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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

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... De Wandele et al., [44] The total autonomic symptom burden was higher in EDS-HT (57.9 ± 21.57) than in controls (11.3 ± 19.22), especially according to orthostatic and gastrointestinal complaints. [36] checked the correlation with lower limbs on a group of professional footballers. ...
... In another work by De Wandele [44], the authors studied the level of autonomy of people with EDS-HT using a series of studies called the Autonomic Symptom Profile (ASP). ASP evaluates orthostatic, secretomotor, urinary tract, gastrointestinal, pupil, vasomotor, reflex syncope and sleep functions. ...
... As the De Wandele [44] group has already noted, one of the symptoms of EDS-HT involves problems with the digestive system. Menys et al., [32] performed magnetic resonance imaging to assess gastric emptying, its motility and accommodation in the group of patients with EDS-HT with dyspepsia. ...
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Introduction and objective Ehlers Danlos Syndrome – Hypermobile Type (EDS-HT), in which the genetic basis could not be determined and mutations of collagen fibrillar proteins were excluded, is one of the most common types of EDS. It is a disease characterized by many symptoms of varying severity. The purpose of the study is to determine the most important diagnostic factors for EDS-HT based on current literature. Material and Methods Searching PubMed publication databases, Google Scholar and Science Direct, by using a combination of key words: hEDS diagnosis, hypermobile EDS, hypermobility. Brief description of the state of knowledge 19 papers were selected for the literature review, among which 8 concern the adequacy of the Beighton result in the diagnosis of EDS-HT, and another 11 the quality of life of people with EDS-HT, as well as the assessment and diagnosis of other symptoms accompanying this disease. Conclusions In order to diagnose EDS-HT, one should be guided not only by the established standard, which is the Beighton score, but also by additional tests that would confirm the diagnostic decision and reduce the risk of error. Extension of diagnostic tests with additional criteria, which are presented in the article, would make diagnoses more accurate and reduce the possibility of false diagnoses. This is very important from the perspective of implementing appropriate treatment and the mental comfort of the patient.
... 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]. ...
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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.
... 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. ...
... 17,27 Adults with JH have greater prevalence of autonomic dysfunction, especially orthostatic and GI complaints, compared with 10% of non-JH healthy controls. 17,28 Another study found that 55% of adult patients with postural tachycardia syndrome (POTS), whose symptoms are mediated by autonomic processes, also meet criteria for generalized JH. 29 In children, studies have been more mixed, with diverse protocols, cutoff criteria, and population samples giving rise to divergent findings. Some studies have shown a close association between JH, ANS, and GI dysfunction. ...
... Wide variability in clinical presentation is a cause of delayed diagnosis and suboptimal care for hEDS patients. 28 Non-musculoskeletal complaints such as GI dysfunction are exceedingly common. 80 Most are labeled with a functional GI disorder, while the underlying connective tissue disorder is frequently missed. ...
... 11,41 The selfreport instrument has also been found to correlate with higher orthostatic and upper gastrointestinal symptom scores. 28 The study population was enrolled at a large tertiary care center which may limit the external validity of findings. However, subjects were recruited from 12 different physicians and three advanced practice providers at both the main academic center and several clinics in surrounding communities, which serve a less complex patient population. ...
Article
Background Joint hypermobility (JH) is associated with autonomic nervous system dysregulation and functional abdominal pain disorders (FAPDs). Understanding the neurophysiological processes linking these conditions can inform clinical interventions. Autonomic activity regulates gastrointestinal (GI) sensorimotor function and may be a key mechanism. The aims of this study were to examine the relation of JH with dynamic autonomic activity and parasympathetic regulation in adolescents with FAPDs and identify optimal JH cutoff scores that best index autonomic regulation in FAPDs. Methods A total of 92 adolescents with FAPDs and 27 healthy controls (age 8–18 years; 80% female) were prospectively enrolled. JH was assessed by Beighton scores. ECG recordings were conducted during supine, sitting, and standing posture challenges. ECG‐derived variables—heart period (HP), respiratory sinus arrhythmia (RSA), and vagal efficiency (VE)—were analyzed using linear regression and mixed effects modeling. Key Results Beighton scores of ≥4 optimally distinguished autonomic function. Adolescents with FAPD and JH had reduced VE compared to adolescents with FAPDs without JH (B = 18.88, SE = 6.25, p = 0.003) and healthy controls (B = 17.56, SE = 8.63, p = 0.044). These subjects also had lower and less dynamic RSA and HP values during posture shifts, with strongest differences in supine position and using the VE metric. Conclusions & Inferences Suboptimal autonomic regulation indexed by reduced vagal efficiency may be a mechanism of symptoms in hypermobile FAPD patients with Beighton score ≥ 4. Autonomic disturbance may serve as potential intervention target for patients with JH and functional GI disorders.
... 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. ...
Article
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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.
... 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]. ...
Article
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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.
... 16 EDS patients may suffer from peripheral neuropathy that consequently leads to autonomic dysfunction. 17,18 In 2017, a review article regarding the association between MCAD and EDS was published. 4 The investigators postulated that migration and differentiation of MC progenitors, MC activation, and the pattern of mediators in the MC granules are affected by components of the extracellular matrix. ...
... These symptoms can be induced by exercise, meals, standing, or a hot environment. 17,18 In a study of a POTS population, a prevalence of 18% was observed in patients who met the criteria for EDS, but its prevalence in the general population was approximately 0.02%. 24 It has been reported that hEDS is the most common disorder associated with POTS. 25 The exact relationship between POTS and hEDS is still unclear. ...
Article
Mast cell activation disorders (MCADs) consist of episodic systemic symptoms due to mast cell mediator release. Diagnosis is based on clinical presentation and determination of high levels of tryptase or histamine. Ehlers-Danlos syndrome (EDS) and postural tachycardia syndrome (POTS) frequently coexist. It has been described that individuals with these syndromes can even present symptoms compatible to MCADs, which could represent a new specific phenotype. Preliminary genetic data suggest a role for tryptase in the pathogenesis of MCADs, EDS, and POTS association. Studies with larger samples evaluating clinics, genetics, and histopathology are required to define the real correlation between these 3 clinical entities.
