The prevalence of actinic keratoses is high and increases with age. Actinic keratoses constitute a significant risk of progression to squamous cell carcinoma Squamous Cell Carcinoma Squamous cell carcinoma is a malignant tumor of epidermal keratinocytes that invades the dermis; this cancer usually occurs in sun-exposed areas. Local destruction may be extensive, and metastases... read more . The estimated rate of progression for an individual actinic keratosis to a squamous cell carcinoma varies widely in the medical literature, but consensus estimates most often range from about < 1% to about 10%. Actinic keratoses that do not progress to squamous cell carcinoma may regress or persist as actinic keratoses. Lesions that regress may subsequently recur.
In addition to many years of sun exposure, other risk factors for actinic keratoses include older age, underlying immunosuppression, blonde or red hair, blue eyes, and skin type I or II (see table Fitzpatrick Skin Type Classification Fitzpatrick Skin Type Classification ).
Symptoms and Signs of Actinic Keratoses
Actinic keratoses often have adherent scales and are sometimes more easily felt than seen. Actinic keratoses can appear thickened or hypertrophic and sometimes form a cutaneous horn. They may be pink, red, or, less commonly, gray or brown. Lesions frequently develop in sun-exposed areas (eg, balding scalp, face, lateral neck, distal upper or lower extremities). Diffuse involvement of the lip is called actinic cheilitis.
Diagnosis of Actinic Keratoses
Diagnosis of actinic keratoses is often based on visual and tactile examination; lesions feel rough and scaly on palpation. They should be differentiated from seborrheic keratoses Seborrheic Keratoses Seborrheic keratoses are superficial, often pigmented, epithelial lesions that are usually warty but may occur as smooth papules. The cause of seborrheic keratosis is unknown, but genetic mutations... read more , which increase in number and size with age. Seborrheic keratoses tend to appear waxy and stuck-on but can take on an appearance similar to that of actinic keratoses. Close inspection usually reveals distinguishing characteristics of the lesion. An actinic keratosis can also be distinguished from a seborrheic keratosis by the rough, gritty feel of the scale and the erythema. Unlike actinic keratoses, seborrheic keratoses also occur on non–sun-exposed areas of the body and are not precancerous.
Treatment of Actinic Keratoses
Lesion-directed therapy or field-directed therapy
Treatment options depend on the number of lesions, their location, extent of photodamage, and patient preference, but typically they are divided into two categories:
In lesion-directed therapy, individual lesions are physically removed. This option may be better if the patient has only a few actinic keratoses, or if the patient is unable or unwilling to undergo other therapy options. Cryosurgery (freezing with liquid nitrogen) is the most common lesion-directed therapy. Curettage (scraping with a curette) is an alternative. Lesion-directed therapies have the benefit of being single, in-office procedures, but they may not address subclinical changes and have a higher risk of scarring.
In field-directed therapy, topical treatments are applied to larger, diffuse areas of involvement. Topical fluorouracil (5-FU) cream and imiquimod cream are the usual first-line drug treatments. Alternatives include diclofenac gel and tirbanibulin ointment.
5-FU inhibits thymidylate synthetase, limiting DNA synthesis and causing death of damaged cells. 5-FU 5% cream is applied 2 times a day for 3 to 4 weeks. A recent study has shown 5-FU to be the most effective treatment for actinic keratoses ( 1 Treatment references Actinic keratoses are precancerous changes in skin cells (keratinocytes) that are a frequent consequence of many years of sun exposure. Diagnosis is clinical. Treatment typically includes lesion-directed... read more ). Early data suggest that combining 5% FU cream with 0.005% calcipotriol may enhance efficacy of 5-FU ( 2 Treatment references Actinic keratoses are precancerous changes in skin cells (keratinocytes) that are a frequent consequence of many years of sun exposure. Diagnosis is clinical. Treatment typically includes lesion-directed... read more ).
Imiquimod is an immune response modifier that stimulates local cytokine induction, resulting in a brisk local inflammatory reaction. Imiquimod 5% cream is applied 2 times a week for 16 consecutive weeks.
Diclofenac is a nonsteroidal anti-inflammatory drug that inhibits both cyclooxygenase and upregulation of the arachidonic acid cascade. Diclofenac 3% (in a 2.5% hyaluronan gel) is applied 2 times a day for 60 to 90 days. Its use is limited by its low efficacy.
Tirbanibulin is a microtubule inhibitor that inhibits tubulin polymerization and Src kinase signaling, inducing death of damaged cells. Tirbanibulin 1% ointment is applied once a day for 5 days; however, the course may need to be extended because recurrence rates are high.
These topical drugs can cause inflammation (often with redness and scaling) and pain during treatment and usually for 1 to 2 weeks afterward.
Photodynamic therapy is another type of field-directed therapy. It involves topical application of a photosensitizer (eg, aminolevulinate, methyl aminolevulinate) followed by light of a specific wavelength that preferentially affects photodamaged skin. Like topical field-directed therapy, photodynamic therapy can cause redness and scaling during treatment. More than one treatment session may be needed.
If patients do not respond to therapy, clinicians should consider doing a biopsy to rule out squamous cell carcinoma.
Patients should also be told about the importance of sun-protective measures Prevention The skin may respond to sunlight with chronic (eg, dermatoheliosis [photoaging], actinic keratosis) or acute (eg, photosensitivity, sunburn) changes. The sun emits a wide range of electromagnetic... read more .
1. Jansen M, JKessels J, Nelemans P, Kouloubis N, et al: Randomized Trial of Four Treatment Approaches for Actinic Keratosis. N Engl J Med 380(10):935–946, 2019. doi: 10.1056/NEJMoa1811850
2. Cunningham TJ, Tabacchi M, Eliane JP, et al: Randomized trial of calcipotriol combined with 5-fluorouracil for skin cancer precursor immunotherapy. J Clin Invest 127(1):106–116, 2017. doi: 10.1172/JCI89820
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