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Background: A high prevalence of disorders of gut‐brain interaction (DGBI) exist in patients with hypermobile Ehlers‐Danlos Syndrome (hEDS) and hypermobility spectrum disorders (HSD). However, it is unknown if clusters of hEDS/HSD patients exist which overlap with different DGBIs and whether this overlap influences presence of comorbidities and quality of life. We aimed to study these knowledge gaps. Methods: A prospectively collected hEDS/HSD cohort of 1044 individuals were studied. We undertook Uniform Manifold Approximation and Projection‐enabled (UMAP) dimension reduction to create a representation of nonlinear interactions between hEDS/HSD and DGBIs, from which individuals were stratified into clusters. Somatization, Postural Tachycardia Syndrome (PoTS), autonomic symptoms, psychological factors and quality of life were statistically compared between clusters. Key Results: The mean age of patients was 40 ± 13.2 years; 87.8% were female. Patients segregated into three clusters: Cluster 0 (n = 466): hEDS/HSD+ functional foregut disorders (FFD) + irritable bowel syndrome (IBS); Cluster 1 (n = 180): hEDS/HSD+ IBS and Cluster 2 (n = 337): hEDS/HSD alone. In cluster 0, we demonstrated increased somatization (p <0.0001), anxiety (p <0.0001), depression (p <0.0001), PoTS prevalence (p = 0.003), autonomic symptoms (p <0.0001) and reduced quality of life (p <0.0001) compared to cluster 2. Cluster 0 had greater comorbidity burden than cluster 1. Conclusions: Within hEDS/HSD, subgroups exist with a high prevalence of FFD and IBS. These subgroups have a higher prevalence of psychological disorders, dysautonomia and poorer quality of life compared with hEDS/HSD alone. Further research should focus on healthcare utilization, management and prognosis in hEDS/HSD and DGBI overlap. [ABSTRACT FROM AUTHOR]

The Ehlers‐Danlos syndromes (EDS), a group of uncommon connective tissue disorders, are, paradoxically, an increasingly common referral to genetics specialists. Of the 13 types of EDS, the most common is hypermobile EDS (hEDS), which lacks a known genetic etiology and for which diagnosis is achieved via a robust set of clinical criteria. While previous investigations have characterized many clinical aspects of EDS as a syndrome and patients' lived experiences, a gap in the literature exists regarding clinicians' experience caring for these individuals. This study sought to understand the effects of hEDS patient referrals from genetic counselors' perspectives. To capture these novel views and values, we conducted semi‐structured interviews with 15 participants who were members of the National Society of Genetic Counselors (NSGC) and had experience working with the hEDS patient population. Interview questions explored the frequency of hEDS referrals in their clinic, investigated their roles and responsibilities as genetic counselors when working with this population, analyzed their workflow for this indication, assessed the impacts on their professional satisfaction, and explored potential options for improving workflow and care for the hEDS patient population. Reflexive thematic analysis yielded four themes: (1) Referrals for hEDS have generally increased over time and many institutions have implemented new policies to control this influx, (2) genetic counselors' primary roles include education and addressing psychosocial matters for this population, (3) genetic counselors feel both rewarded and challenged by these referrals, and (4) genetic counselors call for more education and training on hEDS for all healthcare specialties. Our findings provide a better understanding of the goals of the hEDS patient referrals to genetics specialists and the opportunities and challenges those referrals present. Genetic counselors have specific training and skills in psychosocial counseling and communication, in some ways making them ideal care providers for this population. However, they are simultaneously a scarce resource and the complex medical issues presented by many patients with hEDS make multidisciplinary management essential. We conclude with potential avenues for improving interactions with this population. [ABSTRACT FROM AUTHOR]

Vascular Ehlers‐Danlos, Marfan and Loeys‐Dietz syndromes have increased risk of aortic dilation and dissection. Previous early studies showed hypermobile Ehlers‐Danlos syndrome (hEDS) may also have increased risk, with echocardiography screening recommended; subsequent studies have not confirmed the risk or recommended echocardiography. This pediatric‐based study assessed aortic dilation prevalence in those with hEDS by serial echocardiographic examinations and assessed family history for aortic dissections. We retrospectively identified individuals with hEDS who had echocardiography studies from the electronic medical records at one pediatric center. Aortic root Z‐scores >2.0 were found in 15/225 subjects (average age 12.9 years) on initial echocardiograms, with no Z‐score >3.0. Subsequent studies (n = 68) found statistically significant decline in aortic root Z‐scores. Repeat echocardiography in those with initial aortic root Z‐score >2.0 (n = 10) demonstrated a decline in Z score <2.0 in seven. On final examination, 9/225 (4.0%) had a Z‐score >2.0, not statistically different from the general population. No aortic dissection occurred in first‐ or second‐degree relatives. In conclusion, aortic root dilation rate in hEDS is likely not different from the general population. We propose that in the absence of other cardiac findings or suspicion for another disorder, echocardiography is not required in hEDS. [ABSTRACT FROM AUTHOR]

Objectives 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. Methods In this study we analysed self-reported data from an EDS Clinic intake questionnaire in patients diagnosed with hEDS, HSD or no hypermobile conditions. Results 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. Conclusion 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. [ABSTRACT FROM AUTHOR]

Background: Many patients experience persistent symptoms after COVID-19, a syndrome referred to as Long COVID (LC). The goal of this study was to identify novel new or worsening comorbidities self-reported in patients with LC. Methods: Patients diagnosed with LC (n = 732) at the Mayo Long COVID Care Clinic in Rochester, Minnesota and Jacksonville, Florida were sent questionnaires to assess the development of new or worsening comorbidities following COVID-19 compared to patients with SARS-CoV-2 that did not develop LC (controls). Both groups were also asked questions screening for myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), generalized joint hypermobility (GJH) and orthostatic intolerance. 247 people with LC (33.7%) and 40 controls (50%) responded to the surveys. Results: In this study LC patients averaged 53 years of age and were predominantly White (95%) women (75%). The greatest prevalence of new or worsening comorbidities following SARS-CoV-2 infection in patients with LC vs. controls reported in this study were pain (94.4% vs. 0%, p < 0.001), neurological (92.4% vs. 15.4%, p < 0.001), sleep (82.8% vs. 5.3%, p < 0.001), skin (69.8% vs. 0%, p < 0.001), and genitourinary (60.6% vs. 25.0%, p = 0.029) issues. 58% of LC patients screened positive for ME/CFS vs. 0% of controls (p < 0.001), 27% positive for GJH compared to 10% of controls (p = 0.026), and a positive average score of 4.0 on orthostatic intolerance vs. 0 (p < 0.001). The majority of LC patients with ME/CFS were women (77%). Conclusion: We found that comorbidities across 12 surveyed categories were increased in patients following SARS-CoV-2 infection. Our data also support the overlap of LC with ME/CFS, GJH, and orthostatic intolerance. We discuss the pathophysiologic, research, and clinical implications of identifying these conditions with LC. [ABSTRACT FROM AUTHOR]

