Allergic sensitization to pegylated interferon-[alpha] results in drug eruptions

• Published in: Allergy (Copenhagen) Vol. 70; no. 7; p. 775
• Main Authors: Meller, S, Gerber, P A, Kislat, A, Hevezi, P, Gobel, T, Wiesner, U, Kellermann, S, Bunemann, E, Zlotnik, A, Haussinger, D, Erhardt, A, Homey, B
• Format: Journal Article
• Language: English
• Published: Zurich Blackwell Publishing Ltd 01.07.2015
• Subjects: Allergies; Antiviral drugs; Hepatitis; Immunology; Interferon; Side effects
• ISSN: 0105-4538; 1398-9995
• DOI: 10.1111/all.12618

Background The introduction of pegylated interferon (PEG-IFN)-[alpha] 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)-[alpha], a high frequency of adverse cutaneous reactions has been reported with pegylated IFN-[alpha]. Here, we aimed to investigate the immunological mechanisms underlying pegylated IFN-[alpha]-induced drug eruptions. Methods Hepatitis 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-[alpha]2a, pegylated IFN-[alpha]2b, or ribavirin using intradermal, scratch, and/or patch tests, as well as lymphocyte activation tests (LATs). Skin biopsies obtained from pegylated IFN-[alpha]-associated exanthemas, as well as from localized inflammatory skin reactions at pegylated IFN-[alpha] injection sites, were analyzed for the expression of relevant chemokines by quantitative real-time PCR and immunohistochemistry. Results A subset of patients suffering from pegylated IFN-[alpha]-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-[alpha]-signature, whereas lesional skin of exanthemas showed induction of TH2-associated chemokines. Conclusions Our 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-[alpha] therapy continuation without drug-associated skin eruptions.