What is the differential diagnosis for white tonsillar exudate, taking into account age, immune status, and symptom chronology?

Differential Diagnosis for White Tonsillar Exudate

White tonsillar exudate is most commonly caused by Group A Streptococcus (GAS) in children aged 5–15 years and by viral pathogens (especially adenovirus and Epstein-Barr virus) across all age groups, but microbiological confirmation is mandatory before initiating antibiotics because clinical features alone cannot reliably distinguish bacterial from viral etiologies. 1, 2, 3

Primary Differential Diagnoses

Bacterial Causes

Group A β-Hemolytic Streptococcus (Streptococcus pyogenes)

• Accounts for 15–30% of acute pharyngitis with exudate in children aged 5–15 years and only 5–15% in adults 1, 2, 4
• Classic presentation: sudden-onset severe sore throat, fever ≥101°F (38.3°C), tonsillopharyngeal erythema with patchy discrete exudates, tender enlarged anterior cervical lymph nodes, and absence of viral features (no cough, rhinorrhea, hoarseness, or conjunctivitis) 1, 2, 3
• May present with palatal petechiae, headache, nausea, vomiting, or abdominal pain 2, 3
• Scarlatiniform rash indicates scarlet fever, a GAS complication 2, 3

Groups C and G β-Hemolytic Streptococci

• Can cause exudative pharyngitis with clinical features similar to GAS, though evidence suggests they may present with milder symptoms 1
• Severe or recurrent pharyngitis due to Group C streptococci has been documented, with cases showing exudative tonsillitis and anterior cervical adenopathy 1
• Uncommon complications include reactive arthritis, subdural empyema, and acute glomerulonephritis, though causal relationships are not clearly established 1

Arcanobacterium haemolyticum

• Causes pharyngitis with scarlatiniform rash in adolescents and young adults, typically presenting with fever and systemic symptoms 3

Mycoplasma pneumoniae and Chlamydia pneumoniae

• Associated with non-streptococcal acute pharyngitis in selected studies, though their role in exudative tonsillitis is less clear 1
• Mycoplasma pneumoniae was implicated in 5% of febrile exudative tonsillitis cases in one pediatric study 5

Viral Causes

Adenovirus

• The most frequently recorded viral agent in febrile exudative tonsillitis, accounting for 19% of cases in one pediatric study 5
• Viral infections overall were associated with 42% of febrile exudative tonsillitis cases 5
• Viruses cause 70–95% of all tonsillitis cases 4

Epstein-Barr Virus (Infectious Mononucleosis)

• Presents with severe pharyngitis, tonsillar exudate, white patches, generalized lymphadenopathy, and splenomegaly 2, 3
• Can cause exudative tonsillitis that mimics bacterial infection 5
• Tonsillar tissue may be the primary site of EBV infection 6
• Critical consideration: 30–100% of patients with EBV who receive amoxicillin or ampicillin develop a non-pruritic morbilliform rash 3

Other Respiratory Viruses

• Parainfluenza, influenza A, respiratory syncytial virus, rhinovirus, coronavirus, herpes simplex virus, and enteroviruses can all cause pharyngitis with exudate 2, 3, 5
• Presence of cough, rhinorrhea, hoarseness, or conjunctivitis strongly favors viral etiology 1, 2, 3

Herpes Simplex Virus (HSV)

• Can cause severe necrotizing tonsillitis in immunocompromised patients 7
• Should be considered when antibiotic therapy fails within 24–72 hours in immunosuppressed individuals 7
• Confirmed by polymerase chain reaction; requires early antiviral treatment 7

Coxsackievirus and ECHO Viruses

• Enteroviruses that can cause acute viral pharyngitis 3
• Discrete ulcerative stomatitis or oral ulcers are characteristic of viral causes and argue against bacterial infection 1, 2, 3

Fungal Causes (Immunocompromised Patients)

Invasive Fungal Sinusitis with Pharyngeal Extension

• Observed in immunocompromised patients including those with diabetes, leukemia, solid malignancies with febrile neutropenia, high-dose steroid therapy, or severe T-cell immunodeficiency 1
• Clinical signs include fever, headache, epistaxis, mental status changes, and insensate nasal ulcers 1
• Requires aggressive debridement and systemic antifungal therapy 1

