What are the causes of white tonsillar exudate when streptococcal pharyngitis tests are negative?

White Tonsillar Exudate with Negative Strep Test: Differential Diagnosis

When streptococcal testing is negative, white tonsillar exudate is most commonly caused by viral pharyngitis, particularly Epstein-Barr virus (infectious mononucleosis), adenovirus, or other respiratory viruses—not bacterial infection. 1

Primary Viral Causes

Viral infections account for the vast majority of pharyngitis cases with negative strep tests, and exudates do not reliably distinguish bacterial from viral etiologies. 2, 3

Most Common Viral Pathogens:

• Epstein-Barr virus (infectious mononucleosis) – presents with severe pharyngitis, prominent tonsillar exudate, white patches, posterior cervical lymphadenopathy, and often splenomegaly. 4, 3

• Adenovirus – frequently causes exudative pharyngitis with conjunctivitis (pharyngoconjunctival fever), distinguishing it from streptococcal infection. 1, 3

• Rhinovirus – the most frequent cause of acute pharyngitis overall, though exudates are less common. 3

• Coronavirus, parainfluenza, respiratory syncytial virus, influenza – all can produce pharyngeal inflammation with variable exudate. 3

• Herpes simplex virus, coxsackievirus, echoviruses – may cause pharyngitis with characteristic vesicular or ulcerative lesions rather than classic exudate. 1

Key Clinical Distinguishing Features

The presence of viral symptoms strongly indicates viral rather than bacterial pharyngitis, even when exudates are present. 1

Features Suggesting Viral Etiology:

• Cough – the single most important distinguishing feature pointing away from streptococcal infection. 2, 3, 5

• Coryza (rhinorrhea) – strongly suggests viral cause. 1, 5

• Hoarseness – indicates viral involvement of the larynx. 1

• Conjunctivitis – particularly with adenovirus. 1

• Diarrhea – more common with viral infections. 1, 5

• Characteristic viral exanthems or enanthems – such as vesicles or ulcers. 1

Critical Diagnostic Pitfall

White patches and tonsillar exudate occur with both viral and bacterial infections and cannot be used to make treatment decisions without microbiological confirmation. 2, 3 The American College of Physicians explicitly warns against prescribing antibiotics based on appearance alone, as exudates overlap too broadly between bacterial and viral causes. 2

Streptococcal Carriage vs. Active Infection

A positive strep test in the setting of viral symptoms may reflect asymptomatic streptococcal carriage (15% of school-age children) with concurrent viral pharyngitis, not true streptococcal infection. 1 However, a negative test reliably excludes active streptococcal infection in adults (specificity ≥95%). 2

Recommended Management Approach

For Adults:

• A negative rapid antigen detection test (RADT) alone is sufficient to rule out streptococcal pharyngitis—no backup throat culture is needed. 2, 3

• Withhold all antibiotics and provide only symptomatic therapy with ibuprofen or acetaminophen. 2, 3

For Children and Adolescents:

• A negative RADT must be confirmed with throat culture because RADT sensitivity is only 80-90% in pediatric patients. 4

• Withhold antibiotics until culture results are available (1-2 days); treatment within 9 days of symptom onset still prevents rheumatic fever. 4

Symptomatic Treatment:

• Ibuprofen or acetaminophen for pain and fever control. 2, 3

• Throat lozenges for comfort. 2

• Reassurance that viral pharyngitis typically resolves in less than 1 week. 3

When to Consider Alternative Diagnoses

If symptoms persist beyond 3-4 days or worsen significantly, consider suppurative complications or alternative diagnoses. 2

Red Flags Requiring Urgent Reassessment:

• Severe unilateral throat pain with trismus – suggests peritonsillar abscess. 3, 6

• Neck swelling or tenderness with pulmonary symptoms – raises concern for Lemierre syndrome. 3, 6

• Difficulty swallowing or airway compromise – requires immediate evaluation for epiglottitis or retropharyngeal abscess. 3, 6

• Posterior cervical lymphadenopathy – warrants consideration of infectious mononucleosis if throat culture is negative. 4

Antibiotic Stewardship

Approximately 70% of patients with sore throat receive unnecessary antibiotic prescriptions, while only 20-30% of pediatric patients and 5-10% of adult patients actually have streptococcal pharyngitis. 2 Withholding antibiotics when testing is negative is a key quality indicator and prevents antimicrobial resistance, adverse effects, and microbiota disruption. 2, 4