What are the topical treatments for actinic keratosis?

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Last updated: March 13, 2025View editorial policy

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From the Guidelines

Topical treatments for actinic keratosis include 5-fluorouracil (5-FU), imiquimod, and diclofenac as first-line options, with 5-FU and imiquimod being strongly recommended due to their moderate to high efficacy and relatively low risk of side effects 1.

Treatment Options

  • 5-FU (Efudex, Fluoroplex) is typically applied twice daily for 2-4 weeks and works by interfering with DNA synthesis in rapidly dividing cells.
  • Imiquimod (Aldara, Zyclara) is used 2-3 times weekly for 4-16 weeks and stimulates the immune system to target abnormal cells.
  • Diclofenac 3% gel (Solaraze) is applied twice daily for 60-90 days and works through anti-inflammatory mechanisms.

Considerations

  • For patients with multiple lesions, field therapy with these agents is preferred over treating individual lesions.
  • Cryotherapy remains an option for isolated lesions.
  • Patients should expect skin irritation, redness, and inflammation during treatment as signs the medication is working.
  • Sun protection is essential during and after treatment to prevent recurrence.
  • Treatment selection depends on the number and location of lesions, patient compliance concerns, and tolerance for side effects.

Evidence

The recommendations are based on the guidelines of care for the management of actinic keratosis, which suggest that 5-FU and imiquimod are effective treatments for AK, with moderate to high efficacy and relatively low risk of side effects 1. Diclofenac is also a viable option, although its efficacy is lower compared to 5-FU and imiquimod 1. The British Association of Dermatologists' guidelines for the care of patients with actinic keratosis also support the use of these topical treatments, with 5-FU and imiquimod being considered good treatment options for AK 1. Additionally, research gaps in the management and prevention of cutaneous squamous cell carcinoma in organ transplant recipients highlight the importance of field-based therapies for actinically damaged skin, with imiquimod, 5-FU, and diclofenac being investigated as topical treatment options for AK in this population 1.

From the FDA Drug Label

Fluorouracil Cream USP is recommended for the topical treatment of multiple actinic or solar keratoses. Imiquimod Cream is indicated for the topical treatment of clinically typical, nonhyperkeratotic, nonhypertrophic actinic keratoses on the face or scalp in immunocompetent adults.

The topical treatments for actinic keratosis are:

  • Fluorouracil (TOP), as stated in 2
  • Imiquimod (TOP), as stated in 3

From the Research

Topical Treatments for Actinic Keratosis

The following topical treatments are available for actinic keratosis:

  • 3% diclofenac in 2.5% hyaluronic acid 4
  • 0.5% 5-fluorouracil 4, 5, 6, 7
  • 5% imiquimod 4, 5, 8
  • 0.025% to 0.05% ingenol mebutate 4
  • Photodynamic therapy (PDT) with aminolevulinic acid (ALA) or methyl aminolevulinate (MAL) 4

Efficacy of Topical Treatments

The efficacy of these topical treatments varies:

  • 3% diclofenac in 2.5% hyaluronic acid: significantly favored participant complete clearance compared to vehicle or placebo 4
  • 0.5% 5-fluorouracil: significantly favored participant complete clearance compared to placebo 4
  • 5% imiquimod: significantly favored participant complete clearance compared to placebo 4, 5
  • 0.025% to 0.05% ingenol mebutate: significantly favored participant complete clearance compared to vehicle 4
  • PDT with ALA or MAL: significantly favored participant complete clearance compared to placebo-PDT 4

Comparison of Topical Treatments

Comparisons between these topical treatments show:

  • Imiquimod may have higher efficacy than 5-fluorouracil for actinic keratosis lesions located on the face and scalp 5
  • Daily application of 5% 5-fluorouracil cream is more effective than weekly application at clearing AKs from the scalp and face 6
  • Combination treatment using topical 5-FU and imiquimod cream may be an effective alternative therapeutic strategy for refractory AKs 8

Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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