Ordering Recommendation

Identify patients with increased risk for allopurinol-induced severe cutaneous adverse reactions (SCAR) based on the presence of HLA-B*58:01 allele.

Mnemonic
HLA B5801
Methodology

Polymerase Chain Reaction/Sequence Specific Oligonucleotide Probe Hybridization

Performed

Mon-Fri

Reported

3-7 days

New York DOH Approval Status
This test is New York DOH approved.
Specimen Required
Patient Preparation
Collect

Lavender (EDTA), Pink (K2EDTA), or Yellow (ACD Solution A or B).

Specimen Preparation

Transport 5 mL whole blood. (Min: 3 mL)

Storage/Transport Temperature

Refrigerated.

Unacceptable Conditions

Specimens collected in green (sodium or lithium heparin).

Remarks
Stability

Ambient: 72 hours; Refrigerated: 1 week; Frozen: Unacceptable

Reference Interval

By report

Interpretive Data

Characteristics: Allopurinol is the most commonly used drug for the treatment of hyperuricemia and gout. It inhibits xanthine oxidase, a key enzyme involved in uric acid formation. However, allopurinol is one of the most common causes of life-threatening severe cutaneous adverse reactions (SCAR), which include drug hypersensitivity syndrome, Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN). The presence of HLA-B*58:01 allele shows strong association with allopurinol-induced SCAR, including TEN and SJS. Although allopurinol-induced SCAR is rare with an estimated risk of 0.1-0.4 percent in allopurinol users, the severity can be high, with a mortality rate of up to 25 percent. Symptoms include rash, combined with eosinophilia, leukocytosis, fever, hepatitis and progressive kidney failure. Due to the severity of adverse reactions, it is recommended to test for the HLA-B*58:01 allele prior to initiation of the drug.
Incidence: HLA-B*58:01 allele frequency varies by ethnicity. In the US population, the highest incidence at 5.3 percent is found in Asians, 3.8 percent in African Americans, 1.45 percent in Native Hawaiians or Pacific Islanders, 1.35 percent in Hispanics, 1.19 percent in American Indians or Alaska Natives and 0.8 percent in Caucasians. Frequencies may be higher in other countries, up to 20 percent in Singapore, Taiwan and among Han Chinese, 15.4 percent in India, 14.2 percent in Hong Kong, 12 percent in China and Korea, 11 percent in Indonesia.
Cause: Allopurinol-induced SCAR, including SJS and TEN, is strongly associated with the presence of one or two copies of HLA-B*58:01 allele. The mechanism is immune mediated and involves direct interactions between the allopurine metabolite oxypurinol, and HLA-B*58:01, which may result in drug-induced changes in peptide presentation, allowing activation of self-reactive T lymphocytes.
Alleles tested: HLA-B*58:01 allele.
Clinical Sensitivity and Specificity: 71 percent sensitivity and 92 percent specificity, overall mean values from pooled populations (Yu KH et al, Int J Rheum Dis 2017). Higher in populations with increased HLA-B*58:01 allele frequency.
Methodology: PCR followed by Sequence Specific Oligonucleotide Probe Hybridization of HLA-B locus.
Analytical Sensitivity and Specificity: Greater than 99 percent.
Limitations: Copy number of HLA-B*58:01 will not be reported. Other genetic and non-genetic factors that influence allopurinol hypersensitivity are not evaluated. Other rare, or novel alleles may occur which may lead to false positive or false negative results.

No compliance statements are in use for this test.

Note
Hotline History
N/A
Components
Component Test Code* Component Chart Name LOINC
3001394 HLA-B*58:01 Genotyping, Allopurinol Hype 79711-8
* Component test codes cannot be used to order tests. The information provided here is not sufficient for interface builds; for a complete test mix, please click the sidebar link to access the Interface Map.
Aliases
  • HLA B*58:01
  • Allopurinol Hypersensitivity
  • B58
  • B5801
  • HLA B58
HLA-B*58:01 Genotyping, Allopurinol Hypersensitivity