Genetic Screening May Be Required Prior to Dapsone Treatment to Assess Cutaneous Drug Reaction Risk

Associations between HLA-B*1301 and dapsone-induced cutaneous adverse drug reactions (cADRs) have been reported in both dapsone-tolerant and healthy control groups, according to the results of a systematic review and meta-analysis reported in JAMA Dermatology.

Human studies that investigated the links between HLA-B*1301 and dapsone-induced cADRs were searched systematically from database inception until September 2017.

All relevant studies in which sufficient data were reported to calculate the frequency of HLA-B*1301 carriers in both case and control patients in which all participants received dapsone prior to HLA-B*1301 screening were identified by 2 reviewers. Ultimately, 3 studies met inclusion criteria.

Overall odds ratios (ORs) along with 95% CIs were assessed with the use of a random-effects model in order to determine the association between HLA-B*1301 and dapsone-induced cADRs. Subgroup analyses according to type of cADR were also conducted. The primary study outcome was the association between HLA-B*1301 and dapsone-induced cADRs in dapsone-tolerant controls, reported as ORs.

In the 3 included studies, a total of 111 patients with dapsone-induced cADRs (subsequently used in the meta-analysis), 1165 dapsone-tolerant patients, and 3026 healthy controls were identified. The cases included 49 women and 64 men (2 patients were missing from the meta-analysis); mean patient age was 39.7.

A link between HLA-B*1301 and dapsone-induced cADRs was reported (summary OR 43.0; 95% CI, 24.0-77.2).

Subgroup analyses based on types of cADRs yielded similar findings with respect to dapsone-induced hypersensitivity syndrome (OR 51.7; 95% CI, 16.9-158.5), dapsone-induced severe cADRs (Stevens-Johnson syndrome and toxic epidermal necrolysis [SJS/TENS] plus drug rash along with eosinophilia and systemic symptoms [DRESS]) (OR 54.0; 95% CI, 8.0-366.2), dapsone-induced SJS/TEN (OR 40.5; 95% CI, 2.8-591.0), and dapsone-induced DRESS (OR 60.8; 95% CI, 7.4-496.2).

The investigators concluded that genetic screening for HLA-B*1301 prior to initiation of dapsone treatment is warranted in Asian populations. Outcomes in individuals of other races/ethnicities who carry the HLA-B*1301 gene might differ from those reported in Chinese and Southeast Asian populations.

Reference

Tangamornsuksan W, Lohitnavy M. Association between HLA-B*1301 and dapsone-induced cutaneous adverse drug reactions: a systematic review and meta-analysis. JAMA Dermatol. 2018;154(4):441-446.