scholarly journals Findings by an International Collaboration on SJS/TEN With Severe Ocular Complications

2021 ◽  
Vol 8 ◽  
Author(s):  
Mayumi Ueta
Keyword(s):  
International Collaboration ◽  
Ocular Surface ◽  
Japanese Patients ◽  
Visual Disturbance ◽  
Acute Stage ◽  
European Ancestry ◽  
Stevens Johnson Syndrome ◽  
Ocular Complications ◽  
Johnson Syndrome ◽  
Burn Units

Stevens-Johnson Syndrome (SJS) is an acute inflammatory vesiculobullous reaction of the skin and mucosa, e.g., the ocular surface, oral cavity, and genitals. In patients with extensive skin detachment and a poor prognosis, the condition is called toxic epidermal necrolysis (TEN). Not all, but some patients with SJS/TEN manifest severe ocular lesions. Approximately 50% of SJS/TEN patients diagnosed by dermatologists and in burn units suffer from severe ocular complications (SOC) such as severe conjunctivitis with pseudomembrane and ocular surface epithelial defects in the acute stage. In the chronic stage, this results in sequelae such as severe dry eye and visual disturbance. Before 2005, our group of Japanese scientists started focusing on ophthalmic SJS/TEN with SOC. We found that cold medicines were the main causative drugs of SJS/TEN with SOC and that in Japanese patients, HLA-A*02:06 and HLA-B*44:03 were significantly associated with cold medicine-related SJS/TEN with SOC (CM-SJS/TEN with SOC). We expanded our studies and joined scientists from Korea, Brazil, India, Taiwan, Thailand, and the United Kingdom in an international collaboration to detect the genetic predisposition for SJS/TEN with SOC. This collaboration suggested that in Japanese patients, cold medicines, including NSAIDs, were the main causative drugs, and that HLA-A*02:06 was implicated in Japanese and Korean patients and HLA-B*44:03 in Japanese-, Indian-, and European ancestry Brazilian patients. Our joint findings reveal that there are ethnic differences in the HLA types associated with SJS/TEN with SOC.

scholarly journals Pathogenesis of Stevens-Johnson Syndrome/Toxic Epidermal Necrolysis With Severe Ocular Complications

2021 ◽  
Vol 8 ◽  
Author(s):  
Mayumi Ueta
Keyword(s):  
Toxic Epidermal Necrolysis ◽  
Ocular Surface ◽  
Acute Stage ◽  
Stevens Johnson Syndrome ◽  
Prostaglandin E ◽  
Ocular Complications ◽  
Chronic Stage ◽  
Snp Association ◽  
Johnson Syndrome ◽  
Burn Units

Stevens-Johnson syndrome (SJS)/toxic epidermal necrolysis (TEN) is an acute inflammatory vesiculobullous reaction of the mucosa of the ocular surface, oral cavity, and genitals, and of the skin. Severe ocular complications (SOC) are observed in about half of SJS/TEN patients diagnosed by dermatologists and in burn units. Ophthalmologists treat SOC, and they tend to encounter the patients not only in the acute stage, but also in the chronic stage. Our investigation of the pathogenesis of SJS/TEN with SOC led us to suspect that abnormal innate mucosal immunity contributes to the ocular surface inflammation seen in SJS/TEN with SOC. We confirmed that cold medicines such as NSAIDs and multi-ingredient cold medications are the main causative drugs for SJS/TEN with SOC. Single nucleotide polymorphism (SNP) association analysis of cold medicine-related SJS/TEN with SOC showed that the Toll-like receptor 3 (TLR3)-, the prostaglandin-E receptor 3 (PTGER3)-, and the IKZF1 gene were significantly associated with SNPs and that these genes could regulate mucocutaneous inflammation including that of the ocular surface. We also examined the tear cytokines of SJS/TEN with SOC in the chronic stage and found that IL-8, IL-6, IFN-γ, RANTES, eotaxin, and MIP-1β were significantly upregulated in SJS/TEN with SOC in the chronic stage. Only IP-10 was significantly downregulated in SJS/TEN with SOC in the chronic stage. This mini-review summarizes the pathological mechanisms that we identified as underlying the development of SJS/TEN with SOC.

