Management of Local Skin Reactions Caused by 5-FU 4% Cream for the Treatment of Actinic Keratosis: A Delphi Consensus

Abstract

Introduction: Treatments such as 4% 5-fluorouracil (5-FU) cream have demonstrated strong efficacy in lesion clearance of actinic keratosis; however, local skin reactions (LSR) during treatment remain a significant challenge, potentially affecting patient adherence.

Objective: We sought to build consensus on management of LSR associated with 4% 5-FU using the Delphi methodology.

Methods: Twenty-eight expert dermatologists participated in a 3-round Delphi process. Experts evaluated LSR management strategies, including emollients, antibiotics, steroids, and treatment discontinuation. Agreement levels were measured using a 7-point Likert scale. Consensus was categorized as high if >80% of votes were within the 5-7 rating range and low when >25% were in the 1-3 rating range, with <25% of the votes in the 6-7 rating range. Other combinations of votes were considered as having moderate agreement.

Results: High agreement was achieved for the following statements: the approved daily schedule (once daily for 4 weeks) is the most appropriate (92.9%); mild LSR generally do not require intervention and do not impact treatment adherence (96.4%); severe LSR may benefit from temporary treatment interruption and emollient use, ensuring adherence without compromising efficacy (92.9%). The use of emollients (in parallel with the treatment with 5-FU) was considered not needed by most (moderate consensus, 64.3%). Experts emphasized the importance of clear communication about LSR during baseline consultation to enhance patient compliance.

Conclusion: This consensus provides practical guidance for managing LSR induced by 4% 5-FU, ensuring high adherence and optimizing treatment outcomes. Further research is needed to validate these findings and explore alternative management approaches.

Figure 1

Three types of local skin reactions with 4% 5-fluorouracil cream: mild with small erythematous areas, moderate with larger involved areas, and severe with diffuse erythema, crusts, and scales.

Figure 2

Statement numbers corresponding to the following: Q1. The conventional schedule of 4% 5-FU administration (daily for 4 weeks) is the most appropriate: 92.9% agreed that the daily administration for four weeks is the most appropriate (mean: 5.8, SD: 1.33). Q2. The use of emollients in parallel with the treatment with 5-FU is not necessary: a moderate consensus (64.3% agreement) indicated that emollients are not necessary from the first application (mean: 4.9, SD: 1.93). Q3. Any potential local skin reactions should be explained during the baseline examination: all participants (100%) agreed that potential LSR should be explained during the baseline examination (mean: 6.8, SD: 0.4). Q4. The patient should be checked 4 to 8 weeks after baseline/treatment initiation: 85.7% agreed on following patients 4–8 weeks post-treatment (mean: 5.75, SD: 1.4). Q5. Mild LSR do not require intervention: 96.4% agreed that mild LSR do not require intervention (mean: 6.3, SD: 0.9). Q6. Even without intervention for mild LSR, most patients complete the treatment schedule: 89.3% confirmed that patients generally complete the treatment schedule despite mild LSR (mean: 5.9, SD: 1). Q7. Moderate LSR do not require intervention: 71.4% agreed that moderate LSR do not require intervention (Mean: 5.1, SD: 1.5). Q8. Even without intervention for moderate LSR, most patients complete the treatment schedule: 67.9% indicated that patients usually complete treatment despite moderate LSR (mean: 5.2, SD: 1.4). Q9. In case of severe LSR, treatment should be paused for a few days during which emollients may be prescribed. The treatment schedule should then be completed: 92.9% agreed that treatment should be paused for severe LSR, with the possibility of using emollients (mean: 5.9, SD: 1.3). Q10. The use of local steroids is not recommended in case of severe LSR: 57.1% agreed that local steroids are not recommended for severe LSR (mean: 4.8, SD: 1.7). Q11. This approach for severe LSR controls the reaction while maintaining optimal treatment results: 89.2% affirmed that pausing treatment ultimately leads to successful completion (mean: 5.9, SD: 0.8).