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Background: With increasing rates of hepatitis C virus infection and diagnosis, more patients are being treated with interferon alfa-2b plus ribavirin therapy. Cutaneous side effects to combination therapy are common and may limit treatment. There are few previous case reports of generalized eczematous dermatoses occurring after combination therapy for hepatitis C virus, none in a North American patient, and none of this severity or recalcitrance. Observations: A man with chronic hepatitis C virus infection and no history of atopy developed severe, recalcitrant nummular eczema secondary to interferon alfa-2b plus ribavirin combination therapy. The cutaneous side effect was more severe than in previously reported cases and did not remit on discontinuation of therapy. Conclusions: Greater awareness of the range of dermatologic responses to interferon alfa-2b plus ribavirin therapy may lead to improved surveillance for and treatment of these side effects. Investigating the underlying pathologic mechanisms may ultimately allow for a greater understanding of the immunomodulatory effects of this therapy in the setting of chronic hepatitis C virus infection. [ABSTRACT FROM AUTHOR]