scholarly journals Clinical Aspects of Stevens-Johnson Syndrome and Toxic Epidermal Necrolysis With Severe Ocular Complications in Brazil

2021 ◽  
Vol 8 ◽  
Author(s):  
Tais Hitomi Wakamatsu ◽  
Myrna Serapião dos Santos ◽  
Telma Pereira Barreiro ◽  
Ana Estela Besteti Pires Ponce Sant'Anna ◽  
Fabíola Murta ◽  
...  
Keyword(s):  
Toxic Epidermal Necrolysis ◽  
Amniotic Membrane ◽  
Ocular Surface ◽  
Minor Salivary Gland ◽  
European Ancestry ◽  
Stevens Johnson Syndrome ◽  
Clinical Aspects ◽  
Ocular Complications ◽  
Gram Positive ◽  
Johnson Syndrome

Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are acute and potentially fatal inflammatory vesiculobullous reactions that affect the skin and mucous membranes, and which are most often triggered by particular medications and infections. In Brazil, the drugs most frequently associated with TEN and SJS include cold medicine such as dipyrone and NSAIDs, followed by carbamazepine, phenobarbital, penicillin, and allopurinol. Genetic variations have been found to increase the risk of SJS/TEN in response to triggering factors such as medications. The most closely associated genes found in Brazilian cold-medicine-related SJS/TEN patients with severe ocular complications are HLA-A*66:01 in those of mixed African and European ancestry and HLA-B*44:03 and HLA-C*12:03 in those of solely European ancestry. Our classification system for grading ocular surface complication severity in SJS/TEN patients revealed the most severe complications to be limbal stem cell deficiency and dry eye. Changes to the conjunctival flora have also been observed in SJS/TEN patients. Our group identified bacterial colonization in 95% of the eyes (55.5% of which were gram-positive cocci, 25.5% of which were gram-negative bacilli, and 19% of which were gram-positive bacilli). Several new treatment options in the acute and chronic ocular management of the SJS/TEN patients have been described. This article highlights some Brazilian institutions' contributions to ocular surface care in both the acute phase (including the use of amniotic membrane transplantation) and the chronic phase (such as eyelid margin and fornix reconstruction, minor salivary gland transplantation, amniotic membrane and limbal transplantation, scleral contact lenses, anti-angiogenic eyedrops for corneal neovascularization, ex-vivo cultivated limbal epithelium transplantation, conjunctival-limbal autografting, oral mucosa transplantation, and keratoprosthesis).

scholarly journals Drugs causing severe ocular surface involvements in Japanese patients with Stevens–Johnson syndrome/toxic epidermal necrolysis

2015 ◽  
Vol 64 (4) ◽  
pp. 379-381 ◽  
Author(s):  
Nahoko Kaniwa ◽  
Mayumi Ueta ◽  
Ryosuke Nakamura ◽  
Yoshimi Okamoto-Uchida ◽  
Emiko Sugiyama ◽  
...  
Keyword(s):  
Toxic Epidermal Necrolysis ◽  
Ocular Surface ◽  
Japanese Patients ◽  
Stevens Johnson Syndrome ◽  
Johnson Syndrome

scholarly journals Clinical Aspects of Stevens-Johnson Syndrome/Toxic Epidermal Necrolysis With Severe Ocular Complications in Taiwan

2021 ◽  
Vol 8 ◽  
Author(s):  
David Hui-Kang Ma ◽  
Tsung-Ying Tsai ◽  
Li-Yen Pan ◽  
Shin-Yi Chen ◽  
Ching-Hsi Hsiao ◽  
...  
Keyword(s):  
Toxic Epidermal Necrolysis ◽  
Therapeutic Effect ◽  
Acute Stage ◽  
Stevens Johnson Syndrome ◽  
Amniotic Membrane Transplantation ◽  
Clinical Aspects ◽  
Ocular Complications ◽  
Etanercept Treatment ◽  
Johnson Syndrome

