Comprehensive Assessment of Nutrition and Dietary Influences in Hypermobile Ehlers-Danlos Syndrome-A Cross-Sectional Study.

INTRODUCTION: Disorders of gut-brain interaction (DGBI) are common in patients with hypermobile Ehlers-Danlos syndrome/hypermobility spectrum disorder (hEDS/HSD). Food is a known trigger for DGBI symptoms, which often leads to dietary alterations and, increasingly, nutrition support. We aimed to explore dietary behaviors and influencing factors in patients with hEDS/HSD. METHODS: In a cross-sectional study, patients with hEDS/HSD were recruited from Ehlers-Danlos Support UK (nontertiary) and tertiary neurogastroenterology clinics to complete questionnaires characterizing the following: dietary behaviors, nutrition support, DGBI (Rome IV), gastrointestinal symptoms, anxiety, depression, avoidant restrictive food intake disorder (ARFID), mast cell activation syndrome, postural tachycardia syndrome (PoTS), and quality of life. We used stepwise logistic regression to ascertain which factors were associated with dietary behaviors and nutrition support. RESULTS: Of 680 participants (95% female, median age 39 years), 62.1% altered their diet in the last year and 62.3% regularly skipped meals. Altered diet was associated with the following: reflux symptoms ( P < 0.001), functional dyspepsia ( P = 0.008), reported mast cell activation syndrome ( P < 0.001), and a positive screen for ARFID, specifically fear of eating and low interest ( P < 0.001). Approximately 31.7% of those who altered their diet required nutrition support. The strongest predictor of requiring nutrition support was a positive screen for ARFID, specifically fear of eating (OR: 4.97, 95% CI: 2.09-11.8, P < 0.001). DISCUSSION: Altered diet is very common in the patients with hEDS/HSD we studied and influenced by functional dyspepsia, reflux symptoms, and ARFID. Those with ARFID have a 4-fold increased risk of requiring nutrition support, and therefore, it is paramount that psychological support is offered in parallel with dietary support in the management of DGBI in hEDS/HSD.

Patients' strategies for numeric pain assessment: a qualitative interview study of individuals with hypermobile Ehlers-Danlos Syndrome.

PURPOSE: Chronic pain is a common feature of hypermobile Ehlers-Danlos Syndrome (hEDS), yet how patients assess and communicate their pain remains poorly understood. The objective of the present study was to explore the use of numeric pain assessment in individuals with hEDS, from a patient-centered perspective. MATERIALS AND METHODS: Our analysis is based on in-depth qualitative interviews. The interviews were conducted over the phone. Our participants were patients living with hEDS (N = 35). Interviews were recorded, transcribed, and analyzed to identify factors related to their use of these pain assessment instruments. RESULTS: Three primary themes emerged from these data, namely, (1) confusion around the quantification of multidimensional pain, (2) the subjectivity of pain experience, and (3) a strategic use of assessments for practical purposes beyond the accurate representation of pain.These results demonstrate the need for caution in relying exclusively on numeric pain assessment instruments. We conclude with a brief proposal for a clinical communication strategy that may help to address the limitations of numeric pain assessment that were identified in our interviews.

Chronic pain is a common feature of hypermobile Ehlers­Danlos Syndrome (hEDS), yet how patients assess and communicate their pain remains poorly understood.Clinicians should be aware that patients have difficulties with the Numeric Rating Scale (NRS) for at least three reasons: (1) confusion around the quantification of multidimensional pain, (2) the subjectivity of pain experience, and (3) a strategic use of assessments for practical purposes beyond the accurate representation of pain.Clinicians should use caution in relying exclusively on NRS instruments.Clinicians may benefit from using clinical communication strategies outlined in our paper, which may help to address the limitations of the NRS that were identified in our interviews.

Assessment of functional respiratory complaints and related factors in people with hypermobile Ehlers-Danlos syndrome: Cross-sectional study.

