What are the potential complications of 5-fluorouracil (5-FU) treatment for warts, especially in patients with a history of sensitive skin or allergies?

Complications of 5-Fluorouracil Treatment for Warts

Topical 5-FU consistently causes local skin inflammation, erosions, and pigmentary changes as part of its therapeutic mechanism, with hyperpigmentation or hypopigmentation occurring particularly with prolonged use, and patients with sensitive skin or allergies face additional risk of allergic contact dermatitis. 1, 2, 3

Expected Local Reactions (Not True Complications)

The British Association of Dermatologists emphasizes that inflammation is the intended pharmacological effect, not a complication to avoid:

• Inflammation and erosions occur routinely because 5-FU damages dividing basal layer cells and blocks DNA synthesis 1, 2
• Burning, soreness, redness, crusting, and ulceration are expected reactions that indicate the medication is working 1, 2, 3
• Clinical response is largely proportional to side-effects—patients should be counseled that local irritation is necessary for treatment success, not a reason for immediate discontinuation 2, 4

True Complications Requiring Clinical Attention

Pigmentary Changes

• Hyperpigmentation is the most common pigmentary complication, though hypopigmentation can also occur with prolonged use 1, 5
• Risk increases with longer treatment duration, higher concentrations, and combination with ablative procedures like cryotherapy 5
• Discontinue 5-FU immediately if hypopigmentation develops to prevent worsening 5
• Allow 6-12 months for spontaneous repigmentation before considering interventions, as most cases resolve naturally 5

Allergic Contact Dermatitis

This is the critical concern for patients with sensitive skin or allergy history:

• Allergic contact dermatitis can develop on adjacent normal skin, not just the treatment site 6
• The FDA label identifies allergic contact dermatitis as a distinct adverse reaction separate from expected irritation 3
• For severe, disproportionate pruritus: discontinue 5-FU temporarily, apply weak topical steroid, and consider patch testing before rechallenge 4
• Reactions may occur to vehicle components (propylene glycol, stearyl alcohol) rather than 5-FU itself 6

Scarring and Tissue Damage

• Scarring, blistering, and suppuration are less common but documented complications 3
• Patients with thin or fragile skin should be observed rather than treated due to poor healing potential 2
• Avoid combining 5-FU with ablative laser or aggressive cryotherapy, as this significantly increases scarring and pigmentary risk 5

Management Algorithm for Complications

For mild expected reactions (erythema, burning, mild erosion):

• Continue treatment and counsel that this indicates efficacy 2, 4
• Apply thin emollient between 5-FU applications 4
• Consider reducing application frequency from twice to once daily rather than stopping 4

For severe disproportionate reactions (extensive ulceration, severe pruritus, spreading dermatitis):

• Discontinue 5-FU immediately 4, 5
• Apply weak topical corticosteroid 4
• Consider patch testing before rechallenge to identify true allergy 4

For pigmentary changes:

• Stop 5-FU application immediately 5
• Avoid additional trauma or ablative procedures 5
• Reassure patient that improvement typically occurs over 6-12 months 5

Rare Systemic and Other Complications

• Leukocytosis is the most frequent hematological side effect, though systemic absorption from topical use is minimal 3
• Eosinophilia and thrombocytopenia are rare 3
• No clinically significant blood levels of 5-FU were detected in pediatric studies using topical application 7
• Emotional upset, insomnia, and irritability are infrequently reported 3

Critical Pitfalls to Avoid

• Do not discontinue treatment for expected inflammatory reactions—this is the mechanism of action 2, 4
• Do not assume all pigmentary changes are permanent—most improve after discontinuation 5
• Do not ignore severe pruritus or spreading dermatitis—this suggests true allergic contact dermatitis requiring patch testing 4, 6
• Do not combine with aggressive physical treatments in patients concerned about scarring or pigmentation 5