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. 2015 Jul;70(7):775-83.
doi: 10.1111/all.12618. Epub 2015 May 6.

Allergic sensitization to pegylated interferon-α results in drug eruptions

S Meller  1 , P A Gerber  1 , A Kislat  1 , P Hevezi  1   2 , T Göbel  3 , U Wiesner  1 , S Kellermann  1 , E Bünemann  1 , A Zlotnik  2 , D Häussinger  3 , A Erhardt  3 , B Homey  1
Affiliations

Allergic sensitization to pegylated interferon-α results in drug eruptions

S Meller et al. Allergy. 2015 Jul.

Abstract

Background: The introduction of pegylated interferon (PEG-IFN)-α 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)-α, a high frequency of adverse cutaneous reactions has been reported with pegylated IFN-α. Here, we aimed to investigate the immunological mechanisms underlying pegylated IFN-α-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-α2a , pegylated IFN-α2b , or ribavirin using intradermal, scratch, and/or patch tests, as well as lymphocyte activation tests (LATs). Skin biopsies obtained from pegylated IFN-α-associated exanthemas, as well as from localized inflammatory skin reactions at pegylated IFN-α 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-α-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-α-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-α therapy continuation without drug-associated skin eruptions.

Keywords: chemokines; drug eruption; lymphocyte activation test; maculopapular exanthema; pegylated Interferon.

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