Abstract
Vitiligo is the most common acquired pigmentary disorder, significantly impacting patients' quality of life. Although various treatment modalities exist, none have proven universally effective. Topical 5-fluorouracil (5-FU) and tacrolimus have both shown promise in inducing repigmentation, but comparative data, particularly in the Iranian population, remain limited. This study aimed to compare the efficacy and safety of topical 5-fluorouracil 5% cream versus topical tacrolimus 0.1% ointment in the treatment of patients with vitiligo vulgaris. This prospective double-blind randomized controlled clinical trial was conducted between February 2023 and July 2023 at dermatology clinics in Ilam, Iran. Forty patients aged 18–65 years with clinically diagnosed vitiligo vulgaris were randomly assigned to receive either topical 5-FU 5% cream (n=20) or topical tacrolimus 0.1% ointment (n=20) twice daily for six months. The primary outcome was improvement in lesion repigmentation assessed by the Vitiligo Area Scoring Index (VASI) at month 6. Secondary outcomes included changes in lesion size, clinical repigmentation rate, and adverse events. Data were analyzed using SPSS version 22, with independent t-test, Mann-Whitney U test, and chi-square tests applied as appropriate. A two-sided P-value <0.05 was considered statistically significant. All 40 patients completed the six-month follow-up. The mean VASI score was significantly higher in the 5-FU group compared to the tacrolimus group (1.61 ± 0.25 vs. 1.07 ± 0.24, P < 0.0001). Lesion size reduction was also significantly greater in the 5-FU group, decreasing from 6.01 ± 1.83 cm to 3.29 ± 1.23 cm, compared to a reduction from 5.80 ± 1.58 cm to 4.30 ± 1.27 cm in the tacrolimus group (P = 0.016). The superior efficacy of 5-FU was consistently observed across all age groups, both sexes, and all blood groups. Both treatments were generally well-tolerated, with no serious adverse events reported. While both topical 5-fluorouracil and tacrolimus demonstrated clinical efficacy in treating vitiligo vulgaris, topical 5-FU showed significantly superior results in terms of repigmentation and lesion size reduction. However, given the high concentration of 5-FU used in this study, further investigations with longer follow-up periods are warranted to confirm these findings and evaluate long-term safety and recurrence rates.