Background: Post-burn leucoderma, characterized by persistent hypopigmentation, presents significant therapeutic challenges due to the disruption of melanocyte function and melanin production. Platelet-Rich Plasma (PRP) and 5-Fluorouracil (5-FU) have emerged as promising interventions, but their comparative efficacy remains underexplored.

Objective: This study aimed to evaluate the comparative effectiveness of PRP and 5-FU in repigmentation and scar remodeling in patients with post-burn leucoderma.

Methods: A comparative clinical study was conducted on 20 patients with post-burn leucoderma using a split-lesion design. PRP was prepared through a two-step centrifugation process and applied after microneedling. A 5% 5-FU solution was injected intradermally at specific intervals. Outcomes were assessed through clinical, photographic, and histopathological evaluations over six months.

Results: PRP and 5-FU therapies demonstrated progressive pigmentation improvement, with 55% of participants achieving dark pigmentation by six months. Lesion site and size significantly influenced outcomes, with upper limb lesions responding better than lower limb and trunk lesions. A significant inverse relationship was observed between 5-FU injection volumes and pigmentation improvement. Histopathological analysis showed partial restoration of melanocytes and reduced dermal inflammation.

Conclusion: Both PRP and 5-FU are effective in managing post-burn leucoderma, with PRP demonstrating consistent results and 5-FU requiring precise dosing to optimize outcomes. These findings emphasize the need for tailored therapeutic approaches to improve patient quality of life.