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Original Investigation
March 27, 2019

Evaluation of Prospective HLA-B*13:01 Screening to Prevent Dapsone Hypersensitivity Syndrome in Patients With Leprosy

Author Affiliations
  • 1Shandong Provincial Institute of Dermatology and Venereology, Shandong Academy of Medical Science, Jinan, Shandong, China
  • 2Shandong Provincial Hospital for Skin Diseases, Shandong University, Jinan, Shandong, Chinakrismawati
  • 3Shandong Provincial Key Lab for Dermatovenereology, Jinan, Shandong, China
  • 4Shandong Provincial Medical Center for Dermatovenereology, Jinan, Shandong, China
  • 5Human Genetics, Genome Institute of Singapore, Agency for Science, Technology and Research of Singapore
  • 6Papua Biomedical Research Center, National Institute for Health Research, Indonesian Ministry of Health, Jl Kesehatan 10, Dok II, Jayapura, Papua, Indonesia
  • 7Institute of Dermatology, Chinese Academy of Medical Sciences and Peking Union Medical College, Nanjing, Jiangsu
JAMA Dermatol. 2019;155(6):666-672. doi:10.1001/jamadermatol.2018.5360
Key Points

Question  Can prospective HLA-B*13:01 screening reduce the incidence of dapsone hypersensitivity syndrome by identifying patients with HLA-B*13:01–positive leprosy who should not receive dapsone treatment?

Findings  In this cohort study of 1539 Chinese patients with newly diagnosed leprosy, dapsone hypersensitivity syndrome did not develop in any of those in the HLA-B*13:01–negative group who were receiving dapsone. This finding was significantly lower than the 13 dapsone hypersensitivity syndrome cases that would be expected to occur according to the historical rate of incidence (1.0% per year).

Meaning  Prospective HLA-B*13:01 screening may significantly reduce the incidence of dapsone hypersensitivity syndrome in the Chinese population.


Importance  Dapsone hypersensitivity syndrome (DHS) is the most serious adverse reaction associated with dapsone administration and one of the major causes of death in patients with leprosy, whose standard treatment includes multidrug therapy (MDT) with dapsone, rifampicin, and clofazimine. Although the HLA-B*13:01 polymorphism has been identified as the genetic determinant of DHS in the Chinese population, no studies to date have been done to evaluate whether prospective HLA-B*13:01 screening could prevent DHS by identifying patients who should not receive dapsone.

Objective  To evaluate the clinical use of prospective HLA-B*13:01 screening for reduction of the incidence of DHS by excluding dapsone from the treatment for patients with HLA-B*13:01–positive leprosy.

Design, Setting, and Participants  A prospective cohort study was conducted from February 15, 2015, to April 30, 2018, in 21 provinces throughout China. A total of 1539 patients with newly diagnosed leprosy were enrolled who had not received dapsone previously. After excluding patients who had a history of allergy to sulfones or glucose-6-phosphate dehydrogenase deficiency, 1512 individuals underwent HLA-B*13:01 genotyping. All of the patients were followed up weekly for the first 8 weeks after treatment to monitor for adverse events.

Exposures  Patients who were HLA-B*13:01 carriers were instructed to eliminate dapsone from their treatment regimens, and noncarrier patients received standard MDT.

Main Outcomes and Measures  The primary outcome was the incidence of DHS. The historical incidence rate of DHS (1.0%) was used as a control.

Results  Among 1512 patients (1026 [67.9%] men, 486 [32.1%] women; mean [SD] age, 43.1 [16.2] years), 261 (17.3%) were identified as carriers of the HLA-B*13:01 allele. A total of 714 adverse events in 384 patients were observed during the follow-up period. Dapsone hypersensitivity syndrome did not develop in any of the 1251 patients who were HLA-B*13:01–negative who received dapsone, while approximately 13 patients would be expected to experience DHS, based on the historical incidence rate of 1.0% per year (P = 2.05 × 10−5). No significant correlation was found between other adverse events, including dermatologic or other events, and HLA-B*13:01 status.

Conclusions and Relevance  Prospective HLA-B*13:01 screening and subsequent elimination of dapsone from MDT for patients with HLA-B*13:01–positive leprosy may significantly reduce the incidence of DHS in the Chinese population.