SJS/TEN — SCE Dermatology MCQ

Correct answer: B — HLA-B*5801 typing

The correct answer is B, HLA-B*5801 typing. Allopurinol-induced severe cutaneous adverse reactions (SCAR), including DRESS, Stevens-Johnson syndrome and toxic epidermal necrolysis, are strongly linked to the HLA-B*5801 allele, and the UK product licence specifically flags this risk. The allele frequency is markedly higher in Han Chinese, Thai and Korean populations, so pre-treatment screening is recommended in these groups before starting allopurinol. Detecting the allele allows the clinician to avoid allopurinol in carriers and select an alternative urate-lowering agent, substantially reducing SCAR risk in a population where baseline risk is already elevated. This is a pharmacogenomic, ethnicity-directed screening test distinct from other drug-specific genetic or enzyme tests used in prescribing. Why the other options are wrong: E. HLA-B*5701 typing: this allele predicts abacavir hypersensitivity in HIV treatment, an entirely different drug and receptor interaction, with no link to allopurinol. C. TPMT activity: thiopurine methyltransferase activity is checked before azathioprine or mercaptopurine to predict myelosuppression risk, not relevant to allopurinol (though TPMT and allopurinol interact pharmacokinetically, TPMT testing is not the pre-allopurinol hypersensitivity screen). A. CYP2D6 genotyping: this cytochrome P450 enzyme test predicts variable metabolism of drugs such as codeine and tamoxifen; allopurinol metabolism via xanthine oxidase is unrelated to CYP2D6. D. G6PD assay: glucose-6-phosphate dehydrogenase deficiency screening is relevant before oxidative drugs like primaquine or dapsone to avoid haemolysis, not before allopurinol. Key point: In patients of Han Chinese, Thai or Korean ancestry, HLA-B*5801 testing should be considered before starting allopurinol to reduce the risk of severe cutaneous hypersensitivity reactions.

Reference: electronic medicines compendium (emc), Allopurinol Tablets SmPC, Section 4.4 Special warnings and precautions for use: HLA-B*5801 screening, https://www.medicines.org.uk/emc/product/7004/smpc