Monitoring the acute response in severe hypersensitivity reactions to drugs

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.

Although previous studies demonstrated the pathogenic role of TNF-α, IFN-γ, 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.

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.