Focal Neurotoxicity Associated With Topical 5-Fluorouracil

Topical 5-Fluorouracil (5-FU) is an antineoplastic chemotherapy drug used to treat precancerous and cancerous skin growths, such as actinic keratoses (AKs), squamous cell carcinoma in situ, and superficial basal cell carcinoma. The topical agent may rarely cause neurotoxic adverse effects. Multiple cases of systemic 5-FU and capecitabine chemotherapy-induced neuropathies have been reported. However, until now, the topical administration of the drug has not been reported to cause neurotoxicity. We present a case of an 83-year-old male who was prescribed topical 5-FU 5% cream to treat AKs on the left anterior scalp and returned weeks later with the development of focal neurotoxicity in the treatment area. He presented with focal paralysis of the left medial frontalis muscle, with initial loss of sensation followed by intermittent pain and paresthesias, persisting four months after the cessation of therapy. He was referred to a neurologist and received a diagnosis of supraorbital neuralgia. The temporal relationship of symptom onset and the localization of symptoms to the treated area strongly suggests that the medication contributed to the observed neurologic effects. These effects are more likely to be observed in patients with a genetic deficiency of dihydropyrimidine dehydrogenase (DPD), which is responsible for the majority of 5-FU degradation (80%), therefore potentially leading to toxic levels of unmetabolized 5-FU. Providers should be aware of the potentially neurotoxic effects of topical 5-FU in order to properly counsel patients and to consider this as a possible etiology of neurologic deficits in patients using this drug.