Purpose: Narrative Medicine complements the clinically centered approach, which focuses on the analytical and sanitary aspects, with the illness- and disorder- centered models, which deal respectively, with personal coping and social perception of a condition. Hypermobile Ehlers- Danlos Syndrome and Behçet's Disease are two rare multisystemic chronic disease experienced a myriad of clinical symptoms, psychological distress, and poor quality of life. The purpose of this report is to describe application of a multidisclipinary rehabilitation intervention according to the narrative medicine. Case description and Intervention: a 35-year-old woman with a 23-year history of Hypermobile Ehlers-Danlos Syndrome and Behçet's Disease was admitted. A multimodal rehabilitation approach was implemented and described through the patient's feelings and expected short-, medium-, and long- terms goals. Moreover, she reported her feeling with periodical interview by her therapist. History patient: The patient was seen for 32 weeks. A decreased pain, as well as improved function was recorded immediately post-intervention. Conclusion: Narration is not just an interpretation of the illness experience, but the result of reshaping the interpretations of the story that both patient and health professional. This discipline provides enrichment of care, especially when combined with rehabilitation in chronic disease, by paying attention to and using even in the therapeutic phase the stories of patients, family and health care personnel, giving the opportunity to define a tailored effectiveness rehabilitation approach at the light of the different points of view of the subjects. IMPLICATIONS FOR REHABILITATION: Narrative Medicine might play a key role in an interpretation of the illness experience to implement a multidisciplinary tailored rehabilitation approach. Narrative Medicine can help understand discomfort and difficulty associated with rehabilitation activities, thereby enhancing patient motivation and participation in interdisciplinary care. The Ehlers–Danlos Syndrome is a heterogeneous group of heritable connective tissue disorders representing a challenge in rehabilitation. Behçet's Disease is a rare multisystemic chronic disease experiencing an impaired function and a poor quality of life. A patient-oriented multimodal rehabilitation showed to be a useful approach in the case with both diseases, with a reduction of pain and an improvement of functioning. [ABSTRACT FROM AUTHOR]

Hypermobility spectrum disorders (HSD) and hypermobile Ehlers-Danlos syndrome (hEDS) are the most common joint hypermobility conditions encountered by physicians, with hypermobile and classical EDS accounting for >90% of all cases. Hypermobility has been detected in up to 30-57% of patients with myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), fibromyalgia, postural orthostatic tachycardia syndrome (POTS), and long COVID (LC) compared to the general population. Extrapulmonary symptoms, including musculoskeletal pain, dysautonomia disorders, cognitive disorders, and fatigue, are seen in both LC and HSD. Additionally, ME/CFS has overlapping symptoms with those seen in HSD. Mast cell activation and degranulation occurring in both LC and ME/CFS may result in hyperinflammation and damage to connective tissue in these patients, thereby inducing hypermobility. Persistent inflammation may result in the development or worsening of HSD. Hence, screening for hypermobility and other related conditions including fibromyalgia, POTS, ME/CFS, chronic pain conditions, joint pain, and myalgia is essential for individuals experiencing LC. Pharmacological treatments should be symptom-focused and geared to a patient's presentation. Paced exercise, massage, yoga, and meditation may also provide benefits. [ABSTRACT FROM AUTHOR]

Purpose: Hypermobile Ehlers-Danlos Syndrome (hEDS) and Hypermobility Spectrum Disorders (HSD) are understudied conditions characterized by hallmark hypermobility and chronic pain. Disease manifestations lead to significant disability. Understanding predictors of disability, over and above the univariate construct of pain severity, is necessary to tailor treatment. Thus, the current study examined the impact of the Fear-Avoidance Model [FAM] on disability in hEDS/HSD. Fear of falling was included as a novel fear-avoidance factor impacting disability. Methods: A total of 168 individuals with hEDS/HSD answered a cross-sectional online survey regarding FAM constructs, fear of falling, disability, and clinical-demographic factors. A hierarchical regression analysis was used to assess whether FAM constructs and fear of falling significantly predicted disability, over and above pain severity and age. Results: Pain catastrophizing, anxiety, and fear of falling contributed significant unique predictive relations, above age and average pain severity. Pain severity and fear of falling were the strongest unique predictors of disability. Conclusions: This is the first study to assess the relations among FAM constructs, pain severity, and disability in hEDS/HSD, and introduces fear of falling as a novel fear-avoidance factor specific to this population. Future research should apply these findings towards individualized interventions to improve disability in hEDS/HSD. IMPLICATIONS FOR REHABILITATION: Disability is significant in hypermobile Ehlers-Danlos Syndrome and Hypermobility Spectrum Disorders, and may be predicted by psychosocial factors of anxiety, pain catastrophizing, and fear of falling. Our findings suggest that improving disability in hypermobile Ehlers-Danlos Syndrome and Hypermobility Spectrum Disorders involves the consideration of physical factors, such as pain severity, along with psychosocial factors, the latter of which are amenable to change through individualized intervention plans. Fear of falling is a novel fear-avoidance construct that should be considered in future research and clinical settings to increase functionality in this frequently falling population. [ABSTRACT FROM AUTHOR]

Background: Ehlers–Danlos syndrome (EDS) is a common group of inherited connective tissue disorders with a prevalence as high as 0.75%–2% of the population. Physical manifestations include pain and decreased proprioception, especially in more mobile joints, such as the shoulder. The kinesiology tape (K-Tape) is often used to treat patients with shoulder dysfunction. The effectiveness of the K-Tape is uncertain, and there is a lack of studies specifically studying the K-Tape in an EDS population. Purpose: The purpose of this study was to compare the short-term effects of two different K-Tape procedures on shoulder active joint reposition (AJR) and active range of motion (AROM) in patients with hypermobile EDS (hEDS) and shoulder pain. Methods: All participants were recruited from the EDS support groups and presented with shoulder pain. Baseline demographic information was obtained for each participant, after which AROM and AJR were assessed. The participants were randomized to receive one of two K-Tape procedures. Testing was repeated immediately post-taping and 48 h post-taping. Results: Significant improvements in shoulder external (F = 10.917, p < 0.001) and internal (F = 11.736, p < 0.001) rotations were seen from baseline to immediately post-taping and baseline to 48 h post-taping in the experimental K-Tape group. There were no significant differences in the shoulder rotation in the control K-Tape group and no significant differences in either group for shoulder flexion or AJR at any time point (p > 0.05). Conclusion: K-Tape may offer short-term improvements in shoulder rotation AROM in patients with hEDS and shoulder pain. [ABSTRACT FROM AUTHOR]

