To what extent do the muscles and tendons influence metabolic cost and exercise tolerance in the hypermobile Ehlers-Danlos Syndrome and Hypermobility Spectrum Disorders?

Patients with hypermobile Ehlers-Danlos syndrome (hEDS) and hypermobility spectrum disorders (HSD) experience a wide array of symptoms and system disorders. This study aimed to identify whether differences occurred in 115 self-reported symptoms and comorbidities in patients diagnosed with hEDS or HSD. In this study we analysed self-reported data from an EDS Clinic intake questionnaire in patients diagnosed with hEDS, HSD or no hypermobile conditions. From 1 November 2019 to 7 March 2024, the EDS Clinic saw 2088 patients. Using the 2017 diagnostic criteria, 66.5% were diagnosed with HSD (n = 1389), 20.3% with hEDS (n = 423), 10.6% with historic HSD (H-HSD) or localized HSD (L-HSD) (n = 256) (hypermobile controls) and 2.6% were not diagnosed with hEDS, HSD, H-HSD or L-HSD (n = 55) (controls). Symptoms/comorbidities that occurred with high prevalence in both hEDS and HSD included joint pain (hEDS 82.0%, HSD 88.9%), allergy (hEDS 77.0%, HSD 77.0%), subluxations (hEDS 71.2%, HSD 72.6%), brain fog (hEDS 70.0%, HSD 74.7%), headache (hEDS 68.1%, HSD 69.1%), anxiety (hEDS 60.3%, HSD 69.3%), depression (hEDS 52.2%, HSD 58.0%), migraine (hEDS 53.7%, HSD 52.5%), nausea (hEDS 54.6%, HSD 59.5%) and constipation (hEDS 53.0%, HSD 57.2%). In contrast, 9/115 (8%) symptoms/comorbidities were self-reported significantly more often in hEDS but 42/115 (37%) in HSD. hEDS patients reported more symptoms that suggest a defect in collagen, such as dislocation, hernias and rectal prolapse, while HSD patients reported more joint, muscle, allergy, neurological, gastrointestinal, sleep and psychological symptoms/comorbidities. Although we found an overlap in some symptoms and comorbidities self-reported by hEDS/HSD patients, such as allergy/atopy, headache/migraine and gastrointestinal symptoms, our findings suggest key differences exist between the two diagnoses, suggesting that hEDS and HSD may be distinct conditions.

Background/Aims The Ehlers-Danlos Society is an affiliate of Project ECHO, a non-profit organisation supporting health professionals manage their patients through telehealth case-based learning. To increase access to expert advice and learning, in 2019 the Ehlers-Danlos Society introduced EDS ECHO, a series of programmes for health professionals supporting them in learning and sharing knowledge in the management of Ehlers-Danlos syndromes (EDS) and hypermobility spectrum disorders (HSD). Programmes run from the UK, USA, and Australia; participants and experts joining from all over the world, and, from multiple specialties. This study explores participant perceptions of a 9-session programme covering all aspects of diagnosis and management in EDS and HSD, and, their co-morbidities. Each session is 90 minutes long, providing a total of 13.5 hours of learning. All materials are made available for review. The programme is repeated throughout the year. Methods The study had IRB approval from Penn State, USA. At the beginning of each 9-session programme, participants were invited to join the study. Using REDCap, a series of questions surveyed the participants confidence in managing patients with EDS or HSD; and, re-explored this at 6 months following completion of the programme. In addition, participants were surveyed for their perceptions of the value of the programme. Results 185 of 237 eligible participants completed the baseline and 6-month follow-up survey. At baseline 17%, 47%, and 36% reported their levels of confidence in diagnosing EDS or HSD as either low, moderate, or high respectively. The most reported motivations for joining the programme were: to increase knowledge (90% of responders), access experts (71%), and, increase confidence in managing EDS and HSD (68%). At 6-month follow-up 80-95% of participants reported positive experiences across the various fields of enquiry. With regard to increasing level of knowledge 46% reported a 'slight' increase and 46% a 'great' increase. Levels of confidence in diagnosis and management had risen 'slightly' in 54% and 'greatly' in 40% of participants. 78% of participants reported an overall increase in their interest in EDS and HSD. Conclusion The Project ECHO model of 'all teach all learn', case-based learning, and use of telehealth technology is well-established in supporting healthcare professionals managing patients across the breadth of Medicine. EDS ECHO follows these principles and practices, providing a series of programmes aligned to the multiple disciplines that manage people with EDS and HSD. For the majority of participants their perception was that the EDS ECHO 9-week program increased their knowledge and confidence in assessing and managing EDS and HSD. Further analysis will explore themes for developing the program, and how changes in confidence are influenced by baseline perceptions. In addition, a study is underway to explore perceptions of care among patients of participants in the EDS ECHO programme. Disclosure A. Hakim: Consultancies; The Ehlers-Danlos Society. J. Schubart: Grants/research support; The Ehlers-Danlos Society. C. Francomano: Grants/research support; The Ehlers-Danlos Society. R. Bascom: None. L. Bloom: Corporate appointments; The Ehlers-Danlos Society.

