Inge De Wandele

Dysautonomia and its underlying mechanisms in the hypermobility type of Ehlers–Danlos syndrome

OBJECTIVESnMany non-musculoskeletal complaints in EDS-HT may be related to dysautonomia. This study therefore aims to investigate whether dysautonomia is present and to explore the underlying mechanisms.nnnMETHODSnA total of 39 females with EDS-HT and 35 age-matched controls underwent autonomic function testing. Resting autonomic tone was assessed using heart rate variability (frequency domain) and baroreflex sensitivity analysis (cross correlation). Autonomic reactivity was assessed using the Autonomic Reflex Screen test battery. Factors suspected to contribute to dysautonomia, e.g., neuropathy, medication use, decreased physical activity, depression, pain-induced sympathetic arousal, and connective tissue laxity, were quantified using validated questionnaires, the Beighton score, and measurement of skin extensibility.nnnRESULTSnThe EDS-HT group showed autonomic deregulation with increased sympathetic activity at rest and reduced sympathetic reactivity to stimuli. Increased resting activity was indicated by a higher LF/HF ratio compared to controls (1.7 ± 1.23 vs 0.9 ± 0.75, p = 0.002); decreased reactivity by a greater BP fall during valsalva (-19 ± 12 vs -8 ± 10, p < 0.001), and a smaller initial diastolic BP increase during tilt (7% vs 14%, p = 0.032). Orthostatic intolerance was significantly more prevalent in EDS-HT than controls (74% vs 34%) and was most frequently expressed as postural orthostatic tachycardia. Lowered QSART responses suggest that sympathetic neurogenic dysfunction is common in patients (p < 0.013), which may explain the dysautonomia in EDS-HT. Further, connective tissue laxity and vasoactive medication use were identified as important factors in aggravating dysautonomia (p < 0.035).nnnCONCLUSIONnDysautonomia consisting of cardiovascular and sudomotor dysfunction is present in EDS-HT. Neuropathy, connective tissue laxity, and vasoactive medication probably play a role in its development.

Chronic pain in patients with the hypermobility type of Ehlers–Danlos syndrome: evidence for generalized hyperalgesia

Chronic widespread pain is highly present in patients with the Ehlers–Danlos syndrome hypermobility type (EDS-HT), but up to now, evidence for generalized hyperalgesia is lacking. The aim of this study is to investigate whether pressure pain thresholds (PPTs) at both symptomatic and asymptomatic body areas differ in EDS-HT patients compared to healthy subjects. Twenty-three women with EDS-HT and 23 gender- and age-matched healthy controls participated. All subjects marked on Margolis Pain Diagram where they felt pain lasting longer than 24xa0h in the past 4 weeks. Then, they completed several questionnaires assessing pain cognitions, fatigue, disability, and general health status, in order to take the possible influence of these factors on PPTs into account. Patients also completed a form concerning the type of pain they experienced. Thereupon, a blinded researcher assessed PPTs at 14 body locations on the trunk and extremities. PPTs were compared for the two complete groups. In addition, PPTs of patients and controls who did not report pain in a respective zone were compared. PPTs of the patients were significantly lower compared to those of the control group, also when pain-free samples per zone were compared. The mean (SD) PPT was 2.9 (1.62) kg/cm2 in the EDS-HT patients and 5.2 (1.88) kg/cm2 in the controls (Pu2009<u20090.001). No confounding factors responsible for the observed differences could be revealed. In half of the patient group, a predominantly neuropathic pain component was likely present. This study provides evidence for the existence of hyperalgesia even in asymptomatic areas (generalized secondary hyperalgesia). The generalized hyperalgesia may represent the involvement of a sensitized central nervous system, which inquires an adapted pain management for this patient group.

