MIAMI BEACH, Florida — Children with a severe form of hand, foot, and mouth disease infected during a recent enterovirus outbreak in the United States displayed unusual skin signs that could confuse clinicians, researchers report.
"We were surprised by the variety and extent of this exanthema," said Vikash Oza, MD, a second-year dermatology resident from the University of California at San Francisco, who presented study results here at the American Academy of Dermatology 71st Annual Meeting. "Classic hand, foot, and mouth disease has vesicles restricted to the hands, feet, and diaper region, but this new form is widespread over the entire body."
This insight stems from a case series of 81 affected children assessed at 7 academic dermatology centers in various states.
The analysis, presented during a crowded late-breaking research session, showed that the severe disease was caused by coxsackievirus A6 (CVA6).
Dr. Oza pointed out that CVA6 infection can cause a wide variety of skin manifestations, which can be confused with eczema herpeticum, vasculitis, impetigo, or primary immunobullous disease. When appropriate, herpes simplex and varicella zoster virus infection must also be ruled out, he noted.
"While the cutaneous features can vary, there is usually a clue — such as typical oral erosions, football-shaped vesicles on hands and feet, and viral symptoms — that the patient has an underlying enteroviral infection," Dr. Oza said.
The infections in this study could be distinguished from more serious infections caused by other enteroviral strains by a lack of serious systemic illness.
Although cases can present anytime throughout the calendar year, the peak incidence of enterovirus infection tends to occur in the spring, Dr. Oza said. "In most of North America, enterovirus season is approaching."
To find out more about these atypical exanthems, the researchers, led by Erin Mathes, MD, from the University of California at San Francisco, used clinical criteria to diagnose 63 children with atypical hand, foot and mouth disease and 17 children with CVA6 infection. The median age was 1.5 years old (range, 4 months to 16 years).
To aid in the differential diagnosis, the researchers identified 5 morphologic features of CVA6 infection:
- In 99% of cases, vesiculobullous and erosive eruptions are widespread on the trunk and elsewhere (in infants younger than 1 year, they can include marked perioral distribution and large bullae).
- In 55% of cases, eczema coxsackium, caused by widespread replication of the CVA6 on the skin of children with atopic dermatitis, creates a condition that clinically resembles eczema herpeticum.
- In 33% of cases, Gianotti-Crosti-like eruptions develop.
- In 17% of cases, petechiae and purpura develop.
- Delayed onychomadesis and acral desquamation can arise weeks later.
"CVA6 is an emerging and important cause of hand, foot, and mouth disease worldwide and in the United States," Dr. Oza said.
Scott Norton, MD, from the Children's National Medical Center in Washington, DC, who was asked byMedscape Medical News to comment on the findings, explained that this "new form of hand, foot, and mouth disease can have a dramatic presentation with red, almost hemorrhagic, blisters all over the body."
Benign, But Startling
Ordinarily, hemorrhagic blisters are considered a serious dermatologic emergency because they are typically seen only in the most serious of disorders, he noted. "In this new hand, foot, and mouth disease situation, however, families can be reassured that things are fine."
Dr. Norton added that "one should add this to the differential for disorders with widespread blisters."
Hundreds of emergency department visits across the United States each year are driven by this benign but startling condition.
During the discussion period at the meeting, a delegate asked why researchers are sure that the viral pathogen is driving this phenotype.
"Great question," Dr. Oza replied. "The only pathogen we isolated was coxsackievirus A6. Other data from Taiwan [obtained during a CVA6 outbreak] show the same phenotype with the same oral predilection."
Last March, the Centers for Disease Control and Prevention published initial findings of some of the earlier cases from an outbreak in 4 states (MMWR Morb Mortal Wkly Rep. 2012;61:213-214).
The researchers and Dr. Norton have disclosed no relevant financial relationships.
American Academy of Dermatology (AAD) 71st Annual Meeting. Presented March 2, 2013.