Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Original Article
  • Published:

A marker for Stevens-Johnson syndrome …: ethnicity matters

The Pharmacogenomics Journal volume 6, pages 265–268 (2006)Cite this article

Abstract

Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are rare but severe cutaneous adverse drug reactions, which can be caused by a certain number of specific drugs among which is carbamazepine, an antiepileptic agent. A very strong association of carbamazepine-induced SJS with HLA-B*1502 has recently been described in the Han Chinese population. Here in, we report preliminary results from a European study (RegiSCAR) of 12 carbamazepine-induced SJS/TEN cases (nine French and three German). Among these only four had a HLA-B*1502 allele. Remarkably, these four patients had an Asian ancestry, whereas the others did not as far as we have ascertained. This shows that although the HLA region may contain important genes for SJS, the HLA-B*1502 allele is not a universal marker for this disease and that ethnicity matters.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Similar content being viewed by others

Abbreviations

SJS:

Stevens-Johnson syndrome

TEN:

Toxic epidermal necrolysis

NSAID:

Nonsteroidal anti-inflammatory drug

References

  1. Roujeau JC, Kelly JP, Naldi L, Rzany B, Stern RS, Anderson T et al. Medication use and risk of Stevens-Johnson syndrome or toxic epidermal necrolysis. New Engl J Med 1995; 333: 1600–1607.

    Article  CAS  Google Scholar 

  2. Fagot JP, Mockenhaupt M, Bouwes-Bavinck JN, Naldi L, Viboud C, Roujeau J-C . Nevirapine and the risk of Stevens-Johnson syndrome or toxic epidermal necrolysis: preliminary results of a case-control study. AIDS 2001; 15: 1–6.

    Article  Google Scholar 

  3. Viard I, Wehrli P, Bullani R, Schneider P, Holler N, Salomon D et al. Inhibition of toxic epidermal necrolysis by blockade of CD95 with human intravenous immunoglobin. Science 1998; 282: 490–493.

    Article  CAS  Google Scholar 

  4. Nebert DW . Pharmacogenetics and pharmacogenomics: why is this relevant to the clinical geneticist? Clin Genet 1999; 56: 247–258.

    Article  CAS  Google Scholar 

  5. Mallal S, Nolan D, Witt C, Mosel G, Martin AM, Moore C et al. Association between presence of HLA-B*5701, HLA-DR7, and HLA-DQ3 and hypersensitivity to HIV1 reverse-transcriptase inhibitor abacavir. Lancet 2002; 359: 727–732.

    Article  CAS  Google Scholar 

  6. Hetherington S, Hughes AR, Mosteller M, Shortino D, Baker KL, Spreen W et al. Genetic variation in HLA-B region and hypersensitivity reactions to abacavir. Lancet 2002; 359: 1121–1122.

    Article  CAS  Google Scholar 

  7. Nassif A, Bensussan A, Boumsell L, Deniaud A, Moslehi H, Wolkenstein P et al. Toxic epidermal necrolysis: effector cells are drug specific cytotoxic T cells. J Allergy Clin Immunol 2004; 114: 1209–1215.

    Article  CAS  Google Scholar 

  8. Azukizawa H, Kasaka H, Sano S, Heath WR, Takahashi I, Gao X et al. Induction of T-Cell mediated skin disease specific for antigen transgenically expressed in keratinocytes. Eur J Immunol 2003; 33: 1879–1888.

    Article  CAS  Google Scholar 

  9. Chung WH, Hung SI, Hong HS, Hsih MS, Yang LC, Ho HC et al. A marker for Stevens-Johnson syndrome. Nature 2004; 428: 486.

    Article  CAS  Google Scholar 

  10. Roujeau JC, Huynh TN, Bracq C, Guillaume JC, Revuz J, Touraine R . Genetic susceptibility to toxic epidermal necrolysis. Arch Dermatol 1987; 123: 1171–1173.

    Article  CAS  Google Scholar 

  11. Geer L, Terasaki PI, Gjertson DJ . HLA frequency. HLA. In: Gjertson DW, Terasaki PI (eds). HLA 1998. Lenexa: American Society for Histrocompatibility and Immunogenetics: 1998, pp. 327–363.

    Google Scholar 

  12. Germain RN . MHC-dependent antigen processing and peptide presentation: providing ligands for T lymphocyte activation. Cell 1994; 76: 287–299.

    Article  CAS  Google Scholar 

  13. Madden DR . The three dimensional structure of peptide-MHC complexes. Ann Rev Immunol 1995; 13: 587–622.

    Article  CAS  Google Scholar 

  14. Sette A, Sidney J . Nine major HLA class I supertypes account for the vast preponderance of HLA-A and -B polymorphism. Immunogenetics 1999; 50: 201–212.

    Article  CAS  Google Scholar 

  15. Schnyder B, Burkhart C, Schnyder-Frutig K, von Greyerz S, Naisbitt DJ, Pirmohamed M et al. Recognition of sulfomethoxazole and its reactive metabolites by Drug-Specific CD4+ T cells from allergic Individuals. J Immunol 2000; 164: 6647–6654.

    Article  CAS  Google Scholar 

  16. Hung SH, Chung WH, Liou LB, Chu CC, Lin M, Huang HP et al. HLA-B*5801 allele as a genetic marker for severe cutaneous adverse reactions caused by allopurinol. Proc Natl Acad Sci USA 2005; 102: 4134–4139.

    Article  CAS  Google Scholar 

Download references

Acknowledgements

We thank all SCAR-patients and their physicians as well as the French patients association, Amalyste, for their important contribution.

This study was funded by grants from the European Commission (QLRT-2001-01738), ORPHANET and INSERM “ATC Pharmacogénétique”. NL is funded by a SIDACTION grant.

Author information

Authors and Affiliations

  1. INSERM U563, CHU Purpan, France

    C Lonjou, N Borot, N Ledger & A Hovnanian

  2. Department of Dermatology, Hôpital Henri Mondor, Créteil, Cedex, France

    L Thomas & J-C Roujeau

  3. Fondation Jean Dausset, Paris, France

    C de Toma

  4. Department of Pharmacovigilance, Hôpital Henri Mondor, Créteil, Cedex, France

    H LeLouet

  5. Institute of Med. Biometry and Informatics, University Hospital of Freiburg, Freiburg, Germany

    E Graf & M Schumacher

  6. Department of Dermatology, Documentation centre of severe skin reactions (dZh), University Hospital of Freiburg, Freiburg, Germany

    M Mockenhaupt

Authors
  1. C Lonjou
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. L Thomas
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. N Borot
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. N Ledger
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. C de Toma
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. H LeLouet
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. E Graf
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. M Schumacher
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. A Hovnanian
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. M Mockenhaupt
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. J-C Roujeau
    View author publications

    You can also search for this author in PubMed Google Scholar

Consortia

(for the RegiSCAR group)

Corresponding author

Correspondence to J-C Roujeau.

Additional information

Duality of Interest

None declared.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Lonjou, C., Thomas, L., Borot, N. et al. A marker for Stevens-Johnson syndrome …: ethnicity matters. Pharmacogenomics J 6, 265–268 (2006). https://doi.org/10.1038/sj.tpj.6500356

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/sj.tpj.6500356

Keywords

This article is cited by

Search

Advanced search

Quick links