Hand-Foot-and-Mouth Disease in Emergency Medicine

Hand-foot-and-mouth disease is caused by a group of RNA viruses called enteroviruses. The most commonly implicated enterovirus is coxsackievirus A16.[1] However, coxsackieviruses A5, A9, A10, A16, B1, and B3; human enterovirus 71 (HEV71); as well as herpes simplex viruses (HSV) can cause the illness.

Cases are commonly spread via the fecal-oral or oral-oral route. Respiratory droplet transmission also may occur but is less likely. Typically, the virus seeds the GI tract via the buccal mucosa or the ileum. Over the next 72 hours (accounting for the incubation period), a viremia is established via spread through nearby lymph nodes.[2]

Frequency

International

Distribution of this disease is worldwide, with a peak incidence in the summer and fall in temperate climates and with no seasonal pattern in the tropics.

The largest population-based study of the epidemiology of hand, foot, and mouth disease was conducted in China to better inform vaccine and other interventions. Between 2008 and 2012, the Chinese Center for Disease Control and Prevention recorded 7,200,092 probable cases of hand, foot, and mouth disease (annual incidence, 1·2 per 1000 person-years from 2010-12). Mortality (rare in developed countries) and incidence were highest in children aged 12-23 months.[3]

Mortality/Morbidity

This illness has, essentially, a full recovery rate. However, HEV71 has been recently implicated in several large outbreaks in the Far East with severe complications and deaths. Complications are rare, but as with any pruritic rash, a secondary skin infection may occur.

Severe complications may occur when CNS or cardiopulmonary involvement is present. These sequelae include dysphagia, limb weakness, cardiopulmonary failure, and even death. Although death is very rare, it is most often due to pulmonary hemorrhage or edema.

Enteroviruses as a group are a cause of aseptic meningitis and encephalitis; however, Hand-foot-and-mouth disease is not usually associated with meningitis.[4]

A study that included 1280 stool specimens from pediatric patients hospitalized for treatment of HFMD in China reported that EV71 and CA16 were the most common agents for severe and critical HFM.[18]

Sex

Males and females are affected with equal frequency. Males are more likely to become symptomatically ill.

Age

Hand-foot-and-mouth disease, as well as severe disease complications, are more common among infants and children younger than 5 years.

The usual incubation period of hand-foot-and-mouth (HFM) disease is 4-6 days.

The prodrome is associated with the following:

• Low-grade fever

• Malaise

• Anorexia

• Abdominal pain

• Sore mouth

The prodrome precedes the development of oral lesions, followed shortly by skin lesions, primarily on the hands and feet and occasionally on the buttocks.

Hand-foot-and-mouth disease is the most common cause of mouth sores in pediatric patients.

Yellow ulcers surrounded by red halos characterize the oral lesions. These primarily occur on the labial and buccal mucosal surfaces but may be observed on the tongue, palate, uvula, anterior tonsillar pillars, or gums. Unlike herpetic gingivostomatitis, perioral lesions are uncommon. Coxsackie A virus also causes herpangina, mostly described as palatal and posterior oropharyngeal lesions without any associated exanthem. The oral ulcers are painful. Children younger than 5 years are predominately more symptomatic than older patients.[5]

The exanthem typically involves the dorsal surfaces but frequently may include the palmar, plantar, and interdigital surfaces of the hands and feet. These lesions may be asymptomatic or pruritic. They usually begin as erythematous macules that rapidly progress to thick-walled grey vesicles with an erythematous base. In young infants, these lesions may also be observed on the trunk, thighs, and buttocks. The rash is usually self-limited, lasting approximately 3-6 days. Case reports have documented subacute, chronic, and recurring skin lesions.

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• The enteroviruses, specifically coxsackievirus A16, A-10, and A-5 predominate.

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• Laboratory studies are usually unnecessary in hand-foot-and-mouth (HFM) disease.

• If clinical circumstances dictate, the virus can be recovered from the hand-foot-and-mouth lesions. Typically, the virus can be grown in culture or confirmed by immunologic methods.

