Daylor Victoria, Griggs Molly, Weintraub Amy, Byrd Rebecca, Petrucci Taylor, Huff Matthew, Byerly Kathryn, Fenner Roman, Severance Sydney, Griggs Charlotte, Sharma Amol, Atwal Paldeep, Kautz Steven A, Shapiro Steven, Youkhana Kimberly, Lavallee Mark, Wilkerson Allison, Nichols Michelle, Snyder Alan, Eichinger Josef K, Patel Sunil, Maitland Anne, Gensemer Cortney, Norris Russell A
Department of Regenerative Medicine and Cell Biology, Medical University of South Carolina, Charleston, SC 29407, USA.
Department of Neurosurgery, Medical University of South Carolina, Charleston, SC 29407, USA.
J Clin Med. 2025 Aug 9;14(16):5636. doi: 10.3390/jcm14165636.
Hypermobile Ehlers-Danlos syndrome (hEDS) and hypermobility spectrum disorders (HSDs) are prevalent, complex conditions marked by chronic pain, joint instability, and multisystem involvement. Despite affecting an estimated 1 in 500 individuals, these conditions remain poorly understood and inconsistently diagnosed. This study aimed to define their clinical burden through a large-scale, international survey. A cross-sectional, anonymous survey was distributed globally from September 2023 to March 2024. Of 9258 responses, 3906 met inclusion criteria (hEDS: n = 3360; HSD: n = 546). The 418-item questionnaire assessed symptoms, comorbidities, healthcare utilization, and quality of life. The 95% confidence intervals (CIs) were calculated for comparison. Participants with hEDS reported a mean of 24 comorbid conditions and an average diagnostic delay of 22.1 years. Common diagnoses included gastrointestinal disorders (84.3% [95% CI: 98.3-99.2%]), dysautonomia (71.4% [95% CI: 69.9-72.9%]), and chronic pain (98.9% [95% CI: 98.3-99.2%]). In contrast, HSD respondents reported a mean of 17 comorbidities, a 17.5-year time to diagnosis, and lower rates of key complications. Triggering events, such as puberty and infections were commonly reported preceding hEDS or HSD symptom onset. Comparison to the All of Us dataset revealed significantly elevated prevalence ratios of neurological, immune, and autonomic diagnoses. This global survey highlights the extensive multisystemic burden and diagnostic delays faced by individuals with hEDS and HSDs. The high prevalence of immune, neurological, gastrointestinal, and autonomic dysfunctions challenges the notion of these conditions as isolated connective tissue disorders. These findings highlight the need for updated diagnostic frameworks and mechanistic studies that explore multifactorial etiologies beyond the connective tissue paradigm.
活动度过高型埃勒斯-当洛综合征（hEDS）和活动度过高谱系障碍（HSDs）是常见的复杂病症，其特征为慢性疼痛、关节不稳定和多系统受累。尽管据估计每500人中就有1人受其影响，但这些病症仍未得到充分了解，诊断也不一致。本研究旨在通过一项大规模的国际调查来确定其临床负担。2023年9月至2024年3月在全球范围内开展了一项横断面匿名调查。在9258份回复中，3906份符合纳入标准（hEDS：n = 3360；HSD：n = 546）。这份包含418个条目的问卷评估了症状、合并症、医疗保健利用情况和生活质量。计算了95%置信区间（CIs）用于比较。患有hEDS的参与者报告平均有24种合并病症，平均诊断延迟22.1年。常见诊断包括胃肠道疾病（84.3% [95% CI：98.3 - 99.2%]）、自主神经功能障碍（71.4% [95% CI：69.9 - 72.9%]）和慢性疼痛（98.9% [95% CI：98.3 - 99.2%]）。相比之下，HSD受访者报告平均有17种合并症，诊断时间为17.5年，关键并发症发生率较低。在hEDS或HSD症状发作之前，常见的触发事件如青春期和感染。与“我们所有人”数据集的比较显示，神经、免疫和自主神经诊断的患病率显著升高。这项全球调查凸显了hEDS和HSD患者面临的广泛多系统负担和诊断延迟。免疫、神经、胃肠道和自主神经功能障碍的高患病率挑战了将这些病症视为孤立的结缔组织疾病的观念。这些发现凸显了需要更新诊断框架以及开展机制研究，以探索结缔组织范式之外的多因素病因。
