Test your medicine knowledge with the MKSAP challenge, in partnership with the American College of Physicians.

A 53-year-old man is evaluated for a 5-year history of recurrent gout attacks involving the base of the great toes, mid feet, and ankles. Episodes are becoming more frequent and severe. History is also significant for hypertension and stage 3 chronic kidney disease. Medications are lisinopril and metoprolol. The patient is of Thai descent.

On physical examination, vital signs are normal. There are no tophi or swollen joints.

Laboratory studies show a serum urate level of 9.2 mg/dL (0.54 mmol/L).

Which of the following is the most appropriate next step in management?

A. Begin allopurinol
B. Begin probenecid
C. Measure antinuclear antibodies
D. Order HLA-B*5801 allele testing

MKSAP Answer and Critique

The correct answer is D. Order HLA-B*5801 allele testing.

HLA-B*5801 allele testing is the most appropriate next step in management. This patient with gout is at high risk for allopurinol sensitivity. His risk factors include diuretic use, ethnicity (Thai descent), and chronic kidney disease. Patients of Thai, Han Chinese, and Korean descent have a higher likelihood of having the HLA-B*5801 allele, which confers a high risk for allopurinol sensitivity. Allopurinol hypersensitivity is characterized by DRESS (drug reaction, eosinophilia, and systemic symptoms) syndrome and can result in kidney failure and death; allopurinol should be discontinued at the first sign of a rash. The presence of the HLA-B*5801 allele is a contraindication to prescribing allopurinol; therefore, this patient should be screened before beginning urate-lowering therapy.

The absence of the HLA-B*5801 allele does not guarantee protection against allopurinol hypersensitivity. Febuxostat is a nonpurine, noncompetitive xanthine oxidase inhibitor, which is a viable alternative to allopurinol. It can be used in patients with mild to moderate chronic kidney disease and is safe to try after an adverse reaction or failure with allopurinol. Febuxostat is approximately 10 times more expensive than generic allopurinol.

Probenecid should be avoided in patients with chronic kidney disease, as the drug requires intact kidney function.

There is no suggestion of an antinuclear antibody (ANA)-related disease such as systemic lupus erythematosus, and testing for ANA should not be performed in patients with low pretest probability of disease. The presence of ANA does not correlate with the risk for drug hypersensitivity. Therefore, there is no indication for ANA testing.

Key Point

• Risk factors for allopurinol sensitivity include diuretic use, chronic kidney disease, and the presence of the HLA-B*5801 allele in certain Asian ethnic groups.

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