Infectious Mononucleosis and Cough
Cough is not a typical or characteristic symptom of infectious mononucleosis, and if significant cough is present, you should actively consider alternative or concurrent diagnoses. 1
Classic Presentation of Infectious Mononucleosis
The hallmark clinical features of infectious mononucleosis are:
- The classic triad: fever, tonsillar pharyngitis, and cervical lymphadenopathy 2, 3
- Fatigue: profound but typically resolves within three months 2, 4
- Periorbital/palpebral edema: bilateral, occurs in one-third of patients 2
- Splenomegaly: approximately 50% of cases 2, 3
- Hepatomegaly: approximately 10% of cases 2
- Skin rash: erythematous and maculopapular in 10-45% of cases 2
Why Cough Is Not Part of the Syndrome
Infectious mononucleosis is distinct from the viral upper respiratory tract infections that commonly cause acute cough, according to the American Thoracic Society 1. The common cold syndrome—caused by rhinoviruses, coronaviruses, parainfluenza, RSV, adenoviruses, and enteroviruses—is the single most common cause of acute cough 5. These are fundamentally different pathogens from EBV, which causes mononucleosis through saliva transmission and primarily affects the oropharynx and lymphoid tissue 2, 6.
Post-infectious cough can persist for 3-8 weeks following respiratory viral infections due to epithelial disruption and airway inflammation 5, 7. However, this is not a typical sequela of mononucleosis, as noted by the American College of Chest Physicians 1.
Clinical Approach When Cough Is Present
If a patient with suspected infectious mononucleosis presents with significant cough, you must consider alternative or concurrent diagnoses, as recommended by the American College of Chest Physicians 1. Specifically:
- Rule out concurrent respiratory infection: Common cold viruses, Mycoplasma pneumoniae, Chlamydophila pneumoniae, or Bordetella pertussis can coexist 7
- Consider bacterial sinusitis: Viral URTIs frequently produce rhinosinusitis that can cause cough through postnasal drip 5
- Evaluate for pertussis: Suspect when cough is accompanied by paroxysms, post-tussive vomiting, or inspiratory whooping 7
Common Pitfall to Avoid
Do not assume that cough is simply part of the mononucleosis presentation. The presence of significant cough should prompt you to broaden your differential diagnosis beyond EBV infection alone 1. Children and young adults can have back-to-back infections or coinfections, particularly during winter months, which can complicate the clinical picture 7.
Diagnostic Confirmation
When the clinical picture is atypical (such as prominent cough with minimal pharyngitis), confirm the diagnosis with:
- Heterophile antibody test (Monospot): most widely used, though false negatives occur early in infection 2, 3
- EBV-specific serology: IgM antibody to viral capsid antigen (VCA) is the most valuable finding during acute primary EBV infection 3, 4
- Peripheral blood smear: atypical lymphocytes >10% of total lymphocyte count with lymphocytosis >50% 2, 3