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Association Between Local Skin Reactions and Efficacy with 5-Fluorouracil 4% Cream in Actinic Keratosis: A Post-Hoc Analysis of Two Randomised Clinical Trials.

Dermatol Ther (Heidelb)

January 2025

Medical Direction Pharmaceutical Care and Medical Dermatology, Pierre Fabre Dermatologie, Les Cauquillous, 81500, Lavaur, France.

Introduction: Topical 5-fluorouracil (5-FU), 5% or 4% cream, is recommended among first-line treatments for actinic keratosis (AK). Local skin reactions (LSRs) are an expected and transient response to treatment with 5-FU but can lead to treatment discontinuation when severe. This analysis aimed to investigate whether the severity of LSRs during the treatment was associated with lesion clearance assessed 4 weeks after completing treatment.

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Actinic keratoses (AK) usually occur on sun-exposed areas in elderly patients with Fitzpatrick I-II skin types. Dermatoscopy and ultrasonography are two non-invasive tools helpful in examining clinically suspicious lesions. This study presents the usefulness of image-processing algorithms in AK staging based on dermatoscopic and ultrasonographic images.

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Background/objectives: Skin cancer is becoming increasingly common due to increasing risk factors such as excessive ultraviolet (UV) radiation, genetic predisposition, fair skin, and a history of sunburn. Melanoma accounts for only 1% of cases but causes most skin cancer deaths. Dysplastic nevi (DN) are important precursors of melanoma.

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Nagashima-type palmoplantar keratosis (NPPK) has been shown to represent a form of autosomal recessive palmoplantar keratosis due to biallelic pathological variants of SERPINB7, which encodes a serine protease inhibitor expressed in the epidermis. Approximately 10 years have elapsed since NPPK was demonstrated to be an independent genetic disease, and the most prevalent palmoplantar keratoderma (PPK) in East Asian countries due to a high prevalence of founder mutations in SERPINB7. Since then, it has become evident that biallelic pathological variants of SERPINA12, which encodes a serine protease inhibitor expressed in the epidermis, can also manifest symptoms analogous to those of NPPK.

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Keratitis-ichthyosis-deafness syndrome (KID) is a rare genetic disorder characterized by the triad of hyperkeratosis, ichthyosis, and congenital prelingual sensorineural deafness, with less than 100 cases described in the literature. In addition to many other extra-cutaneous manifestations, these patients are burdened by two principal increased risk factors involving the skin: the risk of developing infections and the risk of developing malignant skin tumors, especially Squamous Cell Carcinoma and Trichilemmal tumors. We present the case of a 7-year-old girl with a unique genetic variant described to date, who developed 4 dyskeratotic neoformation.

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