Abstract Background Intralesional bleomycin has been safely used for decades to treat recalcitrant cutaneous warts. Despite promising clinical outcomes, bleomycin is largely reserved as a last-resort treatment option and remains underused in the management of recalcitrant warts. Objectives To synthesize the evidence on bleomycin for nongenital, treatment-resistant warts, characterizing clearance, recurrence and adverse effects, and contextualizing these outcomes alongside those reported for other commonly used therapies. Methods A PRISMA-guided search was conducted using PubMed, Embase and the Cochrane Central Register of Controlled Trials (CENTRAL). Included studies were evaluated for wart clearance and recurrence rates, as well as the amount of drug injected, number of treatment sessions and adverse effects. Risk-of-bias assessments Cochrane Risk of Bias-2 (RoB-2) and Risk Of Bias In Non-Randomized Studies – of Interventions (ROBINS-I) were used to assess concerns related to randomization, confounding and reporting. The GRADE tool was used to assess the final certainty of evidence. Results Fifteen studies published between 1976 and 2025 were included. Bleomycin was delivered via intralesional injection, multipuncture/dermojet and microneedling. Comparators included trichloroacetic acid, vitamin D3, cryotherapy and saline placebo, as well as uncontrolled trials. Across studies, complete clearance rates for recalcitrant warts ranged from 34% to 95.5%, with many individuals whose warts only partially responded to treatment still demonstrating a substantial reduction in lesions. Recurrence rates were generally low, ranging from 0% to 15.8% of patients across follow-up periods of 3 months to ≥ 5 years. Adverse effects were predominantly localized and transient. Rarely, vascular complications such as Raynaud phenomenon were reported. There was no reported systemic toxicity at the doses used. Conclusions When considered alongside other treatment modalities such as cryotherapy or Candida antigen, bleomycin is a highly effective and safe option for recalcitrant warts. Our synthesis supports its consideration as a more prominent, earlier-line therapy in carefully selected patients.
Sollitto et al. (Wed,) studied this question.