Allergic sensitization to pegylated interferon-α results in drug eruptions.

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.

• Authors: S Meller, P A Gerber, A Kislat, P Hevezi, T Göbel, U Wiesner, S Kellermann, E Bünemann, A Zlotnik, D Häussinger, A Erhardt, B Homey
• Journal: Allergy (Allergy) Vol. 70 Issue 7 Pg. 775-83 (Jul 2015) ISSN: 1398-9995 [Electronic] Denmark
• PMID: 25831972 (Publication Type: Journal Article)
• Copyright: © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Chemical References

• Antiviral Agents
• Cytokines
• Interferon Regulatory Factors
• Interferon alpha-2
• Interferon-alpha
• Recombinant Proteins
• Polyethylene Glycols
• peginterferon alfa-2b
• peginterferon alfa-2a

Topics

• Antiviral Agents (adverse effects, therapeutic use)
• Cytokines (genetics, metabolism)
• Drug Eruptions (diagnosis, etiology)
• Gene Expression
• Hepatitis C, Chronic (complications, drug therapy)
• Humans
• Interferon Regulatory Factors (genetics, metabolism)
• Interferon alpha-2
• Interferon-alpha (adverse effects, therapeutic use)
• Lymphocyte Activation
• Polyethylene Glycols (adverse effects, therapeutic use)
• Recombinant Proteins (adverse effects, therapeutic use)
• Skin (pathology)
• Skin Tests
• T-Lymphocyte Subsets (immunology, metabolism)