- Common, usually multiple, premalignant lesions of sun-exposed areas of the skin. Many resolve spontaneously, and a small proportion progresses to squamous cell carcinoma (SCC).
- Common consequence of excessive cumulative ultraviolet (UV) light exposure
- Synonym(s): solar keratosis
Rare (if child, look for freckling and other stigmata of xeroderma pigmentosum)
- Rates vary with age group and exposure to sun.
- Predominant age: ≥40 years; progressively increases with age
- Predominant sex: male > female
- Common in those with blonde and red hair; rare in darker skin types
- Age-adjusted prevalence rate for actinic keratoses (AKs) in U.S. Caucasians is 6.5%.
- For 65- to 74-year-old males with high sun exposure: ~55%; low sun exposure: ~18%
Etiology and Pathophysiology
- The epidermal lesions are characterized by atypical keratinocytes at the basal layer with occasional extension upward. Mitoses are present. The histopathologic features resemble those of SCC in situ or SCC, and the distinction depends on the extent of epidermal involvement.
- Cumulative UV exposure
The p53 chromosomal mutation has been shown consistently in both AKs and SCCs. Many new genes have been shown recently to have similar expression profiles in AKs and SCCs.
- Exposure to UV light (especially long-term and/or repeated exposure due to outdoor occupation or recreational activities, indoor or outdoor tanning)
- Skin type: burns easily, does not tan
- Immunosuppression, especially organ transplantation
Sun avoidance and protective techniques are helpful.
Commonly Associated Conditions
- Other features of chronic solar damage: lentigines, elastosis, and telangiectasias
- The lesions are frequently asymptomatic; symptoms may include pruritus, burning, and mild hyperesthesia.
- Lesions may enlarge, thicken, or become more scaly. They also may regress or remain unchanged.
- Most lesions occur on the sun-exposed areas (head and neck, hands, forearms).
- Usually small (<1 cm), often multiple red, pink, or brown macules, papules, or plaques that are rough to palpation
- Yellow or brown adherent scale is often present on top of the lesion.
- Several clinical variants exist.
- Atrophic: dry, scaly macules with indistinct borders and an erythematous base
- Hypertrophic: Overlying hyperkeratosis (in an extreme form, cutaneous horn) may be impossible to differentiate from SCC clinically.
- Pigmented: smooth tan/brown plaque, spreading centrifugally
- Bowenoid: red scaly plaques with distinct borders
- Actinic cheilitis: inflammatory lesion involving usually the lower lip
- SCC (hypertrophic type)
- Bowen disease
- Basal cell carcinoma
- Verruca vulgaris
- Less likely: verrucous nevi, warty dyskeratoma, lichenoid keratoses, seborrheic keratoses, porokeratoses, seborrheic dermatitis or psoriasis (near hairline), lentigo maligna, solar lentigo, discoid lupus erythematosus
Diagnostic Tests & InterpretationDiagnostic Procedures/Other
- The diagnosis is usually made clinically, except where there is a suspicion of carcinoma.
- Skin biopsy is especially recommended if large, ulcerated, indurated, or bleeding, or if the lesions are nonresponsive to treatment.
- Dysplastic keratinocytes in lower levels of epidermis with a dermal lymphocytic infiltrate
- Neoplastic cells, mostly found in the lower epidermal layers, are cytologically identical to those of SCCs.
- If neoplastic cells extend throughout entire epidermis or into the dermis, the lesions will qualify as an SCC in situ or invasive SCC, respectively.
- Malignant cells are sparse except of the bowenoid variety.
- Hypertrophic, atrophic, bowenoid, acantholytic, and pigmented varieties show the corresponding epidermal findings.
- First-line treatment is cryotherapy (technically, this is considered surgery, especially by insurance companies) (1,2)[A]. Medical therapy is usually reserved for extensive AKs (“field therapy”).
- Cryotherapy combined with a topical approach resulted in significantly higher complete clearance rates than monotherapy (3)[A].
- Sun-protective techniques
- Sunscreens and physical sun protection recommended
- Topical treatments target both visible and subclinical lesions.
- With the exception of generic 5-fluorouracil, medication cost is high ($600 to $1,200 per course).
- Topical fluorouracil (Efudex, Carac, Fluoroplex cream, Fluoroplex solution)
- Every day—BID for 3 to 6 weeks, depending on the brand, concentration, and formulation
- Can be very irritating
- May be most effective of the topical treatments listed in this section (3)[A]
- Topical imiquimod (Aldara) 5% cream
- Apply 2 days per week at HS for up to 16 weeks to an area not larger than the forehead or one cheek.
