Background: Allopurinol is a frequent cause of severe cutaneous adverse reactions (SCARs), such as drug reaction with eosinophilia and systemic symptoms (DRESS), Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN). The reactions can potentially be fatal. As drug rechallenge in patients with a history of drug-induced SCARs is contraindicated, in vitro testing may have a diagnostic role as a confirmation test.
Objectives: To study the diagnostic value of interferon (IFN)-γ enzyme-linked immunospot (ELISpot) assay as a confirmatory test in patients with a history of allopurinol-induced SCARs.
Methods: Peripheral blood mononuclear cells (PBMCs) from 24 patients with a history of allopurinol-induced SCAR (13 DRESS, 11 SJS/TEN) and 21 control subjects were incubated with allopurinol or oxypurinol in the presence or absence of antiprogrammed death ligand 1 antibody (anti-PD-L1). The numbers of IFN-γ-releasing cells after stimulation in each group were subsequently measured with ELISpot.
Results: The numbers of IFN-γ-releasing cells in allopurinol-allergic subjects were significantly higher than in control subjects when stimulating PBMCs with oxypurinol 100 μg mL-1 , especially when adding anti-PD-L1 supplementation. According to the receiver operating characteristic curve results, the optimal discriminatory power of IFN-γ ELISpot in confirming diagnosis of allopurinol-induced SCARs can be obtained using 16 spot-forming cells per 106 PBMCs as a cut-off value upon oxypurinol/anti-PD-L1 stimulation (79·2% sensitivity and 95·2% specificity).
Conclusions: The measurement of oxypurinol/anti-PD-L1-inducing IFN-γ-releasing cells yields a high diagnostic value in distinguishing between allopurinol-allergic and control subjects. This technique is beneficial in confirming diagnosis of allopurinol-induced SCARs in patients whose reaction develops while taking multiple drugs.
© 2016 British Association of Dermatologists.