What are the typical symptoms and presentation of foot and mouth disease in humans?

Clinical Presentation of Hand, Foot, and Mouth Disease in Humans

Hand, foot, and mouth disease (HFMD) typically presents with fever as the initial symptom, followed 1-2 days later by characteristic vesicular lesions on the hands, feet, and oral cavity, primarily affecting children under 5 years of age. 1, 2

Initial Symptoms (Days 1-2)

• Fever is usually the first manifestation, typically low-grade but can exceed 102.2°F (39°C), particularly in infants and toddlers 2, 3
• General malaise, irritability, and discomfort accompany the fever in most cases 2, 3
• Sore throat is a common early complaint 3
• Respiratory symptoms such as cough and rhinitis may occur, especially in younger children 2, 3
• Gastrointestinal symptoms including nausea, vomiting, and diarrhea are occasionally reported 3

Characteristic Rash Development (Days 2-3)

Oral Lesions

• Small red spots appear first in the mouth, progressing to painful vesicles and ulcers 2
• Distribution includes the tongue, gums, and inside of the cheeks 2
• Oral ulcers may persist for 7-10 days and cause significant discomfort, leading to decreased oral intake 2

Skin Lesions

• The exanthem begins as small pink macules that evolve to vesicular lesions 3
• Highly characteristic distribution on palms and soles is the hallmark finding 3
• Vesicular rash on hands and feet typically appears 1-2 days after fever onset 2
• Buttocks involvement is common 4
• Widespread exanthema beyond the classic distribution may occur, involving the legs and trunk, particularly with certain viral strains 1

Disease Course and Resolution

• Fever usually subsides within 3-4 days 2
• Lesions typically resolve in 7-10 days without scarring 5
• The disease is generally self-limiting in most cases 4, 5

Atypical Presentations

Coxsackievirus A6 (CVA6) has emerged as a cause of atypical HFMD with unusual features that can complicate diagnosis 6, 7:

• Vesiculobullous exanthema with more extensive involvement 6, 7
• Perioral zone involvement 6
• Gianotti-Crosti-like eruptions 7
• Eczema coxsackium (superimposed on pre-existing eczema) 7
• Petechial/purpuric eruptions 7

Warning Signs of Severe Complications

Neurological complications can occur, particularly with Enterovirus 71 (EV-A71) infections 1, 2:

• Persistent high fever beyond 3-4 days 2
• Severe headache or stiff neck suggesting meningitis 2
• Lethargy or unusual irritability 2
• Encephalitis/meningitis 1
• Acute flaccid paralysis (AFP) 1
• Acute flaccid myelitis (AFM) 1
• Respiratory distress indicating potential neurogenic pulmonary edema 2
• Cardiopulmonary complications in severe cases 8

Late Manifestations

• Beau's lines (deep transverse nail grooves) may appear approximately 1-2 months after fever onset 1
• Periungual desquamation typically begins 2-3 weeks after onset of fever 1

Key Differential Diagnoses to Consider

HFMD must be distinguished from several conditions with overlapping features 1, 2:

• Herpes simplex virus infection - critical distinction as HSV has available antiviral treatment whereas HFMD does not 1
• Kawasaki disease - presents with diffuse erythema rather than vesicular lesions, persistent high fever, conjunctival injection, and strawberry tongue 2, 3
• Chickenpox (varicella) - lesions are widely distributed rather than concentrated on hands, feet, and mouth 2, 3
• Erythema multiforme - characterized by target lesions with central clearing on extensor surfaces 2
• Drug hypersensitivity reactions - more diffuse maculopapular rash correlating with medication initiation 1, 2

Epidemiology and Transmission

• Most cases occur in patients younger than 10 years, with peak incidence under 5 years of age 5, 8
• Transmission occurs via fecal-oral, oral-oral, and respiratory droplet contact 5
• Outbreaks typically occur in spring to fall 5
• The disease is highly contagious, with viral shedding occurring even before symptoms appear 1
• Immunocompetent adults can be affected, particularly through familial transmission from infected children 6