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 Clinical Aspects of Stevens-Johnson Syndrome and Toxic Epidermal Necrolysis With Severe Ocular Complications in South Korea

2021 ◽  
Vol 8 ◽  
Author(s):  
Mee Kum Kim ◽  
Kyung Chul Yoon ◽  
Sook Hyun Yoon ◽  
Kyoung Yul Seo
Keyword(s):  
Toxic Epidermal Necrolysis ◽  
Contact Lenses ◽  
Lamellar Keratoplasty ◽  
Deep Anterior Lamellar Keratoplasty ◽  
Stevens Johnson Syndrome ◽  
Clinical Aspects ◽  
Prostaglandin E ◽  
Ocular Complications ◽  
Johnson Syndrome ◽  
Anterior Lamellar Keratoplasty

This review describes the current knowledge regarding genetic susceptibilities and treatment strategies for Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN), with ocular complications, in Korea. In a case-control study, the gene frequencies of both HLA-A*0206 (20.0%) and HLA-Cw*0304 (15.0%) increased but the gene frequency of HLA-Cw*0303 (1.3%) decreased with cold medicine (CM)-SJS/TEN with severe ocular complications (SOCs). In a case-series, positive genotyping of HLA-B*5801 was 80.0% in allopurinol-induced SJS/TEN without SOCs. In a genome-wide association study, HLA-A*0206 was substantially related to CM-SJS/TEN with SOCs. Both HLA-A*0206 and prostaglandin-E receptor 3 (PTGER3) single nucleotide polymorphism (SNP) rs1327464 exert a synergistic effect on SOCs in CM-SJS/TEN. In the acute stage, conventional procedures, amniotic membrane transplantation or suture-less amniotic contact lenses are applied. Applications of intravenous Immunoglobulin (IVIG) or mega-dose steroids are attempted in patients with high acute ocular and systemic involvement scores. In the chronic stage, keratolimbal transplantation and penetrating keratoplasty are the standard procedures. Either autologous nasal or oral mucosal grafts, or biomaterial-free cultured oral mucosal epithelial cell sheets are transplanted as alternative therapies. Deep anterior lamellar keratoplasty is attempted. Combined photodynamic therapy with intrastromal bevacizumab injection or intense pulse laser are used to resolve chronic ocular complication. Corneoscleral contact lenses are available for a visual rehabilitation. As a last resort, Seoul-type keratoprosthesis had been transplanted. There are unmet needs to standardize nationwide ocular grading system and to correct tarsal scarring using mucosal grafting. This review provides a perspective on the current practices to treat ocular complications in SJS/TEN.

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

2021 ◽  
Vol 8 ◽  
Author(s):  
Swapna S. Shanbhag ◽  
Virender S. Sangwan ◽  
Aastha Singh ◽  
Pragnya R. Donthineni ◽  
Sayan Basu ◽  
...  
Keyword(s):  
Quality Of Life ◽  
Toxic Epidermal Necrolysis ◽  
Acute Phase ◽  
Chronic Phase ◽  
Stevens Johnson Syndrome ◽  
Clinical Aspects ◽  
Ocular Involvement ◽  
Ocular Complications ◽  
Johnson Syndrome

Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN) is a spectrum of rare, severe immunological blistering skin reactions which are triggered by medication intake or infections. The acute phase is characterized by necrolysis of the skin and desquamation of mucosa, primarily oral and ocular, with significant mortality rates. The chronic phase is characterized by multi-organ sequelae with increased rates of morbidity and reduced quality of life for patients who have survived the acute phase. Since the primary goal in the acute phase is saving the life of the patient, ocular involvement is often missed and a significant proportion of patients present to an ophthalmologist with the chronic ocular sequelae. In India, chronic ocular sequelae and low vision are observed in two-thirds of patients who present in the chronic phase of SJS/TEN. In the chronic phase of ocular involvement, there are definite windows of opportunity which if targeted with specific interventions such as scleral lenses and mucous membrane grafts can help reduce the incidence of corneal blindness and improve the quality of life for patients with SJS/TEN. Over the last decade, several studies from India have advanced the understanding of the natural course of ocular involvement in SJS/TEN and the outcomes of timely interventions in the chronic phase of the disease. We present an overview of the epidemiology of ocular complications of SJS/TEN in India, the specific challenges faced in the management of ocular complications in the acute stage and recent advances in management of the chronic ocular complications of the disease.

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.

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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