Hand-foot-and-mouth (HFM) disease is a viral syndrome with a distinct exanthem-enanthem.[1]
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. See the image below.
View Image
The lower lip has an ulcer with an erythematous halo.
Signs and symptoms
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.
See Presentation for more detail.
Diagnosis
Physical examination is usually diagnostic, and laboratory studies are typically unnecessary.
See Workup for more detail.
Management
Treatment of HFM disease is primarily supportive.
Standard dosages of antipyretics (eg, acetaminophen, ibuprofen) are recommended on an as-needed basis for fever and analgesia.
Hand-foot-and-mouth disease is caused by a group of RNA viruses called enteroviruses. The most commonly implicated enterovirus is coxsackievirus A16.[2] However, coxsackieviruses A5, A9, A10, A16, B1, and B3; human enterovirus 71 (HEV71); as well as herpes simplex viruses (HSV) can cause the illness. Coxsackievirus A6 has been reported as the most common enterovirus identified in seasonal outbreaks of hand-foot-and-mouth disease among children in Europe.[3]
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.[4]
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.[5]
Sex- and age-related demographics
Males and females are affected with equal frequency. Males are more likely to become symptomatically ill.
Hand-foot-and-mouth disease, as well as severe disease complications, are more common among infants and children younger than 5 years.
Patients have an excellent prognosis with full recovery anticipated.
Morbidity/mortality
This illness has, essentially, a full recovery rate. However, HEV71 has been 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. A meta-analysis by Ni et al identified the following risk factors associated with fatal HFM disease in children: dyspnea, seizures, lethargy, pneumoedema/pneumorrhagia, and coma.[6]
Enteroviruses as a group are a cause of aseptic meningitis and encephalitis; however, Hand-foot-and-mouth disease is not usually associated with meningitis.[7]
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.[8]
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.[9] These are usually associated with HEV71.
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.[10] See the images below.
View Image
The lower lip has an ulcer with an erythematous halo.
View Image
The tongue has an ulcer with an erythematous halo.
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. See the image below.
View Image
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.....
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).[4]
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.
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.
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.[15]
Clinical Context:
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.
Clinical Context:
Effective for treating fever or mild-to-moderate pain. Inhibits inflammatory reactions and pain by decreasing prostaglandin synthesis.
Clinical Context:
Indicated for moderate to severe pain. Binds to opiate receptors in CNS, causing inhibition of ascending pain pathways, altering perception and response to pain.
Clinical Context:
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.
Clinical Context:
PABA derivative ester-type local anesthetic, minimally absorbed. Inhibits neuronal membrane depolarization, blocking nerve impulses. Used to control pain.
What is hand-foot-mouth (HFM) disease?What is the pathophysiology of hand-foot-mouth (HFM) disease?What is the prevalence of hand-foot-mouth (HFM) disease?What is the mortality associated with hand-foot-mouth (HFM) disease?What are the sexual predilections of hand-foot-mouth (HFM) disease?Which age groups have the highest prevalence of hand-foot-mouth (HFM) disease?What are the signs and symptoms of hand-foot-mouth (HFM) disease?Which physical findings are characteristic of hand-foot-mouth (HFM) disease?What causes hand-foot-mouth (HFM) disease?Which conditions are included in the differential diagnoses of hand-foot-mouth (HFM) disease?What are the differential diagnoses for Hand-Foot-and-Mouth Disease in Emergency Medicine?What is the role of lab tests in the workup of hand-foot-mouth (HFM) disease?How is hand-foot-mouth (HFM) disease treated?What is the role of medications in the treatment of hand-foot-mouth (HFM) disease?Which medications in the drug class Analgesic agents are used in the treatment of Hand-Foot-and-Mouth Disease in Emergency Medicine?
Pamela L Dyne, MD, Professor of Clinical Medicine/Emergency Medicine, University of California, Los Angeles, David Geffen School of Medicine; Attending Physician, Department of Emergency Medicine, Olive View-UCLA Medical Center
Disclosure: Nothing to disclose.
Specialty Editors
Mary L Windle, PharmD, Adjunct Associate Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference
Disclosure: Nothing to disclose.
Wayne Wolfram, MD, MPH, Professor, Department of Emergency Medicine, Mercy St Vincent Medical Center; Chairman, Pediatric Institutional Review Board, Mercy St Vincent Medical Center, Toledo, Ohio
Disclosure: Nothing to disclose.
Chief Editor
Russell W Steele, MD, Clinical Professor, Tulane University School of Medicine; Staff Physician, Ochsner Clinic Foundation
Disclosure: Nothing to disclose.
Additional Contributors
Heather Kesler DeVore, MD, Assistant Professor, Clinical Attending Physician, Department of Emergency Medicine, Georgetown University Hospital and Washington Hospital Center
Disclosure: Nothing to disclose.
Stacy Sawtelle, MD, Clinical Instructor, Department of Emergency Medicine, University of California, San Francisco, School of Medicine
Disclosure: Nothing to disclose.
William G Gossman, MD, FAAEM, Associate Clinical Professor of Emergency Medicine, Creighton University School of Medicine; Chairman, Department of Emergency Medicine, Creighton University Medical Center
Wolff K, Johnson RA, Suurmond D. Viral infections of skin and mucosa. Fitzpatrick's Color Atlas & Synopsis of Clinical Dermatology. 5th ed. New York, NY: McGraw-Hill; 2005. 790-92.
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