Intralesional immunotherapy for non-genital warts: A systematic review and meta-analysis.

Background Intralesional immunotherapy has been reported to be effective for warts and to show good safety profiles, but this has not yet been systematically studied. Aims To determine the efficacy and safety of intralesional immunotherapy for treating non-genital warts. Methods We comprehensively searched the MEDLINE, Embase, Web of Science and Cochrane Library databases from the times of their inception to January 3, 2020. The primary outcome was the rate of complete response of all lesions. The distant complete response rate of warts located in an anatomically different body part and the recurrence rate were also analyzed. Results A total of 54 prospective studies was ultimately included. The immunotherapeutic agents used were Mycobacterium w vaccine, measles, mumps and rubella vaccine, purified protein derivative, Candida antigen, interferon, bacillus Calmette-Guérin vaccine and others. The pooled rate of complete response among all patients with non-genital warts treated using intralesional immunotherapy was 60.6% (95% confidence interval 54.8-66.5%). The pooled recurrence rate was 2.0% (95% confidence interval, 1.1-2.9%). All reported adverse events were mild and transient. Limitations The heterogeneity among studies Conclusion Intralesional immunotherapy is suggested for use in patients with multiple warts, given its promising results, good safety profile and low recurrence rate.

Expression of pigment epithelium-derived factor in psoriasis, verrucae, squamous cell carcinoma and normal skin: An immunohistochemical study.

BACKGROUND: Preservation of homeostasis status in the skin needs an equilibrium of keratinocyte proliferation, differentiation, necrosis and apoptosis. Disturbance of these regulatory mechanisms may lead to keratinocyte neoplastic and hyperproliferative diseases. Pigment epithelium-derived factor is a glycoprotein that is endogenously produced in different tissues and has a variety of biological effects in different diseases. OBJECTIVE: To evaluate the keratinocyte expression of pigment epithelium-derived factor in normal skin and three epidermal hyperproliferative diseases, namely, psoriasis, verrucae and squamous cell carcinoma. METHODS: This study included skin biopsy samples from 80 participants who were divided into four equal groups; each containing 20 samples. The first group included skin biopsies from normal skin, the second group from psoriatic lesions, the third group from verruca vulgaris and the fourth group from squamous cell carcinoma. All tissue samples were stained with hematoxylin and eosin stain and later immunohistochemically for pigment epithelium-derived factor expression. RESULTS: Scores of pigment epithelium-derived factor expression were lower in squamous cell carcinoma and verruca and psoriasis than normal skin with a significant difference (P = 0.04). In addition, the pattern of pigment epithelium-derived factor expression was mainly cytoplasmic in normal skin with a significant difference with that seen in psoriasis, squamous cell carcinoma and verruca vulgaris (P = 0.001). CONCLUSION: Pigment epithelium-derived factor may play a role in keratinocyte differentiation.

A double-blind, randomized controlled trial to compare the effectiveness and safety of purified protein derivative of tuberculin antigen with Mycobacterium w vaccine in the treatment of multiple viral warts.

