In a healthy 21‑year‑old man with three days of fever, marked bilateral cervical lymphadenopathy, exudative tonsillitis, headache and dyspnea, should lymphadenitis be considered in the differential diagnosis and what is the appropriate evaluation?

Evaluation of Acute Pharyngotonsillitis with Massive Lymphadenopathy in a Young Adult

Yes, lymphadenitis should absolutely be considered in the differential diagnosis, but the clinical presentation—exudative tonsillitis with massive bilateral cervical lymphadenopathy in a 21-year-old—most strongly suggests infectious mononucleosis (Epstein-Barr virus), which requires specific evaluation to distinguish from Group A streptococcal pharyngitis and to identify potential complications.

Primary Differential Diagnosis

The clinical picture of fever, exudative pharyngitis, "very large bilateral" cervical lymphadenopathy, and headache in a young adult creates a narrow differential:

Most Likely: Infectious Mononucleosis

• EBV is a frequent cause of acute pharyngitis accompanied by generalized lymphadenopathy and splenomegaly in this age group 1
• The combination of exudative tonsillitis with massive bilateral cervical adenopathy is characteristic of infectious mononucleosis 1
• EBV-related exudative tonsillitis accounts for 19% of all viral pharyngeal infections and frequently mimics bacterial etiology 2

Important Alternative: Group A Streptococcal Pharyngitis

• GAS pharyngitis presents with sudden-onset sore throat, fever, tonsillopharyngeal exudates, and tender enlarged anterior cervical lymph nodes (lymphadenitis) 1
• However, the "very large bilateral" lymphadenopathy described is more consistent with EBV than typical GAS lymphadenitis 1
• GAS can cause suppurative complications including cervical lymphadenitis, peritonsillar abscess, and mastoiditis 1

Less Common Considerations

• Groups C and G β-hemolytic streptococci can cause exudative tonsillitis and anterior cervical adenopathy 1
• Adenovirus, parainfluenza, and other respiratory viruses frequently cause acute pharyngitis but typically without massive adenopathy 1

Immediate Evaluation Required

Clinical Assessment

Look specifically for these distinguishing features:

• Presence of splenomegaly strongly suggests infectious mononucleosis over bacterial pharyngitis 1
• Posterior cervical or generalized lymphadenopathy favors EBV; anterior cervical adenopathy alone is more consistent with GAS 1, 3
• Absence of cough, coryza, conjunctivitis, hoarseness, or diarrhea makes bacterial or EBV etiology more likely than other viral causes 1
• Assess for signs of airway compromise given the dyspnea and massive tonsillar enlargement (3-4+) 1

Laboratory Testing

Mandatory initial tests:

• Rapid antigen detection test (RADT) for Group A streptococcus 1
• Throat culture if RADT is negative, as RADT sensitivity is only 70-90% 1
• Complete blood count with differential: look for lymphocytosis with atypical lymphocytes (suggests EBV) versus leukocytosis with neutrophilia (suggests bacterial infection) 1, 4
• Heterophile antibody test (Monospot) if clinical features suggest infectious mononucleosis 5

Additional tests if Monospot is negative but EBV suspected:

• EBV-specific serology (VCA-IgM, VCA-IgG, EBNA) as heterophile antibodies may be negative early in illness 5

Imaging Considerations

Imaging is NOT routinely indicated for uncomplicated pharyngitis but should be obtained if:

• Signs of deep space infection or peritonsillar abscess develop (unilateral tonsillar bulging, trismus, muffled voice) 1
• Persistent or worsening dyspnea suggesting airway compromise 1
• Lymph nodes remain enlarged >2 weeks or have concerning features (fixed, firm, >1.5 cm) 1, 6

Management Algorithm

If GAS Pharyngitis Confirmed:

• Penicillin V 500 mg twice daily for 10 days OR amoxicillin 1000 mg once daily for 10 days 1
• Benzathine penicillin G 1.2 million units IM single dose is equally effective 1
• Treatment prevents suppurative complications including cervical lymphadenitis 1

If Infectious Mononucleosis Confirmed:

• Supportive care only; antibiotics are NOT indicated for viral pharyngitis 1
• Avoid amoxicillin/ampicillin as these cause a characteristic maculopapular rash in 80-100% of EBV patients (general medical knowledge)
• Counsel on spleen precautions: avoid contact sports for 3-4 weeks due to splenic rupture risk (general medical knowledge)
• Monitor airway closely given massive tonsillar enlargement; consider corticosteroids if airway compromise develops (general medical knowledge)

If Both Tests Negative:

• Do NOT prescribe antibiotics empirically without clear bacterial evidence 1, 6
• Reassess in 2 weeks; if lymphadenopathy persists or worsens, proceed to further workup 1, 6

Critical Pitfalls to Avoid

Never prescribe multiple courses of antibiotics without confirmed bacterial etiology, as this significantly delays diagnosis of malignancy or other serious conditions 1, 6, 4

Do not assume this is simple bacterial lymphadenitis without testing for GAS and EBV—the massive bilateral nature of the adenopathy is atypical for uncomplicated bacterial infection 1, 3

Recognize that bacterial superinfection can occur with EBV—Staphylococcus aureus and Haemophilus species are frequently isolated in EBV pharyngitis 2—but treat only if there is clear evidence of bacterial co-infection 1

Monitor for peritonsillar abscess development, which occurs mainly in young adults and is polymicrobial with GAS as the main organism 1

If lymphadenopathy has not completely resolved at 2-week follow-up, proceed to definitive workup including CT imaging, as partial resolution may represent infection in an underlying malignancy 1, 6