Physical therapy (PT) plays a central role in treating individuals with Generalized Hypermobility Spectrum Disorder (G-HSD) and Hypermobile Ehlers-Danlos Syndrome (hEDS). However, there is limited research describing these individuals' PT management. This review aims to systematically map the evidence on PT interventions to treat this patient population. A systematic literature search of PubMed, CINAHL, and Embase from January 2000 to April 2023 was performed. After the screening process, studies were appraised and classified based on the type of PT interventions used. Five reviewers independently assessed the articles. The search produced 757 articles. Twenty-eight met the inclusion criteria. The studies included 630 participants, mostly female, with a mean age of 26.2 (ranging from 2 to 69). The PT interventions used were therapeutic exercise, patient instruction, motor function training, adaptive equipment, manual therapy, and functional training. The evidence indicates that therapeutic exercise and motor function training are efficacious methods to treat individuals with G-HSD and hEDS. There is also weak evidence for using adaptive equipment, patient instruction, manual therapy, and functional training. Recent studies emphasize multidisciplinary care and understanding of the psychological impact of G-HSD/hEDS. Additional research is needed to determine the effectiveness and dosage of PT interventions. The lack of guidelines and consensus on physical therapy (PT) interventions to treat and restore function in people with Generalized Hypermobility Spectrum Disorder (G-HSD) and hypermobile Ehlers-Danlos Syndrome (hEDS) challenges clinicians. This review supports therapeutic exercise and motor function training to improve function, well-being, and quality of life in people with G-HSD and hEDS. There is weak evidence for using adaptive equipment, patient instruction, manual therapy, and functional training. We have gathered existing evidence, appraised the quality, and drawn conclusions on this population's most supported PT interventions. [ABSTRACT FROM AUTHOR]

The most common conditions with symptomatic joint hypermobility are hypermobile Ehlers‐Danlos syndrome (hEDS) and hypermobility spectrum disorders (HSD). Diagnosing these overlapping connective tissue disorders remains challenging due to the lack of established causes and reliable diagnostic tests. hEDS is diagnosed applying the 2017 diagnostic criteria, and patients with symptomatic joint hypermobility but not fulfilling these criteria are labeled as HSD, which is not officially recognized by all healthcare systems. The 2017 criteria were introduced to improve diagnostic specificity but have faced criticism for being too stringent and failing to adequately capture the multisystemic involvement of hEDS. Herein, we retrospectively evaluated 327 patients from 213 families with a prior diagnosis of hypermobility type EDS or joint hypermobility syndrome based on Villefranche and Brighton criteria, to assess the effectiveness of the 2017 criteria in distinguishing between hEDS and HSD and document the frequencies of extra‐articular manifestations. Based on our findings, we propose that the 2017 criteria should be made less stringent to include a greater number of patients who are currently encompassed within the HSD category. This will lead to improved diagnostic accuracy and enhanced patient care by properly capturing the diverse range of symptoms and manifestations present within the hEDS/HSD spectrum. [ABSTRACT FROM AUTHOR]

Introduction: Left renal vein compression (nutcracker physiology) with secondary spinal epidural venous congestion is a newly recognized cause of daily persistent headache. Presently, only women with underlying symptomatic hypermobility issues appear to develop headache from this anatomic issue. The hypothesized etiology is an abnormal reset of the patient's cerebrospinal fluid (CSF) pressure to an elevated state. Headaches that occur during sleep can have a varied differential diagnosis, one of which is elevated CSF pressure. We present the case of an older woman who began to develop severe wake-up headaches at midnight. She was found to have left renal vein compression and spinal epidural venous congestion on imaging. After treatment with lumbar vein coil embolization, which alleviated the spinal cord venous congestion, her headaches alleviated. Case Report: A 61-year-old woman with a history of hypermobile Ehlers-Danlos syndrome began to be awakened with severe head pain at midnight at least several times per week. The headache was a holocranial, pressure sensation, which worsened in the supine position. The headaches were mostly eliminated with acetazolamide. Because of her hypermobility issues and pressure-like headache, she was investigated for underlying nutcracker physiology and spinal epidural venous congestion. This was confirmed using magnetic resonance (MR) angiography and conventional venography, and after lumbar vein coil embolization her wake-up headaches ceased. Conclusion: The case report suggests a possible new underlying and treatable cause for early morning, wake-up headaches: nutcracker physiology with secondary spinal epidural venous congestion. The case expands on the clinical headache presentation of nutcracker physiology. [ABSTRACT FROM AUTHOR]

Background: Using hydrogen breath testing (HBT) to diagnose small intestinal bacterial overgrowth (SIBO) remains controversial in patients with functional gastrointestinal (GI) disorders, and unknown in those with hypermobility Ehlers–Danlos syndrome (hEDS). We assessed prevalence of positive HBTs in these groups, evaluated the predictive value of GI symptoms and the potential role of proton pump inhibitors (PPIs) on test results. Methods: Sequential patients referred for HBT to a tertiary unit were classified into the following groups: GI maldigestion/malabsorption, GI sensorimotor disorders, hEDS, and functional GI disorders. All underwent standardized HBT, and the yield was assessed against symptoms and PPI use. Key Results: A total of 1062 HBTs were performed over 3 years (70% female, mean age 48 ± 16 years). Overall, 7.5% (80/1062) patients had a positive HBT. Prevalence of positive HBT was highest in patients with GI maldigestion/malabsorption (17.9%; DOR 16.16, p < 0.001), GI sensorimotor disorders (15.9%; DOR 8.84, p < 0.001), compared to functional GI disorders (1.6%; DOR 1.0) (p < 0.0001). None of the hEDS patients tested positive for HBT. A positive HBT was independently associated with increased age (DOR 1.03; p < 0.001) and symptoms of diarrhea (DOR 3.95; p < 0.0001). Patients on PPIs tended towards a positive HBT than patients off PPIs (16.1% vs 6.9%; DOR 2.47; p < 0.0001). Conclusions & Inferences: Less than 2% of patients with functional GI disorders, and none of the patients with hEDS had a positive HBT. Pre‐test probability was higher in patients with: GI structural or neurological disorders; use of long‐term PPIs and symptoms of diarrhea. These criteria may be helpful in making appropriate therapeutic decisions and avoiding unnecessary hydrogen breath testing. [ABSTRACT FROM AUTHOR]

