Association of pyrazolone drug hypersensitivity with HLA-DQ and DR antigens

Clin Exp Allergy. 1998 Sep;28(9):1153-8. doi: 10.1046/j.1365-2222.1998.00346.x.

Abstract

Background: In sensitive patients pyrazolone drugs can precipitate adverse reactions ranging from urticaria and angioedema to anaphylactic shock, presumably by immunological, IgE-mediated mechanism. However, up to now no genetic factors influencing the development of allergic reaction have been reported in this type of hypersensitivity.

Objective: The aim of our study was the investigation whether the susceptibility to development of pyrazolone drugs hypersensitivity (PDH) reactions was associated with HLA class II antigens.

Methods: To test this hypothesis we studied the distribution of HLA-DR and DQ antigens in 26 pyrazolone sensitive patients and control groups including unselected general population and clearly defined atopic and non-atopic groups.

Results: Significantly higher frequencies of DQ 7 and DR11 antigens were found in PDH group as compared with control unselected population (RR= 16.48, P < 0.0001; P(cor)< 0.002 and RR = 4.57, P = 0.0002; Pcor = 0.003 for DQ and DR antigen respectively). Similarly, statistically significant increased frequencies of DQ 7 and DR11 in patients with PDH were observed compared with atopic control group (RR= 18.43, P < 0.0001; Pcor <0.002 and RR= 6.33, P= 0.0007; Pcor =0.01, for DQ and DR antigen respectively). However, in comparison to non-atopic control group only the frequency of DQ 7 antigen was significantly increased (RR = 15.42, P = 0.0001; Pcor = 0.0015). DQ 7 antigen was present in 46.1% of PDH patients compared with 4.9%, 4.4% and 5.3% in the general population, atopic and non-atopic groups respectively, suggesting pyrazolone hypersensitivity as a trait positively correlated with this HLA antigen.

Conclusion: Our data suggest a genetic predisposition to pyrazolone hypersensitivity reactions, linked to HLA-DQ locus.

MeSH terms

  • Adolescent
  • Adult
  • Anaphylaxis / chemically induced
  • Anaphylaxis / immunology
  • Angioedema / chemically induced
  • Angioedema / immunology
  • Anti-Inflammatory Agents, Non-Steroidal / adverse effects*
  • Cytotoxicity Tests, Immunologic
  • Drug Hypersensitivity / etiology*
  • Drug Hypersensitivity / immunology
  • Female
  • HLA-DQ Antigens / immunology*
  • HLA-DR Antigens / immunology*
  • Humans
  • Male
  • Middle Aged
  • Pyrazoles / adverse effects*
  • Pyrazolones*
  • Urticaria / chemically induced
  • Urticaria / immunology

Substances

  • Anti-Inflammatory Agents, Non-Steroidal
  • HLA-DQ Antigens
  • HLA-DR Antigens
  • Pyrazoles
  • Pyrazolones
  • pyrazolone