{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,26]],"date-time":"2025-11-26T05:16:07Z","timestamp":1764134167655,"version":"3.46.0"},"reference-count":162,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2025,11,19]],"date-time":"2025-11-19T00:00:00Z","timestamp":1763510400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceuticals"],"abstract":"<jats:p>Rare diseases are conditions that affect up to 65 people per 100,000 individuals. They are also known as \u201corphan diseases\u201d, because they attract limited interest from researchers and pharmaceutical industries. Epidermolysis bullosa (EB), ichthyosis, Hailey\u2013Hailey disease (HHD), Darier disease (DD), erythrokeratoderma, porokeratosis, inflammatory linear verrucous epidermal nevus (ILVEN) and piebaldism are examples of rare genetic skin diseases with few approved treatments. Topical treatments are the principal approach for rare dermatological diseases, and it can be useful to manage the symptoms or the patophysiology of these diseases. This study aimed to conduct a comprehensive review of the topical treatments of EB, ichthyosis, HHD, DD, erythrokeratodermias, porokeratosis, ILVEN, and piebaldism. The search was performed across the SciELO, MEDLINE\u00ae\/PubMed\u00ae, Embase and Cochrane databases. This review identified porokeratosis, EB, and congenital ichthyosis as the rare genodermatoses with the highest number of reported studies and topical treatment options. In contrast, conditions such as piebaldism, erythrokeratodermia, and HHD have fewer reported topical interventions. For most rare genetic dermatological diseases, treatment aims to improve quality of life and control clinical signals and symptoms. Creams, gels, and ointments are frequently used as the main pharmaceutical approaches, and several pharmacological classes are employed, including keratolytics, retinoids, vitamin D analogs, topical corticosteroids, calcineurin inhibitors, and cytotoxic or antiproliferative agents. This review highlights the potential of off-label use of topical therapies as cost-effective alternatives in the treatment of rare genetic skin disorders. It also reinforces the critical role of compounded medicines in allowing for dose optimization, drug repurposing, and formulation adjustments, personalizing treatment to achieve improved therapeutic outcomes.<\/jats:p>","DOI":"10.3390\/ph18111762","type":"journal-article","created":{"date-parts":[[2025,11,19]],"date-time":"2025-11-19T15:03:15Z","timestamp":1763564595000},"page":"1762","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Topical Treatments for Rare Genetic Dermatological Diseases: A Narrative Review"],"prefix":"10.3390","volume":"18","author":[{"given":"Beatriz de Araujo","family":"Oliveira","sequence":"first","affiliation":[{"name":"Laborat\u00f3rio de Desenvolvimento Gal\u00eanico, Faculty of Pharmacy, Federal University of Rio de Janeiro (UFRJ), Rio de Janeiro 21941-971, Brazil"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6077-3580","authenticated-orcid":false,"given":"Ana","family":"Torres","sequence":"additional","affiliation":[{"name":"UCIBIO\u2014Applied Molecular Biosciences Unit, Department of Drug Sciences, Faculty of Pharmacy, University of Porto, 4050-313 Porto, Portugal"},{"name":"Associate Laboratory i4HB, Institute for Health and Bioeconomy, Faculty of Pharmacy, University of Porto, 4050-313 Porto, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2550-696X","authenticated-orcid":false,"given":"Eduardo","family":"Ricci-J\u00fanior","sequence":"additional","affiliation":[{"name":"Laborat\u00f3rio de Desenvolvimento Gal\u00eanico, Faculty of Pharmacy, Federal University of Rio de Janeiro (UFRJ), Rio de Janeiro 21941-971, Brazil"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1498-048X","authenticated-orcid":false,"given":"Isabel F.","family":"Almeida","sequence":"additional","affiliation":[{"name":"UCIBIO\u2014Applied Molecular Biosciences Unit, Department of Drug Sciences, Faculty of Pharmacy, University of Porto, 4050-313 Porto, Portugal"},{"name":"Associate Laboratory i4HB, Institute for Health and Bioeconomy, Faculty of Pharmacy, University of Porto, 4050-313 Porto, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2422-8048","authenticated-orcid":false,"given":"Mariana Sato S. 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