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Ex vivo nonlinear microscopy imaging of Ehlers–Danlos syndrome-affected skin

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Abstract

Ehlers–Danlos syndrome (EDS) is the name for a heterogenous group of rare genetic connective tissue disorders with an overall incidence of 1 in 5000. The histological characteristics of EDS have been previously described in detail in the late 1970s and early 1980s. Since that time, the classification of EDS has undergone significant changes, yet the description of the histological features of collagen morphology in different EDS subtypes has endured the test of time. Nonlinear microscopy techniques can be utilized for non-invasive in vivo label-free imaging of the skin. Among these techniques, two-photon absorption fluorescence (TPF) microscopy can visualize endogenous fluorophores, such as elastin, while the morphology of collagen fibers can be assessed by second-harmonic generation (SHG) microscopy. In our present work, we performed TPF and SHG microscopy imaging on ex vivo skin samples of one patient with classical EDS and two patients with vascular EDS and two healthy controls. We detected irregular, loosely dispersed collagen fibers in a non-parallel arrangement in the dermis of the EDS patients, while as expected, there was no noticeable impairment in the elastin content. Based on further studies on a larger number of patients, in vivo nonlinear microscopic imaging could be utilized for the assessment of the skin status of EDS patients in the future.

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Acknowledgements

Above all, we would like to thank the patients and the control subjects for their cooperation and for providing skin samples and molecular genetic data for this study. We acknowledge the support of Fanni Virág Ralovich and Krisztina Horváth in the collection of the clinical data and Mercédesz Mazán and Flóriánné Adrien Suba for their assistance in the genetic screening.

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Authors and Affiliations

  1. Department of Dermatology, Venereology and Dermatooncology, Semmelweis University, 41 Mária Street, Budapest, 1085, Hungary

    Norbert Kiss, Dóra Haluszka, Kende Lőrincz, Enikő Kuroli, Judit Hársing, Balázs Mayer, Sarolta Kárpáti, Norbert Wikonkál & Márta Medvecz

  2. Institute for Solid State Physics and Optics, Wigner RCP, Budapest, Hungary

    Norbert Kiss, Dóra Haluszka & Róbert Szipőcs

  3. 2nd Department of Pediatrics, Semmelweis University, Budapest, Hungary

    György Fekete

  4. R&D Ultrafast Lasers Ltd, P.O. Box 622, Budapest, 1539, Hungary

    Róbert Szipőcs

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  1. Norbert Kiss
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Correspondence to Márta Medvecz.

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All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

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Informed consent was obtained from all individual participants included in the study.

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Kiss, N., Haluszka, D., Lőrincz, K. et al. Ex vivo nonlinear microscopy imaging of Ehlers–Danlos syndrome-affected skin. Arch Dermatol Res 310, 463–473 (2018). https://doi.org/10.1007/s00403-018-1835-7

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