Comparison of cytokine gene polymorphism in drug-induced maculopapular eruption, urticaria and drug reaction with eosinophilia and systemic symptoms (DRESS)

Authors

  • A. Barbaud,

    Corresponding author
    1. CHU Nancy, Service de Dermatologie and INGRES research Unit, pôle des Spécialités médicales, Vandoeuvre les Nancy, France
    2. INSERM, U954, Vandoeuvre les Nancy, France
    3. Université de Lorraine, Faculté de Médecine, Vandoeuvre les Nancy, France
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  • J. Waton,

    1. CHU Nancy, Service de Dermatologie and INGRES research Unit, pôle des Spécialités médicales, Vandoeuvre les Nancy, France
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  • B. Herbeth,

    1. CHU Nancy, Laboratoire de Biochimie et Biologie Moléculaire, Nutrition et Métabolisme, Vandoeuvre les Nancy, France
    2. Université de Lorraine, Faculté de Pharmacie, Nancy, France
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  • A.C. Bursztejn,

    1. CHU Nancy, Service de Dermatologie and INGRES research Unit, pôle des Spécialités médicales, Vandoeuvre les Nancy, France
    2. INSERM, U954, Vandoeuvre les Nancy, France
    3. Université de Lorraine, Faculté de Médecine, Vandoeuvre les Nancy, France
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  • M. Bollaert,

    1. CHU Nancy, Service de Dermatologie and INGRES research Unit, pôle des Spécialités médicales, Vandoeuvre les Nancy, France
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  • J.L. Schmutz,

    1. CHU Nancy, Service de Dermatologie and INGRES research Unit, pôle des Spécialités médicales, Vandoeuvre les Nancy, France
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  • R.M. Guéant-Rodriguez,

    1. INSERM, U954, Vandoeuvre les Nancy, France
    2. Université de Lorraine, Faculté de Médecine, Vandoeuvre les Nancy, France
    3. CHU Nancy, Laboratoire de Biochimie et Biologie Moléculaire, Nutrition et Métabolisme, Vandoeuvre les Nancy, France
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  • F. Namour,

    1. INSERM, U954, Vandoeuvre les Nancy, France
    2. Université de Lorraine, Faculté de Médecine, Vandoeuvre les Nancy, France
    3. CHU Nancy, Laboratoire de Biochimie et Biologie Moléculaire, Nutrition et Métabolisme, Vandoeuvre les Nancy, France
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  • J.L. Guéant,

    1. INSERM, U954, Vandoeuvre les Nancy, France
    2. Université de Lorraine, Faculté de Médecine, Vandoeuvre les Nancy, France
    3. CHU Nancy, Laboratoire de Biochimie et Biologie Moléculaire, Nutrition et Métabolisme, Vandoeuvre les Nancy, France
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  • I. Aimone-Gastin

    1. Université de Lorraine, Faculté de Médecine, Vandoeuvre les Nancy, France
    2. CHU Nancy, Laboratoire de Biochimie et Biologie Moléculaire, Nutrition et Métabolisme, Vandoeuvre les Nancy, France
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  • Conflict of interest

    • The authors declare that they have no competing interests as defined by the Journal of the European Academy of Dermatology and Venereology, or other interests that might be perceived to influence the results and discussion reported in this article.

    Funding sources

    • This study was sustained by regional research funds from the University Hospital of Nancy (PHRC: UF 9793).

Abstract

Background

Polymorphisms of genes controlling cytokine production have not been studied in the genetic susceptibility to cutaneous adverse drug reactions (CADR).

Objectives

The objective was to determine whether polymorphisms in nine cytokine genes were associated to the occurrence of drug reaction with eosinophilia and systemic symptoms (DRESS) compared to drug-induced maculopapular eruption or urticaria and to controls without drug intolerance.

Methods

Results from 118 patients with a well-defined CADR were compared to 236 controls without drug intolerance living in the same area of France. We assessed nine polymorphisms: interleukin (IL)1-alpha-889C>T (rs 1800587), IL1-beta-511C>T (rs 16944), IL1-RN intron-2-VNTR (rs2234663), IL2-330T>G (rs 2069762), IL4-33C>T (rs 2070874), IL5-745C>T (rs 2069812), IL10-592C>A (rs 1800872), IL16-295T>C (rs 4778889) and tumour necrosis factor-alpha-308G>A (rs 1800629).

Results

Three polymorphisms exhibited a significant association with CADR (P < 0.05). The combination of the IL1-RN-A2 and IL1-beta-511C alleles was statistically different between cases and controls (P = 0.007) and the A2C haplotype was associated with susceptibility to CADR, particularly in drug reaction with eosinophilia and systemic symptoms (DRESS) patients (odds ratio = 3.22; 95% confidence interval = 1.23–8.41; P = 0.016). The frequency of the IL10-592A allele was higher in DRESS patients than in controls (dominant model CC vs. CA + AA: P = 0.035). These abnormalities were not evident in maculopapular eruptions or urticaria.

Conclusions

This is the first study showing that IL1-cluster polymorphisms and haplotypes and the IL10-592A allele (a low IL10 producer) are associated with DRESS. These gene variants may decrease drug tolerance and promote herpes virus reactivation.

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