Expression of prostaglandin E2 receptor 3 in the eyelid epidermis of patients with Stevens-Johnson syndrome/toxic epidermal necrolysis

2019 ◽  
Vol 104 (7) ◽  
pp. 1022-1027 ◽  
Author(s):  
Hiroki Mieno ◽  
Mayumi Ueta ◽  
Keiko Yamada ◽  
Yukito Yamanaka ◽  
Tomomichi Nakayama ◽  
...  
Keyword(s):  
Toxic Epidermal Necrolysis ◽  
Cytokine Production ◽  
Immunohistochemical Study ◽  
Chronic Phase ◽  
Stevens Johnson Syndrome ◽  
Epidermal Keratinocytes ◽  
Prostaglandin E ◽  
Conjunctival Epithelium ◽  
Human Epidermal Keratinocytes ◽  
Johnson Syndrome

Background/aimsIn a previous genome-wide association study of Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN) patients we reported the association between SJS/TEN and the prostaglandin E receptor 3 (PTGER3) gene, and that its protein PGE2 receptor 3 (EP3) was markedly downregulated in the conjunctival epithelium of SJS/TEN patients. Here we examined EP3 expression of the eyelid epidermis in SJS/TEN patients with severe ocular complications and investigated the function of EP3.MethodsFor the immunohistochemical study, we obtained eyelid samples from five SJS/TEN patients and five patients without SJS/TEN (control subjects) who were undergoing surgery to treat trichiasis, and investigated the expression of EP3 protein in the epidermis of those samples. To investigate the EP3 function in the human epidermal keratinocytes, we performed ELISA and quantitative reverse transcription polymerase chain reaction, since it is reported that PGE2 suppresses cytokine production via EP3 in human conjunctival epithelium.ResultsThe results of the immunohistochemical study revealed that EP3 expression in the eyelid epidermis of the SJS/TEN patients was the same as that in the controls. PGE2 and a selective EP3 agonist suppressed cytokine production and expression induced by polyinosine-polycytidylic acid stimulation, such as chemokine ligand 5 and chemokine motif ligand 10.ConclusionOur findings revealed that in chronic-phase SJS/TEN, EP3 protein was expressed in the eyelid epidermis and was not downregulated, unlike in conjunctival epithelium, and that PGE2 could suppress cytokine production via EP3 in human epidermal keratinocytes. Thus, EP3 expression in the epidermis might contribute to a silencing of skin inflammation in chronic-phase SJS/TEN.

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 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.

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