Hand-foot-and-mouth disease differential diagnosis

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] Associate Editor(s)-in-Chief: Aarti Narayan, M.B.B.S [2]; Yamuna Kondapally, M.B.B.S[3]

Overview

Hand-foot-and-mouth disease should be differentiated from other conditions that cause maculopapular or vesicular rash which includes herpes simplex virus infections, herpangina, chicken pox and measles.

Differentiating Hand-foot-and-mouth disease from other Diseases

Hand-foot-and-mouth disease should be differentiated from other conditions that cause maculopapular or vesicular rash include:

Infection	Presentation
Herpes simplex virus stomatitis	Associated with high grade fever, acute gingivitis and oral ulcerations The vesicles are small, grouped together and on an erythematous base. Absence of rash on palms and soles. A Tzanck test shows multinucleated giant cells and direct fluorescent antigens test can also help to differentiate hand-foot-and-mouth disease from herpes simplex virus infection.
Herpangina	Raised white cell count but <15,000 cells/mL and serum creatine <1.5 times baseline
Bacteremia and sepsis	Leucocytosis >15,000 cells/mL OR serum creatinene level >1.5 times baseline or abdominal tenderness and serum albumin < 3 g/dL
Chickenpox	Hypotension or shock, ileus, megacolon, leucocytosis >20,000 cells/mL OR leucopenia <2,000, lactate >2.2 mmol/L, delirium, fever ≥ 38.5 °C, organ failure
Measles	Raised white cell count but <15,000 cells/mL and serum creatine <1.5 times baseline
Pharyngitis	Raised white cell count but <15,000 cells/mL and serum creatine <1.5 times baseline
Stevens-Johnson syndrome Erythema multiforme	Raised white cell count but <15,000 cells/mL and serum creatine <1.5 times baseline
Henoch-Schönlein purpura	Raised white cell count but <15,000 cells/mL and serum creatine <1.5 times baseline
Kawasaki disease	Raised white cell count but <15,000 cells/mL and serum creatine <1.5 times baseline
Behcet's disease	Raised white cell count but <15,000 cells/mL and serum creatine <1.5 times baseline
Pemphigus vulgaris	Raised white cell count but <15,000 cells/mL and serum creatine <1.5 times baseline

• Herpes simplex virus infections
  • Herpes stomatitis
    • Associated with high grade fever, acute gingivitis and oral ulcerations.
    • The vesicles are small, grouped together and on an erythematous base.
    • Absence of rash on palms and soles.
    • A Tzanck test shows multinucleated giant cells and direct fluorescent antigens test can also help to differentiate hand-foot-and-mouth disease from herpes simplex virus infection.
• Herpangina
• Bacteremia and Sepsis
• Chicken pox
• Measles
• Pharyngitis
• Aphthous ulcers/ Gingivitis
  • The ulcers are on the mucosal surface of the mouth and is not associated with fever, malaise or rash.
• Stevens-Johnson syndrome/ Erythema multiforme
• Henoch-Schönlein purpura
• Kawasaki disease
• Other rare conditions in children:
  • Behcet's disease
  • Pemphigus vulgaris