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Autonomic symptom burden in the hypermobility type of Ehlers-Danlos syndrome: A comparative study with two other EDS types, fibromyalgia and healthy controls
... While there are many manifestations of AD, orthostatic disturbances are highly studied and discussed. These are very common in people with hEDS, with 80-94% of people reporting orthostatic disturbances either through self-reported clinical symptom scales or as measured objective signs (12)(13)(14). Orthostatic problems are variable and are classified as orthostatic intolerance when signs and symptoms are present but do not meet the full criteria for postural orthostatic tachycardia syndrome (POTS). Still, for simplicity, we will refer to any degree of orthostatic intolerance as OI. ...
... hEDS patients with POTS have an increase in GI diagnoses and symptoms compared to POTS-negative hEDS patients, including increases in IBS (59% vs. 51%) and functional gastroduodenal disorders (75% vs. 67%) (18). GI and OI symptoms have a high impact on physical quality of life and pain, leading to reduced health outcomes and increased psychological stress (12,21,23). ...
... These frequently begin with complaints of OI and correlate with perceptions of overall health and symptom exacerbation directly. Specifically, AD is frequently identified in people with hEDS, and the overwhelming majority of people with hEDS report some degree of OI (7,10,(12)(13)(14). Clinically, the standard for assessing autonomic function uses HRV, or the changes in time intervals between consecutive heartbeats, from 24-h Holter monitor ECG data (30), but this is costly and can only be done in short durations. ...
Introduction
People with hypermobile Ehlers–Danlos syndrome (hEDS) experience multisystemic dysfunction with varying severity and unpredictability of flare occurrence. Cohort studies suggest that individuals with hEDS have a higher risk for autonomic dysfunction. The gold standard for assessing autonomic function, clinically, is the heart rate variability (HRV) assessment from 24-h Holter monitor electrocardiogram data, but this is expensive and can only be performed in short durations. Since their advent, biometric devices have been a non-invasive method for tracking HRV to assess autonomic function. This study aimed to understand the intra- and inter-individual variability in autonomic function and to associate this variability with gastrointestinal symptoms in individuals with hEDS using wearable devices.
Methods
We studied 122 days of biometric device data from 26 individuals, including 35 days highlighted as high gastrointestinal (GI) dysfunction and 48 days as low GI dysfunction. Utilizing wavelet analysis to assess the frequency domains of heart rate signals, we compared participants’ HRV data for high, low, very low (VLF), and ultralow (ULF) frequency domains associated with physiological differences.
Results
We found a significant difference between the VLF and ULF signals on high-GI symptom days compared with low-symptoms days for 92 and 76% of the signals sampled, respectively.
Discussion
Our pilot data show a change in HRV for individuals with hEDS experiencing a flare day for a single-body system. Future research will focus on evaluating the relationship between longitudinal multisystemic symptom severity fluctuations and HRV.
... Supplemental Digital Content 1 (Table 1, (Coussens et al., 2021;De Wandele et al., 2014), two in Italy Puledda et al., 2015), and one in the Netherlands (Scheper et al., 2016). Two studies were retrospective reviews (Alomari et al., 2020;Schubart et al., 2019), two were longitudinal (Coussens et al., 2021;Schubart et al., 2022), and one each case-control (Puledda et al., 2015), prospective case series (Bénistan & Martinez, 2019), and individual case report (Bergl et al., 2019). ...
... One study compared individuals with migraines and JHS or EDS-HT to individuals with migraines but without JHS/EDS-HT (Puledda et al., 2015). One study compared individuals with EDS-HT to four groups: classical EDS, vascular EDS, fibromyalgia, and healthy control participants (De Wandele et al., 2014). ...
... Two longitudinal studies examined physiologic function or symptom evolution over time (Coussens et al., 2021;Schubart et al., 2022). Other studies evaluated the prevalence of hEDS/HSD-associated symptoms or comorbidities, such as gut dysmotility (Alomari et al., 2020), mucocutaneous findings , autonomic symptoms (De Wandele et al., 2014), gynecologic symptoms (Glayzer et al., 2021;Hugon-Rodin et al., 2016), pain (Bénistan & Martinez, 2019;Kalisch et al., 2019;Murray et al., 2013), migraine headaches (Puledda et al., 2015), muscle strength (Scheper et al., 2016), and suicidal behaviors (Baeza-Velasco et al., 2021). One study used cluster analysis of registry data to delineate EDS phenotypic subgroups (Schubart et al., 2019). ...
Background:
Research on hypermobile Ehlers-Danlos syndrome and hypermobility spectrum disorder (hEDS/HSD) has described its natural history and clinical course in children, adolescents, and young to middle-aged adults. However, more research is needed on the clinical trajectory of hEDS/HSD into older age. Therefore, clinicians, including nurse practitioners, know little about identifying older adults with undiagnosed hEDS/HSD.
Objective:
This review sought to identify studies regarding aging in hEDS/HSD.
Data sources:
This scoping review included PubMed, Cumulative Index to Nursing and Allied Health Literature, and Scopus and found 15 studies that mentioned age or aging on the symptoms and health-related quality of life.
Conclusions:
No study had a stated aim regarding aging in hEDS/HSD, but all studies corroborated earlier natural history studies describing the age-related trajectory of manifestations in younger people. Studies found that symptom progression was heterogeneous, multisystemic, and unpredictable. Studies also noted prolonged diagnosis delays and long symptom duration, but the impact of these factors on outcomes was unclear. The high variability in patient outcomes precludes the prediction of outcomes based on the included studies. The clinical impact of aging on hEDS/HSD remains mostly speculative.
Implications for practice:
Nurse practitioners, especially those in primary care, should consider that older adults presenting with multimorbidity may have undiagnosed hEDS/HSD. More research is needed to identify symptom patterns and clinical history that may suggest an underlying connective tissue disorder.
... Des troubles du système nerveux autonome (SNA) sont fréquemment décrits avec principalement une intolérance orthostatique et un syndrome de tachycardie orthostatique posturale (Celletti et al., 2020;Chan et al., 2019;De Wandele et al., 2014c, 2014a, 2016Hakim et al., 2017b;Rombaut et al., 2011a;. Une étude a montré qu'un patient sur trois qui présentait un syndrome de tachycardie orthostatique posturale correspondait aux critères du SEDh (Miller et al., 2020). ...
... Bien qu'une association soit reconnue entre ces troubles et la fatigue, la douleur, la qualité de vie, le déconditionnement ou les troubles anxieux, les liens de causalité n'ont pas encore été établis (De Wandele et al., 2014a;Hakim et al., 2017b). Des troubles gastro-intestinaux pourraient également être liés à une dérégulation du SNA et sont rapportés par les patients (De Wandele et al., 2014a). ...
... Bien qu'une association soit reconnue entre ces troubles et la fatigue, la douleur, la qualité de vie, le déconditionnement ou les troubles anxieux, les liens de causalité n'ont pas encore été établis (De Wandele et al., 2014a;Hakim et al., 2017b). Des troubles gastro-intestinaux pourraient également être liés à une dérégulation du SNA et sont rapportés par les patients (De Wandele et al., 2014a). Partie 1 : Revue de littérature Chapitre 2 : Présentation clinique du SEDh Des hypothèses ont été émises pour tenter d'expliquer ces troubles comme une hypoperfusion cérébrale, une hyperréactivité adrénergique, une modification de structure des vaisseaux sanguins, une malformation d'Arnold-Chiari (anomalie structurale du cervelet), une neuropathie des petites fibres ou encore un taux élevé d'histamine (De Wandele et al., 2016;Hakim et al., 2017b;Miller et al., 2020). ...
Introduction : Le syndrome d'Ehlers-Danlos hypermobile (SEDh) fait partie des troubles héréditaires du tissu conjonctif et présente une grande variabilité phénotypique avec de nombreux symptômes décrits. Parmi ces derniers on retrouve des symptômes respiratoires qui ont été assez peu étudiés et dont l'étiologie reste inconnue. A ce jour il n'y a pas de de proposition thérapeutique validée scientifiquement pour les patients atteints d'un SEDh.Objectif : L'objectif général de ce travail de thèse était d'optimiser la prise en charge par l'activité physique du SEDh.Méthode : Pour répondre à cet objectif, cinq études ont été menées. Afin de mieux comprendre les attentes des patients, ils ont été interrogé sur les domaines de santé les plus importants à évaluer. Les effets d'une prise en charge par la réadaptation ont ensuite été mesurés rétrospectivement puis prospectivement avec une comparaison à une période contrôle et un suivi à moyen terme. Afin d'étudier les symptômes respiratoires à l'exercice, une exploration des contraintes mécaniques ventilatoires a été menée. Enfin, ce sont la capacité à percevoir le volume pulmonaire et l'impact d'une charge cognitive sur le contrôle de la ventilation qui ont été étudiés dans une dernière étude.Résultats : La première étude a montré que la douleur, la fatigue et les troubles du sommeil ainsi que les troubles musculosquelettiques font partie des domaines les plus importants à évaluer selon les patients. Toutefois, le consensus n'a pas été établi, probablement en raison de la grande variabilité phénotypique de ces patients. Les deux études menées sur les effets d'un programme de réadaptation ont montré des bénéfices de cette forme de prise en charge sur de nombreux domaines. Elles montrent également un maintien modéré des effets à moyen terme qui nécessiterait de développer un programme post-réadaptation. L'étude suivante a montré la présence de contraintes mécaniques ventilatoires à l'exercice chez ces patients avec une tendance à l'hyperinflation dynamique et des limitations du débit expiratoire. Enfin, la dernière étude a montré une perception altérée du volume pulmonaire et une ventilation erratique lors de la réalisation d'une tâche cognitive. L'ensemble de ces travaux, par le biais d'une meilleure compréhension de la maladie et la validation d'outils thérapeutiques, apporte des éléments essentiels pour l'optimisation de la prise en charge du SEDh.
... FMS is common with a prevalence of 18% (95% CI of 11%-25%) among people with widespread pain and between 0.2% and 6.6% among the general population [1][2][3][4]. The symptomatic features of FMS include headache, sleep disturbances and various syndromes such as myofascial pain, restless leg, irritable bowel, and chronic fatigue and it impacts negatively on psychological health [2,[5][6][7]. ...
... It was previously theorized that joint hypermobility in FMS increased the muscular stress which increased nociceptor excitability, leading to chronicity of pain [17][18]. De Wandele et al., (2014) compared the autonomic symptoms in EDS-HT with other types of EDS and FMS [6]. Patients with joint hypermobility were excluded from the FMS group reaching an exclusion rate of 50%. ...
... Patients with joint hypermobility were excluded from the FMS group reaching an exclusion rate of 50%. However, great similarities were still identified between EDS-HT and FMS, in reflex syncope and orthostatic intolerance, vasomotor, secretomotor and gastrointestinal domains [6]. The similarities with FMS were greater than with the other types of EDS [6]. ...
Background: Anecdotally, fibromyalgia syndrome (FMS) and connective tissue disorders (hypermobile Ehlers-Danlos Syndrome (hEDS), Hypermobility Spectrum disorders (HSD) and Generalized Joint Hypermobility (GJH)) manifest overlap in their diagnostic approach and symptomatic features. Understanding this overlap is important for accurate diagnosis and the success of subsequent management. This study therefore aimed to identify the prevalence of concomitant diagnosis of FMS and hEDS/HSD/GJH in adults and their shared symptomatic manifestations using a systematic review.
Methods: MEDLINE (via EBSCO host) was systematically searched. Observational research (case-control or single group) studies were considered for inclusion, where adults screened for hEDS/HSD/GJH and FMS were compared in terms of diagnostic prevalence, and musculoskeletal and non-musculoskeletal manifestations. Studies on pediatric populations were excluded. The quality of the included studies was assessed using the National Institute of Health Quality Assessment of Case-Control Studies and Jonna Briggs Critical Appraisal checklist for prevalence studies. The review was registered prospectively in PROSPERO (CRD42020216283).
Findings: The review included eleven studies: nine case-control studies and two single group studies. The prevalence of concomitant diagnosis of hEDS/HSD and FMS ranged from 68%-88.9% and from 8.0-64.2% for GJH and FMS. The prevalence and severity of a range of objective and patient-reported features were similar between hEDS/HSD and FMS, including joint pain (duration, persistence, SF-36-pain component score); joint swelling; muscle weakness; neurological problems; multidimensional pain inventory-activity; dysautonomia and total autonomic symptoms burden (including orthostatic intolerance, reflex syncope, vasomotor, gastrointestinal, diarrhea, constipation and pupillomotor domains); function; and quality of life. Shared symptomatic features between GJH and FMS were mean pain level, tender points count, total myalgia score and psychological impact.