BACKGROUND: Hypermobile Ehlers-Danlos Syndrome (hEDS) is the most common type of EDS. Apart from joint symptoms, people with hEDS have systemic manifestations as a chronic modification of the breathing pattern (functional respiratory complaints (FRCs)) and mental disorders. However, the prevalence of FRCs, and its relationship with mental disorders, have not yet been estimated for this population. OBJECTIVES: To assess the FRCs, central sensitization, disease perception, depression, and anxiety in people with hEDS from Belgium; and to identify the clustering of FRCs and determine any association with the characteristics assessed for this sample. METHODS: This cross-sectional study assessed socio-demographic characteristics, Nijmegen questionnaire (NQ), Central Sensitization Inventory (CSI), Brief Illness Perception Questionnaire, and the Hospital Anxiety and Depression Scale (HADS) in people with hEDS from Belgium. A two-step cluster analysis was performed to identify clusters according to NQ, and to understand how the other questionnaires are grouped among these clusters. RESULTS: The Spearman correlation coefficients showed that all the outcomes were significantly and positively correlated with each other (p<0.05). Furthermore, 84.9% of the sample had symptoms suggestive of FRCs, and 54.3% had probable anxiety. Three clusters were grouped (no FRCs, mild FRCs, and severe FRCs), with NQ, HADS-D and CSI-part A being the variables that contributed the most. People from cluster of severe FRCs got the worst scores for all the questionnaires. CONCLUSION: FRCs, central sensitization, depression, and anxiety are prevalent comorbidities in people with hEDS. Moreover, those people with FRCs had worse results in the investigated parameters, with depression being the variable that contributed the most to the clusters of FRCs. Consequently, investigating mechanisms for these co-occurring symptom profiles may improve our understanding of pathogenesis and indicate new management strategies to alleviate these symptoms and lead to the development of more effective care for persons with hEDS.

Assessment of gastrointestinal function and its' effect on bone mineral density and body composition in hypermobility spectrum disorder and hypermobile Ehlers-Danlos syndrome.

BACKGROUND: Hypermobile Ehlers-Danlos Syndrome (hEDS) and Hypermobility Spectrum Disorders (HSD) are associated with hypermobility, musculoskeletal pain, a decreased bone mineral density (BMD) and gastrointestinal (GI) complications. The role of GI symptoms and diet in BMD has not been established in this population. The GI complications can lead to an energy deficit due to lack of essential macronutrients. The primary objective of this study was to determine the severity of GI symptoms compared to body composition and BMD in individuals with hEDS/HSD. The secondary objective is to examine GI symptoms on energy balance, body composition and strength. METHODOLOGY: This study was IRB approved. Eighteen female participants (aged 28.2 ± 4.9; BMI 22.5 ± 4.9) with a diagnosis of hEDS or HSD and 18 female healthy control participants (aged 28.1 ± 3.8; BMI 22.8 ±3.9) signed consent to participate. Participants were matched by sex, age, and BMI. The Gastrointestinal Symptom Rating Scale (GSRS) was used to investigate severity of GI symptoms. Dual X-ray absorptiometry was used to determine body composition (body fat%, lean body mass (LBM). BMD was measured by Z- scores of both femurs and lumbar spine. Resting metabolic rate (RMR) was measured using indirect calorimetry and strength was determined using a hand grip dynamometer. RESULTS: All hEDS/HSD participants reported GI symptoms. There was no difference in body composition between hEDS/HSD and controls. Participants with hEDS/HSD had lower BMD both femoral z scores (p=0.02,0.004) and spine z scores (p= 0.04). There was no difference in caloric intake between groups; yet both groups demonstrated caloric deficits. Additionally, hEDS/HSD consumed less protein and more carbohydrates (p=0.03, p=0.03). There were no differences in grip strength. CONCLUSIONS: This study identified that pre-menopausal women with hEDS/HSD presented with significant GI complications and lower BMD than age matched controls. The GI complications and the reduced protein intake long-term may have a lasting impact on bone health. This study found that the GSRS identified and quantified GI symptoms in persons with hEDS/HSD. Future studies are needed for the longitudinal effects of a caloric/protein deficit in this population and to help guide future preventive and nutritional treatment approaches in individuals with hEDS/HSD.

Gastrointestinal medication burden among persons with the Ehlers-Danlos syndromes.

