title: 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.affiliation: Department of Dermatology, Medical Faculty, Heinrich-Heine-University, Duesseldorf, Germany.
authors.forename: S
authors.initials: S
authors.lastname: Meller
authors.affiliation: Department of Dermatology, Medical Faculty, Heinrich-Heine-University, Duesseldorf, Germany.
authors.forename: P A
authors.initials: PA
authors.lastname: Gerber
authors.affiliation: Department of Dermatology, Medical Faculty, Heinrich-Heine-University, Duesseldorf, Germany.
authors.forename: A
authors.initials: A
authors.lastname: Kislat
authors.affiliation: Department of Dermatology, Medical Faculty, Heinrich-Heine-University, Duesseldorf, Germany.|Physiology and Biophysics, University of California Irvine, Irvine, CA, USA.
authors.forename: P
authors.initials: P
authors.lastname: Hevezi
authors.affiliation: Clinic of Gastroenterology, Hepatology and Infectiology, Medical Faculty, Heinrich-Heine-University, Duesseldorf, Germany.
authors.forename: T
authors.initials: T
authors.lastname: Göbel
authors.affiliation: Department of Dermatology, Medical Faculty, Heinrich-Heine-University, Duesseldorf, Germany.
authors.forename: U
authors.initials: U
authors.lastname: Wiesner
authors.affiliation: Department of Dermatology, Medical Faculty, Heinrich-Heine-University, Duesseldorf, Germany.
authors.forename: S
authors.initials: S
authors.lastname: Kellermann
authors.affiliation: Department of Dermatology, Medical Faculty, Heinrich-Heine-University, Duesseldorf, Germany.
authors.forename: E
authors.initials: E
authors.lastname: Bünemann
authors.affiliation: Physiology and Biophysics, University of California Irvine, Irvine, CA, USA.
authors.forename: A
authors.initials: A
authors.lastname: Zlotnik
authors.affiliation: Clinic of Gastroenterology, Hepatology and Infectiology, Medical Faculty, Heinrich-Heine-University, Duesseldorf, Germany.
authors.forename: D
authors.initials: D
authors.lastname: Häussinger
authors.affiliation: Clinic of Gastroenterology, Hepatology and Infectiology, Medical Faculty, Heinrich-Heine-University, Duesseldorf, Germany.
authors.forename: A
authors.initials: A
authors.lastname: Erhardt
authors.affiliation: Department of Dermatology, Medical Faculty, Heinrich-Heine-University, Duesseldorf, Germany.
authors.forename: B
authors.initials: B
authors.lastname: Homey
mesh_terms: D000998:Antiviral Agents / Q000009:adverse effects* / Q000627:therapeutic use; D016207:Cytokines / Q000235:genetics / Q000378:metabolism; D003875:Drug Eruptions / Q000175:diagnosis / Q000209:etiology*; D015870:Gene Expression; D019698:Hepatitis C, Chronic / Q000150:complications / Q000188:drug therapy; D006801:Humans; D050835:Interferon Regulatory Factors / Q000235:genetics / Q000378:metabolism; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000009:adverse effects* / Q000627:therapeutic use; D008213:Lymphocyte Activation; D011092:Polyethylene Glycols / Q000009:adverse effects* / Q000627:therapeutic use; D011994:Recombinant Proteins / Q000009:adverse effects / Q000627:therapeutic use; D012867:Skin / Q000473:pathology; D012882:Skin Tests; D016176:T-Lymphocyte Subsets / Q000276:immunology / Q000378:metabolism
chemical_list: D000998:Antiviral Agents; D016207:Cytokines; D050835:Interferon Regulatory Factors; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D011994:Recombinant Proteins; D011092:Polyethylene Glycols; C417083:peginterferon alfa-2b; C100416:peginterferon alfa-2a
keywords: chemokines; drug eruption; lymphocyte activation test; maculopapular exanthema; pegylated Interferon