Interpretation: There may be overlapping symptomatology and diagnostic prevalence of FMS and hEDS/HSD/GJH. Clinicians should consider both diagnoses to ensure appropriate diagnosis and management.
... Collagen is an essential component in skin, joint capsules, and ligaments. A defect in the genes that regulate the biosynthesis, assembly and organization of collagen fibrils can cause joint hypermobility, a1111111111 a1111111111 a1111111111 a1111111111 a1111111111 tissue fragility and skin hyperextensibility [2]. EDS has a wide range of symptoms and clinical signs, of which the core features are joint hypermobility, hyperextensible or soft skin, and soft tissue fragility [3,4]. ...
... However, the symptoms in daily life and functional complications in HSD are similar as in patients with hEDS. Pain and fatigue interfere with everyday functioning and have a significant impact on activities and participation and lead to a reduced quality of life [2]. Often, lifestyle and professional choices may need to be adapted [8]. ...
... Both pain and fatigue are known to be important determinants for disability in individuals with hEDS [12][13][14][15][16][17][18]. Moreover, research in hypermobile patient groups has demonstrated that certain non-musculoskeletal symptoms, among which orthostatic intolerance and irritable bowel, contribute to decreased quality of life [2,19]. As a consequence of their symptoms, most patients have problems in participating in physical activities and social functioning, as well as in leisure activities [20][21][22]. ...
Ehlers-Danlos syndrome and hypermobility spectrum disorder affect daily life. There is a lack of research that investigates how the disease affects aspects of participation. This study investigates whether there is a difference in the level of participation in society in persons with vascular EDS (N = 18), hypermobile EDS (N = 20), classical EDS (N = 4) and Hypermobility Spectrum Disorder (N = 27), compared to a healthy control group (N = 69) and fibromyalgia (N = 69). In this retrospective case-control study, the Ghent Participation Scale was completed by all participants. Each patient with EDS and HSD was matched by age and sex to healthy controls. The hEDS and HSD group were compared with the healthy control group and a positive control group (persons with fibromyalgia). The results show that there was a significant lower overall participation score for persons with hEDS/HSD compared to the healthy control group. In addition, significant differences were observed in the subscores self-performed activities and delegated activities in the hEDS/HSD group compared to healthy controls, being HEDS/HSD patients who obtained the lower scores. Further research is needed to obtain representative results of the participation level for the EDS/HSD population. In this way, interventions can be set up for patients with EDS in an evidence-based way and that are appropriate to the patient’s level of participation.
... Each of these chronic diseases showed a specific profile of autonomic symptoms according to the prevalence, frequency, and severity of the autonomic symptoms. To this extent, orthostatic and gastrointestinal problems seem to be prevalent in patients with Ehlers-Danlos syndrome, while orthostatic intolerance and sweating problems are more frequent in COPD patients [5][6][7][8][9]. ...
... Few studies also suggest that early identification of autonomic symptoms in patients with chronic disease is essential to improve patient's daily quality of life by managing specific autonomic symptoms by adjusting lifestyle and disease treatment of patients [16]. Nowadays, autonomic symptoms are often overlooked in clinical practice and are mainly attributed to the poor health condition of the patient or the side effects of CHF treatment [4,5]. ...
... Orthostatic intolerance has been described as a major complaint in chronic diseases and the elderly [5,6,[27][28][29]. Our study indicates that this is also the case in CHF. ...
Objective
Autonomic disorders are common in chronic illness, and their symptoms may restrict the daily functioning of patients. However, in chronic heart failure, extensive knowledge about autonomic symptoms is still lacking. This study aims to explore self-perceived autonomic symptoms, associated factors, and their relationship with health-related quality of life in chronic heart failure.
Methods
One hundred and twenty-four patients with documented chronic heart failure (men and women; 50–86 years) and 124 sex and age-matched controls participated in this study. The participants filled validated questionnaires about autonomic symptom profile (COMPASS 31), fatigue (CIS, Checklist for individual strength), anxiety and depression (HADS, Hospital Anxiety and Depression), and health-related quality of life (SF36). Non-parametric statistics were performed to analyse the data.
Results
Total score for autonomic symptoms was higher in chronic heart failure compared to controls [Median: 14.9; IQR: 6.2–25.1 vs. 7.3; 0–18; p < 0.001], especially for orthostatic hypotension [Median: 8; IQR: 0–16 vs. 0; 0–12; p < 0.001], vasomotor [Median: 0; IQR: 0–0 vs. 0; 0–0; p < 0.001] and secretomotor function [Median: 0; IQR: 0–4.2 vs. 0; 0–2.1; p = 0.013]. High scores for autonomic symptoms were moderate correlated with higher scores of fatigue, anxiety and depression (0.343 ≤ rs ≥ 0.420; p < 0.001) and with decreased health-related quality of life (−0.454; p < 0.01).
Conclusion
Autonomic symptoms, especially for orthostatic intolerance, vasomotor and secretomotor subdomains, are prevalent and are associated with fatigue complaints and poor health-related quality of life in CHF.
... Pain is a constant from childhood and onward for a majority of individuals with SGJH [11]. Apart from pain and fatigue, other frequently reported symptoms are headache, heart palpitations, light-headedness and syncope, intestine related problems, and problems with the temperature regulation, [12] all with severe negative effects on functional capacity. Inner organ symptoms linked to SGJH are mainly of a functional gastro-intestinal origin (pain, bloating, diarrhea and constipation) possibly caused by changed mechanical traits of the intestinal wall and decreased gut motility [13,14]. ...
... Subsequent studies supported that a peripheral neuropathy in this group could trigger both pain and autonomic dysfunction [19,21]. In a study with 80 patients with hEDS, participants' sensory profile (Pain Detect Questionnaire) revealed a high prevalence of neuropathic symptoms: paresthesia, numbness and burning pain [12]. Bénistan and Martinez [11] evaluated pain in 37 French patients with hEDS (clinical examination, Quantitative sensory testing (QST), questionnaires) and concluded that neuropathic pain was prevalent in the joint found most painful to the patient. ...
... Small fiber neuropathy has also been suggested to cause autonomic symptoms (Table 2), such as the orthostatic intolerance common in SGJH, [12] that can limit time in standing position to about 5-15 minutes, and affect daily activities like social events. Sympathetic denervation, especially in the lower extremities, can negatively affect venous constriction capacity. ...
... Fibromyalgia and hEDS share several clinical manifestations, including chronic pain, fatigue, gastrointestinal abnormalities, autonomic dysfunction, postural orthostatic tachycardia syndrome and migraine (6). Chronic pain is the most common symptom between both conditions and is associated with various psychosocial and physical symptoms (7,9). However, hEDS has been linked to greater chronicity and pain severity, as well as interference with daily life, it is less responsive to treatments with antidepressants and anticonvulsants than fibromyalgia (10), hEDS is more prevalent in children and women while fibromyalgia tends to be more common with increasing age (8,10). ...
... While some authors have suggested that patients with EDS have an intraepidermal reduction in nerve fiber density of unknown etiology, up to 40% of patients with fibromyalgia have small fiber neuropathy (12,13). Dysautonomia, central nervous system neuronal plasticity for pain centralization, sympathetic hyperreactivity at rest, hypoactivity in response to acute stressors and prolonged use of postoperative opioids are some pathophysiological mechanisms shared between fibromyalgia and hEDS (7,(14)(15)(16). ...
Introduction: Ehlers-Danlos syndrome (EDS) is a genetic disorder that affects the connective tissue. Hypermobile subtype (hEDS), which is the most common, is characterized by joint hyperlaxity, diffuse generalized pain, and chronic fatigue. Meanwhile, fibromyalgia is a pain regulation disorder of chronic, widespread musculoskeletal pain, fatigue, cognitive disturbance, psychiatric and multiple somatic symptoms. Objective: To examine the similarities and differences between hEDS, fibromyalgia and highlight the importance of their proper diagnosis and treatment. Methods: A systematic search of PubMed and Scopus databases was performed for all English - Spanish language studies published between 2013 and May 2023. Two reviewers independently selected studies, extracted data and applied quality criteria. Study quality was assessed using PRISMA and a synthesis of the best evidence was obtained. Results: A total of 20 studies met the criteria and were therefore analyzed. Conclusion: Diagnosing EDS and fibromyalgia can be challenging in medical practice as their clinical manifestations can overlap, and they may even coexist in the same patient.
... Studies using standing challenges suggest between 11 % (Reynolds et al., 2014) and 27 % (Hoad et al., 2008) of participants with a CFS diagnosis also have a diagnosis of POTS. Of note, not only is POTS common to individuals with CFS, fibromyalgia and hypermobile variants of EDS, but pain and fatigue, which are the defining feature of fibromyalgia and CFS respectively, are frequently experienced in individuals with hypermobile variants of EDS (De Wandele et al., 2014a;De Wandele et al., 2013;De Wandele et al., 2016). Indeed, commonalities between these conditions have prompted investigators to propose they are overlapping pathologies (De Wandele et al., 2016;Wells et al., 2018b). ...
... Only one case study, with a participant with CFS i.e., (Ballantine et al., 2019), was found. This deficit of information coupled with the emerging evidence of the prevalence of POTS in these populations e.g., (De Wandele et al., 2014b;van Campen et al., 2020b) and its significant impact on quality of life e.g., (Roma et al., 2019;De Wandele et al., 2014a) highlights the need for high-quality future studies to guide safe and effective implementation of exercise for POTS management with a dedicated focus on these groups. ...
... There is a well-recognized association between joint hypermobility and chronic fatigue, and between joint hypermobility and orthostatic intolerance [19][20][21][22][23][24][25][26][27]. As a result, we routinely assess joint hypermobility in our evaluation of individuals with fatigue. ...
... These abnormalities can begin insidiously or can be triggered by a variety of infections, trauma, autoimmune responses, or other factors [6]. Orthostatic intolerance is more common in women and in individuals with joint hypermobility [19][20][21][22][23][24][25][26][27]. Treatment of orthostatic intolerance consists of non-pharmacologic interventions such as increased dietary sodium intake, adequate fluid intake, graded aerobic exercise, and compression garments such as compression stockings and abdominal binders [39][40][41][42]. ...
Background
Athletic underperformance is characterized by fatigue and an inability to sustain a consistent exercise workload. We describe five elite swimmers with prolonged fatigue and athletic underperformance. Based on our work in myalgic encephalomyelitis /chronic fatigue syndrome, we focused on orthostatic intolerance as a possible contributor to symptoms.
Methods
Participants were referred for evaluation of fatigue and underperformance to the Chronic Fatigue Clinic at the Johns Hopkins Children’s Center. All patients were evaluated for overtraining syndrome, as well as for features commonly seen in myalgic encephalomyelitis/chronic fatigue syndrome. The latter included joint hypermobility, orthostatic intolerance, and non-IgE mediated milk protein intolerance. Orthostatic intolerance was tested by performing a ten-minute passive standing test or a head-up tilt table test.
Results
Orthostatic testing provoked fatigue and other symptoms in all five swimmers, two of whom met heart rate criteria for postural tachycardia syndrome. Treatment was individualized, primarily consisting of an increased intake of sodium chloride and fluids to address orthostasis. All patients experienced a relatively prompt improvement in fatigue and other orthostatic symptoms and were able to either return to their expected level of performance or improve their practice consistency.
Conclusions
Orthostatic intolerance was an easily measured and treatable contributor to athletic underperformance in the five elite swimmers we describe. We suggest that passive standing tests or formal tilt table tests be incorporated into the clinical evaluation of athletes with fatigue and underperformance as well as into scientific studies of this topic. Recognition and treatment of orthostatic intolerance provides a new avenue for improving outcomes in underperforming athletes.
... Symptoms of autonomic dysfunction can include presyncope, orthostatic intolerance, chest pain, palpitations, thermoregulatory difficulties, and gastrointestinal complaints and are commonly reported in patients with HSD/hEDS. [63][64][65] For example, they are almost three times more likely than healthy controls to experience presyncopal symptoms (41% vs 15%) and experience orthostatic intolerance frequently (94% of HSD/hEDS in one study). 15,63,65 Cardiovascular autonomic dysfunction can include orthostatic hypotension, orthostatic intolerance, neurally-mediated hypotension and postural orthostatic tachycardia syndrome (PoTS), the latter of which is commonly associated with HSD/hEDS. ...
