Allergic sensitization to pegylated interferon- results in drug eruptions

BackgroundThe introduction of pegylated interferon (PEG-IFN)- in the treatment of chronic hepatitis C has led to an increase in sustained virological response. Despite reduced immunogenicity of the pegylated form in comparison with native interferon (IFN)-, a high frequency of adverse cutaneous reactions has been reported with pegylated IFN-. Here, we aimed to investigate the immunological mechanisms underlying pegylated IFN--induced drug eruptions. MethodsHepatitis C patients suffering from drug eruptions in association with administration of pegylated interferons were enrolled in the study (n=22). Subjects were tested for sensitivity to pegylated IFN-(2a), pegylated IFN-(2b), or ribavirin using intradermal, scratch, and/or patch tests, as well as lymphocyte activation tests (LATs). Skin biopsies obtained from pegylated IFN--associated exanthemas, as well as from localized inflammatory skin reactions at pegylated IFN- injection sites, were analyzed for the expression of relevant chemokines by quantitative real-time PCR and immunohistochemistry. ResultsA subset of patients suffering from pegylated IFN--associated exanthemas displayed positive intradermal tests to PEG-IFNs but not to conventional IFN (11/22). In selected patients, this observation correlated with the presence of pegylated IFN-specific T cells (3/11). Chemokine profiles of inflammatory skin reactions at the injection sites reflected an IFN--signature, whereas lesional skin of exanthemas showed induction of TH2-associated chemokines. ConclusionsOur results indicate that specific sensitizations are one cause of exanthemas under therapy with PEG-IFNs. Clinical proof-of-concept analyses demonstrate that affected patients may benefit from a switch to conventional,nonpegylated drugs, enabling IFN- therapy continuation without drug-associated skin eruptions.