Purpose This cross-sectional mixed-method study examined healthcare experiences among individuals in the US with hypermobile Ehlers-Danlos syndrome (hEDS) and hypermobility spectrum disorder (HSD), genetic connective tissue disorders. We hypothesized that many individuals with these conditions would report low satisfaction with healthcare and low health-related quality of life, and that lower healthcare satisfaction would be related to lower health-related quality of life and self-efficacy for symptom management. Methods Adults living in the US with hEDS or HSD (N= 2125) completed an online survey assessing satisfaction with healthcare, health-related quality of life, and symptom management self-efficacy. Qualitative data also were gathered on desired changes to improve healthcare. Results Participants reported low satisfaction with healthcare and lower health-related quality of life and symptom management self-efficacy than norm groups. Lower satisfaction with healthcare was associated with lower health-related quality of life and lower symptom management self-efficacy, ps <.001. The most common desired change to improve healthcare was more knowledge about hEDS and HSD among healthcare professionals. Conclusions U.S. adults with joint hypermobility report negative healthcare experiences and poor health-related quality of life. Future research should explore ways to improve the healthcare experiences and quality of care for individuals with hEDS and HSD. Implications for Rehabilitation Individuals with hypermobility spectrum disorder (HSD) and hypermobile Ehlers-Danlos syndrome (hEDS) score worse than the U.S. population on most health-related quality of life domains and symptom management self-efficacy. Individuals with HSD and hEDS report low levels of satisfaction with healthcare compared to norm groups. Participants particularly wanted to see improvements in the level of awareness and education about HSD and hEDS among healthcare professionals, provider attitudes about HSD and hEDS, and healthcare accessibility and convenience. Individuals who were less satisfied with their healthcare reported lower health-related quality of life and lower symptom management self-efficacy, underscoring the importance of improving healthcare experiences.

Chronic pain is a common manifestation of Ehlers-Danlos syndrome and hypermobility spectrum disorders; thus it is often suggested that patients undergo generic interdisciplinary pain rehabilitation, despite there being little evidence to support this decision. The aim of this study is to examine the effectiveness of standard rehabilitation programmes for chronic pain on patients with Ehlers-Danlos syndrome and hypermobility spectrum disorders, compared with patients with other chronic pain disorders. Data, collected between 2008 and 2016, were extracted from a Swedish national registry. The patient data comprised of 406 cases with Ehlers-Danlos syndrome or hypermobility spectrum disorders, 784 cases with a whiplash-related diagnosis, 3713 cases with diagnoses relating to spinal pain, and 2880 cases of fibromyalgia. The differences between groups on key outcome measures from pre- to 1-year follow-up after interdisciplinary pain rehabilitation were analysed using linear mixed effects models. Sensitivity analysis in the form of pattern-mixture modelling was conducted to discern the impact of missing data. No significant differences were found in improvements from pre- to 1-year follow-up for patients with Ehlers-Danlos syndrome or hypermobility spectrum disorder compared with other diagnostic groups regarding measures of health-related quality of life, mental health, or fatigue. At follow-up, differences in pain interference (d = -0.34 (95% confidence interval [95% CI] -0.5 to -0.18)), average pain (d = 0.22 (95% CI 0.11-0.62)) and physical functioning (d = 2.19 (95% CI 1.61-2.77)) were detected for the group with spinal-related diagnoses in relation to those with EDS/HSD, largely due to pre-treatment group differences. Sensitivity analysis found little evidence for missing data influencing the results. This study suggests that patients with Ehlers-Danlos syndrome/hypermobility spectrum disorders may benefit from inclusion in an interdisciplinary pain rehabilitation programme.