... [63][64][65] For example, they are almost three times more likely than healthy controls to experience presyncopal symptoms (41% vs 15%) and experience orthostatic intolerance frequently (94% of HSD/hEDS in one study). 15,63,65 Cardiovascular autonomic dysfunction can include orthostatic hypotension, orthostatic intolerance, neurally-mediated hypotension and postural orthostatic tachycardia syndrome (PoTS), the latter of which is commonly associated with HSD/hEDS. 66 PoTS is a heterogeneous syndrome that is manifested by a rapid increase in heart rate (> 30 bpm in adults) within 10 minutes of changing from recumbent to upright position without orthostatic hypotension. ...
Background:
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.
Aims:
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.
... Because there is a well-recognized association between joint hypermobility and chronic fatigue, and between joint hypermobility and orthostatic intolerance (19)(20)(21)(22)(23)(24)(25)(26)(27), we routinely assess joint hypermobility in our evaluation of individuals with fatigue. The physical examination therefore included the nine-point Beighton score, a commonly used and reliable measure of joint hypermobility (28). ...
... These abnormalities can begin insidiously or can be triggered by a variety of infections, trauma, autoimmune responses, or other factors (6). Orthostatic intolerance is more common in women and in individuals with joint hypermobility (19)(20)(21)(22)(23)(24)(25)(26)(27). ...
Background
Athletic underperformance is characterized by fatigue and an inability to sustain a consistent exercise workload. We describe five elite swimmers with prolonged fatigue and athletic underperformance in whom an approach that focused on orthostatic intolerance was associated with improved function.
Methods
Participants were referred for evaluation of fatigue and underperformance to the Chronic Fatigue Clinic at the Johns Hopkins Children’s Center. All patients were evaluated for overtraining syndrome, as well as for features commonly seen in myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). The latter included joint hypermobility, orthostatic intolerance, and non-IgE mediated milk protein intolerance. Orthostatic intolerance was tested by performing a ten-minute passive standing test or a head-up tilt table test.
Results
Orthostatic testing provoked fatigue and other symptoms in all five swimmers, two of whom met heart rate criteria for postural tachycardia syndrome. Treatment was individualized, primarily consisting of an increased intake of sodium chloride and fluids to address orthostasis. All patients experienced a relatively prompt improvement in fatigue and other orthostatic symptoms and were able to either return to their expected level of performance or improve their practice consistency.
Conclusions
Orthostatic intolerance was an easily measured and treatable contributor to athletic underperformance in the five elite swimmers we describe. We suggest that passive standing tests or formal tilt table tests be incorporated into the clinical evaluation of athletes with fatigue and underperformance as well as into scientific studies of this topic. Recognition and treatment of orthostatic intolerance provides a new avenue for improving outcomes in underperforming athletes.
... hEDS is a complex, chronic disorder leading to disabilities that limit daily activities (2). Several studies reported that hEDS causes physical and psychosocial impairments (7,8). ...
... (6) A lack of professional understanding. (7) Living a restricted life due to the fluctuating nature, and fear of future injuries, which on its turn leads to limited social participation, (8)Trying to keep up, in order to not "ruin" the perception of others of them. (9) Gaining control of their lives also seems to be of great importance in matters such as "redefining normality" (17,18). ...
Background
People with Ehlers-Danlos Syndromes and Hypermobility Spectrum Disorders are hampered in their social participation, especially in the social relationships they have.
Objective
The aim of this study is to research the impact of hypermobile Ehlers-Danlos Syndrome (hEDS) and Hypermobile Spectrum Disorders (HSD) on interpersonal interactions and relationships.
Methods
A phenomenological hermeneutic study was performed. Semi-structured interviews were used to explore the experiences of 11 participants.
Results
Four themes emerged from the data analysis. (1) people with hEDS or HSD can no longer do what they want to do and that affects their identity, (2) people with hEDS or HSD have to find a balance in the amount of activities they participate in, (3) having hEDS or HSD influences how to ask for, accept and give help, and (4) Relationships are affected in persons with hEDS or HSD. As well as changes in the social network, different types of relationships are influenced by the disease, including relationship with their partner, their children, their friends, strangers, fellow-sufferers and health care professionals.
... The plausible anxiety-proneness in patients with hEDS could reflect an elevated autonomic symptom burden. In a study by De Wandele et al. (2014), the total autonomic symptom burden (i.e., hypermobility, fatigue, pain, affective distress, and physical inactivity) was higher in hEDS than in controls (classical and vascular EDS subtypes). The same study revealed that the autonomic symptoms in hEDS correlated with lowered HRQoL, fatigue, and pain severity (De Wandele et al., 2014). ...
... In a study by De Wandele et al. (2014), the total autonomic symptom burden (i.e., hypermobility, fatigue, pain, affective distress, and physical inactivity) was higher in hEDS than in controls (classical and vascular EDS subtypes). The same study revealed that the autonomic symptoms in hEDS correlated with lowered HRQoL, fatigue, and pain severity (De Wandele et al., 2014). ...
Patients with Ehlers-Danlos Syndrome, hypermobile type (hEDS) often report a decrease of health-related quality of life (HRQoL), symptoms of anxiety and depression, and show a prevalent incidence of psychiatric disorders. Still, there seems to be a lack of a more thorough analysis addressing the relations between these entities. We studied the HRQoL and its relations with depressive symptoms and subgroups of anxiety in a group of patients with hEDS ( n = 81) compared to a comparison group ( n = 90) of healthy controls (HC). HRQoL was assessed with the RAND 36-item health survey, depressive symptoms were measured with the 21-item Beck Depression Inventory (BDI-II) and State/trait anxiety inventory (STAI) was used to estimate levels of state and trait anxiety. The hEDS group showed significantly lower scores on total HRQoL, on all subscales as well on calculated subgroups of physical and mental HRQoL than the HC group. Depression, state, and trait anxiety scores were significantly higher in hEDS group than in the HC group. However, both state and trait anxiety showed a lower degree of negative associations with social functioning in the hEDS group when compared to the HC group. Patients with hEDS present with a lower HRQoL and greater psychological distress than healthy individuals. These factors play a significant role in the patients’ overall functional capacity and should be noticed when examining and treating patients with hEDS.
... Because there is a well-recognized association between joint hypermobility and chronic fatigue, and between joint hypermobility and orthostatic intolerance (19)(20)(21)(22)(23)(24)(25)(26)(27), we routinely assess joint hypermobility in our evaluation of individuals with fatigue. The physical examination therefore included the nine-point Beighton score, a commonly used and reliable measure of joint hypermobility (28). ...
... These abnormalities can begin insidiously or can be triggered by a variety of infections, trauma, autoimmune responses, or other factors (6). Orthostatic intolerance is more common in women and in individuals with joint hypermobility (19)(20)(21)(22)(23)(24)(25)(26)(27). ...
Background
Athletic underperformance is characterized by fatigue and an inability to sustain a consistent exercise workload. We describe five elite swimmers with prolonged fatigue and athletic underperformance in whom an approach that focused on orthostatic intolerance was associated with improved function.
Methods
Participants were referred for evaluation of fatigue and underperformance to the Chronic Fatigue Clinic at the Johns Hopkins Children’s Center. All patients were evaluated for overtraining syndrome, as well as for features commonly seen in myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). The latter included joint hypermobility, orthostatic intolerance, and non-IgE mediated milk protein intolerance. Orthostatic intolerance was tested by performing a ten-minute passive standing test or a head-up tilt table test.
Results
Orthostatic testing provoked fatigue and other symptoms in all five swimmers, two of whom met heart rate criteria for postural tachycardia syndrome. Treatment was individualized, primarily consisting of an increased intake of sodium chloride and fluids to address orthostasis. All patients experienced a relatively prompt improvement in fatigue and other orthostatic symptoms and were able to either return to their expected level of performance or improve their practice consistency.
Conclusions
Orthostatic intolerance was an easily measured and treatable contributor to athletic underperformance in the five elite swimmers we describe. We suggest that passive standing tests or formal tilt table tests be incorporated into the clinical evaluation of athletes with fatigue and underperformance as well as into scientific studies of this topic. Recognition and treatment of orthostatic intolerance provides a new avenue for improving outcomes in underperforming athletes.
... Diagnosis relies on clinical criteria including the hEDS checklist and Beighton scoring, with an exam demonstrating hypermobility, skin extensibility, and atrophic scarring. Additional features include dysautonomia [10,11], POTS, dysmotility/gastrointestinal complaints [12], recurrent hernias, dislocations/subluxations, headaches, fatigue, and pain. Gastrointestinal manifestations include both structural (hernias, rectoceles, prolapse) and functional (dysmotility) abnormalities [13]. ...
Hypoglycemia in the absence of diabetes is often multifactorial and challenging to diagnose definitively. We present a case report and an expanded series of adult females with reactive hypoglycemia who were diagnosed with Ehlers-Danlos syndrome (EDS). These patients exhibited predominantly postprandial hypoglycemia, with some fasting and activity-induced episodes. Clinical findings included autonomic dysfunction, gastrointestinal symptoms, and joint hypermobility. Interventions focused on medical nutrition therapy, continuous glucose monitoring, and, in some cases, medication. Many patients continued to experience hypoglycemic episodes despite treatment. Key learning points include the potential association between hypermobile EDS and hypoglycemia, the importance of confirming the Whipple triad, and the need for multidisciplinary management. This case series highlights the need for further research into the prevalence and pathophysiology of hypoglycemia in EDS.
... 5 Additionally, dysautonomia and PoTS are frequently reported in adults with hEDS and have been linked with lower quality of life (QoL), increased pain, and fatigue. 8 However, there is scant literature on PoTS, dysautonomia, and cardiovascular autonomic symptoms in pediatric patients 9 despite half of all patients with PoTS receiving the diagnosis during adolescence. 10 This represents a gap in the medical literature that needs to be addressed. ...
Objectives
Hypermobile Ehlers–Danlos syndrome is a connective tissue disorder characterized by joint hypermobility and other systemic manifestations. Cardiovascular, autonomic symptoms and dysautonomia are frequently reported in adults with hypermobile Ehlers–Danlos syndrome and have been shown to have a negative impact on quality of life. However, there is scant literature on autonomic symptoms in pediatric patients with hypermobile Ehlers–Danlos syndrome. This study aims to characterize cardiovascular symptoms and diagnoses in pediatric patients with hypermobile Ehlers–Danlos syndrome and evaluate the impact of autonomic symptoms on quality of life.
Methods
As part of a longitudinal study, a consecutive sample of 70 patients with Ehlers–Danlos syndromes were recruited at routine clinical care visits. Medical history was reviewed, demographics were obtained, and patient-reported outcomes were completed by the patients.
Results
The average age of 70 patients was 15.8 years, and the majority were females (89%) and Caucasian (89%). The most common cardiovascular diagnoses were orthostatic intolerance (59%), dysautonomia (47%), and postural orthostatic tachycardia syndrome (21%). Most patients had an echocardiogram (77%), that was normal (82%). No patients had mitral valve prolapse, and only one patient had mild aortic root dilation (2%). Patient-reported outcomes revealed decreased quality of life associated with autonomic symptoms.
Conclusions
This study shows that most children with hypermobile Ehlers–Danlos syndrome have cardiovascular and autonomic symptoms, which have a negative impact on quality of life. Few patients with hypermobile Ehlers–Danlos syndrome have structural abnormalities on echocardiogram, which suggests that the cardiovascular symptoms experienced by patients are not due to structural cardiovascular disease and possibly reflective of autonomic pathology, though further studies will need to confirm this. This study confirms that cardiovascular and symptoms are prevalent and have a dramatic impact on quality of life in pediatric and young adult patients diagnosed with hypermobile Ehlers–Danlos syndrome.
... 6,[19][20][21][22] EDS has been linked to all these conditions, as well as to TMJ and other joint pain and migraines. 1,[23][24][25][26][27][28][29][30][31] Here, symptom prevalence and treatment effects, as measured by reported scores, were reviewed for 21 individual nonpelvic symptoms. These 21 were selected for analysis because each has its own International Classification of Diseases, Tenth Revision (ICD-10) code (Table S1). ...
Objective
To report the prevalence and severity of nonpelvic symptoms for patients with venous-origin chronic pelvic pain (VO-CPP) and to describe outcomes after pelvic vein stenting and embolization.
Methods
We retrospectively reviewed outcomes of 45 women with VO-CPP who underwent treatment with iliac vein stenting and/or embolization. Patients completed symptom-severity questionnaires before and after treatment that assessed for pelvic pain, and multiple other symptoms, including brain fog, anxiety, depression, musculoskeletal pain, fatigue, migraines and more.
