A Multistep Voriconazole-Related Phototoxic Pathway May Lead to Skin Carcinoma: Results From a French Nationwide Study

Abstract

Our results suggest that long-term voriconazole prescription may be associated with a multistep phototoxic process involving acute skin lesions followed by AK then by SCC. Discontinuation of voriconazole should be strongly considered in patients experiencing chronic phototoxicity.

Voriconazole-Induced Multiple Squamous Cell Carcinomas in a Patient With Chronic Lymphocytic Leukemia

“…The leading theories revolve around phototoxic effects related to UVB interaction with voriconazole and/or its N-oxide metabolite and an interaction with retinoid metabolism. 1 Lung transplant patients have a marked increase in SCC mortality after chronic voriconazole exposure. 2,3 Recent reports have shown similar effects in hematopoietic stem cell transplantation patients.…”

“…1 It is most commonly used as a sinus decongestant, available over the counter. In their practice, they use over-thecounter oxymetazoline in a regular spray formulation, although it is additionally available as a gel.…”

“…1 Several reports suggest that prolonged voriconazole exposure is associated with development of cutaneous squamous cell carcinomas (cSCCs) whose incidence may be dose dependent in organ transplant recipients (OTRs). 2,3 The association between cSCC in solid OTRs and voriconazole is now established.…”

Antifungal Agents

“…Severe phototoxicity progressing to actinic keratosis and/or squamous cell carcinoma (SCC) has been reported in some patients receiving prolonged voriconazole therapy (i.e., > 6 months), which may be accelerated in transplant populations [39,40]. Although the mechanism of voriconazole-induced SCC is unknown, there are multiple retrospective studies associating the use of voriconazole with SCC possibly due to the photosensitizing effects of the voriconazole N-oxide metabolite [40].…”

Photosensitivity reactions and skin tumours associated with voriconazole

“…36 In 14 patients acute phototoxicity during the first year of therapy was followed by actinic keratoses on the same sun-exposed skin area in the second/third year, and then by squamous cell carcinomas during the third year or later. There were five cases of actinic keratosis without squamous cell carcinomas and 37 cases of other skin lesions.…”