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. 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. 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. 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.

In this retrospective study, we investigate the frequency and types of psychiatric disorders and their relationship to systemic manifestations in a cohort of 391 Ehlers-Danlos syndromes (EDS) and hypermobility spectrum disorder (HSD) patients based on the current 2017 International Classification of EDS diagnostic criteria. A detailed, systematic retrospective chart review was undertaken for patients assessed for HSD or EDS at two Canadian health centres. Patients were diagnosed according to the Villefranche criteria and reclassified for this study according to the 2017 International Classification of EDS. Data validation and statistical analyses were conducted. Psychiatric disorders were very common, with 49.4% of the total cohort affected; 28.9% reported multiple psychiatric diagnoses. Mood (34.5%) and somatoform (28.6%) disorders were most common. Interestingly, attention-deficit/hyperactivity disorder (ADHD) was significantly enriched in the HSD, but not EDS cohort (p = 0.0002, 95% CI 3.48-9.00) compared to the general population. There were no differences in the systemic associations with having psychiatric manifestations in the HSD compared to the EDS subsets. Muscle/body pain (OR 1.99) and gastrointestinal dysfunction (OR 2.07) were significantly associated with having mood disorders, and gastrointestinal dysfunction (OR 2.61) and nerve-related pain (OR 3.27) were associated with having somatoform disorders across the cohort. The common systemic associations with the presence of psychiatric manifestations in both HSD and EDS reaffirm that the conditions should be treated as a spectrum rather than as wholly separate entities, particularly with respect to psychiatric management. EDS and HSD patients share common psychiatric presentations, though ADHD is more common with HSD.

Patients with Ehlers-Danlos Syndrome (EDS) and hypermobility spectrum disorder (HSD) often complain of palpitations, presyncope/syncope, attributable to postural orthostatic tachycardia syndrome (POTS). Occasionally, the etiology of these complaints is not positional, unclear, and may require further cardiac evaluation, including cardiac monitoring. To our knowledge, the utility of implantable loop recorders (ILRs) has yet to be explored in this population. This study aimed to evaluate the utility of the ILRs in diagnosing and/or excluding arrhythmias not attributable to POTS in symptomatic patients with EDS andHSD. Patients with EDS and HSD were referred from the New York Institute of Technology (NYIT) Ehlers-Danlos Syndrome/Hypermobility Treatment Center to the Long Island Heart Rhythm Center (LIHRC) for cardiac evaluation between January 2019 and November 2023. A retrospective analysis of observational de-identified data from the LIHRC was permitted by the NYIT College of Osteopathic Medicine Institutional Review Board (BHS-1465). Patients were monitored monthly, and the utility of the ILRs was assessed based on a correlation of symptoms to an arrhythmia, the ability of the device to monitor therapy efficacy, and/or to rule out an arrhythmia as the explanation of symptoms. Data is reported as percentages and mean±standard deviation(SD). A total of 116 hypermobile patients (81 EDS/35 HSD) were evaluated. Among these patients, 31 (26.7 %) received an ILR (length of follow-up, 27.3months±14.0months), 29 females/2 males, 28 patients had EDS, 3 patients had HSD, age 34.1±11.4 years. Symptomatic sinus tachycardia (ST) occurred in 16 patients (51.6 %), and ST helped diagnose POTS and/or monitor therapy in 15 (48.4 %). Symptomatic premature ventricular complexes (PVCs) occurred in 8 patients (25.8 %), supraventricular tachycardia (SVT) in 6 (19.4 %), and ventricular tachycardia (VT) in 1 (3.2 %). In 2 patients, ILR findings led to further interventions, including PVC ablation and an implantable cardioverter-defibrillator (ICD) for symptomatic VT. The ILR demonstrated utility in all patients. This study demonstrated the utility of the ILR in identifying symptomatic arrhythmias in patients with EDS and HSD. ILR monitoring also aided in solidifying a POTS diagnosis and guiding patient management/treatment efficacy. Further evaluation in a larger cohort is needed to further understand the impact of ILR monitoring in hypermobile patients.

