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Author: Pamela L Dyne, MD, Associate Professor, Program Director, Department of Medicine, Division of Emergency Medicine, University of California at Los Angeles School of Medicine

Pamela L Dyne is a member of the following medical societies: American College of Emergency Physicians and Society for Academic Emergency Medicine

Coauthor(s): Stacy Sawtelle, MD, Staff Physician, Department of Emergency Medicine, University of California at Los Angeles/Olive View; Heather Kesler DeVore, MD, Staff Physician, Department of Emergency Medicine, University of California at Los Angeles Olive View Medical Center

Editors: William G Gossman, MD, Associate Clinical Professor of Emergency Medicine, Creighton University School of Medicine; Consulting Staff, Department of Emergency Medicine, Creighton University Medical Center; Mary L Windle, PharmD, Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy, Pharmacy Editor, eMedicine.com, Inc; Wayne Wolfram, MD, MPH, Clinical Associate Professor, Departments of Pediatrics, Children's Hospital and University of Cincinnati; John Halamka, MD, Chief Information Officer, CareGroup Healthcare System, Assistant Professor of Medicine, Department of Emergency Medicine, Beth Israel Deaconess Medical Center; Assistant Professor of Medicine, Harvard Medical School; Richard G Bachur, MD, Assistant Professor of Pediatrics, Harvard Medical School; Associate Chief and Fellowship Director, Attending Physician, Division of Emergency Medicine, Children's Hospital of Boston

Author and Editor Disclosure

Synonyms and related keywords: HFM, enteroviruses, coxsackievirus A16, coxsackievirus A5, coxsackievirus A9, coxsackievirus A10, coxsackievirus A16, coxsackievirus B1, coxsackievirus B3, herpes simplex virus, yellow ulcers surrounded by red halos, hand-foot-mouth disease, hand-foot and mouth disease

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.



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.



Herpes Simplex
Pediatrics, Bacteremia and Sepsis
Pediatrics, Chicken Pox or Varicella
Pediatrics, Dehydration
Pediatrics, Fever
Pediatrics, Henoch-Schönlein Purpura
Pediatrics, Kawasaki Disease
Pediatrics, Measles
Pharyngitis
Stevens-Johnson Syndrome

Other Problems to be Considered

Mucocutaneous lymph node syndrome
Herpangina
Drug reaction
Aphthous stomatitis



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



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.



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 NameAcetaminophen (Feverall, Tempra, Tylenol)
DescriptionInhibits 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.
Adult Dose325-650 mg PO q4-6h or 1000 mg tid/qid; not to exceed 4 g/d
Pediatric Dose<12 years: 10-15 mg/kg/dose PO q4-6h prn; not to exceed 2.6 g/d
>12 years: 325-650 mg PO q4h; not to exceed 4 g/d
ContraindicationsDocumented hypersensitivity; known G-6-PD deficiency
InteractionsRifampin can reduce analgesic effects of acetaminophen; coadministration with barbiturates, carbamazepine, hydantoins, and isoniazid may increase hepatotoxicity
PregnancyB - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals
PrecautionsHepatotoxicity possible in chronic alcoholics following various dose levels; severe or recurrent pain or high or continued fever may indicate a serious illness; contained in many OTC products and combined use with these products may result in toxicity due to cumulative doses exceeding recommended maximum dose

Drug NameIbuprofen (Advil, Motrin)
DescriptionEffective for treating fever or mild-to-moderate pain. Inhibits inflammatory reactions and pain by decreasing prostaglandin synthesis.
Adult Dose400 mg PO q4-6h, 600 mg q6h, or 800 mg q8h while symptoms persist; not to exceed 3.2 g/d
Pediatric Dose20-70 mg/kg/d PO divided tid/qid; start at lower end of dosing range and titrate; not to exceed 2.4 g/d
ContraindicationsDocumented hypersensitivity; peptic ulcer disease; recent GI bleeding or perforation; renal insufficiency; high risk of bleeding
InteractionsCoadministration 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
PregnancyB - 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
PrecautionsCaution in congestive heart failure, hypertension, and decreased renal and hepatic function; caution in coagulation abnormalities or during anticoagulant therapy

Drug NameCodeine
DescriptionIndicated for moderate to severe pain. Binds to opiate receptors in CNS, causing inhibition of ascending pain pathways, altering perception and response to pain.
Adult Dose10-60 mg/dose PO/IM/SC q4-6h prn; not to exceed 360 mg/d
Pediatric Dose0.5 mg/kg/dose PO/IM/SC q4-6h prn; not to exceed 60 mg/dose
ContraindicationsDocumented hypersensitivity; HACE diagnosis or elevated ICP
InteractionsToxicity increases with concurrent administration of tricyclic antidepressants, MAO inhibitors, neuromuscular blockers, CNS depressants, phenothiazines, and narcotic analgesics
PregnancyC - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
PrecautionsUse 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 NameDiphenhydramine elixir (Benylin)
DescriptionElicits antipruritic activity and weak local anesthetic action. Used topically for temporary relief of pruritus or pain.
Adult DoseApply to affected area prn with cotton-tipped applicator or swish in mouth for 2 min, then expectorate
Pediatric DoseAdminister as in adults
ContraindicationsDocumented hypersensitivity; MAO inhibitors
InteractionsPotentiates effect of CNS depressants; because of alcohol content, do not give syrup dosage form to patient taking medications that can cause disulfiramlike reactions
PregnancyC - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
PrecautionsMay exacerbate angle-closure glaucoma, hyperthyroidism, peptic ulcer, or urinary tract obstruction; xerostomia may occur

Drug NameLidocaine (Xylocaine)
DescriptionAvailable 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 DoseApply to affected area prn with cotton-tipped applicator
Pediatric DoseAdminister as in adults
ContraindicationsDocumented hypersensitivity; avoid use in Adams-Stokes syndrome and Wolff-Parkinson-White syndrome
InteractionsNone reported
PregnancyB - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals
PrecautionsFor external or mucous membrane use only; do not use in eyes

Drug NameBenzocaine (Cepacol, Orajel)
DescriptionPABA derivative ester-type local anesthetic, minimally absorbed. Inhibits neuronal membrane depolarization, blocking nerve impulses. Used to control pain.
Adult Dose10-20% gel, apply to affected areas qid prn
Pediatric DoseAdminister as in adults
ContraindicationsDocumented hypersensitivity
InteractionsNone reported
PregnancyC - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
PrecautionsNot for use when infection is present; methemoglobinemia associated with overuse to mouth or throat



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.



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Pediatrics, Hand-Foot-and-Mouth Disease excerpt

Article Last Updated: Dec 20, 2007