Background: 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. Methods: 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. Results: 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. Conclusions: 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.

To perform a retrospective clinical study in order to investigate phenotypic penetrance within a large registry of patients with hypermobile Ehlers-Danlos syndrome (hEDS) to enhance diagnostic and treatment guidelines by understanding associated comorbidities and improving accuracy in diagnosis. From May 1, 2021 to July 31, 2023, 2149 clinically diagnosed patients with hEDS completed a self-reported survey focusing on diagnostic and comorbid conditions prevalence. K-means clustering was applied to analyze survey responses, which were then compared across gender groups to identify variations and gain clinical insights. Analysis of clinical manifestations in this cross-sectional cohort revealed insights into multimorbidity patterns across organ systems, identifying 3 distinct patient groups. Differences among these phenotypic clusters provided insights into diversity within the population with hEDS and indicated that Beighton scores are unreliable for multimorbidity phenotyping. Clinical data on the phenotypic presentation and prevalence of comorbidities in patients with hEDS have historically been limited. This study provides comprehensive data sets on phenotypic presentation and comorbidity prevalence in patients with hEDS, highlighting factors often overlooked in diagnosis. The identification of distinct patient groups emphasizes variations in hEDS manifestations beyond current guidelines and emphasizes the necessity of comprehensive multidisciplinary care for those with hEDS.

Collagen, the most abundant protein in the body, is a key component of the extracellular matrix (ECM), which plays a crucial role in the structure and support of connective tissues. Abnormalities in collagen associated with connective tissue disorders (CTD) can lead to neuroinflammation and weaken the integrity of the blood–brain barrier (BBB), a semi-permeable membrane that separates the brain’s extracellular fluid from the bloodstream. This compromise in the BBB can result from disruptions in ECM components, leading to neuroinflammatory responses, neuronal damage, and increased risks of neurological disorders. These changes impact central nervous system homeostasis and may exacerbate neurological conditions linked to CTD, manifesting as cognitive impairment, sensory disturbances, headaches, sleep issues, and psychiatric symptoms. The Ehlers-Danlos syndromes (EDS) are a group of heritable CTDs that result from varying defects in collagen and the ECM. The most prevalent subtype, hypermobile EDS (hEDS), involves clinical manifestations that include joint hypermobility, skin hyperextensibility, autonomic dysfunction, mast cell activation, chronic pain, as well as neurological manifestations like chronic headaches and cerebrospinal fluid (CSF) leaks. Understanding the connections between collagen, CSF, inflammation, and the BBB could provide insights into neurological diseases associated with connective tissue abnormalities and guide future research.

The Ehlers-Danlos Syndromes (EDS) represent a group of hereditary connective tissue disorders, with the hypermobile subtype (hEDS) being the most prevalent. hEDS manifests with a diverse array of clinical symptoms and associated comorbidities spanning the musculoskeletal, neurological, gastrointestinal, cardiovascular, and immunological systems. hEDS patients may experience spinal neurological complications, including cervico-medullary symptoms arising from cranio-cervical and/or cervical instability/hypermobility, as well as tethered cord syndrome (TCS). TCS is often radiographically occult in nature, not always detectable on standard imaging and presents with lower back pain, balance issues, weakness in the lower extremities, sensory loss, and bowel or bladder dysfunction. Cervical instability due to ligament laxity can lead to headaches, vertigo, tinnitus, vision changes, syncope, radiculopathy, pain, and dysphagia. TCS and cervical instability not only share clinical features but can also co-occur in hEDS patients, posing challenges in diagnostics and clinical management. We present a review of the literature and a case study of a 20-year-old female with hEDS, who underwent surgical interventions for these conditions, highlighting the challenges in diagnosing and managing these complexities and underscoring the importance of tailored treatment strategies to improve patient outcomes.

