促使我们推迟对受影响的寡症状儿童进行 IL-1 阻断治疗。本报告说明了密切的跨学科合作的重要性。