Purpose: Over the last decade, there has been tremendous progress in the treatment of Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN). To understand whether this has resulted in better ophthalmic outcomes, we aimed to study the incidence of severe ocular complications (SOCs) in the acute and chronic stage among SJS/TEN patients, major causative medications, and therapeutic effect of medical and surgical treatment.Methods: Using electronic medical records review of patients of Chang Gung Memorial Hospital Linkou Branch from 2010 to 2020, 119 patients (236 eyes) received ophthalmic consultation during the acute stage and were retrospectively studied. Sotozono's grading score systems for acute and chronic SJS/TEN were employed for accessing correlation between acute and chronic presentations, the therapeutic effect of systemic etanercept treatment, and outcome of early amniotic membrane transplantation (AMT) performed in patients with severe acute SOCs.Results: There were 46 male and 73 female patients with a mean age of 45.6 ± 22.7 years old (2–90 years), and follow-up time of 408.3 ± 351.0 (116–1,336) days. The numbers of patients with SJS, overlap syndrome, and TEN were 87, 9, and 23, respectively. In total, 109 eyes (55 patients) had acute SOCs, which comprised 46.2% of patients who underwent ophthalmic examination. Antiepileptics were the most common category of culprit drugs causing SOCs in the acute stage. At the end of follow-up, there were 14 eyes (9 patients) with chronic SOCs (5.9%), and non-steroidal anti-inflammatory drugs and cold medicine were the most common causative medications that were associated with severe chronic sequela. The correlation between Sotozono's acute and chronic grading score showed a positive relationship [Spearman's rank correlation coefficient (r) = 0.52, p < 0.001]. The average chronic grading scores in patients receiving systemic corticosteroid combined with etanercept treatment were significantly lower than those receiving corticosteroid only, Finally, the average chronic grading scores in patients receiving AMT <7 days after onset were significantly lower than those performed beyond 7 days.Conclusion: Our study implies that acute manifestation can be an indicator for chronic sequelae. Additional early etanercept treatment and early AMT showed beneficial effect in reducing chronic ocular sequela.

scholarly journals Categorization of the Ocular Microbiome in Japanese Stevens–Johnson Syndrome Patients With Severe Ocular Complications

2021 ◽  
Vol 11 ◽  
Author(s):  
Mayumi Ueta ◽  
Koji Hosomi ◽  
Jonguk Park ◽  
Kenji Mizuguchi ◽  
Chie Sotozono ◽  
...  
Keyword(s):  
Ocular Surface ◽  
Cross Sectional Study ◽  
Stevens Johnson Syndrome ◽  
Ocular Complications ◽  
Cross Sectional ◽  
Commensal Microbiota ◽  
Control Subjects ◽  
Persistent Inflammation ◽  
Johnson Syndrome ◽  
Healthy Control

The commensal microbiota is involved in a variety of diseases. Our group has noticed that patients with Stevens–Johnson syndrome (SJS)/toxic epidermal necrolysis (TEN) often present with persistent inflammation of the ocular surface, even in the chronic stage, and that this inflammation is exacerbated by colonization of the mucosa by certain bacteria. However, the changes in the composition of the ocular microbiome in SJS/TEN patients with severe ocular complications (SOCs) remain to be fully investigated. Here, we conducted a cross-sectional study of 46 Japanese subjects comprising 9 healthy control subjects and 37 SJS/TEN patients with SOC. The 16S rRNA-based genetic analyses revealed that the diversity of the ocular microbiome was reduced in SJS/TEN patients with SOC compared with that in healthy control subjects. Principal coordinate analysis based on Bray–Curtis distance at the genus level revealed that the relative composition of the ocular microbiome was different in healthy control subjects and SJS/TEN patients with SOC, and that the SJS/TEN patients with SOC could be divided into four groups based on whether their microbiome was characterized by enrichment of species in genus Corynebacterium 1, Neisseriaceae uncultured, or Staphylococcus or by simultaneous enrichment in species in genera Propionibacterium, Streptococcus, Fusobacterium, Lawsonella, and Serratia. Collectively, our findings indicate that enrichment of certain bacteria at the ocular surface could be associated with ocular surface inflammation in SJS/TEN patients with SOC.

