Hand, Foot, and Mouth Disease: CVA6 Diagnostic Clues Found

Jenni Laidman

June 17, 2013

The unusual characteristics of hand, foot, and mouth disease (HFMD) caused by coxsackievirus A6 (CVA6) are easily confused with several other diseases, but the authors of an analysis of the 2011 to 2012 outbreak have characterized distinctive morphologies of this more severe enterovirus in a study published online June 17 in Pediatrics.

Erin F. Mathes, MD, assistant clinical professor, Department of Dermatology and Department of Pediatrics, University of California, San Francisco, and colleagues examined the medical records of 80 children who tested positive for CVA6 (n = 17), using nucleotide sequencing, or who met clinical criteria for atypical HFMD between July 2011 and June 2012 at 7 academic pediatric dermatology centers around North America.

The authors found 4 morphologies that distinguished this coxsackievirus-associated outbreak from classic HFMD, including widespread vesiculobullous and erosive lesions extending beyond the palms and soles; eczema herpeticum-like eruptions in areas previously or currently affected by atopic dermatitis; eruptions similar to those in Gianotti-Crosti and focused in areas of previous skin injury, such as in areas of sunburn; and petechial or purpuric eruptions, frequently on acral sites, as in acral purpura.

"The phenotypic variability and unusual skin eruptions can be confused with other infectious disease and inflammatory skin diseases," the authors write.

The current analysis could help sort out this confusion, Dean Morrell, MD, professor, director of pediatric and adolescent dermatology, University of North Carolina Department of Dermatology, Chapel Hill, told Medscape Medical News in an email. Dr. Morrell was not involved in the current study.

"This paper is an excellent and timely review of a new clinical entity," Dr. Morrell noted. "Eczema coxsackium was seen across the country and initially fooled many of us. The first case seen at [the University of North Carolina] was initially diagnosed as eczema herpeticum, but that diagnosis didn't really fit the clinical constellation of findings. This manuscript will further educate medical caregivers, who will certainly have the condition come through their practices."

The authors found that the most common symptoms of CVA6 were widespread vesicles, bullae, and/or erosions. Ninety-nine percent of patients had vesiculobullous and erosive eruptions. Infants younger than 1 year were more likely to have bullae than older children (38% of patients younger than 1 year compared with 7% aged 1 to 5 years and 18% of those older than 5 years; P = .039).

Although classical HFMD generally involves hands, feet, and occasionally the buttocks, with enanthem of small vesicles and eruptions of the oral mucosa, the exanthem differed in the CVA6 HFMD by frequently including the perioral area, extremities, and torso. Intraoral outbreaks also occur less frequently in the classic condition.

In most patients (61%), the vesicles, erosions, and bullae of various sizes covered more than 10% of body surface area, which has not been reported in previous HFMD outbreaks.

CVA6 often appeared in areas of previous trauma or inflammation, including diaper rash or healing lacerations, the authors report. Forty-four (55%) of the 80 patients had eruptions in areas of eczematous dermatitis, and 14 patients (18%) had eruptions in other areas of skin injury.

"Enteroviral infections, particularly CVA6, should now be considered in the differential diagnosis of patients presenting with new-onset vesicles and extensive erosions in preexisting areas of eczema," the authors write.

More than one third of the patients with CVA6 had Gianotti-Crosti-like distribution, with lesions on cheeks, extensor surfaces of extremities, and buttocks, but not on the trunk (28/76, 37%).

One coauthor is a consultant and has received payment for lectures and has a grant/pending grant from bioMérieux, which makes the enterovirus assay used in diagnosis at North Shore-Long Island Jewish Health Systems Laboratories. The other authors and Dr. Morrell have disclosed no relevant financial relationships.

Pediatrics. Published online June 17, 2013. Abstract

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