In recent years, there has been a noteworthy revival of interest in the function of mast cells (MCs) in the human body. It is now acknowledged that MCs impact a wide array of processes beyond just allergies, leading to a shift in research direction. Unfortunately, some earlier conclusions were drawn from animal models with flawed designs, particularly centered around the receptor tyrosine kinase (Kit) pathway. Consequently, several subsequent findings may have been unreliable. Thus, what is now required is a re-examination of these earlier findings. Nevertheless, the remaining data are fascinating and hold promise for a better comprehension of numerous diseases and the development of more effective therapies. As the field continues to progress, many intriguing issues warrant further investigation and analysis. For instance, exploring the bidirectional action of MCs in rheumatoid arthritis, understanding the extent of MCs' impact on symptoms associated with Ehlers–Danlos syndrome, and unraveling the exact role of the myofibroblast–mast cell–neuropeptides axis in the joint capsule during post-traumatic contractures are all captivating areas for exploration. Hence, in this review, we summarize current knowledge regarding the influence of MCs on the pathogenesis of selected musculoskeletal diseases, including rheumatoid arthritis, spondyloarthritis, psoriatic arthritis, gout, muscle and joint injuries, tendinopathy, heterotopic ossification, and Ehlers–Danlos syndrome. We believe that this review will provide in-depth information that can guide and inspire further research in this area. [ABSTRACT FROM AUTHOR]

Ehlers–Danlos syndromes are a heterogeneous group of Heritable Connective Tissue Disorders characterized by joint hypermobility, skin hyperextensibility, and tissue fragility. Among the different types, the hypermobile Ehlers–Danlos syndrome is the most frequent and includes generalized joint hypermobility as the major diagnostic criterion. Joint hypermobility in hypermobile Ehlers–Danlos syndrome is often associated with pain that does not always allow the use of effective pain-reducing treatments. Patients with hEDS constantly describe their pain in detail. Eighty-nine patients with hEDS diagnoses were recruited and evaluated. They were asked to describe their pain in writing. The texts were examined through Linguistic Inquiry and Word Count. Correlational analyses were conducted between pain perception and language. A comparison of high/low pain perception and the quality of metaphors was carried out. The results showed that language quality varies depending on how much pain is perceived. The greater the pain is perceived, the lesser the positive effects and the greater the negative effects and dehumanizing metaphors are being used. Moreover, a greater pain seems to be related to a verbal experience of greater isolation and less self-care. In conclusion, the use of metaphors is a useful tool for examining illness experience and may help clinicians in the rehabilitation program. [ABSTRACT FROM AUTHOR]

To investigate the effectiveness of two home-based exercise programs for treating multidirectional shoulder instability (MDI) in patients diagnosed with Hypermobile Ehlers-Danlos syndrome (hEDS) or Hypermobility Spectrum Disorders (HSD). Twenty-one hEDS/HSD patients with MDI were recruited from the Center for Medical Genetics of the Ghent University Hospital. Patients were randomly assigned to either the experimental or the control group. Both groups received a 6-month home-based exercise program. The primary outcome measure was the Western Ontario Shoulder Index (WOSI). Secondary outcomes included the Disabilities of the Arm, Shoulder and Hand (DASH), Tampa Scale for Kinesiophobia (TSK), Patient-Specific Functional Scale (PSFS), Global Rating of Change (GROC), and pain pressure thresholds. Outcomes were assessed at baseline, after 6 weeks, 12 weeks, and 24 weeks. Significant main effects for time were observed for all questionnaires, except for the TSK (p = 0.12). Patients improved 240 and 325 points on the WOSI after 12 (p = 0.02) and 24 weeks (p = 0.001), respectively. Additionally, patients improved 8.6 points on the DASH (p = 0.002), 4.3 points on the PSFS (p = 0.01), and 1.02 points on the GROC (p = 0.001) after 24 weeks. No significant differences were found between group A and B. Both home-based exercise programs led to significant improvements in shoulder function. Home-based exercise therapy may be effective for treating MDI in the hEDS/HSD population. Home-based training is beneficial for improving shoulder function, but a multidisciplinary, supervised approach might be more effective for altering kinesiophobia in this patient population. [ABSTRACT FROM AUTHOR]

Cardiovascular system involvements have been frequently reported in hypermobile Ehlers‐Danlos Syndrome (hEDS). Mitral valve prolapse (MVP) and aortic root dilatation are included in the 2017 international classification criteria for hEDS. Different studies have found conflicting results regarding the significance of cardiac involvement in hEDS patients. We conducted a retrospective review of cardiac involvement in patients diagnosed with hEDS based on the 2017 International diagnostic criteria to provide further evidence toward more defined and reliable diagnostic criteria and recommended cardiac surveillance. A total of 75 hEDS patients with at least one diagnostic cardiac evaluation were included in the study. The most common reported cardiovascular complaints were lightheadedness (80.6%), followed by palpitations (77.6%), fainting (44.8%), and chest pain (32.8%). Of the 62 echocardiogram reports, 57 (91.9%) showed trace/trivial to mild valvular insufficiency, and 13 (21%) had additional abnormalities such as grade I diastolic dysfunction, mild aortic sclerosis, and trivial or small pericardial effusion. Of the 60 electrocardiograms (ECG) reports, 39 (65%) were normal, and 21 (35%) reported minor abnormalities or normal variants. Even though many hEDS patients in our cohort experienced cardiac symptoms, the presence of a significant cardiac abnormality was very low. [ABSTRACT FROM AUTHOR]

Key Clinical Message: Omalizumab may be a beneficial adjunct treatment option for hEDS patients require to improve pain control, ability to perform ADLs and functionality and social engagement, and most importantly, quality of life. [ABSTRACT FROM AUTHOR]