Treatment Modalities, Pain Response, and Referrals for Hypermobile Ehlers-Danlos Syndrome and Hypermobility Spectrum Disorders: A Retrospective Study

Purpose Hypermobility spectrum disorders (HSD) and Ehlers–Danlos syndromes (EDS) are frequently underdiagnosed, contributing to patient dissatisfaction in the healthcare system. This study evaluated the health service utilization, care, and subjective experiences of living with chronic illness among adults with HSD and EDS in the United States and Canada. Methods This was an anonymous, web-based, cross-sectional healthcare survey. The survey obtained basic demographic information, the Patient Assessment of Chronic Illness Care (PACIC+), as well as responses to questions on the use of healthcare and integrative medicine. Results A total of 353 surveys were received. The most common complementary therapies used were physical therapy (82%), massage (68%), yoga (58%), chiropractic (48%), and meditation (43%). Mean (SD) summary PACIC and PACIC 5 As scores were 2.16 (0.77) and 2.25 (0.83), respectively. Across all PACIC domains, mean scores of individuals whose typical doctor visit was 30 min or at least an hour were significantly higher than those of individuals who indicated typical visits of 15 min (all p < 0.0001 by one-way ANOVA). There was widespread agreement on the importance of patient-provider relationship and trust, physicians’ understanding of the individual’s complete medical history, and prioritization of physical and emotional safety (>95% agree or strongly agree to each). Conclusion Individuals with HSD or EDS report low satisfaction with chronic illness care and commonly seek out complementary and self-administered therapies, likely in an attempt to manage symptoms. Respondents reported a desire for greater time and attention from physicians. Results from this study could educate the healthcare community to improve support mechanisms for HSD and EDS populations. IMPLICATIONS FOR REHABILITATION Patients with hypermobility spectrum disorders (HSD) or Ehlers–Danlos syndromes (EDS) express a desire for patient-centered care and peer support from other individuals with HSD or EDS. Individuals with HSD or EDS have typically seen multiple doctors for their condition and their satisfaction with chronic care, as measured by the Patient Assessment of Chronic Illness Care (PACIC+), is low. The use of various complementary and integrative health treatments, as well as specialized diets, is common in this population, and might be beneficial for symptom management. Healthcare delivery for HSD and EDS may require a multidisciplinary healthcare team, as complementary and self-care modalities are typically used in addition to physical therapy, pain medication, and other conventional care.

