What are the treatment options for actinic keratosis?

Treatment of Actinic Keratosis

For actinic keratosis, use cryosurgery for isolated lesions or field-directed therapy with 5-fluorouracil or imiquimod for multiple lesions, with UV protection mandatory for all patients. 1

Universal Recommendation: UV Protection

• All patients with actinic keratosis must use UV protection to prevent new lesions, regardless of which treatment modality is selected. 1
• Minimize or avoid exposure to natural or artificial sunlight (tanning beds or UVA/B treatment) during and after treatment. 2

Treatment Selection Algorithm

For Isolated or Few Lesions: Lesion-Directed Therapy

• Cryosurgery with liquid nitrogen is the strongly recommended first-line treatment for isolated actinic keratoses. 1
• Clearance rates range from 57% to 98.8% depending on follow-up duration. 3
• Longer freeze times (>20 seconds) achieve significantly higher clearance rates (83%) compared to shorter freeze times (<5 seconds, 39% clearance). 3
• Cryosurgery offers the convenience of a single office visit. 3

For Multiple Lesions: Field-Directed Therapy

Strong Recommendations (Moderate Quality Evidence):

• 5-fluorouracil (5-FU) is strongly recommended for field treatment of multiple actinic keratoses. 1

  • The 0.5% concentration achieves complete clearance in 136 per 1000 participants compared to 15 per 1000 with placebo (RR 8.86). 4
  • Treatment typically requires application twice daily for 2-4 weeks. 1
  • Expect significant local skin reactions including erythema, crusting, and erosions during treatment. 1

• Imiquimod 5% cream is strongly recommended for field treatment of actinic keratoses on the face or scalp. 1, 2

  • FDA-approved for clinically typical, nonhyperkeratotic, nonhypertrophic actinic keratoses in immunocompetent adults. 2
  • Complete clearance rates of 44-46% at 8 weeks post-treatment. 2
  • Apply 2 times per week for 16 weeks, leaving on for approximately 8 hours before washing. 2
  • 371 per 1000 participants achieve complete clearance compared to 48 per 1000 with placebo (RR 7.70). 4

Conditional Recommendations:

• Diclofenac 3% in 2.5% hyaluronic acid gel is conditionally recommended with lower efficacy than 5-FU or imiquimod. 1

  • Complete clearance in 313 per 1000 participants compared to 127 per 1000 with vehicle (RR 2.46). 4
  • Carries black box warning for cardiovascular and gastrointestinal side effects as with all NSAIDs. 1

• Tirbanibulin is strongly recommended with the advantage of much shorter treatment duration. 3

  • Apply once daily for only 5 consecutive days. 3
  • Complete clearance rate of 49.3% at day 57. 3

Photodynamic Therapy (PDT)

• ALA-red light PDT is conditionally recommended with complete clearance rates of 77.1% at 12 weeks. 1, 3
• MAL-red light PDT achieves 527-656 complete clearances per 1000 participants compared to 89-147 per 1000 with placebo-PDT (RR 4.46). 4
• PDT with conventional light sources causes significant pain and discomfort, while daylight PDT is less painful but equally effective. 3, 5
• PDT demonstrates better cosmetic outcomes than cryotherapy or 5-fluorouracil. 4

Combination Therapy Approaches

• 5-fluorouracil plus cryosurgery is conditionally recommended over cryosurgery alone (moderate quality evidence). 1, 3
• Imiquimod plus cryosurgery is conditionally recommended over cryosurgery alone (low quality evidence). 1, 3
• Diclofenac plus cryosurgery is conditionally recommended against compared to cryosurgery alone. 3

Special Considerations

Immunocompromised Patients

• Safety and efficacy of imiquimod have not been established in immunosuppressed patients. 2
• Use imiquimod with caution in patients with pre-existing autoimmune conditions. 2
• Immunosuppressed patients require special consideration as they have higher rates of progression to squamous cell carcinoma. 1

Treatment Site Considerations

• The ear requires special attention due to higher risk of metastasis when squamous cell carcinoma develops at this site. 3
• Curettage may be warranted for thicker actinic keratoses, especially when suspicion of early squamous cell carcinoma exists, and histology must always be obtained. 3
• Below-the-knee lesions have poor healing as a particular concern, and all modalities can lead to ulceration. 1

Critical Pitfalls to Avoid

• Actinic keratoses have a recurrence rate as high as 50% within the first year, necessitating ongoing monitoring. 1, 3
• The risk of progression to squamous cell carcinoma varies from less than 0.1% to 20%, with higher risk in immunosuppressed patients. 1, 3
• Subclinical lesions may become apparent during treatment and should not be mistaken for treatment failure. 2
• Patients must be counseled that local skin reactions (erythema, erosions, crusting) are expected and indicate treatment efficacy, not failure. 2
• Treatment periods should not be extended beyond recommended durations due to missed doses or rest periods. 2
• 6% of imiquimod-treated patients who appeared clinically clear had evidence of tumor on excision, highlighting the importance of follow-up. 2

Expected Adverse Events

• Withdrawal due to adverse events occurs in 144 per 1000 participants with diclofenac compared to 40 per 1000 with vehicle alone. 4
• With imiquimod, 56 per 1000 participants withdraw due to adverse events compared to 21 per 1000 with placebo. 4
• Most patients experience erythema, flaking/scaling/dryness, and scabbing/crusting at the application site with normal dosing. 2
• Systemic flu-like symptoms (malaise, fever, nausea, myalgias, rigors) may occur and warrant dosing interruption. 2