Abstract
Dermatologic pathologies are the fourth most common cause of non-fatal disease worldwide; however, they produce a psychosocial, economic, and occupational impact equal to or greater than other chronic conditions. The most prevalent are actinic keratosis, followed by basal-cell carcinoma, in a lesser proportion acne vulgaris, psoriasis, and hidradenitis suppurativa, among others, and more rarely dermatitis herpetiformis. To treat actinic keratosis and basal-cell carcinoma, 5-fluorouracil (5-FU) 0.5% is administered topically with good results, although in certain patients it produces severe toxicity. On the other hand, dapsone is a drug commonly used in inflammatory skin conditions such as dermatitis herpetiformis; however, it occasionally causes hemolytic anemia. Additionally, biologic drugs indicated for the treatment of moderate-to-severe psoriasis and hidradenitis suppurativa have proved to be effective and safe; nevertheless, a small percentage of patients do not respond to treatment with biologics in the long term or they are ineffective. This interindividual variability in response may be due to alterations in genes that encode proteins involved in the pathologic environment of the disease or the mechanism of action of the medication. Pharmacogenetics studies the relationship between genetic variations and drug response, which is useful for the early identification of non-responsive patients and those with a higher risk of developing toxicity upon treatment. This review describes the pharmacogenetic recommendations with the strongest evidence at present for the treatments used in dermatology, highlighting those included in clinical practice guides. Currently, we could only find pharmacogenetic clinical guidelines for 5-FU. However, the summary of product characteristics for dapsone contains a pharmacogenetic recommendation from the United States Food and Drug Administration. Finally, there is an enormous amount of information from pharmacogenetic studies in patients with dermatologic pathologies (mainly psoriasis) treated with biologic therapies, but they need to be validated in order to be included in clinical practice guides.
Highlights
Skin diseases are among the most prevalent reasons for seeking health care, varying between 5.5% and 22.5%
This section describes the current PGx findings in the treatment of dermatologic pathologies. It is classified into three levels according to the type of treatment: topical treatment: 5-FU in actinic keratosis and basal-cell carcinoma; systemic treatment: dapsone in dermatitis herpetiformis; treatment with biologic therapies in moderate-to-severe psoriasis and hidradenitis suppurativa (Table 1)
The Savva et al team evaluated the impact of various polymorphisms in the tumor necrosis factor (TNF) and TLR4 genes on the treatment response with anti-TNF drugs in 190 Caucasian patients diagnosed with Hidradenitis suppurativa (HS), 32 of whom were treated with ADA [103]
Summary
Skin diseases are among the most prevalent reasons for seeking health care, varying between 5.5% and 22.5%. This literature review presents the information currently available on pharmacogenetically significant drugs used to treat skin diseases It indicates the recommendations in PGx clinical guidelines for 5-fluorouracil, when used topically in patients diagnosed with actinic keratosis and/or basal-cell carcinoma, and the PGx recommendation in the summary of product characteristics for the drug dapsone when administered systemically to treat dermatitis herpetiformis. It highlights the most important PGx studies on biologic therapies indicated for hidradenitis suppurativa and moderate-to-severe psoriasis (Figure 1)
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