• Although not suggested since physical examination is usually diagnostic, a Tzanck smear performed on vesicular fluid would be negative for the presence of multinucleated giant cells, which may help to differentiate the disease from herpes simplex virus (HSV).[2]

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• Treatment of hand-foot-and-mouth (HFM) disease is primarily supportive.

• Examining the patient's hydration status by evaluation and documentation of lacrimation, mucosal membranes, skin turgor, urine output, and pulse or capillary refill time is extremely important.

• Antipyretics should be given as needed for fever.

• Intravenous hydration should be given if the clinical assessment indicates.

• Acetaminophen and ibuprofen can be used as first-line therapy for mouth pain. For patients with significant dysphagia (irritability, refusal of oral fluids, or drooling), codeine and topical anesthetics can be administered.

No specific therapy for hand-foot-and-mouth (HFM) disease has been identified. Antibiotics are not indicated unless a complicating secondary skin infection is present.

Standard dosages of antipyretics (eg, acetaminophen, ibuprofen) are recommended on an as-needed basis for fever and analgesia.

Codeine can be used for significant pain that is not controlled with ibuprofen or acetaminophen. Topical treatments include diphenhydramine and lidocaine (or benzocaine). Lidocaine or benzocaine should only be applied with a cotton swab (and infrequently) to specific areas to avoid toxicity.[8]

Class Summary

Pain control is essential for quality patient care. Some analgesics (eg, acetaminophen, ibuprofen) also are effective for treating fever.

Acetaminophen (Feverall, Tempra, Tylenol)

Inhibits action of endogenous pyrogens on heat-regulating centers; reduces fever by a direct action on the hypothalamic heat-regulating centers, which, in turn, increase the dissipation of body heat via sweating and vasodilation. Effective for treating fever and relieving mild-to-moderate pain.

Ibuprofen (Advil, Motrin)

Effective for treating fever or mild-to-moderate pain. Inhibits inflammatory reactions and pain by decreasing prostaglandin synthesis.

Codeine

Indicated for moderate to severe pain. Binds to opiate receptors in CNS, causing inhibition of ascending pain pathways, altering perception and response to pain.

Diphenhydramine (Benylin)

Elicits antipruritic activity and weak local anesthetic action. Used topically for temporary relief of pruritus or pain.

Lidocaine anesthetic (Xylocaine)

Available as a gel or viscous oral solution. Decreases permeability of neuronal membranes to sodium ions, resulting in inhibition of depolarization and blocking transmission of nerve impulses. Initial treatment of choice for small sparse ulcers. Does not decrease healing time but may allow patient to better tolerate eating and drinking. Pain relief may be short lived, and frequent applications may be necessary.

Benzocaine (Cepacol, Orajel)

PABA derivative ester-type local anesthetic, minimally absorbed. Inhibits neuronal membrane depolarization, blocking nerve impulses. Used to control pain.

Numerous potential remedies for the pain associated with the oral lesions (which may cause the child to decrease oral intake) in hand-foot-and-mouth (HFM) disease have been reported. These remedies have not been studied in any comparative or validated methodology; however, anecdotally they have been successful. These include the following:

• "Magic mouthwash" consists of equal parts liquid Benadryl and Mylanta; mix and have the patient swish in the mouth and spit out.

• The above is mixed with a crushed Carafate tablet; have the patient swish and spit out.

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• A secondary skin infection is the main complication.

• These children can become dehydrated, resulting from decreased oral intake because of the discomfort of the oral lesions.

• Rare neurologic and/or cardiopulmonary complications may occur.[17] These are usually associated with HEV71.

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• Patients have an excellent prognosis with full recovery anticipated.

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• Instruct patients' families regarding coxsackievirus contagion.

• Instruct patients' families on home monitoring of hydration status and on warning signs of potentially complicating secondary skin infections.

• The patient and family must be warned to minimize contact with the patient's oral and respiratory secretions for up to 2 weeks.

• Good compulsive handwashing is important to minimize the spread of disease.

• The virus may be present in the patient's feces for up to 1 month.