Background/Aims Hypermobility spectrum disorders and hypermobile Ehlers–Danlos syndrome are multisystem, connective tissue disorders, associated with problems such as joint hyperextensibility, tissue fragility, poor proprioception and pain. Fabric orthoses might improve proprioception and assist with joint protection. No previous research has investigated this possibility. This study aimed to explore the perceptions and experiences of experts with experience of fabric orthoses who have used fabric orthoses with individuals with hypermobility spectrum disorders and hypermobile Ehlers–Danlos syndrome. Methods A total of six experts in fabric orthoses and hypermobility spectrum disorders/hypermobile Ehlers–Danlos syndrome participated in semi-structured interviews. A thematic analysis was undertaken by two analysers. Themes were validated with a member checking exercise involving three of the original participants. Results Three themes were identified. The first theme, ‘it is immediate’, described the reported positive effects when the orthosis is first donned. The second theme described a proposed mechanism of effect in which improved proprioception and realignment work together to support improved joint stability. The third theme, ‘tips for success’, captured ways in which effectiveness and acceptability are maximised, with importance ascribed to collaborative assessment. Conclusions Fabric orthoses have the potential to be effective in people with hypermobile Ehlers–Danlos syndrome or hypermobility spectrum disorders. This study is to inform futher research into the use of fabric orthoses. Further research could prioritise short-term effect, using mixed methods to explore users’ experiences alongside measures of pain, joint stability and function. Crossover studies could compare custom-made orthoses vs off-the-shelf, or orthoses with directional support vs compression alone. If short-term studies support effectiveness and acceptability, longer-term studies could include the role of fabric orthoses in prevention of disability.

Background:Ehlers-Danlos Syndromes (EDS) and Hypermobility Spectrum Disorders (HSD) are a heterogeneous group of heritable genetic connective tissue disorders with multiple characteristics including joint hypermobility, tissue fragility, and multiple organ dysfunction. Respiratory manifestations have been described in EDS patients, but have not been systematically characterized. A narrative review was undertaken to describe the respiratory presentations and management strategies of individuals with EDS and HSD.Methods:A broad literature search of Medline, Embase, Cochrane Database of Systematic Reviews, and Cochrane CENTRAL was undertaken from inception to November 2020 of all study types, evaluating EDS/ HSD and pulmonary conditions. This narrative review was limited to adult patients and publications in English.Results:Respiratory manifestations have generally been described in hypermobile EDS (hEDS), classical and vascular EDS subtypes. Depending on EDS subtype, they may include but are not limited to dyspnea, dysphonia, asthma, sleep apnea, and reduced respiratory muscle function, with hemothorax and pneumothorax often observed with vascular EDS. Respiratory manifestations in HSD have been less frequently characterized in the literature, but exertional dyspnea is the more common symptom described. Respiratory symptoms in EDS can have an adverse impact on quality of life. The respiratory management of EDS patients has followed standard approaches with thoracotomy tubes and pleurodesis for pleural manifestations, vocal cord strengthening exercises, continuous positive pressure support for sleep apnea, and exercise training. Reduced respiratory muscle function in hEDS patients responds to inspiratory muscle training.Conclusion:Respiratory symptoms and manifestations are described in EDS and HSD, and have generally been managed using conservative non-surgical strategies. Research into the prevalence, incidence and specific respiratory management strategies in EDS and HSD is needed to mitigate some of the associated morbidity.

Defective connective tissue structure may cause individuals with hypermobile Ehlers-Danlos syndrome (hEDS) or hypermobility spectrum disorders (HSD) to develop cardiac defects. We conducted a retrospective chart review of adult patients treated in the EDS Clinic from November 1, 2019, to June 20, 2022 to identify those with cardiac defects. Echocardiogram data were collected using a data collection service. All EDS Clinic patients were evaluated by a single physician and diagnosed according to the 2017 EDS diagnostic criteria. Patient demographic, family and cardiac history were extracted from self-reported responses from a REDCap clinical intake questionnaire. Patients with at least 1 available echocardiogram (ECHO) were selected for the study (n = 568). The prevalence of aortic root dilation in patients with hEDS was 2.7% and for HSD was 0.6%, with larger measurements for males than females and with age. Based on self-reported cardiac history that was verified from the medical record, patients with hEDS with bradycardia (p = 0.034) or brain aneurysm (p = 0.015) had a significantly larger average adult aortic root z-score. In contrast, patients with HSD that self-reported dysautonomia (p = 0.019) had a significantly larger average aortic root z-score. The prevalence of diagnosed mitral valve prolapse in patients with hEDS was 3.5% and HSD was 1.8%. Variants of uncertain significance were identified in 16 of 84 patients that received genetic testing based on family history. These data reveal a low prevalence of cardiac defects in a large cohort of well-characterized hEDS and HSD patients. Differences in cardiovascular issues were not observed between patients with hEDS vs. HSD; and our findings suggest that cardiac defects in patients with hEDS or HSD are similar to the general population.

