INTRODUCTION

Section 2 of 10  

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• Introduction
• Clinical
• Differentials
• Workup
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• Medication
• Follow-up
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• References

Background

Hand-foot-and-mouth disease (HFMD) is a viral illness with a distinct clinical presentation of oral and characteristic distal extremity lesions. Most commonly, the etiologic agents are coxsackieviruses, members of the Picornaviridae family.

Pathophysiology

Epidemic HFMD viral infections are usually caused by members of the Enterovirus genus, namely, coxsackievirus A16 or enterovirus 71. In addition, sporadic cases with coxsackievirus types A4-A7, A9, A10, B1-B3, and B5 have been reported. Infections usually occur as isolated events, but epidemics occur regularly.

The incubation period averages 3-6 days. Coxsackievirus infection is highly contagious. During epidemics, the virus is spread by horizontal transmission from child to child and from mother to fetus. Transmission occurs by means of direct contact with nasal and/or oral secretions, fecal material, or aerosolized droplets in a fecal-oral or oral-oral route. Initial viral implantation in the buccal and ileal mucosa is followed by spread to lymph nodes within 24 hours. Viremia rapidly ensues, with spread to the oral mucosa and skin. By day 7, neutralizing antibody levels increase and the virus is eliminated.

Frequency

United States

Epidemics tend to occur every 3 years in the United States.

International

Worldwide occurrences are reported. A seasonal pattern is present in temperate climates, with a peak incidence in late summer and early fall.

Mortality/Morbidity

• HFMD is more severe in infants and children than adults, but generally, the disease has a mild course.
• Enteroviral infections may also cause myocarditis, pneumonia, meningoencephalitis and even death.
• Rarely, disease recurs.
• Infection in the first trimester may lead to spontaneous abortion or intrauterine growth retardation.
• Recently, a large outbreak of HFMD in Taiwan caused by enterovirus 71 had a high mortality rate of 19.3% in the severe cases; the deaths resulted from pulmonary hemorrhage. During this outbreak, mortality rates were highest in children younger than 3 years.
• In a large epidermic (138 cases) of HFMD related to enterovirus 71 in Singapore, 7 fatalities occurred, most from interstitial pneumonitis or brainstem encephalitis. The report's conclusions were that in general, HFMD is a benign disease but the presence of unusual physical findings, elevated total white blood cell count, and vomiting and the absence of oral ulcers may signify a patient with higher risk of a fatal outcome.
• A later study of an HFMD epidermic (14 children) in Australia, again with enterovirus 71, reported that 9 (64%) developed severe neurologic disease in which the host immune response seemed to cause most of the neurologic manifestations.

Race

No racial predilection is recognized.

Sex

The male-to-female ratio is 1:1.

Age

Most cases of HFMD affect children younger than 10 years, although cases in adults are reported.

CLINICAL

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History

• A brief prodrome of 12-36 hours duration is part of the usual presentation, which consists of the following:
• • Low-grade fever with an average temperature of 38.3°C and duration of 2-3 days
  • Anorexia
  • Malaise
  • Abdominal pain
  • Sore mouth
  • Cough
• In one study, 80% of the children presented with anorexia and mouth soreness.
• The enanthem usually precedes the exanthem that is asymptomatic, but both may occur simultaneously.
• The lesions on the hands and feet are present for 5-10 days.
• The mucosal and cutaneous lesions heal spontaneously in 5-7 days.

