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Hand-foot-and-mouth disease (HFMD) is an acute viral illness that presents as a vesicular eruption in the mouth (see the image below), but it can also involve the hands, feet, buttocks, and/or genitalia. Coxsackievirus A type 16 (CVA16) is the etiologic agent involved in most cases of HFMD, but the illness is also associated with coxsackievirus A5, A7, A9, A10, B2, and B5 strains. Enterovirus 71 (EV-71) has caused outbreaks of HFMD with associated neurologic involvement in the western Pacific region.
See Clues in the Oral Cavity: Are You Missing the Diagnosis?, a Critical Images slideshow, to help identify the causes of abnormalities of the oral cavity.
Also, see the 15 Rashes You Need to Know: Common Dermatologic Diagnoses slideshow to help identify and treat various rashes and the 15 Back-to-School Illnesses You Should Know slideshow to help identify conditions that may occur in young patients after they return to the classroom.
Signs and symptoms
The history in patients with HFMD is as follows:
Sore mouth or throat
Rarely, vomiting occurs in HFMD cases caused by EV-71
Physical findings include the following:
Initially, macular lesions appear on the buccal mucosa, tongue, and/or hard palate
These mucosal lesions rapidly progress to vesicles that erode and become surrounded by an erythematous halo
Lesions may also be found on the hands, feet, buttocks, and genitalia
A fever of 38-39°C may be present for 24-48 hours
Atypical clinical features include concomitant aseptic meningitis in HFMD caused by coxsackievirus strains (rare). HFMD caused by EV-71 has a higher incidence of neurologic involvement, including the following :
A poliolike syndrome
Acute cerebellar ataxia
Acute transverse myelitis
Benign intracranial hypertension
See Clinical Presentation for more detail.
The diagnosis of HFMD is typically based on clinical grounds. Laboratory studies are usually unnecessary, but the following may be done:
The virus can be isolated and identified via culture and immunoassay from cutaneous lesions, mucosal lesions, or stool samples; oral specimens have the highest isolation rate
In patients with vesicles, vesicle swabs are also a good source for viral collection
In patients without vesicles, rectal swabs can be collected
For viral isolation, 2 swab collections are recommended: From the throat and from either vesicles or the rectum
Serologic testing (eg, acute and convalescent antibody levels) may be obtained
Differentiating coxsackievirus-associated HFMD from EV-71–associated HFMD may have prognostic significance
PCR and microarray technology are among the various ways of identifying the causative virus 
See Workup for more detail.
There is no antiviral agent specific for the etiologic agents of HFMD. Instead, the treatment is supportive, as follows:
Ensure adequate fluid intake to prevent dehydration; cold liquids are generally preferable
Spicy or acidic substances may cause discomfort
Intravenous hydration may be necessary if the patient has moderate-to-severe dehydration or if discomfort precludes oral intake
Fever may be treated with antipyretics
Pain may be treated with standard doses of acetaminophen or ibuprofen
Direct analgesia may also be applied to the oral cavity via mouthwashes or sprays
IVIG and milrinone have shown some efficacy in a few reports [4, 5, 6]
See Treatment and Medication for more detail.
Hand-foot-and-mouth disease (HFMD) is an acute viral illness that presents as a vesicular eruption in the mouth. HFMD can also involve the hands, feet, buttocks, and/or genitalia. Coxsackievirus A type 16 (CV A16) is the etiologic agent involved in most cases of HFMD, but the illness is also associated with coxsackievirus A5, A7, A9, A10, B2, and B5 strains. Enterovirus 71 (EV-71) has also caused outbreaks of HFMD with associated neurologic involvement in the western Pacific region.
Coxsackievirus is a subgroup of the enteroviruses and is a member of the family Picornaviridae. This family consists of small, nonenveloped, single-stranded RNA viruses.