BackgroundPain is a major symptom in adolescents with hypermobility spectrum disorder or hypermobile Ehlers-Danlos syndrome. Although the underlying mechanism causing generalized pain in children with hypermobility spectrum disorder or hypermobile Ehlers-Danlos syndrome is unclear, central sensitization has been suggested as a possible explanation. The aim of this study was to explore the feasibility of a study protocol for a future case–control study, investigating features of central sensitization in adolescents with hypermobility spectrum disorder or hypermobile Ehlers-Danlos syndrome.MethodsCentral sensitization features were measured in ten patients and nine healthy controls aged 13–17 years via experimental pain measurement quantifying primary and secondary hyperalgesia, endogenous pain modulation, and exercise-induced hyperalgesia. Descriptive statistics were used. Frequency, median, and range values were calculated.ResultsEleven out of 57 patients chose to participate. No control could be recruited through public schools. Therefore, a convenience sampling strategy was used for the recruitment of the control group. The process of assessing primary and secondary hyperalgesia, endogenous pain modulation, and exercise-induced hyperalgesia was well tolerated by all participants (patients and controls). When assessing endogenous pain modulation via conditioned pain modulation, two participants in the patient group and three in the control group did not achieve a pain experience ≥ 3 on the numerical rating scale when immersing their hands in cold water.ConclusionThis study investigated the feasibility, safety, and toleration of experimental pain measurements in adolescents with hypermobility spectrum disorder or hypermobile Ehlers-Danlos syndrome. Although the test protocol proved to be sufficiently feasible for use with the participant group, it will need to be adapted in the main study in order to obtain more reliable data. Recruitment, especially of participants for the control group, can be a major obstacle for future studies and requires careful planning.Trial registrationResearchweb.org, 270,501. Registered on 9 May 2019.

Prevalence of joint hypermobility syndromes in pediatric postural orthostatic tachycardia syndrome.

Objectives: To investigate the prevalence of joint hypermobility classes, hypermobility spectrum disorders, hypermobile Ehlers-Danlos syndrome and their relations with sex ina university population. They are notable topics in rehabilitation, since they represents the basis for some secondary disability conditions. Methods: Three hundred and thirty-five students met the inclusion criteria (university students who are not disabled, without known disease, aged 18-25 years). Joint hypermobility were classified as generalized, peripheral and localized asymptomatic or hypermobility spectrum disorders. Hypermobile Ehlers-Danlos syndrome was defined according to; 1) Brighton criteria with cut-off Beighton scoring ≥ 4/9, 2) Villefranche criteria with cut-off Beighton scoring ≥ 5/9, and 3) The 2017 International Classification of Ehlers-Danlos syndrome. Results: In total, 77.3% (n = 259) of participants had any class of joint hypermobility and 25.9% (n=87) of them had generalized class. Asymptomatic joint hypermobility and hypermobility spectrum disorders prevalence in a university population were found to be 38.8% and 38.5%, respectively. Generalized, peripheral, localized asymptomatic joint hypermobility and hypermobility spectrum disorders were found; 13.1%, 4.2%, 21.5%, and 12.8%, 7.5%, 18.2%, respectively. Prevalence of hypermobile Ehlers-Danlos syndrome according to three classifications were found to be; 19.4%, 15.2%, and 1.2%, respectively. Conclusions: The most common classes are localized asymptomatic joint hypermobility in women and localized hypermobility spectrum disorders in men. Awareness of the prevalence of joint hypermobility, hypermobility spectrum disorders and hypermobile Ehlers-Danlos syndrome in healthy young population may contribute prevention of disability.