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—primarily coxsackievirus A16, coxsackievirus A6, and enterovirus 71—that predominantly affects children under 5 years of age and is characterized by fever followed by vesicular lesions on the oral mucosa, palms, and soles. 1, 2

Causative Agents

• Coxsackievirus A16 (CVA16) and Enterovirus 71 (EV-A71) are the traditional major etiological agents 2, 3
• Coxsackievirus A6 (CVA6) has emerged as a major cause of HFMD outbreaks since 2000, associated with more severe and atypical presentations that can affect adults 4, 5
• Enterovirus 71 is associated with more severe outbreaks, particularly in Asia, with higher rates of neurological complications 1, 2

Clinical Presentation

Initial Symptoms

• Fever is typically the first symptom, usually low-grade but can exceed 102.2°F (39°C), accompanied by malaise, sore throat, and irritability in children 6, 7
• The incubation period ranges from 3 to 10 days before symptoms appear 2
• Respiratory symptoms (cough, rhinitis) and gastrointestinal symptoms (nausea, vomiting, diarrhea) may accompany the classic presentation 6

Characteristic Rash Pattern

• The exanthem begins as small pink macules that evolve to vesicular lesions with highly characteristic distribution on palms and soles 6
• Oral lesions develop as vesicles or erosions in the mouth, often causing painful swallowing 8
• The classic triad involves hands, feet, and mouth, though buttocks are also commonly affected 2, 5

Atypical Presentations

• Widespread exanthema beyond the classic distribution can occur, involving legs, arms, and trunk—particularly with CVA6 infections 1, 5
• Peri-oral rash is specifically associated with CVA6 5
• Up to 87.6% of confirmed cases have skin lesions on sites other than the classic hand-foot-mouth distribution 5
• Adults can be affected, particularly during CVA6 outbreaks, with more severe symptoms than typical HFMD 4

Epidemiology and Transmission

• The disease is highly contagious, with adults most infectious during the first week of illness and viral shedding continuing for up to 5 days after symptom onset 7
• Predominantly affects children under 5 years of age, with highest incidence in the 0-3 year age group 8, 3
• Shows slight male preponderance (approximately 61% male) 8
• Seasonal peaks often occur in late summer and early fall 8

Complications

Neurological Complications

• Encephalitis and meningitis can occur in severe cases, particularly with EV-71 1, 7
• Acute flaccid myelitis (AFM) and acute flaccid paralysis (AFP) are rare but serious neurological complications 1
• Severe progressive forms may present with sudden onset of fever and severe respiratory symptoms including pulmonary edema 2

Other Complications

• Onychomadesis (nail loss) can occur up to 2 months after initial symptoms, particularly with CVA6 infections 2
• Cardiac complications have been observed during severe outbreaks 2
• Immunocompromised patients may experience more severe disease 1, 7

Diagnosis

• Diagnosis is primarily clinical, based on the characteristic distribution of lesions 7
• Reverse transcriptase PCR (RT-PCR) targeting the 5′ non-coding region is the preferred laboratory confirmation method due to its sensitivity and specificity 1
• Vesicle fluid samples have the highest viral loads and are ideal for testing 1
• Respiratory samples and stool specimens can also be used for diagnosis 1

Differential Diagnosis

Important conditions to distinguish from HFMD:

• Kawasaki disease: presents with diffuse erythema rather than vesicular lesions and typically has persistent high fever 6
• Chickenpox: vesicles are widely distributed rather than concentrated on hands, feet, and mouth 6
• Drug hypersensitivity reactions and infective endocarditis can present with palmar/plantar rash 6, 7
• Syphilis and meningococcal infection should be considered when palmar/plantar rash is present 6
• Rocky Mountain spotted fever can present with petechial rash 6

Management

Supportive Care

• Treatment is primarily supportive, as no specific antiviral therapy is generally recommended for uncomplicated cases 2, 7
• Oral analgesics such as acetaminophen or NSAIDs for limited duration to relieve pain and reduce fever 1, 7

Oral Lesion Management

• Apply white soft paraffin ointment to lips every 2 hours to prevent drying and cracking 1
• Clean mouth daily with warm saline mouthwashes 1
• Benzydamine hydrochloride oral rinse or spray every 3 hours, particularly before eating, to reduce inflammation and pain 1
• Chlorhexidine oral rinse twice daily as antiseptic measure 1
• Betamethasone sodium phosphate mouthwash four times daily for more severe oral involvement 1

Skin Lesion Management

• Intensive skin care with moisturizing creams, particularly urea-containing products 1, 7
• Avoid friction and heat exposure to affected areas 1
• Zinc oxide may help reduce itchiness by forming a protective barrier on the skin 1, 7
• Avoid applying zinc oxide to open or weeping lesions 1

Severe Cases

• Mechanical ventilation may be necessary for severe respiratory complications 2
• Antiviral agents such as ribavirin have been used in severe cases, though evidence is limited 2

Prevention and Control

• Hand hygiene is the most important preventive measure, with thorough handwashing with soap and water being more effective than alcohol-based hand sanitizers 1
• Environmental cleaning, particularly of toys and objects that may be placed in children's mouths 1
• Avoid sharing utensils, cups, or food 1
• Children can return to daycare once fever has resolved and mouth sores have healed, even if skin rash is still present 1
• Adults can return to work once fever has resolved, mouth sores have healed, and no new lesions have appeared for 48 hours 7

Vaccination Status

• An inactivated EV-A71 vaccine approved by China FDA provides high protection against EV-A71-related HFMD 3
• No broadly protective vaccine is currently available for all HFMD-causing enteroviruses 2, 3

Prognosis

• Most cases follow a benign and self-limiting course, with symptoms resolving spontaneously within 7-10 days 2, 4
• CVA6-associated HFMD often has higher fever and longer duration of disease than typical HFMD 4
• Severe neurological and cardiac complications can result in fatalities, particularly with EV-71 outbreaks 2