Autonomic symptom burden in the hypermobility type of Ehlers–Danlos syndrome: A comparative study with two other EDS types, fibromyalgia, and healthy controls

AIMnThis study provides insight into the profile and importance of autonomic symptoms in the hypermobility type (HT) of Ehlers-Danlos syndrome (EDS). The impact of these symptoms is put into perspective by comparing with fibromyalgia (FM) and two other EDS types.nnnMETHODSnOverall, 80 patients with EDS-HT participated, as well as 11 with classical EDS (cEDS), seven with vascular EDS (vEDS), 38 with FM, and 43 healthy controls. All participants filled out the autonomic symptom profile (ASP). Furthermore, they were inquired about quality of life (QOL, SF-36) and factors contributing to the EDS disease burden, e.g., hypermobility (5-point questionnaire, GHQ), fatigue (checklist individual strength, CIS), pain (pain detect questionnaire, PDQ), affective distress (hospital anxiety and depression scale, HADS), and physical activity (Baecke).nnnRESULTSnThe total autonomic symptom burden was higher in EDS-HT (57.9 ± 21.57) than in controls (11.3 ± 19.22), cEDS (32.3 ± 19.47), and vEDS (29.1 ± 19.18), but comparable to FM (53.8 ± 19.85). Especially orthostatic and gastrointestinal complaints were prevalent. The importance of autonomic symptoms in EDS-HT was emphasized by the correlation with lowered QOL (r = -0.402), fatigue (r = 0.304), and pain severity (r = 0.370). Although affective distress and decreased physical activity are often suggested as possible causes for dysautonomia, the ASP did not correlate with the HADS and Baecke score. By contrast, the correlation of the GHQ (r = 0.298) and PDQ (r = 0.413) with the ASP supports the hypothesis that joint hypermobility and neuropathy may play a role in the development of autonomic symptoms.nnnCONCLUSIONnAutonomic symptoms, especially orthostatic and gastrointestinal complaints, are frequent extraarticular manifestations of EDS-HT and contribute to the disease burden.

Orthostatic intolerance and fatigue in the hypermobility type of Ehlers-Danlos Syndrome

OBJECTIVEnTo investigate whether orthostatic intolerance (OI) is a significant predictor for fatigue in Ehlers-Danlos Syndrome, hypermobility type (EDS-HT).nnnMETHODSnEighty patients with EDS-HT and 52 controls participated in the first part of the study, which consisted of questionnaires. Fatigue was evaluated using the Checklist Individual Strength (CIS). As possible fatigue determinants OI [Autonomic Symptom Profile (ASP)], habitual physical activity (Baecke), affective distress [Hospital Anxiety and Depression Scale (HADS)], pain (SF36), medication use and generalized hypermobility (5-point score of Grahame and Hakim regarding generalized joint hypermobility) were studied. Next, a 20 min head-up tilt (70°) was performed in a subsample of 39 patients and 35 controls, while beat-to-beat heart rate and blood pressure were monitored (Holter, Finometer Pro). Before and after tilt, fatigue severity was assessed using a numeric rating scale.nnnRESULTSnPatients scored significantly higher on the CIS [total score: EDS: 98.2 (18.63) vs controls: 45.8 (16.62), P < 0.001] and on the OI domain of the ASP [EDS: 22.78 (7.16) vs controls: 6.5 (7.78)]. OI was prevalent in EDS-HT (EDS: 74.4%, controls: 34.3%, P = 0.001), and frequently expressed as postural orthostatic tachycardia (41.0% of the EDS group). Patients responded to tilt with a higher heart rate and lower total peripheral resistance (p < 0.001; p = 0.032). This altered response correlated with fatigue in daily life (CIS). In the EDS-HT group, tilt provoked significantly more fatigue [numeric rating scale increase: EDS: +3.1 (1.90), controls: +0.5 (1.24), P < 0.001]. Furthermore, the factors OI, pain, affective distress, decreased physical activity and sedative use explained 47.7% of the variance in fatigue severity.nnnCONCLUSIONnOI is an important determinant of fatigue in EDS-HT.

