Post-acne Erythema: A Systematic Review of Randomized Controlled Trials on the Comparative Efficacy and Safety of Interventions Across Clinical, Instrumental, and Patient-Reported Outcomes

Abstract

Post-acne erythema (PAE) is a persistent acne sequela without an established standard treatment. This systematic review evaluated the comparative efficacy and safety of interventions tested in randomized trials. PubMed/MEDLINE, Scopus, and Web of Science were searched from inception through August 1, 2026. Randomized parallel-group and split-face trials reporting erythema outcomes were eligible. Risk of bias was assessed with the Cochrane Risk of Bias 2 (RoB 2) tool. Heterogeneity precluded meta-analysis, and available findings were synthesized narratively. Nine trials involving 301 participants contributed 11 pairwise comparisons. Against untreated or blank controls, favorable effects were reported for picosecond alexandrite laser, narrow-spectrum vascular intense pulsed light (IPL), and non-cross-linked hyaluronic acid mesotherapy. A 577-nm semiconductor laser showed interim instrumental benefit, but blinded assessors found no final between-side difference. In active-treatment and add-on comparisons, narrow-spectrum IPL was favored over broad-spectrum IPL, neodymium-doped yttrium aluminum garnet (Nd) laser added to low-dose isotretinoin was favored over isotretinoin alone, and 577-nm pro-yellow laser was favored over topical brimonidine. Botulinum toxin type A was favored over broadband light at the earliest assessment only. Fractional laser and pulsed dye laser did not differ significantly, while delicate pulsed light and Q-switched 1064-nm Nd laser showed no sustained difference at the final assessment. Adverse events were mild and transient, although pigmentation and blistering occurred with one broad-spectrum IPL protocol. Five trials had some concerns, and four had high overall risk of bias. Trials suggested potential benefits, but small samples, heterogeneity, short follow-up, and reporting limitations precluded identification of a preferred treatment. Larger, prospectively registered trials using blinded assessment and standardized outcomes are needed.