BACKGROUND: The Ehlers-Danlos syndromes (EDSs) are a group of heritable disorders of connective tissue associated with an increased prevalence of both structural and functional GI conditions. METHODS: We used 10 years (2005-2014) of administrative claims data comprised of 4294 people with clinician-diagnosed EDS, aged 5-62 years, and compared their frequency of GI drug prescription claims to their age-, sex-, state of residence-, and earliest claim date-matched controls. We categorized the GI medications into the following groups: acid suppressants, anti-emetics, irritable bowel syndrome drugs, and visceral hypersensitivity (VHS) medications. KEY RESULTS: Compared to controls, a significantly higher proportion of persons with EDS had prescription claims for at least one GI drug group, as well as for drugs in each of the four GI drug groups included in our study. By age-group, 25.7% children and 45.1% adults with EDS had prescription claims for at least one GI drug group compared with only 7.4% and 21.0% of controls, respectively (p < 0.0001). By gender, 44.0% of women and 25.3% of men with EDS had prescription claims for at least one class of GI drugs compared with 19.2% and 9.6% of controls, respectively (p < 0.0001). CONCLUSIONS AND KEY INFERENCES: Predominant medication burden occurs among women with EDS, beginning peri-pubertally for anti-emetics and VHS drugs. High GI medication burden underscores previous evidence that GI dysmotility is common among persons with EDS.

Trends of vascular surgery procedures in Marfan syndrome and Ehlers-Danlos syndrome.

OBJECTIVES: Marfan syndrome and Ehlers-Danlos syndrome represent two connective tissue vascular diseases requiring unique consideration in their vascular surgical care. A comprehensive national review encompassing all hospitalizations for the Marfan Syndrome and Ehlers-Danlos syndrome patient population is lacking. METHODS: The National (Nationwide) Inpatient Sample from 2010 to 2014 was reviewed for all inpatient vascular surgery procedures including those with a diagnosis of Marfan syndrome and Ehlers-Danlos syndrome. National estimates of vascular surgery rates were generated from provided weights. Patient demographics, procedure type, and outcomes were assessed. RESULTS: There were 3103 Marfan syndrome and 476 Ehlers-Danlos syndrome vascular procedures identified as well as 3,895,381 vascular procedures in the remainder of population (control group). The percent of aortic procedures from all vascular procedures in Marfan syndrome (23.5%) and Ehlers-Danlos syndrome (23.5%) were 2.5-fold higher than controls (9.1%), p < 0.0001. Open aortic aneurysm repair was also significantly greater in both Marfan syndrome (16.8%) and Ehlers-Danlos syndrome (11.2%) compared to controls (4.4%), p < 0.0001. Endovascular aortic repair (p < 0.2302) was similar among the groups. Marfan syndrome (7.7%) and Ehlers-Danlos syndrome (5.1%) had more thoracic endovascular aortic repair performed than controls (0.7%), p < 0.0001. Percutaneous procedures were fewer in Marfan syndrome (6.3%) than controls (31.3%) and Ehlers-Danlos syndrome (26.3%), p < 0.0001, while repair of peripheral arteries was greater in Marfan syndrome (5.9%) and Ehlers-Danlos syndrome (4.1%) than controls (1.5%), p < 0.0001. For total aortic procedures, the mean age of aortic procedures was 68.2 years in controls vs 45.8 years in Marfan syndrome and 55.3 years in Ehlers-Danlos syndrome, p < 0.0001. Marfan syndrome and Ehlers-Danlos syndrome had fewer comorbidities overall, while controls had significantly higher rates of coronary artery disease (controls 39.9% vs Marfan syndrome 8.3% and Ehlers-Danlos syndrome 13.0%, p < 0.0001), peripheral vascular disease (controls 34.5% vs Marfan syndrome 4.2% and Ehlers-Danlos syndrome 8.7%, p < 0.0001), and diabetes (controls 20.6% vs Marfan syndrome 6.6 and Ehlers-Danlos syndrome 4.4%, p < 0.0001). Marfan syndrome and Ehlers-Danlos syndrome had higher overall complication rate (65.5% and 52.2%) compared to controls (44.6%), p < 0.0001. Postoperative hemorrhage was more likely in Marfan syndrome (42.9%) and Ehlers-Danlos syndrome (39.1%) than controls (22.2%), p < 0.0001. Increased respiratory failure was noted in Marfan syndrome (20.2%) vs controls (10.7%) and Ehlers-Danlos syndrome (8.7%), p = .0003. Finally, length of stay was increased in Marfan syndrome 12.5 days vs Ehlers-Danlos syndrome 7.4 days and controls 7.2 days (p < 0.0001) as well as a higher median costs of index hospitalization in Marfan syndrome ($57,084 vs Ehlers-Danlos syndrome $22,032 and controls $26,520, p < 0.0001). CONCLUSIONS: Patients with Marfan syndrome and Ehlers-Danlos syndrome differ from other patients undergoing vascular surgical procedures, with a significantly higher proportion of aortic procedures including open aneurysm repair and thoracic endovascular aortic repair. While they are younger with fewer comorbidities, due to the unique pathogenesis of their underlying connective tissue disorder, there is an overall higher rate of procedural complications and increased length of stay and cost for Marfan syndrome patients undergoing aortic surgery.