... This finding is supported by an earlier report, which describes both orthostatic intolerance and secretomotor disorders as the best predictors of autonomic failure in both healthy and diseased populations [11]. This finding is clinically important for a few reasons: orthostatic intolerance is linked to sudden tachycardia and cerebral vasoconstriction [30], and orthostatic intolerance symptoms is a major clinical test that is capable of ascertaining symptoms of cerebral hypo-perfusion (following an upright position) that is secondary to inadequate hemodynamic regulation by the ANS [13,31,32]. It is not surprising that subjects with COPD in our study reported high rates of orthostatic symptoms. ...
... It is not surprising that subjects with COPD in our study reported high rates of orthostatic symptoms. Orthostatic intolerance can appear in many forms such as fatigue, diminished concentration, a feeling of absence, brain fog, chest pain, shortness of breath, palpitations, coat-hanger headache and vision disturbances [31]. Moreover, COPD patients who have shortness of breath due to reduced ventilatory capacity, hypercapnia and/or lowered oxygen saturation have been reported to be at more risks of orthostatic symptoms compared to those without these symptoms [33]. ...
Article
Objectives: A synoptic description of the autonomic symptoms profile (ASP) of patients with COPD is not available. Therefore, we aimed to provide an overview of autonomic symptoms and its associates in COPD. Methods: We evaluated 89 subjects with COPD (65 ± 7.3 years; 66 males; GOLD II-IV) with an equal number of age- and sex-matched control subjects by means of the composite autonomic symptom score (COMPASS 31) questionnaire, which assesses autonomic symptoms across six domains (orthostatic intolerance, vasomotor, secretomotor, gastrointestinal, urinary and pupillomotor). Lung function, medication use and health status variables (quality of life: physical/mental component summary [PCS/MCS], fatigue, anxiety, depression and dyspnea levels) were also assessed. Results: Compared to controls, all subjects with COPD reported significantly higher orthostatic intolerance, secretomotor and total autonomic symptom scores (p < .05). Additionally, subjects with moderate COPD also reported significantly higher scores for vasomotor, gastrointestinal, urinary and pupillomotor symptoms compared to controls (p < .05). Nevertheless, these symptoms were comparable between the moderate and severe COPD subgroups (p > .05). The COPD subjects had poorer health status compared to controls as exhibited by significantly higher scores for depression, anxiety, fatigue and dyspnea, and lower scores values for PCS and MCS scores (p < .05). These health status variables were mildly associated with autonomic symptoms (0.214 ≤ r ≥ 0.421; p < .05), but not with demographic and lung function (p > .05). The MCS was the only significant predictor of total autonomic symptoms score in COPD (p = 0.001; β = -0.430). Conclusion: Autonomic symptoms are present in all domains of the COMPASS-31 in COPD, irrespective of disease severity and demographic variables. Autonomic symptoms in COPD were mainly influenced by poor mental health.
... 17,18 In adults with CMP, the fearavoidance model (FAM) (Figure 1.3), explains the disabling role of pain-related fear. 83 As a result of the growing evidence on the role of pain-related fear in youth, this framework has also been applied to paediatric chronic pain. 84,85 Exposure in vivo is a cognitivebehavioural treatment that targets to restore the normal pattern of daily functioning by reducing pain-related fear and catastrophic thinking, through exposing the individual to fear-provoking daily life activities and movements. ...
... 71 2 and decreased quality of life in G-HSD/hEDS. 79,81 In addition, increased autonomic dysfunctions were related to higher pain severity 82,83 and autonomic dysfunction may result in increased interoceptive sensitivity. 84 Higher pain severity in combination with increased interoceptive sensitivity may have additional emotional consequences, such as anxiety and fear, which also may contribute to higher disability levels. ...
... 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). ...
Article
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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). ...
Article
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.
... Ehlers-Danlos syndrome (EDS), a group of connective tissue disorders caused by genetic defects in collagen, is a known risk factor for developing OI. 32 De Wandele and colleagues found that 41% of their cohort with known hypermobile EDS met criteria for POTS based on tilt table testing compared with 11% of controls (P = .003). 32 The increased prevalence of OI in EDS patients may be due to increased laxity in vascular wall compliance, resulting in increased pooling of blood during upright posture, with secondary elevations in HR and drops in BP. 33 Interestingly, we found that our OI population had a median Beighton score of 1, which is far below the threshold of 6 needed to diagnose joint hypermobility in adolescents. ...
... 32 De Wandele and colleagues found that 41% of their cohort with known hypermobile EDS met criteria for POTS based on tilt table testing compared with 11% of controls (P = .003). 32 The increased prevalence of OI in EDS patients may be due to increased laxity in vascular wall compliance, resulting in increased pooling of blood during upright posture, with secondary elevations in HR and drops in BP. 33 Interestingly, we found that our OI population had a median Beighton score of 1, which is far below the threshold of 6 needed to diagnose joint hypermobility in adolescents. 34 This discrepancy may indicate that the trauma of concussion itself can create sufficient autonomic disruption to cause OI without the predisposing presence of hypermobility. ...
Article
Following concussion, children often experience nonspecific symptoms that overlap with those of other common pediatric conditions, including orthostatic intolerance (OI). The primary goal of this study was to evaluate OI in youth presenting for clinical care for concussion and reporting symptoms frequently observed in OI. Eighty-two of 114 patients aged 10 to 22 years endorsed symptoms based on 8 screening questions, and 24 of those 82 patients met criteria for OI based on an active standing test. No screening question generated clinically useful likelihood ratios for predicting OI. The prevalence of OI in this cohort is considerably higher than estimates in the general pediatric population, suggesting a link between concussion and OI. Future work is needed to evaluate the best method of testing for OI, the natural history of OI symptoms in youth with concussion, and the response to intervention in children with both concussion and OI.
... As with autism, dysautonomias are common extraarticular manifestations in EDS, particularly in the hypermobile type, and they significantly influence quality of life for these individuals. According to one study, the extent of autonomic burden in hEDS is similar to that seen in fibromyalgia, both of which are comparatively more severe than that found in classic and vascular types of EDS [120]. Similar to the profile in autism, hEDS patients typically exhibit high resting sympathetic tone but blunted sympathetic reactivity to certain stimuli (e.g., valsalva maneuver, tilt test) [120,121]. ...
