Generalized Nummular Eczema Secondary to Peginterferon Alfa-2b and Ribavirin Combination Therapy for Hepatitis C Infection

We read with interest the article by Moore et al¹ titled “Severe, Generalized Nummular Eczema Secondary to Interferon Alfa-2b Plus Ribavirin Combination Therapy in a Patient With Chronic Hepatitis C Virus Infection.” We report 2 additional cases of severe generalized nummular eczema developing after combination immunotherapy for chronic hepatitis C virus (HCV).

A 39-year-old white man with a medical history notable for treated malaria and dengue fever as well as chronic HCV infection was started on combination treatment for his HCV with peginterferon alfa-2b injections weekly and ribavirin administered orally twice daily. Four months after therapy was initiated, the patient developed a diffuse intensely pruritic rash unresponsive to oral diphenhydramine hydrochloride. He had no personal or family history of atopy or other dermatologic disease. Combination immunotherapy was stopped because of this eruption, with subsequent gradual improvement of skin lesions and pruritus. Physical examination findings 2 weeks later revealed nummular erythematous patches with scale on the trunk, extremities (Figure), and face. The patient’s condition cleared with the administration of 0.1% triamcinolone ointment twice daily.

A 53-year-old white woman with a 1-year history of chronic active HCV infection was started on peginterferon alfa-2b injections weekly and ribavirin orally 3 times daily after failing monotherapy with interferon alfa. Six months after the first combined dose, the patient was seen in the dermatology clinic for evaluation of a pruritic eruption on the trunk and extremities. The patient had no personal or family history of atopy or other dermatologic disease. Physical examination findings revealed erythematous nummular patches with scale on the extremities, chest, and back with extensive linear excoriations. Combination immunotherapy was discontinued, and the eruption resolved within several weeks while the patient received 0.1% triamcinolone ointment twice daily. Because of this eruption in addition to severe headaches and pancytopenia, the patient elected not to restart combination immunotherapy for her HCV infection.

While combination immunotherapy with interferon and ribavirin is considered to be the treatment of choice for HCV, adverse effects may limit therapy. Commonly reported dermatologic effects include localized reactions such as injection site inflammation and necrosis and worsening of other skin disorders, including psoriasis, lichen planus, or vitiligo.² Generalized eczematous eruptions have been reported to occur uncommonly in patients treated with interferon and ribavirin in the European literature.^{3 - 5} Moore et al¹ documented the first North American report of severe recalcitrant nummular eczema occurring after combination immunotherapy with interferon alfa-2b and ribavirin for HCV. The onset in our cases at 3 to 6 months after initiation of therapy and the lack of an atopic history are consistent with prior reports.^{1 ,3} The eruption may be seen with standard^{1 ,4} or pegylated^{3 ,5} interferon, although both our patients received peginterferon. Inflammation at injection site may also be present^{1 ,4} but more commonly, as in our patients, is not.³ Previous reports indicate that the diffuse eczematous eruption necessitated premature cessation of immunotherapy in up to half of patients.³ While the eruption regressed in our 2 patients after therapy was discontinued and topical steroids were added, it may continue after cessation of therapy and require systemic steroids to control.¹ The mechanism by which immunotherapy with interferon and ribavirin causes eczema has not been elucidated, and intradermal and patch skin testing do not seem to be helpful in identifying susceptible patients.³ We agree with the authors’ suggestion that this problem likely occurs at a higher frequency than is reflected in the North American literature. Patient education prior to initiation of combination immunotherapy regarding this potential adverse effect, an interdisciplinary approach during treatment, and possibly even preventative skin care could help decrease the rate of premature discontinuation owing to this complication.

Correspondence: Dr Hsu, Department of Dermatology, One Baylor Plaza, FB840, Houston, TX 77030 (shsu@bcm.tmc.edu).

Financial Disclosure: None.