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