Voriconazole, approved for use against serious fungal infections in 2002, has been linked to five more cases of melanoma in situ in two patients, according to a report published online Jan. 18 in the Archives of Dermatology.
Both patients, aged 20 and 39 years, first exhibited photosensitivity followed by extensive photodamage before the lesions were identified in affected areas.
These cases, even added to the four already reported in the literature, are not enough to establish that the drug plays “a definitive causal role” in skin malignancy. However, “we believe that the presence of accelerated photodamage in [two relatively young] patients, coupled with the recent reports supporting an association between voriconazole use and [aggressive] squamous cell carcinoma, warrant further exploration of the role of the drug in skin cancer formation,” said Dr. Daniel D. Miller of the University of California, San Francisco, and his associates (Arch Dermatol. 2010 [doi:10.1001/archdermatol.2009.362]).
“Until such studies further define the skin cancer risk associated with voriconazole, we recommend surveillance for skin cancer formation in all patients who require long-term voriconazole treatment, particularly those who manifest signs or symptoms of photosensitivity or chronic photodamage,” the investigators noted.
They described the two most recent patients in case reports.
The first patient was a 39-year-old woman who was first referred for severe photosensitivity and extensive lentigines on the photoexposed surfaces of the face, upper trunk, and extensor extremities. There was no personal or family history of photosensitivity or skin cancer.
The woman lived in an area endemic for coccidioidomycosis and had been receiving oral voriconazole for 3 years to treat coccidioidomycosis meningitis. Severe erythema with eruptive pigmented macules had developed 1 year after starting treatment.
Histopathology of a specimen taken from an erythematous macule on the right helix showed melanoma in situ.
Five months later, Dr. Miller and his colleagues discovered another ill-defined lesion on the patient —“a brownish blue patch within a field of solar lentigines on severely sun-damaged skin on the mid-upper chest”— that proved to be another melanoma in situ.
One year later, two additional in situ melanomas were identified on the right forearm and the dorsal surface of the left hand. Voriconazole therapy was discontinued, and the patient continues to be monitored for suspicious skin lesions every 3-6 months.
In the second case, an adolescent male with chronic granulomatous disease had been taking long-term voriconazole to treat pulmonary Aspergillus infection. After 2 years of the therapy, he had begun to develop lentigines on sun-exposed areas of his body, including the face, forearms, and dorsal surfaces of his hands.
At age 20 years, after 55 months of treatment, an irregular, darkly pigmented macule on his left forearm was found to be melanoma in situ. His therapy was switched from voriconazole to posaconazole. No subsequent lesions have been identified, and the patient reports fading of his extensive lentigines since discontinuing voriconazole.
The courses of these two patients are clinically similar to what happens in patients who undergo long-term PUVA therapy and in those with xeroderma pigmentosum. However, in the two case reports, "the rapid onset of extensive lentigines, as well as the short interval of voriconazole therapy before melanoma developed (relative to that seen due to PUVA), suggest perhaps an even more accelerated process of carcinogenesis," Dr. Miller and his colleagues said.
“Future comparisons between xeroderma pigmentosum-associated melanomas and those occurring in the setting of voriconazole-associated phototoxic effects may provide valuable insight into the contribution of UV light to melanoma genesis,” they added.
Dr. Miller reported no relevant conflicts of interest.