What dermatological conditions is 5-fluorouracil (5-FU) used for?

Dermatological Conditions Treated with 5-Fluorouracil

5-fluorouracil (5-FU) is FDA-approved for topical treatment of actinic keratoses and superficial basal cell carcinomas, with strong guideline support also for Bowen's disease (squamous cell carcinoma in situ). 1

FDA-Approved Indications

Actinic Keratoses (Primary Indication)

• The American Academy of Dermatology strongly recommends field treatment with 5-fluorouracil for actinic keratoses (Strength: Strong, Quality: Moderate) 2
• Apply 5% cream twice daily for 2-4 weeks until inflammatory response reaches erosion stage 1
• Complete healing may take 1-2 months after stopping therapy 1
• Field-directed treatment addresses multiple lesions and subclinical damage simultaneously 2

Superficial Basal Cell Carcinomas

• Only the 5% strength is FDA-approved for this indication 1
• Apply twice daily for at least 3-6 weeks, potentially extending to 10-12 weeks 1
• Success rate approximately 93% based on FDA data (1 failure in 25 lesions with solution, 7 failures in 88 lesions with cream) 1
• Reserved for situations where conventional surgery is impractical (multiple lesions, difficult treatment sites) 1
• Surgery remains preferred for isolated, easily accessible lesions with nearly 100% success rate 1

Guideline-Supported Off-Label Uses

Bowen's Disease (Squamous Cell Carcinoma In Situ)

• The British Association of Dermatologists provides Strength of Recommendation B (Level of Evidence 1+) for 5-FU in Bowen's disease 2
• Standard regimen: 5% cream once or twice daily for 3-4 weeks, repeated if needed 2, 3
• 83% complete response rate at 3 months when applied once daily for 1 week, then twice daily for 3 weeks 3
• Long-term data shows only 8% recurrence rate with twice daily application for up to 9 weeks 3
• Cure rates of 90-100% reported in multiple studies 2

Site-Specific Recommendations for Bowen's Disease:

• Small, single/few lesions at poor healing sites (e.g., elderly lower leg): Generally good choice (Score: 2) 2
• Facial lesions: Reasonable but not usually required (Score: 4) 2
• Digital lesions: Generally fair choice (Score: 3) 2
• Perianal lesions: Probably should not be used (Score: 6) 2
• Penile lesions (erythroplasia of Queyrat): Generally fair choice (Score: 3), though inflammation frequently limits the 4-5 week twice-daily regimen 2, 3

Other Documented Uses

• Actinic cheilitis, arsenical keratoses, radiodermatitis, X-ray-induced keratoses, and leukoplakia have historical support 4
• Intralesional 5-FU shows strongest evidence for keloids, hypertrophic scars, and keratoacanthomas 5
• Additional conditions with variable evidence: warts, nail psoriasis, keratoacanthoma, vitiligo, and mycosis fungoides 6, 7

Critical Treatment Considerations

Concentration Requirements

• Concentrations lower than 5% are less effective and should not be used 2, 3

Enhanced Efficacy Techniques

• Application under occlusion increases efficacy 2
• Iontophoresis improves follicular penetration 2
• Laser pretreatment (erbium:YAG) ablates stratum corneum to enhance penetration 2

Common Pitfalls to Avoid

• Hyperkeratotic lesions may not respond due to inability of drug to penetrate thick keratin layer 2
• In elderly patients with lower leg lesions and poor healing potential, observation may be preferable to treatment 2, 3
• For immunocompromised patients with Bowen's disease, 5-FU is generally a poor choice (Score: 5) 2
• Hands must be washed immediately after application if applied with fingers 1

Safety Monitoring

• DPD (dihydropyrimidine dehydrogenase) testing should be considered before initiating treatment to identify patients at risk for systemic toxicity 8
• For partial DPD deficiency, treat smaller areas with close monitoring or consider alternatives 8

Expected Treatment Response

• Normal sequence: erythema → vesiculation → desquamation → erosion → re-epithelialization 1
• Terminate treatment when inflammatory response reaches erosion stage 1