Risk of squamous cell carcinoma in immunosuppressed patients with voriconazole-related actinic keratosis

Voriconazole is commonly administered for a long period to patients receiving immunosuppressive therapy. Although voriconazole potentially induces skin cancers in association with sun exposure, this has not yet been examined in detail in a single ethnic patient group. Therefore, the present study investigated the risk of developing squamous cell carcinoma (SCC) in Japanese patients with voriconazole-related actinic keratosis (AK) and the prognosis of Japanese patients with voriconazole-related SCC. We retrospectively examined 37 Japanese patients with AK, including five voriconazole-treated patients (mean age, 57.9  ±  16.3  years) and 32 non-treated patients (74.9  ±  9.2  years), and 18 Japanese patients with SCC, including four voriconazole-treated patients (55.4  ±  16.7  years) and 14 non-treated patients (74.1  ±  10.7  years). Among the 37 patients with AK, SCC developed in five, including four with a history of treatment with both voriconazole and immunosuppressive agents, independent of AK progression. In these four patients, the mean period from the diagnosis of AK to that of SCC was 13.8  ±  11.6  months. Kaplan--Meier analyses showed that the risk of developing SCC was significantly higher in patients with both voriconazole and immunosuppressants/corticosteroid-treated patients with AK than in non-voriconazole-treated patients with AK (the Log-rank test, p < 0.001). The analyses also showed that the mortality rate was significantly higher in patients with both voriconazole and immunosuppressants/corticosteroid-treated patients with SCC than in non-voriconazole-treated patients with SCC (p =  0.018). The present results suggest that voriconazole-related AK precedes the development of cutaneous SCC and voriconazole-related SCC leads to a poor prognosis under the immunosuppressive condition.