Evaluation of papillomaviruses associated with cyclosporine-induced hyperplastic verrucous lesions in dogs

OBJECTIVE: To determine whether cyclosporine A-induced hyperplastic skin lesions of dogs were associated with papillomavirus infections. ANIMALS: 9 dogs that were treated with cyclosporine A and developed hyperplastic skin lesions. PROCEDURE: History and clinical and histopathologic data were collected. Paraffin-embedded skin biopsy specimens from hyperplastic skin lesions were immunostained for common papillomavirus genus-specific structural antigens by use of a polyclonal rabbit anti-bovine papillomavirus type 1 antiserum. Sections from each tissue block underwent DNA extraction, and polymerase chain reaction (PCR) assays were performed with several sets of primers to amplify a wide range of papillomavirus DNA from humans and other animals. RESULTS: In 7 of 9 dogs, there were more than 10 hyperplastic skin lesions that microscopically resembled those of psoriasiform lichenoid dermatosis. In those dogs, results of testing for papillomavirus via immunohistochemical analyses and PCR assays were negative. In the other 2 dogs, there were only 1 and 3 verrucous lesions, and in those dogs, histologic evaluation revealed koilocytes and nuclear viral inclusions that were immunoreactive for papillomavirus antigens. Papillomavirus DNA was amplified from both dogs. One of the sequences was characteristic for the canine oral papillomavirus, whereas the other had similarities with the recently described canine papillomavirus 2. CONCLUSIONS AND CLINICAL RELEVANCE: In dogs, hyperplastic skin lesions occasionally develop during treatment with cyclosporine A. Most of the lesions resemble those of psoriasiform lichenoid dermatosis, although papillomavirus can be detected in some instances.