Keratosis, Actinic

Description

• 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

Geriatric Considerations
Frequent problem

Pediatric Considerations
Rare (if child, look for freckling and other stigmata of xeroderma pigmentosum)

Epidemiology

Incidence

• 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

Prevalence

• 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

Genetics
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.

Risk Factors

• 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

General Prevention

Sun avoidance and protective techniques are helpful.

Commonly Associated Conditions

• SCC
• Other features of chronic solar damage: lentigines, elastosis, and telangiectasias

History

• 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).

Physical Exam

• Usually small (<1 cm), often multiple red, pink, or brown macules, papules, or plaques that are rough to palpation, sometimes more easily felt than seen.
• 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

Differential Diagnosis

• SCC (hypertrophic type)
• Keratoacanthoma
• 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 & Interpretation

Diagnostic 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.

Test Interpretation

• 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 for the bowenoid variety.
• Hypertrophic, atrophic, bowenoid, acantholytic, and pigmented varieties show the corresponding epidermal findings.

General Measures

• Sun-protective techniques
• Sunscreens and physical sun protection recommended

Medication

First Line

• 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
  • Likely the most effective of the topical treatments listed in this section (2)[A],(4)[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
• Diclofenac (Solaraze) 3% gel
  • Apply BID for 60 to 90 days
  • The least irritating of the topical AK treatments therefore patients tend to be more compliant with it

Second Line

• Topical tretinoin (Retin-A) or tazarotene (Tazorac): may be used to enhance the efficacy of topical fluorouracil
• Systemic retinoids: used infrequently
• Delta aminolevulinate and methyl aminolevulinate combined with laser (photodynamic therapy) (see below)

Additional Therapies

Close monitoring with no treatment is an appropriate option for mild lesions.

Surgery/Other Procedures

• 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
• Dermabrasion
• Surgical excision (excisional biopsy)

Follow-up Recommendations

Patient Monitoring
Depends on associated malignancy and frequency with which new AKs appear

Patient Education

• 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
  • http://dermnetnz.org/lesions/solar-keratoses.html

Prognosis

Very good; a significant proportion of the lesions may resolve spontaneously (5), with regression rates of 20–30% per lesion per year.

Complications

• 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.

ICD-10

• L57.0 Actinic keratosis

SNOMED

• 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)