For neonates and young infants with nonspecific febrile illness, follow regional guidelines for workup and treatment.

Hand, foot and mouth disease (HFMD) is a common illness mostly affecting patients younger than 10 years, though adults can be affected as well. It is caused by human enteroviruses and coxsackieviruses. Generally, this disease causes a low-grade fever, with pink macules on the hands, feet, oral mucosa. The lesions typically resolve in 7-10 days although rarely may be complicated by neurological or cardiac manifestations. Outbreaks typically occur between spring and fall⁽¹⁾.

The disease is spread through respiratory droplet/contact, as well as fecal-oral and oral-oral. Disease is most transmissible during the first week of illness, however the virus may be shed in stool for 4-8 weeks⁽¹⁾.

Coxsackievirus A6 is associated with a more severe presentation affecting both children and adults. It presents with fever and generalized rash affecting the face, proximal extremities, trunk, hands, feet and buttocks. It tends to cause more severe pain, dehydration and desquamation of the palms and soles. It may also be complicated by encephalitis, acute flaccid paralysis, myocarditis, pericarditis and shock⁽²⁾.

Diagnosis of Typical and Atypical Hand, Foot and Mouth Disease

Clinical diagnosis based on typical clinical features:

• Maculopapular or papulovesicular rash on hands and feet.
• Painful oral ulcerations.
• Usually, fever + coryza prodrome⁽²⁾.

Typical lesions appear on hands and feet, usually dorsal surfaces though palms and soles may be affected as well. Lesions are 3-7mm and are typically tender. Oral ulcerations are often painful vesicles which may ulcerate⁽²⁾.

Atypical lesions may be present, including hemorrhagic/purpuric lesions, bullae and pustules on the trunk, involvement of the trunk, cheek or genitals, desquamation of palms and soles.

Laboratory Investigations

Diagnosis is generally made on history and physical exam.

May consider RT-PCR for enteroviruses in CSF, serum, urine, NP or oropharyngeal swab which are highly specific and sensitive for acute infection⁽²⁾. However, this is not necessary for diagnosis.

Other laboratory testing is not necessary for most cases of hand, foot and mouth disease, although they may be considered for investigating acute complications.

Investigations for Acute Complications of Hand, Foot and Mouth Disease

Asses for complications of hand, foot and mouth disease and initiate investigations where there is clinical suspicion:

• Herpangina – Acute-onset fever, pharyngitis, dysphagia and painful lesions to posterior pharynx. Fevers may reach 41˚ May present with seizures. Mild cases generally have no complications; however this presentation presents with more severe dehydration and is associated with meningitis⁽²⁾.
• Neurologic manifestations⁽²⁾.
  • Meningitis
    • <1 year – often lack meningeal signs. Present with fever, irritability, malaise, photophobia, nausea/vomiting, anorexia, lethargy, hypotonia.
    • >1-2 years – nuchal rigidity present in >50%.
    • Investigations: LP with viral panel, cell count, glucose, chemistry, culture. CSF parameters may be normal in up to 50% of young infants, despite detection of enterovirus.
  • Encephalitis
    • Confusion, weakness, lethargy, irritability, +/- focal motor signs.
    • Investigations: same as meningitis.
  • Cardiac manifestations(2) – myocarditis, pericarditis. Mortality 0-4%, most have full recovery.
    • ECG: ST segment, T-wave and/or rhythm abnormalities.
    • Cardiac enzyme elevation.
    • Echo: ventricular dilatation, reduced contractility, pericardial effusion.

Differential Diagnosis:

• Other Viral illnesses⁽²⁾:
  • Herpes – clear vesicles on an erythematous base. PCR from lesion swab can confirm if clinical uncertainty and severe illness.
  • Varicella – clear vesicles on an erythematous base. PCR from lesion swab can confirm if clinical uncertainty and severe illness.
  • Measles – Fever, cough, coryza. Maculopapular rash with cephalocaudal spread. May be preceded by Koplik spots on buccal mucosa.
• Non-viral exanthems:
  • Atopic dermatitis – recurring presentation. Clinical diagnosis based on history and exam.
  • Scabies – intense pruritis, linear distribution. Clinical diagnosis +/- skin scraping with mite visualization on microscope.
  • Erythema multiforme – target lesions on face and limbs.
• Bullous impetigo – flaccid bullae on trunk and extremities. Clinical diagnosis.
• Systemic illness:
  • Drug reaction (delayed hypersensitivity/Stevens-Johnson syndrome) – fever, malaise, erythematous skin with painful lesions/flaccid bullae to skin and mucous membranes. Skin biopsy can confirm diagnosis.
  • Pemphigus vulgaris – presents with bullae of oral mucosa, lip and oral mucosal erosions. Potential involvement of genitals and eyes. Biopsy should be taken for diagnosis, or serum testing.
  • Behçet syndrome – recurrent oral/genital aphthous ulcers, papulopustular acneiform lesions, erythema nodosum anterior uveitis.
    • Clinical diagnosis based on Behçet syndrome International Study Group Criteria: https://qxmd.com/calculate/calculator_707/behcet-s-syndrome-international-study-group-criteria

Treatment directed at hydration, relief of pain and fever as disease is self-limited.

Pain and fever can be treated with acetaminophen or ibuprofen. Oral topical lidocaine is not recommended⁽¹⁾.

There is currently no antiviral therapy approved in North America for use against hand, foot and mouth disease.

Pediatric referral should be considered in severe or complicated cases.

• Inability to maintain adequate hydration.
• Cardiac complications – admit to pediatrics/pediatric ICU.
• Neurological complications – admit to pediatrics/pediatric ICU.

• Able to maintain adequate hydration.
• Absence of clinical neurological findings.

1. https://dermnetnz.org/images/hand-foot-and-mouth-disease-images

   Prevention of spread⁽¹⁾:

   • Handwashing, particularly after diaper changes, toileting and before eating.
   • Disinfection of surfaces (e.g., toys).

   Vaccines: none available.

   Breastfeeding: no impact on incidence of hand-foot-and-mouth disease. No need to stop breastfeeding to prevent transmission⁽¹⁾.

   
   

1. Saguil A, Kane SF, Lauters R, Mercado MG. Hand-Foot-and-Mouth Disease: Rapid Evidence Review. Am Fam Physician. 2019 Oct 1;100(7):408–14.

   
   

2. Kliegman R, St Geme JW, Blum NJ, Shah SS, Tasker RC, Wilson KM, et al. Nelson Textbook of Pediatrics. 21st ed. Philadelphia, PA: Elsevier Inc.; 2020.

   
   

3. Leung AKC, Lam JM, Barankin B, Leong KF, Hon KL. Hand, Foot, and Mouth Disease: A Narrative Review. Recent Adv Inflamm allergy drug Discov. 2022 Oct 26;17.