Ehlers-Danlos Syndrome

ObjectivesTo describe the epidemiology of diagnosed hypermobility spectrum disorder (HSD) and Ehlers-Danlos syndromes (EDS) using linked electronic medical records. To examine whether these conditions remain rare and primarily affect the musculoskeletal system.DesignNationwide linked electronic cohort and nested case-control study.SettingRoutinely collected data from primary care and hospital admissions in Wales, UK.ParticipantsPeople within the primary care or hospital data systems with a coded diagnosis of EDS or joint hypermobility syndrome (JHS) between 1 July 1990 and 30 June 2017.Main outcome measuresCombined prevalence of JHS and EDS in Wales. Additional diagnosis and prescription data in those diagnosed with EDS or JHS compared with matched controls.ResultsWe found 6021 individuals (men: 30%, women: 70%) with a diagnostic code of either EDS or JHS. This gives a diagnosed point prevalence of 194.2 per 100 000 in 2016/2017 or roughly 10 cases in a practice of 5000 patients. There was a pronounced gender difference of 8.5 years (95% CI: 7.70 to 9.22) in the mean age at diagnosis. EDS or JHS was not only associated with high odds for other musculoskeletal diagnoses and drug prescriptions but also with significantly higher odds of a diagnosis in other disease categories (eg, mental health, nervous and digestive systems) and higher odds of a prescription in most disease categories (eg, gastrointestinal and cardiovascular drugs) within the 12 months before and after the first recorded diagnosis.ConclusionsEDS and JHS (since March 2017 classified as EDS or HSD) have historically been considered rare diseases only affecting the musculoskeletal system and soft tissues. These data demonstrate that both these assertions should be reconsidered.

BackgroundHypermobile Ehlers-Danlos syndrome (hEDS) and hypermobility spectrum disorders (HSD) are debilitating conditions. Diagnosis is currently clinical in the absence of biomarkers, and criteria developed for adults are difficult to use in children and biologically immature adolescents. Generalized joint hypermobility (GJH) is a prerequisite for hEDS and generalized HSD. Current literature identifies a large proportion of children as hypermobile using a Beighton score ≥ 4 or 5/9, the cut off for GJH in adults. Other phenotypic features from the 2017 hEDS criteria can arise over time. Finally, many comorbidities described in hEDS/HSD are also seen in the general pediatric and adolescent population. Therefore, pediatric specific criteria are needed. The Paediatric Working Group of the International Consortium on EDS and HSD has developed a pediatric diagnostic framework presented here. The work was informed by a review of the published evidence.ObservationsThe framework has 4 components, GJH, skin and tissue abnormalities, musculoskeletal complications, and core comorbidities. A Beighton score of ≥ 6/9 best identifies children with GJH at 2 standard deviations above average, based on published general population data. Skin and soft tissue changes include soft skin, stretchy skin, atrophic scars, stretch marks, piezogenic papules, and recurrent hernias. Two symptomatic groups were agreed: musculoskeletal and systemic. Emerging comorbid relationships are discussed. The framework generates 8 subgroups, 4 pediatric GJH, and 4 pediatric generalized hypermobility spectrum disorders. hEDS is reserved for biologically mature adolescents who meet the 2017 criteria, which also covers even rarer types of Ehlers-Danlos syndrome at any age.ConclusionsThis framework allows hypermobile children to be categorized into a group describing their phenotypic and symptomatic presentation. It clarifies the recommendation that comorbidities should be defined using their current internationally accepted frameworks. This provides a foundation for improving clinical care and research quality in this population.

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.

ObjectivesDisorders of gut-brain interaction (DGBI) affect about 40% of children and are often comorbid with hypermobility spectrum disorders (HSDs) and orthostatic intolerance (OI). However, how these comorbidities impact outcomes in pediatric DGBI is not well understood. This study aimed to compare outcomes in DGBI patients with HSD, OI, both, or neither.MethodsWe reviewed records of patients aged 9-21 years from a multidisciplinary DGBI clinic. Patients met Rome IV criteria for DGBI and had documented HSD and/or OI diagnoses from specialists in gastroenterology, rheumatology, genetics, cardiology, adolescent medicine, and others. HSD terms included Ehlers-Danlos syndrome, hypermobile Ehlers-Danlos syndrome, and generalized hypermobility; OI terms included postural orthostatic tachycardia syndrome, dysautonomia, and orthostatic hypotension. Clinical data included the following validated questionnaires: abdominal pain index, nausea severity scale, functional disability inventory, patient health questionnaire-9 (Depression), children somatization inventory, pediatric insomnia severity index, pain catastrophizing scale for children, and screen for child anxiety related disorders (Anxiety). We compared DGBI patients with both HSD and OI, those with either disorder, and those without.ResultsOf 175 patients, 46% had HSD and 43% had OI. Patients with both HSD and OI had significantly worse nausea, depression, disability, and somatization scores than others (p ConclusionsComorbid HSD and OI worsen DGBI symptoms. Accurate diagnosis and treatment are critical to improving outcomes due to shared autonomic dysfunction.