AUTHOR AND EDITOR INFORMATION

Section 1 of 9  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• References

INTRODUCTION

Section 2 of 9  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• References

Background

Hand-foot-and-mouth (HFM) disease is a viral syndrome with a distinct exanthem-enanthem.

This clearly recognizable syndrome is characterized by vesicular lesions on the mouth and an exanthem on the hands and feet (and buttocks) in association with fever.

Pathophysiology

HFM disease is caused by a group of RNA viruses called enteroviruses. The most commonly implicated enterovirus is coxsackievirus A16. However, coxsackieviruses A5, A9, A10, A16, B1, and B3; human enterovirus 71 (HEV71); as well as herpes simplex viruses 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.¹

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.

Mortality/Morbidity

This illness has, essentially, a full recovery rate. However, HEV71 has been recently implicated in several large outbreaks 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, HFM disease is usually not associated with meningitis.

Sex

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

Age

HFM disease as well as severe disease complications are more common among infants and children younger than 5 years.

CLINICAL

Section 3 of 9  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• References

History

• The usual incubation period is 4-6 days.
• Prodrome
• • 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.

Physical

HFM disease is the most common cause of mouth sores in pediatric patients.

• Yellow ulcers surrounded by red halos characterize the oral lesions.
• • These occur primarily on the labial and buccal mucosal surfaces, but they 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.
• 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 also may 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.

Causes

The enteroviruses, specifically coxsackievirus A16, predominate.

DIFFERENTIALS

Section 4 of 9  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• References

Other Problems to be Considered

Mucocutaneous lymph node syndrome
Herpangina
Drug reaction
Aphthous stomatitis

WORKUP

Section 5 of 9  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• References

Lab Studies

• Laboratory studies usually are unnecessary.
• If clinical circumstances dictate, the virus can be recovered from the HFM 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 HSV.¹

TREATMENT

Section 6 of 9  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• References

Emergency Department Care

• Treatment is primarily supportive.
• It is extremely important to examine the patient's hydration status by evaluation and documentation of lacrimation, mucosal membranes, skin turgor, urine output, and pulse or capillary refill time.
• Antipyretics should be given as needed for fever.
• IV 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.

MEDICATION

Section 7 of 9  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• References

No specific therapy for this viral illness exists. 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.

Drug Category: Analgesic agents

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

Drug Name	Ibuprofen (Advil, Motrin)
Description	Effective for treating fever or mild-to-moderate pain. Inhibits inflammatory reactions and pain by decreasing prostaglandin synthesis.
Adult Dose	400 mg PO q4-6h, 600 mg q6h, or 800 mg q8h while symptoms persist; not to exceed 3.2 g/d
Pediatric Dose	20-70 mg/kg/d PO divided tid/qid; start at lower end of dosing range and titrate; not to exceed 2.4 g/d
Contraindications	Documented hypersensitivity; peptic ulcer disease; recent GI bleeding or perforation; renal insufficiency; high risk of bleeding
Interactions	Coadministration with aspirin increases risk of inducing serious NSAID-related adverse effects; probenecid may increase concentrations and, possibly, toxicity of NSAIDs; may decrease effect of hydralazine, captopril, and beta-blockers; may decrease diuretic effects of furosemide and thiazides; may increase PT when taking anticoagulants (instruct patients to watch for signs of bleeding); may increase risk of methotrexate toxicity; phenytoin levels may be increased when administered concurrently
Pregnancy	B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals D - Fetal risk shown in humans; use only if benefits outweigh risk to fetus
Precautions	Caution in congestive heart failure, hypertension, and decreased renal and hepatic function; caution in coagulation abnormalities or during anticoagulant therapy

Drug Name	Codeine
Description	Indicated for moderate to severe pain. Binds to opiate receptors in CNS, causing inhibition of ascending pain pathways, altering perception and response to pain.
Adult Dose	10-60 mg/dose PO/IM/SC q4-6h prn; not to exceed 360 mg/d
Pediatric Dose	0.5 mg/kg/dose PO/IM/SC q4-6h prn; not to exceed 60 mg/dose
Contraindications	Documented hypersensitivity; HACE diagnosis or elevated ICP
Interactions	Toxicity increases with concurrent administration of tricyclic antidepressants, MAO inhibitors, neuromuscular blockers, CNS depressants, phenothiazines, and narcotic analgesics
Pregnancy	C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions	Use to treat cough in HACE diagnosed patients only if absolutely necessary; may depress hypoxic ventilatory rate and respiratory drive during sleep; caution when combined with acetaminophen to hepatotoxicity toxicity