... According to one study, the extent of autonomic burden in hEDS is similar to that seen in fibromyalgia, both of which are comparatively more severe than that found in classic and vascular types of EDS [120]. Similar to the profile in autism, hEDS patients typically exhibit high resting sympathetic tone but blunted sympathetic reactivity to certain stimuli (e.g., valsalva maneuver, tilt test) [120,121]. Some individuals with these conditions, particularly those with POTS (mentioned in the previous section), also seem to exhibit a weakened baroreflex response due to dysregulated vagal (parasympathetic) efferent activity [102]. ...
Article
Full-text available
Considerable interest has arisen concerning the relationship between hereditary connective tissue disorders such as the Ehlers-Danlos syndromes (EDS)/hypermobility spectrum disorders (HSD) and autism, both in terms of their comorbidity as well as co-occurrence within the same families. This paper reviews our current state of knowledge, as well as highlighting unanswered questions concerning this remarkable patient group, which we hope will attract further scientific interest in coming years. In particular, patients themselves are demanding more research into this growing area of interest, although science has been slow to answer that call. Here, we address the overlap between these two spectrum conditions, including neurobehavioral, psychiatric, and neurological commonalities, shared peripheral neuropathies and neuropathologies, and similar autonomic and immune dysregulation. Together, these data highlight the potential relatedness of these two conditions and suggest that EDS/HSD may represent a subtype of autism.
... Authorities cite several hypotheses to explain the association between GI symptoms and chronic pain, including: Fig. 3 Comparison of the autonomic symptom profile between groups. Reprinted with permission from de Wandele, I., Calders, P., Peersman, W., Rimbaut, S., de Backer, T., Malfait, F., de Paepe, A. and Rombaut, L. (2014a). Autonomic symptom burden in the hypermobility type of Ehlers-Danlos syndrome: A comparative study with two other EDS types, fibromyalgia, and healthy controls. ...
... If cardiovascular in nature, symptoms can be managed with a combination of nonpharmacological strategies, such as a structured exercise training program, and some pharmacological support (see further reading). The noncardiovascular features of dysautonomia are dominated by GI dysfunction, with symptoms akin to irritable bowel syndrome (IBS), such as diarrhea, constipation and gastroparesis (De Wandele et al., 2014a) and thus a symptomatic treatment approach is recommended. A nutritional approach to symptom management may be also be advocated to some patients with an IBS-like profile, see section: "Nutritional Approach". ...
Chapter
https://doi.org/10.1016/B978-0-12-801238-3.65656-8 Ehlers-Danlos syndrome (EDS) comprises a heterogeneous group of noninflammatory disorders of connective tissue, characterized by varying degrees of joint hypermobility, skin hyperextensibility and tissue fragility with far-reaching, systemic complications. A growing body of evidence posits a putative relationship between EDS and disorders of the gastrointestinal (GI) tract. Case-reports and case-control studies suggest that a range of upper and lower GI symptoms may be associated with altered physiology in patients with EDS which cause considerable morbidity. Furthermore, the management of EDS-related GI abnormalities has also been described. The significant findings of the seminal studies will be explored throughout this article.
... The 2017 International Classification has been published for update the EDS nosology and develop best practice clinical guidelines on diagnosis of EDS recently [4]. Although hypermobile EDS is defined as benign, it is a structural predisposition leading to a decline in the quality of life due to multi-systemic manifestations [5][6][7][8][9]. ...
Article
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Objectives: To investigate the prevalence of joint hypermobility classes, hypermobility spectrum disorders, hypermobile Ehlers-Danlos syndrome and their relations with sex ina university population. They are notable topics in rehabilitation, since they represents the basis for some secondary disability conditions. Methods: Three hundred and thirty-five students met the inclusion criteria (university students who are not disabled, without known disease, aged 18-25 years). Joint hypermobility were classified as generalized, peripheral and localized asymptomatic or hypermobility spectrum disorders. Hypermobile Ehlers-Danlos syndrome was defined according to; 1) Brighton criteria with cutoff Beighton scoring ≥ 4/9, 2) Villefranche criteria with cutoff Beighton scoring ≥ 5/9, and 3) The 2017 International Classification of Ehlers-Danlos syndrome. Results: In total, 77.3% (n = 259) of participants had any class of joint hypermobility and 25.9% (n = 87) of them had generalized class. Asymptomatic joint hypermobility and hypermobility spectrum disorders prevalence in a university population were found to be 38.8% and 38.5%, respectively. Generalized, peripheral, localized asymptomatic joint hypermobility and hypermobility spectrum disorders were found; 13.1%, 4.2%, 21.5%, and 12.8%, 7.5%, 18.2%, respectively. Prevalence of hypermobile Ehlers-Danlos syndrome according to three classifications were found to be; 19.4%, 15.2%, and 1.2%, respectively. Conclusions: The most common classes are localized asymptomatic joint hypermobility in women and localized hypermobility spectrum disorders in men. Awareness of the prevalence of joint hypermobility, hypermobility spectrum disorders and hypermobile Ehlers-Danlos syndrome in healthy young population may contribute prevention of disability.
... seen in patients with joint hypermobility syndrome (JHS),23 which is regarded as identical to hEDS by several experts.24 Dysautonomia is a complex condition and possible explanations for the correlation between dysautonomia and hEDS include abnormalities in the structure or function of either the autonomic nervous system or the end organs due to defects of the connective tissue or the result of medication side effects.25 Some hEDS in the present study reported the use of different medications that can cause a xerostomic effect. ...
