Hand, foot, and mouth disease: Identifying and managing an acute viral syndrome
ABSTRACTHand, foot, and mouth disease (HFMD) is a common, typically self-limited viral syndrome in children and adults. It is marked by fever, oral ulcers, and skin manifestations affecting the palms, soles, and buttocks, with symptoms usually lasting less than 1 week. Because it has the potential to reach epidemic levels in the United States, general practitioners need to be aware of it.
KEY POINTS
- In Asian and Pacific nations, HFMD has been a significant public health concern since 1997, with recurrent epidemics and, in some cases, severe complications, including central nervous system disease, pulmonary edema, and death.
- Coxsackievirus A16 and enterovirus 71 are the most common agents of HFMD. In addition, coxsackievirus A6 seems to be emerging.
- Neurologic and cardiopulmonary involvement are more often associated with enterovirus 71 infection.
- In March 2012, 63 cases of severe HFMD were reported in Alabama, California, Connecticut, and Nevada. Fifteen of the patients were adults, and more than half had positive sick contacts. Of the 34 patients who underwent serologic testing, 25 were positive for coxsackievirus A6, an unusual pathogen for HFMD in the United States, associated with more severe skin findings.
- Treatment focuses on supportive care and prevention.
FEVER, ORAL ULCERS, RASH ON HANDS AND FEET
The typical clinical manifestations of HFMD are fever, stomatitis with oral ulcers, and an exanthem affecting the palms, soles, and other parts of the body. These last less than 7 to 10 days, usually occur during the spring to fall months, and have a benign course.
The incubation period is 3 to 5 days, with a prodrome that may include fever, malaise, abdominal pain, and myalgia before the onset of oral and cutaneous findings. Painful oral ulcers may precede the exanthem and can result in dehydration.16
The cutaneous manifestation of HFMD is typically a papulovesicular rash affecting the palms, soles, and buttocks (Figure 1). Other sites may include the knees, elbows, and the dorsal surfaces of the hands and feet. The lesions may be maculopapular and can be either asymptomatic or tender and painful. Desquamation can follow the exanthem, and lesions usually resolve without scarring or secondary infection.16,17
Table 1 and Table 2 compare HFMD with other common illnesses that can cause similar skin and mucosal findings. In particular, herpangina has the identical clinical presentation as HFMD except that it does not cause skin lesions. It is caused by many of the same enteroviruses linked to HFMD.
Different viruses, different signs?
The numerous viruses that cause HFMD usually cause similar signs and symptoms during bouts of typical, self-limited disease. However, neurologic and cardiopulmonary involvement, which are fortunately rare, are more often associated with enterovirus 71 infection.
Nail manifestations are common in HFMD. Nail separation from the nail matrix (onychomadesis) was associated with coxsackievirus A6 infection during a 2010 outbreak of HFMD in Taiwan and in a 2009 outbreak in Finland.18 Moreover, this virus was cultured from a nail specimen in one patient, suggesting viral infiltration as the cause of nail-matrix arrest.19
Perioral skin eruptions, desquamation, and Beau lines have also been associated with coxsackievirus A6.18 Beau lines are transverse depressions of the nail, most evident in the central nail plate; when seen on multiple nails, they imply a systemic illness causing disruption of nail matrix growth.20
Atypical HFMD and coxsackievirus A6
Atypical HFMD has recently been described in connection with coxsackievirus A6. Lott et al21 reported five cases of coxsackievirus A6-associated HFMD in 2013. Atypically, three of the affected patients presented in winter months, two were adults, and two had widespread skin involvement.21
Mathes et al22 reported a series of 80 cases of enteroviral infections in which the lesions had a predilection for the antecubital and popliteal fossae and were similar in severity and distribution to those seen in eczema herpeticum or Kaposi varicelliform eruption in patients with and patients without a history of atopic dermatitis. They named this find-clinical finding of pronounced coxsackievirus-associated skin disease at sites previously affected by atopic dermatitis.
Additional cutaneous findings of coxsackievirus A6 infection may include onychomadesis, Beau lines, and vesiculobullous lesions. Patients with atypical, coxsackievirus A6-associated HFMD may not have oral lesions.23
In the five cases reported by Lott et al,21 significant systemic symptoms (fever, chills, diarrhea, and myalgias) led all but one of the patients to seek care in an emergency department. However, atypical HFMD has not been associated with life-threatening illness.
Atypical HFMD associated with coxsackievirus A6 is an emerging entity in the United States, and the acuity of both cutaneous and systemic symptoms poses a diagnostic dilemma. Furthermore, infection has been documented in immunocompetent adults.23 Familiarity with the clinical findings may expedite appropriate care, prevent spread to contacts, and avoid unnecessary testing.
Neurologic and cardiopulmonary manifestations
Enteroviruses are the most common causes of viral meningoencephalitis in the United States. They mainly affect children and cause serious and potentially chronic disease in those with humoral immunodeficiencies.24 Neurologic and cardiopulmonary manifestations of HFMD are varied and extremely rare in the United States but should always be viewed clinically as signs of concern and severe disease.
Signs of potentially fatal disease that have been observed in young children include tachycardia, tachypnea, hypotension, hypertension, gastrointestinal bleeding, neurologic symptoms, leukocytosis, absence of oral lesions, and vomiting.2 Signs of dysautonomia, myoclonus, ataxia, and brainstem involvement may portend fatal disease in which rapid decompensation is the result of cardiogenic shock due to loss of ventricular contractility, causing pulmonary edema and end-organ dysfunction.16
Neurologic manifestations associated with enterovirus 71 infection include aseptic meningitis, a poliomyelitis-like syndrome, brainstem encephalitis, neurogenic pulmonary edema, opsoclonus-myoclonus syndrome, cerebellar ataxia, Guillain-Barré syndrome, and transverse myelitis.
Because some patients who have neurologic disease respond to treatment with high-dose methylprednisolone and intravenous immune globulin, there is reason to suspect that an autoimmune phenomenon triggered by the culprit enterovirus may be the cause of many of the neurologic symptoms.25
A 2012 meta-analysis26 found that an elevated white blood cell count and hyperglycemia could be clinically useful in distinguishing benign from severe HFMD. In patients with benign HFMD, white blood cell counts and blood glucose values were no different from those in healthy controls.26
