What is the workup and management of infectious mononucleosis?

Workup and Management of Infectious Mononucleosis

The diagnostic workup for infectious mononucleosis should begin with a heterophile antibody test (Monospot), with EBV-specific serologic testing recommended when clinical suspicion remains high despite a negative heterophile test. Management is primarily supportive with adequate hydration, rest, and antipyretics, while avoiding contact sports for at least 8 weeks or while splenomegaly persists. 1, 2

Clinical Presentation

• The classic triad of infectious mononucleosis includes fever, tonsillar pharyngitis, and lymphadenopathy (particularly posterior cervical) 3
• Fatigue may be profound and can persist for several months after the acute infection has resolved 4
• Periorbital/palpebral edema (typically bilateral) occurs in approximately one-third of patients 3
• Splenomegaly occurs in approximately 50% of cases and hepatomegaly in about 10% 3
• Skin rash (erythematous and maculopapular) occurs in 10-45% of cases, with a significantly higher incidence in patients treated with ampicillin or amoxicillin 3
• Oral manifestations include erythema and diffuse injection of oral and pharyngeal mucosae, cracking lips, and "strawberry tongue" 5

Diagnostic Workup

Laboratory Testing

• Heterophile antibody test (Monospot) is the recommended initial test, typically becoming positive between the 6th and 10th day after symptom onset 1
• Complete blood count (CBC) with differential - look for:
  • Leukocytosis with lymphocytes making up at least 50% of the white blood cell count
  • Atypical lymphocytes constituting >10% of the total lymphocyte count 3
• Liver function tests - transaminase elevations are common 2

EBV-Specific Serologic Testing

• Recommended when clinical suspicion remains high despite a negative heterophile test 1
• Should include:
  • IgM antibodies to viral capsid antigen (VCA)
  • IgG antibodies to VCA
  • Antibodies to Epstein-Barr nuclear antigen (EBNA) 1
• Interpretation:
  • VCA IgM (with or without VCA IgG) in the absence of EBNA antibodies indicates recent primary EBV infection
  • Presence of EBNA antibodies indicates infection more than 6 weeks prior 1

Differential Diagnosis

• Consider other causes of mononucleosis-like illness when heterophile tests are negative:
  • Cytomegalovirus (CMV) infection
  • HIV infection
  • Toxoplasma gondii infection
  • Adenovirus infection 1

Management

General Supportive Care

• Adequate hydration and rest as tolerated (bed rest should not be enforced; patient's energy level should guide activity) 4
• Antipyretics for fever control 5
• Analgesics for pain management 4

Specific Symptom Management

• For painful oral lesions:
  • Topical analgesics such as benzydamine hydrochloride rinses
  • Warm saline mouthwashes to cleanse the oral cavity
  • Topical anesthetics and antiseptic oral rinses to reduce bacterial colonization 5

Medications to Avoid

• Aciclovir therapy does not ameliorate the course of infectious mononucleosis in otherwise healthy individuals 6, 5
• Corticosteroids are not recommended for routine treatment and should be reserved for:
  • Impending airway obstruction
  • Severe pharyngeal edema
  • Significant hematological complications 5, 7
• Prolonged steroid therapy for uncomplicated infectious mononucleosis may lead to severe complications including sepsis 7
• Antihistamines are not recommended for routine treatment 4

Activity Restrictions

• Patients should be withdrawn from contact or collision sports for at least 8 weeks or while splenomegaly is still present 2, 3
• This precaution is due to the risk of splenic rupture, which occurs in 0.1-0.5% of patients and is potentially life-threatening 3
• Strenuous exercise should also be avoided during this period 3

Special Considerations for Immunocompromised Patients

• Immunomodulator therapy should be reduced or discontinued if possible in patients with primary EBV infection 6
• In severe primary EBV infection in immunocompromised patients, consider antiviral therapy with ganciclovir or foscarnet despite limited supporting evidence 6, 5
• These agents are more potent than aciclovir for replicative EBV infection but have higher toxicity 5
• Immunocompromised patients have an increased risk of lymphoproliferative disorders and require careful monitoring 6, 5

Common Pitfalls and Caveats

• False-positive heterophile antibody results may occur in patients with leukemia, pancreatic carcinoma, viral hepatitis, and CMV infection 1
• False-negative heterophile results are common early in the course of infection and in young children 1
• Over 90% of normal adults have IgG antibodies to VCA and EBNA antigens, reflecting past infection 1
• Approximately 5-10% of patients who have been infected with EBV fail to develop antibodies to EBNA antigen 1
• Splenic rupture typically occurs within the first month of symptom onset 2