Age-Specific Considerations

Children < 3 Years

• GAS pharyngitis and acute rheumatic fever are uncommon in this age group 1, 2, 3
• Viral etiologies predominate, with viral tonsillitis most common in children younger than 3 years 5
• Routine GAS testing is not indicated unless specific risk factors exist (e.g., older sibling with confirmed GAS) 2, 3

Children 5–15 Years

• Highest prevalence of GAS pharyngitis (15–30% of cases) 1, 2, 4
• GAS tonsillitis most common in children 6 years or older 5
• Two-step testing (RADT followed by backup throat culture if negative) is mandatory due to 10–20% false-negative rate of RADT and risk of acute rheumatic fever 2, 3, 8

Adults

• GAS accounts for only 5–15% of acute pharyngitis cases 2, 3, 4
• Viral etiologies predominate (70–95% of cases) 4
• Negative RADT alone is sufficient to rule out GAS; backup culture not required due to extremely low risk of acute rheumatic fever 2, 3, 8

Immune Status Considerations

Immunocompetent Patients

• Standard differential includes GAS, other streptococci, and common viral pathogens 1, 2, 3
• Clinical features overlap extensively between bacterial and viral causes 1, 3, 5

Immunocompromised Patients

• Consider HSV-1 necrotizing tonsillitis, especially if no improvement with antibiotics within 24–72 hours 7
• Invasive fungal infections should be considered in patients with diabetes, malignancy, neutropenia, high-dose steroids, or T-cell immunodeficiency 1
• Early recognition and targeted therapy (antiviral or antifungal) are essential 1, 7

Diagnostic Algorithm

Step 1: Clinical Assessment

• Determine presence of viral features (cough, rhinorrhea, hoarseness, conjunctivitis, oral ulcers, diarrhea) – if present, testing for GAS is not recommended 1, 2, 3
• Assess for bacterial features: sudden-onset sore throat, high fever, tonsillar exudates, tender anterior cervical lymphadenopathy, absence of viral symptoms 1, 2, 3

Step 2: Microbiological Confirmation

• Mandatory before prescribing antibiotics – clinical features alone cannot reliably differentiate bacterial from viral causes, even for experienced clinicians 1, 2, 3
• Perform rapid antigen detection test (RADT) for GAS 1, 2, 3
• Positive RADT is diagnostic (specificity ≥95%); initiate treatment 2, 3, 8
• Negative RADT in children/adolescents: must obtain backup throat culture (sensitivity 80–90%, misses 10–20% of infections) 2, 3, 8
• Negative RADT in adults: no backup culture needed (low prevalence, minimal rheumatic fever risk) 2, 3, 8

Step 3: Consider Alternative Diagnoses

• If monospot or heterophile antibody test is positive, diagnose EBV infectious mononucleosis 2, 3
• If immunocompromised and antibiotics fail within 24–72 hours, obtain HSV PCR from throat swab 7
• If severely immunocompromised with systemic signs, consider invasive fungal infection 1

Common Pitfalls to Avoid

• Do not treat based on clinical appearance alone – exudates and white patches occur with both viral and bacterial infections; only 35–50% of clinically suspected cases are culture-positive 2, 3
• Do not assume all exudative pharyngitis is bacterial – viruses (especially adenovirus and EBV) frequently produce exudative tonsillitis 3, 5
• Do not skip backup throat culture in children with negative RADT – this misses 10–20% of GAS infections and increases rheumatic fever risk 2, 3, 8
• Do not prescribe amoxicillin to adolescents/young adults without ruling out EBV – 30–100% will develop severe rash 3
• Do not test or treat asymptomatic household contacts – up to one-third are carriers; prophylaxis does not reduce infection rates 2, 3, 8
• Recognize that positive tests may reflect asymptomatic carriage – 10–15% of the population carries GAS asymptomatically 3
• In immunocompromised patients, consider HSV if antibiotics fail – early antiviral therapy is critical 7