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:

• 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

Differential diagnosis

Stomatitis must be differentiated from its different kinds and from various other diseases that can mimic stomatitis or have accompanying features involving other organs:

• Tumors of the tongue
  • Squamous cell carcinoma
  • Leukoplakia
  • Melanoma
  • Torus Palatinus
• Autoimmune diseases
  • Behcet's syndrome
  • Crohn's disease
• Agranulocytosis
• Fordyce's spots
• Drug induced
• Burning mouth syndrome
• Syphilis
• Coxsackie virus accompanies involvement of the hands and the mouth
• HIV
• VZV or Chicken pox

Disease	Presentation	Risk Factors	Diagnosis	Affected Organ Systems	Important features	Picture
Diseases predominantly affecting the oral cavity
Coxsackie virus	Fever Sores in the mouth Rash with blisters Aches	Pregnancy immunodeficiency	History and Physical exam Throat swabs Swabs from the lesion Tzanck test	Oral cavity Skin	Symptomatic treatment
Chicken pox	Conjunctival symptoms Catarrhal symptoms Characteristic spots on the trunk appearing in two or three waves Itching	Pregnancy Premature infants born to susceptible mothers All infants born at less than 28 weeks gestation or who weigh ≤1000 grams Immunocompromised	History and physical exam PCR to detect VZV in skin lesions (vesicles, scabs, maculopapular lesions)	Oral cavity Skin	Sodium bicarbonate in baths or antihistamines for itching Paracetamol (acetaminophen) for fever Prednisolone is contraindicated
Measles	Fever Rash Cough Coryza (runny nose) Conjunctivitis (pink eye) Malaise Koplick spots in mouth	Unvaccinated individuals Crowded and/or unsanitary conditions Traveling to less developed and developing countries Immunocompromized Winter and spring seasons Born after 1956 and never fully vaccinated Health care workers	History and examination PCR for Measles-specific IgM antibody PCR for Measles RNA	Oral cavity Skin Respiratory tract Eyes Throat	Caused by Morbillivirus Primary site of infection is the respiratory epithelium of the nasopharynx Transmitted in respiratory secretions, via aerosol droplets containing virus particles