OBJECTIVE: Allopurinol, an antihyperuricaemic agent, is one of the common causes 
of life-threatening severe cutaneous adverse reactions (SCAR), including drug 
rash with eosinophilia and systemic symptoms (DRESS), Stevens-Johnson syndrome 
(SJS) and toxic epidermal necrosis (TEN). The prognostic factors for 
allopurinol-related SCAR remain unclear. This study aimed to investigate the 
relationship of dosing, renal function, plasma levels of oxypurinol and 
granulysin (a cytotoxic protein of SJS/TEN), the disease severity and mortality 
in allopurinol-SCAR.
METHODS: We prospectively enrolled 48 patients with allopurinol-SCAR (26 SJS/TEN 
and 22 DRESS) and 138 allopurinol-tolerant controls from 2007 to 2012. The human 
leucocyte antigen (HLA)-B*58:01 status, plasma concentrations of oxypurinol and 
granulysin were determined.
RESULTS: In this cohort, HLA-B*58:01 was strongly associated with 
allopurinol-SCAR (p<0.001, OR (95% CI) 109 (25 to 481)); however, the 
initial/maintenance dosages showed no relationship with the disease. Poor renal 
function was significantly associated with the delayed clearance of plasma 
oxypurinol, and increased the risk of allopurinol-SCAR (p<0.001, OR (95% CI) 8.0 
(3.9 to 17)). Sustained high levels of oxypurinol after allopurinol withdrawal 
correlated with the poor prognosis of allopurinol-SCAR. In particular, the 
increased plasma levels of oxypurinol and granulysin linked to the high 
mortality of allopurinol-SJS/TEN (p<0.01), and strongly associated with 
prolonged cutaneous reactions in allopurinol-DRESS (p<0.05).
CONCLUSIONS: Impaired renal function and increased plasma levels of oxypurinol 
and granulysin correlated with the poor prognosis of allopurinol-SCAR. 
Allopurinol prescription is suggested to be avoided in subjects with renal 
insufficiency and HLA-B*58:01 carriers. An early intervention to increase the 
clearance of plasma oxypurinol may improve the prognosis of allopurinol-SCAR.