Transl Clin Pharmacol.  2017 Jun;25(2):63-66. 10.12793/tcp.2017.25.2.63.

Allopurinol-induced severe cutaneous adverse reactions: A report of three cases with the HLA-B*58:01 allele who underwent lymphocyte activation test

• Kim EY
• Seol JE
• Choi JH
• Kim NY
• Shin JG

• KMID: 2386762
• DOI: http://doi.org/10.12793/tcp.2017.25.2.63

Abstract

Allopurinol-induced severe cutaneous adverse reactions (SCARs) such as Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), and drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome are reportedly associated with the HLA-B*58:01 genotype. Three patients who developed SCARs after allopurinol administration were subjected to HLA-B genotyping and lymphocyte activation test (LAT) to evaluate genetic risk and to detect the causative agent, respectively. All three patients given allopurinol to treat gout were diagnosed with DRESS syndrome. Symptom onset commenced 7-24 days after drug exposure; the patients took allopurinol (100-200 mg/d) for 2-30 days. HLA-B genotyping was performed using a polymerase chain reaction (PCR)-sequence-based typing (SBT) method. All patients had a single HLA-B*58:01 allele: HLA-B*13:02/*58:01 (a 63-year-old male), HLA-B*48:01/*58:01 (a 71-year-old female), and HLA-B*44:03/*58:01 (a 22-year-old male). Only the last patient yielded a positive LAT result, confirming that allopurinol was the causative agent. These findings suggest that patients with HLA-B*58:01 may develop SCARs upon allopurinol administration. Therefore, HLA-B genotyping could be helpful in preventing serious problems attributable to allopurinol treatment, although PCR-SBT HLA-B genotyping is time consuming. A simple genotyping test is required in practice. LAT may help to identify a causative agent.

Keyword

allopurinol; severe cutaneous adverse reactions; HLA-B*58:01; lymphocyte activation test; DRESS syndrome

MeSH Terms

Aged
Alleles*
Allopurinol
Cicatrix
Drug Hypersensitivity Syndrome
Genotype
Gout
HLA-B Antigens
Humans
Lymphocyte Activation*
Lymphocytes*
Methods
Middle Aged
Polymerase Chain Reaction
Stevens-Johnson Syndrome
Young Adult
Allopurinol
HLA-B Antigens

Figure

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  Figure 1 Patient 3: Erythematous macules with edema on the face (A); erythematous macules on the upper and lower extremities (B-C); and lymphocyte infiltration evident on skin biopsy (D-E).

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  Figure 2 An allopurinol-positive lymphocyte activation test (stimulation index >2). CD69 was upregulated by allopurinol in CD4+ T cells from Patient 3 at both 48 and 72 h after culture. Sequence: negative control; various drug concentrations, and the phytohemagglutinin A (PHA) positive control.

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