Dermatologic Manifestations of Enteroviral Infections Workup

Updated: May 21, 2018
  • Author: Mercè Alsina-Gibert, MD; Chief Editor: Dirk M Elston, MD  more...
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Laboratory Studies

Enteroviral infections are diagnosed mainly on the basis of clinical features; however, a specific diagnosis of enterovirus infection requires detection of the virus in patient samples. In some cases, complementary tests may be useful.

Serologic studies

The detection of virus-specific immunoglobulin M (IgM) antibodies by means of enzyme-linked immunosorbent assay (ELISA) can aid diagnosis and can be detected as early as the second day of infection.

Serum samples should be obtained during the acute phase of the disease since IgM antibodies rapidly disappear. The antibodies are usually group specific and not serotype specific.

No universal antibody or antigen assay exists because no single antigen is present in all enterovirus serotypes. Serology has no role in routine diagnosis.

Cell culture

Cell culture may allow isolation of the virus. Samples are obtained from the blood, stool, pharyngeal secretions, or vesicular fluid. Some reports suggest that the best results are achieved when samples are collected from the upper respiratory tract, gastrointestinal tract, or cerebrospinal fluid. However, the most specific findings are found in samples from blood and blister fluid. Findings in fecal specimens are least specific because enteroviruses may be shed for weeks after acute infection and can be detected well after the clinical illness has resolved. A 2007 study revealed that a throat culture plus a culture of two sterile vesicles (or from the rectum if no sterile vesicles are present) may have the highest yield for detecting enterovirus 71 (EV71) in patients with hand-foot-and-mouth disease (HFMD). [51]

Although enteroviruses take 4-8 days to grow and results are not usually available in sufficient time to have an impact on treatment of the patient, culture remains an important epidemiologic tool. Viral culture allows the clinician to isolate and identify the serotype of the virus causing disease.

Polymerase chain reaction

The reverse-transcriptase polymerase chain reaction (RT-PCR) has made enteroviral subtyping possible and has increased the enterovirus detection rate, especially in the analysis of cerebrospinal fluid.

As a reaction to the August, 2014 enterovirus D68 outbreak in the United States, the CDC has developed and begun using a new and faster laboratory test for enterovirus D68. [52] With RT-PCR testing, new outbreaks can be identified within a few days, rather than the weeks it took previously.

RT-PCR assays permit shorter turnover times, especially for the detection of enterovirus RNA. [53]

PCR techniques require small amounts of clinical material and are rapid (within 5-24 h of receipt of the sample), sensitive, and specific. PCR is superior to viral culture for the diagnosis of many enterovirus infections, particularly enteroviral meningitis. [54] Specimen sources are the same as those for cell cultures, as outlined above.

Because of their extreme sensitivity, these tests are subject to false-positive results due to contamination and to false-negative results due to levels below assay detection.

RT-PCR provides the potential for a reduction in unnecessary hospitalization and diagnostic or therapeutic interventions.

New techniques such as rapid polymerase recombinase polymerase amplification assay for coxsackie A6 have extremely high sensitivity and specificity and may be useful in public health control and outbreak notification. [55]


Histologic Findings

In most cases, histopathologic findings are nonspecific and are not necessary for diagnosis.

When a skin biopsy is performed to evaluate hand-foot-mouth disease (HFMD), findings may include spongiosis, intraepidermal vesicles that contain neutrophils and mononuclear cells, and some necrotic keratinocytes. [56, 57, 58] Edema and a perivascular infiltrate composed of lymphocytes and neutrophils may be seen in the dermis. Atypical forms of HFMD caused by coxsackie A6, mainly occurring in adults, show neutrophil-rich infiltrates with involvement of the stratum granulosum and spinosum. [40] Keratinocyte necrosis and vacuolization of the basal membrane may also be found. Adnexal structures can also be involved with neutrophil infiltrates. [41]

In eruptive pseudoangiomatosis (EP), lesions are composed of dilated superficial vessels with plump endothelial cells and mild lymphocytic infiltrate. The lesions are easily distinguished from true angiomas since there is no increase in the number of vessels.


Other Tests

There are no clear biomarkers. However, High levels of serum acetylcholinesterase were seen in a large cohort of Chinese patients with hand-foot-mouth disease (HFMD) caused by enterovirus 71 (EV71). [59]