What are the treatment options for actinic keratosis?

Treatment Options for Actinic Keratosis

For actinic keratosis, the American Academy of Dermatology strongly recommends UV protection for all patients, cryosurgery for isolated lesions, and field-directed therapy with 5-fluorouracil or imiquimod for multiple lesions, with tirbanibulin emerging as a newer option offering the shortest treatment duration (5 days) with high efficacy. 1, 2

Treatment Selection Algorithm

Step 1: Assess Lesion Distribution

For isolated or few lesions (1-4 lesions):

• Cryosurgery is the first-line treatment, with clearance rates of 57-98.8% depending on freeze duration 2
• Longer freeze times (>20 seconds) achieve 83% clearance versus 39% with shorter freeze times (<5 seconds) 2
• Advantage: single office visit with immediate treatment 2
• Consider curettage for thicker lesions when squamous cell carcinoma is suspected, always obtaining histology 2

For multiple lesions (≥4-8 lesions in contiguous area):

• Field-directed therapy is recommended to treat both clinically visible and subclinical lesions 1, 2

Step 2: Select Field-Directed Therapy

The American Academy of Dermatology provides strong recommendations for three topical agents 1:

Tirbanibulin 1% (Newest, Shortest Duration)

• Applied once daily for only 5 consecutive days to a 25 cm² treatment area 1, 2
• Complete clearance: 49.3% at day 57 (versus 8.6% with vehicle) 1
• Partial clearance (≥75%): 72.2% 1
• Key advantage: Much shorter treatment duration compared to all other topical agents 2
• Side effects: Application site pruritus (9.1%) and pain (9.9%), with <1% experiencing severe reactions 1
• High certainty evidence with strong recommendation 1, 2

5-Fluorouracil (5-FU) - Highest Efficacy Rating

• Multiple concentration options: 1
  • 0.5% cream: once daily for 7-28 days
  • 5% cream: twice daily for 28 days
• Complete clearance: 38% at 6 months with 5% formulation (versus 17% placebo) 1
• The American Academy of Dermatology rates 5-FU with the highest efficacy among field treatments 2
• Enhanced efficacy with calcipotriol combination: 87.8% mean reduction in facial AKs (versus 26.3% with vehicle), though this increases skin redness (69% vs 25%) and burning (39% vs 13%) 1
• Expect >90% of patients to experience irritation with 0.5% formulation 1

Imiquimod (FDA-Approved for AK)

• Multiple dosing regimens: 1, 3
  • 5% cream: 3 times per week for 16 weeks (FDA-approved regimen)
  • 3.75% cream: daily for 2 weeks, 2-week rest, then 2 more weeks
  • 2.5% cream: similar cycling regimens
• Complete clearance: 44-47% at 8 weeks post-treatment (versus 3-7% placebo) 1, 3
• Partial clearance (≥75%): 58-64% 1, 3
• FDA-approved specifically for "clinically typical, nonhyperkeratotic, nonhypertrophic actinic keratoses on the face or scalp in immunocompetent adults" 3
• Important: 48% of patients experience increase in visible AK lesions during treatment as subclinical lesions become apparent, but these patients have similar response rates 3

Diclofenac 3% Gel (Conditional Recommendation)

• Applied twice daily for 60-90 days 1
• Moderate efficacy with low morbidity for mild AKs 1
• The American Academy of Dermatology gives only a conditional recommendation due to lower efficacy 1
• Consider for patients who cannot tolerate more effective but more irritating options 1

Step 3: Consider Photodynamic Therapy (PDT)

PDT is conditionally recommended for field treatment 1, 2:

• ALA-red light PDT: 77.1% complete clearance at 12 weeks 2
• ALA-blue light PDT: Moderate quality evidence, conditional recommendation 2
• ALA-daylight PDT: Less painful but equally effective as ALA-red light 2
• Advantage: Can treat large areas in single session
• Disadvantage: Requires office visit, specialized equipment, and photosensitivity precautions

Step 4: Combination Therapy Options

When monotherapy fails or for extensive disease 1, 2:

Conditionally recommended combinations:

• 5-FU + Cryosurgery: Moderate quality evidence supporting superiority over cryosurgery alone 2
• Imiquimod + Cryosurgery: Low quality evidence, but conditionally recommended over cryosurgery alone 2

Not recommended:

• Diclofenac + Cryosurgery: Conditionally recommended AGAINST compared to cryosurgery alone 2

Universal Recommendations

UV Protection (Strong Recommendation)

• The American Academy of Dermatology strongly recommends UV protection for ALL patients with AKs to prevent new lesions 1, 2
• Sunscreen application slows return of actinic keratoses 1
• Patients should minimize or avoid natural/artificial sunlight during treatment 3

Site-Specific Considerations

High-Risk Locations (Ear)

• The ear requires special consideration due to higher risk of metastasis when squamous cell carcinoma develops 2
• Consider more aggressive treatment or closer monitoring for ear lesions 2
• Curettage with histology is warranted for thicker lesions on the ear 2

Face and Scalp

• All major topical therapies (5-FU, imiquimod, tirbanibulin) are FDA-approved and strongly recommended for facial/scalp lesions 1, 3
• Cryosurgery achieves excellent results on face with proper technique 2

Critical Pitfalls to Avoid

Recurrence and Monitoring

• AKs have recurrence rates up to 50% within the first year, necessitating ongoing monitoring 2
• Regular follow-up is essential, particularly after treatment of superficial basal cell carcinoma with imiquimod 3

Progression Risk

• Risk of progression to squamous cell carcinoma ranges from <0.1% to 20%, with higher risk on the ear 2
• While individual lesion risk is low (0.25-1% per year), 60% of cutaneous squamous cell carcinomas arise from AKs 4

Treatment Duration Errors

• Do not extend imiquimod treatment beyond 16 weeks for AK, even with missed doses 3
• Do not extend superficial basal cell carcinoma treatment beyond 6 weeks 3
• Tirbanibulin is applied for exactly 5 consecutive days only 1

Application Technique

• Wash treatment area 8 hours after 5-FU or imiquimod application for AK 3
• For tirbanibulin, apply to 25 cm² field containing the lesions 1
• Avoid eyes, lips, and nostrils with all topical agents 3
• Do not occlude treatment area 3

Managing Local Reactions

• Most patients experience erythema, scaling, and crusting with normal dosing of topical agents 1, 3
• Rest periods may be necessary but should not extend total treatment duration beyond recommended limits 3
• Severe reactions warrant treatment interruption and physician contact 3

Immunosuppressed Patients

• Safety and efficacy of imiquimod have not been established in immunosuppressed patients 3
• Use with caution in patients with pre-existing autoimmune conditions 3

Practical Treatment Selection

For patients prioritizing convenience: Tirbanibulin (5 days) > Cryosurgery (single visit) 1, 2

For patients prioritizing efficacy: 5-FU (highest efficacy rating) > Tirbanibulin > Imiquimod 1, 2

For patients with low tolerance for irritation: Diclofenac (lowest morbidity but lower efficacy) > Tirbanibulin (shortest duration of irritation) 1, 2

For extensive field cancerization: PDT or 5-FU field therapy 1, 2