Results
Patient age ranged from 18 to 65 years. The prevalence of common symptoms was as follows: migraines, 69%; brain fog, 76%; anxiety attacks, 58%; excess sweating, 64%; hip pain, 73%; diarrhea, 62%; constipation, 76%; and abdominal bloating, 82%. After treatment, most symptom scores improved by more than 50%; exceptions were excessive sweating (41% improvement) and bloating (47% improvement). Prevalence of individual symptoms that bundle into POTS ranged from 29% to 76%, where symptom improvement ranged from 23% to 59% after treatment. Overlapping individual symptoms characteristic of fibromyalgia and myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) were present in 64% to 82% of patients and all improved by 49% to 63% after treatment.
Conclusions
Pelvic venous flow abnormality is linked causally to a spectrum of interrelated symptoms, of which many can be bundled into named syndromes of unknown cause. With catheter- based treatment of pelvic venous pooling, nonpelvic symptom and syndrome scores improved.
... Whilst these are less commonly used in hypermobility research, they are validated with strong psychometric properties in other chronic health conditions [47,48]. Finally, in the fatigue domain, the CIS was the preferred comparator, being widely used in hypermobility research [49][50][51], but it did not contain a question about sleep. As such, the PSQI was added to evaluate sleep quality and fatigue and the scores combined with the CIS. ...
Introduction
Hypermobility spectrum disorders (HSD) and hypermobile Ehlers-Danlos syndrome (hEDS) are often accompanied by varied and complex multisystemic comorbid symptoms/conditions. The Spider questionnaire was developed to evaluate the presence and impact of eight common multisystemic comorbidities. Thirty-one questions across eight symptom domains assess neuromusculoskeletal, pain, fatigue, cardiac dysautonomia, urogenital, gastrointestinal, anxiety, and depression symptoms. This study aimed to evaluate the Spider’s construct validity in adults.
Method
A cross-sectional observational study was conducted over four stages. Three international patient charities aided recruitment of participants through social media and website advertisements. Adults aged 18 to 65 years, with and without HSD/hEDS, were invited to participate. Validated, frequently used comparator questionnaires were used to establish convergent validity of Spider symptom domains. A control group was recruited for known-group validity analysis. Participants answered each Spider domain and the corresponding comparator questionnaire via surveys hosted by REDCap. Anonymous data were analysed using SPSS. Convergent validity was assessed through Spearman’s correlational analysis and known-group validity through Mann–Whitney U analysis.
Results
A total of 11,151 participants were recruited across the four stages. Statistically significant, moderate-to-strong correlations were found between all Spider domains and their comparators ( p < 0.001, r = 0.63 to 0.80). Known-group validity analysis showed statistically significant differences ( p < 0.001) between the hypermobile and control groups in all eight domains.
Conclusions
Convergent and known-group validity of the Spider was established with adults. These results suggest the Spider can measure the presence and impact of multisystemic comorbid symptoms/conditions in adults with HSD/hEDS, providing a tool which guides multidisciplinary management. Key Points • The Spider questionnaire is a novel tool assessing the presence and impact of the multisystemic comorbid symptoms/conditions associated with HSD/hEDS. • Convergent and known-group validity of the Spider questionnaire was established in adults aged 18 to 65. • This tool provides a quick and easy method to visualise the symptom profile of those with HSD/hEDS to guide symptom management.
... Причиной многих патологических проявлений является сужение позвоночного канала на уровне краниовертебрального перехода (КВП), в частности С1-С2, которое приводит к компрессии спинного мозга и напряжению нижних отделов ствола головного мозга с обструкцией оттока спинномозговой жидкости, последствия которой и вызывают головную боль и неврологический дефицит, перегибы позвоночных артерий с возможной перемежающейся ишемией [2,3]. Дело в том, что область КВП представляет собой очень сложный сегмент. ...
The objective of the discussion is clinical and instrumental specifics of the atlantoaxial region in rheumatic diseases. Pathological changes of the cervical spice are not uncommon in rheumatic diseases. Area of atlantoaxial articulation attracts particular attention, which is discussed rarely by rheumatologists. This review discusses the magnetic resonance imaging (MRI) specific pattern of the atlantoaxial region pathology in rheumatic diseases. The pathogenesis, clinical picture and the craniometric criteria pathology are the areas of concern.
Conclusions. The atlantoaxial region is a complicated anatomical structure. Pathological processes that occur in this area due to rheumatic diseases can manifest severe neurological symptoms. MRI makes it possible to recognize many structural disorders at an early stage. As a result, images of craniometric measurements on MRI allow to timely detect deviations that subsequently lead to serious complications, which could be corrected and prevented.
... However, HSD is multisystemic, including adverse effects on the cardiovascular, digestive, and autonomic nervous systems due to abnormalities in the connective tissues of these systems [2,3,5]. Consequently, various non-musculoskeletal features have been reported in HSD including mitral valve prolapse, irritable bowel syndrome, dysautonomia, bladder dysfunction, fatigue, sleep disturbances, functional impartment, cognitive and emotional distress, and reduced quality of life [8][9][10][11]. HSD is considered a complex and disabling condition due to its multisystemic involvement and wide range of musculoskeletal and non-musculoskeletal complaints [12]. The complexity and the disabling impact of HSD challenges healthcare professionals in robustly evaluating its impact and the effectiveness of management strategies. ...
Background: The Bristol Impact of Hypermobility questionnaire (BIoH) is the first condition-specific patient reported outcome measure for people with hypermobility-related conditions. The BIoH original version is in English, which limits its use for patients who speak other languages. The study aimed to translate and culturally adapt the BIoH into Arabic and determine its concurrent validity, reliability, internal consistency and smallest detectable change.
Methods: Forward-backward translation and cross-sectional designs were used. The Ethics Committee of Kuwait Ministry of Health approved the study. Spearman correlation coefficient, intraclass correlation coefficient (ICC), and Cronbach's α were used for statistical analysis. Patients with hypermobility spectrum disorders (HSD) were included, diagnosed using the 2017 classification framework.
Results: 55 HSD patients were included, aged 26.0 (18.0) years old; median (IQR), and 85.5% were women. The BIoH showed very good concurrent validity when correlated with the SF-12 total and physical component scores; r = -0.743 and -0.740, respectively (p<0.05). Good correlation was identified between the BIoH and the SF-12 mental component score; r = -0.496 (p<0.05). The BIoH demonstrated excellent test-retest reliability; ICC = 0.934 (0.749-0.983 95% CI) (p<0.05), and high internal consistency (Cronbach's α = 0.933). The smallest detectable change was 30.90 points, representing 19.8% of the mean baseline score.
Conclusions: The study successfully translated the BIoH into Arabic and demonstrated high psychometric properties. The translated score can help Arabic patients with HSD in their clinical evaluation process. Future research needs to determine the responsiveness of the Arabic version and translate the BIoH to other languages.
... In our patient, the main comorbid problems were the range of motion abnormalities, mast cell activation, allergic inflammation, and orthostatic intolerance. Other ME/CFS comorbidities, which were not present in our patient, can include neurogenic thoracic outlet syndrome [43,44], venous insufficiency (pelvic congestion syndrome with ovarian and internal iliac vein varices, May Thurner syndrome with compression of the left common iliac vein) [45][46][47], gastrointestinal motility disturbances [48][49][50], migraine headaches [51,52], Ehlers-Danlos syndrome or non-syndromic joint hypermobility [17,[53][54][55][56][57][58][59], and neuroanatomic abnormalities (Chiari malformation [60], cervical spinal stenosis [14], atlantoaxial instability [22] or craniocervical instability [23]). It is reasonable to assume that some proportion of patients with long COVID will also have had some of these comorbid conditions preceding their acute SARS-CoV-2 infection. ...
Persistent fatigue is one of the most common symptoms of post-COVID conditions, also termed long COVID. At the extreme end of the severity spectrum, some individuals with long COVID also meet the criteria for myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), raising the possibility that symptom management approaches for ME/CFS may benefit some long COVID patients. We describe the long-term outcomes of a 19-year-old male who developed profound impairment consistent with ME/CFS after a SARS-CoV-2 infection early in the pandemic. We evaluated and treated him using our clinic’s approach to ME/CFS. This included a history and physical examination that ascertained joint hypermobility, pathological reflexes, physical therapy maneuvers to look for a range of motion restrictions in the limbs and spine, orthostatic testing, and screening laboratory studies. He was found to have profound postural tachycardia syndrome, several ranges of motion restrictions, and mast cell activation syndrome. He was treated according to our clinic’s guidelines for managing ME/CFS, which included manual physical therapy maneuvers and both non-pharmacologic measures and medications directed at postural tachycardia syndrome and mast cell activation. He experienced significant improvement in his symptoms over 30 months. His case emphasizes how the application of the principles of treating ME/CFS has the potential to provide a direction for treating long COVID.
... Dysautonomia has been prospectively investigated in hEDS in the cardiovascular, sudomotor and gastrointestinal systems. Studies revealed an overactivity of the resting parasympathetic tone and a decreased sympathetic reactivity to stimuli [77,78]. These symptoms are common features with a major impact on health and quality of life in hEDS/HSD, yet the 2017 criteria do not include cardiovascular dysautonomia nor functional gastrointestinal disorders [79,80]. ...
Hypermobile Ehlers Danlos Syndrome (hEDS)/hypermobility spectrum disorders (HSD) are incapacitating and painful syndromes involving a generalized connective tissue disorder with joint hypermobility and musculoskeletal complications. A neuropathic component is clinically likely given frequent burning sensations, hypoesthesia, or allodynia. Small fiber neuropathy (SFN) refers to the dysfunction or damage of A‐I and C‐fibers, which relay thermal and nociceptive information as well as mediating autonomic function. SFN has been suggested by prior studies in hEDS but these early findings (case series Na20) with sole reliance on intraepidermal nerve fiber density (IENFD) called for a larger sample combined with functional testing. In this retrospective chart extraction from 79 hEDS/HSD patients referred to a pain center due to neuropathic pain or dysautonomia, both functional (Quantitative Sensory Testing (QST), N=79) and structural (IENFD, N=69) evaluations of small nerve fibers were analyzed in combination with clinical data.A small fiber neuropathy was definite (both abnormal IENFD and QST) in 40/69 patients (58%), possible (one abnormal test) in 23/69 patients (33%) and excluded (both normal) in only 6/69 patients (9%). These results add strong evidence for a peripheral neuropathic contribution to pain symptoms in hEDS/HSD, in addition to the known nociceptive and central sensitization components. Such neuropathic contribution could raise the hypothesis of a neurological cause of hEDS, the only EDS syndrome still without a known genetic cause. Hence, our data is leading the way to a better stratification of this very heterogeneous population, which could improve symptom management and expand pathophysiological research. This article is protected by copyright. All rights reserved
... Patients with hEDS may show apprehension or nervousness in discussing their symptoms, which often results in diagnoses of anxiety, depression, and fibromyalgia. However, rather than having primary psychiatric or rheumatologic disorders, these patients are instead in a state of dysautonomia, and may also have post-traumatic stress from repeated medical complications (10,15). Therefore, physicians should take the initiative to understand these correlations to proactively prevent unnecessary complications for patients during their hospital course. ...
Ehlers-Danlos syndrome, hypermobility type, is a complex medical condition understood to be a genetic disorder resulting in abnormal collagen synthesis. It is characterized by joint hypermobility as well as skin laxity, poor wound healing, and other manifestations. It may present in conjunction with autonomic, neurologic, and immune abnormalities. Hypermobility spectrum disorder is similarly characterized by joint hypermobility but holds less extensive diagnostic criteria. When in the hospital setting, systemic differences resulting from hypermobility syndromes must be recognized to avoid harm. Here, we present the first case, to our knowledge, of a full hospital course with hypermobility syndrome–comorbidity-related complications described.
... Hakim and Grahame (14) demonstrated for the first time the significantly increased risk of these symptoms in hEDS. Wandele et al. (77) concluded that autonomic symptoms contribute to the burden of symptoms such as fatigue, dizziness, fainting, syncope, memory, and concentration problems (56)(57)(58). ...
Objectives
To identify psychosocial and motor aspects related to joint hypermobility (JH) in a sample from almost all Brazilian states by age range and sex; to characterize JH by the Beighton total score ≥4, ≥5, and ≥6 according to sex and age and atypicality in the sitting position and in the hands; identify, in the total sample, manifestations of “growing pain” and its location, fatigue, attention deficit, anxiety, insomnia, drowsiness, apathy, depression, delay in walking, not crawling or crawling differently, school performance, spatial orientation and/or temporally impaired, social isolation, and being stigmatized as “lazy/clumsy/apathetic”.