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The use of dynamic elastomeric fabric orthoses is examined in a young woman with hypermobile Ehlers‐Danlos syndrome (hEDS) referred for physiotherapy with hip dysplasia, prior to a right periacetabular osteotomy. Dynamic elastomeric fabric orthoses plus rigorous subjective examination, therapists' listening skills, and patient‐centered goals were useful for this hEDS patient. [ABSTRACT FROM AUTHOR]

Hypermobile Ehlers–Danlos syndrome (hEDS) and hypermobility spectrum disorders (HSD) are clinically overlapping connective tissue disorders of unknown etiology and without any validated diagnostic biomarker and specific therapies. Herein, we in-depth characterized the cellular phenotype and gene expression profile of hEDS and HSD dermal fibroblasts by immunofluorescence, amplicon-based RNA-seq, and qPCR. We demonstrated that both cell types show a common cellular trait, i.e., generalized extracellular matrix (ECM) disarray, myofibroblast differentiation, and dysregulated gene expression. Functional enrichment and pathway analyses clustered gene expression changes in different biological networks that are likely relevant for the disease pathophysiology. Specifically, the complex gene expression dysregulation (mainly involving growth factors, structural ECM components, ECM-modifying enzymes, cytoskeletal proteins, and different signal transducers), is expected to perturb many ECM-related processes including cell adhesion, migration, proliferation, and differentiation. Based on these findings, we propose a disease model in which an unbalanced ECM remodeling triggers a vicious cycle with a synergistic contribution of ECM degradation products and proinflammatory mediators leading to a functional impairment of different connective tissues reflecting the multisystemic presentation of hEDS/HSD patients. Our results offer many promising clues for translational research aimed to define molecular bases, diagnostic biomarkers, and specific therapies for these challenging connective tissue disorders. [ABSTRACT FROM AUTHOR]

Background and Aim: Hypermobile Ehlers–Danlos syndrome (hEDS) and the hypermobility spectrum disorders (HSD) can be challenging to diagnose and manage. Gastrointestinal symptoms and disorders of gut‐brain interaction are common in this cohort and multifactorial in origin. The primary aim of this review is to arm the gastroenterologist with a clinically useful understanding of HSD/hEDS, by exploring the association of gastrointestinal disorders with HSD/hEDS, highlighting current pathophysiological understanding and providing a pragmatic approach to managing these patients. Methods: Literature relevant to the gastrointestinal system and hypermobile Ehlers–Danlos syndrome was systematically searched, critically appraised, and summarized. Results: Diagnosis is based upon clinical criteria and a genetic basis is yet to be defined. The prevalence of many gut symptoms, including abdominal pain (69% vs 27%, P < 0.0001), postprandial fullness (34% vs 16%, P = 0.01), constipation (73% vs 16%, P < 0.001), and diarrhea (47% vs 9%, P < 0.001) are significantly higher in HSD/hEDS compared with non‐HSD/hEDS individuals. Disorders of gut‐brain interaction are also common, particularly functional dyspepsia. The pathophysiology of gut symptoms is poorly understood but may involve effects of connective tissue laxity and its functional consequences, and the influence of autonomic dysfunction, medication and comorbid mental health disorders. Awareness is the key to early diagnosis. Management is limited in evidence‐base but ideally should include an integrated multidisciplinary approach. Conclusions: HSD/hEDS is a multisystemic disorder in which gastrointestinal symptoms, particularly related to disorders of gut‐brain interaction are common. Deficiencies in knowledge regarding the pathophysiological processes limit evidence‐based interventions and remain important areas for future research. [ABSTRACT FROM AUTHOR]

Orthostatic intolerance (OI) is frequently reported in young women with generalized hypermobility spectrum disorder (G‐HSD) and hypermobile EDS (hEDS). However, it remains currently unclear whether OI is a comorbidity or fundamental part of the pathophysiology of G‐HSD or hEDS. This study investigated the prevalence and impact of OI in young women across the hypermobility spectrum. Forty‐five women (14–30 years, 15 controls, 15 G‐HSD, and 15 hEDS) undertook a head‐up tilt (HUT) and active stand test. Postural Orthostatic Tachycardia Syndrome (POTS) and Orthostatic Hypotension (OH) were assessed using age‐related criteria. Autonomic dysfunction and quality‐of‐life questionnaires were also completed. The prevalence of POTS was higher in women with G‐HSD than hEDS and control groups during HUT (43% vs. 7% and 7%, respectively, p < 0.05), but similar between groups during the active stand (47%, 27%, and 13% for G‐HSD, hEDS, and control, respectively). No participants had OH. hEDS and G‐HSD participants reported more severe orthostatic symptoms and poorer quality of life than controls. Although POTS was observed in hypermobile participants, there is no conclusive evidence that its prevalence differed between groups due to differences between the HUT and active stand assessments. Nevertheless, OI and broader autonomic dysfunction impacted on their quality of life. [ABSTRACT FROM AUTHOR]

Dysautonomia is a recognized manifestation in patients with joint hypermobility (JH) disorders. Symptoms can be highly debilitating and commonly include physical deconditioning and poor aerobic fitness. In this study, the prevalence of dysautonomia, range of associated symptoms, patient‐reported physical activity levels, and echocardiographic features were assessed retrospectively in a cohort of 144 patients (94% female) with hypermobile Ehlers–Danlos syndrome (hEDS) or hypermobility spectrum disorder (HSD). Echocardiographic parameters of left ventricular size and function were compared between patients with and without dysautonomia as well as to reported values from healthy controls. Dysautonomia was identified in 65% of female and 44% of male subjects and was associated with a high burden of symptomatology, most commonly exercise intolerance (78%). Exercise capacity was limited by dysautonomia, often postural symptoms, in half of all patients. We observed a reduction in physical activity following the onset or significant flare of hEDS/HSD, most strikingly noting the proportion of dysautonomic patients with sedentary lifestyle, which increased from 44% to 85%. JH‐related dysautonomia was associated with smaller cardiac chamber sizes, consistent with the previous reports in positional orthostatic tachycardia syndrome. Dysautonomia is prevalent in patients with hEDS/HSD, and exercise intolerance is a key feature and leads to drastic decline in physical activity. Unfavorable cardiac geometry may underlie dysautonomia symptoms and may be due to cardiac atrophy in the setting of aerobic deconditioning. [ABSTRACT FROM AUTHOR]

