Exuberant inflammatory reaction to occlusion of topical 5-fluorouracil (FU) under a continuous positive airway pressure (CPAP) mask: A warning to dermatologists and patients

Actinic keratoses (AKs) are precancerous cutaneous lesions with a prevalence of 11% to 25%.1 Fair skin (Fitzpatrick type I and II) with light eyes and hair along with increased age, male gender, excessive ultraviolet light exposure, and immunosuppression increase the risk of AKs. AKs are most commonly found in ultraviolet-exposed sites, such as the head, neck, and upper extremities.2 They present as erythematous gritty macules, patches, papules, or plaques. Induration, ulceration, hemorrhage, rapid growth, or pain may indicate malignant transformation to squamous cell carcinoma. This transformation can be attributed to ultraviolet-induced mutation of the p53 gene and subsequent clonal proliferation of squamous cells in the epidermis.3, 4 Mutations in p53 are seen in approximately 53% of AKs and 70% to 90% of squamous cell carcinomas, and the progression of AKs to squamous cell carcinomas is estimated at 0.1% to 10%.2, 4 Hence, the treatment of all AKs is recommended and considered an important step in preventative dermatology.1, 2 The treatments for AKs are myriad and depend on the extent of disease (ie, number, location, and depth). All therapeutic interventions have advantages and disadvantages, and it is paramount to balance them with the patient's preference. For few, well-defined AKs, lesion-directed therapy is often preferred and cryotherapy is the treatment of choice. Other options include electrodessication and curettage and laser surgery. For numerous, ill-defined AKs, field therapy is typically recommended as it treats both clinically apparent and subclinical lesions. Field-directed therapies include 5-fluorouracil (FU), diclofenac, imiquimod, ingenol mebutate, chemical peels, and photodynamic therapy.1 Topical 5-FU is an antineoplastic medication that has been used to treat AKs since the 1970s when it was first approved by the Food and Drug Administration for topical dermatologic use.3 It is a pyrimidine analog that irreversibly binds and inhibits thymidylate synthetase and leads to a reduction in DNA and RNA synthesis.3 It preferentially targets AKs over normal epidermis. Topical 5-FU can cause an erosive dermatitis, pain, pruritus, hypopigmentation, and hyperpigmentation, which can result in poor medication compliance. Occlusion and extensive exposure to sunlight can precipitate these reactions.3, 5 Patient education about expected reactions and precipitating factors should be considered standard of care.