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.

Clinical-functional features of individuals with Osteogenesis Imperfecta and Ehlers-Danlos syndromes: A scoping review of assessment tools and ICF model.

BACKGROUND: Clinical-functional assessment of patients affected by Osteogenesis Imperfecta and Ehlers-Danlos Syndromes is essential for clinical management. However, there is no clear information on disease-specific tools of assessment for clinical practice, thus limiting quantification and management of the diseases-related impairments. OBJECTIVE: The present scoping review was aimed at investigating the most common clinical-functional features and assessment tools in individuals with Osteogenesis Imperfecta and Ehlers-Danlos Syndromes, and to provide an updated International Classification of Functioning (ICF) model related to functional impairments for each disease. METHODS: The literature revision was conducted on PubMed, Scopus and Embase databases. Articles reporting an ICF model of clinical-functional features and assessment tools for Osteogenesis Imperfecta and Ehlers-Danlos Syndromes individuals were included. RESULTS: A total of 27 articles were included, 7 reporting an ICF model, and 20 reporting clinical-functional assessment tools. It was reported that patients with Osteogenesis Imperfecta and Ehlers-Danlos Syndromes show impairments in both Body Function and Structure, and Activities and Participation domains of the ICF. A heterogeneous number of assessment tools was found for both diseases regarding proprioception, pain, endurance to exercise, fatigue, balance and motor coordination, and mobility. CONCLUSION: Patients with Osteogenesis Imperfecta and Ehlers-Danlos Syndromes show several impairments and limitations in Body Function and Structure, and Activities and Participation domains of the ICF. Thus, an appropriate and ongoing assessment of the disease-related impairments is necessary to improve clinical practice. Several functional tests and clinical scales can be used to assess the patients despite the heterogeneity of assessment tools found in previous literature.

Prescription Claims for Immunomodulator and Antiinflammatory Drugs Among Persons With Ehlers-Danlos Syndromes.

OBJECTIVE: Joint hypermobility in Ehlers-Danlos Syndromes (EDS) predisposes persons with EDS to frequent subluxations and dislocations, chronic arthralgia, and soft-tissue rheumatism. Epidemiologic trends of rheumatologic conditions among persons with EDS are lacking. Prescription claims databases can reflect underlying disease burdens by using medication claims as disease proxies. We examined the prevalence of prescription claims for commonly prescribed immunomodulator and antiinflammatory (IMD) drugs among persons with EDS compared with their matched control person, and hypothesized peripubertal increases among female persons with EDS. METHODS: We compared the percentages of IMD drug prescription claims among 3,484 persons with EDS (ages 5-62 years) against their age-, sex-, state of residence-, and earliest claim date-matched control persons using 10 years (2005-2014) of private prescription claims data and a minimum 2-year enrollment inclusion criterion. RESULTS: Our cohort comprised 70% adults and 74% female persons. At least 1 IMD medication was prescribed to 65.4% of persons with EDS compared with 47.4% of control persons. We observed 1.3 to 4.2 times higher odds (P < 0.0001) for 5 out of 6 IMD drug classes among persons with EDS compared with matched control persons, except for biologic agents (conditional odds ratio 1.3, 95% confidence interval 0.8-2.0). Peripubertal increases were observed for nonsteroidal antiinflammatory drugs, oral, and injectable steroids. CONCLUSIONS: To our knowledge, our study is the first to examine the full range of IMD drug prescription claim trends among persons with EDS. We believe our research findings can have notable diagnostic and management implications for EDS patients who present with multiple comorbidities and generally require a more granular assessment of their medical conditions.

Feasibility of video-based joint hypermobility assessment in individuals with suspected Ehlers-Danlos syndromes/generalised hypermobility spectrum disorders: a single-site observational study protocol.

INTRODUCTION: Ehlers-Danlos syndromes (EDS)/generalised hypermobility spectrum disorders (G-HSD) affect the connective tissue of the body and present with a heterogeneous set of symptoms that pose a challenge for diagnosis. One of the main diagnostic criteria of EDS/G-HSD is generalised joint hypermobility, which is currently assessed by clinicians during a physical exam. However, the practice for measuring joint hypermobility is inconsistent between clinicians, leading to high inter-rater variability. Often patients are misdiagnosed with EDS/G-HSD based on an incorrect hypermobility assessment, leading to increased referral rates and resource utilisation at specialised EDS clinics that results in unnecessary emotional distress for patients. An objective, validated and scalable method for assessing hypermobility might mitigate these issues and result in improved EDS/G-HSD patient care. METHODS AND ANALYSIS: This study will examine the use of videos obtained using a smartphone camera to assess the range of motion (ROM) and hypermobility of the joints assessed in Beighton score and more (spine, shoulders, elbows, knees, ankles, thumbs and fifth fingers) in individuals with suspected EDS/G-HSD. Short videos of participants will be captured as they undergo a formal assessment of joint hypermobility at the GoodHope EDS Clinic at Toronto General Hospital. Clinicians will measure the ROM at each joint using a clinical-grade goniometer to establish ground truth measurements. Open-source human pose-estimation libraries will be used to extract the locations of key joints from the videos. Deterministic and machine learning systems will be developed and evaluated for estimating the ROM at each joint. Results will be analysed separately for each joint and human pose-estimation library. ETHICS AND DISSEMINATION: This study was approved by the Research Ethics Board of the University Health Network in Toronto on 26 April 2022. Participants will provide written informed consent. Findings from this study will be published in peer-reviewed journals and presented at conferences. TRIAL REGISTRATION NUMBER: NCT05366114.