Objectives The aim was to ascertain occupational therapist (OT) and physiotherapist (PT) experiences of managing hypermobility spectrum disorders (HSDs) and hypermobile Ehlers-Danlos syndrome (hEDS) patients, specifically the training and confidence levels of therapists, use of evidence-based practice, accessibility of pain management and clinical psychology services, and perceived usefulness of a specialist centre in Scotland. Methods A mixed-method survey was distributed to Rheumatology OTs/PTs in Scotland. It included multiple choice and open text questions, which were analysed to reflect therapists' experiences and perception of service need. Results We found that therapists in Scotland do have expertise in the management of HSD/hEDS patients; however, this expertise tends to be concentrated in secondary care, which makes it difficult for patients who are managed in primary care to access. The majority of respondents reported lack of access to external training (80%). There was difficulty in referral to pain management services (55%) and clinical psychology (28%) among adult therapists. Paediatric services provided considerably better access to these disciplines. Of note, the majority of respondents were in favour of a specialist centre in Scotland for the training and education of therapists (94.7%) and the diagnosis and management of complex HSD/hEDS patients (73.7%). Conclusion More research is needed urgently to evaluate the effectiveness of therapy interventions to underpin a national guideline in order that we can improve outcomes for HSD/hEDS patients. A specialist centre with expert and engaged clinicians would be a valuable asset in coordinating patient-focused research and conducting good-quality clinical trials. [ABSTRACT FROM AUTHOR]

Objectives: A significant proportion of adolescents with chronic musculoskeletal pain (CMP) experience difficulties in physical functioning, mood and social functioning, contributing to diminished quality of life. Generalized joint hypermobility (GJH) is a risk factor for developing CMP with a striking 35-48% of patients with CMP reporting GJH. In case GJH occurs with one or more musculoskeletal manifestations such as chronic pain, trauma, disturbed proprioception and joint instability, it is referred to as generalized hypermobility spectrum disorder (G-HSD). Similar characteristics have been reported in children and adolescents with the hypermobile Ehlers-Danlos Syndrome (hEDS). In the management of CMP, a biopsychosocial approach is recommended as several studies have confirmed the impact of psychosocial factors in the development and maintenance of CMP. The fear-avoidance model (FAM) is a cognitive-behavioural framework that describes the role of pain-related fear as a determinant of CMP-related disability. Content: Pubmed was used to identify existing relevant literature focussing on chronic musculoskeletal pain, generalized joint hypermobility, pain-related fear and disability. Relevant articles were cross-referenced to identify articles possibly missed during the primary screening. In this paper the current state of scientific evidence is presented for each individual component of the FAM in hypermobile adolescents with and without CMP. Based on this overview, the FAM is proposed explaining a possible underlying mechanism in the relations between GJH, pain-related fear and disability. Summary and outlook: It is assumed that GJH seems to make you more vulnerable for injury and experiencing more frequent musculoskeletal pain. But in addition, a vulnerability for heightened pain-related fear is proposed as an underlying mechanism explaining the relationship between GJH and disability. Further scientific confirmation of this applied FAM is warranted to further unravel the underlying mechanism. In explaining disability in individuals with G-HSD/hEDS, it is important to focus on both the physical components related to joint hypermobility, in tandem with the psychological components such as pain-related fear, catastrophizing thoughts and generalized anxiety. [ABSTRACT FROM AUTHOR]

Postural orthostatic tachycardia syndrome (POTS) is a disorder of orthostatic intolerance associated with many GI manifestations that can be broadly classified into two different categories: those present all the time (non‐positional) and those that occur with orthostatic position change. There are also many conditions that can co‐exist with POTS such as mast cell activation syndrome and the hypermobile form of Ehlers‐Danlos syndrome (hEDS) that are also oftentimes associated with GI symptoms. In the current issue of Neurogastroenterology and Motility, Tai et al. explored the relationship between functional GI disorders among hEDS patients with and without concomitant POTS and showed that the hEDS‐POTS cohort was more likely to have more than one GI organ involved compared to the cohort with hEDS alone, and certain GI symptoms were also more common in the hEDS‐POTS cohort. In this review article, we will briefly review the literature surrounding putative mechanisms responsible for GI symptoms in POTS with an emphasis on the contributory role of concomitant hEDS and then discuss management strategies for GI symptoms in POTS. [ABSTRACT FROM AUTHOR]

In recent years, an association between hypermobile Ehlers-Danlos syndrome (hEDS), mast cell activation syndrome (MCAS), and postural orthostatic tachycardia syndrome (POTS) has garnered attention and patients are increasingly presenting with this triad. However, a real relationship between these entities is unclear due to a lack of scientific validity. We conducted an extensive review of the literature using two different search strategies. A narrower strategy included 88 searches of various combinations of terms for each of the three conditions, yielding 19 unique papers. A broader search included 136 searches of various combinations of terms but included all forms of EDS and yielded 40 unique papers. Of these, only four and nine papers from the narrower and broader search strategies were original research articles. None of these papers resulted from a combination of the search terms for the three conditions. All three clinical entities are controversial in either existence or pathogenesis. MCAS is a poorly defined clinical entity, and many studies do not adhere to the proposed criteria when establishing the diagnosis. Patients previously diagnosed with EDS hypermobility type may not meet the new, stricter criteria for hEDS but may for a less severe hypermobility spectrum disorder (HSD). The pathophysiology of POTS is still unclear. An evidence-based, common pathophysiologic mechanism between any of the two, much less all three conditions, has yet to be described. Our review of the literature shows that current evidence is lacking on the existence of MCAS or hEDS as separate or significant clinical entities. Studies proposing a relationship between the three clinical entities are either biased or based on outdated criteria. The reason behind the purported association of these entities stems from an overlapping pool of vague, subjective symptoms, which is inadequate evidence to conclude that any such relationship exists. [ABSTRACT FROM AUTHOR]

There is an association between joint hypermobility, hypermobile Ehlers-Danlos syndrome (hEDS) and different forms of orthostatic intolerance. Objective: to explore autonomic profile in a large cohort of adults with hEDS and hypermobility spectrum disorder (hEDS/HSD) with a multimodal approach. In this observational retrospective study, heart rate, blood pressure and baroreflex sensitivity were estimated in 102 hEDS/HSD subjects during deep breathing, Valsalva maneuver, standing up: 30-15 ratio, Head-Up Tilt and sustained handgrip. Abnormal results and headup tilt test were common and included postural orthostatic tachycardia syndrome (POTS; 48%), orthostatic intolerance (25.5%) and hypotension (3.9%). Baroreflex sensitivity was significantly different in individuals with POTS compared to the others. This study confirms the high rate and heterogeneity of abnormal autonomic regulation in hEDS/HSD, and suggests the baroreflex sensitivity might distinguish comorbid POTS from other profiles in this subgroup of patients. Abnormal autonomic regulation is common in adults with hEDS/HSD and should be regularly assessed for tailoring the management approach. [ABSTRACT FROM AUTHOR]

