<scp>Ehlers–Danlos</scp> syndromes, hypermobility spectrum disorders, and associated <scp>co‐morbidities</scp>: Reports from <scp>EDS ECHO</scp>

Abstract

In both community care and across a broad range of hospital specialties, many healthcare professionals (nurses, midwives, physical and other therapists, psychologists, and doctors) will likely attend to people with Ehlers–Danlos syndromes (EDS) or hypermobility spectrum disorders (HSD). The belief that EDS is rare or ultra-rare is true for several forms of the syndrome, but increasingly the hypermobile type of EDS (hEDS) is thought more common, and HSD (a population previously described within joint hypermobility syndrome prior to the 2017 nosology changes; Castori et al., 2017; Tinkle et al., 2017) much more common. Together the prevalence of hEDS and HSD is likely greater than 1 in 500 in the general population (Demmler et al., 2019), and a common presentation in general musculoskeletal clinics (Grahame & Hakim, 2006). Yet often the journey to diagnosis and treatment is challenging for patients, who may receive no diagnosis, or misdiagnoses. In addition, misconceptions that the issues are solely mental health concerns are commonly reported. Too often there is more than a decade delay in diagnosis, and the negative impact on quality of life from living with under-managed disease is significant (Bell & Pearce, 2021; Berglund, Pettersson, Pigg, & Kristiansson, 2015; Castori, Camerota, Celletti, Grammatico, & Padua, 2010; Demmler et al., 2019; Mu et al., 2019). Multiple morbidities can arise from structural pathologies throughout the body in EDS. These pathologies include musculoskeletal, dermatological, neurological, ocular, oro-dental, laryngeal, pulmonary, gastrointestinal, vascular, and uro-gynecological disorders. Symptoms of chronic widespread pain and chronic fatigue are almost universal (Hakim et al., 2020; Schubart, Schaefer, Hakim, Francomano, & Bascom, 2019). The phenotype, in part, depends on the type of EDS, but features can overlap between them, most clearly seen in the musculoskeletal system and skin, for example. These pathologies have been well documented and are increasingly understood through the determination of their molecular genetics and the ensuing abnormalities of collagens and other molecules of the extracellular matrix (Malfait et al., 2017). In HSD, the principal structural morbidity is in the musculoskeletal system, sharing similar concerns to EDS in presenting with joint instability, ease of joint injury, musculoskeletal, and neuropathic pain, and chronic fatigue (Castori et al., 2017). In addition, several co-morbidities are associated with EDS and HSD. These include disorders of autonomic function, gastrointestinal function, neurodevelopment, mental health, and inflammation and systemic manifestations of mast cell activation. In 2017, alongside the new criteria for EDS and the framework for diagnosing HSD, the International Consortium on the EDS and HSD published a series of review articles exploring what was known of the associations and management of many of these co-morbidities in these conditions (Tinkle, Malfait, Francomano, & Byers, 2017). These and more areas of health concern continue to be explored. Recent large population and registry data affirm their high prevalence in EDS and HSD (Boris & Bernadzikowski, 2021; Cederlöf et al., 2016; Demmler et al., 2019; Hakim et al., 2020; Ritelli, Venturini, Cinquina, Chiarelli, & Colombi, 2020; Schubart et al., 2019), and reports also describe similar severity of co-morbidities in hEDS and HSD (Aubry-Rozier et al., 2021; Copetti et al., 2019; Hakim, 2019). With substantial growth in knowledge in the field, keeping up to date with advances in epidemiology, pathophysiology, and management of this heterogeneous group of conditions is challenging. No individual healthcare professional can truly manage all aspects of these conditions at an expert level. Care typically requires a holistic and multidisciplinary approach. Yet such care, ideally embedded in the community, supported by subspecialty medical, therapies, and social care (Whitty et al., 2020) is substantially lacking for EDS and HSD internationally. Currently, there are small numbers of expert clinics, centers, and networks striving to support patients and colleagues. Access to care is profoundly limited, yet management of many of the common concerns is well within the ability of most generalists with specialist support when needed. Recognizing the exponential growth in knowledge, the multifaceted challenges faced by healthcare systems internationally, and the need for greater numbers of healthcare professionals to feel informed and confident in the diagnosis and management of EDS and HSD, the Ehlers-Danlos Society in 2019 established EDS ECHO, an affiliate of Project ECHO® (Project ECHO, 2021; The Ehlers-Danlos Society, 2021). Project ECHO's philosophies include “all teach, all learn” and “move knowledge, not people.” The ECHO model primarily seeks to increase access to care. Embracing this, EDS ECHO has established several programs for healthcare professionals and for community leaders and advocates in EDS and HSD across the world. Participation is free, and all can access a large repository of teaching material, continuing education credits, and support from a truly multidisciplinary and international network of peers. We have shown participants gain both knowledge and confidence in managing EDS and HSD (Hakim, Schubart, Francomano, Bascom, & Bloom, 2021). In October 2020, EDS ECHO (led by author A.J.H) brought together experts from across the breadth of the co-morbidities seen in EDS and HSD. Plenary sessions included expert reviews of the latest literature, case reports, and selected original research abstracts. This special issue of the American Journal of Medical Genetics, Part C, is an extension of that conference. It explores: the patient journey; the value of coalitions; the tools used by physical therapists in their assessment and management; current evidence for surgical outcomes in orthopedics; pain mechanisms; pathophysiology of mast cell activation, and the potential role of inflammatory mediators in EDS and HSD; mental health concerns; associations between EDS, HSD and neurodevelopmental disorders; autonomic dysfunction, and its relationship with mental and physical health; dental disease; upper and lower airway disease; functional bowel disorders, and vascular compression syndromes as a cause of gastrointestinal symptoms; urological concerns; and gynecological concerns, and considerations in pregnancy. It seeks to compliment or update most of the aforementioned reviews from 2017, introduces reviews in subjects that were not covered at that time, and shares new insights through the inclusion of several original research articles. In an ongoing commitment to sharing knowledge and supporting clinicians and patients, we hope colleagues find this issue insightful and valuable in supporting them in the assessment and care of their patients. The authors wish to thank all those who have contributed to this special issue, and the many more colleagues and EDS and HSD community advocates working tirelessly to expand and disseminate knowledge in this field of Medicine. The authors express immense gratitude to the staff responsible for managing EDS ECHO at The Ehlers-Danlos Society, and in particular Stacey Simmonds without whom the EDS ECHO conference upon which this issue is based would not have happened. Our gratitude also goes to Anne Slavotinek, Editor-in-Chief, Subhasri Thiagarajan, and the editorial team at the American Journal of Medical Genetics for their oversight of the production of this issue. The authors declare no potential conflict of interest. Alan J. Hakim and Clair A. Francomano conceived of and contributed to the issue; and, with Brad T. Tinkle peer-reviewed and edited the works in this issue. All three wrote this editorial. Does not apply since no data was created.

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