Independent strong association of HLA-A*02:06 and HLA-B*44:03 with cold medicine-related Stevens-Johnson syndrome with severe mucosal involvement.
Stevens-Johnson syndrome (SJS) and its severe variant, toxic epidermal necrolysis (TEN), are acute inflammatory vesiculobullous reactions of the skin and mucous membranes. Cold medicines including non-steroidal anti-inflammatory drugs (NSAIDs) and multi-ingredient cold medications are reported to be important inciting drugs. We used two sample sets of Japanese patients to investigate the association between HLA genotypes and cold medicine-related SJS/TEN (CM-SJS/TEN), including acetaminophen-related SJS/TEN (AR-SJS/TEN) with severe mucosal involvement such as severe ocular surface complications (SOC). HLA-A*02:06 was strongly associated with CM-SJS/TEN with SOC and AR-SJS/TEN with SOC. HLA-B*44:03 was also detected as an independent risk allele for CM-, including AR-SJS/TEN with SOC. Analyses using data obtained from CM-SJS/TEN patients without SOC and patients with CM-unrelated SJS/TEN with SOC suggested that these two susceptibility alleles are involved in the development of only CM-SJS/TEN with SOC patients.
1] Department of Ophthalmology, Kyoto Prefectural University of Medicine, Kyoto, Japan [2] Research Center for Inflammation and Regenerative Medicine, Faculty of Life and Medical Sciences, Doshisha University, Kyoto, Japan.
Mayumi
M
Ueta
Division of Medicinal Safety Science, National Institute of Health Sciences, Tokyo, Japan.
Nahoko
N
Kaniwa
Department of Ophthalmology, Kyoto Prefectural University of Medicine, Kyoto, Japan.
Chie
C
Sotozono
Department of Human Genetics, Graduate School of Medicine, University of Tokyo, Tokyo, Japan.
Katsushi
K
Tokunaga
Division of Medicinal Safety Science, National Institute of Health Sciences, Tokyo, Japan.
Yoshiro
Y
Saito
Department of Human Genetics, Graduate School of Medicine, University of Tokyo, Tokyo, Japan.
Hiromi
H
Sawai
Department of Human Genetics, Graduate School of Medicine, University of Tokyo, Tokyo, Japan.
Hiroko
H
Miyadera
Division of Medicinal Safety Science, National Institute of Health Sciences, Tokyo, Japan.
Emiko
E
Sugiyama
Division of Medicinal Safety Science, National Institute of Health Sciences, Tokyo, Japan.
Keiko
K
Maekawa
Division of Medicinal Safety Science, National Institute of Health Sciences, Tokyo, Japan.
Ryosuke
R
Nakamura
Molecular Diagnostics Division, Wakunaga Pharmaceutical Co., Hiroshima, Japan.
Masaki
M
Nagato
Department of Environmental Immuno-Dermatology, Yokohama City University Graduate School of Medicine, Kanagawa, Japan.
Michiko
M
Aihara
Department of Dermatology, Fujita Health University School of Medicine, Aichi, Japan.
Kayoko
K
Matsunaga
National Epilepsy Center, Shizuoka Institute of Epilepsy and Neurological Disorders, Shizuoka, Japan.
Yukitoshi
Y
Takahashi
Department of Neurology, Faculty of Medicine, Kochi University, Kochi, Japan.
Hirokazu
H
Furuya
Molecular Epidemiology, Medical Research Institute, Tokyo Medical and Dental University, Tokyo, Japan.
Masaaki
M
Muramatsu
Department of Dermatology, International University of Health and Welfare (IUHW) Atami Hospital, Shizuoka, Japan.
Zenrou
Z
Ikezawa
Department of Ophthalmology, Kyoto Prefectural University of Medicine, Kyoto, Japan.
Shigeru
S
Kinoshita
D000082:Acetaminophen / Q000009:adverse effects; D000293:Adolescent; D000328:Adult; D000368:Aged; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000009:adverse effects*; D016022:Case-Control Studies; D002648:Child; D005260:Female; D015234:HLA-A Antigens / Q000235:genetics*; D015235:HLA-B Antigens / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009092:Mucous Membrane / Q000473:pathology*; D013262:Stevens-Johnson Syndrome / Q000150:complications / Q000209:etiology* / Q000473:pathology*; D014786:Vision Disorders / Q000209:etiology; D055815:Young Adult
D000894:Anti-Inflammatory Agents, Non-Steroidal; D015234:HLA-A Antigens; D015235:HLA-B Antigens; D000082:Acetaminophen