Physical

• HFMD is more severe in infants and children than adults, but generally, the disease has a mild course.
• • Symptoms such as malaise, low-grade fever, and anorexia are often present.
  • Occasionally, patients have high fever, marked malaise, diarrhea, and arthralgias.
  • Enteroviral infections may also cause myocarditis, pneumonia, meningoencephalitis and even death.
  • Rarely, disease recurs. One report (Sutton-Hayes, 2006) describes a 15-year-old white boy with recurrent episodes of HFMD at 3 weeks and 7 months following the initial viral illness. The lesions in the recurrent episodes were located in the same distribution as the initial presentation. His workup after the last case revealed an absence of immunodeficiency and a greater than 4-fold increase in coxsackievirus B titers. No serologic evidence of acute infection was identified, and titers of immunoglobulin G remained elevated for 1 year following this third episode.
  • Infection in the first trimester may lead to spontaneous abortion or intrauterine growth retardation.
• Oral lesions begin as erythematous macules that evolve into 2-3 mm vesicles on an erythematous base.
• The vesicles are rarely observed because they rapidly become ulcerated.
• • They are painful and may interfere with eating.
  • The total number of ulcers averages 5-10.
• The vesicles may involve the palate, buccal mucosa, gingiva, and tongue. The tongue is involved in 44% of the cases, and, in addition to the ulcers, the tongue may be edematous and tender.
• Cutaneous lesions are characteristic and are present in two-thirds of patients.
• • Typically, the hands, feet, and buttocks are involved.
  • The hands are involved more often than the feet, and the dorsal aspect of the hands and sides of the fingers are more commonly involved than the palmar surfaces.
  • Each lesion begins as a 2-10 mm erythematous macule on which a central, gray, oval vesicle develops.
  • The lesions are characteristically elliptical; their long axis parallels the skin lines.
  • These lesions are asymptomatic and resolve in 3-7 days as a result of fluid resorption.
• Erythematous maculopapular eruptions may also occur on the buttocks and arms.
• In one report, 22% of the patients also had marked cervical or submandibular lymphadenopathy.

Causes

• Epidemic hand foot and mouth infections are usually caused by coxsackievirus A16 or enterovirus 71.
• In addition, sporadic cases with coxsackievirus types A4-A7, A9, A10, B1-B3, and B5 are reported.

DIFFERENTIALS

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Other Problems to be Considered

Herpangina

WORKUP

Section 5 of 10  

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Lab Studies

• Generally, no laboratory studies are necessary.
• • Leukocyte counts are 4000-16,000/µL.
  • Occasionally, atypical lymphocytes are present.
• The virus can be isolated from swabs of the vesicles or mucosal surfaces or from stool specimens and then inoculated into mice or cultured on viral tissue media.
• Neutralizing antibodies rapidly disappear; thus, they are usually detectable only in the acute phase.
• High levels of complement-fixing antibodies are present in the convalescent phase.
• Recent studies have illustrated the usefulness of a molecular assay using polymerase chain reaction primers to arrive at a rapid and specific diagnosis in order to distinguish between coxsackievirus A16 and enterovirus 71. This may hold promise in future outbreaks because infections with enterovirus 71 tend to be associated with more severe complications and fatalities.

Histologic Findings

Classic histopathologic findings include an intra-epidermal vesicle that contains neutrophils and eosinophilic cellular debris. The adjacent epidermis has reticular degeneration, that is, intercellular and intracellular edema. The dermis has a mixed infiltrate. Eosinophilic intranuclear inclusions are observed with electron microscopic studies.

TREATMENT

Section 6 of 10  

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Medical Care

Usually, no medical care is necessary.

MEDICATION

Section 7 of 10  

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The topical application of anesthetics is beneficial. Viscous lidocaine, dyclonine solution, or diphenhydramine (Benadryl) may be used to treat painful oral ulcers. Antipyretics may be used to manage fever, and analgesics may be used to treat arthralgias.

A recent case report of severe HFMD from enterovirus infection in an immunocompromised patient reported a faster resolution of symptoms and lesions with oral acyclovir. Low-level laser therapy has also been shown to shorten the duration of painful oral ulcers.

Drug Category: Anesthetic agents, topical

These agents provide symptomatic relief of pain as a result of mucosal lesions.

Drug Category: Antihistamines

Antihistamines act by means of the competitive inhibition of histamine at the H1 receptor. This effect mediates wheal and flare reactions, bronchial constriction, mucous secretion, smooth muscle contraction, edema, hypotension, CNS depression, and cardiac arrhythmias.

Drug Category: Antacid/antiulcer agents

These agents are used for the symptomatic treatment of acid-induced gastritis and the treatment of GI ulcers.