Infection generally occurs via the fecal-oral route or via contact with skin lesions and oral secretions. Viremia develops, followed by invasion of the skin and mucous membranes. Widespread apoptosis likely results in the characteristic lesion formation.
Epidemics of HFMD generally occur in the summer to early fall months, although cases can occur sporadically all year.
HFMD epidemics associated with EV-71 have been more frequent in Southeast Asia in recent years, including Taiwan (1998) and Singapore (2000). Risk factors in these epidemics include attendance at child care centers, contact with HFMD, large family number, and rural residence.
HFMD caused by coxsackievirus is generally a mild self-limited illness that resolves in 7-10 days; rarely, HFMD may recur or persist. Serious complications are also rare.
Severe oral ulcerations can create painful stomatitis. This may interfere with oral intake and cause dehydration, the most common complication of HFMD. Rarely, aseptic meningitis accompanies coxsackievirus-induced HFMD.
HFMD caused by EV-71 has a higher incidence of neurologic involvement, including a poliolike syndrome, aseptic meningitis, encephalitis, encephalomyelitis, acute cerebellar ataxia, acute transverse myelitis, Guillain-Barré syndrome, opsomyoclonus syndrome, and benign intracranial hypertension. These neurological complications have been attributed to either immunopathology or virus-induced damage to gray matter.[1, 8]
Rarely, cardiopulmonary complications such as myocarditis, interstitial pneumonitis, and pulmonary edema may occur. Neurologic involvement with sequelae is less likely to occur in patients with HFMD caused by coxsackievirus strains than with HFMD caused by EV-71. Chang et al analyzed the Taiwan HFMD epidemic of 1998 and revealed that 68% of the EV-71 cases were uncomplicated. Thirty-two percent of the cases had complications; 7.3% involved aseptic meningitis, 10% involved encephalitis, 2.3% involved poliolike syndrome, 4.5% involved encephalomyelitis, and 6.8% involved fatal pulmonary edema (7.9% of patients died and 4% of patients had sequelae). In the coxsackievirus A16 group, 94% of the cases of were uncomplicated; only 6.3% cases were complicated by aseptic meningitis; no fatalities or sequelae were reported.
Chong et al observed vomiting, leukocytosis, and an absence of mouth ulcers as predictive risk factors for fatal cases of EV-71 HFMD during the Singapore epidemic in 2000.
Most reports indicate that HFMD has no sexual predilection. Some epidemic data observe a slight male-to-female predominance ratio of 1.2-1.3:1.
Children younger than 10 years are most commonly affected with HFMD, and subsequent outbreaks among family members and close contacts may develop.
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|Illness||Etiologic Agent||Usual Severity of Clinical Illness||Appearance of Lesions||Locations of Lesions||Other Features|
|HFMD||Coxsackie-virus A16 (most common), A5, A7, A9, A10, B2, B5
Vesicles → ulcerations on an erythematous base
Usually 2-6 mm
|Lesions may also be found on hands, feet, buttocks, and genitalia.
|Herpangina||Coxsackie-virus A1-A10, A16, A22
Echovirus 3, 6, 9, 16, 17, 25, 30
|Moderate; can be severe||Papules →
Vesicles → ulcerations on an erythematous base
Usually 2-4 mm
|Posterior oral cavity
Tonsils, soft palate, uvula
|Temperature generally high|
|Herpetic gingivostomatitis||Herpes simplex virus-1||Moderate to severe||Vesicles
|Anterior oral cavity
Lips, gingiva, buccal mucosa
|Temperature generally high
|Aphthous stomatitis||Unknown||Mild to severe||Ulcerations; larger than in viral enanthems||Lips, tongue, buccal mucosa; generally not diffuse||Afebrile
May be recurrent
|Stevens-Johnson syndrome||Immunologic||Moderate to severe||Coalescent vesicles, which then ulcerate||Lips, gingiva, buccal mucosa, tongue, pharynx||Targetlike cutaneous lesions
Diffuse mucous membrane involvement