Actinic Keratoses

ByJulia Benedetti, MD, Harvard Medical School
Reviewed/Revised Oct 2023
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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 or field-directed therapy.

The prevalence of actinic keratoses is high and increases with age. Actinic keratoses constitute a significant risk of progression to squamous cell carcinoma. 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 < 1% to 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, blond or red hair, blue eyes, and skin type I or II (see table Fitzpatrick Skin Type Classification).

Table
Table

(See also Overview of Effects of Sunlight.)

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

  • Clinical examination

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, 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 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 2 categories:

  • Lesion-directed therapy

  • Field-directed therapy

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,

  • 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). Early data suggest that combining 5% FU cream with 0.005% calcipotriol may enhance efficacy of 5-FU (2).

These topical drugs can cause inflammation (often with redness and scaling) and pain during treatment and usually for 1 to 2 weeks afterward.

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.

Treatment references

  1. 1. Jansen M, Kessels 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. 2. Cunningham TJ, Tabacchi M, Eliane JP, et alJ Clin Invest 127(1):106–116, 2017. doi: 10.1172/JCI89820

Drugs Mentioned In This Article
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