Vesiculobullous rash with atopic dermatitis

Fluid cultured from the child's blisters failed to demonstrate herpes simplex virus (HSV) or varicella-zoster virus (VZV), and a bacterial culture revealed normal skin flora. The patient's mother had also learned that the other child at the day-care center had...

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Fluid cultured from the child’s blisters failed to demonstrate herpes simplex virus (HSV) or varicella-zoster virus (VZV), and a bacterial culture revealed normal skin flora. The patient’s mother had also learned that the other child at the day-care center had hand, foot, and mouth disease (HFMD). 


The patient in this case was diagnosed with eczema coxsackium, a condition wherein atopic dermatitis becomes superinfected with one of the enteroviruses (usually coxsackievirus) that cause HFMD. 


First described in 1968 by Nahmias et al.,¹ eczema coxsackium represents one of the rarer manifestations of HFMD that has been reported. The classic and most common form of eczema coxsackium usually affects children aged less than 5 years who present in the spring and early summer with acute onset of fever, malaise, and subsequent oral and cutaneous lesions. There is no gender or geographic predilection.² 


The enanthem is characterized by small vesicles that unroof to form painful erosions of the oral mucosa, and the exanthem is characterized by asymptomatic erythematous, elliptical-shaped papules, vesicles, and erosions on the hands, feet, and buttocks.³ The virus is transmitted person-to-person when infected oropharyngeal secretions, feces, or vesicle fluid are transferred to the hands or fomites, which then come into contact with the nose, mouth, or eyes.⁴ The incubation period for the virus is 3 to 5 days, and symptoms last 7 to 10 days. Oral pain can lead to poor intake by mouth and dehydration, but this is unusual. Depending on the causative enterovirus, other rare complications have been reported. In the United States, the coxsackie A16 serotype is the most common cause of HFMD, followed by the enterovirus 71 serotype. The coxsackie A16 strain has been linked to a more severe phenotype of the disease that has been reported to involve the central nervous system and cardiopulmonary function, albeit infrequently.^2,5 


Since HFMD is quite common and rarely causes complications, typical manifestations are not reported to public-health authorities in the United States. However, from November 2011 through March 2012, the Centers for Disease Control and Prevention (CDC) was informed of 63 patients with features deviating from classic HFMD.⁶ Nearly a quarter of the patients were adults, the rash reported was more severe and extensive, and hospitalization occurred in nearly 20% of the patients. Clinical specimens were collected from 34 patients. Coxsackievirus A6, which had been implicated in outbreaks in other countries but not at that time in the United States, was detected by polymerase chain reaction (PCR) in 25 of the 34 patients. 


In response to this report, Mathes et al. retrospectively reviewed patients with atypical HFMD, delineating 4 distinct morphologic variants:³ (1) widespread vesiculobullous and erosive lesions extending beyond the palms and soles; (2) an eczema-herpeticum-like eruption termed eczema coxsackium; (3) an eruption similar to Gianotti-Crosti syndrome; and (4) a petechial or purpuric eruption. Interestingly, the investigators noted that the eruption was concentrated in areas of skin injury, such as sites of sunburn or pre-existing dermatoses. The patients in the study who had a history of atopic dermatitis were far more likely to develop the morphology associated with eczema coxsackium. No serious systemic or neurologic complications occurred in any of the patients, although the researchers noted nail shedding, Beau lines of the nails, and acral desquamation as delayed cutaneous findings. A small portion (17) of the cases underwent confirmatory testing for coxsackievirus A6, and all of these cases tested positive. Other case reports and case series followed, with patients demonstrating such atypical HFMD features as adult onset (usually in the setting of exposure to an affected child), onset in winter months, and lesions extending beyond the classic sites. These patients also tested positive for coxsackievirus A6.^5,7 


Patients with atopic dermatitis have an impaired skin barrier and alterations in cell-mediated immunity, which predispose them to cutaneous infections. Coxsackieviruses A16 and A6, the causative viruses of eczema coxsackium, are 2 such examples. The differential diagnoses for eczema coxsackium also includes other viral and bacterial superinfections of atopic dermatitis. Eczema herpeticum, the superinfection of atopic dermatitis with HSV, occurs in all ages, with patients presenting with acute onset of circular vesicles and punched-out erosions that start on the head and neck and then spread in a generalized distribution. Eczema may also become infected with the molluscum contagiosum virus, which occurs in young children; these youths present with a more subacute onset that causes skin-colored, smooth, dome-shaped, umbilicated papules, usually concentrated in areas of atopic dermatitis. The varicella virus can also infect eczema, usually in unvaccinated children, causing the abrupt appearance of vesicles on an erythematous base, starting on the head and spreading to the trunk and, to a lesser extent, the extremities. Staphylococcus aureus commonly infects skin affected by atopic dermatitis, causing superimposed weeping, crusting, oozing, and occasional pustules. It is important to note that S. aureus may co-exist with any of the above-mentioned viral infections; therefore, bacterial cultures from affected skin should be performed. 


The diagnoses of HFMD and eczema coxsackium are usually made clinically, and a skin biopsy is not needed. Given that coxsackievirus A6 is difficult to culture, Lott et al.⁵ proposed that clinicians suspect atypical HFMD when papulovesicles extend beyond a typical distribution pattern, lesions favor sites of atopic dermatitis as in eczema herpeticum, disease presents in winter, or adults are affected. In such cases, they recommended the following diagnostic laboratory evaluation: Direct fluorescent antibody assay or PCR of keratinocytes from the floor of an intact vesicle to exclude HSV or VZV infection; reverse transcriptase(RT-)PCR of vesicle fluid to confirm enterovirus infection; if vesicle fluid is unavailable, then RT-PCR of an oropharyngeal or a stool specimen can be used; and if an epidemic is suspected, cases should be reported to the appropriate agencies. 


Because our patient was seen before these recommendations were published, confirmatory testing was not performed.


Treatment is aimed at supportive measures for this self-limited infection. There is no effective antiviral therapy at this time. The CDC recommends frequent washing of hands, disinfecting of surfaces and fomites, and avoiding close contact with infected patients.² 


Our patient had negative viral and bacterial cultures. She was given antihistamines and a mild topical corticosteroid for pruritus and the underlying atopic dermatitis, with close follow-up and recommendations to report any changes in symptoms. A follow-up visit 2 weeks later showed healing erosions and desquamative scale on her palms and soles. A follow-up 2 months later revealed nail shedding.

Matthew B. Innes is a fourth-year medical student at Virginia Commonwealth University School of Medicine in Richmond, Virginia. Erin L. Reese, MD, is an assistant professor of dermatology at Virginia Commonwealth University.


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This The Clinical Advisor CME activity consists of 3 articles. To obtain credit, read Nodule on scaphoid fossa of the ear and Plaques with hyperpigmented borders. Then take the post-test here.

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