title: Efficacy and tolerability of nitric-zinc complex in the treatment of external genital warts and "difficult-to-treat" warts: a "proof of concept", prospective, multicentre, open study.
abstract: OBJECTIVE
  Treatment of plantar and periungueal warts (so called "difficult-to-treat" warts, DTW) and external genital warts (EGW) remains unsatisfactory. Medical or invasive procedures are partially effective and/or painful. Furthermore recurrences rates after treatments are still a relevant problem for all the available therapies. Nitric-zinc complex is a solution for topical application containing nitric acid, zinc, copper and organic acids able to induce a caustic effect of the wart trough mummification and proteins denaturation/coagulation action. Nitric-zinc complex has been shown to be an effective and well tolerated treatment of common warts.
  
  
  METHODS
  We evaluated in a prospective open label 4-centre trial, the efficacy and local tolerability of nitric-zinc complex in the treatment of EGW and DTW. A total of 37 immunocompetent subjects (20 men and 17 women; mean age: 45 years) with single or multiple lesions, were enrolled, after their informed consent. A total of 30 subjects had EGW, 2 subjects had plantar warts, 2 warts of the hand and 3 periungueal lesions. Nitric-zinc aqueous solution was applied topically using a 30 mL capillary tube over the lesions until a whitening/yellowish reaction appeared. A second (or more, if needed) application was performed at two-week interval until a complete clinical cure rate was observed. Primary outcome of the study was the clinical evaluation with picture documentation of the evolution of lesions classified as total cure, partial disappearance or no effect. Topical tolerability was evaluated through patient's reported adverse events.
  
  
  RESULTS
  All subjects completed the study. A complete cure of lesions was observed in 31 subjects (90%) after one and up to four applications. Three patients with EGW (8%) showed a partial disappearance of lesions and one (2%) subject was no responder to four nitric-zinc complex applications. The product was well tolerated. No serious adverse events were observed or recorded.
  
  
  CONCLUSIONS
  Nitric-zinc complex topical solution has shown to be an effective and well tolerated treatment of EGW and "difficult-to-treat" warts with a 90% of subjects with a total cure after one or up to four applications. A total or partial response was observed in 99% of the subjects. Nitric-zinc complex could be considered an easy-to-use effective treatment strategy of "difficult-to-treat" warts and external genital warts. Additional studies comparing nitric-zinc complex to other strategies are warranted.
authors.affiliation: Sexual Transmitted Disease, University of Milan, Milan, Italy - massimo.milani@isdin.com.
authors.forename: M
authors.initials: M
authors.lastname: Cusini
authors.forename: G
authors.initials: G
authors.lastname: Micali
authors.forename: F
authors.initials: F
authors.lastname: Lacarrubba
authors.forename: M
authors.initials: M
authors.lastname: Puviani
authors.forename: A
authors.initials: A
authors.lastname: Barcella
authors.forename: M
authors.initials: M
authors.lastname: Milani
mesh_terms: D000287:Administration, Topical; D000328:Adult; D003218:Condylomata Acuminata / Q000188:drug therapy; D003879:Dermatologic Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D005260:Female; D005533:Foot Dermatoses / Q000188:drug therapy; D005831:Genital Diseases, Female / Q000188:drug therapy; D005832:Genital Diseases, Male / Q000188:drug therapy; D006229:Hand Dermatoses / Q000188:drug therapy; D006801:Humans; D007121:Immunocompetence; D008297:Male; D008875:Middle Aged; D017942:Nitric Acid / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D011446:Prospective Studies; D012996:Solutions; D016896:Treatment Outcome; D014860:Warts / Q000188:drug therapy*; D015032:Zinc / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use
chemical_list: D003879:Dermatologic Agents; D012996:Solutions; D017942:Nitric Acid; D015032:Zinc