Jane R. Schubart

Purpose: Dercum disease and lipedema commonly present with joint hypermobility, yet the relationship between these adipose disorders (AD) and hypermobile Ehlers-Danlos syndrome (hEDS) remains insufficiently understood. To date, no research has simultaneously examined hEDS and adipose disorders, leaving a critical gap in understanding their interplay. This investigation seeks to address diagnostic challenges and provide insights to inform more effective management strategies for these complex, overlapping conditions. Methods: The study included 25 participants: 17 with hEDS and co-occurring adipose disorders (Dercum disease or lipedema) and 8 with hEDS alone. Ultrasound imaging was conducted to evaluate the superficial and deep fascia over the lower limbs and torso. Imaging sites included the right malleolus, anterior tibia, lateral fibula, thigh, and the abdomen to the right of the navel. Angiolipomas in these regions were also assessed. Fascial thickness measurements were compared between the two groups using the Mann–Whitney U-test. The 17 participants with co-occurring adipose disorders and hEDS completed a survey that included assessments of medical history, COMPASS-31 dysautonomia scores, immune dysfunction symptoms, a lipedema questionnaire, and a Dercum-associated symptoms list. A correlation matrix was used to evaluate relationships between symptomatology, systemic comorbidities, and fascial thickness in the group with hEDS and co-occurring adipose disorders and those with hEDS alone. Results: Participants with hEDS and co-occurring adipose disorders exhibited significantly increased deep and superficial fascia thickness across all lower limb regions compared to those with hEDS alone (p < 0.05). Deep fascia thickness was significantly greater in the thigh (2.4 ± 1.1 mm vs. 1.3 ± 0.6 mm, p < 0.0001), lateral leg (1.5 ± 0.4 mm vs. 0.8 ± 0.2 mm, p = 0.012), and pretibial region (1.3 ± 0.3 mm vs. 0.9 ± 0.2 mm, p = 0.003). Superficial fascia thickness was also significantly increased in the thigh (21.7 ± 9.5 mm vs. 7.7 ± 3.1 mm, p < 0.0001), pretibial region (7.9 ± 3.7 mm vs. 4.0 ± 1.2 mm, p = 0.001), and supramalleolar region (4.6 ± 1.4 mm vs. 3.3 ± 1.4 mm, p = 0.022). A moderate correlation was observed between deep and superficial fascia thickness across all regions except the lateral leg. Pretibial superficial fascia thickness demonstrated a moderate positive correlation with immune dysfunction scores (r = 0.48). No significant correlations were found between fascial thickness and lipedema stage, lipedema type, lipedema questionnaire scores, Dercum symptom list, or COMPASS-31 scores. However, a moderate positive correlation was noted between immune dysfunction symptoms and COMPASS-31 scores (r = 0.52) in participants with co-occurring hEDS and adipose disorders. Conclusions: In hEDS with co-occurring adipose disorders, distinct patterns of fascial remodeling are evident. Integrating ultrasound into diagnostic and management strategies may enhance the identification and treatment of these overlapping conditions. The observed relationship between fascia thickness and immune dysfunction highlights a potential role of immune dysfunction in driving inflammatory changes.

Patients with Ehlers-Danlos syndromes (EDS) often experience high rates of joint subluxations and dislocations, and associated pain that may require surgical interventions. Orthopaedic surgical management is challenging in this population, and patients will often undergo multiple unsuccessful surgeries. Outcomes data specific to patients with EDS are sparse in the orthopaedic surgery literature. We conducted a scoping review to evaluate the evidence and outcomes for orthopaedic surgery specifically for the EDS population. PubMed MEDLINE, Embase, The Cochrane Library, Cochrane Controlled Register of Trials (CENTRAL), CINHL, and Scopus from their inception to February 28, 2024 for all studies that reported outcomes for orthopaedic surgery in patients with EDS. Two reviewers independently determined study eligibility, rated study quality, and extracted data. Methodology followed the Preferred Reporting Items for Systematic reviews and Meta-Analyses extension for Scoping Reviews (PRISMA-ScR). The studies in this scoping review include Level III (retrospective cohort and case control) and Level IV (case series) evidence. The literature search yielded a total of 71 citations published between 1990 and 2023. All were primary studies. 38 were single case studies, 14 were case series, and 19 were retrospective cohort studies. No randomized clinical studies or systematic reviews were identified. Overall, the reported findings for the various anatomical sites and procedures indicated that surgery outcomes were inconsistent. Our review highlights the need for future research to determine whether currently established surgical approaches for various orthopaedic conditions offer long-term clinical benefit in patients with EDS. This is clearly a challenging diagnosis, and more rigorous clinical studies are required to identify optimal treatment approaches. Our review found little evidence-based research to guide optimal surgical treatment in EDS. Established surgical techniques that have been shown to be successful in the wider orthopaedic population should be studied to determine their efficacy in the EDS population.