Background: Adolescents and young adults frequently present to the emergency department (ED) for medical care and continue to have many unmet sexual health needs. Digital interventions show promise to improve adolescent and young adult sexual health; yet, few interventions focus on male ED patients, despite their infrequent use of contraceptives and rising rates of sexually transmitted infections. Objective: This paper describes the design and development of Dr. Eric (Emergency Room Interventions to Improve Care), a digital app focused on promoting condom use among sexually active adolescent and young adult male ED patients. Methods: This study followed 4 phases of app development, which were based on user-centered design and the software development lifecycle. In phase 1, define, we explored our target population and target health problem (infrequent condom use among male ED patients) by collecting key stakeholder input and conducting in-depth interviews with male patients and urban ED medical providers. In phase 2, discover, we partnered with a digital product agency to explore user experience and digital strategy. In phase 3, design, we refined Dr. Eric’s content, a 5-part sexual health educational module and a 10-week SMS text messaging program that focuses on condom use and partner communication about effective contraceptives. We conducted semistructured interviews with male adolescent and young adults to gather feedback on the app and perform usability testing, editing the app after each interview. We also interviewed informatics experts to assess the usability of a high-fidelity prototype. Interviews were recorded and analyzed via descriptive thematic analysis; informatic expert feedback was categorized by Nielsen’s heuristic principles. In phase 4, develop, we created the technical architecture and built a responsive web app. These findings were gathered leading to the final version of the digital Dr. Eric program. Results: Using data and key stakeholder input from phases 1 and 2, we iteratively created the Dr. Eric prototype for implementation in the ED setting. Interviews with 8 adolescent and young adult male ED patients suggested that users preferred (1) straightforward information, (2) a clear vision of the purpose of Dr. Eric, (3) open-ended opportunities to explore family planning goals, (4) detailed birth control method information, and (5) games presenting novel information with rewards. Five usability experts provided heuristic feedback aiming to improve the ease of use of the app. These findings led to the final version of Dr. Eric. Conclusions: Following these mobile health development phases, we created a digital sexual health mobile health intervention incorporating the principles of user experience and interface design. Dr. Eric needs further evaluation to assess its efficacy in increasing condom use among adolescent and young adult male ED patients. Researchers can use this framework to form future digital health ED-based digital interventions.

Background: Hypermobile Ehlers-Danlos syndrome (hEDS) is a collagen disorder affecting multiple organ systems, including the musculoskeletal system. We sought to determine the type and severity of orthopaedic manifestations experienced by these patients. The purpose of this study was to identify the most common orthopaedic manifestations in patients with hEDS and to examine the patient-reported helpfulness of treatments. Of note, collagen disorders such as hEDS may affect the success rates of orthopaedic interventions. The success or failure of treatment is not currently fully understood for this patient population. Methods: A total of 1,999 patients who were enrolled in an international EDS registry were contacted to complete a 260-question survey regarding their experience with nonoperative and operative treatments for musculoskeletal instability and/or pain. Participants reported their demographic characteristics, hEDS diagnosis characteristics, symptomatic joints, nonoperative and operative treatments, and satisfaction with each treatment. Results: Over a 30-day period, 1,075 responses were received. Participants were predominately female (95.3%) and had a median age of 40.0 years (interquartile range width, 17.0 years). The majority (60.8%) of respondents reported a mental health burden every day, with the remainder reporting a mental health burden weekly (24.4%), monthly (11.0%), or never (3.80%). Compared with those who underwent standard physical therapy (n = 378), individuals who underwent physical therapy tailored to EDS (n = 602) more frequently reported improved posture (78.6% versus 43.1%; p < 0.001), greater helpfulness (p < 0.001), and a longer duration of attending therapy (p < 0.001). A total of 1,120 primary and 261 revision operations for joint or spine instability and/or pain were reported. The reported complication rates were 35.7% and 42.9% for joint and spine surgeries, respectively. Physical therapy was the only nonoperative treatment for which the median reported helpfulness sometimes equaled or exceeded that of a joint or spine surgery. Conclusions: This study offers insights into the demographics and management of hEDS. The high rate of surgical complications reported by patients indicates the need for a better understanding of surgical indications and treatment options. These findings should guide physicians in managing hEDS and highlight the importance of incorporating this knowledge into clinical practice to improve the management of orthopaedic manifestations in patients with hEDS. Level of Evidence: Prognostic Level V. See Instructions for Authors for a complete description of levels of evidence.