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JAMA Dermatol. 2019 Mar 27. doi: 10.1001/jamadermatol.2018.5360. [Epub ahead of print]

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

Author information

Shandong Provincial Institute of Dermatology and Venereology, Shandong Academy of Medical Science, Jinan, Shandong, China.
Shandong Provincial Hospital for Skin Diseases, Shandong University, Jinan, Shandong, Chinakrismawati.
Shandong Provincial Key Lab for Dermatovenereology, Jinan, Shandong, China.
Shandong Provincial Medical Center for Dermatovenereology, Jinan, Shandong, China.
Human Genetics, Genome Institute of Singapore, Agency for Science, Technology and Research of Singapore.
Papua Biomedical Research Center, National Institute for Health Research, Indonesian Ministry of Health, Jl Kesehatan 10, Dok II, Jayapura, Papua, Indonesia.
Institute of Dermatology, Chinese Academy of Medical Sciences and Peking Union Medical College, Nanjing, Jiangsu.
Yunnan Provincial Center for Disease Control and Prevention, Kunming, Yunnan.
Guizhou Provincial Center for Disease Control and Prevention, Guiyang, Guizhou.
Sichuan Provincial Institute of Dermatology, Chengdu, Sichuan.
Guangdong Provincial Institute of Dermatology, Guangzhou, Guangdong.
Guangxi Provincial Institute of Dermatology, Nanning, Guangxi.
Hunan Provincial Center for Disease Control and Prevention, Changsha, Hunan.
Jiangxi Provincial Institute of Parasitic Diseases, Nanchang, Jiangxi.
Chongqing Center for Disease Control and Prevention, Chongqing.
Jiangsu Provincial Center for Disease Control and Prevention, Nanjing, Jiangsu.
Shanxi Provincial Institute for Endemic Disease Control, Xi'an, Shanxi.
Zhejiang Provincial Institute of Dermatology, Huzhou, Zhejiang.
Fujian Center for Disease Control and Prevention, Fuzhou, Fujian.
Anhui Provincial Institute of Dermatology, Hefei, Anhui.
Hubei Provincial Center for Disease Control and Prevention, Wuhan, Hubei.
Xinjiang Center for Disease Control and Prevention, Urumchi, Xinjiang.
Hainan Provincial Center for Skin Disease and STI Control, Haikou, Hainan.



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.


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.


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.


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.

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