Blue-gray mucocutaneous discoloration: A new adverse effect of ezogabine

Tali Garin Shkolnik, Hana Feuerman, Elena Didkovsky, Ilana Kaplan, Reuven Bergman, Lev Pavlovsky, Emmilia Hodak*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

65 Scopus citations

Abstract

IMPORTANCE Many drugs have been reported to induce skin and/or mucous membrane discoloration. Ezogabine (retigabine) was recently approved as an add-on drug for the treatment of partial seizures in adults with epilepsy. Mucocutaneous discoloration induced by antiepileptic drugs in general and ezogabine in particular has not been previously reported.

OBSERVATIONS Two patients who had received multiple antiepileptic drugs for several years presented with a blue-gray skin dyspigmentation that was most pronounced on the face and lips and was associated with nail pigmentation, blue pigmentation on the hard palate, and black pigment deposits on the conjuctivae. The sole drug common to the therapeutic regimens of both patients was ezogabine. Histopathologically, the main finding was perivascular and periadnexal dermal cells heavily laden with coarse melanin granules, which appeared ultrastructurally as intracellular electron-dense granules. Four months after discontinuing ezogabine, our first patient showed a significant improvement in the mucocutaneous and nail dyspigmentation.

CONCLUSIONS AND RELEVANCE The temporal relationship, clinical features, histologic and ultrastructure findings, and improvement following withdrawal of ezogabine indicate that the dyspigmentation was drug induced. Ezogabine should be added to the list of drugs that can induce mucocutaneous discoloration. The incidence of this significant adverse effect requires further investigation.

Original languageEnglish
Pages (from-to)984-989
Number of pages6
JournalJAMA Dermatology
Volume150
Issue number9
DOIs
StatePublished - 1 Sep 2014

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