Efficacy of Cryotherapy Combined With Intralesional Purified Protein Derivative (PPD) Versus Intralesional PPD Monotherapy in the Treatment of Multiple Common Warts

Abstract

Introduction Intralesional antigen immunotherapy represents a promising therapeutic approach for the treatment of different types of warts, particularly if multiple and/or recalcitrant. Aim to investigate the efficacy and safety of combined cryotherapy with intralesional purified protein derivative (PPD) immunotherapy in the treatment of multiple common warts. Methods Fifty patients were randomly divided into two groups (25 patients each): Group A: receiving intralesional PPD immunotherapy for the largest wart, while group B: receiving cryotherapy for all warts plus intralesional PPD for the largest wart. Treatments were performed every 2 weeks for a maximum of four sessions. Photographs were taken at baseline and at each visit and clinical response was evaluated by the reduction in number and size of warts. Adverse effects were recorded. Results There was a significant reduction in size and number of warts in both groups ( P < .001), with no significant difference between the two groups. Complete clearance of the lesions was observed in 48% of patients in group A and 44% in group B ( P = .39). Higher rates of near complete/complete response were achieved after fewer sessions (2, 3 sessions) in group B ( P = .002). Blistering was common after cryotherapy. Higher rate of hypopigmentation was noticed after combined treatment than after PPD monotherapy (56%, 8% respectively; P < .001), which resolved gradually. Conclusion Both intralesional PPD alone and combined cryotherapy with PPD are safe and effective in clearing of common warts. Cryotherapy may be a successful adjunct to intralesional PPD immunotherapy that helps in reducing the number of treatment sessions. The study protocol was registered at ClinicalTrials.gov with ID: NCT04288817

Systematic Review of Intralesional Therapies for Cutaneous Warts

“…Two studies trialed intralesional PPD in the largest wart compared with cryotherapy for all warts plus intralesional PPD in the largest wart and found no significant difference in response rates. However, both found a shortened time to clearance in the combination group ( Awad et al, 2023 ; Ibrahim et al, 2022 ). A combination of IFN alfa-2b with pulsed dye laser had a statistically significant higher clearance rate than either therapy alone ( Choi et al, 2002 ).…”

“…Wart types most commonly included verruca vulgaris, followed by verruca plantaris and verruca palmaris, and least commonly included verruca plana and periungual warts. Only 4 therapies were trialed in greater than 10 RCTs: these 4 most common therapies were MMR (n = 24), PPD (n = 19), vitamin D (n = 15), and Candida (n = 14) ( Table 3 ) ( Abd-Elazeim et al, 2014 ; Abd El-Magiud et al, 2020 ; Agrawal et al, 2018 ; Ahmed et al, 2020 ; Amin et al, 2021 ; Amirnia et al, 2016 ; Awad et al, 2023 ; Awal and Kaur, 2018 ; Baaniya et al, 2021 ; Bhalala et al, 2021 ; Eldahshan et al, 2022 ; ElGhareeb, 2019 ; El Sayed et al, 2020 ; Elsayed Ghaly et al, 2021 ; Fathy et al, 2019 ; Fawzy et al, 2020 ; Hodeib et al, 2021 ; Ibrahim et al, 2022 , 2020 ; Jain and Marfatia, 2021 ; Jartarkar et al, 2021 ; Kareem et al, 2019 ; Kaur et al, 2021 ; Khozeimeh et al, 2017 ; Khurshid and Pal, 2009 ; Mehta et al, 2021 ; Milante et al, 2019 ; Mohammed et al, 2021 ; Mohta et al, 2022 , 2021 ; Nassar et al, 2022 ; Nofal et al, 2022a , 2022b , 2022c , 2021a , 2021b , 2020b ; Nofal and Nofal, 2010 ; Rageh et al, 2021 ; Rajegowda et al, 2020 ; Rezai et al, 2019 ; Rutnin et al, 2023 ; Shaldoum et al, 2020 ; Wan Ahmad Kammal et al, 2021 ; Zamanian et al, 2014 ; Zainab et al, 2021 ). The most common therapy, MMR, was reported in 807 patients across studies.…”

“…Intralesional immunotherapeutic agents work by introducing an antigen to promote T-cell–mediated immunity nonspecifically against HPV, resulting in clearance of HPV at local and distant sites ( Awad et al, 2023 ; Ju et al, 2022 ). More specifically, these therapies result in (i) delayed hypersensitivity reactions against HPV, (ii) trauma induced by injection, and (iii) proliferation of peripheral mononuclear cells that then promote T helper 1 (Th1) cell cytokine responses ( Abd-Elazeim et al, 2014 ).…”

Cryogenic Media in Biomedical Applications: Current Advances, Challenges, and Future Perspectives

“…In addition, a growing body of evidence, mainly from clinical experience, has shown cryotherapy to be an excellent second line treatment in the protocols when the initial agent application is unsuccessful (94). A study by Awad et al (95) has shown that adding N 2 cryotherapy prior to intralesional (IL) antigen immunotherapy is a promising therapeutic approach in multiple and recalcitrant warts. It works on the principle of the effector immune cells attraction to HPVloaded keratinocytes, highlighting the safety and efficacy of the combination therapy with the potential of reducing the number of treatment sessions.…”