Adverse skin reactions due to pegylated interferon alpha 2b plus ribavirin combination therapy in a patient with chronic hepatitis C virus

Abstract

Pegylated interferon (IFN)-alpha-2b with ribavirin has recently replaced "standard" IFN-alpha for the treatment of chronic hepatitis C. The most common side-effect of pegylated IFN-alpha-2b plus ribavirin combination therapy is localized inflammatory skin lesions at the site of injection. A 66-year-old female treated with once-weekly pegylated IFN-alpha-2b plus ribavirin for active chronic hepatitis C developed inflammatory skin lesions 2 months after starting antiviral treatment. The type of skin reactions observed were vesicle erythematous eruptions at the injection sites, and pruritic papular erythematous eruptions located on the face, neck, distal limbs, dorsa of the hands, trunk and buttocks away from the injection sites. Histological examination was performed on the pruritic papular erythematous eruption located on the left forearm, away from the injection sites. It showed epidermal spongiosis, a spongiotic microvesicle, and perivascular infiltration of the upper dermis with lymphocytes. The treatment was interrupted subsequently and the patient was rechallenged with pegylated IFN-alpha-2b plus ribavirin combination therapy, oral prednisolone with olopatadine hydrochloride and topical 0.1% diflucortolone valerate, which led to a significant improvement of skin lesions. Erythema with infiltration can occur at the injection sites of pegylated IFN-alpha-2b. However, the occurrence of vesicle erythematous eruptions away from the injection sites and autosensitization dermatitis apart from injection sites have not yet been frequently reported.

Study of pruritus in chronic hepatitis C patients

“…Adverse skin reactions and pruritus during IFN treatment for chronic hepatitis C may be caused by either immune changes or an excessive immune reaction [12,13] . Peginterferon induces injection site reactions in 36%-59% of cases [14,15] and can sometimes cause generalized dermatitis [13,16,17] .…”

“…Peginterferon induces injection site reactions in 36%-59% of cases [14,15] and can sometimes cause generalized dermatitis [13,16,17] . In our study of chronic hepatitis C patients, we only assessed the presence of pruritus and excluded injection site reactions and atopic dermatitis from the analysis.…”

“…Comparison between PEG-IFN α2a and PEG-IFN α2b monotherapies would have been preferable; however, this was not possible because the Japanese health insurance system stipulates that PEG-IFN α2b must be administered with RBV. RBV itself has been reported to cause pruritus [13,19] . When combined with PEG-IFN, a synergistic effect may result in a delayed-type hypersensitivity reaction, with a shift in the helper T (Th) cell balance towards a Th1-dominant response due to the influence of IFN.…”

Dermatologic adverse events of protease inhibitor-based combination therapy in patients with chronic hepatitis C

“…6 The 13% incidence of "dermatitis" associated with PEG-INF monotherapy increased to 21% in combination with RBV. [7][8][9] The DAEs associated with triple therapy using TVR during the phase II/III clinical trials involving over 3800 patients have been reported with a higher frequency and more severe presentations than seen with dual therapy PEG-INF/RBV (56% of patients in triple therapy compared to 34% in dual therapy). 2,3,5,[10][11][12][13] Because of high rates of DAEs noted in phase II trials of TVR, a grading system and management protocol was implemented for the future use in clinical trials.…”

Cytokines Induced Skin Adverse Reactions

“…A review of the literature suggests that dermatological adverse reactions induced by pegylated IFN-a plus ribaverin (RBV) are various and frequent. Generalized eczema, hyperpigmented skin and tongue lesionsmultiple fixed drug eruption, vitiligopruritis, eruption, erythema, and hair shedding, eczema-like skin lesions, photosensitivity, vesicle erythematous eruptions, pruritic papular erythematous eruptionssecondary to combined treatment with peginterferon alfa-2a and ribavirin had been reported [9][10][11][12][13][14][15][16][17]. Tavakoli-Tabasi and Bagree [18] made a longitudinal cohort study, and suggested mucocutaneous reactions during IFN and ribavirin treatment of hepatitis C are associated with HIV infection and use of pegylated IFN.…”