Amatucci Anthony J, Padnick-Silver Lissa, LaMoreaux Brian, Bulbin David H
Horizon Therapeutics plc, 1 Horizon Way, Deerfield, IL, 60015, USA.
Division of Rheumatology, Geisinger Medical Center, Danville, PA, USA.
Rheumatol Ther. 2023 Aug;10(4):809-823. doi: 10.1007/s40744-023-00565-x. Epub 2023 Jun 19.
Gout is an inflammatory, metabolic disease associated with a high comorbidity burden including cardiovascular disease, hypertension, type 2 diabetes, hyperlipidemia, renal disease, and metabolic syndrome. Approximately 9.2 million Americans have gout, making prognosis and treatment outcome predictors highly important. About 600,000 Americans have early-onset gout (EOG), generally defined as first gout attack at ≤ 40 years of age. However, data on EOG clinical features, comorbidity profile, and treatment response are sparse; this systematic literature review provides insight.
PubMed and American College of Rheumatology (ACR)/European Alliance of the Associations for Rheumatology (EULAR) abstract archives were searched for early-onset gout, "early onset gout," and ("gout" AND "age of onset"). Duplicate, foreign language, single case report, older (before 2016), and irrelevant/data insufficient publications were excluded. The age of diagnosis categorized patients as having common gout (CG, generally > 40 years) or EOG (generally ≤ 40 years). Applicable publications were extensively reviewed/discussed among authors for inclusion/exclusion consensus.
A total of 283 publications were identified, with 46 (35 articles, 10 abstracts) reviewed and 17 (12 articles, 5 abstracts) ultimately included. Eleven reported clinical characteristics, with 6 EOG-CG retrospective/cross-sectional comparisons. Gout diagnosis preceded cardiometabolic comorbidity and renal comorbidities were less prevalent in EOG than CG patients. EOG patients had more severe disease (more gout flares, polyarticular disease), higher pre-therapy serum urate (SU), and worse oral urate-lowering therapy response. Genetics-focused publications reported higher incidences of dysfunctional urate transporter mutations in EOG patients.
This review suggests that EOG is more recalcitrant to urate-lowering therapy, is associated with urate transporter defects, and carries heavy disease burden. Therefore, early rheumatology referral and urate-lowering in a treat-to-target fashion may benefit EOG patients. Interestingly, EOG patients had fewer cardiometabolic comorbidities at diagnosis than CG patients, presenting a potential "window of opportunity" to attenuate cardiometabolic comorbidity development with SU control. Preventing gout-related suffering and health burden is particularly important in these young EOG patients who will live with gout and its sequelae for decades.
痛风是一种炎症性代谢疾病，与包括心血管疾病、高血压、2型糖尿病、高脂血症、肾脏疾病和代谢综合征在内的高合并症负担相关。约920万美国人患有痛风，因此预后和治疗结果预测因素非常重要。约60万美国人患有早发性痛风（EOG），通常定义为首次痛风发作年龄≤40岁。然而，关于EOG临床特征、合并症情况和治疗反应的数据稀少；本系统文献综述提供了相关见解。
在PubMed和美国风湿病学会（ACR）/欧洲风湿病联盟（EULAR）摘要存档中检索早发性痛风、“early onset gout”以及（“痛风”且“发病年龄”）。排除重复、外语、单病例报告、较旧（2016年之前）以及不相关/数据不足的出版物。根据诊断年龄将患者分为患有普通痛风（CG，一般>40岁）或EOG（一般≤40岁）。作者们对适用的出版物进行了广泛审查/讨论，以达成纳入/排除共识。
共识别出283篇出版物，其中46篇（35篇文章，10篇摘要）经过审查，最终纳入17篇（12篇文章，5篇摘要）。11篇报告了临床特征，其中6篇进行了EOG与CG的回顾性/横断面比较。痛风诊断先于心脏代谢合并症，且EOG患者中肾脏合并症的患病率低于CG患者。EOG患者的疾病更严重（痛风发作更频繁、多关节疾病），治疗前血清尿酸（SU）水平更高，口服降尿酸治疗反应更差。聚焦遗传学的出版物报告EOG患者中尿酸转运蛋白功能障碍突变的发生率更高。
本综述表明，EOG对降尿酸治疗更具顽固性，与尿酸转运蛋白缺陷相关，且疾病负担较重。因此，早期转诊至风湿病专科并以达标为导向进行降尿酸治疗可能使EOG患者受益。有趣的是，EOG患者在诊断时的心脏代谢合并症比CG患者少，这为通过控制SU来减轻心脏代谢合并症的发展提供了一个潜在的“机会窗口”。对于这些将与痛风及其后遗症共处数十年的年轻EOG患者来说，预防痛风相关的痛苦和健康负担尤为重要。
