Abstract
Vitiligo is a chronic autoimmune skin condition characterized by the progressive loss of melanocytes, resulting in well-defined hypopigmented or achromic patches. Oxidative stress is believed to play a role in its pathogenesis, and superoxide dismutase (SOD), an antioxidant enzyme, has emerged as a potential therapeutic option. This systematic review aimed to evaluate the efficacy of oral or topical SOD, used either alone or in combination with other interventions, in the treatment of vitiligo. Following the Preferred Reporting Items for Systematic reviews and Meta-analyses (PRISMA) 2020 guidelines, a comprehensive search of PubMed (MEDLINE), Cochrane, ClinicalTrials.gov, EBSCO, LILACS, Scopus, and Tesis UNAM was conducted, and randomized clinical trials published up to April 14, 2025, were included. Eight randomized controlled trials (RCTs) were analyzed, including four with split-body and four with parallel-group designs. SOD was administered either alone or in combination with other therapies such as narrowband ultraviolet B (NB-UVB) phototherapy, excimer lamp, or calcineurin inhibitors. The primary outcome assessed across studies was the percentage of repigmentation. Six studies found no significant difference in repigmentation compared to controls, while two reported improved outcomes when SOD was combined with NB-UVB in responsive areas. One study showed a significantly greater improvement in the Vitiligo Extent Score (19.85% vs. 8.83%), and another reported excellent or good repigmentation in 46.7% of lesions with combination therapy, compared to none in the monotherapy group. All studies described a favorable safety profile. The risk of bias was low in four studies, some concerns were identified in four studies, and three studies were rated as high risk, primarily due to the lack of blinding of participants and outcome assessors, as well as unclear allocation concealment and randomization procedures. Although SOD appears to be well-tolerated and has demonstrated a favorable safety profile across all included studies, its efficacy remains uncertain. Only two studies reported modest improvements in repigmentation, both in combination with NB-UVB, making it difficult to isolate the contribution of SOD. While current evidence does not support the use of SOD as a standalone or first-line treatment, it may have potential as an adjunctive option. Further high-quality trials are needed to clarify its role in clinical practice, particularly in combination regimens.