Research ArticleDrug Sensitivity

Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS): A Multiorgan Antiviral T Cell Response

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Science Translational Medicine  25 Aug 2010:
Vol. 2, Issue 46, pp. 46ra62
DOI: 10.1126/scitranslmed.3001116

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Drug Sensitivity: Don’t Wake Up the Baby (Virus)

The benefits of drugs almost always come with a cost. Anticonvulsants and antibiotics are no exception. Some of these commonly used drugs can cause a skin reaction so severe, appearing several weeks after use, that the patient is treated as a burn victim. Called DRESS (drug reaction with eosinophilia and systemic symptoms), this response results in death 10% of the time. A better understanding of DRESS would be a boon to diagnosis and treatment. Data from 40 DRESS patients gathered by Picard and his colleagues now move us a few steps closer to this goal. They find that the symptoms of DRESS are largely a result of activated immune cells directed at herpes virus–related antigens, which home to the skin and visceral organs. The culprit drugs may reactivate quiescent herpes viruses lurking in the patients’ genomes, triggering expansion of these misguided cells.

A careful look at the T lymphocytes from 40 patients with DRESS—induced by carbamazepine, allopurinol, or sulfamethoxazole—revealed excess numbers of activated cytotoxic CD8+ T cells, which had surface proteins directing them to skin and other organs. The cells secreted cytokines such as tumor necrosis factor–α (TNF-α) and interferon-γ (IFN-γ) and expressed genes characteristic of inflammation. To get a better handle on the antigen targets of these activated T cells, the authors tested whether the patients showed viral reactivation, which had been noted before in some patients with DRESS. Not only did 76% of the patients show activation of previously quiescent Epstein-Barr virus (EBV) or human herpes viruses 6 or 7 (HHV-6, HHV-7), but a large proportion of the activated CD8 T cells in blood and affected organs carried T cell receptor sequences known to be specific for antigens from EBV. (Specific sequences for HHV-6 or HHV-7 are not available.) Cellular stimulation by antigenic peptides from EBV confirmed this result.

The authors propose that DRESS is caused by an EBV (or other similar virus)–driven selection of CD8+ T lymphocytes, which in turn inappropriately attack multiple organs. They think that the culprit drugs may trigger activation of the patients’ dormant EBV by an as yet undefined mechanism, possibly directly. Indeed, they found that the three culprit drugs induce EBV production in EBV-transformed cells from DRESS patients but not from healthy controls, setting the stage for discovering just what it is that makes some people susceptible to DRESS.

Footnotes

  • * These authors contributed equally to this work.

  • Citation: D. Picard, B. Janela, V. Descamps, M. D'Incan, P. Courville, S. Jacquot, S. Rogez, L. Mardivirin, H. Moins-Teisserenc, A. Toubert, J. Benichou, P. Joly, P. Musette, Drug reaction with eosinophilia and systemic symptoms (DRESS): A multiorgan antiviral T cell response. Sci. Transl. Med. 2, 46ra62 (2010).