**7.4 MMR vaccine***, Candida, Trichophyton and tuberculin* **antigens**

Various types of vaccines and antigens were tried for wart management. Measles, mumps and rubella (MMR) viral vaccine accelerates the clearance of virus and viral infected cells by stimulation of cell-mediated and humoral immunity [151]. In this double-blind RCT, MMR vaccine was tried for three injections in 2-week interval with normal saline as control; 75% of patients had complete clearance, and another 16.6% had more than 50% clearance. There were no side effects, and in 6-month follow-up, there was no relapse [151]. In another study of MMR vaccine, 81.4% of patients had complete clearance; another 10% had partial clearance, in comparison to 27.5% and 15% with saline control [152]. A preliminary, open-label (PPD: purified protein derivative) study to investigate the effectiveness of the tuberculin antigen in the treatment of recalcitrant warts, taking advantage of the vaccination schedule in their country was designed. Three consecutive intralesional tuberculin (5TU PPD RT23-tween 80 solution) injections with 3-week intervals into each target wart, depending on the tuberculin reactivity, were performed. Injections of 0.3, 0.2 and 0.1 mL of antigen were administered to patients with indurations of 5–9, 10–15 and > 15 mm, respectively. Five patients (29.4%) demonstrated complete clearance, five (29.4%) had partial and five (29.4%) minimal response. Some patients showed complete clearance of untreated facial warts also. Patients with initial PPD test site in duration less than 10 mm had no or minimal response [153]. Mumps and *Candida* antigen injection in paediatric age group with recalcitrant warts had 47% complete resolution, and 13% had partial resolution. Injections were given in three weekly intervals, and an average of 3.87 injections was given. Patients with initial high response to skin antigen test shows excellent result [154]. Injection with mumps, *Candida* or *Trichophyton* antigen, alone or in combination, is given in 3-week interval, up to 10 injections. In patients who have completed the study, 50% had complete clearance, and the other 50% had 75–90% clearance. Local erythema and oedema were the only side effects, in 30% of patients. Patients who had complete clearance had clearance also in their distant verruca lesions [155]. *Candida albicans* intralesional immunotherapy in single also came as safe, well tolerated and suitable for multiple warts of hand and fingers, plantar warts and recalcitrant warts, even in non-injected warts [156]. In a randomised, single blinded, placebo-controlled large study of mumps, *Candida* and *Trichophyton* antigen, with or without interferon α 2b, 41% of patients with antigen alone, 57% antigen and interferon and 9% in only interferon had complete clearance in comparison to 19% only in the normal saline group [157]. The combination of mumps, *Candida* and *Trichophyton* also came to be effective as 74% of patients responded to test antigen had complete clearance with significant number also showing resolution of untreated distant warts [158]. Response of other studies with *Candida* antigen varied as 72% [159], 74% [160], 85% [161], 56% [162] and 87% [163], indicating antigen therapy in wart is a good hope for target and distant wart lesions with minimum side effects.

### **7.5 Interferons**

Interferon has been shown to be active against HPV both in vitro and in vivo, to protect murine cells against infection with bovine papillomaviruses and to eliminate extrachromosomal viral DNA from infected cells [164, 165]. In a systematic meta-analysis, the rate of complete response in locally used interferon was 44.4% in comparison to placebo, 16.1%. The complete response rate of systemically used interferon as compared to placebo for treating genital warts had no perceivable discrepancy, for systemically used interferon 27.4% and placebo 26.4%. Both groups had near same recurrence rate (interferon 21.1% vs. placebo 34.2%, p > 0.05). In subgroup analysis, it was noticed that relapse was less in intralesional interferon in comparison to placebo group, but relapse rate were the same in between systemic and placebo groups. Adverse events were mostly mild and transient and could be tolerated [166].

### **7.6 Zinc**

Dietary zinc has profound effects on the human immune system and deficiency leads to reduced immune capacity [167, 168]. It can be given as topical preparation, oral medication or intralesional. Topical preparation as 10% zinc sulphate lotion yields complete clearance in 80% in plane wart [169]; plane warts were seen in 85.7% [170]. Complete clearance noticed in 61% patients after 1 month therapy and 87% after 2 months of therapy with oral zinc sulphate 10 mg/kg/day in a placebocontrolled trial [171]. But it was not the same in other studies, 50% complete clearance with the same dose after 2 months in another open level clinical study [172]. Intralesional 2% zinc sulphate too has been found to induce clearance of warts [173].

### **7.7 H2 receptor blockers**

H2 blockers, such as cimetidine and ranitidine, have been tried in treatment of warts. They block the type 2 histamine receptors on suppressor T cells and augment cell-mediated immunity [174]. It increases the levels of IFNγ and IL-2 and decreases the levels of IL-18 [175]. It has been used in a dose of 20–40 mg/kg/day for 3–4 months with response rate ranging from 30 to 87% [176, 177]. There is no significant difference between cimetidine and placebo [178], and some author proposed a placebo effect for cimetidine [179].
