Research ArticleCUTANEOUS DRUG REACTIONS

An annexin A1–FPR1 interaction contributes to necroptosis of keratinocytes in severe cutaneous adverse drug reactions

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Science Translational Medicine  16 Jul 2014:
Vol. 6, Issue 245, pp. 245ra95
DOI: 10.1126/scitranslmed.3008227

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Subduing a Severe Skin Side Effect

Certain pain relievers and antiepileptic drugs can cause a very rare, but sometimes fatal, side effect in which skin painfully blisters and peels, caused by the patients’ immune response to the drug. Saito et al. now find that, in susceptible patients, the drug causes secretion of the protein annexin A1 from immune cells, with deadly effect on skin cells. Annexin acts on these cells to cause necroptosis, a programmed form of cell death. The authors confirmed their results in mice, showing that an inhibitor of necroptosis blocked skin blistering. With these findings, Saito et al. lay the groundwork for a countermeasure to this dangerous side effect of otherwise extremely beneficial drugs.

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