摘要:Background: Lichen planopilaris is an inflammatory cicatricial alopecia, and its management is a challenge for dermatologists. We aimed to compare the efficacy of methotrexate and hydroxychloroquine on refractory lichen planopilaris. Methods: In a randomized clinical trial, 29 patients were randomly allocated to receive either 15 mg methotrexate/week or 200 mg hydroxychloroquine twice a day for 6 months. Side effects, symptoms/signs, and laboratory tests were assessed periodically. Lichen Planopilaris Activity Index (LPPAI) was measured before intervention and at 2, 4, and 6 months after. The changes from baseline to the end of the study were analyzed within each group and between the two groups by per-protocol and intention-to-treat analysis. Results: After 2 months, mean (standard deviation [SD]) decrease in LPPAI in methotrexate group was significantly more than that in hydroxychloroquine group (1.68 [1.24] vs. 0.8 [0.71], respectively, P = 0.047). Furthermore, after 6 months, mean (SD) decrease in LPPAI in methotrexate group was significantly higher than that in hydroxychloroquine group (3.3 [2.09] vs. 1.51 [0.91], respectively, P = 0.01). The following symptoms/signs showed significant improvements in frequency and/or severity in methotrexate group after intervention: pruritus ( P = 0.007), erythema ( P = 0.01), perifollicular erythema ( P = 0.01), perifollicular scaling ( P = 0.08), spreading ( P = 0.001), and follicular keratosis ( P = 0.04). In hydroxychloroquine group, only erythema ( P = 0.004) showed significant improvement. Conclusions: Methotrexate was more effective than hydroxychloroquine in treating refractory lichen planopilaris.