Arthritis & Rheumatism, Volume 60,
October 2009 Abstract Supplement

The 2009 ACR/ARHP Annual Scientific Meeting
Philadelphia October 16-21, 2009.

Allopurinol Hypersensitivity Reactions: A Case-Control Study of the Role of Renal Dosing

Silverberg1,  Miriam S., Mallela2,  Rajitha, Lesse1,  Alan J., Bonner1,  Matthew R., Baer3,  Alan N., Li1,  Carl

University at Buffalo, Buffalo, NY
University of Rochester, Rochester, NY
Johns Hopkins University School of Medicine, Baltimore, MD


The use of standard dose allopurinol in patients with impaired renal function has been linked with the development of allopurinol hypersensitivity reactions. In 1984, Hande et al (Am J Med 76:47–56) noted an increased frequency of renal impairment among reported patients with severe allopurinol hypersensitivity reactions and proposed guidelines for the reduction of the dose of allopurinol based on estimated glomerular filtration rate (GFR). The objective of this study was to determine whether allopurinol doses higher than those recommended in these guidelines are associated with an increased frequency of hypersensitivity reactions among gout patients.


We conducted a case-control study among patients with a diagnosis of gout (n= 66) from 10/2004 – 11/2007 in the VA computerized chart system. Cases (n=15) were defined based on the presence of an allopurinol hypersensitivity reaction in the adverse reactions section of the patient's medical record. Controls (n = 51) were patients with gout on allopurinol who had not had an adverse reaction to allopurinol. Each study patient was categorized as to whether or not allopurinol dose was high, low, or appropriate for GFR based on published guidelines. Charts were reviewed for description of allopurinol reactions.


Adverse cutaneous reactions occurred in 13 patients (rash 12, pruritus 1), agranulocytosis in one, and angioedema in one. A higher percentage of cases had allopurinol dosed low or appropriate according to the guidelines compared to controls, although the difference was not statistically significant (66.7 vs 43.1%, p=0.109). More patients in the control group were taking ACE inhibitors (51.0 vs 20.0%, p=0.034). Otherwise there was no significant difference between the 2 groups (Table).

Table (percentage appears in brackets)

 Cases n=15Controls n=51p Value
Mean Age (yrs) [95%CI]72.3 [61.8, 86.1]71.3 [60.4, 82.2]0.425
Caucasian10 (66.7)44 (86.3)0.125
Male gender15 (100)50 (98.0) 
Thiazide diuretic0 (0)9 (17.6)0.106
Other diuretic4 (26.7)15 (29.4)1.00
Ampicillin/Amoxicillin0 (0)4 (7.8)0.567
ACE inhibitor3 (20.0)26 (51.0)0.034
ARB1 (6.7)3 (5.9)1.00
Allopurinol dose:   
100 mg8 (53.3)22 (43.1)NS
300 mg6 (40.0)29 (56.9) 
other1 (5.9)0 
Average creatinine clearance (ml/min) [range]54.6 [27–75]63.5 [35–99] 
Dose low or appropriate according to guidelines of Hande et al10 (66.7)22 (43.1)0.109


Our study did not demonstrate a relationship between the development of hypersensitivity reactions and the prescription of allopurinol at doses higher then recommended by the guidelines. Surprisingly, the cases were more likely to be taking allopurinol at appropriate doses or doses lower than recommended by the guidelines, although the difference between cases and controls was not statistically significant. These results are important as adherence to these guidelines may lead to suboptimal control of hyperuricemia and therefore recurrent flares of gout.

To cite this abstract, please use the following information:
Silverberg, Miriam S., Mallela, Rajitha, Lesse, Alan J., Bonner, Matthew R., Baer, Alan N., Li, Carl; Allopurinol Hypersensitivity Reactions: A Case-Control Study of the Role of Renal Dosing [abstract]. Arthritis Rheum 2009;60 Suppl 10 :1106
DOI: 10.1002/art.26181

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