title: Peripheral neuropathy exacerbation associated with topical 5-fluorouracil.
abstract: Peripheral neuropathy secondary to 5-flourouracil and capecitabine (Xeloda) has been reported. We report the first case of exacerbation of peripheral neuropathy related to topical 5-flourouracil (Efudex). A 70-year-old Caucasian male with a history of actinic keratosis for 15 years was treated intermittently with topical application of 5-flourouracil. He also developed sensory peripheral neuropathy around the same time, but extensive work-up disclosed no clear etiology. In early 2005, he developed an exacerbation of his peripheral neuropathy following a 21-day course of topical 5-flourouracil for actinic keratosis, especially pain and parasthesias. Dihydropyrimidine dehydrogenase activity was evaluated in the peripheral mononuclear cells both by radioassay and by [2-C] uracil breath test. Dihydropyrimidine dehydrogenase activity was within the normal range by both methods. Stopping topical 5-flourouracil resolved the symptoms to baseline. Instead of topical 5-flourouracil, topical imiquimod was used which did not exacerbate his neuropathy. He was not re-challenged with topical 5-flourouracil. Topical 5-flourouracil has been known to cause mainly dermatological adverse effects, but systemic effects because of absorption are possible, especially in dihydropyrimidine dehydrogenase-deficient patients. As our patient had no other cause responsible for his neuropathy, the onset of symptoms coincided historically with topical application of 5-flourouracil and the 5-flourouracil usage preceded an exacerbation of sensory symptoms, we conclude that this drug was responsible for his polyneuropathy.
authors.affiliation: Section of Medical Oncology, Yale Cancer Center, Yale University School of Medicine, New Haven, Connecticut 06520, USA. wasif.saif@yale.edu
authors.forename: Muhammad Wasif
authors.initials: MW
authors.lastname: Saif
authors.forename: Shahrukh
authors.initials: S
authors.lastname: Hashmi
authors.forename: Lori
authors.initials: L
authors.lastname: Mattison
authors.forename: William B
authors.initials: WB
authors.lastname: Donovan
authors.forename: Robert B
authors.initials: RB
authors.lastname: Diasio
mesh_terms: D000368:Aged; D000964:Antimetabolites, Antineoplastic / Q000009:adverse effects*; D054067:Dihydropyrimidine Dehydrogenase Deficiency; D042943:Dihydrouracil Dehydrogenase (NADP) / Q000378:metabolism; D005472:Fluorouracil / Q000008:administration & dosage / Q000009:adverse effects*; D006801:Humans; D008297:Male; D010523:Peripheral Nervous System Diseases / Q000139:chemically induced*
chemical_list: D000964:Antimetabolites, Antineoplastic; D042943:Dihydrouracil Dehydrogenase (NADP); D005472:Fluorouracil