Should I test a patient with elevated monocytes, elevated erythrocyte sedimentation rate (ESR), and elevated C-reactive protein (CRP) for mononucleosis?

Testing for Mononucleosis in a Patient with Elevated Monocytes, ESR, and CRP

Testing for infectious mononucleosis is recommended for patients presenting with elevated monocytes, ESR, and CRP, as these laboratory findings are consistent with several inflammatory conditions including mononucleosis.

Laboratory Findings and Diagnostic Approach

When evaluating a patient with elevated monocytes, ESR, and CRP, the following diagnostic approach is warranted:

Initial Assessment

• Elevated inflammatory markers (ESR and CRP) indicate ongoing inflammation but are nonspecific 1
• Monocytosis can occur in various inflammatory and infectious conditions 2
• The combination of these findings warrants investigation for several potential causes:
  • Infectious etiologies (including mononucleosis)
  • Inflammatory disorders
  • Autoimmune conditions

Specific Testing for Mononucleosis

1. Complete blood count with differential:

   • Look for >40% lymphocytes and >10% atypical lymphocytes which strongly suggest mononucleosis 3
   • Assess for other abnormalities including anemia or thrombocytopenia

2. Heterophile antibody test (Monospot):

   • Cost-effective first-line test with 87% sensitivity and 91% specificity 3
   • Can be false negative in the first week of illness or in young children
   • Rapid results make this preferable as an initial test

3. Liver function tests:

   • Elevated liver enzymes increase clinical suspicion for mononucleosis when heterophile antibody is negative 3
   • Mild to moderate elevations in transaminases occur in 40-60% of patients with inflammatory conditions 1

4. EBV-specific serologic testing:

   • More sensitive and specific than heterophile antibody testing but more expensive and time-consuming 3
   • Consider when clinical suspicion is high but heterophile test is negative

Differential Diagnosis Considerations

The combination of elevated monocytes, ESR, and CRP is seen in multiple conditions that should be considered:

1. Infectious causes:

   • Mononucleosis (EBV, CMV)
   • Bacterial infections
   • Tuberculosis 1
   • Giardiasis 1

2. Inflammatory disorders:

   • Kawasaki disease 1
   • Inflammatory bowel disease 1
   • Autoimmune enteropathy 1

3. Rheumatologic conditions:

   • Undifferentiated peripheral inflammatory arthritis 1
   • IL-1 mediated autoinflammatory diseases 1

Clinical Pearls and Pitfalls

• Pearl: In viral infections like mononucleosis, SAA (serum amyloid A) may be more elevated than CRP, while in bacterial infections both tend to rise simultaneously 4
• Pitfall: Relying solely on ESR or CRP for diagnosis is not recommended as they are nonspecific markers 1
• Pitfall: A negative heterophile antibody test early in the course of illness does not rule out mononucleosis 3
• Pearl: Monocyte function may actually be impaired in infectious mononucleosis despite elevated counts 5

Conclusion

The presence of elevated monocytes, ESR, and CRP warrants testing for infectious mononucleosis, particularly when accompanied by clinical features such as fever, pharyngitis, and lymphadenopathy. A cost-effective approach begins with CBC with differential and heterophile antibody testing, with EBV-specific serology reserved for cases with high clinical suspicion but negative initial testing.