Article
Background: Ehlers-Danlos syndrome (EDS) is a hereditary disorder that affects the connective tissue and collagen structures in the body characterized by joint hypermobility, skin hyperextensibility and tissue fragility. Objective: The aim of the study was to investigate the oro-dental characteristics including measurements of tooth size of 26 patients with hypermobile EDS (hEDS), differentiated by a genetic test, compared to 39 healthy controls. Methods: Interview, clinical, and radiological examination on panoramic radiograph and cone-beam computed tomographic (CBCT) scan were performed. Statistical analyses included Fishers Exact Test, paired t-test and multiple logistic and linear models adjusted for age and gender. Results: The experience of xerostomia (p=0.039), local anesthetic insufficiency (p=<0.001) and tooth extraction complications (p=<0.003) were significantly higher in hEDS compared to controls. The debris index was significantly higher in hEDS (p=<0.001) and the distance between the cement-enamel-junction (CEJ) and the bone level on the upper left first incisor and -molar and the lower right first molar were significantly larger in hEDS compared to controls (p=0.021,p=0.024,p=0.021, respectively). The crown heights of the upper and lower first incisors were significantly smaller (p=0.001, p=0.003, p=0.002, p=<0,001, respectively) in hEDS compared to controls. When adjusting for debris index only the distance between CEJ and the marginal bone level on the upper left -and lower right molar was associated with hEDS. Conclusion: The results indicate that xerostomia, resistance to local anaesthesia, tooth extraction complications, poor oral hygiene, larger distance between CEJ and marginal bone level and small crown heights can be found in patients with hEDS. This article is protected by copyright. All rights reserved.
... 31 The HCTD population is known to have an increased prevalence of autonomic symptoms and orthostatic intolerance. [32][33][34][35] We have reported elsewhere on the diagnosis, surgical technique, and neurological outcomes of this cohort. 36 This paper addresses the prevalence of syncope, presyncope, and orthostatic intolerance in this cohort, and emphasizes the potential for improvement in autonomic symptoms after atlantoaxial stabilization surgery. ...
Article
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Background The proclivity to atlanto-axial instability (AAI) has been widely reported for conditions such as rheumatoid arthritis and Down syndrome. Similarly, we have found a higher-than-expected incidence of AAI in the hereditary connective tissue disorders. We demonstrate a strong association of AAI with manifestations of dysautonomia, in particular syncope and lightheadedness, and make preliminary observations as to the salutary effect of surgical stabilization of the atlanto-axial motion segment. Methods In an IRB-approved retrospective study, twenty subjects (16 women, 4 men) with hereditary connective tissue disorders had AAI diagnosed by CT. Subjects underwent realignment (reduction), stabilization and fusion of C1-C2 motion segment. All subjects completed pre-operative and postoperative questionnaires in which they were asked about performance, function and autonomic symptoms, including lightheadedness, pre-syncope, and syncope. Results All patients with AAI reported lightheadedness, and 15 had refractory syncope or pre-syncope despite maximal medical management and physical therapy. Postoperatively, subjects reported statistically significant improvement in lightheadedness (p=.003), pre-syncope (p=.006), and syncope (p=.03), and in the frequency (p < 0.05) of other symptoms related to autonomic function, such as nausea, exercise intolerance, palpitations, tremors, heat intolerance, gastroesophageal reflux, and sleep apnea. Conclusions This study draws attention to the potential for AAI to present with syncope or pre-syncope that is refractory to medical management, and for surgical stabilization of AAI to lead to improvement of these and other autonomic symptoms.
... hEDS is a complex, chronic disorder leading to disabilities that limit daily activities [2], and it affects many aspects of daily life. Several studies reported that hEDS causes physical and psychosocial impairments [9,10], and consequently, reduces participation in work [11]. "Living with limitations" is a central theme for patients with hEDS [12,13]. ...
Article
Background: “Ehlers–Danlos syndrome” (EDS) is a heritable connective disorder influencing multiple aspects of daily life. Most studies have focused on describing the physical symptoms and level of disability, but little knowledge exists about the psychosocial effects of the pathology. Participation in employment is an aspect that strongly influences quality of life of patients with chronic pathologies. This study, therefore, aimed to explore the lived experiences in employment participation of patients diagnosed with “hypermobile EDS”. Methods: An inductive thematic analysis, using semi-structured interviews was used. Nine patients, purposively selected by a continuum sampling strategy, were included. Interviews were audio-recorded and transcribed verbatim. Results: Data analysis resulted in three main themes: (1) elements assisting participation in employment, (2) limitations in employment participation, and (3) unemployment due to the “hypermobile EDS”. On the one hand, the results show that related health complaints can impede employment participation to an important extent. On the other hand, patients also report several aspects of work that can affect their well-being in a positive way. Conclusion: There are specific reasons for a person with “hypermobile EDS” to participate in employment. These reasons are different for each person and may even vary in time. • Implications for rehabilitation • “Hypermobile EDS” greatly impacts activities and participation in daily life. “Living with limitations” is the central theme in the lives of “Hypermobile EDS” patients. • Various aspects influence work participation in people with “Hypermobile EDS”, such as work pressure, tasks, and transport to work. • Work has positive effects in the lives of people with “Hypermobile EDS.” • Work can create difficulties when the job requirements and tasks do not match the functional abilities of a person with “Hypermobile EDS.”
... Furthermore, there is a growing evidence of autonomic nervous system dysfunction in G-HSD/hEDS, including symptoms such as hypotension, orthostatic intolerance, presyncope, palpitations, postural orthostatic tachycardia, gastrointestinal dysfunction, and disturbed bladder function [71,[79][80][81][82]. Autonomic dysfunction contributes to disability and decreased quality of life in G-HSD/hEDS [79,81]. In addition, increased autonomic dysfunctions were related to higher pain severity [82,83] and autonomic dysfunction may result in increased interoceptive sensitivity [84]. Higher pain severity in combination with increased interoceptive sensitivity may have additional emotional consequences such as anxiety and fear, which also may contribute to higher disability levels. ...