Introduction: Patients with Ehlers-Danlos syndromes (EDS) and hypermobility spectrum disorders (HSD) have significant health challenges that are well-documented, however their impact in terms of cost is not known. Our research objective was to examine the cost burden of EDS and HSD in the United States. We focused this analysis on those with commercial insurance plans.Methods: We queried the MarketScan® database for year 2021 for claims that contained an ICD-10 diagnosis code for EDS or hypermobility. Excess costs for patients in the EDS and HSD cohorts were determined by matching each patient to one patient in the database that did not have a claim for EDS or HSD and comparing total costs for the calendar year. We determined whether patients had claims for selected comorbid conditions likely to impact costs during the calendar year.Results: Sample sizes were 5,113 for adult (age ≥ 18) patients with EDS, 4,880 for adult patients with HSD, 1,059 for child (age 5–17) patients with EDS, and 2,427 for child patients with HSD. The mean excess costs were $21,100 for adult EDS patients, $11,600 for adult HSD patients, $17,000 for child EDS patients, and $11,000 for child HSD patients. EDS and HSD cohorts, both adults and children, with any of the comorbidities had greater healthcare costs. The largest difference was found in the EDS cohort with gastrointestinal comorbid conditions, with more than double the costs for adults.Discussion: We found that patients in the MarketScan database, adults and children, who had EDS or HSD had substantially higher associated excess healthcare costs than patients without EDS or HSD when considering age, sex, geographic location, and comorbidities. These disproportionate healthcare costs in this population have health policy and economic implications, including the need for rapid diagnosis, access to treatment, and accelerated research to advance treatments.

Introduction: Individuals with Ehlers-Danlos syndromes (EDS) often have complex and multi-faceted symptoms across the lifespan. Pain and the related symptoms of fatigue and sleep disorders are common. The objective of this qualitative study was to understand how participants manage their pain and related symptoms.Methods: The design was a qualitative thematic content analysis. Twenty-eight interviews were conducted to collect data from individuals who were participants in a prior quantitative longitudinal study. A semi-structured interview guide was designed to focus on and understand the trajectory of pain, sleep, fatigue, and general function. The interview continued with questions about coping mechanisms and obstacles to maintaining a sense of well-being.Results: Symptoms reported by participants were widespread and often interwoven. Pain was universal and often resulted in fatigue and disordered sleep which impacted physical function. Most participants reported that their symptoms worsened over time. Participants reported a wide range of effective interventions and most reported developing self-care strategies to adapt to their disabilities/limitations. Solutions included complementary interventions discovered when conventional medicine was unsuccessful. Very few relied on a “system” of health care and instead developed their own strategies to adapt to their disabilities/limitations.Discussion: EDS symptoms are often debilitating, and their progression is unknown. For most participants, symptoms worsened over the time. Even though participants in our study, by experience, were self-reliant, the importance of knowledgeable medical providers to help guide self-care should be emphasized.

Our study extends a cross‐sectional dataset on the Ehlers‐Danlos syndromes (EDS) assembled by the National Institute on Aging (NIA), under a protocol entitled Clinical and Molecular Manifestations of Heritable Disorders of Connective Tissue. We were successful in contacting 171 of the original 252 participants with EDS. Our study cohort included 91 participants who completed at least one of the following surveys: Brief Pain Inventory (BPI), Pittsburgh Sleep Quality Index (PSQI), Multidimensional Fatigue Inventory (MFI‐20), and Short Form (SF‐36) Health Survey, at both baseline and follow‐up. Follow‐up surveys occurred a median of 11.6 years after the baseline survey. We used mixed effects linear regression models to examine the change in scores for multiple indices reported by participants. There were small mean changes reflected in our estimates for the EDS population as a whole. There was wide heterogeneity between reported individual experiences, with some participants markedly improved and some dramatically worse. Men had a greater increase in mean pain severity over time than women. This is the first study to report a decade of longitudinal data in EDS.

