Autoinflammatory Diseases Clinical Unit, Department of Autoimmune Diseases, Working Group of Adult Rare Diseases, Hospital Clínic, University of Barcelona, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Catalonia, Spain; Vasculitis Research Unit, Department of Autoimmune Diseases, Working Group of Adult Rare Diseases, Hospital Clínic, University of Barcelona, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Catalonia, Spain.
Autoinflammatory Diseases Laboratory Unit, Department of Immunology, Working Group of Adult Rare Diseases, Hospital Clínic, University of Barcelona, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Catalonia, Spain.
Autoimmun Rev. 2016 Jan;15(1):9-15. doi: 10.1016/j.autrev.2015.08.008. Epub 2015 Aug 21.
Autoinflammatory diseases (AID) are usually diagnosed during the pediatric age. However, adult-onset disease or diagnosis during adulthood has been occasionally described.
To assess the clinical and genetic characteristics of adult patients diagnosed with an AID in an adult referral center for AID.
We retrospectively evaluated clinical and genetic features of adult patients (≥16 years) diagnosed with an AID or referred after AID diagnosis to the Clinical Unit of AID, at the Department of Autoimmune Diseases, Hospital Clínic of Barcelona, from 2008 to 2014.
During the study period, a genetic study for suspected AID was requested to 90 patients at the Department of Autoimmune Diseases. A final diagnosis of monogenic AID was achieved in 17 patients (19% of patients tested). Five additional cases were diagnosed with periodic fever, aphthous stomatitis, pharyngitis and cervical adenitis (PFAPA) syndrome and 10 patients with AID were referred from other adult departments. Finally, a total of 32 patients with AID were finally diagnosed or monitored in our Clinical Unit. These included 12 (37.5%) familial Mediterranean fever, 6 (18.8%) tumour necrosis factor-receptor associated periodic syndrome, 8 (25%) cryopirin-associated periodic syndromes (Muckle-Wells syndrome [MWS] or overlap familial cold-associated periodic syndrome/MWS), 1 (3.1%) mevalonate kinase deficiency, and 5 (15.6%) PFAPA. Clinical evidence of disease-onset during childhood and adulthood was observed in 15 (47%) and 17 (53%) patients, respectively. Overall, the final diagnosis was obtained after a delay of a mean of 12 years (range 0-47 years). Compared to children, adult patients with AID in our series presented more frequently with non-severe manifestations and none of them developed amyloidosis during follow-up. Adult patients also carried higher proportion of low-penetrance mutations or polymorphisms and all genetic variants were presented in heterozygosis or as heterozygous compounds.
Adult disease-onset or delayed diagnosis of AID during adulthood is associated with milder disease phenotypes, and seem to be driven by mild genotypes, with predominant presence of low-penetrance mutations or polymorphisms.
自身炎症性疾病（AID）通常在儿科时期得到诊断。然而，偶尔也会描述成人发病或成年期诊断的疾病。
评估在成人自身免疫疾病转诊中心诊断为 AID 的成年患者的临床和遗传特征。
我们回顾性评估了 2008 年至 2014 年期间，在巴塞罗那临床医院自身免疫疾病科自身免疫疾病临床科就诊或在该科诊断为 AID 后转诊的成年患者（≥16 岁）的临床和遗传特征。
在研究期间，在自身免疫疾病科共向 90 名患者请求进行疑似 AID 的基因研究。在接受检测的患者中，最终诊断为单基因 AID 的患者为 17 例（19%）。另外 5 例被诊断为周期性发热、口疮性口炎、咽炎和颈淋巴结炎（PFAPA）综合征，10 例患者从其他成人科室转诊。最终，我们的临床科共诊断或监测了 32 例 AID 患者。这些患者包括 12 例（37.5%）家族性地中海热、6 例（18.8%）肿瘤坏死因子受体相关周期性综合征、8 例（25%）冷球蛋白血症相关周期性综合征（Muckle-Wells 综合征[MWS]或重叠家族性冷相关周期性综合征/MWS）、1 例（3.1%）甲羟戊酸激酶缺乏症和 5 例（15.6%）PFAPA。分别有 15 例（47%）和 17 例（53%）患者的疾病发病表现为儿童期和成年期。总体而言，平均延迟 12 年（0-47 年）后最终获得诊断。与儿童相比，我们系列中的成年 AID 患者更常出现非严重表现，且在随访期间均未发生淀粉样变性。成年患者还携带更高比例的低外显率突变或多态性，且所有遗传变异均以杂合子或杂合化合物的形式存在。
成年期发病或成年期 AID 延迟诊断与较轻的疾病表型相关，且似乎由轻度基因型驱动，以低外显率突变或多态性为主。
