What is hand, foot, and mouth disease?

What is Hand, Foot, and Mouth Disease?

Hand, foot, and mouth disease (HFMD) is a highly contagious viral illness caused by enteroviruses—most commonly Coxsackievirus A16, Coxsackievirus A6, and Enterovirus 71—that predominantly affects children under 5 years of age and presents with characteristic vesicular lesions on the hands, feet, and mouth. 1, 2

Causative Agents

• Primary pathogens: Coxsackievirus A16 (CVA16), Coxsackievirus A6 (CVA6), and Enterovirus 71 (EV-A71) are the main viral agents responsible for HFMD 3, 2, 4
• Enterovirus 71 is associated with more severe outbreaks, particularly in Asia, and carries a higher risk of serious complications compared to other causative viruses 1, 4
• The disease belongs to the Picornaviridae family in the genus enterovirus 5

Clinical Presentation

Initial Symptoms

• Fever is typically the first symptom, usually low-grade but can exceed 102.2°F (39°C), accompanied by malaise, general discomfort, sore throat, and irritability in young children 6, 7
• Constitutional symptoms may include respiratory symptoms (cough, rhinitis) and occasionally gastrointestinal symptoms (nausea, vomiting, diarrhea) 6
• The incubation period ranges from 3 to 10 days before symptoms appear 3

Characteristic Rash Pattern

• The exanthem begins as small pink macules that evolve into vesicular lesions with a highly characteristic distribution on palms, soles, and oral cavity 6
• Oral lesions present as painful vesicles or ulcers in the mouth, making swallowing difficult 1, 8
• Vesiculopapular rash on hands and feet is the most common clinical finding 8
• In some cases, widespread exanthema may extend beyond the classic distribution to involve the legs and other areas 1

Epidemiology and Transmission

• The disease predominantly affects children under 5 years of age, with the highest incidence in children 0-3 years old 8, 2, 4
• Adults can also be affected, particularly through intra-familial transmission from infected children 7, 5
• Patients are most infectious during the first week of illness, with viral shedding continuing for up to 5 days after symptom onset 7
• The disease is highly contagious and spreads through respiratory droplets, direct contact with vesicle fluid, and fecal-oral transmission 2, 5

Disease Course and Complications

Typical Course

• In most cases, HFMD follows a benign, self-limiting course, resolving in 7-10 days without sequelae 3, 4
• Nail changes (onychomadesis) may occur up to 2 months after initial symptoms in some cases, particularly with Coxsackievirus A6 infections 3

Severe Complications

• Neurological complications can occur, including encephalitis/meningitis, acute flaccid myelitis, and acute flaccid paralysis, particularly with EV-71 infections 1, 7, 3
• Severe respiratory complications such as pulmonary edema may develop 3
• Circulatory failure secondary to myocardial impairment and neurogenic pulmonary edema secondary to brainstem damage are the main causes of death in severe cases 4
• Immunocompromised patients may experience more severe disease and require close monitoring 1, 7

Diagnosis

• Diagnosis is primarily clinical, based on the characteristic distribution of vesicular lesions on hands, feet, and mouth 7
• Laboratory confirmation uses reverse transcriptase PCR (RT-PCR) targeting the 5' non-coding region, with vesicle fluid samples being ideal due to high viral loads 1, 7
• Respiratory samples and stool specimens can also be used for RT-PCR testing 1

Important Differential Diagnoses

• Unlike chickenpox, HFMD vesicles are concentrated on hands, feet, and mouth rather than widely distributed 6
• Unlike Kawasaki disease, HFMD presents with vesicular lesions rather than diffuse erythema and does not typically have persistent high fever 6
• Other conditions with palmar/plantar rash to consider include syphilis, meningococcal infection, Rocky Mountain spotted fever, drug hypersensitivity reactions, and infective endocarditis 6, 7
• Chemotherapy-induced hand-foot syndrome presents with dysesthesia, burning pain, and hyperkeratosis rather than discrete vesicles 6