PT  - JOURNAL ARTICLE
AU  - Chung, Wen-Hung
AU  - Chang, Wan-Chun
AU  - Stocker, Sophie L
AU  - Juo, Chiun-Gung
AU  - Graham, Garry G
AU  - Lee, Ming-Han H
AU  - Williams, Kenneth M
AU  - Tian, Ya-Chung
AU  - Juan, Kuo-Chang
AU  - Jan Wu, Yeong-Jian
AU  - Yang, Chih-Hsun
AU  - Chang, Chee-Jen
AU  - Lin, Yu-Jr
AU  - Day, Richard O
AU  - Hung, Shuen-Iu
TI  - Insights into the poor prognosis of allopurinol-induced severe cutaneous adverse reactions: the impact of renal insufficiency, high plasma levels of oxypurinol and granulysin
AID  - 10.1136/annrheumdis-2014-205577
DP  - 2015 Dec 01
TA  - Annals of the Rheumatic Diseases
PG  - 2157--2164
VI  - 74
IP  - 12
4099  - http://ard.bmj.com/content/74/12/2157.short
4100  - http://ard.bmj.com/content/74/12/2157.full
SO  - Ann Rheum Dis2015 Dec 01; 74
AB  - 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.