Human Leukocyte Antigen Class I Genes Associated With Stevens-Johnson Syndrome and Severe Ocular Complications Following Use of Cold Medicine in a Brazilian Population

Wakamatsu, Tais Hitomi; Ueta, Mayumi; Tokunaga, Katsushi; Okada, Yukinori; Loureiro, Renata Ruoco; Costa, Kassandra Silva Falcão; Sallum, Juliana Maria Ferraz; Milhomens, José Arthur; Inoue, Chikara; Sotozono, Chie; Gomes, José Álvaro Pereira; Kinoshita, Shigeru

doi:10.1001/jamaophthalmol.2017.0074

Cited by 32 publications

(39 citation statements)

References 36 publications

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“…Significant risk factors for ocular involvement in SJS include exposure to drugs such as NSAIDs and cold medications 5 , 7 . About 80% of Japanese- and 53% of Brazilian SJS/TEN with SOC patients had taken cold medicines 7 – 9 .…”

Section: Introductionmentioning

confidence: 99%

Association of Human Leukocyte Antigen Class 1 genes with Stevens Johnson Syndrome with severe ocular complications in an Indian population

Kannabiran¹,

Ueta

Sangwan

et al. 2017

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Stevens Johnson syndrome (SJS) is part of a spectrum of adverse drug reactions resulting in the destruction of skin, mucous membranes, and the ocular surface. A similar, more severe form of the disorder included in this spectrum is toxic epidermal necrolysis (TEN). Approximately 35% of patients suffer chronic sequelae such as vascularization, corneal scarring, conjunctival inversion to the cornea, keratinization, symblepharon, scarring of the palpebral conjunctiva, trichiasis, and severe dry eye. We focused on 80 Indian patients with SJS/TEN with severe ocular complications (SOC) and investigated the association of alleles at HLA -A, HLA-B and HLA-C loci; the controls were 50 healthy Indian volunteers. Genotyping at HLA-A, HLA-B, and HLA-C loci showed a significant positive association with HLA-A*33:03, HLA-B*44:03, and HLA-C*07:01 alleles, and a significant negative association with HLA-B*57:01 and HLA-C*06:02. This indicates that HLA-A*33:03, HLA-B*44:03 and HLA-C*07:01 are risk alleles, and HLA-B*57:01 and HLA-C*06:02 are protective alleles in this population. We also found that the haplotypes consisting of HLA-B*44:03 and HLA-C*07:01 were strongly associated with SJS/TEN with SOC in our Indian population (p = 1.1 × 10−7, odds ratio = 11.0). Describing the association of the haplotype could facilitate the understanding of increased risk factors for developing SJS/TEN with SOC.

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Section: Introductionmentioning

confidence: 99%

Association of Human Leukocyte Antigen Class 1 genes with Stevens Johnson Syndrome with severe ocular complications in an Indian population

Kannabiran¹,

Ueta

Sangwan

et al. 2017

Sci Rep

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“…However, there was no similar association found in our Korean data. Similarly, HLA-A*66:01, HLA-B*08:01 and HLA-C*12:03 were associated with CM-SJS/TEN with SOC in Brazilian population13; however, none of our subjects displayed these haplotypes suggesting that these haplotypes are rare in the Korean population. Taken together, all of these studies indicate that the association between HLA genetic variability and disease is further complicated by differences between ethnic groups and race.…”

Section: Discussionmentioning

confidence: 52%

“…The association of these HLAs with CM-SJS/TEN was confirmed by our trans-ethnic study in which Indian, Brazilian and Korean populations were included 10. HLA-A*66:01 and HLA-C*12:03 were associated with the development of CM-SJS/TEN with SOCs in the Brazilian population 13. In the Indian population, HLA-A*33:03 and HLA-C*07:01 alleles showed a significant positive association while HLA-B*57:01 and HLA-C*06:02 showed a negative association with the development of CM-SJS/TEN with SOCs 12…”

Section: Introductionmentioning

confidence: 52%

“…We previously reported that HLA-C*03:04 tended to show a positive association with CM-SJS/TEN with SOC among the Kyoto Prefectural University of Medicine subjects, although it could not pass the Bonferroni correction 11 34. Additionally, no association was reported between HLA-C*03:04 and CM-SJS/TEN with SOC in the Brazilian population 13. Thus, this variant may cause susceptibility towards CM-SJS/TEN with SOC only in the East Asian population.…”

