What are the treatment options for actinic keratosis?

Treatment of Actinic Keratosis

For patients with actinic keratosis, use 5-fluorouracil (5-FU) as first-line field treatment for multiple lesions and cryosurgery for isolated individual lesions. 1, 2

Initial Assessment and Treatment Selection

The choice between lesion-directed versus field-directed therapy depends on the number and distribution of lesions 1:

• For isolated or few lesions: Use cryosurgery as first-line treatment with clearance rates of 57-98.8% 2
• For multiple lesions or field cancerization: Use topical 5-fluorouracil as first-line field treatment due to superior efficacy 1, 2
• For thicker or hyperkeratotic lesions: Consider curettage with histological examination, especially when suspecting early squamous cell carcinoma 3, 4

Field-Directed Treatment Options (Ranked by Efficacy)

First-Line: 5-Fluorouracil (5-FU)

• 5% 5-FU cream: Apply twice daily for 3-4 weeks, reduces approximately 70% of lesions for up to 12 months 3
• 0.5% 5-FU cream: Apply once daily for 4 weeks, achieves 67% reduction in lesions with better tolerability than 5% formulation 5
• 4% 5-FU cream: Newer formulation with high efficacy and low recurrence rates 6
• Daily application is significantly more effective than weekly application (median lesion count of 0 vs. 3 at 52 weeks, P < 0.05) 7
• Strong recommendation from the American Academy of Dermatology 1

Second-Line: Imiquimod

• 5% imiquimod cream: Apply three times weekly for 16 weeks, achieves 47% complete response rate 1, 2, 3
• Strong recommendation from the American Academy of Dermatology 1

Third-Line: Diclofenac

• 3% diclofenac gel: Apply for 60-90 days, moderate efficacy with low morbidity for mild actinic keratoses 2, 3
• Conditional recommendation due to lower efficacy compared to 5-FU and imiquimod 1
• Important caveat: NSAIDs carry black box warning for cardiovascular and gastrointestinal side effects 1

Lesion-Directed Treatment Options

Cryosurgery

• Strong recommendation for isolated lesions 1, 2
• Achieves 75% complete response rate 4
• Double freeze-thaw cycle more effective than single cycle (75% vs. 68% response) 4
• For periorbital lesions, use contact probe to avoid eye contact 2, 3

Photodynamic Therapy (PDT)

• Aminolevulinic acid (ALA) with red light PDT: FDA-approved for lesion-directed and field-directed treatment of mild-to-moderate actinic keratoses on face and scalp 8
• Conditional recommendation with 1-4 hour incubation time 1
• Particularly effective for confluent lesions on scalp and difficult-to-treat areas 3
• Lower risk of unfavorable scarring on legs compared to other physical therapies 3

Other Physical Modalities

• Curettage: Warranted for grade 3 (thick) lesions resistant to topical treatments or when suspecting early squamous cell carcinoma 2, 3
• 100% phenol: Apply once monthly for up to 8 months, shows no recurrence at 12 months 3
• CO2 laser ablation: Conditional recommendation favoring cryosurgery over laser 1

Location-Specific Considerations

High-Risk Sites Requiring Special Attention

Ears:

• Higher risk of transformation to squamous cell carcinoma 3, 4
• Perform histological biopsy for thick lesions 2, 3, 4

Periorbital area:

• Avoid product contact with eyes 2, 3
• Prefer cryotherapy with contact probe 2, 3

Legs:

• Risk of poor healing 3
• PDT presents less scarring risk than other physical therapies 3

Backs of hands:

• Topical treatments may require longer periods 3
• Pretreatment with 5% salicylic acid improves results 3

Scalp (especially with hair loss):

• Frequent site for involvement 1
• PDT particularly effective for confluent lesions 3

Combination Treatment Strategies

When single-agent therapy proves insufficient:

• Diclofenac 3% followed by 5-FU 0.5% in 10% salicylic acid: Effective sequential treatment 3
• 5-FU 5% for 5-7 days as pretreatment: Enhances efficacy when combined with cryotherapy or PDT 3
• PDT followed by imiquimod twice weekly for 16 weeks: More beneficial than PDT alone 3

Critical Clinical Pitfalls

When to escalate care:

• Failure of individual lesion to respond to physical therapy requires further evaluation, potentially formal excision 3
• Ulcerated lesions require curettage with histological examination to rule out invasive squamous cell carcinoma 4
• Two or three cycles of curettage may be necessary for hyperkeratotic or ulcerated lesions 4

Managing treatment expectations:

• Inflammation is necessary for therapeutic effect with 5-FU (mean inflammation score 3.8 in patients who cleared vs. 1.9 in those who didn't, P < 0.05) 7
• Patient education on side effects is essential as treatments cause redness, pain, and crusting 3, 4
• Spontaneous regression occurs in 15-25% of cases over one year, but recurrence rate can reach 50% within first year 1, 2, 3

Risk Stratification

Progression risk to squamous cell carcinoma:

• Individual lesion progression: less than 0.1% to 20% 1, 4
• For patient with average 7.7 lesions: approximately 10% cumulative risk over 10 years that at least one will transform 2, 3
• Higher risk in immunosuppressed patients, advanced age, or previous skin cancer history 1

When observation may be considered:

• Limited life expectancy where treatment morbidity outweighs benefits 1
• Shared decision-making essential given varying degrees of patient participation and discomfort between modalities 1

Prevention (Essential Component of Management)

• Strong recommendation for UV protection in all patients with actinic keratosis 1
• Regular use of high-index sunscreen reduces appearance of new lesions 2, 3, 4
• Sunscreen with SPF ≥17 applied twice daily for 7 months superior to emollient in reducing total lesion count 2, 3