How is mononucleosis (infectious mononucleosis) presenting with pharyngitis diagnosed and managed?

Diagnosis and Management of Infectious Mononucleosis with Pharyngitis

Infectious mononucleosis presenting with pharyngitis requires laboratory confirmation with complete blood count showing >40% lymphocytes with >10% atypical forms plus a rapid heterophile antibody test, followed by supportive care only—avoid antibiotics and routine corticosteroids. 1

Diagnostic Approach

Clinical Recognition and Differentiation

The pharyngitis of infectious mononucleosis occurs in 70-92% of cases and can be easily mistaken for streptococcal pharyngitis, but key distinguishing features include: 2

• More generalized lymphadenopathy (not just anterior cervical nodes) 2
• Significant fatigue as a prominent symptom 2
• Absence of cough and rhinorrhea (unlike viral upper respiratory infections) 2, 3
• Absence of exudates on pharyngeal examination (unlike bacterial pharyngitis) 2
• Oral manifestations include diffuse pharyngeal erythema, cracking lips, and "strawberry tongue" 2

Laboratory Confirmation Algorithm

Step 1: Initial Testing 1

• Complete blood count with differential looking for:
  • Greater than 40% lymphocytes 1
  • Greater than 10% atypical lymphocytes 1, 3
• Rapid heterophile antibody test (Monospot):
  • Sensitivity 87%, specificity 91% 1
  • Critical pitfall: Can be false-negative in the first week of illness and in children under 5 years 1

Step 2: If Heterophile Test is Negative but Clinical Suspicion Remains High 1

• Check liver enzymes—elevated transaminases increase suspicion for infectious mononucleosis 1
• Consider EBV viral capsid antigen IgM antibody testing (more sensitive and specific but more expensive and slower) 4, 1

Common Diagnostic Pitfalls to Avoid

• Do not rely on clinical presentation alone—the overlap between bacterial and viral pharyngitis is too broad for accurate clinical diagnosis 5, 3
• Do not prescribe antibiotics empirically without ruling out infectious mononucleosis, as this leads to unnecessary treatment 2
• Do not assume a negative heterophile test rules out mononucleosis in the first week of illness—repeat testing or use EBV-specific serology 1
• Recognize that patients may be GAS carriers experiencing concurrent viral mononucleosis 6, 3

Management

Supportive Care Only

Treatment is entirely supportive—routine use of antivirals and corticosteroids is not recommended. 1

• Manage symptoms with rest and hydration 4, 1
• For painful oral lesions, consider topical analgesics such as benzydamine hydrochloride rinses 2
• Warm saline mouthwashes to cleanse the oral cavity 2
• Topical anesthetics and antiseptic oral rinses to reduce bacterial colonization 2

Activity Restrictions

• Patients must not participate in athletic activity for 3 weeks from symptom onset due to risk of splenic rupture (the most common potentially fatal complication) 4, 1
• Use shared decision-making to determine exact timing of return to activity after the 3-week period 1

When to Suspect Complications

• Monitor for severe disease involving pulmonary, ophthalmologic, neurologic, or hematologic systems 4
• Immunosuppressed populations are at higher risk of severe disease and significant morbidity 1
• Neurologic complications such as Guillain-Barré syndrome can occur, though rarely 7

Special Consideration for Concurrent Bacterial Infection

If laboratory testing confirms both infectious mononucleosis and Group A Streptococcus (which can occur in carriers), treat the streptococcal infection appropriately while managing mononucleosis supportively. 6, 3