Section: Discussionmentioning

confidence: 89%

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Association of human antigen class I genes with cold medicine-related Stevens-Johnson syndrome with severe ocular complications in a Korean population

et al. 2019

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Background/aimsStevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are a spectrum of diseases that cause an acute vesiculobullous reaction in the skin and mucous membranes. The occurrence of these diseases is associated with various drugs, a large proportion of which is comprised cold medicines (CM). We try to investigate the association between human leucocyte antigen (HLA) class I genes and CM-related SJS/TEN (CM-SJS/TEN) with severe ocular complications (SOC) in the Korean population.MethodsThis multicentre case-control study enrolled 40 Korean patients with CM-SJS/TEN with SOC and 120 age-matched and sex-matched Korean healthy volunteers between January 2012 and May 2014. HLA genotyping was performed using PCR followed by hybridisation with sequence-specific oligonucleotide probes.Results The carrier frequency and gene frequency of HLA-A*02:06 were 37.5 % and 20.0 %, respectively, in patients, and 16.7 % and 9.6 %, respectively, in controls (p=0.018). The carrier frequency of HLA-C*03:04 was 30 % in patients and 10.8 % in controls, and gene frequency of HLA-C*03:04 was 15 % in patients and 5.4 % in controls (p=0.003). The carrier frequency and gene frequency of HLA-C*03:03 were 2.5 % and 1.3 %, respectively, in patients, and 20 % and 10.4 %, respectively, in controls (p=0.006).Conclusions As per our results, we suggest that HLA-A*02:06 and HLA-C*03:04 might be positive markers for CM-SJS/TEN with SOC, and HLA-C*03:03 might be an indicator of protection against CM-SJS/TEN with SOC in the Korean population.

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“…5,7,8,14,[16][17][18][19][20] We reported that 80% of our SJS/TEN with SOC patients developed SJS/TEN within several days after taking cold medicines including multi-ingredient cold medications and nonsteroidal anti-inflammatory drugs (NSAIDs) to combat the common cold. 2,5,8,20 Our Brazilian collaborators also found that more than half of their SJS/TEN with SOC patients had taken cold medicines, 21 suggesting that such medicines are major causative drugs for SJS/TEN with SOC. Our Thailand collaborators also reported that cold medicines are main causative drugs for SJS/TEN with severe chronic ocular complications: 49 of 71 patients with SJS/TEN with SOC (69%) had a history of taking CM before the onset of SJS/TEN in Thailand.…”

Section: Cold Medicine and Hla Analysismentioning

confidence: 88%

Results of Detailed Investigations Into Stevens-Johnson Syndrome With Severe Ocular Complications

Ueta

2018

Invest. Ophthalmol. Vis. Sci.

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Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are acute inflammatory vesiculobullous reactions of the mucosa of the ocular surface, oral cavity, and genitals, and of the skin. Severe ocular complications (SOC) are present in about half of SJS/TEN patients diagnosed by dermatologists. We review our group's findings on the genetic predisposition for and the etiology of SJS/TEN with SOC. We suspected that abnormal innate mucosal immunity, resulting in an anomalous response to commensal bacteria that usually do not elicit such a response, contributes to the ocular surface inflammation seen in SJS/TEN with SOC. We found that cold medicines, including multi-ingredient cold medications and nonsteroidal antiinflammatory drugs, were the main causative drugs especially in patients with SJS/TEN with SOC. Cold medicine-related SJS/TEN (CM-SJS/TEN) with SOC was strongly associated with HLA-A*02:06 in the Japanese populations, and significantly associated with HLA-B*44:03 in the Japanese and in Indian and Brazilian populations. Single nucleotide polymorphism association analysis showed that the Toll-like receptor 3 (TLR3), prostaglandin-E receptor 3 (PTGER3), and IKZF1 gene were significantly associated with CM-SJS/TEN with SOC and that they could regulate mucocutaneous inflammation including that of the ocular surface. As we found several HLA-SNP sets with a high odds ratio, we postulated that they may help to predict the possible development of SJS/TEN with SOC. From our findings we suggest that besides microbial infection and cold medicines, a combination of multiple gene polymorphisms and their interactions contribute strongly to the onset of CM-SJS/TEN with SOC.

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Human Leukocyte Antigen Class I Genes Associated With Stevens-Johnson Syndrome and Severe Ocular Complications Following Use of Cold Medicine in a Brazilian Population

Cited by 32 publications

References 36 publications

Association of Human Leukocyte Antigen Class 1 genes with Stevens Johnson Syndrome with severe ocular complications in an Indian population

Association of Human Leukocyte Antigen Class 1 genes with Stevens Johnson Syndrome with severe ocular complications in an Indian population

Association of human antigen class I genes with cold medicine-related Stevens-Johnson syndrome with severe ocular complications in a Korean population

Results of Detailed Investigations Into Stevens-Johnson Syndrome With Severe Ocular Complications

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