Features of the pain in hypermobile Ehlers‐Danlos syndrome (hEDS) are complex and insufficiently known by clinicians. We enrolled 37 hEDS patients. Disease status was ascertained using revised 2017 International Classification criteria, in the EDS French National Reference Center. Patients were evaluated with a clinical examination, quantitative sensory testing, and validated questionnaires. Thirty‐seven patients were evaluated. Pain had appeared at 10 ± 5 years old and became chronic at 20 ± 9 years old. hEDS was diagnosed at only 24 ± 10 years old. Ninety‐seven percent of them had severe chronic pain, which gradually increased over time in 75% of them. The main location of pain was in joints and predominated in lower limbs. Patients with a generalized presentation of pain had older chronic pain and a higher impact on the affective component. Neuropathic pain was frequent in the most painful joint and associated with heat hypoesthesia. An asymmetric proprioception was found in one third of the patients. A very high rate of attempted suicide was observed. To conclude, pain in hEDS is severe, chronic, and disabling. Sensorial and proprioceptive sensibilities are also affected. Peripheral neuropathic pain is frequent and central sensitization appears to be a key step in the evolution of disease. [ABSTRACT FROM AUTHOR]

Hypermobile Ehlers‐Danlos syndrome (hEDS) is a hereditary disorder of connective tissue, often presenting with complex symptoms can include chronic pain, fatigue, and dysautonomia. Factors influencing functional disability in the pediatric hEDS population are incompletely studied. This study's aims were to assess factors that affect quality of life in children and adolescents with hEDS. Individuals with hEDS between the ages 12–20 years and matched parents were recruited through retrospective chart review at two genetics clinics. Participants completed a questionnaire that included the Pediatric Quality of Life Inventory (PedsQL™), PedsQL Multidimentional Fatigue Scale, Functional Disability Inventory, Pain‐Frequency‐Severity‐Duration Scale, the Brief Illness Perception Questionnaire, measures of anxiety and depression, and helpful interventions. Survey responses were completed for 47 children and adolescents with hEDS/hypermobility spectrum disorder (81% female, mean age 16 years), some by the affected individual, some by their parent, and some by both. Clinical data derived from chart review were compared statistically to survey responses. All outcomes correlated moderately to strongly with each other. Using multiple regression, general fatigue and pain scores were the best predictors of the PedsQL total score. Additionally, presence of any psychiatric diagnosis was correlated with a lower PedsQL score. Current management guidelines recommend early intervention to prevent disability from deconditioning; these results may help identify target interventions in this vulnerable population. [ABSTRACT FROM AUTHOR]

Abstract: Background: Joint hypermobility syndrome (JHS) is characterized by excessive connective tissue laxity manifest as joint hypermobility (JH) together with musculoskeletal symptoms. Previous studies have shown an association between JH/JHS and gastrointestinal symptoms, including irritable bowel syndrome (IBS), although its association with specific IBS subtypes is incompletely understood. We aimed to determine the prevalence of JH according to the subtypes of IBS, in particular IBS‐C and IBS‐D. Methods: Data of 228 consecutive IBS patients were analyzed. IBS was subtyped into constipation and diarrhea predominant IBS (IBS‐C and IBS‐D), IBS with mixed bowel habits (IBS‐M) and unsubtyped IBS (IBS‐U). JH was defined as a Beighton Score ≥4/9 points and JHS diagnosed according to revised Brighton Criteria. Data of IBS patients were analyzed for psychological comorbidities assessed by Hospital Anxiety and Depression Scale (HADS) and Visceral Sensitivity Index (VSI). Key Results: Of 228 IBS patients, 64 (28.1%) suffered from IBS‐C, 89 (39.0%) from IBS‐D, 48 (21.1%) from IBS‐M, and 27 (11.8%) from IBS‐U. JH was diagnosed in 95 patients (41.7%). The prevalence of JH was significantly higher in IBS‐C than IBS‐D (57.8% vs 34.8%, P = .031). There was no significant difference in VSI and HADS according to JH or IBS subtype. Conclusions and Interferences: The prevalence of JH was significantly higher in IBS‐C compared to IBS‐D. Abnormalities in the connective tissue biomechanics in those with JH may contribute to a degree of colonic inertia which could result in constipation in JH‐positive IBS patients. Further work is needed to determine the colonic biomechanics in patients with JH. [ABSTRACT FROM AUTHOR]

Aim: To assess the prevalence, severity and impact of fatigue on individuals with joint hypermobility syndrome (JHS)/Ehlers-Danlos syndrome - hypermobility type (EDS-HT) and establish potential determinants of fatigue severity in this population. Methods: Questionnaires on symptoms and signs related to fatigue, quality of life, mental health, physical activity participation and sleep quality were completed by people with JHS/EDS-HT recruited through two social media sites. Multiple regression analysis was performed to identify predictors of fatigue in this population. Results: Significant fatigue was reported by 79.5% of the 117 participants. Multiple regression analysis identified five predictors of fatigue severity, four being potentially modifiable, accounting for 52.3% of the variance in reported fatigue scores. Predictors of fatigue severity were: the self-perceived extent of joint hypermobility, orthostatic dizziness related to heat and exercise, levels of participation in personal relationships and community, current levels of physical activity and dissatisfaction with the diagnostic process and management options provided for their condition. Conclusion: Fatigue is a significant symptom associated with JHS/EDS-HT. Assessment of individuals with this condition should include measures of fatigue severity to enable targeted management of potentially modifiable factors associated with fatigue severity. Implications for rehabilitation: Fatigue is a significant symptom reported by individuals affected by joint hypermobility syndrome/Ehlers-Danlos syndrome - hypermobility type. Potentially modifiable features that contribute to fatigue severity in this population have been identified. Targeted management of these features may decrease the severity and impact of fatigue in joint hypermobility syndrome/Ehlers-Danlos syndrome - hypermobility type. [ABSTRACT FROM AUTHOR]

