The Expanding Multisystem Research Landscape of Hypermobile Ehlers-Danlos Syndrome: An Analysis of Orthopedic, Autonomic, Immunologic, and Neuropsychiatric Comorbidities

Introduction Hypermobile Ehlers-Danlos syndrome (hEDS) and hypermobility spectrum disorder (HSD) are increasingly recognized among orthopedic physicians to cause joint instability, frequent dislocation, and chronic musculoskeletal pain. Yet, patients with these disorders frequently have coexisting conditions, such as postural tachycardia syndrome (POTS), mast cell activation syndrome (MCAS), autoimmune and allergic disease, and neuropsychiatric conditions including anxiety, depression, ADHD, and autism. These comorbidities complicate diagnosis and treatment, therefore potentially decreasing the overall quality of care these patients receive. Despite the clinical relevance of comorbidities, the extent of research linking hypermobility disorders to these conditions has not been comprehensively examined. Methods A bibliometric analysis was conducted using the Web of Science Core Collection to identify articles and journals related to the topic. Articles with hEDS and hypermobility spectrum disorder (HSD) as the main topic and addressing at least one of the four comorbidity domains (orthopedic, autonomic, immunologic, or neuropsychiatric) were included without restriction on the type of document. The trend in the year of publication was graphed using the Web of Science Analyze results tool, while the collected bibliographic data was analyzed using VOSviewer to assess the coauthorship network and keyword co-occurrence patterns. Microsoft Excel was also utilized to visualize the articles with the most citations. Results Between 1967 and June 18, 2026, 1,281 publications were published, with 97.1% in English. About 65.8% of the articles were published within the last ten years, showing the rapid growth of research in this field. The country with the highest number of publications was the United States (482, 37.6%), followed by England (223, 17.4%) and Italy (114, 8.9%). The organization contributing the greatest number of articles in the dataset was the University of London, with 97 articles. Isolated author collaboration networks were observed, featuring small clusters with rare interactions, typically separated by country. Conclusion Research connecting hEDS and HSD to their orthopedic, autonomic, immunologic, and neuropsychiatric comorbidities has expanded rapidly over the past decade, driven largely by a few geographically isolated research clusters. Despite this growth, the immunologic and mast cell activation literature remains substantially underdeveloped, and collaboration across these research groups remains limited. Future efforts should prioritize cross-disciplinary and cross-national collaboration, with particular attention to expanding research on the immunologic and mast cell activation dimensions of hypermobility disorders.