Exploring the mechanism of differential responses to combination therapy in melasma: pigmentary versus mixed pigmentary–vascular types—a clinical study based on interaction analysis

Background Melasma shows clinical heterogeneity, but the role of vascular components in treatment resistance remains unclear.Methods This retrospective cohort study included 75 melasma patients stratified by severity (mild/moderate/severe, n = 25 each) and classified into pure pigmentary (M-type, n = 42) and mixed pigmentary-vascular (M + V-type, n = 33). All received low-fluence Q-switched 1064 nm laser plus oral tranexamic acid. Primary outcome was modified Melasma Area and Severity Index (mMASI) reduction. Multiple regression and interactionanalyses were performed.Results M-type showed significantly higher mMASI reduction than M + V-type (p < 0.001). Treatment resistance rate was markedly higher in M + V-type (p < 0.001). M + V-type, diseaseduration ≥5 years, and severe disease were independent negative predictors. A significantclinical type × severity interaction was detected (p = 0.018), with the M + V effect most pronounced in severe patients.Conclusion Mixed pigmentary-vascular type is independently associated with poor response, aggravated by severe disease. For severe M + V-type, adjunctive anti-vascular or anti-inflammatory strategies may be warranted.