The evidence-based rationale for physical therapy treatment of children, adolescents, and adults diagnosed with joint hypermobility syndrome/hypermobile Ehlers Danlos syndrome

New insights into the phenotype of Joint Hypermobility Syndrome (JHS) and Ehlers‐Danlos Syndrome‐hypermobile type (hEDS) have raised many issues in relation to classification, diagnosis, assessment, and treatment. Within the multidisciplinary team, physical therapy plays a central role in management of individuals with hypermobility related disorders. However, many physical therapists are not familiar with the diagnostic criteria, prevalence, common clinical presentation, and management. This guideline aims to provide practitioners with the state of the art regarding the assessment and management of children, adolescents, and adults with JHS/hEDS. Due to the complexity of the symptoms in the profile of JHS/hEDS, the International Classification of Functioning, Disability and Health (ICF) is adopted as a central framework whereby the umbrella term of disability is used to encompass functions, activities and participation, as well as environmental and personal factors. The current evidence‐based literature regarding the management of JHS/hEDS is limited in size and quality and there is insufficient research exploring the clinical outcomes of a number of interventions. Multicenter randomized controlled trials are warranted to assess the clinical and cost‐effectiveness of interventions for children and adults. Until further multicenter trials are conducted, clinical decision‐making should be based on theoretical and the current limited research evidence. For all individuals diagnosed with JHS/hEDS, international consensus and combined efforts to identify risk profiles would create a better understanding of the pathological mechanisms and the potential for optimizing health care for affected individuals.

Cardiovascular autonomic dysfunction in Ehlers–Danlos syndrome—Hypermobile type

Autonomic dysfunction contributes to health‐related impairment of quality of life in the hypermobile type of Ehlers–Danlos syndrome (hEDS). Typical signs and symptoms include tachycardia, hypotension, gastrointestinal dysmotility, and disturbed bladder function and sweating regulation. Cardiovascular autonomic dysfunction may present as Orthostatic Intolerance, Orthostatic Hypotension, Postural Orthostatic Tachycardia Syndrome, or Neurally Mediated Hypotension. The incidence, prevalence, and natural history of these conditions remain unquantified, but observations from specialist clinics suggest they are frequently seen in hEDS. There is growing understanding of how hEDS‐related physical and physiological pathology contributes to the development of these conditions. Evaluation of cardiovascular symptoms in hEDS should include a careful history and clinical examination. Tests of cardiovascular function range from clinic room observation to tilt‐table assessment to other laboratory investigations such as supine and standing catecholamine levels. Non‐pharmacologic treatments include education, managing the environment to reduce exposure to triggers, improving cardiovascular fitness, and maintaining hydration. Although there are limited clinical trials, the response to drug treatments in hEDS is supported by evidence from case and cohort observational data, and short‐term physiological studies. Pharmacologic therapy is indicated for patients with moderate‐severe impairment of daily function and who have inadequate response or tolerance to conservative treatment. Treatment in hEDS often requires a focus on functional maintenance. Also, the negative impact of cardiovascular symptoms on physical and psycho‐social well‐being may generate a need for a more general evaluation and on‐going management and support.

Knowledge, assessment, and management of adults with joint hypermobility syndrome/Ehlers–Danlos syndrome hypermobility type among flemish physiotherapists

