Efficacy and safety of intralesional tuberculin purified protein derivative versus cryotherapy in the treatment of warts: An assessor‐blinded, randomized controlled trial

Abstract

Cryotherapy is a standard treatment for warts. Tuberculin immunotherapy is a novel therapeutic option. We compared the efficacy and safety of cryotherapy versus tuberculin immunotherapy in a randomized, assessor‐blinded study. 15 patients were treated with intralesional tuberculin and 15 patients received cryotherapy every 2 weeks until complete wart resolution or a maximum of six sessions. Wart diameter, total number of warts and adverse effects were documented. Complete clearance of treated warts was achieved in 13(86.7%) and 11(73.3%) of patients with immunotherapy and cryotherapy respectively. Immunotherapy showed greater wart size reduction (51.88 ± 89.36 mm) than cryotherapy (32.99 ± 36.19 mm), (p = 0.46). Immunotherapy resulted in 64% reduction in total number of warts compared to 23.2% with cryotherapy, p < 0.01. More blisters developed with cryotherapy (46.7%) than immunotherapy (6.7%), (p = 0.01). Compartment syndrome‐like features complicate immunotherapy in 1 patient. Tuberculin immunotherapy and cryotherapy are equally effective in treating warts. Immunotherapy has added benefit with resolution of distant warts. Safety profiles were similar except for blisters which were more common with cryotherapy.

Systematic Review of Intralesional Therapies for Cutaneous Warts

“…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.…”

“…The next highest response rate was 90% complete response after treatment with MMR in a study of 19 adults treated with 0.3 ml every 2 weeks for up to 5 sessions ( Rutnin et al, 2023 ). For PPD, the highest response rate was 87% reported in a study of 15 adults treated with 1 ml of 2.5 TU every 2 weeks for up to 6 sessions ( Wan Ahmad Kammal et al, 2021 ). Finally, for Candida, the highest response rate was 84% in a study of 50 adults treated with 0.3 ml of 10 mg/ml every 2 weeks for up to 5 sessions ( Nofal et al, 2022a ) ( Table 3 ).…”

“…Assume this regimen in the discussion unless otherwise noted. PPD at various regimens has 4 studies showing its superiority to cryotherapy or normal saline ( Abd-Elazeim et al, 2014 ; Amirnia et al, 2016 ; Ibrahim et al, 2022 ; Wan Ahmad Kammal et al, 2021 ). The highest rate of complete response, 87%, was achieved using 1 ml of 2.5 TU injected into the largest wart every 2 weeks for up to 6 sessions ( Wan Ahmad Kammal et al, 2021 ).…”

“…PPD at various regimens has 4 studies showing its superiority to cryotherapy or normal saline ( Abd-Elazeim et al, 2014 ; Amirnia et al, 2016 ; Ibrahim et al, 2022 ; Wan Ahmad Kammal et al, 2021 ). The highest rate of complete response, 87%, was achieved using 1 ml of 2.5 TU injected into the largest wart every 2 weeks for up to 6 sessions ( Wan Ahmad Kammal et al, 2021 ). As mentioned previously, 0.1 ml of PPD every 2 weeks for up to 5 sessions was shown to have a complete response rate similar to MMR and Candida in an RCT comparing all 3 therapies.…”

Efficacy and Safety Profile of Tuberculin Protein Purified Derivative Injection As Immunotherapy For the Treatment of Cutaneous and Anogenital Warts: A Review Article

“…6 sessions 56 N/A 6 Pain, erythema, inflammation, itching Tawfik et al 56 2022 (Egypt) RCT PPD (A) Candida antigen (B) A: 40 B: 40 Simple; anogenital Test dose: 0.1 mL PPD and 0.1 mL Candida antigen, intradermal on forearm Group A: PPD-5TU, volume injected determined by the size of skin test reactivity according to Kus et al 13 intralesion on largest wart Group B: Candida antigen 1/1000, volume injected determined by the size of skin test reactivity: 0.3; 0.2; and 0.1 mL if the reaction diameter was 5–20 mm, 21–40 mm, and >40 mm, intralesion on largest wart 2-weeks interval, max. 4 sessions A: 72.5 B: 85 A: 3.4 B: 2.9 6 All groups: mild pain, burning sensation after injection A: itching, erythema B: erythema, edema Wan Ahmad Kammal et al 57 2021 (Malay-sia) RCT Cryo-therapy (1) PPD (2) 1: 15 2: 15 Simple, recalcitrant; common, Group 1: liquid nitrogen sprayed perpendicularly at a distance of 2 cm to all warts, margin 2 mm (2 freeze-thaw cycle) Group 2: PPD-2.5TU, intralesion on largest wart 2-weeks interval, max. 6 sessions 1: 73.3 2: 86.7 1: 27.3 2: 13.4 4 1: blister, hypo-pigmentation, hyperpigmentation, compartment-like syndrome-like symptoms and sign with swelling, cyanosis, and hypoaesthesia at the tip of the finger 2: pain, edema, erythema …”