Fractional CO₂ Laser-Assisted Methotrexate Rivals 5-FU in Stable Vitiligo
Key Takeaways
- Fractional CO₂ laser-assisted delivery of topical methotrexate produced repigmentation outcomes comparable to 5-fluorouracil in patients with stable, nonsegmental vitiligo.
- Both treatment approaches significantly reduced modified Vitiligo Area Scoring Index (VASI) scores and were associated with declines in serum and lesional IL-23 levels.
- Investigators identified IL-23 as a potential biomarker for treatment response.

Topical methotrexate (MTX) delivered through fractional CO₂ laser (FCL) demonstrated efficacy and safety comparable to laser-assisted 5-fluorouracil (5-FU) for stable, nonsegmental vitiligo, according to a study published in Dermatologic Surgery.
The prospective study enrolled 42 patients with stable vitiligo who underwent three monthly treatment sessions. Investigators compared FCL-assisted topical MTX with FCL-assisted topical 5-FU using two laser energy settings (50 mJ and 100 mJ). Clinical response was assessed using the modified Vitiligo Area Scoring Index (VASI), standardized photography, and serum and lesional interleukin-23 (IL-23) measurements.
Comparable Repigmentation, Distinct Response Patterns
Both treatment groups experienced significant reductions in modified VASI scores, with no statistically significant difference between MTX and 5-FU. Photographic assessment also demonstrated meaningful repigmentation across all treatment arms. Patients treated with higher-energy FCL plus 5-FU showed earlier clinical improvement immediately after treatment, whereas those receiving FCL-assisted MTX continued to demonstrate progressive repigmentation during follow-up.
Biomarker analyses revealed post-treatment reductions in both serum and lesional IL-23 across all groups. Serum IL-23 declined to a greater extent in the MTX-treated patients, while higher-energy FCL was associated with a greater reduction in lesional IL-23.
"MTX provides comparable efficacy and safety with 5-FU after FCL for stable, nonsegmental vitiligo," the authors wrote. "IL-23 is a new treatment biomarker in vitiligo."
Source
Ismail SA, et al. Dermatol Surg. 2026;52(8):e45-e51. Doi:10.1097/DSS.0000000000005222