FOLLOW-UP

Section 8 of 10  

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In/Out Patient Meds

• For symptomatic pain control for oral ulcers, elixirs such as diphenhydramine (Benadryl), aluminum and magnesium hydroxide (Mylanta), and sucralfate (Carafate) can be helpful. Several times daily, the patient should swish the elixir in his or her mouth and spit it out.
• The application of topical viscous lidocaine with a cotton-tipped swab several times daily can help in controlling the pain caused by oral ulcers.

Complications

• Dehydration occasionally occurs in children.
• Rarely, complications include meningoencephalitis, myocarditis, pulmonary edema, and death.

Prognosis

• The prognosis is excellent.

Patient Education

• The virus may be present in the patient's stool for 1 month.
• The patient’s exclusion from school is generally not required.
• Good hand-washing is necessary to reduce the potential spread of disease.
• To reduce viral spreading, do no rupture blisters.

MULTIMEDIA

Section 9 of 10  

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• Clinical
• Differentials
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Media file 1:  The lower lip has an ulcer with an erythematous halo.
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Media file 2:  The tongue has an ulcer with an erythematous halo.
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Media file 3:  A typical cutaneous lesion has an elliptical vesicle surrounded by an erythematous halo. The long axis of the lesion is oriented along the skin lines.
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Media type:  Photo

REFERENCES

Section 10 of 10

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
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• References

• Adams SP. Dermacase. Hand-foot-and-mouth disease. Can Fam Physician. May 1998;44:985, 993. [Medline].
• Chang LY, King CC, Hsu KH, et al. Risk factors of enterovirus 71 infection and associated hand, foot, and mouth disease/herpangina in children during an epidemic in Taiwan. Pediatrics. Jun 2002;109(6):e88. [Medline]. [Full Text].
• Chong CY, Chan KP, Shah VA, et al. Hand, foot and mouth disease in Singapore: a comparison of fatal and non-fatal cases. Acta Paediatr. Oct 2003;92(10):1163-9. [Medline].
• Faulkner CF, Godbolt AM, DeAmbrosis B, Triscott J. Hand, foot and mouth disease in an immunocompromised adult treated with aciclovir. Australas J Dermatol. Aug 2003;44(3):203-6. [Medline].
• Ferson MJ, Bell SM. Outbreak of Coxsackievirus A16 hand, foot, and mouth disease in a child day-care center. Am J Public Health. Dec 1991;81(12):1675-6. [Medline].
• Hood AF, Mihm MC. Hand-foot-and-mouth disease. In: Fitzpatrick TB, Austen KF, Wolff K, Eisen AZ, Freedberg IM, eds. Dermatology in General Medicine. 4th ed. New York, NY: McGraw-Hill; 1993:. 2521-3.
• Hurwitz S. The exanthematous diseases of childhood. In: Hurwitz, ed. Clinical Pediatric Dermatology: A Textbook of Skin Disorders of Childhood and Adolescence. 2nd ed. Philadelphia, Pa: WB Saunders; 1993:. 359-61.
• McMinn P, Stratov I, Nagarajan L, Davis S. Neurological manifestations of enterovirus 71 infection in children during an outbreak of hand, foot, and mouth disease in Western Australia. Clin Infect Dis. Jan 15 2001;32(2):236-42. [Medline].
• Sutton-Hayes S, Weisse ME, Wilson NW, Ogershok PR. A recurrent presentation of hand, foot, and mouth disease. Clin Pediatr (Phila). May 2006;45(4):373-6.
• Thomas I, Janniger CK. Hand, foot, and mouth disease. Cutis. Nov 1993;52(5):265-6. [Medline].
• Toida M, Watanabe F, Goto K, Shibata T. Usefulness of low-level laser for control of painful stomatitis in patients with hand-foot-and-mouth disease. J Clin Laser Med Surg. Dec 2003;21(6):363-7. [Medline].
• Tsao KC, Chang PY, Ning HC, et al. Use of molecular assay in diagnosis of hand, foot and mouth disease caused by enterovirus 71 or coxsackievirus A 16. J Virol Methods. Apr 2002;102(1-2):9-14. [Medline].

Article Last Updated: Mar 9, 2007