Infectious Mononucleosis in Adolescents and Young Adults
Clinical Presentation
Infectious mononucleosis presents with the classic triad of fever (often reaching 40°C), tonsillar pharyngitis, and cervical lymphadenopathy, most commonly affecting patients aged 15-24 years. 1, 2, 3
Core Clinical Features
- Fever: High-grade, may reach 40°C 2
- Pharyngitis: Tonsillar inflammation with or without exudates 3, 4
- Lymphadenopathy: Posterior cervical nodes are characteristically enlarged 3, 4
- Fatigue: Profound but typically resolves within 3 months 3
Additional Common Findings
- Periorbital/palpebral edema: Bilateral, occurs in one-third of patients 3
- Splenomegaly: Present in approximately 50% of cases 3, 4
- Hepatomegaly: Occurs in approximately 10% of cases 3
- Rash: Maculopapular, erythematous, widely scattered; occurs in 10-45% of cases 2, 3
Clinical Presentation Patterns
The presentation typically fits one of three forms: pharyngeal (predominant sore throat), glandular (predominant lymphadenopathy), or febrile (predominant fever), which helps anticipate the clinical course and differential diagnosis 4
Diagnostic Work-Up
Initial Laboratory Testing
Order a complete blood count with differential and a rapid heterophile antibody (Monospot) test as first-line diagnostic studies. 1
Complete Blood Count Findings
- Lymphocytosis: Absolute lymphocytosis with lymphocytes comprising ≥50% of the white blood cell differential 1, 3
- Atypical lymphocytes: Constitute >10% of total lymphocyte count 1, 3
- Liver function tests: Elevated AST, ALT, and bilirubin in approximately 90% of cases 1, 4
Heterophile Antibody Testing
- Sensitivity: 87% 1
- Specificity: 91% 1
- Timing: Typically becomes positive between days 6-10 after symptom onset 1
- False-negative rate: Approximately 10% overall, particularly common in children <10 years and during the first week of illness 1
Critical Timing Consideration
A single negative heterophile test obtained in the first week should not exclude mononucleosis; repeat testing after 7-10 days or proceed directly to EBV-specific serology if clinical suspicion remains high. 1
EBV-Specific Serologic Testing
When clinical suspicion persists despite a negative heterophile test, obtain EBV serology immediately, ordering three antibodies together: IgM to viral capsid antigen (VCA), IgG to VCA, and antibodies to Epstein-Barr nuclear antigen (EBNA). 1, 5
Interpretation of EBV Serology
- Acute primary infection: VCA IgM present (with or without VCA IgG) AND EBNA antibodies absent 1
- Past infection (>6 weeks): EBNA antibodies present, effectively ruling out acute mononucleosis 1
- Important caveat: Over 90% of normal adults have IgG antibodies to VCA and EBNA from past infection; 5-10% of EBV-infected patients fail to develop EBNA antibodies 1
Pitfalls in Heterophile Testing
- False-positives: May occur in leukemia, pancreatic carcinoma, viral hepatitis, and CMV infection 1
- False-negatives: Common early in infection, in children <10 years, and occur in ~10% of adolescents overall 1
Differential Diagnosis Testing
When heterophile and EBV testing are negative or equivocal, test for alternative causes of mononucleosis-like illness. 1
Consider testing for:
- Cytomegalovirus (CMV) infection 1, 6
- HIV infection (particularly important in adolescents) 1
- Toxoplasma gondii infection 1
- Adenovirus infection 1
- Streptococcal pharyngitis (may coexist with EBV-IM) 1
Management Recommendations
Supportive Care
Treatment is primarily supportive with activity restriction; avoid amoxicillin and other aminopenicillins as they precipitate severe rash in 80-100% of patients with active EBV infection. 1, 3
Activity Restrictions
- Counsel patients to restrict vigorous physical activity and contact sports for 8 weeks from symptom onset or while splenomegaly persists 1, 3
- Rationale: Spontaneous splenic rupture occurs in 0.1-0.5% of cases and is potentially life-threatening 1, 3
- Bed rest as tolerated is recommended 3
Symptomatic Management
- Adequate analgesia for sore throat and fever 4
- Maintain hydration 3
- Antipyretics for fever management 2
Corticosteroid Use
Corticosteroids are indicated for upper airway obstruction and may be helpful for neurologic, hematologic, or cardiac complications, but should NOT be used routinely. 3, 4
- Reserve corticosteroids for specific complications only 1
- Important caveat: High erythrocyte sedimentation rate may indicate bacterial superinfection, which could be exacerbated by corticosteroid administration 7
Antiviral Therapy
Acyclovir does not ameliorate the course of infectious mononucleosis in otherwise healthy individuals and is not recommended. 1
- Antiviral agents (acyclovir, ganciclovir, foscarnet) have no proven role in established disease in immunocompetent patients 1
- In immunocompromised patients with severe primary EBV infection, antiviral therapy with ganciclovir or foscarnet may be considered despite lack of supporting evidence 1
Special Population: Immunocompromised Patients
In immunocompromised patients with suspected primary EBV infection, reduce or discontinue immunomodulator therapy if possible and seek specialist consultation. 1
- Increased risk of severe disease, lymphoproliferative disorders, and hemophagocytic syndrome 1
- Primary EBV infection poses particular threat in patients on thiopurines, with reports of fatal infectious mononucleosis-associated lymphoproliferative disorders 1
- Specialist consultation should be sought for suspected lymphoproliferative disease 1
Complications Requiring Medical Attention
Life-Threatening Complications
- Splenic rupture: Most feared complication, occurs in 0.1-0.5% of cases 1, 3
- Upper airway obstruction: Requires corticosteroid therapy 4
- Neurologic complications: Headache, rare severe manifestations including encephalitis 2, 4
Other Complications
- Hematologic: Anemia, thrombocytopenia, neutropenia in severe cases 2
- Peritonsillar abscess: Rare, may indicate bacterial superinfection 7
- Splenic infarction: Rare, may remain asymptomatic 7
- Interstitial pneumonitis: Can develop in some cases 2
- Chronic fatigue syndrome: Infectious mononucleosis is a risk factor 3
Warning Signs
- Persistent high fever unresponsive to antipyretics 2
- Severe abdominal pain (consider splenic rupture) 3
- Respiratory distress (consider airway obstruction) 4
Infection Control and Contagiousness
The main contagious period extends approximately 7-10 days from symptom onset; patients should avoid close contact, sharing personal items, and practice strict hand hygiene during this period. 5
- Avoid sharing items contaminated with saliva: towels, pillows, eating utensils, drinking containers 5
- Hand hygiene with soap and water is essential 5
- Healthcare workers and childcare providers should avoid close contact for at least 7-10 days from symptom onset 5
- Some experts suggest considering patients potentially contagious for 10-14 days due to variable infectivity between individuals 5