Clinicopathologic Analysis of Coxsackievirus A6 New Variant Induced Widespread Mucocutaneous Bullous Reactions Mimicking Severe Cutaneous Adverse Reactions

Chung, Wen Hung; Shih, Shin Ru; Chang, Ching Fen; Lin, Tzou Yien; Huang, Yhu Chering; Chang, Shinn‐Jen; Liu, Ming Tsan; Ko, Yu Shien; Deng, Ming Chung; Liau, Yea Ling; Lin, Lung Huang; Chen, Tou Hwei; Yang, Chao-Ping; Ho, Hung‐Yao; Lin, Jui-Yen; Lu, Chun‐Wei; Lu, Chin Fang; Hung, Shuen Lu

doi:10.1093/infdis/jit383

Cited by 64 publications

(45 citation statements)

References 34 publications

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“…In addition to drugs, SJS/TEN may be also induced by pathogens, such as Mycoplasma pneumoniae or herpes simplex virus infections. Our recent study showed that a new variant of coxsackievirus A6, classified as a human enterovirus, may also induce severe mucocutaneous blistering reactions which are mainly mediated by CTL and NK cells expressing granulysin and their clinical presentations mimic the features of erythema multiforme major or SJS . In fact, there remains approximately 20% of SJS/TEN cases without an identified causality.…”

Section: Environmental and Non‐genetic Factorsmentioning

confidence: 99%

Severe cutaneous adverse drug reactions

Chung

Wang

Dao

2016

The Journal of Dermatology

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179

163

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The clinical manifestations of drug eruptions can range from mild maculopapular exanthema to severe cutaneous adverse drug reactions (SCAR), including drug-induced hypersensitivity syndrome/drug reaction with eosinophilia and systemic symptoms, Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) which are rare but occasionally fatal. Some pathogens may induce skin reactions mimicking SCAR. There are several models to explain the interaction of human leukocyte antigen (HLA), drug and T-cell receptor (TCR): (i) the "hapten/prohapten" theory; (ii) the "p-i concept"; (iii) the "altered peptide repertoire"; and (iv) the "altered TCR repertoire". The checkpoints of molecular mechanisms of SCAR include specific drug antigens interacting with the specific HLA loci (e.g. HLA-B*15:02 for carbamazepine-induced SJS/TEN and HLA-B*58:01 for allopurinol-induced SCAR), involvement of specific TCR, induction of T-cell-mediated responses (e.g. granulysin, Fas ligand, perforin/granzyme B and T-helper 1/2-associated cytokines) and cell death mechanism (e.g. miR-18a-5p-induced apoptosis; annexin A1 and formyl peptide receptor 1-induced necroptosis in keratinocytes). In addition to immune mechanism, metabolism has been found to play a role in the pathogenesis of SCAR, such as recent findings of strong association of CYP2C9*3 with phenytoin-induced SCAR and impaired renal function with allopurinol SCAR. With a better understanding of the mechanisms, effective therapeutics and prevention for SCAR can be improved.

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Section: Environmental and Non‐genetic Factorsmentioning

confidence: 99%

Severe cutaneous adverse drug reactions

Chung

Wang

Dao

2016

The Journal of Dermatology

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179

163

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“…Acute graft‐versus‐host disease in its most severe form is virtually identical to SJS/TEN . Widespread blistering eruptions with some resemblance clinically (and histologically) to SJS/TEN were recently described in association with a new variant of coxsackievirus A6 . Burns are usually distinguished by the history and distribution of lesions.…”

Section: Differential Diagnosismentioning

confidence: 99%

Erythema multiforme, Stevens–Johnson syndrome and toxic epidermal necrolysis: a comparative review

Yager

2014

Veterinary Dermatology

139

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“…In some cases, TEM has also been used to confirm a diagnosis previously established with molecular techniques . Figure illustrates the detection of a reovirus strain in MRC5 cells cultured in the presence of urine and throat swab specimens from two children with unexplained neurologic symptoms of encephalitis.…”

Section: Current Role Of Tem In the Diagnosis Of Viral Infectionmentioning

confidence: 99%

Virus detection by transmission electron microscopy: Still useful for diagnosis and a plus for biosafety

Roingeard

Raynal

Eymieux

et al. 2018

Reviews in Medical Virology

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Summary Transmission electron microscopy (TEM) is the only imaging technique allowing the direct visualization of viruses, due to its nanometer‐scale resolution. Between the 1960s and 1990s, TEM contributed to the discovery of many types of viruses and served as a diagnostic tool for identifying viruses directly in biological samples, either in suspension or in sections of tissues or mammalian cells grown in vitro in contact with clinical samples. The diagnosis of viral infections improved considerably during the 1990s, with the advent of highly sensitive techniques, such as enzyme‐linked immunosorbent assay (ELISA) and PCR, rendering TEM obsolete for this purpose. However, the last 20 years have demonstrated the utility of this technique in particular situations, due to its “catch‐all” nature, making diagnosis possible through visualization of the virus, without the need of prior assumptions about the infectious agent sought. Thus, in several major outbreaks in which molecular techniques failed to identify the infectious agent, TEM provided the answer. TEM is also still occasionally used in routine diagnosis to characterize infections not diagnosed by molecular assays. It is also used to check the microbiological safety of biological products. Many biopharmaceuticals are produced in animal cells that might contain little‐known, difficult‐to‐detect viruses. In this context, the “catch‐all” properties of TEM make it possible to document the presence of viruses or virus‐like particles in these products.

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Clinicopathologic Analysis of Coxsackievirus A6 New Variant Induced Widespread Mucocutaneous Bullous Reactions Mimicking Severe Cutaneous Adverse Reactions

Cited by 64 publications

References 34 publications

Severe cutaneous adverse drug reactions

Severe cutaneous adverse drug reactions

Erythema multiforme, Stevens–Johnson syndrome and toxic epidermal necrolysis: a comparative review

Virus detection by transmission electron microscopy: Still useful for diagnosis and a plus for biosafety

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