CONFLICT OF INTEREST
The authors state no conflict of interest.
SUPPLEMENTARY MATERIAL
Supplementary material is linked to the online
version of the paper at http://www.nature.com/jid
ACKNOWLEDGMENTS
This research was supported by the Milstein
Medical Program and in part by grant no.
UL1RR024143 from the National Center for
Research Resources, National Institutes of
Health. NG was supported by NIH MSTP grant
GM07739.
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Kennedy-Crispin M, Billick E, Mitsui H et al. (2012)
Human keratinocytes response to injury
upregulates CCL20 and other genes linking
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Koster MI (2009) Making an epidermis. Ann N Y
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TO THE EDITOR
Dapsone (4,40-diaminodiphenylsulfone)
has been widely used in the treatment
of leprosy since its discovery in the
1940s, and some of its reported side
effects include methemoglobinemia,
hemolysis, agranulocytosis, and dapsone-induced hypersensitivity reactions
(DIHRs) (Zhu and Stiller, 2001). DIHR is
a life-threatening drug reaction, which
has been reported in B2% of leprosy
patients on dapsone therapy; thus, with
12.5% mortality, DIHR is one of the
major causes of mortality in leprosy
patients (Pandey et al., 2007; Shen
et al., 2011). DIHR is clinically manifested through fever, rash, lymphadenopathy, and hepatitis, and is categorized
under the drug-induced hypersensitivity
or drug rash with eosinophilia and
systemic symptoms syndromes (Sener
et al., 2006; Kardaun et al., 2007;
Abbreviations: AUC, area under the curve; CYP2C9, cytochrome P450 2C9; DIHR, dapsone-induced
hypersensitivity reaction; HLA, human leukocyte antigen; MHC, major histocompatibility complex; NAT2,
N-acetyltransferase2
Accepted article preview online 19 April 2013; published online 16 May 2013
H Wang et al.
Association between HLA-B*1301 and Dapsone-Induced Hypersensitivity Reactions
Leprosy patients
with DIHR
(n 21)
DDS-tolerant
leprosy patients
(n 105)
Healthy
controls1
(n 100)
38.211.7
40.311.8
39.510.7
11 (52.4%)
55 (52.4%)
53 (53.0%)
10 (47.6%)
50 (47.6%)
47 (47%)
o8
48
12 (57.1%)
55 (52.4%)
52 (52.0%)
9 (42.9%)
50 (47.6%)
48 (48.0%)
Miao group
4 (19.0%)
22 (21.0%)
20 (20.0%)
Tu group
2 (9.5%)
12 (11.4%)
12 (12.0%)
Zhuang group
2 (9.5%)
12 (11.4%)
12 (12.0)
Buyi group
1 (4.8%)
4 (3.8%)
4 (4.0%)
Leprosy patients
with DIHR
(n 20)
DDS-tolerant
leprosy patients
(n 102)
Healthy
controls1
n 96)
18 (90%)
7(6.9%)
11(11.5%)
OR
(95% CI)
pc
6.038 10 12
1.961 10 11
2
3
2 (10%)
1 (1.0%)
0 (0%)
C*0304
19 (95%)
22 (21.6%)
24 (25%)
B*1301, C*0304
17 (85%)
6 (5.9%)2
4 (4.2%)
4.280 10 11
B*1301 or B*1313
20 (100%)
8 (7.9%)2
11 (11.5%)3
470.0 (25.98521.3)2
154.6 (18.81267.4)3
8.320 10 15
4.040 10 13
13 (68.4%, n 19)
3 (3.0%, n 101)
70. 8 (15.8317.8)
216.7 (24.11944.6)5
8 2
1.668 10
4.644 10 10
Abbreviations: CI, confidence interval; DDS, diamino diphenyl sulphone (dapsone); DIHR, dapsone-induced hypersensitivity reaction; HLA, human leukocyte
antigen; OR, odds ratio.
1
Healthy controls: healthy non-leprosy controls not exposed to dapsone.
2
Cases/dapsone-tolerant controls.
3
Cases/healthy controls.
4
Failure in genotyping for HLA A in 1 leprosy patient with DIHR and 1 DDS-tolerant leprosy patient.
5
Cases/dapsone-tolerant controls (analysis of the haplotype of linkage disequilibrium for HLA-A*1101-B*1301-Cw*0304).
www.jidonline.org 2643
H Wang et al.
Association between HLA-B*1301 and Dapsone-Induced Hypersensitivity Reactions
REFERENCES
CONFLICT OF INTEREST
ACKNOWLEDGMENTS
This study was supported by grants from the
National Natural Science Foundation of China
(No. 30972651) and the Research Special Fund
for Public Welfare Industry of Health of China
(No. 201002016), as well as by funding from the
Key Clinical Program of the Ministry of Health
of China (No. 2010-2012-125). Support for the
HLA analyses was provided by Liming Wu and
Ruixiao Ma.
DISCLAIMER
The sponsor of the study had no role in the study
design, data collection, data analysis, data interpretation, or manuscript preparation. HW and LY
had full access to data collected for the study, and
BW and HW had final responsibility and decision
for publication submission.