Extracutaneous features and complications of the Ehlers-Danlos syndromes: A systematic review

Brent J Doolan; Mark E Lavallee; Ingrid Hausser; Jane R Schubart; F Michael Pope; Suranjith L Seneviratne; Ingrid M Winship; Nigel P Burrows

doi:10.3389/fmed.2023.1053466

Extracutaneous features and complications of the Ehlers-Danlos syndromes: A systematic review

Front Med (Lausanne). 2023 Jan 23:10:1053466. doi: 10.3389/fmed.2023.1053466. eCollection 2023.

Authors

Brent J Doolan¹, Mark E Lavallee², Ingrid Hausser³, Jane R Schubart⁴, F Michael Pope⁵, Suranjith L Seneviratne^{6

7}, Ingrid M Winship^{8

9}, Nigel P Burrows¹⁰

Affiliations

¹ School of Basic and Medical Biosciences, St. John's Institute of Dermatology, King's College London, London, United Kingdom.
² Department of Orthopedics, University of Pittsburgh Medical Center of Central PA, Pittsburgh, PA, United States.
³ Institute of Pathology, Heidelberg University Hospital, Heidelberg, Germany.
⁴ Department of Surgery, Penn State College of Medicine, Hershey, PA, United States.
⁵ Department of Dermatology, Chelsea and Westminster Hospital NHS Foundation Trust (West Middlesex University Hospital), London, United Kingdom.
⁶ Institute of Immunity and Transplantation, Royal Free Hospital and University College London, London, United Kingdom.
⁷ Nawaloka Hospital Research and Education Foundation, Nawaloka Hospitals, Colombo, Sri Lanka.
⁸ Department of Genetic Medicine, The Royal Melbourne Hospital, Melbourne, VIC, Australia.
⁹ Department of Medicine, The University of Melbourne, Melbourne, VIC, Australia.
¹⁰ Department of Dermatology, Cambridge University Hospitals NHS Foundation Trust, Cambridge, United Kingdom.

Abstract

Introduction: The Ehlers-Danlos syndromes (EDS) comprise a group of inherited connective tissue disorders presenting with variable fragility to skin, soft tissue, and certain internal organs, which can cause significant complications, particularly arterial rupture, bowel perforation and joint difficulties. Currently, there are 14 proposed subtypes of EDS, with all except one subtype (hypermobile EDS) having an identified genetic etiology. An understanding of the extracutaneous features and complications within each subtype is key to maximizing clinical care and reducing the risk of further complications.

Methods: A systematic review of EDS-related extracutaneous features and complications was undertaken.

Results: We identified 839 EDS cases that met the inclusion criteria. We noted a high prevalence of joint hypermobility amongst kyphoscoliotic (39/39, 100%), spondylodysplastic (24/25, 96.0%), and hypermobile (153/160, 95.6%) EDS subtypes. The most common musculoskeletal complications were decreased bone density (39/43, 90.7%), joint pain (217/270, 80.4%), and hypotonia/weakness (79/140, 56.4%). Vascular EDS presented with cerebrovascular events (25/153, 16.3%), aneurysm (77/245, 31.4%), arterial dissection/rupture (89/250, 35.5%), and pneumothorax/hemothorax. Chronic pain was the most common miscellaneous complication, disproportionately affecting hypermobile EDS patients (139/157, 88.5%). Hypermobile EDS cases also presented with chronic fatigue (61/63, 96.8%) and gastrointestinal complications (57/63, 90.5%). Neuropsychiatric complications were noted in almost all subtypes.

Discussion: Understanding the extracutaneous features and complications of each EDS subtype may help diagnose and treat EDS prior to the development of substantial comorbidities and/or additional complications.

Systematic review registration: https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42022308151, identifier CRD42022308151.

Keywords: Ehlers-Danlos syndrome; complications; extracutaneous; heritable connective tissue disorders (HCTD); joint hypermobility.

Publication types

Systematic Review

Grants and funding

This research was in part funded by a microgrant from the Ehlers-Danlos Society.