Dermatologic manifestations and diagnostic assessments of the Ehlers-Danlos syndromes: A clinical review

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

doi:10.1016/j.jaad.2023.01.034

Dermatologic manifestations and diagnostic assessments of the Ehlers-Danlos syndromes: A clinical review

J Am Acad Dermatol. 2023 Sep;89(3):551-559. doi: 10.1016/j.jaad.2023.01.034. Epub 2023 Feb 8.

Authors

Brent J Doolan¹, Mark Lavallee², Ingrid Hausser³, F Michael Pope⁴, Suranjith L Seneviratne⁵, Ingrid M Winship⁶, Nigel P Burrows⁷

Affiliations

¹ St John's Institute of Dermatology, School of Basic and Medical Biosciences, King's College London, London, UK; St John's Institute of Dermatology, Guy's and St Thomas' NHS Foundation Trust, London, UK. Electronic address: b.doolan@nhs.net.
² Department of Orthopedics, University of Pittsburgh Medical Center of Central PA, Pittsburgh, Pennsylvania.
³ Institute of Pathology, Heidelberg University Hospital, Heidelberg, Germany.
⁴ Department of Dermatology, Chelsea and Westminster Hospital NHS Foundation Trust (West Middlesex University Hospital), London, UK.
⁵ Institute of Immunity and Transplantation, Royal Free Hospital and University College London, London, UK; Nawaloka Hospital Research and Education Foundation, Nawaloka Hospitals, Colombo, Sri Lanka.
⁶ Department of Genetic Medicine, The Royal Melbourne Hospital, Melbourne, Victoria, Australia; Department of Medicine, The University of Melbourne, Melbourne, Victoria, Australia.
⁷ Department of Dermatology, Cambridge University Hospitals NHS Foundation Trust, Cambridge, UK.

PMID: 36764582
DOI: 10.1016/j.jaad.2023.01.034

Abstract

Background: The Ehlers-Danlos syndromes (EDSs) comprise a group of connective tissue disorders that manifest with skin hyperextensibility, easy bruising, joint hypermobility and fragility of skin, soft tissues, and some organs. A correct assessment of cutaneous features along with the use of adjunct technologies can improve diagnostic accuracy.

Objectives: To systematically review the cutaneous features and adjunct investigations of EDS.

Methods: A search of PubMed and Web of Science for EDS-related cutaneous features and additional investigations was undertaken from publication of the 2017 International Classification of EDS until January 15, 2022.

Results: One-hundred-and-forty studies involved 839 patients with EDS. The EDS female-to-male ratio was 1.36:1 (P < .001). A high prevalence of skin hyperextensibility, bruising, and soft skin were noted. Most patients with vascular Ehlers-Danlos syndrome showed venous visibility, skin fragility, and acrogeria. Classical EDS showed subcutaneous spheroids and molluscoid pseudotumours. In patients that underwent skin biopsies, only 30.3% and 71.4% showed features suggestive of EDS using light microscopy and transmission electron microscopy, respectively.

Limitations: Retrospective study and small cases numbers for some EDS-subtypes.

Conclusions: An accurate clinical diagnosis increases the chances of a molecular diagnosis, particularly for rarer EDS subtypes, whilst decreasing the need for genetic testing where there is a low clinical suspicion for a monogenic EDS-subtype.

Keywords: Ehlers-Danlos syndrome; heritable connective tissue disorders; joint hypermobility; skin fragility; skin hyperextensibility.

Publication types

Review

MeSH terms

Connective Tissue Diseases*
Ehlers-Danlos Syndrome* / diagnosis
Ehlers-Danlos Syndrome* / genetics
Ehlers-Danlos Syndrome* / pathology
Female
Humans
Male
Retrospective Studies