Introduction Warts can be resistant to treatment or recur despite the use of various destructive and immunotherapeutic modalities. Combination immunotherapy might contribute to better response rates. The aim of this study was to assess the effectiveness and safety of a triple intralesional immunotherapy combination composed of purified protein derivative (PPD), Candida antigen, and measles–mumps–rubella vaccine (MMR), versus each agent alone, in the management of multiple recalcitrant warts. Methods In total, 160 patients with numerous resistant extragenital warts were included in the research. They were randomly assigned to one of four groups (each with 40 patients): PPD, Candida antigen, and MMR, or combination of the three antigens. Injections into the biggest wart were repeated every 2 weeks until clearance or for a total of five sessions. Results Complete wart clearance was reported in 31 patients (77.5%) who received triple-antigen immunotherapy, 23 patients (57.5%) who received intralesional PPD, 29 patients (72.5%) injected with Candida antigen, and 25 patients (62.5%) who received MMR. The combined therapy was found to be superior to the other therapies and had the lowest recurrence rate, but the difference was not statistically significant. Conclusions Triple intralesional antigen immunotherapy is as safe as, and more effective than, monoantigen immunotherapy, and can be added to the armamentarium against recalcitrant human papilloma virus (HPV) infections.
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