Clinicopathologic analysis of coxsackievirus A6 new variant induced widespread mucocutaneous bullous reactions mimicking severe cutaneous adverse reactions

Wen Hung Chung, Shin Ru Shih, Ching Fen Chang, Tzou Yien Lin, Yhu Chering Huang, Shih Chen Chang, Ming Tsan Liu, Yu Shien Ko, Ming Chung Deng, Yea Ling Liau, Lung Huang Lin, Tou Hwei Chen, Chih Hsun Yang, Hsin Chun Ho, Jheng Wei Lin, Chun Wei Lu, Chin Fang Lu, Shuen Lu Hung

Research output: Contribution to journalArticle

43 Citations (Scopus)

Abstract

Background. The cutaneous manifestations of human enterovirus (HEV) infection are usually limited, such as hand-foot-mouth disease. By comparison, Stevens-Johnson syndrome (SJS) is a life-threatening severe cutaneous adverse reaction (SCAR), mainly caused by drugs. During the HEV outbreaks in 2010-2012 in Taiwan, we identified 21 patients who developed widespread blistering mucocutaneous reactions without any suspected drug causality. Methods. We screened possible pathogen(s) for detecting human herpes virus (HHV1-HHV7), HEV, or Mycoplasma pneumoniae infections using throat swab virus cultures, real-time PCR, DNA sequencing, immunochemis-try and electron microscopy analyses. Results. Coxsackievirus A6 (CVA6) DNA was identified in the blistering skin lesions in 6 of 21 patients. Cytotoxic T lymphocytes and natural killer cells expressing granulysin predominantly infiltrated into the skin lesions, sharing the histopathological features with SJS. Intact CVA6 viral particles were identified in the blister fluids and skin lesions by electron microscopy. The phylogenetic analysis of the viral genome showed the CVA6 DNA sequence sharing higher similarity (97.6%-98.1%) to CVA6 strains reported from Finland at 2008. Conclusions. This study identifies a new variant of CVA6 as the causative agent for severe mucocutaneous blistering reactions mimicking SCAR. An awareness of this unusual presentation of HEV infection is needed in the epidemic area.

Original languageEnglish
Pages (from-to)1968-1978
Number of pages11
JournalJournal of Infectious Diseases
Volume208
Issue number12
DOIs
Publication statusPublished - Dec 15 2013
Externally publishedYes

Fingerprint

Enterovirus
Skin
Enterovirus Infections
Stevens-Johnson Syndrome
Electron Microscopy
Hand, Foot and Mouth Disease
Viruses
Skin Manifestations
Mycoplasma pneumoniae
Viral Genome
Cytotoxic T-Lymphocytes
Blister
Finland
Pharynx
Taiwan
DNA Sequence Analysis
Natural Killer Cells
Causality
Pharmaceutical Preparations
Virion

Keywords

  • Coxsackievirus A6
  • Granulysin
  • Hand-foot-mouth disease
  • Severe cutaneous adverse reactions

ASJC Scopus subject areas

  • Infectious Diseases
  • Immunology and Allergy
  • Medicine(all)

Cite this

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, Shih Chen; Liu, Ming Tsan; Ko, Yu Shien; Deng, Ming Chung; Liau, Yea Ling; Lin, Lung Huang; Chen, Tou Hwei; Yang, Chih Hsun; Ho, Hsin Chun; Lin, Jheng Wei; Lu, Chun Wei; Lu, Chin Fang; Hung, Shuen Lu.

In: Journal of Infectious Diseases, Vol. 208, No. 12, 15.12.2013, p. 1968-1978.

Research output: Contribution to journalArticle

Chung, WH, Shih, SR, Chang, CF, Lin, TY, Huang, YC, Chang, SC, Liu, MT, Ko, YS, Deng, MC, Liau, YL, Lin, LH, Chen, TH, Yang, CH, Ho, HC, Lin, JW, Lu, CW, Lu, CF & Hung, SL 2013, 'Clinicopathologic analysis of coxsackievirus A6 new variant induced widespread mucocutaneous bullous reactions mimicking severe cutaneous adverse reactions', Journal of Infectious Diseases, vol. 208, no. 12, pp. 1968-1978. https://doi.org/10.1093/infdis/jit383
Chung, Wen Hung ; Shih, Shin Ru ; Chang, Ching Fen ; Lin, Tzou Yien ; Huang, Yhu Chering ; Chang, Shih Chen ; Liu, Ming Tsan ; Ko, Yu Shien ; Deng, Ming Chung ; Liau, Yea Ling ; Lin, Lung Huang ; Chen, Tou Hwei ; Yang, Chih Hsun ; Ho, Hsin Chun ; Lin, Jheng Wei ; Lu, Chun Wei ; Lu, Chin Fang ; Hung, Shuen Lu. / Clinicopathologic analysis of coxsackievirus A6 new variant induced widespread mucocutaneous bullous reactions mimicking severe cutaneous adverse reactions. In: Journal of Infectious Diseases. 2013 ; Vol. 208, No. 12. pp. 1968-1978.
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title = "Clinicopathologic analysis of coxsackievirus A6 new variant induced widespread mucocutaneous bullous reactions mimicking severe cutaneous adverse reactions",
abstract = "Background. The cutaneous manifestations of human enterovirus (HEV) infection are usually limited, such as hand-foot-mouth disease. By comparison, Stevens-Johnson syndrome (SJS) is a life-threatening severe cutaneous adverse reaction (SCAR), mainly caused by drugs. During the HEV outbreaks in 2010-2012 in Taiwan, we identified 21 patients who developed widespread blistering mucocutaneous reactions without any suspected drug causality. Methods. We screened possible pathogen(s) for detecting human herpes virus (HHV1-HHV7), HEV, or Mycoplasma pneumoniae infections using throat swab virus cultures, real-time PCR, DNA sequencing, immunochemis-try and electron microscopy analyses. Results. Coxsackievirus A6 (CVA6) DNA was identified in the blistering skin lesions in 6 of 21 patients. Cytotoxic T lymphocytes and natural killer cells expressing granulysin predominantly infiltrated into the skin lesions, sharing the histopathological features with SJS. Intact CVA6 viral particles were identified in the blister fluids and skin lesions by electron microscopy. The phylogenetic analysis of the viral genome showed the CVA6 DNA sequence sharing higher similarity (97.6{\%}-98.1{\%}) to CVA6 strains reported from Finland at 2008. Conclusions. This study identifies a new variant of CVA6 as the causative agent for severe mucocutaneous blistering reactions mimicking SCAR. An awareness of this unusual presentation of HEV infection is needed in the epidemic area.",
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T1 - Clinicopathologic analysis of coxsackievirus A6 new variant induced widespread mucocutaneous bullous reactions mimicking severe cutaneous adverse reactions