The Ehlers‐Danlos Society Extension for Community Health Care Outcomes (EDS ECHO) is a portfolio of teleconferencing programs developed around the principles and practices of Project ECHO®, aimed at increasing awareness of Ehlers‐Danlos syndromes (EDS) and hypermobility spectrum disorders (HSD) among clinicians, enhancing their confidence in the assessment and management of these complex conditions, and generating networks of clinicians across specialties. We assessed the outcomes of the first EDS ECHO program, launched in April 2019, with two hub locations: Indiana University Health, Indianapolis, Indiana, USA, and The Royal Society of Medicine, London, UK. Clinicians were surveyed before and 6 months after their participation. We describe the initial outcomes of the first four EDS ECHO programs, each comprising nine sessions. Participants reported increased levels of knowledge and confidence in providing care (93% and 95%, respectively) and an increase in referral network participation (65%). Additionally, 80% reported that their interest in EDS and HSD increased; 57% reporting a great increase. Also, 59% reported a decrease in feeling overwhelmed by EDS and HSD, and nearly half reported a decrease in their level of frustration because of participating in EDS ECHO. Clinicians participating in EDS ECHO programs know more, have more confidence in their ability to provide care, and feel energized by their participation.

Objective: Joint hypermobility in Ehlers‐Danlos Syndromes (EDS) predisposes persons with EDS to frequent subluxations and dislocations, chronic arthralgia, and soft‐tissue rheumatism. Epidemiologic trends of rheumatologic conditions among persons with EDS are lacking. Prescription claims databases can reflect underlying disease burdens by using medication claims as disease proxies. We examined the prevalence of prescription claims for commonly prescribed immunomodulator and antiinflammatory (IMD) drugs among persons with EDS compared with their matched control person, and hypothesized peripubertal increases among female persons with EDS.Methods: We compared the percentages of IMD drug prescription claims among 3,484 persons with EDS (ages 5–62 years) against their age‐, sex‐, state of residence‐, and earliest claim date–matched control persons using 10 years (2005–2014) of private prescription claims data and a minimum 2‐year enrollment inclusion criterion.Results: Our cohort comprised 70% adults and 74% female persons. At least 1 IMD medication was prescribed to 65.4% of persons with EDS compared with 47.4% of control persons. We observed 1.3 to 4.2 times higher odds (P < 0.0001) for 5 out of 6 IMD drug classes among persons with EDS compared with matched control persons, except for biologic agents (conditional odds ratio 1.3, 95% confidence interval 0.8–2.0). Peripubertal increases were observed for nonsteroidal antiinflammatory drugs, oral, and injectable steroids.Conclusions: To our knowledge, our study is the first to examine the full range of IMD drug prescription claim trends among persons with EDS. We believe our research findings can have notable diagnostic and management implications for EDS patients who present with multiple comorbidities and generally require a more granular assessment of their medical conditions.

We previously reported increased pain and gastrointestinal (GI) medication prescription claims among persons with Ehlers–Danlos syndromes (EDS) and peripubertal increase in opioid and anti‐emetic claims among women with EDS. Herein, we hypothesized a higher proportion of respiratory and co‐occurring respiratory and GI medication prescription claims among persons with EDS compared to their matched controls with increases among peripubertal women with EDS. We compared the proportions of respiratory and co‐occurring respiratory and GI medication prescription claims among persons with EDS (aged 5–62) against their age‐, sex‐, state of residence‐, and earliest claim date‐matched controls using 10 years of private prescription claims data. Prescription claims among persons with EDS versus matched controls were increased for eight medication classes (p < .0001): intranasal/inhaled corticosteroids (ICS) (30.8% vs. 19.0%), oral steroids (30.0% vs. 16.5%), H1‐antihistamines (26.2% vs. 12.2%), short‐acting beta agonists (22.7% vs. 11.6%), decongestants (21.6% vs. 15.9%), leukotriene modifiers (8.9% vs. 3.6%), ICS/long‐acting beta agonists (5.7% vs. 2.9%), muscarinic antagonists (2.5% vs. 0.9%), and co‐occurring prescriptions (29% vs. 10%). Our results suggest a critical time window for peripubertal intervention and research and a need to focus on the pathogenesis and clinical evaluation of EDS‐specific respiratory and aerodigestive disorders.