Assessment of the beliefs, needs, and expectations for genetic counseling of patients with hypermobile Ehlers-Danlos syndrome.

Ehlers-Danlos syndrome, hypermobility type (hEDS) is a heritable connective tissue disorder that currently does not have a known molecular etiology. Previous studies have explored the complex symptomology, clinical diagnosis, and psychological aspects of hEDS. Genetics providers currently aid in the diagnosis and management guidance of patients with hEDS, but there is limited data describing the needs and expectations of individuals with hEDS from a clinical genetics appointment. Our study sought to explore these items through the use of an online survey to assess participants' beliefs, needs and expectations (BNE) for genetic counseling as well as questions about demographics, hEDS symptoms, and current medical care. A total of 460 respondents with hEDS completed the survey. Most participants felt joint pain/weakness (n = 392; 88%) was one of the most disruptive symptoms of hEDS and 63% (n = 289) reported having psychiatric conditions. BNE scores were highest in two domains: expectations to have psychosocial concerns addressed during a genetic counseling appointment (mean score = 4.4/5; SD = 0.56) and desire for positive feelings after a genetic counseling session (mean score = 4.3/5; SD = 0.59). Participants who previously had genetic counseling felt less unsure about their diagnosis (p = 0.02) and had lower need for information about hEDS (p < 0.001). Majority of participants did not feel that their doctors were knowledgeable about hEDS (n = 269; 58%) and strongly supported a multidisciplinary approach to their care (n = 445; 97%). This research provides a framework for genetics providers and other healthcare professionals to assess the needs and expectations of patients with hEDS and consider re-structuring their appointment formats to service this population.

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.

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.

Assessment of the Information Sources and Interest in Research Collaboration Among Individuals with Vascular Ehlers-Danlos Syndrome.

BACKGROUND: Patient-centered research requires active engagement of patients. The vascular Ehlers-Danlos Syndrome (vEDS) research collaborative was established to ascertain patient-centered vEDS research priorities and to engage affected individuals as research partners. Evaluation of access to information and interest in research among individuals with vEDS was the first step undertaken as part of this work. METHODS: A 28-question survey was created to evaluate 4 domains of interest: diagnostic and clinical care history, vEDS experience, information resources, and willingness to collaborate with researchers. The survey was created in REDCap™ and disseminated between January and April 2018 via the vEDS social media pages, blogs, and advocacy Web sites. Results were collated and described. A single open-ended question yielded additional narrative data, which were analyzed qualitatively. RESULTS: Of the 300 responses, 228 (76%) were completed on behalf of oneself. The vEDS diagnosis was confirmed by genetic testing for 85% of respondents. When asked "Did a physician explain vEDS to you and how to manage it?" 25% answered no. Most had a primary care provider (65%), cardiologist (56%), and vascular surgeon (52%). Only 32% had a local vascular surgeon. The most commonly reported frustration was no cure/treatment available and the emergency rooms do not know what VEDS is (64.5% and 61.8%, respectively). The Internet was the most useful information source (62.3%) followed by a geneticist (18.4%). Most (87.7%) are willing to share their medical records for research studies (87.7%) and wished to be contacted about future studies (83.8%); however, only 65.4% would be willing to upload medical records via a secure confidential Web application. The most common reason for interest in research partnership was to advance research for a treatment/cure (83.8%) and helping others learn from their experiences (82.9%). The qualitative analysis provided additional insights into the patient experience living with vEDS. CONCLUSIONS: Among individuals with vEDS, there is substantial frustration with the lack of treatment, lack of knowledge among health care providers, and a high degree of interest in research involvement. The survey highlights an opportunity to discuss the optimal modality for research participation and methodologies for building trust in the research teams. The methodology lessons learned can also be applied to other rare vascular diseases.

Aortic Surgery Outcomes of Marfan Syndrome and Ehlers-Danlos Syndrome Patients at Teaching and Nonteaching Hospitals.