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Objectives A significant proportion of adolescents with chronic musculoskeletal pain (CMP) experience difficulties in physical functioning, mood and social functioning, contributing to diminished quality of life. Generalized joint hypermobility (GJH) is a risk factor for developing CMP with a striking 35-48% of patients with CMP reporting GJH. In case GJH occurs with one or more musculoskeletal manifestations such as chronic pain, trauma, disturbed proprioception and joint instability, it is referred to as generalized hypermobility spectrum disorder (G-HSD). Similar characteristics have been reported in children and adolescents with the hypermobile Ehlers-Danlos Syndrome (hEDS). In the management of CMP, a biopsychosocial approach is recommended as several studies have confirmed the impact of psychosocial factors in the development and maintenance of CMP. The fear-avoidance model (FAM) is a cognitive-behavioural framework that describes the role of pain-related fear as a determinant of CMP-related disability. Content Pubmed was used to identify existing relevant literature focussing on chronic musculoskeletal pain, generalized joint hypermobility, pain-related fear and disability. Relevant articles were cross-referenced to identify articles possibly missed during the primary screening. In this paper the current state of scientific evidence is presented for each individual component of the FAM in hypermobile adolescents with and without CMP. Based on this overview, the FAM is proposed explaining a possible underlying mechanism in the relations between GJH, pain-related fear and disability. Summary and outlook It is assumed that GJH seems to make you more vulnerable for injury and experiencing more frequent musculoskeletal pain. But in addition, a vulnerability for heightened pain-related fear is proposed as an underlying mechanism explaining the relationship between GJH and disability. Further scientific confirmation of this applied FAM is warranted to further unravel the underlying mechanism. In explaining disability in individuals with G-HSD/hEDS, it is important to focus on both the physical components related to joint hypermobility, in tandem with the psychological components such as pain-related fear, catastrophizing thoughts and generalized anxiety.
... However, there has been little assessment of this issue within the JHS/EDS-HT literature. In JHS/EDS-HT research populations women typically outnumber men, and in a recent study of autonomic dysfunction symptoms, the majority of men with EDS-HT did not want to complete the erectile dysfunction symptom profile, so its impact was not recorded [55]. These results indicate the need for greater support and recognition of potential intimacy issues in JHS/EDS-HT, particularly for health professionals in primary care, as problems with sexual functioning may markedly influence the patient's quality of life. ...
Article
Purpose: Little attention has been paid to psychosocial factors in Joint Hypermobility Syndrome and Ehlers–Danlos Syndrome (hypermobility type). This study sought to identify the psychosocial impact by examining participants’ lived experiences; and identify characteristics of effective coping. Materials and methods: Adults with Joint Hypermobility Syndrome and Ehlers–Danlos Syndrome (Hypermobility Type) were invited to discuss their own lived experiences and the impact of the condition. All met recognized criteria for clinically significant joint hypermobility, and had a self-confirmed diagnosis. The transcripts were coded and analyzed using inductive thematic analysis. Results: Seventeen participants (14 women, 3 men) purposively selected to broadly represent different genders, ages and ethnicities. Analysis identified five key themes: healthcare limitations, a lack of aware- ness of Joint Hypermobility, and Ehlers–Danlos Syndrome (Hypermobility Type) among healthcare profes- sionals; a restricted life; social stigma; fear of the unknown; and ways of coping. Conclusions: The results highlight the significant psychosocial impact on participants’ lives. Coping approaches identified included acceptance, building social networks, learning about joint hypermobility, and adapting activities. Physiotherapists supported regular exercise. Further research should consider potential interventions to improve information provision, address psychological support, and increase awareness of hypermobility among healthcare professionals.
... 4,14-16 One explanation for this variability is the use of separate methods of autonomic testing, ranging from questionnaires to validated measurements. 4,[14][15][16] In addition, studies have used different criteria for dysautonomia; some measured subjective presyncopal symptoms while others used specialized testing and exam maneuvers. 4,14-16 Even when utilizing formal diagnostic criteria, current literature is also limited by factors such as age, duration/type of challenge, or medication use during testing. ...
Article
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Ehlers-Danlos syndrome (EDS) is a multifaceted debilitating disease. Affected patients are at risk for complications such as joint hypermobility and cardiac disease, but the prevalence, course, and management of these conditions are not well understood. The objective of this retrospective cohort study was to investigate the demographic characteristics and systemic manifestations in EDS. We performed a retrospective analysis of 98 EDS patients seen in a physical medicine and rehabilitation clinic between January 2015 and April 2019. Charts were reviewed for demographic information, subtype of EDS, characteristics of musculoskeletal pain, and presence of certain systemic comorbid diagnoses: autonomic dysfunction, headaches/migraines, gastrointestinal conditions, cardiovascular anomalies, mast cell activation syndrome, and temporomandibular joint dysfunction. Of 98 patients, 75 were diagnosed with EDS-hypermobile type (EDS-HT); 94 patients were women, and the mean age was 36.7 years. On average, each patient reported involvement of 5.4 joints, with the shoulder, knee, and lumbar spine as the most common. The average number of comorbid systemic conditions was 2.8, of which autonomic dysfunction was the most common. This study aims to provide a better understanding of this disease to promote earlier and more accurate diagnoses to guide treatment and prevent complications.
... 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). ...
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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, 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) is a novel therapy combining cognitive approaches from clinical health psychology targeting the catastrophisation of internal sensations, with bio-behavioural training improving 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 anxiety, 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 the £11.7 billion that anxiety disorders cost the UK economy annually. WHO trial registration serial number 40233 registered 20/2/2019 available at https://doi.org/10.1186/ISRCTN17018615
... The mechanism of small nerve fiber degeneration in these patients is unclear. Autonomic complaints, especially POTS and gastrointestinal and bladder dysfunction are common in patients with EDS hypermobility type [66][67][68]. ...
Article
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Purpose of Review Small fiber neuropathy (SFN) could cause significant morbidity due to neuropathic pain and autonomic dysfunction. SFN is underdiagnosed and the knowledge on the condition is limited among general public and health care professionals. This review is intended to enhance the understanding of SFN symptoms, causes, diagnostic tools, and therapeutic options. Recent Findings There is evidence of SFN in up to 40% patients with fibromyalgia. The causes of SFN are glucose metabolism defect, dysimmune, gluten sensitivity and celiac disease, monoclonal gammopathy, vitamin deficiencies, toxic agents, cancer, and unknown etiology. Auto-antibodies targeting neuronal antigens trisulfated heparin disaccharide (TS-HDS) and fibroblast growth factor 3 (FGFR3) are found in up to 20% of patients with SFN. Treatment of SFN includes treating the etiology and managing symptoms. Summary SFN should be considered in patients with wide-spread body pain. The search for known causes of SFN is a crucial step in disease management.
