Department of Pediatric Rheumatology, Istanbul University Medical School, Fatih, Istanbul, Turkey.
Department of Pediatric Rheumatology, University of Health Sciences, Kanuni Sultan Süleyman Research and Training Hospital, Istanbul, Turkey.
Rheumatol Int. 2021 Jan;41(1):113-120. doi: 10.1007/s00296-020-04592-7. Epub 2020 Apr 28.
Familial Mediterranean fever (FMF) is the most common monogenic autoinflammatory disease manifesting with phenotypic heterogeneity. The phenotype-genotype correlation is not established clearly yet. Furthermore, some comorbidities such as vasculitis and inflammatory arthritis may accompany FMF. Herein, we aimed to define phenotype-genotype correlation and comorbid diseases of children with FMF. The medical records of 1687 children diagnosed and followed up as FMF were reviewed retrospectively. Disease severity was assessed by PRAS score. A total of 1687 children (841 girls, 846 boys) were involved in the study. The mean ± standard deviation of current age, age at symptom onset, and age at diagnosis were 13.1 ± 5.4, 5.4 ± 4, and 8 ± 4.2 years, respectively. Median (min-max) follow-up period was 3 (0.5-18) years. Among them, 118 (7%) patients had at least one concomitant disease and 72% of them were carrying at least one M694V mutation. Patients with a concomitant disease expressed a more severe course of disease when compared to ones without a concomitant disease (23.7% vs 8.8%, p < 0.001). Children carrying homozygous M694V mutation had significantly earlier age of disease onset and severe disease course (p < 0.001). Forty-four patients (2.6%) were colchicine resistant and most of them were carrying homozygous M694V mutation. Sixteen colchicine-resistant patients were treated with anakinra while 28 received canakinumab. Juvenile idiopathic arthritis (JIA) and immunoglobulin A vasculitis were the most commonly seen associated diseases and the patients with a concomitant disease demonstrated more severe course. This is the largest pediatric cohort studied and presented since now. We confirmed that carrying M694V mutation is associated both with a severe disease course and a predisposition to comorbidities.
家族性地中海热（FMF）是最常见的单基因自身炎症性疾病，表现为表型异质性。表型-基因型相关性尚未明确。此外，一些合并症，如血管炎和炎症性关节炎，可能与 FMF 同时存在。在此，我们旨在确定 FMF 患儿的表型-基因型相关性和合并症。回顾性分析了 1687 例诊断并随访为 FMF 的儿童的病历。疾病严重程度通过 PRAS 评分评估。共纳入 1687 例儿童（841 名女孩，846 名男孩）。当前年龄、症状发作年龄和诊断年龄的平均值±标准差分别为 13.1±5.4、5.4±4 和 8±4.2 岁。中位数（最小-最大）随访时间为 3（0.5-18）年。其中，118 例（7%）患者至少有一种合并症，72%的患者至少有一种 M694V 突变。与无合并症的患者相比，有合并症的患者疾病过程更严重（23.7%比 8.8%，p<0.001）。携带纯合 M694V 突变的儿童疾病发病年龄更早，疾病过程更严重（p<0.001）。44 例（2.6%）对秋水仙碱耐药，其中大多数携带纯合 M694V 突变。16 例秋水仙碱耐药患者接受阿那白滞素治疗，28 例接受卡那单抗治疗。幼年特发性关节炎（JIA）和免疫球蛋白 A 血管炎是最常见的合并症，且有合并症的患者疾病过程更严重。这是迄今为止研究和报道的最大儿科队列。我们证实，携带 M694V 突变与疾病严重程度和合并症易感性相关。