- Can be irritating
- Topical imiquimod (Zyclara) 3.75% cream
- Apply once a day for 2 weeks, followed by no treatment for the next 2 weeks, and then apply once a day for another 2 weeks.
- Can be irritating
- Topical ingenol mebutate (Picato) 0.015% and 0.05% gel
- Apply to the face and scalp once a day for 3 consecutive days.
- Apply to the trunk and extremities once a day for 2 consecutive days.
- It should only be used on one contiguous skin area of not >25 cm2.
- Cases of severe allergic reactions (including anaphylaxis) and herpes zoster reactivation unrelated to application errors have been reported.
- Diclofenac (Solaraze) 3% gel
- Apply BID for 60 to 90 days.
- Topical tretinoin (Retin-A) or tazarotene (Tazorac): may be used to enhance the efficacy of topical fluorouracil
- Systemic retinoids: used infrequently
Close monitoring with no treatment is an appropriate option for mild lesions.
- Cryosurgery (“freezing,” liquid nitrogen)
- Most common method for treating AK
- Cure rate: 75–98.8%
- May cause atrophy and hypopigmentation
- May be superior to photodynamic therapy for thicker lesions
- Photodynamic therapy with a photosensitizer (e.g., aminolevulinic acid) and “blue light”
- May clear >90% of AKs
- Less scarring than cryotherapy
- May be superior to cryotherapy, especially in the case of more extensive skin involvement
- Curettage and electrocautery (electrodesiccation and curettage [ED&C]; “scraping and burning”)
- Medium-depth peels, especially for the treatment of extensive areas
- CO2 laser therapy
- Surgical excision (excisional biopsy)
Depends on associated malignancy and frequency with which new AKs appear
- Teach sun-protective techniques.
- Limit outdoor activities between 10 AM and 4 PM.
- Wear protective clothing and wide-brimmed hat.
- Proper use (including reapplication) of sunscreens with SPF >30, preferably a preparation with broad-spectrum (UV-A and UV-B) protection
- Teach self-examination of skin (melanoma, squamous cell, basal cell).
- Patient education materials
Very good. A significant proportion of the lesions may resolve spontaneously (4), with regression rates of 20–30% per lesion per year.
- AKs are premalignant lesions that may progress to SCCs. The rate of malignant transformation is unclear; the reported percentages vary but range from 0.1% to a few percent per year per lesion.
- Patients with AKs are at increased risk for other cutaneous malignancies.
- Approximately 60% of SCCs arise from an AK precursor.
Feldman SR, Fleischer AB Jr. Progression of actinic keratosis to squamous cell carcinoma revisited: clinical and treatment implications. Cutis. 2011;87(4):201–207. [PMID:21644496]
- 201101007 Actinic keratosis (disorder)
- 254667001 Hypertrophic solar keratosis
- 304524009 Bowenoid actinic keratosis (disorder)
- 403198004 lichenoid actinic keratosis (disorder)
- 403199007 Acantholytic actinic keratosis
- 403200005 Atrophic actinic keratosis
- 449732002 Pigmented actinic keratosis (disorder)
- AKs are premalignant lesions, although most will not progress to squamous cell cancer and many will regress with time.
- Often more easily felt than seen
- Therapy-resistant lesions should be biopsied, especially on the face.
Solar keratosis. Note the erosions and crusting on the lower lip.
- Helfand M, Gorman AK, Mahon S, et al. Actinic Keratoses: Final Report. Rockville, MD: Agency for Healthcare Research and Quality; 2001.
- de Berker D, McGregor JM, Hughes BR; for British Association of Dermatologists Therapy Guidelines and Audit Subcommittee. Guidelines for the management of actinic keratoses. Br J Dermatol. 2007;156(2):222–230. [PMID:17223860]
- Heppt MV, Steeb T, Ruzicka T, et al. Cryosurgery combined with topical interventions for actinic keratosis: a systematic review and meta-analysis [published online ahead of print November 17, 2018]. Br J Dermatol. doi:10.1111/bjd.17435. [PMID:23550994]
- Criscione VD, Weinstock MA, Naylor MF, et al; for Department of Veterans Affairs Topical Tretinoin Chemoprevention Trial Group. Actinic keratoses: natural history and risk of malignant transformation in the Veterans Affairs Topical Tretinoin Chemoprevention Trial. Cancer. 2009;115(11):2523–2530. [PMID:19382202]
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