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Mononucleosis-Like Syndrome

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Mononucleosis-Like Syndrome, Mononucleosis Differential Diagnosis, Mononucleosis Diagnostic Approach

  • See Also
  1. Mononucleosis
  2. Heterophil Antibody Test (Monospot Test)
  3. Epstein-Barr Virus Antibody
  • Differential Diagnosis
  • Mononucleosis-Like Syndromes
  1. Presentations most common to Mononucleosis
    1. Epstein-Barr Virus (EBV) or Mononucleosis
    2. Acute Cytomegalovirus (CMV)
    3. Toxoplasmosis
    4. Streptococcal Pharyngitis
    5. Acute Retroviral Syndrome (HIV Infection)
    6. Human Herpesvirus 6
  2. See Pharyngitis
  3. See Fatigue Causes
  4. Viruses
    1. Epstein-Barr Virus (EBV): Most common cause
    2. Cytomegalovirus (CMV)
    3. Rubella
    4. Adenovirus
    5. Acute Viral Hepatitis
    6. Human Herpesvirus 6
    7. Acute Retroviral Syndrome (Acute HIV Infection)
  5. Parasites
    1. Toxoplasmosis
    2. Malaria
  6. Bacteria
    1. Syphilis
    2. Listeria
    3. Tularemia
    4. Brucellosis
    5. Lyme Disease
  7. Medications
    1. Dilantin
    2. Azulfidine
    3. Dapsone
    4. Serum-sickness type Drug Reaction
  8. Miscellaneous Causes
    1. Systemic Lupus Erythematosus
    2. Lymphoma
    3. Subacute Bacterial Endocarditis
  1. Step 1: Monospot Test (heterophile Antibody) Positive
    1. Diagnose Epstein-Barr Virus
  2. Step 2: Complete Blood Count with differential
    1. Evaluate for >10% Atypical lymphocytes
    2. Lymphocytosis >50% and Atypical lymphocytes >10% may be sufficient alone to diagnose Mononucleosis without further testing
      1. Test Sensitivity: 75%
      2. Test Specificity: 92%
  3. Step 3a: Absolute Lymphocyte Count <4000/mm3
    1. Consider alternative diagnoses
      1. Consider HIV Test if <10% Atypical lymphocyte
      2. See Acute Retroviral Syndrome for testing
  4. Step 3b: Absolute Lymphocyte Count >4000/mm3 and >10% Atypical lymphocytes
    1. Consider Viral Capsid Antigen (VCA) IgM (replaces EBV IgM)
      1. VCA IgM positive: Diagnose Epstein-Barr Virus
    2. Consider EBV IgM (if VCA IgM not available)
      1. EBV IgM Positive: Diagnose Epstein-Barr Virus
      2. EBV IgM Negative: Go to Step 4
  5. Step 4: Obtain CMV IgM
    1. CMV IgM Positive: Diagnose CMV-Induced Mononucleosis
    2. CMV IgM Negative: Evaluate for differential diagnosis
      1. Toxoplasmosis
      2. Acute Viral Hepatitis
      3. Human Herpesvirus 6
  • References
  1. Tsaparas (2000) Arch Pathol Lab Med 124:1324-30 [PubMed]
  2. Womack (2015) Am Fam Physician 91(6): 372-6 [PubMed]