Methods
This retrospective, observational, quantitative, and cross-sectional study used data obtained through analyses of descriptive and inferential crossings between 2012 and 2020 of 482 medical records of individuals between 1 and 76 years of age, from most Brazilian states. All patients previously diagnosed with “joint hypermobility syndrome” (JHS) and “Ehlers-Danlos syndrome hypermobility type” (EDS-HT) had their medical records reassessed, following the guidelines established in 2017. The analysis of GJH was performed using the updated method by Beighton method; atypical characteristics were investigated in the hands and the ability to sit in the “W” and the “concave” positions. The characteristics and manifestations of “growing pain” and its location were analyzed in the total sample, fatigue, insomnia, drowsiness, apathy, depression, social isolation, attention deficit, anxiety, stigmatization as “lazy,” clumsy/restless, impaired school performance, and spatial and/or temporal orientation. Descriptive and inferential statistical methods were used, such as Mean, Median, Mode, Standard Deviation, Standard Error, Maximum Value, Minimum Value, Komolgorov-Smirnov, Significance, Relative Value, Absolute Value, Mann-Whitney U, and Correlation of Spearman.
Results
JH in the total sample predominated in the upper limbs, the majority were women, represented by 352 (73.02%), 15 years old or older with 322 (66.80%), 312 (64.73%) had a Beighton total score ≥6, which decreased as the age increased. Always sitting in the “concave” position was represented by 54.15% and the ability to sit in the “W” position by 39.21%; signs on the hands totaled between 27.59 and 44.19% with a significant correlation between the variables. Among the characteristics, fatigue predominated, followed by an awkward/clumsy/restless individual, attention deficit, anxiety and stigmatized as “lazy,” insomnia, drowsiness, apathy, depression, impaired spatial and/or temporal orientation, and social isolation. From the total sample, pain in the lower limbs was reported by 55.81% and having or having had “growing pain” was reported by 36.93%, delay in walking occurred in 19.92%, 15.35% did not crawl or crawled differently, and for 12.86%, school performance was impaired. Higher Beighton total scores showed a trend towards motor implications and correlation between variables. Ability to still sit in the “concave” position was possible for 54.15% and to sit in the “W” position for 39.21%.
Conclusion
In the total sample, the JH characteristic prevails in the upper limbs of female children, adolescents and adults, with a total Beighton score ≥6. Most sit in the “concave” position and less than half also sit in the “W” position and with atypical hand postures. The higher Beighton scores, which include the upper limbs, show a tendency to not crawl or crawl differently, delayed ambulation, and impaired school performance. The predominance of JH in the upper limbs is suggestive of a justification for not crawling or crawling differently. Characteristics of atypical motor performance in hands and sitting posture, in addition to fatigue, pain since childhood, anxiety, apathy, depression, sleep disorders, stigmatization, attention deficit, spatial and/or temporal orientation impairment, and social isolation are characteristics. suggestive of psychosocial implications at different ages. Future studies with motor and psychosocial aspects of people with JH will help to identify the phenotype of this population and consequent guidance for clinical management based on the motor and psychosocial aspects of people with JH.
... Symptoms of orthostatic intolerance can be debilitating (12). Associated syncope, fatigue, and migraines add to clinical burden and reduce quality of life (30). ...
Objectives
Autism, attention deficit hyperactivity disorder (ADHD), and tic disorder (Tourette syndrome; TS) are neurodevelopmental conditions that frequently co-occur and impact psychological, social, and emotional processes. Increased likelihood of chronic physical symptoms, including fatigue and pain, are also recognized. The expression of joint hypermobility, reflecting a constitutional variant in connective tissue, predicts susceptibility to psychological symptoms alongside recognized physical symptoms. Here, we tested for increased prevalence of joint hypermobility, autonomic dysfunction, and musculoskeletal symptoms in 109 adults with neurodevelopmental condition diagnoses.
Methods
Rates of generalized joint hypermobility (GJH, henceforth hypermobility) in adults with a formal diagnosis of neurodevelopmental conditions (henceforth neurodivergent group, n = 109) were compared to those in the general population in UK. Levels of orthostatic intolerance and musculoskeletal symptoms were compared to a separate comparison group (n = 57). Age specific cut-offs for GJH were possible to determine in the neurodivergent and comparison group only.
Results
The neurodivergent group manifested elevated prevalence of hypermobility (51%) compared to the general population rate of 20% and a comparison population (17.5%). Using a more stringent age specific cut-off, in the neurodivergent group this prevalence was 28.4%, more than double than the comparison group (12.5%). Odds ratio for presence of hypermobility in neurodivergent group, compared to the general population was 4.51 (95% CI 2.17–9.37), with greater odds in females than males. Using age specific cut-off, the odds ratio for GJH in neurodivergent group, compared to the comparison group, was 2.84 (95% CI 1.16–6.94). Neurodivergent participants reported significantly more symptoms of orthostatic intolerance and musculoskeletal skeletal pain than the comparison group. The number of hypermobile joints was found to mediate the relationship between neurodivergence and symptoms of both dysautonomia and pain.
Conclusions
In neurodivergent adults, there is a strong link between the expression of joint hypermobility, dysautonomia, and pain, more so than in the comparison group. Moreover, joint hypermobility mediates the link between neurodivergence and symptoms of dysautonomia and pain. Increased awareness and understanding of this association may enhance the management of core symptoms and allied difficulties in neurodivergent people, including co-occurring physical symptoms, and guide service delivery in the future.
... Dysautonomia has been prospectively investigated in hEDS in the cardiovascular, sudomotor and gastrointestinal systems. Studies revealed an overactivity of the resting parasympathetic tone and a decreased sympathetic reactivity to stimuli [77,78]. These symptoms are common features with a major impact on health and quality of life in hEDS/HSD, yet the 2017 criteria do not include cardiovascular dysautonomia nor functional gastrointestinal disorders [79,80]. ...
Hypermobile Ehlers Danlos Syndrome (hEDS)/hypermobility spectrum disorders (HSD) are incapacitating and painful syndromes involving a generalized connective tissue disorder with joint hypermobility and musculoskeletal complications. A neuropathic component is clinically likely given frequent burning sensations, hypoesthesia, or allodynia. Small fiber neuropathy (SFN) refers to the dysfunction or damage of A-δ and C-fibers, which relay thermal and nociceptive information as well as mediating autonomic function. SFN has been suggested by prior studies in hEDS but these early findings (case series N≤20) with sole reliance on intraepidermal nerve fiber density (IENFD) called for a larger sample combined with functional testing.
In this retrospective chart extraction from 79 hEDS/HSD patients referred to a pain center due to neuropathic pain or dysautonomia, both functional (Quantitative Sensory Testing (QST), N=79) and structural (IENFD, N=69) evaluations of small nerve fibers were analyzed in combination with clinical data and standardized questionnaires.
All the patients reported moderate to severe pain interfering with daily life. A decreased thermal detection (QST) was shown in 55/79 patients (70%) and a decreased IENFD in 54/69 patients (78%). Hence a small fiber neuropathy (both abnormal IENFD and QST) was definite in 40/69 patients (58%), possible in 23/69 patients (33%) and excluded in only 6/69 patients (9%).
These results add strong evidence for a peripheral neuropathic contribution to pain symptoms in hEDS/HSD, in addition to the known nociceptive and central sensitization components. Such neuropathic contribution could raise the hypothesis of a neurological cause of hEDS, the only EDS syndrome still without a known genetic cause. Hence, our data is leading the way to a better stratification of this very heterogeneous population, which could improve symptom management and expand pathophysiological research.
... Generally, musculoskeletal disorders are associated with impairments in physical, psychological functioning and health-related quality of life [5] and work functioning [6]. Therefore, the burden on quality of life can be substantial in those with hypermobility [7]. ...
Background
Hypermobility is a poorly recognised and understood musculoskeletal disorder thought to affect around 20% of the population. Hypermobility is associated with reduced physiological and psychological functioning and quality of life and is a known risk factor for the development of an anxiety disorder. To date, no evidence-based, targeted treatment for anxiety in the context of hypermobility exists. The present intervention (ADAPT—Altering Dynamics of Autonomic Processing Therapy) is a novel therapy combining bio-behavioural training with cognitive approaches from clinical health psychology targeting the catastrophisation of internal sensations, with aim to improve autonomic trait prediction error.
Method
Eighty individuals with diagnosed hypermobility will be recruited and the efficacy of ADAPT to treat anxiety will be compared to an Emotion-Focused Supportive Therapy (EFST) comparator therapy in a randomised controlled trial. The primary treatment target will be post therapy score on the Beck Anxiety Inventory, and secondary outcomes will also be considered in relation to interoception, depression, alexithymia, social and work adjustment, panic symptoms and dissociation. Due to COVID restrictions, the intervention will be moved to online delivery and qualitative assessment of treatment tolerance to online therapy will also be assessed.
Discussion
Online delivery of an intervention targeting anxiety would improve the quality of life for those experiencing anxiety disorder and help to reduce the £11.7 billion that anxiety disorders cost the UK economy annually.
Trial registration
World Health Organization ISRCTN17018615 . Registered on 20th February 2019; trial protocol version 2
... On a molecular level, identification of a causative variant(s) in the respective gene is possible in 12 subtypes. Despite a probable autosomal dominant inheritance [11] and reports of haploinsufficiency or missense of tenascin X in a few cases [12,13], no gene has been identified for hEDS [11,14]. ...
Diagnosing hypermobile Ehlers–Danlos syndrome (hEDS) remains challenging, despite new 2017 criteria. Patients not fulfilling these criteria are considered to have hypermobile spectrum disorder (HSD). Our first aim was to evaluate whether patients hEDS were more severely affected and had higher prevalence of extra-articular manifestations than HSD. Second aim was to compare their outcome after coordinated physical therapy. Patients fulfilling hEDS/HSD criteria were included in this real-life prospective cohort (November 2017/April 2019). They completed a 16-item Clinical Severity Score (CSS-16). We recorded bone involvement, neuropathic pain (DN4) and symptoms of mast cell disorders (MCAS) as extra-articular manifestations. After a standardized initial evaluation (T0), all patients were offered the same coordinated physical therapy, were followed-up at 6 months (T1) and at least 1 year later (T2), and were asked whether or not their condition had subjectively improved at T2. We included 97 patients (61 hEDS, 36 HSD). Median age was 40 (range 18–73); 92.7% were females. Three items from CSS-16 (pain, motricity problems, and bleeding) were significantly more severe with hEDS than HSD. Bone fragility, neuropathic pain and MCAS were equally prevalent. At T2 (20 months [range 18–26]) 54% of patients reported improvement (no difference between groups). On multivariable analysis, only family history of hypermobility predicted (favorable) outcome ( p = 0.01). hEDS and HDS patients showed similar disease severity score except for pain, motricity problems and bleeding, and similar spectrum of extra-articular manifestations. Long-term improvement was observed in > 50% of patients in both groups. These results add weight to a clinical pragmatic proposition to consider hEDS/HSD as a single entity that requires the same treatments.
Background : We have noted that some adolescents and young adults with myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) report difficulty with arms-overhead activities, suggestive of brachial plexus dysfunction or thoracic outlet syndrome (TOS). In the TOS literature, diagnostic maneuvers focus on the provocation of upper limb symptoms (arm fatigue and heaviness, paresthesias, neck and upper back pain), but not on systemic symptoms. Objectives : To estimate the proportion of patients with fatiguing illness who experience systemic symptoms during a common maneuver used in evaluating TOS—the elevated arm stress test (EAST). Methods : Patients were eligible for this retrospective study if they had been referred to the Johns Hopkins Chronic Fatigue Clinic between January 2020 and July 2023 and (a) reported difficulty with arms-overhead postures, (b) were evaluated with an abbreviated one-minute EAST, and (c) had not undergone surgery in the upper limb, neck, or skull base. Modified EAST procedure: patients sat with their arms in a “hands up” or “candlestick” position while opening and closing their hands every 2-3 seconds repeatedly for 1 minute, rather than the customary 3 minutes. The test was considered abnormal for local symptoms if the participant experienced pain, fatigue, heaviness, paresthesias, warmth or tremulousness in the upper limb, shoulder, neck, head, or upper back. The test was considered abnormal for systemic symptoms if the participant experienced overall fatigue, cognitive fogginess, lightheadedness, racing heart, diaphoresis, dyspnea, overall warmth, or nausea. Results : Of 154 patients evaluated during the study period, 64 (42%) met the eligibility criteria (61/64 female, median age 18 years [range, 13 to 50]). Of the 64, 50 (78%) had ME/CFS, 13 (20%) had idiopathic chronic fatigue with associated orthostatic intolerance (OI), and one had idiopathic chronic fatigue without OI. Of the 64, 58% had evidence of joint hypermobility. Local symptoms were provoked by EAST in 62/64 (97%) within a median of 20 seconds. During EAST, 26/64 (41%) reported systemic symptoms (1 had only systemic but no upper limb symptoms), most commonly lightheadedness (19%) and generalized fatigue (11%). Conclusions : Even with an abbreviated test duration, the EAST maneuver provoked local and systemic symptoms in a substantial proportion of patients with chronic fatigue, OI, and ME/CFS who had reported difficulty with arms-overhead postures. Further studies are needed to explore the prevalence of brachial plexus or TOS symptoms in unselected individuals with ME/CFS or OI, and the proportion with systemic symptoms during and after EAST.