AU - Chung, Wen Hung

AU - Shih, Shin Ru

AU - Chang, Ching Fen

AU - Lin, Tzou Yien

AU - Huang, Yhu Chering

AU - Chang, Shih Chen

AU - Liu, Ming Tsan

AU - Ko, Yu Shien

AU - Deng, Ming Chung

AU - Liau, Yea Ling

AU - Lin, Lung Huang

AU - Chen, Tou Hwei

AU - Yang, Chih Hsun

AU - Ho, Hsin Chun

AU - Lin, Jheng Wei

AU - Lu, Chun Wei

AU - Lu, Chin Fang

AU - Hung, Shuen Lu

PY - 2013/12/15

Y1 - 2013/12/15

N2 - Background. The cutaneous manifestations of human enterovirus (HEV) infection are usually limited, such as hand-foot-mouth disease. By comparison, Stevens-Johnson syndrome (SJS) is a life-threatening severe cutaneous adverse reaction (SCAR), mainly caused by drugs. During the HEV outbreaks in 2010-2012 in Taiwan, we identified 21 patients who developed widespread blistering mucocutaneous reactions without any suspected drug causality. Methods. We screened possible pathogen(s) for detecting human herpes virus (HHV1-HHV7), HEV, or Mycoplasma pneumoniae infections using throat swab virus cultures, real-time PCR, DNA sequencing, immunochemis-try and electron microscopy analyses. Results. Coxsackievirus A6 (CVA6) DNA was identified in the blistering skin lesions in 6 of 21 patients. Cytotoxic T lymphocytes and natural killer cells expressing granulysin predominantly infiltrated into the skin lesions, sharing the histopathological features with SJS. Intact CVA6 viral particles were identified in the blister fluids and skin lesions by electron microscopy. The phylogenetic analysis of the viral genome showed the CVA6 DNA sequence sharing higher similarity (97.6%-98.1%) to CVA6 strains reported from Finland at 2008. Conclusions. This study identifies a new variant of CVA6 as the causative agent for severe mucocutaneous blistering reactions mimicking SCAR. An awareness of this unusual presentation of HEV infection is needed in the epidemic area.

AB - Background. The cutaneous manifestations of human enterovirus (HEV) infection are usually limited, such as hand-foot-mouth disease. By comparison, Stevens-Johnson syndrome (SJS) is a life-threatening severe cutaneous adverse reaction (SCAR), mainly caused by drugs. During the HEV outbreaks in 2010-2012 in Taiwan, we identified 21 patients who developed widespread blistering mucocutaneous reactions without any suspected drug causality. Methods. We screened possible pathogen(s) for detecting human herpes virus (HHV1-HHV7), HEV, or Mycoplasma pneumoniae infections using throat swab virus cultures, real-time PCR, DNA sequencing, immunochemis-try and electron microscopy analyses. Results. Coxsackievirus A6 (CVA6) DNA was identified in the blistering skin lesions in 6 of 21 patients. Cytotoxic T lymphocytes and natural killer cells expressing granulysin predominantly infiltrated into the skin lesions, sharing the histopathological features with SJS. Intact CVA6 viral particles were identified in the blister fluids and skin lesions by electron microscopy. The phylogenetic analysis of the viral genome showed the CVA6 DNA sequence sharing higher similarity (97.6%-98.1%) to CVA6 strains reported from Finland at 2008. Conclusions. This study identifies a new variant of CVA6 as the causative agent for severe mucocutaneous blistering reactions mimicking SCAR. An awareness of this unusual presentation of HEV infection is needed in the epidemic area.

KW - Coxsackievirus A6

KW - Granulysin

KW - Hand-foot-mouth disease

KW - Severe cutaneous adverse reactions

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