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.