The Case of Ms D: A Family's Request for Posthumous Procurement of Ovaries.

The MedStar Washington Hospital Center clinical ethics team became involved in a case when the family requested the posthumous removal of a patient's ovaries for future reproductive use. This case presents a novel question for clinical ethicists, since the technology for posthumous female reproduction is still in development. In the bioethics literature, the standard position is to refuse to comply with such a request, unless there is explicit consent or evidence of explicit conversations that demonstrate the deceased would have wanted this option pursued. Ms D's case, we suggest, offers an exception to this default position; complying with the family's request could have been ethically permissible in this case, had it been medically feasible.

Pain control methods in use and perceived effectiveness by patients with Ehlers-Danlos syndrome: a descriptive study.

PURPOSE: The purpose of this study was to assess the pain control methods in use by patients who have Ehlers-Danlos Syndrome (EDS), a group of connective tissue disorders, and their perceived effectiveness. METHOD: This descriptive study involved 1179 adults diagnosed with EDS who completed an anonymous on-line survey. The survey consisted of demographics information, the Patient Reported Outcomes Measurement Information System (PROMIS) Pain-Behavior, PROMIS Pain-Interference, and Neuro QOL Satisfaction with Social Roles and Activities scales, as well as a modified version of the Pain Management Strategies Survey. RESULTS: Respondents reported having to seek out confirmation of their EDS diagnosis with multiple healthcare providers, which implies the difficulty many people with EDS face when trying to gain access to appropriate treatment. Patients with EDS experience higher levels of pain interference and lower satisfaction with social roles and activities compared to national norms. Among the treatment modalities in this study, those perceived as most helpful for acute pain control were opioids, surgical interventions, splints and braces, avoidance of potentially dangerous activities and heat therapy. Chronic pain treatments rated as most helpful were opioids, splints or braces and surgical interventions. For methods used for both acute and chronic pain, those perceived as most helpful were opioids, massage therapies, splints or braces, heat therapy and avoiding potentially dangerous activities. CONCLUSIONS: EDS is a complex, multi-systemic condition that can be difficult to diagnose and poses challenges for healthcare practitioners who engage with EDS patients in holistic care. Improved healthcare provider knowledge of EDS is needed, and additional research on the co-occurring diagnoses with EDS may assist in comprehensive pain management for EDS patients. IMPLICATIONS FOR REHABILITATION: Ehlers-Danlos Syndrome (EDS) is a group of connective tissue disorders associated with defective production of collagen, which can dramatically reduce musculoskeletal functioning by symptoms of joint laxity and frequent dislocations eventually leading to disability. Respondents to an on-line survey reported having to seek out confirmation of their EDS diagnosis with multiple physicians, which implies the difficulty many people with EDS face when trying to gain access to appropriate treatment. Participants with EDS reported the most helpful methods for managing acute pain were opioids, surgical interventions, splints and braces, heat therapy, nerve blocks and physical therapy, while chronic pain was treated most effectively with opioids, heat therapy, splints or braces and surgical interventions.

Quality of life prediction in children with joint hypermobility syndrome.