Physiotherapy plays a fundamental role in managing adults with the joint hypermobility syndrome/Ehlers–Danlos syndrome hypermobility type (JHS/EDS‐HT). However, it is a challenge for both the patient and the physiotherapist as the condition is poorly understood and treatment for JHS/EDS‐HT is currently undefined. Insight into current practice is, therefore, necessary in order to establish baseline knowledge in this area and in the long term to improve the standard of patient care. Therefore, the purpose of this study was to evaluate current physiotherapists knowledge of JHS/EDS‐HT and to gain insight into current physiotherapy practice with emphasis on assessment, management, and treatment efficacy. Three hundred twenty‐five Flemish physiotherapists participated in the study by filling out electronically a modified version of the “Hypermobility and Hypermobility Syndrome Questionnaire” (HHQ), which covered theoretical constructs such as general knowledge, assessment, management, and learning in relation to generalized joint hypermobility and JHS/EDS‐HT. The results show that physiotherapists report a low level of confidence with regard to assessment and management of JHS/EDS‐HT. Knowledge of hypermobility and JHS/EDS‐HT is weak, especially regarding the features associated with JHS/EDS‐HT. Many treatment approaches are used by physiotherapists with the majority showing preference for education, reassurance, muscle strengthening, proprioceptive and core stability training. Almost all approaches were perceived as being clinically effective by the physiotherapists, highlighting a lack of consensus. In conclusion, this study in Flemish physiotherapists confirms that JHS/EDS‐HT is under‐recognized, not well known and deemed difficult to treat. Further education is required and sought by the physiotherapists surveyed, and future research is needed.

Chronic fatigue in Ehlers–Danlos syndrome—Hypermobile type

Chronic fatigue is an important contributor to impaired health‐related quality of life in Ehlers–Danlos syndrome. There is overlap in the symptoms and findings of EDS and chronic fatigue syndrome. A proportion of those with CFS likely have EDS that has not been identified. The evaluation of chronic fatigue in EDS needs to include a careful clinical examination and laboratory testing to exclude common causes of fatigue including anemia, hypothyroidisim, and chronic infection, as well as dysfunction of major physiological or organ systems. Other problems that commonly contribute to fatigue in EDS include sleep disorders, chronic pain, deconditioning, cardiovascular autonomic dysfunction, bowel and bladder dysfunction, psychological issues, and nutritional deficiencies. While there is no specific pharmacological treatment for fatigue, many medications are effective for specific symptoms (such as headache, menstrual dysfunction, or myalgia) and for co‐morbid conditions that result in fatigue, including orthostatic intolerance and insomnia. Comprehensive treatment of fatigue needs to also evaluate for biomechanical problems that are common in EDS, and usually involves skilled physical therapy and attention to methods to prevent deconditioning. In addition to managing specific symptoms, treatment of fatigue in EDS also needs to focus on maintaining function and providing social, physical, and nutritional support, as well as providing on‐going medical evaluation of new problems and review of new evidence about proposed treatments.

Autonomic symptoms in patients with moderate and severe chronic obstructive pulmonary disease

Abstract 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.

Postural tachycardia syndrome and other forms of orthostatic intolerance in Ehlers-Danlos syndrome

OBJECTIVEnTo review the association between orthostatic intolerance syndromes and both joint hypermobility and Ehlers-Danlos syndrome, and to propose reasons for identifying hereditary connective tissue disorders in those with orthostatic intolerance in the context of both clinical care and research.nnnMETHODSnWe searched the published peer-reviewed medical literature for papers reporting an association between joint hypermobility or Ehlers-Danlos syndrome and orthostatic intolerance.nnnRESULTSnWe identified 10 relevant papers. Although methodological variability between studies introduces some limitations, the published literature consistently identifies a significantly higher prevalence of orthostatic intolerance symptoms in patients with joint hypermobility or Ehlers-Danlos syndrome than in healthy controls, and a significantly higher prevalence of cardiovascular and autonomic abnormalities both at rest and during orthostatic challenge. Postural tachycardia syndrome is the most commonly recognized circulatory disorder. The severity of orthostatic symptoms in those with EDS correlates with impairments in quality of life.nnnCONCLUSIONnThere is a strong association between several forms of cardiovascular dysfunction, most notably postural tachycardia syndrome, and joint hypermobility or Ehlers-Danlos syndrome. We propose that recognition of joint hypermobility and Ehlers-Danlos syndrome among those with orthostatic intolerance syndromes has the potential to improve clinical care and the validity of research findings.