What are the diagnostic and treatment approaches for infectious mononucleosis (mono)?

Diagnosis and Treatment of Infectious Mononucleosis

Diagnostic Approach

For suspected infectious mononucleosis, begin with a complete blood count with differential and a rapid heterophile antibody test (Monospot), which has 87% sensitivity and 91% specificity. 1

Initial Laboratory Testing

• Order a CBC with differential looking specifically for >40% lymphocytes and >10% atypical lymphocytes, which strongly supports the diagnosis 2, 1
• Perform a rapid heterophile antibody (Monospot) test as the initial diagnostic test, which becomes positive between the sixth and tenth day after symptom onset 2, 3
• Check liver enzymes, as elevated transaminases increase clinical suspicion when the heterophile test is negative 1

When Heterophile Test is Negative

If clinical suspicion remains high despite a negative Monospot test, order EBV-specific serologic testing including VCA IgM, VCA IgG, and EBNA antibodies. 2, 3

• VCA IgM present (with or without VCA IgG) in the absence of EBNA antibodies confirms recent primary EBV infection 2
• EBNA antibodies develop 1-2 months after primary infection; their presence indicates infection occurred more than 6 weeks prior and makes acute mononucleosis unlikely 2
• Be aware that heterophile tests have false-negative results in approximately 10% of patients, especially in children younger than 10 years and during the first week of illness 2, 1

Important Diagnostic Pitfalls

• False-positive heterophile results can occur in leukemia, pancreatic carcinoma, viral hepatitis, and CMV infection 2
• Consider alternative diagnoses when heterophile is negative: CMV infection, HIV, Toxoplasma gondii, and adenovirus 2, 3
• Over 90% of normal adults have IgG antibodies to VCA and EBNA from past infection, so only specific antibody patterns confirm acute infection 2, 3

Treatment Approach

Treatment is entirely supportive; aciclovir does not ameliorate the course of infectious mononucleosis in otherwise healthy individuals. 2, 3

Supportive Care Measures

• Provide adequate hydration, analgesics, and antipyretics for symptom control 4
• Allow activity as tolerated based on the patient's energy level rather than enforcing strict bed rest 4
• Advise patients that fatigue may persist for several months after acute infection resolves 4

Corticosteroid Use

• Reserve corticosteroids only for airway obstruction or severe pharyngeal edema causing respiratory compromise 2, 4
• Do not use corticosteroids routinely, as they provide no benefit in uncomplicated cases 4, 1

Activity Restrictions

Patients must avoid contact sports and strenuous exercise for at least 3-4 weeks from symptom onset or while splenomegaly persists to prevent splenic rupture. 4, 1

• Splenic rupture occurs in 0.1-0.5% of cases and is potentially life-threatening 5
• Use shared decision-making to determine exact timing of return to athletic activity 1

Special Populations and Complications

Immunocompromised Patients

• In immunocompromised patients with suspected primary EBV infection, reduce or discontinue immunomodulator therapy if possible 2
• Consider antiviral therapy with ganciclovir or foscarnet in severe cases, though evidence is limited 2
• These patients have increased risk of EBV-associated lymphoproliferative disease and require specialist consultation 2, 3

Monitoring for Serious Complications

• Obtain full blood count, blood film, and liver function tests in patients with possible primary EBV infection on immunosuppressive therapy 2
• Biopsy with EBER in situ hybridization is required to differentiate infectious mononucleosis from lymphoproliferative disease when clinically indicated 2

Prevention Considerations

• Avoid sharing personal items contaminated with saliva (cups, utensils, toothbrushes) 6
• Practice hand hygiene during outbreaks in close community settings 6