Medication tendencies for inducing severe ocular surface symptoms in Japanese Stevens-Johnson Syndrome / toxic epidermal necrolysis patients

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.

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HLA association with antipyretic analgesics-induced Stevens-Johnson Syndrome/toxic epidermal necrolysis with severe ocular surface complications in japanese patients

Clinical and Translational Allergy ◽

10.1186/2045-7022-4-s3-p89 ◽

2014 ◽

Vol 4 (S3) ◽

Author(s):

Ryosuke Nakamura ◽

Nahoko Kaniwa ◽

Mayumi Ueta ◽

Chie Sotozono ◽

Emiko Sugiyama ◽

...

Keyword(s):

Toxic Epidermal Necrolysis ◽

Ocular Surface ◽

Japanese Patients ◽

Stevens Johnson Syndrome ◽

Hla Association ◽

Johnson Syndrome

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Prosthetic Replacement of the Ocular Surface Ecosystem as Treatment for Ocular Surface Disease in Patients with a History of Stevens–Johnson Syndrome/Toxic Epidermal Necrolysis

Ophthalmology ◽

10.1016/j.ophtha.2014.08.015 ◽

2015 ◽

Vol 122 (2) ◽

pp. 248-253 ◽

Cited By ~ 31

Author(s):

Thanos D. Papakostas ◽

Hong-Gam Le ◽

James Chodosh ◽

Deborah S. Jacobs

Keyword(s):

Toxic Epidermal Necrolysis ◽

Ocular Surface ◽

Ocular Surface Disease ◽

Stevens Johnson Syndrome ◽

Prosthetic Replacement ◽

Johnson Syndrome ◽

History Of

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

Frontiers in Medicine ◽

10.3389/fmed.2021.649369 ◽

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).

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