Old molecule, new scrutiny: Benzoyl peroxide in dermatology

Benzoyl peroxide (BPO) is a widely available over-the-counter topical medication approved in the 1960s for acne vulgaris treatment. NICE guidelines recommend BPO as a monotherapy or in combination with topical retinoids or antibiotics. However, concerns persist regarding optimal concentration and long-term safety, particularly following recent controversies surrounding benzene formation.

To systematically assess evidence on the indications, efficacy, and safety of topical BPO across dermatological conditions.

A literature search following the PRISMA-P guidelines was performed using MEDLINE, Scopus and EMBASE databases from 1992 to 2025. Eligible studies included primary research involving patients with dermatological conditions treated with topical BPO. Primary outcomes were lesion count reduction, investigator global assessment and any treatment-related adverse effects (AEs).

Of 2347 identified records, 111 articles met the inclusion criteria. BPO monotherapy achieved 75% median lesion reduction versus placebo, with comparable efficacy across concentrations (2.5% vs 5%). Adapalene-BPO combination showed superior outcomes to monotherapy (P<0.001) among 2453 patients, though with increased irritation. Antibiotic-BPO combinations demonstrated 71.3% IGA improvement by week 2 versus 19.3% vehicle control. In rosacea, BPO-clindamycin reduced papules and pustules up to 71%. Local application site reactions, including skin irritation, dryness and bleaching represented the most common AEs. Large population studies demonstrated no significant association between BPO use and detectable blood benzene levels or malignancy risk. Evidence for perioral dermatitis and folliculitis remains limited and heterogenous.

BPO has a favourable safety profile with predominantly mild, localised AEs. Further randomised controlled trials using validated outcome measures are required to establish efficacy in other dermatological conditions.