Ehlers–Danlos syndrome (EDS) is a heterogeneous heritable connective tissue disorder with various neurological manifestations, including chronic pain. The neurological manifestations in EDS are often regarded as being caused by the associated musculoskeletal disorders or polyneuropathy. Here, we present two patients with hypermobile EDS (hEDS), presenting with relapsing central nervous system (CNS) manifestations. Although the two patients showed relapsing signs of CNS manifestations like multiple sclerosis (MS) or neuromyelitis optica spectrum disorder (NMOSD), they were unique in that they had widespread opioid-dependent chronic pain, which is not consistent with the symptoms of MS/NMOSD. Unexpectedly, the serious pain of unknown origin was remarkably mitigated by plasmapheresis, and magnetic resonance imaging (MRI) examinations conducted for one of the patients were negative. Collectively, we speculate that hEDS may be more susceptible to ‘normal-appearing imaging, neuroimmunologically justified, autoimmune-mediated encephalomyelitis (NINJA).’ Analysis of the presented cases and an additional three patients with EDS with chronic pain indicates that treatable immune-mediated mechanisms deserve considerations for neurological symptoms observed in hEDS. [ABSTRACT FROM AUTHOR]

Hypermobile Ehlers-Danlos syndrome (hEDS) is the most frequent type of EDS and is characterized by generalized joint hypermobility and musculoskeletal manifestations which are associated with chronic pain, and mild skin involvement along with the presence of more than a few comorbid conditions. Despite numerous research efforts, no causative gene(s) or validated biomarkers have been identified and insights into the disease-causing mechanisms remain scarce. Variability in the spectrum and severity of symptoms and progression of hEDS patients' phenotype likely depend on a combination of age, gender, lifestyle, and the probable multitude of genes involved in hEDS. However, considering the clinical overlap with other EDS forms, which lead to abnormalities in extracellular matrix (ECM), it is plausible that the mechanisms underlying hEDS pathogenesis also affect the ECM to a certain extent. Herein, we performed a series of in vitro studies on the secretome of hEDS dermal fibroblasts that revealed a matrix metalloproteinases (MMPs) dysfunction as one of the major disease drivers by causing a detrimental feedback loop of excessive ECM degradation coupled with myofibroblast differentiation. We demonstrated that doxycycline-mediated inhibition of MMPs rescues in hEDS cells a control-like ECM organization and induces a partial reversal of their myofibroblast-like features, thus offering encouraging clues for translational studies confirming MMPs as a potential therapeutic target in hEDS with the expectation to improve patients' quality of life and alleviate their disabilities. [ABSTRACT FROM AUTHOR]

Heritable Connective Tissue Disorders (HCTD) show an overlap in the physical features that can evolve in childhood. It is unclear to what extent children with HCTD experience burden of disease. This study aims to quantify fatigue, pain, disability and general health with standardized validated questionnaires. Methods. This observational, multicenter study included 107 children, aged 4–18 years, with Marfan syndrome (MFS), 58%; Loeys-Dietz syndrome (LDS), 7%; Ehlers-Danlos syndromes (EDS), 8%; and hypermobile Ehlers-Danlos syndrome (hEDS), 27%. The assessments included PROMIS Fatigue Parent–Proxy and Pediatric self-report, pain and general health Visual-Analogue-Scales (VAS) and a Childhood Health Assessment Questionnaire (CHAQ). Results. Compared to normative data, the total HCTD-group showed significantly higher parent-rated fatigue T-scores (M = 53 (SD = 12), p = 0.004, d = 0.3), pain VAS scores (M = 2.8 (SD = 3.1), p < 0.001, d = 1.27), general health VAS scores (M = 2.5 (SD = 1.8), p < 0.001, d = 2.04) and CHAQ disability index scores (M = 0.9 (SD = 0.7), p < 0.001, d = 1.23). HCTD-subgroups showed similar results. The most adverse sequels were reported in children with hEDS, whereas the least were reported in those with MFS. Disability showed significant relationships with fatigue (p < 0.001, rs = 0.68), pain (p < 0.001, rs = 0.64) and general health (p < 0.001, rs = 0.59). Conclusions. Compared to normative data, children and adolescents with HCTD reported increased fatigue, pain, disability and decreased general health, with most differences translating into very large-sized effects. This new knowledge calls for systematic monitoring with standardized validated questionnaires, physical assessments and tailored interventions in clinical care. [ABSTRACT FROM AUTHOR]

Background: Four out of five patients with hypermobility spectrum disorder (HSD) or hypermobile Ehlers-Danlos syndrome (hEDS) experience shoulder complaints including persistent pain and instability. Evidence suggests that patients with HSD/hEDS who experience knee and back complaints improve with exercise-based therapy. However, no study has focused on exercise-based treatment for the shoulder in this patient group. The potential benefits of strengthening the shoulder muscles, such as increased muscle-tendon stiffness, may be effective for patients with HSD/hEDS who often display decreased strength and increased shoulder laxity/instability. The primary aim is to investigate the short-term effectiveness of a 16-week progressive heavy shoulder strengthening programme and general advice (HEAVY) compared with low-load training and general advice (LIGHT), on self-reported shoulder symptoms, function, and quality of life.Methods: A superiority, parallel group, randomised controlled trial will be conducted with 100 patients from primary care with HSD/hEDS and shoulder complaints (persistent pain and/or instability) for more than 3 months. Participants will be randomised to receive HEAVY (full range of motion, high load) or LIGHT (neutral to midrange of motion, low load) strengthening programme three times weekly with exercises targeting scapular and rotator cuff muscles. HEAVY will be supervised twice weekly, and LIGHT three times during the 16 weeks. The primary outcome will be between-group difference in change from baseline to 16-week follow-up in the Western Ontario Shoulder Instability Index (WOSI, 0-2100 better to worse). Secondary outcomes will include a range of self-reported outcomes covering symptoms, function, and quality of life, besides clinical tests for shoulder strength, laxity/instability, and proprioception. Outcome assessors will be blinded to group allocation. Participants will be kept blind to treatment allocation through minimal information about the intervention content and hypotheses. Primary analyses will be performed by a blinded epidemiologist.Discussion: If effective, the current heavy shoulder strengthening programme will challenge the general understanding of prescribing low-load exercise interventions for patients with HSD/hEDS and provide a new treatment strategy. The study will address an important and severe condition using transparent, detailed, and high-quality methods to potentially support a future implementation.Trial Registration: ClinicalTrials.gov NCT03869307 . Registered on 11 March 2019. [ABSTRACT FROM AUTHOR]