Hypermobile Ehlers-Danlos syndrome (EDS) is an inherited condition marked by joint hypermobility, instability, chronic pain and fatigue, significantly impacting quality of life and autonomy. Management focuses solely on symptom alleviation. After experiencing a rapid decline in functional abilities, a patient in late adolescence with hypermobile EDS underwent hippotherapy rehabilitation (30 hours). She saw substantial improvements in fatigue, chronic pain and regained walking abilities. Hippotherapy played a crucial role in refining her postural balance, motor skills, proprioception, muscle function and endurance. It also positively affected her cognitive and emotional regulation by stimulating sensory inputs that activate neural pathways, providing relief from pain and fatigue. Notably, the patient transitioned from wheelchair reliance to walking with crutches, and then greatly enhanced both gait quality and speed. These findings demonstrate the relevance of hippotherapy for the rehabilitation of hypermobile EDS, reducing the need for pharmacological interventions and fostering a proactive approach to future challenges.
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.
Gastrointestinal involvement is a well known complication of Ehlers-Danlos syndromes (EDSs), mainly in form of abdominal emergencies due to intestinal/abdominal vessels rupture in vascular EDS. In the last decade, a growing number of works investigated the relationship between a wide spectrum of chronic gastrointestinal complaints and various EDS forms, among which the hypermobility type (a.k.a. joint hypermobility syndrome; JHS/EDS-HT) was the most studied. The emerging findings depict a major role for gastrointestinal involvement in the health status and, consequently, management of JHS/EDS-HT patients. Nevertheless, fragmentation of knowledge limits its impact on practice within the boundaries of highly specialized clinics. In this paper, literature review on gastrointestinal manifestations in JHS/EDS-HT was carried out and identified papers categorized as (i) case-control/cohort studies associating (apparently non-syndromic) joint hypermobility and gastrointestinal involvement, (ii) case-control/cohort studies associating JHS/EDS-HT and gastrointestinal involvement, (iii) case reports/series on various gastrointestinal complications in (presumed) JHS/EDS-HT, and (iv) studies reporting gastrointestinal features in heterogeneous EDS patients' cohorts. Gastrointestinal manifestations of JHS/EDS-HT were organized and discussed in two categories, including structural anomalies (i.e., abdominal/diaphragmatic hernias, internal organ/pelvic prolapses, intestinal intussusceptions) and functional features (i.e., dysphagia, gastro-esophageal reflux, dyspepsia, recurrent abdominal pain, constipation/diarrhea), with emphasis on practice and future implications. In the second part of this paper, a summary of possible nutritional interventions in JHS/EDS-HT was presented. Supplementation strategies were borrowed from data available for general population with minor modifications in the light of recent discoveries in the pathogenesis of selected JHS/EDS-HT features.
Background:
Hypermobile Ehlers-Danlos Syndrome (hEDS) is a connective tissue disorder characterized by joint hypermobility and other systemic manifestations, such as cardiovascular symptoms, musculoskeletal pain, and joint instability. Cardiovascular symptoms, such as lightheadedness and palpitations, and types of dysautonomia, including postural orthostatic tachycardia syndrome (POTS), are frequently reported in adults with hEDS and have been shown to negatively impact quality of life (QoL).
Objective:
This brief review will be an overview of co-occurring symptoms in POTS and hEDS to inform potential cardiovascular screening procedures.
Results:
While many patients with hEDS report cardiovascular symptoms, few have structural abnormalities, suggesting that dysautonomia is likely responsible for these symptoms. One validated screening measure for dysautonomia symptom burden is the Composite Autonomic Symptom Scale (COMPASS-31). Studies have found that adults with POTS, hEDS, and both POTS and hEDS have higher COMPASS-31 scores than the general population, suggesting a high symptom burden due to dysautonomia, which leads to impaired QoL.
Conclusion:
While studies have examined cardiovascular symptoms and the impact of dysautonomia in adults with and without hEDS, there is scant literature on dysautonomia in pediatric patients with hEDS. Therefore, more studies on cardiovascular symptoms and dysautonomia, as they relate to the quality of life in pediatric patients with hEDS, are needed. This brief review summarizes the current literature on dysautonomia and cardiovascular symptoms in pediatric and adult populations with hEDS.
The new 2017 Nosology has made contributions for geneticists and difficulties for clinicians with more robust criteria for hEDS. Also in 2017, exclusion criteria were established for hEDS in the absence of other collagen disorders. In this way, hypermobility spectrum disorders prioritise musculoskeletal manifestations in the presence of joint hypermobility. It is now evident that these are the same conditions which were established by Kirk, Ansell and Bywaters. Specifically, they refer to the original joint hypermobility syndrome, but now disregarding the benign nature of the disorder. This nomenclature overcomes enormous cultural difficulties, despite now emphasising the pathological issues. There are several subtypes of Ehlers-Danlos syndromes, among which hypermobile Ehlers-Danlos Syndrome, which has the highest frequency. The historical contributions, in particular of Dr. Peter Beighton, are acquired and discussed in this chapter. Medical geneticist Peter Beighton has made diverse contributions to hypermobility and EDS, including the Beighton Method for quantifying the magnitude of joint hypermobility. This approach was scientifically validated in 1973 and is employed in both clinical practice and research. A numerical score derived from this method was developed during an epidemiological investigation in Africa. and remains among the current criteria for the diagnosis of EDS. Over time, clinicians and geneticists have developed an increased understanding of the characteristics of hypermobility, its disorders and manifestations in the context of hypermobile EDS. Historically, while some have dedicated themselves to genetic factors to explain hereditary connective tissue disorders in EDS type III, Kirk, Ansell & Bywaters in 1967 and other rheumatologists have concentrated on clinical issues related to the joints and the overlapping of this syndrome with hereditary connective tissue disorders. Both viewpoints continue to be the focus of discussions to this day.KeywordsEhlers-Danlos syndromeHypermobilityNosologyConnective tissue
Background: Ehlers-Danlos Syndrome (EDS) is a serious chronic condition that leads to diminished quality of life and psychological problems. The current study aimed to systematically reviewed the existing literature on EDS patients' health-related quality of life (HRQoL), calculate mean HRQoL value, and determine the association between demographical and publication-related characteristics with HRQoL.
Methods: Four electronic databases were used to identify papers on HRQOL in adults with EDS (Scopus, Medline (by Pubmed), Epistemonikos, and Web of Science). A random-effects meta-analysis was also performed on the 36-item Short Form Survey (SF-36) measure.
Results: We contained 37 studies that fulfilled the inclusion criteria. According to the SF-36 meta-analysis, EDS patients and the general population had significant differences in all HRQoL components (p0.01). In EDS patients, the Physical Component Summary (35.34/100) was more seriously impacted than the Mental Component Summary (45.21/100) in these patients.
Conclusion: Individuals with EDS have significantly lower HRQoL in all aspects compared to the general population, with the physical component of wellbeing being the most pronounced disparity. Future research should look into the impact of different patient characteristics, evaluate the complications of EDS and their effects on wellbeing, and develop multiple intervention strategies to improve HRQoL.
OBJECTIVE: To evaluate the literature on children and young people with symptomatic hypermobility using a developmental framework. METHODS: A search was conducted in EMBASE, Medline, CINAHL, Web of Science and grey literature. Full text articles reporting children and young people (birth to 24 years) with a confirmed diagnosis of symptomatic hypermobility, (including Hypermobility Spectrum Disorder or hypermobile Ehlers Danlos Syndrome) using internationally recognised criteria or equivalent diagnoses were included. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews methodology was followed. RESULTS: Of the 1619 studies screened, 163 were included in the scoping review. Studies were published from 1967-2021, 30% were narrative reviews and 24% were case reports, from a range of journals. Musculoskeletal and cutaneous characteristics were common in all developmental stages. Cardiovascular characteristics including autonomic dysfunction, fatigue, and gastrointestinal issues were reported more frequently by adolescents. Young adult studies were scarce and included mostly case reports. Varied diagnostic criteria and assessment methods were identified. The Beighton Score was frequently used (93%), but rarely standardised (12%) and lacked consensus regarding the cut-off point of hypermobility. CONCLUSIONS: This novel systematic scoping review identifies the changing phenotype of symptomatic hypermobility from childhood to adolescence, and the unique stage of young adulthood. There is a lack of guidance regarding the utilisation of standardised tools to assess hypermobility in clinical practice and research. Numerous and inconsistent diagnostic criteria and assessment methods limit the data analysis. Case control and longitudinal studies using defined, bespoke criteria and assessments are needed.
In Kap. 3 werden viele der bekannten komorbiden Erkrankungen, deren Management und aktuelle Forschungslage näher beleuchtet. Darunter z. B. Osteoporose, Arthrose, Skoliose, Gastroparese und andere gastrointestinale Komplikationen, Blutungs- und Hämatomneigung, neurologische und muskuläre Beschwerden, die verschiedenen Schmerzarten, Müdigkeit und Erschöpfung, Herz- und Gefäßkomplikationen, Augenprobleme, Temporomandibuläre Dysfunktion, Hernien und Prolapse, psychiatrische und psychologische Aspekte, gynäkologische Probleme und zusätzliche Erkrankungen wie Fibromyalgie. Außerdem werden die Entstehungsmechanismen der häufigsten Komorbiditäten sowie deren Zusammenhang mit den EDS diskutiert. Hier wird vor allem dem Mastzellaktivierungssyndrom, den autonomen Neuropathien, der Chiari-Malformation, dem Tethered Cord Syndrome sowie der kraniozervikalen Instabilität besonders viel Platz eingeräumt.
Background
As chronic conditions, rare and complex connective tissue and musculoskeletal diseases (rCTDs) significantly affect the quality of life generating an impact on the physical, psychological, social, and economic dimensions of the patients’ lives, having implications on the family, changing the lifestyle and interpersonal relationships. Traditionally, generic and disease-specific measures for Quality of Life (QoL) provide valuable information to clinicians since QoL affects healthcare services utilization, predicts morbidities and mortalities, workability, etc. Moreover, the assessment of unmet clinical needs, satisfaction, the experience with the treatment and the care, the psychological dimensions, and the effects of the diseases, such as fatigue, could represent valuable dimensions to be considered in the QoL impact assessment. It is also necessary to measure the impact of rCTDs by considering the perspectives of family members/informal caregivers, for instance considering values, beliefs, experiences, life circumstances, psychological aspects, family relationships, economic issues, changes in social activities, etc.
Objective
The aim of this scoping review is to better understand the status of QoL metrics used in clinical and economic research for the assessment of the individual’s perspective on living with rCTDs.
Research question
What are the main challenges in QoL measures (and/or) measurement/assessment in rCTDs?
Materials and methods
Scoping review of the literature referring to QoL measures in rCTDs. Database: PUBMED, ISI-Web of Science; last date: 21/09/2021.
Results
Anxiety and depression, body image satisfaction, daily activity, fatigue, illness perception, pain, personality, QoL, resilience, satisfaction with the relationship, self-management, sexual QoL, sleep quality, social support, stress, uncertainty, and work productivity are the observed dimensions covered by the included studies. However, “more shadows than lights” can summarize the review’s outcome in terms of Patient Reported Outcome Measures (PROMs) domains covered for each of the rCTDs. Also, for those diseases characterized by a relatively high prevalence and incidence, such as Systemic Lupus Erythematosus, Sjögren’s Syndrome, and Systemic Sclerosis, the analysis of patients’ resilience, satisfaction with the quality of the relationship, personality, and stress are still missing dimensions. It has been observed how reducing items, increasing the number of domains, and disease-specific questionnaires characterize the “technological trajectory,” such as the evolution of questionnaires’ characteristics for assessing QoL and QoL-related dimensions and the burden of rCTDs.
Conclusion
The scoping review presents an overview of studies focused on questionnaires used to evaluate the different dimensions of quality of life in terms of general instruments and disease-specific questionnaires. Future research should include the co-design with patients, caregivers, and patient representatives to create questionnaires focused on the unmet needs of people living with rCTDs.