BACKGROUND: Despite improvements in prevention and management, aortic aneurysm repair remains a high-risk operation for patients with Marfan syndrome (MFS) and Ehlers-Danlos syndrome (EDS). The goal of this study was to examine differences in characteristics and outcomes of patients with MFS or EDS undergoing aortic aneurysm repair at teaching versus nonteaching hospitals. METHODS: We used the National Inpatient Sample to study patients with MFS or EDS undergoing open or endovascular aortic aneurysm repair from 2000 to 2014. RESULTS: Of 3487 patients (MFS = 3375, EDS = 112), 2974 (85%) had repair at a teaching hospital. Patients who underwent repair at a teaching hospital were slightly younger than those who underwent repair at a nonteaching hospital (38 vs. 43 years, P < 0.01) but otherwise were similar in gender (29% vs. 28% female), race (70% vs. 78% white), and connective tissue disorder diagnosis (97% vs. 97% MFS, all P ≥ 0.1). There were no differences in anatomy (17% vs. 19% abdominal, 67% vs. 66% thoracic, and 15% vs. 15% thoracoabdominal, all P ≥ 0.1) or type of repair (5% vs. 5% endovascular), but patients at nonteaching hospitals were more likely to have a dissection (49% vs. 38%, P = 0.02). There was no difference in perioperative mortality (4% vs. 6%, P = 0.5) or length of stay (median 8 days vs. 7 days, P = 0.3) between teaching and nonteaching hospitals. There was also no difference in hemorrhagic (47% vs. 43%), pulmonary (9% vs. 16%), renal (12% vs. 14%), or neurologic (5% vs. 6%) complications between teaching and nonteaching hospitals, respectively (all P ≥ 0.05). In analysis stratified by anatomic extent of repair, there was a lower prevalence of pulmonary complications in thoracic aorta repairs at teaching hospitals (8.1% vs. 18.4%, P = 0.01) but a higher prevalence of hemorrhage in abdominal aortic repairs at teaching hospitals (45.6% vs. 20.6%, P = 0.04) as compared with nonteaching hospitals. CONCLUSIONS: Patients with MFS and EDS who undergo aortic aneurysm repair have their operations predominantly at teaching hospitals, but those patients who undergo repair at nonteaching hospitals do not have worse mortality or morbidity despite a higher incidence of dissection.

The Upper Limb Hypermobility Assessment Tool: A novel validated measure of adult joint mobility.

BACKGROUND: Existing measures of generalized joint hypermobility do not include commonly affected upper limb joints. OBJECTIVE: To evaluate the reliability of a novel clinically-applicable measure of upper limb joint mobility, its ability to discriminate between varying extents of hypermobility, identify generalized joint hypermobility, and to establish a cut-point for hypermobility classification. DESIGN: Validation of a diagnostic tool. METHOD: Participants were sought from three groups - healthy controls, likely and known hypermobiles, and assessed using the Upper Limb Hypermobility Assessment Tool (ULHAT), Beighton score and clinical opinion. Pearson's correlation coefficient examined individual group and whole cohort relationships between upper limb hypermobility, age, gender and ethnicity. MANOVA investigated between-group differences in ULHAT scores. Median interquartile ranges and ROC Curve analysis identified the cut-off score for identification of upper limb hypermobility. Percent agreement with clinical opinion assessed the ability of the ULHAT to identify generalized joint hypermobility. RESULTS: 112 adult participants (mean age 24.3 ± 5.5years) across the three groups were assessed. Inter-rater reliability of the tool was high (ICC2,1 = 0.92). The cut-point was established at ≥7/12 (sensitivity 0.84, specificity 0.77, +LR 3.7, -LR 0.2). Upper limb hypermobility did not vary with age or ethnicity (both p > 0.12), but was greater in females (p < 0.001). The ULHAT discriminated between the three groups and identified generalized hypermobility. CONCLUSIONS: The 12-item ULHAT measures mobility of multiple upper limb joints in all movement planes. Using a cut-off of ≥7/12 in adults, the ULHAT is a reliable and valid tool for identifying upper limb hypermobility and generalized joint hypermobility.

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.

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.

Genotyping and prenatal assessment of collagen lysyl hydroxylase deficiency in a family with Ehlers-Danlos syndrome type VI.

Collagen lysyl and prolyl hydroxylase activities were measured in cultured fibroblasts from a child with clinical features of Ehlers-Danlos syndrome. Lysyl-to-prolyl hydroxylase activity ratios in cells from the proband, mother, father, and control were .24, .86, .52, and 1.00, respectively, providing a biochemical diagnosis of Ehlers-Danlos syndrome type VI and indicating an autosomal recessive mode of inheritance in this family. Prenatal assessment of lysyl hydroxylase deficiency was requested and accomplished for the first time during a subsequent pregnancy in the family. A series of control cultures established lysyl hydroxylase activity to be similar in cultured amniotic fluid cells (AF and F cells) and in cultured dermal fibroblasts. Cultured F and AF cells from the monitored pregnancy had enzyme activity similar to controls, indicating that the fetus should not be affected by lysyl hydroxylase deficiency. This finding was confirmed by demonstration of normal lysyl hydroxylase activity in fibroblasts cultured from the newborn baby. These studies show that cells cultured from second trimester amniotic fluid have collagen lysyl hydroxylase activity similar to that in dermal fibroblasts, making prenatal diagnosis of lysyl hydroxylase deficiency possible.