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, immunochemistry 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.
authors.affiliation: Department of Dermatology, Drug hypersensitivity clinic and research center.
authors.forename: Wen-Hung
authors.initials: WH
authors.lastname: Chung
authors.forename: Shin-Ru
authors.initials: SR
authors.lastname: Shih
authors.forename: Ching-Fen
authors.initials: CF
authors.lastname: Chang
authors.forename: Tzou-Yien
authors.initials: TY
authors.lastname: Lin
authors.forename: Yhu-Chering
authors.initials: YC
authors.lastname: Huang
authors.forename: Shih-Chen
authors.initials: SC
authors.lastname: Chang
authors.forename: Ming-Tsan
authors.initials: MT
authors.lastname: Liu
authors.forename: Yu-Shien
authors.initials: YS
authors.lastname: Ko
authors.forename: Ming-Chung
authors.initials: MC
authors.lastname: Deng
authors.forename: Yea-Ling
authors.initials: YL
authors.lastname: Liau
authors.forename: Lung-Huang
authors.initials: LH
authors.lastname: Lin
authors.forename: Tou-Hwei
authors.initials: TH
authors.lastname: Chen
authors.forename: Chih-Hsun
authors.initials: CH
authors.lastname: Yang
authors.forename: Hsin-Chun
authors.initials: HC
authors.lastname: Ho
authors.forename: Jheng-Wei
authors.initials: JW
authors.lastname: Lin
authors.forename: Chun-Wei
authors.initials: CW
authors.lastname: Lu
authors.forename: Chin-Fang
authors.initials: CF
authors.lastname: Lu
authors.forename: Shuen-Iu
authors.initials: SI
authors.lastname: Hung
mesh_terms: D000945:Antigens, Differentiation, T-Lymphocyte / Q000032:analysis / Q000737:chemistry; D001706:Biopsy; D001768:Blister / Q000473:pathology / Q000821:virology*; D001826:Body Fluids / Q000737:chemistry / Q000821:virology; D002648:Child; D002675:Child, Preschool; D004279:DNA, Viral / Q000235:genetics / Q000302:isolation & purification; D004770:Enterovirus / Q000145:classification / Q000235:genetics / Q000302:isolation & purification*; D005260:Female; D006232:Hand, Foot and Mouth Disease / Q000473:pathology / Q000821:virology*; D006801:Humans; D007694:Killer Cells, Natural; D008297:Male; D010802:Phylogeny; D012867:Skin / Q000737:chemistry / Q000473:pathology / Q000821:virology; D013602:T-Lymphocytes, Cytotoxic; D014771:Virion / Q000235:genetics / Q000302:isolation & purification
chemical_list: D000945:Antigens, Differentiation, T-Lymphocyte; D004279:DNA, Viral; C075005:GNLY protein, human
keywords: coxsackievirus A6; granulysin; hand-foot-mouth disease; severe cutaneous adverse reactions