AIMS: To assess the child- and parent-reported health-related quality of life (HRQOL) of children with joint hypermobility syndrome (JHS), to compare these with other chronic paediatric conditions and to determine whether symptoms experienced by children with JHS can predict their HRQOL. METHODS: Eighty-nine children with JHS and one of their parents completed the Pediatric Quality of Life Inventory 4.0 Generic Core Scale, the Multidimensional Fatigue Scale and the Pediatric Pain Questionnaire. Anthropometric measures and reported symptoms were recorded. Child-reported HRQOL scores were compared with parent report, and both child- and parent-reported HRQOL scores of children with JHS were compared with those of children with other chronic conditions. Stepwise multiple regression was undertaken to determine whether any combination of measures could predict HRQOL. RESULTS: Parent- and child-reported HRQOL scores were strongly correlated (r = 0.6-0.84, all P < 0.001); however, parents of children with JHS perceived lower overall HRQOL (mean difference = 4.44, P = 0.001), physical (mean difference = 7.11, P < 0.0001) and emotional functioning (mean difference = 5.24, P = 0.011) than their children. When considered together with previously reported HRQOL scores for children with other chronic conditions, parent and child scores were similarly strongly correlated (r = 0.93, P = 0.001). Multiple regression revealed that 75% of the variance in child-reported HRQOL scores was accounted for by a child's level of pain and fatigue, and presence of stress incontinence symptoms (P < 0.0001). CONCLUSION: Children with JHS experience poor HRQOL and disabling fatigue, with parent scores providing a good proxy. Pain, fatigue and the presence of stress incontinence symptoms have the greatest impact on their HRQOL.

Cross-sectional and longitudinal assessment of aortic root dilation and valvular anomalies in hypermobile and classic Ehlers-Danlos syndrome.

OBJECTIVES: To delineate the prevalence of cardiac findings in hypermobile and classic Ehlers-Danlos syndrome and provide longitudinal analysis of aortic root growth. STUDY DESIGN: A retrospective chart review was conducted, and data were analyzed for cross-sectional prevalence of aortic dilation and valvular anomalies. The clinical implications of aortic root growth were determined by assessment of progression of aortic root measurements over time and clinical symptoms. RESULTS: Patients whose first echocardiogram was obtained in late childhood or adulthood were less likely to have aortic dilation (P < .002) than those whose first echocardiogram was obtained in early childhood. Longitudinally, seven individuals had dilated aortas before age 14, and only one individual continued to show dilation after age 14 (P = .0143). No patient with a normal aortic root in childhood had development of dilation in adulthood. Fifteen of the 252 patients (6.0%) had mitral valve prolapse (MVP), although only one patient (0.4%) had MVP that was mild to moderate. CONCLUSIONS: Although aortic root size and MVP are increased in patients with these types of Ehlers-Danlos syndrome, they tend to be of little clinical consequence. Echocardiography may still be warranted as part of cardiovascular assessment, but decreased frequency of screening is recommended especially in symptom-free adults.

Contemporary management of vascular complications associated with Ehlers-Danlos syndrome.

OBJECTIVES: There has been debate regarding the safety of performing elective procedures in patients with vascular manifestations associated with Ehlers-Danlos syndrome (EDS). The purpose of this study was to review the surgical management and clinical outcomes of EDS patients undergoing vascular procedures at a tertiary medical center with multimodality expertise in connective tissue disorders. METHODS: All patients with EDS undergoing endovascular and open vascular procedures at a single-institution academic medical center from 1994 to 2009 were retrospectively reviewed. Clinical data were evaluated including patient demographics, length of stay (LOS), and mortality outcomes during hospital course and long-term follow-up. RESULTS: A total of 40 patients with EDS were identified, including individuals diagnosed with classic (n = 15), hypermobility (n = 16), and vascular (n = 9) types of EDS. These patients collectively underwent 45 endovascular and 18 open procedures for vascular disease during the time period, including embolization (n = 37), angioplasty (n = 8), arterial bypass (n = 5), and aortic aneurysm repair (n = 13). All cases were performed electively, except for one (2%) urgent endovascular and one (5%) emergent open procedure. Endovascular procedures were associated with a median LOS (interquartile range [IQR]) of 2 (1 to 3) days with no procedure-related mortality or in-hospital deaths among all EDS types, whereas open vascular procedures had median LOS (IQR) of 6 (5 to 8) days with one (6%) in-hospital death occurring in a vascular EDS patient. Survival free of any complication at 5 years was 85% and 54% following endovascular and open procedures, respectively. CONCLUSIONS: The elective surgical management of vascular disorders in EDS patients using open and endovascular procedures has been associated with good outcomes. Our results suggest that vascular interventions in these EDS patients can be safely performed and should not be withheld until rupture or acute symptoms arise.

