Monitoring the acute response in severe hypersensitivity reactions to drugs.

PURPOSE OF REVIEW: Severe adverse drug reactions (ADRs) including Stevens-Johnson syndrome (SJS)/toxic epidermal necrolysis (TEN) and drug-induced hypersensitivity syndrome (DiHS)/drug reaction with eosinophilia and systemic symptoms (DRESS) are acute life-threatening conditions. There is the urgent need for reliable, noninvasive and standardized laboratory tests for identifying patients at higher risk of developing severe ADRs. RECENT FINDINGS: Although previous studies demonstrated the pathogenic role of TNF-alpha, IFN-gamma, IL-10, perforin/granzyme B, Fas L and granulysin in the development of severe ADRs, there have been no biomarkers predicting progression to severe ADRs. We, therefore, measured serum levels of cytokines/chemokines as well as other biological markers in patients who presented with clinical symptoms suggestive of ADRs at their initial presentation. The results show that sFas L represents a useful early biomarker that can predict the subsequent progression to TEN, but not SJS, particularly when combined with the increase in IL-6 and IP-10. The increased levels of IL-6 and IP-10 are reliable biomarkers predictive of the progression to severe ADRs, such as SJS/TEN and DiHS/DRESS. SUMMARY: The use of a combination of several early biomarkers, although not sufficiently sensitive or specific on its own when used alone, could increase the diagnostic and prognostic utility for the prediction of severe ADRs.