Ethnic Differences in the Association Between Human Leukocyte Antigen and Stevens-Johnson Syndrome

2009 ◽  
Vol 03 (01) ◽  
pp. 15 ◽  
Author(s):  
Mayumi Ueta ◽  
Keyword(s):  
Ethnic Differences ◽  
Human Leukocyte ◽  
Japanese Patients ◽  
Han Chinese ◽  
Stevens Johnson Syndrome ◽  
Antiinflammatory Drugs ◽  
Ocular Complications ◽  
Drug Induced ◽  
Johnson Syndrome ◽  
Specific Association

The HLA-B12 antigen is significantly increased in Caucasian patients with Stevens-Johnson syndrome (SJS) with ocular complications, whileHLA-A*0206is strongly associated with Japanese patients with SJS/toxic epidermal necrolysis (TEN) with ocular complications. There are strong ethnic differences in the association between HLA and SJS/TEN. Regarding the association between HLA and drug-induced severe cutaneous adverse reactions (SCAR), including SJS and TEN, the strong allopurinol-specific association betweenHLA-B*5801and allopurinol-induced SCAR may be a universal phenomenon, since it has been identified in all Han Chinese, Caucasian and Japanese patients. In contrast, the carbamazepine-specific association betweenHLA-B*1502and carbamazepine-induced SJS may be specific to certain ethnic groups, as it has been identified in Han Chinese but not in Caucasian and Japanese patients. Dermatologists have reported that allopurinol and anticonvulsant drugs such as carbamazepine are commonly associated with SJS/TEN, while many of the author’s patients developed SJS after receiving treatment for the common cold with antibiotics, cold remedies and/or non-steroidal antiinflammatory drugs (NSAIDs). This article posits that the SJS/TEN patients seen by dermatologists are not always the same as the SJS/TEN patients consulting opthalmologists.

Long-term Progression of Ocular Surface Disease in Stevens–Johnson Syndrome and Toxic Epidermal Necrolysis

Cornea ◽  
2020 ◽  
Vol 39 (6) ◽  
pp. 745-753
Author(s):  
Yamato Yoshikawa ◽  
Mayumi Ueta ◽  
Hideki Fukuoka ◽  
Tsutomu Inatomi ◽  
Isao Yokota ◽  
...  
Keyword(s):  
Toxic Epidermal Necrolysis ◽  
Ocular Surface ◽  
Ocular Surface Disease ◽  
Stevens Johnson Syndrome ◽  
Johnson Syndrome

scholarly journals Human leukocyte antigen B*0702 is protective against ocular Stevens–Johnson syndrome/toxic epidermal necrolysis in the UK population

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Gibran F. Butt ◽  
Ali Hassan ◽  
Graham R. Wallace ◽  
Shigeru Kinoshita ◽  
Sajjad Ahmad ◽  
...  
Keyword(s):  
Human Leukocyte Antigen ◽  
Toxic Epidermal Necrolysis ◽  
Human Leukocyte ◽  
Stevens Johnson Syndrome ◽  
Ocular Complications ◽  
Leukocyte Antigen ◽  
Asian Populations ◽  
Risk Alleles ◽  
Johnson Syndrome ◽  
The Uk

AbstractStevens–Johnson Syndrome and Toxic Epidermal Necrolysis (SJS/TEN) are part of a disease continuum of vesiculobullous mucocutaneous reactions affecting the skin and mucous membranes including the ocular surface. Manifestations of disease range from mild dry eye to progressive conjunctival cicatrisation, limbal epithelial stem cell failure and corneal blindness. In Far Eastern and South East Asian populations where SJS/TEN is prevalent, numerous human leukocyte antigen (HLA) gene variants at the A, B and C loci have been identified as risk factors for developing SJS/TEN with severe ocular complications (SOC). By contrast, the incidence of SJS/TEN with SOC in European countries is relatively low. To date, ocular SJS/TEN risk altering alleles have not been widely investigated in European populations. In this study, we analysed the association of HLA -A, -B and -C alleles with SJS/TEN in 33 patients residing in the UK with age matched controls. The data showed statistically significant novel negative allele association with HLA-B*0702 and a trend with HLA-C*0702 in the patient group, indicating these alleles are protective. Further characterisation of protective and risk alleles in other ethnic groups is required to fully elucidate the putative role of these alleles in the susceptibility of SJS/TEN with or without severe ocular complications in patients in the UK.

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