Author Affiliations: Department of Dermatology, Venereology, and Leprology, S. M. S. Medical College and Associated Hospitals, Jaipur, India.
Prior approval was obtained for the study from the institutional review board, and each patient provided written informed consent prior to study entry. Forty patients with multiple cutaneous warts (≥3) were then included in an open-label, interventional study conducted at the Department of Dermatology, Venereology, and Leprology of Sawai ManSingh (S.M.S.) Medical College, Jaipur, India, from December 2010 to August 2011 (8 months). Pregnant women, lactating mothers, children younger than 12 years, patients with a history of hypersensitivity or allergy to vaccines, and those with ulcerated or inflamed warts were excluded from the study.
The demographic data, complete medical history, and findings of clinical examination, including a lesion count and photographic documentation, were recorded for all patients at baseline (J.K.M.). The Mycobacterium w (Mw) vaccine (IMMUVAC; Cadila Pharmaceuticals, Licensed by National Institute of Immunology, New Delhi, India) was administered intradermally at a dose of 0.1 mL, using an insulin syringe, in each deltoid at baseline. After 2 weeks, the injected sites were examined for immunologic reaction (induration and or ulceration at the site of intradermal injection). In sensitized patients, the Mw vaccine was injected intralesionally into 3 to 5 lesions (lesions chosen at random) and repeated every week until either complete clearance of warts or a maximum of 10 injections (12 weeks), whichever was earlier. Lesion count and response data from the injected lesions as well as untreated lesions were recorded at each follow-up visit along with adverse events (if any).
The demographic and clinical data of patients are listed in the Table. Thirty-seven of 40 patients completed the study; 3 patients were lost to follow-up, one each at weeks 2, 3, and 4. Complete clearance of warts was seen in 33 (83%) patients (Figure 1 and Figure 2); 1 patient had 50% clearance, while 3 patients had only 25% to 30% reduction in number of lesions. The mean (SD) time to complete clearance was 9.7 (2.6) weeks. Twenty-three of 33 patients showed resolution of distant untreated warts (70%); in the remaining 10 patients, all lesions received intralesional Mw vaccine. Recurrence was seen in 3 patients during the posttreatment follow-up period of 4.48 (1.32) months.
Figure 1. Multiple periungual and subungual warts before treatment.
Figure 2. Resolved multiple periungual and subungual warts after treatment.
Tender erythematous papules and/or pustules developed at the site of sensitization in all patients, and it healed leaving a small BCG vaccine–like scar. Erythema in the treated warts was the most common adverse effect, seen in 25 patients (70%), followed by swelling in 6 patients (16%). Superficial ulceration at the site of treated warts was seen in 1 patient. Two patients reported low-grade fever not associated with any systemic symptoms only on the day when the Mw vaccine was given intralesionally in the warts from the fourth week onward. Two patients who received intralesional Mw vaccine injection on facial lesions developed tenderness and swelling of submandibular lymph nodes, and their treatment was discontinued for 2 weeks. Patients recovered completely under treatment with oral amoxicillin/clavulanic acid, 625 mg combination therapy 3 times a day for 5 days.
Treatment of multiple and extensive cutaneous warts is a challenge. Intralesional immunotherapy with Candida antigen, BCG vaccine, MMR vaccine (measles, mumps, rubella) and Trichophyton has been reported to be effective in the treatment of cutaneous and/or genital warts.1 We used Mw vaccine that contains killed nonpathogenic, saprophytic, cultivable, atypical mycobacterium belonging to Runyon Group IV, which has now been renamed Mycobacterium indicus pranii (MIP).2Mycobacterium w vaccine is primarily used for immunotherapy of multibacillary leprosy, but its immunomodulatory effects have also been demonstrated in other mycobacterial infections such as pulmonary tuberculosis, human immunodeficiency infection and malignant neoplasms of the head, neck, bladder, and lung.3- 6 Our research team has previously reported an 88.9% cure rate with Mw vaccine in genital warts.7
The exact mechanism of the wart clearance with Mw vaccine is yet to be studied. The strong proinflammatory signals against Mw attract antigen-presenting cells with production of helper T-cell type 1 cytokines and activation of cytotoxic and natural killer T cells that probably also recognize and process low-profile human papillomavirus particles in the infected tissue.7 The strong adaptive immune response clears not only treated lesions but also distant lesions. Mw vaccine appears to be an effective immunotherapy for extensive and multiple cutaneous warts, and it should be further evaluated in randomized controlled trials.
Correspondence: Dr D. C. Mathur, Department of Dermatology, Venereology, and Leprology, Charak Bhawan, J.L.N. Marg, Sawai ManSingh (S. M. S.) Hospital, Jaipur, India (firstname.lastname@example.org).
Accepted for Publication: August 2, 2012.
Author Contributions: All authors had full access to all of the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis. Study concept and design: Malhotra, D. K. Mathur, and D. C. Mathur. Acquisition of data: Meena. Analysis and interpretation of data: Meena and Malhotra. Drafting of the manuscript: Meena, Malhotra, and D. K. Mathur. Critical revision of the manuscript for important intellectual content: Malhotra and D. C. Mathur. Statistical analysis: Meena and Malhotra. Administrative, technical, and material support: D. C. Mathur. Study supervision: Malhotra, D. K. Mathur, and D. C. Mathur.
Conflict of Interest Disclosures: None reported.
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