BACKGROUND: Present day therapeutic modalities for viral warts are mostly ablative in nature, limited by high recurrence rates and are unsuitable for numerous lesions. Immunotherapy has the potential to overcome these limitations. AIMS: This study aimed at comparing efficacy and safety of and quality of life changes with intradermal purified protein derivative (PPD) of tuberculin antigen and Mycobacterium w (Mw) vaccine in immunotherapy of warts. METHODS: Patients with multiple (≥5) warts were randomized (1:1) into two groups (PPDand, Mw vaccine groups). Fortnightly, 0.1 ml of either medicine was injected intradermally over the deltoidregion till complete resolution or a maximum of six doses. Patients were followed-up for another 3 months for recurrence. RESULTS: Sixty-four participants received either PPD or Mw vaccine. The number of warts were comparable at baseline (P = 0.089, Mann-Whitney test), and reduced significantly with treatment in both groups (P < 0.001, Friedman's ANOVA), as seen from the fourth follow-up onwards with Mw and fifth follow-up onwards with PPD (P < 0.05, Post hoc Dunn's test). Intergroup comparison showed significantly more (P < 0.05, Mann-Whitney test) reduction with Mw than PPD at the sixth and seventh follow-up. The size of warts also reduced significantly (P < 0.001) in both groups from the third follow-up onwards. Complete remission was more (P = 0.539, Fischer's exact test) in the Mw group (68.8%) than the PPD group (50%); and was significantly higher (P = 0.049, Mann-Whitney test) in patients having shorter duration of warts. Adverse events were significantly more (P < 0.001) with Mw including ulceration (50%), discharge (15.6%), pain-swelling-induration and scar at the injection site (97% each), whereas some of those receiving PPD noted erythema and scaling at the injection site (18.8%), and post-inflammatory hyperpigmentation (12.5%). No recurrence was seen till the end of the study. LIMITATION: Unicentric trial. CONCLUSION: Intradermal injection of Mw vaccine was more effective but had a higher incidence of adverse effects compared to PPD of tuberculin antigen in patients with warts.

Falknor's needling method as a potential immunotherapy in palmo-plantar warts.

BACKGROUND AND AIM: Treatment of palmoplantar warts is a challenge for dermatologists. We aimed to study the efficacy and safety of Falknor's needling method in palmoplantar warts. METHODS: In an open, nonrandomized study, the index wart of eligible patients was punctured several times with a 26-gauge needle to produce a "beefy" red wound. Patients were followed up to 6 months. RESULTS: Out of 82 patients, complete resolution occurred in 58 (70.7%) and partial response in 5 (6.1%) patients. Nine (10.9%) patients developed secondary infection. LIMITATIONS: Small sample size, No comparison group. CONCLUSION: Falknor's needling method provides a high rate of complete resolution after a single treatment session. It is easy to perform and is cost effective.

Evaluation of efficacy and safety of intralesional bleomycin in the treatment of common warts: Results of a pilot study.

BACKGROUND: This study evaluated the efficacy and safety of intralesional bleomycin in the treatment of common warts in 50 (32 men, 18 women) patients aged between 14 and 80 (mean ± SD, 28.5 ± 13.27) years. METHODS: The warts were present over dorsal hands, feet, palms, soles and periungual skin for 1 month to 10 years. They were infiltrated with bleomycin (1 mg/ml) till blanching. The total cumulative dose did not exceed 2 mg in one session. The treatment was repeated after paring of eschar at 2 weeks in case there was no or partial response. The patients were reviewed at 4, 12 and 24 weeks for cure, adverse effects or recurrences and outcome satisfaction levels. RESULTS: Complete cure without recurrence occurred in 40 (80%) patients and partial response occurred in 7 (14%) patients at the end of the 24-week study period. Three patients did not complete follow-up. No major systemic or local adverse effects other than injection site pain for 2-3 days were noted. All cured patients were very satisfied (Likert scale 5). CONCLUSION: Intralesional bleomycin appears to be an effective and safe treatment for common warts including palmoplantar and periungual warts. It carries the advantage of low dose, no significant adverse effects and high patient satisfaction. Small number of patients, lack of a control group, comparing different bleomycin concentrations and a short follow-up are a few limitations of this study. Better designed studies are warranted for this useful treatment modality.

Toenail concentrations of zinc, selenium and nickel in patients with chronic recurrent warts: A pilot two-group comparative study.

