Background: The treatment of keloids remains challenging. Cryosurgery and intralesional corticosteroids have been considered as the mainstream of therapy; however, the long-term use of corticosteroids has been found to be associated with serious side effects. Intralesional 5-fluorouracil (5-FU) has only been used in one study for the treatment of hypertrophic scars and keloids, mostly in combination with other treatments. The efficacy of 5-FU as an individual therapeutic agent is unknown. Objective: To evaluate the efficacy and safety of intralesional injections of 5-FU in the treatment of small keloid lesions. Methods: Twenty-four (12 male, 12 female) consecutive patients with keloids of 6 cm or less in their maximum dimension were treated with intralesional injections of 50–150 mg 5-FU per week for a maximum of 16 injections. Results: One third (8/24, 33.3%) of the patients showed more than 75% flattening of the keloid. Three out of 8 patients (with >75% flattening) required less than 16 (13, 13 and 15) injections for achieving the desired response. Overall, about half of the patients showed more than 50% flattening of the treated keloid. A correlation with the duration of keloid was found. Six (54.5%) out of 11 patients with keloids of ≤5 years duration, in contrast to only 2 (15.4%) out of 13 patients with keloids of >5 years duration showed more than 75% flattening (p < 0.05). Side effects included pain (all patients), hyperpigmentation (all patients) and ulceration (1 patient). No difference in peripheral blood count was noted before, during and after the therapy. Conclusion: Intralesional 5-FU can be safely used for the management of small keloids of shorter duration.

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