Pharmacological Agents Used in the Prevention and Treatment of Actinic Keratosis: A Review

Abstract

Actinic keratosis (AK) is among the most commonly diagnosed skin diseases with potentially life-threatening repercussions if left untreated. Usage of pharmacologic agents represents one of many therapeutic strategies that can be used to help manage these lesions. Ongoing research into these compounds continues to change our clinical understanding as to which agents most benefit particular patient populations. Indeed, factors such as past personal medical history, lesion location and tolerability of therapy only represent a few considerations that clinicians must account for when prescribing appropriate treatment. This review focuses on specific drugs used in either the prevention or treatment of AKs. Nicotinamide, acitretin and topical 5-fluorouracil (5-FU) continue to be used with fidelity in the chemoprevention of actinic keratosis, although some uncertainty persists in regard to which agents should be used in immunocompetent vs. immunodeficient/immunosuppressed patients. Topical 5-FU, including combination formulations with either calcipotriol or salicylic acid, as well as imiquimod, diclofenac and photodynamic light therapy are all accepted treatment strategies employed to target and eliminate AKs. Five percent of 5-FU is regarded as the most effective therapy in the condition, although the literature has conflictingly shown that lower concentrations of the drug might also be as effective. Topical diclofenac (3%) appears to be less efficacious than 5% 5-FU, 3.75-5% imiquimod and photodynamic light therapy despite its favorable side effect profile. Finally, traditional photodynamic light therapy, while painful, appears to be of higher efficacy in comparison to its more tolerable counterpart, daylight phototherapy.

Keywords: 5-FU; ALA; MAL; NMSC; PDT; SCC; acitretin; actinic keratosis; calcipotriol; dPDT; daylight; diclofenac; imiquimod; nicotinamide; pharmacotherapy; photodynamic light therapy; salicylic acid; squamous cell carcinoma.

Figure 1

An overview regarding the initiation and progression of actinic keratosis lesions. The process is primarily driven by UVB-mediated keratinocytic DNA damage in the basal layer of the epidermis, particularly implicating tumor suppressor gene, p53. UVA-mediated reactive oxygen species (ROS) formation in the context of hydroxyl radical production in the dermis also promotes a pro-inflammatory, pro-tumorigenic environment via suppression of immune homeostasis and function. These factors combined allow for keratinocyte dysplasia to continue unchecked, eventually leading to the formation of visible actinic keratosis lesions on the surface of the epidermis.