Membrive Jiménez Cristina, Pérez Ramírez Cristina, Sánchez Martín Almudena, Vieira Maroun Sayleth, Arias Santiago Salvador, Ramírez Tortosa María Carmen, Jiménez Morales Alberto
Pharmacy Service, Pharmacogenetics Unit, University Hospital Virgen de las Nieves, 18014 Granada, Spain.
Center of Biomedical Research, Department of Biochemistry and Molecular Biology II, Institute of Nutrition and Food Technology "José Mataix", University of Granada, Avda. del Conocimiento s/n., Armilla, 18016 Granada, Spain.
Pharmaceuticals (Basel). 2021 Sep 6;14(9):905. doi: 10.3390/ph14090905.
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.
皮肤病理学是全球非致命性疾病的第四大常见病因;然而,它们产生的社会心理、经济和职业影响与其他慢性疾病相当或更大。最常见的是光化性角化病,其次是基底细胞癌,痤疮、银屑病、化脓性汗腺炎等比例较小,疱疹样皮炎则更为罕见。为治疗光化性角化病和基底细胞癌,局部使用0.5%的5-氟尿嘧啶(5-FU)效果良好,尽管在某些患者中会产生严重毒性。另一方面,氨苯砜是一种常用于治疗疱疹样皮炎等炎症性皮肤病的药物;然而,它偶尔会导致溶血性贫血。此外,已证明用于治疗中重度银屑病和化脓性汗腺炎的生物药物是有效且安全的;然而,一小部分患者长期对生物药物治疗无反应或治疗无效。这种个体反应差异可能是由于编码参与疾病病理环境或药物作用机制的蛋白质的基因发生改变。药物遗传学研究基因变异与药物反应之间的关系,这有助于早期识别无反应患者以及治疗后发生毒性风险较高的患者。本综述描述了目前皮肤科治疗中证据最充分的药物遗传学建议,重点介绍了临床实践指南中包含的建议。目前,我们仅能找到关于5-FU的药物遗传学临床指南。然而,氨苯砜的产品特性摘要包含了美国食品药品监督管理局的药物遗传学建议。最后,在接受生物治疗的皮肤病患者(主要是银屑病患者)中,有大量来自药物遗传学研究的信息,但这些信息需要经过验证才能纳入临床实践指南。