... 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]. ...
Article
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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.
... 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]. ...
Article
Full-text available
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
... 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]. ...
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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.
... Symptoms of orthostatic intolerance can be debilitating (12). Associated syncope, fatigue, and migraines add to clinical burden and reduce quality of life (30). ...
Article
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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.
... FGD's are becoming increasingly recognised as being commonly associated with joint hypermobility (Fikree et al., 2017), especially in children (Kovacic et al., 2014). Other autonomic related comorbidities include Chronic Fatigue that may be directly related to the effects of the disease burden associated with autonomic symptoms (De Wandele et al., 2014). GJH is more common in individuals with Chronic Fatigue syndrome and Fibromyalgia, overlapping disorders, though diagnostically different, compared with healthy volunteers. ...
... 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). ...
Article
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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.
... 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. ...
Article
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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.
... 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]. ...
Article
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
Article
Die Ehlers-Danlos-Syndrome (EDS) sind eine Gruppe seltener, hereditärer, multisystemischer Bindegewebserkrankungen, die Gelenke, Sehnen, Muskeln, Organe, Haut und Gefäße betreffen können. Durch die Vielfalt der Symptome und die unterschiedliche Krankheitsausprägung selbst bei gleichem EDS-Typ ist die Diagnostik für viele Ärzte eine Herausforderung. Doch erstmals seit 20 Jahren wurden 2017 eine neue Klassifikation und striktere Kriterien veröffentlicht, die dazu beitragen sollen, dass Patienten schneller diagnostiziert und besser behandelt werden können. Laut der neuen Klassifikation differenziert man 13 Typen der Ehlers-Danlos-Syndrome, die sich durch ihre genetischen Ursachen und Verlaufsformen unterscheiden. Am häufigsten kommt das hypermobile EDS (hEDS) vor, welches gleichzeitig in Kombination mit anderen Komorbiditäten wie dem posturalen orthostatischen Tachykardiesyndrom (POTS), dem Mastzellaktivierungssyndrom (MCAS), der Osteoporose, der Neuropathie, der Myopathie, der Mitralklappeninsuffizienz und vielen anderen auftritt. Gerade aufgrund dieser Komorbiditäten ist die Behandlung der EDS schwierig und stellt die verschiedensten Fachärzte vor große Herausforderungen. Neue Managementguidelines widmen sich nicht nur der Behandlung, sondern fokussieren gleichermaßen auf die gegenseitige Beeinflussung durch komorbide Erkrankungen und geben einen Leitfaden für die derzeit nur symptomatische Therapie der EDS. Diese besteht aus konservativer physikalischer Therapie, einer Schmerztherapie, der Nutzung diverser Hilfsmittel, operativen Interventionen und der Behandlung aller komorbiden Faktoren, um die bestmögliche Lebensqualität zu erzielen. Die Krankheitsausprägung kann von leichter Hypermobilität bis zu schwerer körperlicher Behinderung reichen.
Article
Attention-deficit/hyperactivity disorder (ADHD) and generalized joint hypermobility (JH) are two separated conditions, assessed, and managed by different specialists without overlapping interests. Recently, some researchers highlighted an unexpected association between these two clinical entities. This happens in a scenario of increasing awareness on the protean detrimental effects that congenital anomalies of the connective tissue may have on human health and development. To review pertinent literature to identify possible connections between ADHD and generalized JH, special emphasis was put on musculoskeletal pain and syndromic presentations of generalized JH, particularly the hypermobile Ehlers–Danlos syndrome. A comprehensive search of scientific databases and references lists was conducted, encompassing publications based on qualitative and quantitative research. Impaired coordination and proprioception, fatigue, chronic pain, and dysautonomia are identified as potential bridges between ADHD and JH. Based on these findings, a map of the pathophysiological and psychopathological pathways connecting both conditions is proposed. Although ADHD and JH are traditionally separated human attributes, their association may testify for the dyadic nature of mind-body connections during critical periods of post-natal development. Such a mixed picture has potentially important consequences in terms of disability and deserves more clinical and research attention.
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Hypermobile Ehlers‐Danlos syndrome (hEDS) is a hereditary disorder of connective tissue, often presenting with complex symptoms can include chronic pain, fatigue, and dysautonomia. Factors influencing functional disability in the pediatric hEDS population are incompletely studied. This study's aims were to assess factors that affect quality of life in children and adolescents with hEDS. Individuals with hEDS between the ages 12–20 years and matched parents were recruited through retrospective chart review at two genetics clinics. Participants completed a questionnaire that included the Pediatric Quality of Life Inventory (PedsQL™), PedsQL Multidimentional Fatigue Scale, Functional Disability Inventory, Pain‐Frequency‐Severity‐Duration Scale, the Brief Illness Perception Questionnaire, measures of anxiety and depression, and helpful interventions. Survey responses were completed for 47 children and adolescents with hEDS/hypermobility spectrum disorder (81% female, mean age 16 years), some by the affected individual, some by their parent, and some by both. Clinical data derived from chart review were compared statistically to survey responses. All outcomes correlated moderately to strongly with each other. Using multiple regression, general fatigue and pain scores were the best predictors of the PedsQL total score. Additionally, presence of any psychiatric diagnosis was correlated with a lower PedsQL score. Current management guidelines recommend early intervention to prevent disability from deconditioning; these results may help identify target interventions in this vulnerable population.
Article
The hypermobile Ehlers–Danlos syndrome (hEDS) GENE study is a multicenter, cohort study with the goal to identify genes associated with hypermobile EDS. Of the 148 people enrolled in the hEDS GENE study, 98 meet the 2017 hEDS criteria, 27 have a hypermobility spectrum disorder (HSD) and 23 are asymptomatic family members. More than 80% of participants are female with an average age of 41 years. Each participant has completed seven questionnaires to quantify disease‐related symptomatology. People with hypermobility experience a variety of physical and somatic symptoms, especially in the areas of fatigue, kinesiophobia, gastrointestinal, and autonomic function. These cause a significant decrease in health‐related quality of life. The frequency and severity of most symptoms were indistinguishable between participants with hEDS and HSD; however, there were significant differences in autonomic symptoms. Less than 20% of participants had autoantibodies known to be associated with dysautonomia. Subtle symptomatic differences in people meeting the 2017 diagnostic criteria suggest focusing further etiologic studies on autonomic pathways.