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.
Ehlers-Danlos syndrome (EDS) is a heterogeneous group of inherited disorders of connective tissue. EDS hypermobility type (EDS-HT), characterized by joint hypermobility, is most common and increasingly recognized in pediatrics. Treatment involves protecting joints, preventing injuries, and managing symptoms/comorbidities. Pediatric EDS-HT patients often see multiple medical providers; however, data on healthcare utilization (HCU) in this population are lacking. This retrospective, electronic chart review examines HCU data 1 year prior and subsequent to a new diagnosis of EDS-HT using Villefranche criteria. Demographics, diagnoses, and HCU (office visits, therapies, hospital encounters/procedures, and tests) were obtained for N = 102 youth attending a Connective Tissue Disorder Clinic over a 21-month timeframe. After EDS-HT diagnosis, HCU patterns shifted to reflect greater involvement of therapy (physical, psychological, and occupational) and symptom management. More genetics, rheumatology, and orthopedics visits occurred prediagnosis, and more physical therapy, pain management, cardiology, and neurology visits occurred postdiagnosis. Testing and hospital encounter/procedure frequencies did not change. Overall, the pattern of HCU changed from diagnostic to treatment, in accordance with evidence-based EDS-HT care. Understanding HCU patterns of pediatric patients with EDS-HT can elucidate patient interaction with the health care system, with the potential to inform and improve the standard of care.
The symptoms of joint hypermobility extend beyond articular pain. Hypermobile people commonly experience autonomic symptoms (dysautonomia), and anxiety or related psychological issues. We tested whether dysautonomia might mediate the association between hypermobility and anxiety in adults diagnosed with mental health disorders and/or neurodevelopmental conditions (hereon referred to as patients), by quantifying joint hypermobility and symptoms of autonomic dysfunction. Prevalence of generalized joint laxity (hypermobility) in 377 individuals with diagnoses of mental health disorders and/or neurodevelopmental conditions was compared to prevalence recorded in the general population. Autonomic symptom burden was compared between hypermobile and non-hypermobile patients. Mediation analysis explored relationships between hypermobility, autonomic dysfunction, and anxiety. Patient participants had elevated prevalence of generalized joint laxity (38%) compared to the general population rate of 19% (odds ratio: 2.54 [95% confidence interval: 2.05, 3.16]). Hypermobile participants reported significantly more autonomic symptoms. Symptoms of orthostatic intolerance mediated the relationship between hypermobility and diagnosis of an anxiety disorder. Patients with mental health disorders and/or neurodevelopmental conditions have high rates of joint hypermobility. Accompanying autonomic dysfunction mediates the association between joint hypermobility and clinical anxiety status. Increased recognition of this association can enhance mechanistic understanding and improve the management of multimorbidity expressed in physical symptoms and mental health difficulties.
There has been increasing recognition in recent years of the prevalence and impact of symptoms which extend beyond the musculoskeletal system on the lives of people with hypermobility‐related disorders. This has led researchers to develop more comprehensive assessment tools to help direct and monitor treatment. This article presents some of the latest assessment and diagnostic developments and their implications for practice from a physical therapy perspective.
Irritable bowel syndrome (IBS) is common, but its cause remains unknown. IBS patients present with gastrointestinal (GI) symptoms such as abdominal pain with altered bowel habits; however, some patients also have non‐GI symptoms including muscle and joint pains. It is thus plausible that within large IBS cohorts, subgroups exist with distinct clinical phenotypes. Yet, these subgroups have not been clearly identified or characterized. Due to lack of segmentation, treatment‐focused symptomatic management is similar for all with IBS and follows indiscriminate algorithms regardless of possible differing clinical phenotype. This universal approach to IBS management may account for the reported lack of efficacy of treatment. One emerging subgroup receiving increasing attention is that with overlap IBS and the underlying heritable connective tissue disorder, hypermobile Ehlers–Danlos syndrome (hEDS). Current evidence suggests that up to 62% of patients with hEDS suffer from IBS. However, despite recognition of the presence of IBS in hEDS, this overlap IBS/hEDS group has not been characterized and these patients are managed in a similar way to those with IBS alone. Future studies are required to characterize and deep phenotype in this overlap IBS/hEDS group.
The Ehlers-Danlos syndrome (EDS) is a heterogeneous group of heritable disorders of connective tissue characterized by articular hypermobility, skin hyperextensibility, and tissue fragility affecting skin, ligaments, joints, blood vessels, and internal organs. In this chapter, we try to cover the EDS in a comprehensive and authoritative way, to consider the different aspects as objectively as possible, and to clarify earlier concepts and conclusions that today are no longer tenable. To give the reader an idea of how knowledge was gained, references are often cited in a historical sequence.
Adolescents with postural tachycardia syndrome (POTS) often experience ill-defined cognitive impairment referred to by patients as "brain fog." The objective of this study was to evaluate the symptom of brain fog as a means of gaining further insight into its etiology and potential palliative interventions.
Eligible subjects who reported having been diagnosed with POTS were recruited from social media web sites. Subjects were asked to complete a 38-item questionnaire designed for this study, and the Wood mental fatigue inventory (WMFI).
Responses were received from 138 subjects with POTS (88 % female), ranging in age from 14 to 29 years; 132 subjects reported brain fog. WMFI scores correlated with brain fog frequency and severity (P < 0.001). The top ranked descriptors of brain fog were "forgetful," "cloudy," and "difficulty focusing, thinking and communicating." The most frequently reported brain fog triggers were fatigue (91 %), lack of sleep (90 %), prolonged standing (87 %), dehydration (86 %), and feeling faint (85 %). Although aggravated by upright posture, brain fog was reported to persist after assuming a recumbent posture. The most frequently reported interventions for the treatment of brain fog were intravenous saline (77 %), stimulant medications (67 %), salt tablets (54 %), intra-muscular vitamin B-12 injections (48 %), and midodrine (45 %).
Descriptors for "brain fog" are most consistent with it being a cognitive complaint. Factors other than upright posture may play a role in the persistence of this symptom. Subjects reported a number of therapeutic interventions for brain fog not typically used in the treatment of POTS that may warrant further investigation.
A 36-item short-form (SF-36) was constructed to survey health status in the Medical Outcomes Study. The SF-36 was designed for use in clinical practice and research, health policy evaluations, and general population surveys. The SF-36 includes one multi-item scale that assesses eight health concepts: 1) limitations in physical activities because of health problems; 2) limitations in social activities because of physical or emotional problems; 3) limitations in usual role activities because of physical health problems; 4) bodily pain; 5) general mental health (psychological distress and well-being); 6) limitations in usual role activities because of emotional problems; 7) vitality (energy and fatigue); and 8) general health perceptions. The survey was constructed for self-administration by persons 14 years of age and older, and for administration by a trained interviewer in person or by telephone. The history of the development of the SF-36, the origin of specific items, and the logic underlying their selection are summarized. The content and features of the SF-36 are compared with the 20-item Medical Outcomes Study short-form.
Hypermobility type Ehlers–Danlos syndrome (HT-EDS) is a relatively frequent, although commonly misdiagnosed variant of Ehlers–Danlos syndrome, mainly characterized by marked joint instability and mild cutaneous involvement. Chronic pain, asthenia, and gastrointestinal and pelvic dysfunction are characteristic additional manifestations. We report on 21 HT-EDS patients selected from a group of 40 subjects with suspected mild hereditary connective tissue disorder. General, mucocutaneous, musculoskeletal, cardiovascular, neurologic, gastrointestinal, urogynecological, and ear–nose–throat abnormalities are investigated systematically and tabulated. Six distinct clinical presentations of HT-EDS are outlined, whose tabulation is a mnemonic for the practicing clinical geneticist in an attempt to diagnose this condition accurately. With detailed clinical records and phenotype comparison among patients of different ages, the natural history of the disorder is defined. Three phases (namely, hypermobility, pain, and stiffness) are delineated based on distinguishing manifestations. A constellation of additional, apparently uncommon abnormalities is also identified, including dolichocolon, dysphonia, and Arnold–Chiari type I malformation. Their further investigation may contribute to an understanding of the pathogenesis of the protean manifestations of HT-EDS, and a more effective approach to the evaluation and management of affected individuals. © 2010 Wiley-Liss, Inc.
Objectives
To determine the prevalence of autonomic dysfunction (dysautonomia) among patients with primary Sjögren's syndrome (PSS) and the relationships between dysautonomia and other clinical features of PSS.
Methods
Multicentre, prospective, cross-sectional study of a UK cohort of 317 patients with clinically well-characterised PSS. Symptoms of autonomic dysfunction were assessed using a validated instrument, the Composite Autonomic Symptom Scale (COMPASS). The data were compared with an age- and sex-matched cohort of 317 community controls. The relationships between symptoms of dysautonomia and various clinical features of PSS were analysed using regression analysis.
Results
COMPASS scores were significantly higher in patients with PSS than in age- and sex-matched community controls (median (IQR) 35.5 (20.9–46.0) vs 14.8 (4.4–30.2), p<0.0001). Nearly 55% of patients (vs 20% of community controls, p<0.0001) had a COMPASS score >32.5, a cut-off value indicative of autonomic dysfunction. Furthermore, the COMPASS total score correlated independently with EULAR Sjögren's Syndrome Patient Reported Index (a composite measure of the overall burden of symptoms experienced by patients with PSS) (β=0.38, p<0.001) and disease activity measured using the EULAR Sjögren's Syndrome Disease Activity Index (β=0.13, p<0.009).
Conclusions
Autonomic symptoms are common among patients with PSS and may contribute to the overall burden of symptoms and link with systemic disease activity.
Postural tachycardia syndrome (PoTS) is a poorly understood but important cause of orthostatic intolerance resulting from cardiovascular autonomic dysfunction. PoTS is distinct from the syndromes of autonomic failure usually associated with orthostatic hypotension, such as pure autonomic failure and multiple system atrophy. Individuals affected by PoTS are mainly young (aged between 15 years and 40 years) and predominantly female. The symptoms--palpitations, dizziness and occasionally syncope--mainly occur when the patient is standing upright, and are often relieved by sitting or lying flat. Common stimuli in daily life, such as modest exertion, food ingestion and heat, are now recognized to be capable of exacerbating the symptoms. Onset of the syndrome can be linked to infection, trauma, surgery or stress. PoTS can be associated with various other disorders; in particular, joint hypermobility syndrome (also known as Ehlers-Danlos syndrome hypermobility type, formerly termed Ehlers-Danlos syndrome type III). This Review describes the characteristics and neuroepidemiology of PoTS, and outlines possible pathophysiological mechanisms of this syndrome, as well as current and investigational treatments.
Autonomic dysfunction is common in patients with the joint hypermobility syndrome (JHS). However, there is a paucity of reported data on clinical features of Postural orthostatic tachycardia syndrome (POTS) in patients suffering from JHS.
This retrospective study was approved by our local Institutional Review Board (IRB). Over a period of 10 years, 26 patients of POTS were identified for inclusion in this study. All these patients had features of Joint Hypermobility Syndrome (by Brighton criterion). A comparison group of 39 patients with other forms of POTS were also followed in the autonomic clinic during the same time. We present a descriptive report on the comparative clinical profile of the clinical features of Postural Orthostatic Tachycardia patients with and without Joint Hypermobility syndrome. The data is presented as a mean+/-SD and percentages wherever applicable.
Out of 65 patients, 26 patients (all females, 20 Caucasians) had POTS and JHS. The mean age at presentation of POTS was 24+/-13 (range 10-53 years) vs 41+/-12 (range 19-65 years), P=0.0001, Migraine was a common co morbidity 73 vs 29% p=0,001. In two patients POTS was precipitated by pregnancy, and in three by surgery, urinary tract infection and a viral syndrome respectively. The common clinical features were fatigue (58%), orthostatic palpitations (54%), presyncope (58%), and syncope (62%).
Patients with POTS and JHS appear to become symptomatic at an earlier age compared to POTS patients without JHS. In addition patients with JHS had a greater incidence of migraine and syncope than their non JHS counterparts.
To investigate autonomic dysfunction (AD) development in patients with primary SS (pSS) and the associations between AD and clinical, inflammatory and serological features of pSS.
Twenty-seven patients with pSS, who had previously been evaluated for AD, were included in the study. The patients were studied at baseline and at follow-up by objective autonomic reflex tests (ARTs) and by the autonomic symptom profile (ASP) questionnaire, evaluating AD symptoms. The median follow-up time was 5 years for the ART and 4 years for the ASP variables. The results were compared with previously investigated healthy ART controls and population-based ASP controls. Fatigue, anxiety and depression were assessed by the profile of fatigue and by the Hospital Anxiety and Depression scale.