Assessment of skin extensibility and joint hypermobility in patients with spontaneous cervical artery dissection and Ehlers-Danlos syndrome.

Ehlers-Danlos syndrome (EDS) is a hereditary connective tissue disorder. One important clinical characteristic of classical type EDS is skin hyperextensibility. Examination of clinical evidence and electron microscopic views of skin biopsies suggest that connective tissue abnormalities resembling very mild EDS are present in a sizable proportion of patients with spontaneous cervical artery dissection (sCAD). Manual assessment of skin extensibility is difficult. Therefore, non-invasive machine-aided measurement of skin extensibility was used and compared with manual assessment of skin extensibility and joint hyperextensibility. Patients with classical EDS, vascular-type EDS, sCAD and healthy patients were evaluated. Skin extensibility was measurably and palpably elevated in all patients with classical type EDS but not in sCAD patients or patients with vascular-type EDS compared to healthy control individuals. Our method is able to measure the increased skin extensibility in classical type EDS. Increased skin extensibility is not present in sCAD patients.

Assessment of bone in Ehlers Danlos syndrome by ultrasound and densitometry.

OBJECTIVE: Ehlers Danlos syndrome (EDS) is an inherited disorder of connective tissue characterised by hyperextensible skin, joint laxity, and easy bruising. There are phenotypic similarities with osteogenesis imperfecta, but in EDS a tendency to fracture or altered bone mass has not previously been considered to be a cardinal feature. METHOD: This case-control design study investigates whether 23 patients with EDS had differences in fracture rates, bone mass, and calcaneal ultrasound parameters compared with age and sex matched controls. RESULTS: 23 cases of EDS (mean (SD) age 38.5 (15.5)) were compared with 23 controls (mean age 37.8 (14.5)). A significant reduction in bone density measured by dual energy x ray absorptiometry was found at the neck of femur by 0.9 SD, p = 0.05, and lumbar spine by 0.74 SD, p = 0.02. At the calcaneum, broad band ultrasound attenuation and speed of sound were significantly reduced compared with controls by 0.95 SD (p = 0.004) and 0.49 SD (p = 0.004) for broad band ultrasound attenuation and speed of sound respectively. Broad band ultrasound attenuation and speed of sound remained significantly reduced after adjusting for bone mineral density (BMD). After adjusting for functional status (HAQ), age and sex, hypermobility was inversely correlated with broad band ultrasound attenuation and SOS, but not BMD at hip or spine. Previous fracture was 10 times more common in EDS (p < 0.001), with 86.9% of patients reporting a total of 47 low impact fractures, compared with 8.7% of controls. CONCLUSION: This study has identified a tendency of EDS patients to fracture, have low bone mass and abnormal bone structure. The aetiology is likely to be multifactorial, with an inherited structural element, accentuated by immobility or reduced exercise. This is one of the first clinical studies to suggest ultrasound can detect structural differences in bone, independent of dual energy x ray absorptiometry.

The Ehlers-Danlos syndrome and colonic perforation. Report of a case and physiologic assessment of underlying motility disorder.

The Ehlers-Danlos syndrome is a genetically determined disorder of connective tissue which is generally known for its features of fragile, hyperextensible skin, hypermobile joints, and tissue fragility. Less commonly, colorectal complications can occur, including bleeding, prolapse, and diverticulitis. A rare case of colonic perforation associated with Ehlers-Danlos syndrome is presented. Additionally, in vitro electromyographic studies of the colonic tissue were performed which suggested a possible link between abnormal myogenic activity and the colonic perforations. The authors recommend that treatment be either a permanent colostomy or a subtotal colectomy with anastomosis to the rectum for similar cases.