What is the likely diagnosis and treatment for a young patient with an inflamed and tender upper cervical lymph node, sore throat, and chills, without evidence of bacterial strep infection or cough?

Likely Diagnosis: Infectious Mononucleosis (EBV)

This clinical presentation—inflamed rubbery tender upper cervical lymph nodes, sore throat, chills, absence of cough, and negative strep testing—is highly suggestive of infectious mononucleosis caused by Epstein-Barr virus (EBV), not bacterial pharyngitis. 1

Key Diagnostic Features

The constellation of findings points away from Group A Streptococcus and toward viral etiology, specifically EBV:

• Rubbery lymphadenopathy: This texture is characteristic of EBV-related lymph node enlargement, distinct from the firm tender nodes of bacterial infection 1
• Negative strep workup: Excludes the most common bacterial cause requiring specific treatment 2
• Absence of cough: While this increases the probability of bacterial pharyngitis when present with other Centor criteria, the negative strep test overrides this consideration 2, 1
• Systemic symptoms (chills): Suggests more generalized viral illness rather than localized bacterial infection 2

Why EBV/Infectious Mononucleosis is Most Likely

The CDC and American College of Physicians specifically identify EBV as a frequent cause of acute pharyngitis that is "often accompanied by the other clinical features of infectious mononucleosis (e.g., generalized lymphadenopathy and splenomegaly)" 2. The guidelines emphasize suspecting EBV when you find:

• Generalized or prominent lymphadenopathy (especially posterior cervical nodes, though anterior can occur) 1
• Significant fatigue 1
• Sore throat without bacterial confirmation 2
• Absence of cough/rhinorrhea 1

Young patients are the typical demographic for infectious mononucleosis 2.

Diagnostic Workup

Order the following tests to confirm EBV:

• Monospot (heterophile antibody) test: Rapid screening test for infectious mononucleosis 1
• Complete blood count with differential: Look for atypical lymphocytosis (>10% atypical lymphocytes) and possible thrombocytopenia 1
• Liver function tests: Transaminitis occurs in most EBV cases 1
• EBV-specific serology (VCA-IgM, VCA-IgG, EBNA): If monospot is negative but clinical suspicion remains high, particularly in young children where heterophile antibodies may be absent 1

Examine for splenomegaly on physical exam, as this occurs in approximately 50% of infectious mononucleosis cases 2, 1.

Critical Treatment Considerations

DO NOT prescribe amoxicillin or ampicillin if EBV is suspected. The CDC explicitly warns that these antibiotics cause a severe maculopapular rash in 80-100% of patients with infectious mononucleosis 1. This is a pathognomonic reaction and a common pitfall.

Management Approach:

• Supportive care only: Analgesics (acetaminophen or NSAIDs) for throat pain and fever, adequate hydration, and rest 1, 3
• No antibiotics indicated: This is a viral illness that does not respond to antibacterial therapy 3
• Activity restriction: Avoid contact sports and heavy lifting for 3-4 weeks due to splenomegaly and risk of splenic rupture 1
• Symptom monitoring: Fatigue may persist for weeks to months 1

Alternative Considerations (Less Likely)

If EBV testing is negative, consider:

• Other viral pharyngitis: Adenovirus, influenza, parainfluenza, or other respiratory viruses can cause similar presentations 2
• Group C or G streptococci: Can cause pharyngitis with lymphadenopathy but are not routinely tested and do not require treatment to prevent rheumatic fever 2
• Cytomegalovirus: Can mimic EBV but is less common 2

Red Flags Requiring Urgent Evaluation

Return immediately or refer if the patient develops:

• Difficulty swallowing or drooling (suggests peritonsillar abscess or airway compromise) 3
• Severe left upper quadrant pain (splenic rupture) 1
• Respiratory distress or stridor (airway obstruction from tonsillar hypertrophy) 3
• Persistent high fever >4 days despite supportive care 3
• Severe neck swelling or tenderness (Lemierre syndrome, though rare) 3, 4

Why Not Bacterial Pharyngitis?

The negative strep workup definitively excludes Group A Streptococcus, which is the only bacterial pharyngitis requiring specific diagnosis and treatment to prevent rheumatic fever 2, 5. The IDSA guidelines are clear that when strep testing is negative, antibiotics should not be prescribed, as viral causes are far more common (70-85% of adult pharyngitis cases) 1, 3. The rubbery quality of the lymph nodes and systemic presentation further support viral rather than bacterial etiology 1, 6.