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Background: Fibromyalgia is characterised by chronic widespread pain. Quality of life is further reduced by autonomic and cognitive symptoms, including subjective brain-fog and dissociative experiences. Although an association with joint hypermobility suggests variant connective tissue is a factor in both fibromyalgia and dysautonomia, the mechanisms underlying the neuropsychiatric symptoms are poorly understood. Methods: 21 fibromyalgia patients and 21 healthy controls were assessed for joint hypermobility dissociative experiences, autonomic symptoms and interoceptive sensibility. Mediation analyses were conducted according to the method of Baron and Kenny. Results: Patients with fibromyalgia reported greater dissociative experiences and autonomic symptoms. The relationship between fibromyalgia and dissociative experiences was fully mediated by symptoms of orthostatic intolerance. Fibromyalgia, dissociative experiences and orthostatic intolerance all were associated with joint hypermobility and interoceptive sensibility. Conclusions: This exploratory investigation highlights the relationship between dissociative experiences in the context of fibromyalgia and subjective experience of aberrant physiological responses. These findings can enhance the recognition and management of neuropsychiatric symptoms in patients with fibromyalgia, wherein dissociative experiences reflect disturbance of self-representation that can arise through abnormalities in internal agency, autonomic (dys)control and interoceptive prediction errors.
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Background Individuals with hypermobility spectrum disorders/hypermobile Ehlers‐Danlos syndrome (HSD/hEDS) frequently fulfill criteria for Rome IV functional gastrointestinal disorders (FGIDs). Postural orthostatic tachycardia syndrome (POTS) is also commonly reported in HSD/hEDS and may impact on co‐morbidity with and severity of FGIDs, although this remains to be studied. We determined the impact of concomitant POTS and HSD/hEDS on their association with Rome IV FGIDs. Methods With the help of the charity organization Ehlers‐Danlos Support UK, an online cross‐sectional health survey was completed by individuals with HSD/hEDS. The survey enquired for (a) self‐reported doctor diagnosis of POTS, chronic fatigue syndrome, and fibromyalgia, (b) the presence and symptom frequency of Rome IV FGIDs, and (c) anxiety and depression scores. Key Results Of 616 subjects with HSD/hEDS, 37.5% reported a doctor diagnosis of POTS. POTS‐positive individuals were significantly younger than POTS‐negative subjects (37 vs 40 years, P = 0.002), more likely to report chronic fatigue syndrome (44% vs 31%, P < 0.0001), and showed a trend toward increased prevalence of fibromyalgia (44% vs 37%, P = 0.06) and higher depression score (P = 0.07). POTS‐positive subjects were also more likely to fulfill criteria for Rome IV FGIDs across various organ domains and experienced both upper and lower gastrointestinal symptoms significantly more frequently. The increased associations for FGIDs and GI symptom frequency remained unchanged in HSD/hEDS subjects with POTS following adjustments for age, chronic fatigue syndrome, fibromyalgia, and depression scores. Conclusions and Inferences The high FGID burden in HSD/hEDS is further amplified in the presence of POTS. Future studies should elucidate the mechanism by which POTS arises in HSD/hEDS and is associated with increased GI symptoms.
Thesis
‘Ehlers-Danlos Syndrome’ (EDS) and ‘Hypermobility Spectrum Disorder’ (HSD) are chronic pathologies that often lead to disability, which in turn creates limited functioning and participation in daily life. This dissertation provides an overview of the research that has been conducted regarding this topic in the past years. Based on the results, we present conclusions on different levels of a person’s functioning. The use of the International Classification of Functioning, disability and health in the determination of a person’s functioning and disability has never been studied in a population of persons with EDS and HSD. Highlighting the effective level of participation (considering objective and subjective variables) is an important outcome measure. Furthermore, this dissertation emphasises the combination of two different research methodologies. First, we used a qualitative research method to explore the ‘lived experiences’ of persons with HSD and EDS. In the literature, no previous research has reported utilising this specific approach. Second, use used quantitative method to to determine the level of participation in persons with hEDS, cEDS, vEDS and HSD compared to persons with fibromyalgia and a healthy control group. No similar topics have been reported in literature within this population. The combination of both methods provide us with a rich overview of information on the levels of MICRO-, MESO- and MACRO-participation. MICRO-participation is influenced by EDS, mainly regarding the organisation of participants’ lives. The disease requires them to find a new balance, with a focus on personal priorities. EDS, and the functional consequences of this chronic disabling condition, markedly influence one’s personal life. Affected social relationships, difficulties in intimate relations and difficulties in taking care of the household chores, are important reasons for a lower participation level. MESO-participation, when the focus is on work-related capacities, is common in many persons with EDS and HSD. Finding work that is in line with your personal capacities seems to be hard, and executing tasks that exceed your personal limits, such as lifting heavy subject or repetitive jobs, often leads to leaving the labour market due to complications. On the other hand, work often also brings positive elements to the lives of persons with EDS and HSD, this ranges from socio-economic benefits to friendships. Working life can also be supported by external factors, such as workplace adaptations and financial benefits from the government. While discussing the level of MACRO-participation within a sample of persons with EDS and HSD, it seems obvious that persons with hEDS experience a significantly lower level of participation compared to a sample of healthy controls. This dissertation offers an overview of the level and difficulties in participating in society in persons with EDS and HSD and provides some relevant clinical recommendations. There is a strong need for correct and state-ofthe-art information. These endeavours include educating patients so that they are aware of their own condition and possibilities in societal participation, as well as informing (para)medical professionals in order to guide people to a correct diagnosis and subsequent treatment. Notably, this approach can only be achieved when including bio-psychosocial aspects within a multidisciplinary approach of persons with EDS and HSD.
