What are the initial blood work and treatment approaches for a young adult suspected of having mononucleosis, presenting with fever, sore throat, and fatigue?

Initial Blood Work and Treatment for Suspected Mononucleosis

Diagnostic Laboratory Testing

Order a heterophile antibody test (Monospot) as the initial diagnostic test for suspected infectious mononucleosis in young adults presenting with fever, sore throat, and fatigue. 1

First-Line Testing

• Heterophile antibody test (Monospot) is the most widely used initial test with 87% sensitivity and 91% specificity, though it typically becomes positive only between the sixth and tenth day after symptom onset 1
• Complete blood count (CBC) with differential should be obtained, looking specifically for:
  • Lymphocytosis ≥50% of white blood cell differential 1
  • Atypical lymphocytosis ≥10% of total lymphocyte count 1
  • Note: Infectious mononucleosis is unlikely if the absolute lymphocyte count is less than 4,000/mm³ 2

When to Order EBV-Specific Serologic Testing

If the heterophile test is negative but clinical suspicion remains high, order EBV-specific antibody testing including VCA IgM, VCA IgG, and EBNA antibodies 1

• Acute primary EBV infection is confirmed by the presence of VCA IgM (with or without VCA IgG) in the absence of EBNA antibodies 1
• Past infection (more than 6 weeks prior) is indicated by the presence of EBNA antibodies 1
• EBV-specific testing is particularly important for children younger than 10 years, patients in the first week of illness, and those with atypical presentations 3

Common Pitfalls in Testing

• False-negative heterophile results occur in approximately 25% of patients during the first week of illness and are common in children younger than 10 years 1, 2
• False-positive heterophile results may occur in patients with leukemia, pancreatic carcinoma, viral hepatitis, and CMV infection 1
• Over 90% of normal adults have IgG antibodies to VCA and EBNA from past infection, so only the specific antibody pattern confirms acute infection 1

Additional Laboratory Tests

• Liver function tests (ALT, AST) should be considered, as hepatomegaly occurs in approximately 10% of cases and transaminase elevations are common 4
• Consider testing for alternative diagnoses if heterophile and EBV testing are negative: CMV infection, HIV infection, Toxoplasma gondii infection, adenovirus infection, and streptococcal pharyngitis 1, 3

Initial Treatment Approach

Treatment is primarily supportive, as antiviral agents have no proven role in immunocompetent patients with infectious mononucleosis. 1

Supportive Care Measures

• Activity modification: Patients should reduce activity and rest as tolerated, avoiding contact sports or strenuous exercise for 8 weeks or while splenomegaly is present 4, 5
• Symptomatic relief: Provide adequate hydration, analgesics, and antipyretics as needed 5
• Avoid enforced bed rest: The patient's energy level should guide activity rather than strict bed rest 5

When NOT to Use Specific Therapies

• Acyclovir therapy does not ameliorate the course of infectious mononucleosis in otherwise healthy individuals and is not recommended 1
• Corticosteroids should be reserved for specific complications only, such as respiratory compromise from airway obstruction or severe pharyngeal edema 1, 5
• Antihistamines are not recommended for routine treatment 5

Critical Safety Considerations

• Splenic rupture occurs in 0.1 to 0.5% of patients and is the most feared complication, making activity restriction essential 4
• Airway obstruction is the most common cause of hospitalization, particularly in children 2
• Avoid ampicillin or amoxicillin if considering antibiotics for possible streptococcal superinfection, as these cause a maculopapular rash in up to 90% of patients with infectious mononucleosis 4

Special Population Considerations

In immunocompromised patients with suspected primary EBV infection, reduce or discontinue immunomodulator therapy if possible and consider specialist consultation 1

• Antiviral therapy with ganciclovir or foscarnet may be considered in severe cases despite lack of supporting evidence 1
• These patients have increased risk of lymphoproliferative disorders and hemophagocytic syndrome requiring careful monitoring 1