Conference Coverage

Beware drug reactions from methotrexate, voriconazole, and BRAF inhibitors



– Cutaneous necrosis. Porphyria cutanea tarda, accelerated photoaging, and actinic keratosis (AK). Cutaneous keratinocytic neoplasias. Two drugs – and a class of drugs commonly used in oncologic dermatology – can produce these skin conditions, a dermatologist cautioned his colleagues.

J. Mark Jackson, MD, of the University of Louisville (Ky.), highlighted these drug reactions in a presentation at the annual Coastal Dermatology Symposium. The medications that can cause these skin-related adverse events are methotrexate, voriconazole (Vfend), and BRAF inhibitors.

Dr. Jackson referred to reports of cutaneous necrosis associated with methotrexate and highlighted a 2017 case series that compared 24 patients who developed the condition with a control population of patients taking methotrexate who did not develop it. The patients with this reaction were more likely to be older, had a higher starting dose, and had signs of kidney problems. They were also less likely to be taking folic acid supplements (J Am Acad Dermatol. 2017 Aug;77[2]:247-55.e2).

“It’s pretty alarming,” he said. “They look like Stevens-Johnson syndrome/TEN [toxic epidermal necrolysis], but the pathology was differentiated,” he pointed out.

He cautioned, though, that this is not “a typical reaction.”

The oral antifungal drug voriconazole is often used in immunosuppressed patients, such as transplant patients, either as prophylaxis or therapy. It is highly photosensitizing and has been linked to porphyria cutanea tarda, accelerated photoaging, development of AKs, and aggressive cutaneous squamous cell carcinoma (Am J Transplant 2008 Apr;8[4]:877-80; AIDS. 2008 Apr 23;22[7]:905-6; J Am Acad Dermatol. 2010 Jan;62[1]:31-7; Dermatol Surg. 2010 Nov;36[11]:1752-5).

The risk of nonmelanoma skin cancer may be quadrupled in patients who take this medication, Dr. Jackson said.

There also are reports of patients on voriconazole developing tense bullae that are suggestive of porphyria cutanea tarda but with normal porphyrin levels, he said. This resolves over time, once therapy has ceased.

The BRAF inhibitor chemotherapy drugs – vemurafenib (Zelboraf), dabrafenib (Tafinlar), and encorafenib (Braftovi) – are used to treat metastatic melanoma. They’ve been linked to rash and cutaneous keratinocytic neoplasias. Patients on these agents should be “closely monitored” for these conditions (Chem Immunol Allergy. 2012;97:191-202). Dr. Jackson emphasized the importance of photoprotection with these patients and noted that it’s crucial to see these patients every month because neoplasias can develop quickly, even within 4 weeks of starting the medication.

The Coastal Dermatology Symposium is jointly presented by the University of Louisville and Global Academy for Medical Education. This publication and Global Academy for Medical Education are both owned by Frontline Medical Communications.

Dr. Jackson reported relationships with AbbVie, Accuitis, Aclaris, Galderma, Janssen, Lilly, Medimetriks, Novartis, Promius, Ralexar, and TopMD.

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