Chapter
Gastroparesis presents with upper gastrointestinal symptoms of nausea, vomiting, bloating, abdominal discomfort, early satiety, and postprandial fullness. While the established definition of gastroparesis rests on gastric emptying delay without mechanical obstruction, patients may not always have delayed gastric emptying as the disease is chronic but can also wax and wane. A lack of widely used standards for assessing delayed gastric emptying may account for these findings. Gastroparesis has varying symptoms, stemming from differences in its underlying etiology. These exist not only from the main three etiologies of gastroparesis—idiopathic, diabetic, and postsurgical—but also from differences amongst its less well-known and less common etiologies. Additionally, patients with disorders of brain-gut interaction such as functional dyspepsia may report symptoms similar to gastroparesis that stem from syndromes entirely separate from gastroparesis itself. This chapter explores the full spectrum of these diseases and disorders from which patients report symptoms of gastroparesis.
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The importance of autonomic neurology has grown exponentially since the development of neuroscience, genetics, and immunology. Advances in this field have made it possible to elucidate the pathomechanism of dysautonomia and autonomic nervous system interactions in both health and disease. In the special issue “Recent Advances in Autonomic Neurology,” four articles covering a wide range of topics in clinical neuroscience, including degenerative diseases, genetic disorders, immune‐mediated neuropathy, and autoimmune encephalitis, were published. This review focused on presenting the recent progress in the clinical approaches for dysautonomia in autoimmune diseases, Ehlers‐Danlos syndrome, myalgic encephalomyelitis/chronic fatigue syndrome, and coronavirus disease 2019 (COVID‐19). Of particular current concern, is Long COVID, defined as the persistence of symptoms after 3 weeks from being infected with severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2), may involve autonomic dysfunction. The research and clinical practice for autonomic dysfunction in neurology is constantly evolving, which is exemplified by the current clinical research on Long COVID.
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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.
Article
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.
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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.
Article
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.
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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.
Article
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.
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Objective The aim of this study was to determine the basis of dissociative experiences in patients with fibromyalgia, testing a hypothesised link to ‘internal agency’ through interoception and autonomic control. Fibromyalgia is a complex polysymptomatic musculoskeletal disorder affecting 5% of the population. Common neuropsychiatric features include emotional fatigue, subjective cognitive dysfunction (e.g. ‘brain-fog’) and dissociation. The combination of brain-fog and dissociation is linked to higher levels of pain symptom intensity and decreased mental well-being. Patients describe such disturbances are as ‘nearly universal’ and important, yet the mechanisms underlying neuropsychiatric symptoms in fibromyalgia are poorly understood. Interestingly fibromyalgia is associated with dysautonomia, notably orthostatic intolerance. Moreover, fibromyalgia and dysautonomia (e.g. Postural Tachycardia Syndrome; PoTS) are both associated with connective tissue disorders, specifically joint hypermobility syndromes (Ehlers Danlos Syndrome hypermobile type; EDS-HT). Method Twenty-one patients with fibromyalgia (20 female; mean age 41.86 years) and twenty-two healthy controls (16 female; mean age 44.00 years) were recruited. Each participant completed the Dissociative Experiences Scale and the ASQoLS, which measures symptoms of autonomic dysfunction including orthostatic intolerance. All participants underwent assessment for joint hypermobility/EDS-HT using Brighton Criteria. Statistical comparison between groups was performed using independent samples t test. Mediation analyses were conducted according to the method of Baron and Kenny. Results Patients with fibromyalgia reported greater (mean, SEM) dissociative experiences (48.67, 9.99) than the control group (18.14, 2.72), (t40=2.95, p=0.005) and greater symptoms of orthostatic intolerance (41.90, 4.93) than controls (8.64, 1.02), (t41=6.611, p<0.001). The relationship between fibromyalgia (independent variable) and dissociation (dependent variable) remained significant after adjusting for the gender (r=0.391, p=0.011). This relationship was rendered non-significant when adjusted for symptoms of orthostatic intolerance (r=0.175, p=0.281), indicating full mediation. Interestingly all three variables (fibromyalgia, dissociative experiences and orthostatic intolerance) correlated significantly with the presence of joint hypermobility syndrome/EDS-HT. Conclusion In a patient population vulnerable to neuropsychiatric symptoms, we found that dissociative experiences are fully mediated by symptoms of orthostatic intolerance. This is also the first study, to our knowledge, to explore dissociation and orthostatic intolerance in the context of fibromyalgia. Moreover, dissociation and brain-fog appear closely linked and are frequently reported by both patients with fibromyalgia and those with PoTS. Our observations are consistent with the hypothesised basis to dissociative symptoms in abnormalities in self-representation and internal agency linked to autonomic control and interoceptive prediction, revealed by subjective symptoms of orthostatic intolerance. This study suggests possibilities for recognition and treatment of neuropsychiatric symptoms.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
Article
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.
Article
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.
Article
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.
Chapter
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.
Chapter
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.
Article
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.
Article
To describe medication use, surgery, and physiotherapy, and to examine the effect of these treatment modalities on functional impairment and amount of complaints among patients with the hypermobility type of Ehlers-Danlos syndrome (EDS-HT). Cross-sectional study. Physical and rehabilitation medicine department and center for medical genetics. Patients with EDS-HT (N=79; 8 men, 71 women) were recruited for this study. Not applicable. Patients filled out questionnaires regarding type of complaints, medication use, surgery, physiotherapy, and outcome of treatment. Functional impairment in daily life was measured by the Sickness Impact Profile. Pain severity was assessed with visual analog scales. Patients reported a large number of complaints, a considerable presence of severe pain, and a clinically significant impact of disease on daily functioning. Most patients (92.4%) used medications, among which analgesics were the most prevalent. Fifty-six patients (70.9%) underwent surgery, including mainly interventions of the extremities and abdomen. Forty-one patients (51.9%) are currently enrolled in a physical therapy program, mainly comprising neuromuscular exercises, massage, and electrotherapy. Patients with a high consumption of analgesics, who visited the physiotherapist, or who underwent surgery had a higher dysfunction in daily life. Only 33.9% of the patients who underwent surgery and 63.4% of patients in physical therapy reported a positive outcome. Patients with EDS-HT have numerous complaints and an impaired functional status that strongly determine their high rate of treatment consumption. The outcome of surgical and physiotherapy treatment is disappointing in a large percentage, which illustrates a strong need for evidence-based therapy.