BACKGROUND: Normal immune functioning requires sufficient levels of trace elements including zinc and selenium, while elements such as nickel can be immunotoxic. AIM: To assess long-term abnormalities in zinc, selenium and nickel levels in patients with chronic recurrent warts. METHODS: Toenail samples were taken from 28 patients with chronic recurrent warts and 30 apparently healthy matching controls were analysed. Toenail concentrations of zinc, selenium and nickel were measured using inductively-coupled plasma-optical emission spectroscopy. RESULTS: Selenium levels were significantly higher in patients than in controls (P = 0.03). Levels of trace elements did not correlate with the number or duration of warts. Toenail nickel levels in all subjects were higher than globally reported values. LIMITATIONS: A small sample size and the absence of regional reference ranges for concentrations of trace elements in toenails. CONCLUSION: Zinc does not seem to be involved in the chronicity of warts, and it is unclear if selenium has a protective role against warts. Our finding of high concentrations of nickel in both patients and controls raises concerns about environmental exposure.

Immunotherapy in viral warts with intradermal Bacillus Calmette-Guerin vaccine versus intradermal tuberculin purified protein derivative: A double-blind, randomized controlled trial comparing effectiveness and safety in a tertiary care center in Eastern India.

BACKGROUND: Current therapeutic modalities for viral warts are mostly ablative and are limited by high recurrence rates besides being unsuitable for numerous lesions. Immunotherapy has the potential to overcome these limitations. AIMS: The aim of this study was to compare the effectiveness and safety of Bacillus Calmette-Guerin vaccine versus tuberculin purified protein derivative in the immunotherapy of warts. METHODS: Patients received three doses of 0.1 ml of Bacillus Calmette-Guerin vaccine or tuberculin purified protein derivative intradermally over the deltoid region at 4-weekly intervals. They were followed-up for another month. Number of warts, complete cure rates and quality of life were assessed. RESULTS: A total of 60 patients were included. Complete clearance was noted in 16 (48.5%) out of 33 patients in the Bacillus Calmette-Guerin group and in 5 (18.5%) out of 27 in the tuberculin purified protein derivative group (P = 0.121). The number of lesions reduced statistically significantly from baseline in both the groups (P < 0.001) from the first follow-up visit onward (P < 0.05). The reduction was statistically significantly more in the Bacillus Calmette-Guerin group than in the tuberculin purified protein derivative group from the second follow-up onward. Dermatologic life quality index improved statistically significantly with both treatments. Adverse events (pain during injection, abscess formation and scarring at injection site) were more frequent with Bacillus Calmette-Guerin. No recurrence was seen after lesions cleared. LIMITATIONS: Patients were not followed up for more than 4 weeks after treatment. We could not estimate the cytokine levels or the peripheral blood mononuclear cell proliferation in response to Bacillus Calmette-Guerin/tuberculin purified protein derivative injections. CONCLUSION: Both intradermal Bacillus Calmette-Guerin and tuberculin purified protein derivative hold promise in the treatment of viral warts. Bacillus Calmette-Guerin may be more effective, though it had more adverse events in our study.

Immunotherapy using purified protein derivative in the treatment of warts: An open uncontrolled trial.

BACKGROUND: Warts are known to clear spontaneously with the development of cell-mediated immunity (CMI) to the virus. Purified protein derivative (PPD) of tuberculin bacilli has been used as a non-specific stimulant of CMI to achieve this outcome. AIM: To study the effect of PPD in the treatment of warts. METHODS: Patients with difficult-to-treat warts were selected for immunotherapy. Each patient received 2.5 TU of PPD intralesionally in a few warts. A total of four sessions were given at 2 weekly intervals and patients were followed up for 6 months after the last dose. RESULTS: Sixty-one patients were recruited of which 55 completed 6 months follow up and were available for analysis. Of these, 25 had verruca vulgaris, 18 had verruca plana and 12 had plantar warts. Forty two (76%) patients showed complete clearance after four sessions while the remaining 13 (24%) patients were non-responders. One patient developed a recurrence after total clearance during the follow-up period. Adverse effects were erythema, edema and pain at the site of injections. LIMITATIONS: As this was an uncontrolled trial, there is no comparison with a non-intervention group. Also, a Mantoux test was not done due to practical difficulties. CONCLUSION: Immunotherapy with PPD is helpful in the treatment of cutaneous warts.