Three of five ART variables as well as the ASP total score were significantly abnormal both at baseline and at follow-up in pSS patients in comparison with controls. When comparing ART and ASP results in pSS patients between baseline and follow-up, only the lowest diastolic blood pressure (lDBP) ratio significantly deteriorated during the follow-up period. The ART and ASP variables were not significantly correlated. However, the ASP total score significantly correlated with measurements of fatigue, anxiety and depression.
Both objective signs and subjective symptoms of parasympathetic and sympathetic dysfunction were seen in pSS patients, both at baseline and at follow-up. During follow-up, only the lDBP ratio was found to significantly deteriorate. AD symptoms were significantly associated with fatigue, anxiety and depression.
It has been suggested that autonomic nervous system dysfunction may explain all of fibromyalgia (FM) multisystem features. Such proposal is based mostly on the results of diverse heart rate variability analyses. The Composite Autonomic Symptom Scale (COMPASS) is a different validated method to recognize dysautonomia.
The main objective of our study was to investigate symptoms of autonomic dysfunction in FM patients by means of COMPASS. A secondary objective was to define whether there is a correlation between COMPASS and Fibromyalgia Impact Questionnaire (FIQ) scores in FM patients.
Design, analytical cross-sectional study. Our study population included 3 different groups of women: 30 patients with FM, 30 patients with rheumatoid arthritis, and 30 women who considered themselves healthy. All participants filled out COMPASS and FIQ questionnaires.
FM patients had significantly higher values in all COMPASS domains. COMPASS total score (54.6 +/- 20.9; mean +/- standard deviation) clearly differentiated FM patients from the other 2 groups (21.6 +/- 16.5 and 9.5 +/- 10.2, respectively). P < 0.0001. The majority of FM patients gave affirmative answers to questions related to orthostatic, digestive, sleep, sudomotor, or mucosal dysfunction. There was a significant correlation between COMPASS and FIQ scores (Spearman r = 0.5, P < 0.005).
Patients with FM have multiple nonpain symptoms related to different expressions of autonomic dysfunction. There is a correlation between a questionnaire that measures FM severity (FIQ) and an autonomic dysfunction questionnaire (COMPASS). Such correlation suggests that autonomic dysfunction is inherent to FM.
A 36-item short-form (SF-36) was constructed to survey health status in the Medical Outcomes Study. The SF-36 was designed for use in clinical practice and research, health policy evaluations, and general population surveys. The SF-36 includes one multi-item scale that assesses eight health concepts: 1) limitations in physical activities because of health problems; 2) limitations in social activities because of physical or emotional problems; 3) limitations in usual role activities because of physical health problems; 4) bodily pain; 5) general mental health (psychological distress and well-being); 6) limitations in usual role activities because of emotional problems; 7) vitality (energy and fatigue); and 8) general health perceptions. The survey was constructed for self-administration by persons 14 years of age and older, and for administration by a trained interviewer in person or by telephone. The history of the development of the SF-36, the origin of specific items, and the logic underlying their selection are summarized. The content and features of the SF-36 are compared with the 20-item Medical Outcomes Study short-form.
Physical component summary (PCS) and mental component summary (MCS) measures make it possible to reduce the number of statistical comparisons and thereby the role of chance in testing hypotheses about health outcomes. To test their usefulness relative to a profile of eight scores, results were compared across 16 tests involving patients (N = 1,440) participating in the Medical Outcomes Study. Comparisons were made between groups known to differ at a point in time or to change over time in terms of age, diagnosis, severity of disease, comorbid conditions, acute symptoms, self-reported changes in health, and recovery from clinical depression. The relative validity (RV) of each measure was estimated by a comparison of statistical results with those for the best scales in the same tests. Differences in RV among scales from the Medical Outcomes Study 36-Item Short-Form Health Survey (SF-36) were consistent with those in previous studies. One or both of the summary measures were significant for 14 of 15 differences detected in multivariate analyses of profiles and detected differences missed by the profile in one test. Relative validity coefficients ranged from .20 to .94 (median, .79) for PCS in tests involving physical criteria and from .93 to 1.45 (median, 1.02) for MCS in tests involving mental criteria. The MCS was superior to the best SF-36 scale in three of four tests involving mental health. Results suggest that the two summary measures may be useful in most studies and that their empiric validity, relative to the best SF-36 scale, will depend on the application. Surveys offering the option of analyzing both a profile and psychometrically based summary measures have an advantage over those that do not.
Categorization of the Ehlers-Danlos syndromes began in the late 1960s and was formalized in the Berlin nosology. Over time, it became apparent that the diagnostic criteria established and published in 1988 did not discriminate adequately between the different types of Ehlers-Danlos syndromes or between Ehlers-Danlos syndromes and other phenotypically related conditions. In addition, elucidation of the molecular basis of several Ehlers-Danlos syndromes has added a new dimension to the characterization of this group of disorders. We propose a revision of the classification of the Ehlers-Danlos syndromes based primarily on the cause of each type. Major and minor diagnostic criteria have been defined for each type and complemented whenever possible with laboratory findings. This simplified classification will facilitate an accurate diagnosis of the Ehlers-Danlos syndromes and contribute to the delineation of phenotypically related disorders.
To evaluate the validity of the checklist individual strength questionnaire (CIS) in the working population. This 20 item self reported questionnaire has often been used in patients with chronic fatigue. To date, no research has focused on the validity of the CIS in occupational groups.
To evaluate the discriminant validity the CIS was filled out by five groups of employees with expected differences in fatigue. The convergent validity was evaluated by comparing the results of the CIS with the results of three related measures: measured unidimensional fatigue, burnout, and need for recovery.
The CIS was able to discriminate between fatigued and non-fatigued employees in occupational groups. The expected agreement between the results of the CIS and related measures was confirmed.
The CIS seems to be an appropriate instrument for measuring fatigue in the working population.
The construct validity and the test-retest reliability of a self-administered questionnaire about habitual physical activity were investigated in young males (n = 139) and females (n = 167) in three age groups (20 to 22, 25 to 27, and 30 to 32 yr) in a Dutch population. By principal components analysis three conceptually meaningful factors were distinguished. They were interpreted as: 1) physical activity at work; 2) sport during leisure time; and 3) physical activity during leisure time excluding sport. Test-retest showed that the reliability of the three indices constructed from these factors was adequate. Further, it was found that level of education was inversely related to the work index, and positively related to the leisure-time index in both sexes. The subjective experience of work load was not related to the work index, but was inversely related to the sport index, and the leisure-time index in both sexes. The lean body mass was positively related to the work index, and the sport index in males, but was not related to the leisure-time index in either sex. These differences in the relationships support the subdivision of habitual physical activity into the three components mentioned above.
Physical component summary (PCS) and mental component summary (MCS) measures make it possible to reduce the number of statistical comparisons and thereby the role of chance in testing hypotheses about health outcomes. To test their usefulness relative to a profile of eight scores, results were compared across 16 tests involving patients (N = 1,440) participating in the Medical Outcomes Study. Comparisons were made between groups known to differ at a point in time or to change over time in terms of age, diagnosis, severity of disease, comorbid conditions, acute symptoms, self-reported changes in health, and recovery from clinical depression. The relative validity (RV) of each measure was estimated by a comparison of statistical results with those for the best scales in the same tests. Differences in RV among scales from the Medical Outcomes Study 36-Item Short-Form Health Survey (SF-36) were consistent with those in previous studies. One or both of the summary measures were significant for 14 of 15 differences detected in multivariate analyses of profiles and detected differences missed by the profile in one test. Relative validity coefficients ranged from .20 to .94 (median, .79) for PCS in tests involving physical criteria and from .93 to 1.45 (median, 1.02) for MCS in tests involving mental criteria. The MCS was superior to the best SF-36 scale in three of four tests involving mental health. Results suggest that the two summary measures may be useful in most studies and that their empiric validity, relative to the best SF-36 scale, will depend on the application. Surveys offering the option of analyzing both a profile and psychometrically based summary measures have an advantage over those that do not.
Joint hypermobility syndrome (JHS) and Ehlers-Danlos syndrome, hypermobility type (EDS-HT) are two clinically overlapping connective tissue disorders characterized by chronic/recurrent pain, joint instability complications, and minor skin changes. Fatigue and headache are also common, although are not yet considered diagnostic criteria. JHS/EDS-HT is a unexpectedly common condition that remains underdiagnosed by most clinicians and pain specialists. This results in interventions limited to symptomatic and non-satisfactory treatments, lacking reasonable pathophysiologic rationale. In this manuscript the fragmented knowledge on pain, fatigue, and headache in JHS/EDS is presented with review of the available published information and a description of the clinical course by symptoms, on the basis of authors' experience. Pathogenic mechanisms are suggested through comparisons with other functional somatic syndromes (e.g., chronic fatigue syndrome, fibromyalgia, and functional gastrointestinal disorders). The re-writing of the natural history of JHS/EDS-HT is aimed to raise awareness among clinical geneticists and specialists treating chronic pain conditions about pain and other complications of JHS/EDS-HT. Symptoms' clustering by disease stage is proposed to investigate both the molecular causes and the symptoms management of JHS/EDS-HT in future studies. © 2013 Wiley Periodicals, Inc.
Categorization of the Ehlers-Danlos syndromes began in the late 1960s and was formalized in the Berlin nosology. Over time, it became apparent that the diagnostic criteria established and published in 1988 did not discriminate adequately between the different types of Ehlers-Danlos syndromes or between Ehlers-Danlos syndromes and other phenotypically related conditions. In addition, elucidation of the molecular basis of several Ehlers-Danlos syndromes has added a new dimension to the characterization of this group of disorders. We propose a revision of the classification of the Ehlers-Danlos syndromes based primarily on the cause of each type. Major and minor diagnostic criteria have been defined for each type and complemented whenever possible with laboratory findings. This simplified classification will facilitate an accurate diagnosis of the Ehlers-Danlos syndromes and contribute to the delineation of phenotypically related disorders. Am. J. Med. Genet. 77:31–37, 1998. © 1998 Wiley-Liss, Inc.
EDS-HT is a connective tissue disorder characterized by large inter-individual differences in the clinical presentation, complicating diagnosis and treatment. We aim to describe the clinical heterogeneity and to investigate whether differences in the symptom profile are also reflected as disparity in functional impairment and pain experience. In this study, 78 patients were asked to describe their symptoms due to EDS-HT. Next, a hierarchical cluster analysis was performed using the Jaccard measure of similarity to assess whether subgroups could be distinguished based on the symptoms reported. This analysis yielded 3 clusters of participants with distinct complaint profiles. The key differences were found in the domain of non-musculoskeletal complaints, which was significantly larger in cluster 2. Furthermore, cluster 2 was characterized by a worse physical and psychosocial health, a higher pain severity and a larger pain interference in daily life. The results emphasize that non-musculoskeletal symptoms are an important complication of EDS-HT, as the number of these complaints was found to be a significant predictor for both functional health status (SIP) and pain experience (MPI). In conclusion, this study confirms that EDS-HT is a heterogeneous entity and encourages the clinician to be more aware of the large variety of EDS-HT symptoms, in order to improve disease recognition and to establish more tailored treatment strategies.
Sulfated proteoglycans are abundant components of skeletal and connective tissues and particularly of cartilage. In this chapter we show that genetic defects in the metabolism of sulfate may affect the biosynthesis or the degradation of sulfated proteoglycans and thus perturb the homeostasis of the extracellular matrix.
Prolidase deficiency is a rare, autosomal recessively inherited disorder in which deficient activity of prolidase results in a massive urinary excretion of X-Pro and X-Hyp dipeptides derived from generalized protein breakdown. The chapter includes discussions on the clinical features of the disorder, inheritance and prevalence, diagnosis, prognosis and management.
The absence of laboratory tests and clear criteria to identify homogeneous (sub)groups in patients presenting with unexplained fatigue, and to assess clinical status and disability in these patients, calls for further assessment methods. In the present study, a multi-dimensional approach to the assessment of chronic fatigue syndrome (CFS) is evaluated. Two-hundred and ninety-eight patients with CFS completed a set of postal questionnaires that assessed the behavioural, emotional, social, and cognitive aspects of CFS. By means of statistical analyses nine relatively independent dimensions of CFS were identified along which CFS-assessment and CFS-research can be directed. These dimensions were named: psychological well-being, functional impairment in daily life, sleep disturbances, avoidance of physical activity, neuropsychological impairment, causal attributions related to the complaints, social functioning, self-efficacy expectations, and subjective experience of the personal situation. A description of the study sample on these dimensions is presented.