Drug Name	Diphenhydramine elixir (Benylin)
Description	Elicits antipruritic activity and weak local anesthetic action. Used topically for temporary relief of pruritus or pain.
Adult Dose	Apply to affected area prn with cotton-tipped applicator or swish in mouth for 2 min, then expectorate
Pediatric Dose	Administer as in adults
Contraindications	Documented hypersensitivity; MAO inhibitors
Interactions	Potentiates effect of CNS depressants; because of alcohol content, do not give syrup dosage form to patient taking medications that can cause disulfiramlike reactions
Pregnancy	C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions	May exacerbate angle-closure glaucoma, hyperthyroidism, peptic ulcer, or urinary tract obstruction; xerostomia may occur

Drug Name	Lidocaine (Xylocaine)
Description	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.
Adult Dose	Apply to affected area prn with cotton-tipped applicator
Pediatric Dose	Administer as in adults
Contraindications	Documented hypersensitivity; avoid use in Adams-Stokes syndrome and Wolff-Parkinson-White syndrome
Interactions	None reported
Pregnancy	B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals
Precautions	For external or mucous membrane use only; do not use in eyes

Drug Name	Benzocaine (Cepacol, Orajel)
Description	PABA derivative ester-type local anesthetic, minimally absorbed. Inhibits neuronal membrane depolarization, blocking nerve impulses. Used to control pain.
Adult Dose	10-20% gel, apply to affected areas qid prn
Pediatric Dose	Administer as in adults
Contraindications	Documented hypersensitivity
Interactions	None reported
Pregnancy	C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions	Not for use when infection is present; methemoglobinemia associated with overuse to mouth or throat

FOLLOW-UP

Section 8 of 9  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• References

In/Out Patient Meds

• A number of potential remedies exist for the pain associated with the oral lesions (which may cause the child to decrease oral intake). 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.

Complications

• 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. These are usually associated with HEV71.

Prognosis

• Patients have an excellent prognosis with full recovery anticipated.

Patient Education

• 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.

REFERENCES

Section 9 of 9

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• References

1. Wolff K, Johnson RA, Suurmond D. Viral infections of skin and mucosa. In: Fitzpatrick's Color Atlas & Synopsis of Clinical Dermatology. 5^th ed. New York, NY: McGraw-Hill; 2005:790-92.
2. Chang LY, Tsao KC, Hsia SH, et al. Transmission and clinical features of enterovirus 71 infections in household contacts in Taiwan. JAMA. Jan 14 2004;291(2):222-7. [Medline].
3. Chen KT, Chang HL, Wang ST, Cheng YT, Yang JY. Epidemiologic features of hand-foot-mouth disease and herpangina caused by enterovirus 71 in Taiwan, 1998-2005. Pediatrics. Aug 2007;120(2):e244-52. [Medline].
4. Cherry JD. Enteroviruses: polioviruses, coxsackieviruses, echoviruses and enteroviruses. In: Textbook of Pediatric Infectious Diseases. 5^th ed. 2005:2007.
5. Cherry JD. Viral exanthems. Curr Probl Pediatr. Apr 1983;13(6):1-44. [Medline].
6. Davis H, Karasic R. Pediatric infectious disease. In: Atlas of Pediatric Physical Diagnosis. 3^rd ed. 1997:347-8.
7. Marks M. Viral and presumably viral syndromes. In: Pediatric Infectious Diseases for the Practitioner. 1985:494-6.
8. Sasidharan CK, Sugathan P, Agarwal R, et al. Hand-foot-and-mouth disease in Calicut. Indian J Pediatr. Jan 2005;72(1):17-21. [Medline].
9. Wang CY, Li Lu F, Wu MH, et al. Fatal coxsackievirus A16 infection. Pediatr Infect Dis J. Mar 2004;23(3):275-6. [Medline].

Article Last Updated: Dec 20, 2007