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Ichthyosis

Nature Reviews Disease Primers volume 9, Article number: 2 (2023) Cite this article

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Abstract

The ichthyoses are a large, heterogeneous group of skin cornification disorders. They can be inherited or acquired, and result in defective keratinocyte differentiation and abnormal epidermal barrier formation. The resultant skin barrier dysfunction leads to increased transepidermal water loss and inflammation. Disordered cornification is clinically characterized by skin scaling with various degrees of thickening, desquamation (peeling) and erythema (redness). Regardless of the type of ichthyosis, many patients suffer from itching, recurrent infections, sweating impairment (hypohidrosis) with heat intolerance, and diverse ocular, hearing and nutritional complications that should be monitored periodically. The characteristic clinical features are considered to be a homeostatic attempt to repair the skin barrier, but heterogeneous clinical presentation and imperfect phenotype–genotype correlation hinder diagnosis. An accurate molecular diagnosis is, however, crucial for predicting prognosis and providing appropriate genetic counselling. Most ichthyoses severely affect patient quality of life and, in severe forms, may cause considerable disability and even death. So far, treatment provides only symptomatic relief. It is lifelong, expensive, time-consuming, and often provides disappointing results. A better understanding of the molecular mechanisms that underlie these conditions is essential for designing pathogenesis-driven and patient-tailored innovative therapeutic solutions.

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Fig. 1: Structure of the epidermis.
Fig. 2: Ceramide pathway in the epidermis.
Fig. 3: Cholesterol and dolichol synthesis pathways in the epidermis.
Fig. 4: Symptomatic presentation of the ichthyoses.
Fig. 5: Decision tree for the diagnosis of ichthyosis.
Fig. 6: Histological characteristics of the ichthyoses.

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Acknowledgements

The authors thank the anonymous patient and caregiver for their contribution in Boxes 2 and 3, and the Spanish Association of Ichthyosis Patients (ASIC) for their support.

Author information

Authors and Affiliations

  1. Department of Medicine, Faculty of Medicine, University of Salamanca, Salamanca, Spain

    Carlos Gutiérrez-Cerrajero & Rogelio González-Sarmiento

  2. Biomedical Research Institute of Salamanca (IBSAL), Salamanca, Spain

    Carlos Gutiérrez-Cerrajero & Rogelio González-Sarmiento

  3. Division of Dermatology, Tel Aviv Sourasky Medical Center, Tel Aviv, Israel

    Eli Sprecher

  4. Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel

    Eli Sprecher

  5. Departments of Dermatology and Paediatrics, Northwestern University Feinberg School of Medicine, Chicago, IL, USA

    Amy S. Paller

  6. Department of Dermatology, Nagoya University Graduate School of Medicine, Nagoya, Aichi, Japan

    Masashi Akiyama

  7. Centre for Rare Skin Diseases, Dermatology Department, Larrey Hospital, Toulouse, France

    Juliette Mazereeuw-Hautier

  8. Department of Dermatology, Hospital Infantil Niño Jesús, Madrid, Spain

    Angela Hernández-Martín

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  1. Carlos Gutiérrez-Cerrajero
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Contributions

Introduction (A.H.-M., C.G.-C. and R.G.-S.); Epidemiology (A.H.-M., C.G.-C., E.S. and R.G.-S.); Mechanisms/pathophysiology (C.G.-C., E.S., M.A. and R.G.-S.); Diagnosis/screening/prevention (A.H.-M., C.G.-C., E.S., A.S.P. and R.G.-S.); Management (A.H.-M., E.S., A.S.P., M.A. and J.M.-H.); Quality of life (A.H.-M., C.G.-C., E.S. and A.S.P.); Outlook (A.H.-M., C.G.-C. and R.G.-S.); Overview of the Primer (A.H.-M.).

Corresponding author

Correspondence to Angela Hernández-Martín.

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Competing interests

The authors declare the following competing interests: A.S.P.: investigator for AbbVie, AnaptysBio, Eli Lilly, Incyte, Janssen, Krystal Biotech, Regeneron Pharmaceuticals Inc. and UCB; consultant with honorarium for AbbVie, Acrotech, Almirall, Amgen, Amryt Pharma, Arcutis Biotherapeutics, Arena Pharmaceuticals, Azitra, BioCryst, BiomX, BMS, BridgeBio, Castle Creek Biosciences, Catawba Research, Eli Lilly, Exicure, Gilead, Incyte, Janssen, Johnson & Johnson, Kamari Pharma, LEO Pharma, Novartis, OM Pharma, Pfizer, Pierre Fabre, RAPT Therapeutics, Regeneron Pharmaceuticals, Inc., Sanofi, Seanergy and UCB; data and safety monitoring board for AbbVie, Abeona Therapeutics, Bausch Health, Galderma and Novan. J.M.-H.: investigator for Sanofi, Mayne Pharma and Timber Pharmaceuticals. A.H.-M.: investigator for Mayne Pharma and Celgene. C.G.-C., E.S., M.A. and R.G.-S. declare no competing interests.

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Gutiérrez-Cerrajero, C., Sprecher, E., Paller, A.S. et al. Ichthyosis. Nat Rev Dis Primers 9, 2 (2023). https://doi.org/10.1038/s41572-022-00412-3

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