What is the differential diagnosis and treatment approach for a patient presenting with a sore throat, considering potential causes such as viral pharyngitis, streptococcal pharyngitis, and other bacterial infections?

Differential Diagnosis for Sore Throat

Primary Etiologic Categories

The vast majority of acute pharyngitis cases are viral in origin, with Group A Streptococcus (GAS) being the most important bacterial pathogen requiring antibiotic treatment. 1

Viral Causes (Most Common)

• Respiratory viruses including rhinovirus, coronavirus, adenovirus, influenza virus, parainfluenza virus, and respiratory syncytial virus are the most frequent causes 1, 2
• Coxsackievirus and echoviruses can cause pharyngitis, often with characteristic oral vesicles (herpangina) 1, 3
• Herpes simplex virus presents with vesicular lesions in the oropharynx 1, 3
• Epstein-Barr virus (EBV) causes infectious mononucleosis with pharyngitis accompanied by generalized lymphadenopathy and splenomegaly 1
• Cytomegalovirus can cause pharyngitis as part of systemic infection 1, 3

Bacterial Causes

Group A Streptococcus (Most Important)

• GAS is the predominant bacterial pathogen requiring antibiotic treatment to prevent complications including acute rheumatic fever and peritonsillar abscess 1
• Accounts for 15-30% of pharyngitis cases in children aged 5-15 years 2
• Peak incidence in winter and early spring in temperate climates 1, 2

Other Bacterial Pathogens

• Groups C and G β-hemolytic streptococci can cause pharyngitis similar to GAS 1
• Fusobacterium necrophorum implicated in 10-20% of endemic pharyngitis cases in adolescents and can lead to Lemierre syndrome, a rare life-threatening condition 1
• Mycoplasma pneumoniae and Chlamydia pneumoniae are uncommon causes, often associated with atypical pneumonia 1
• Neisseria gonorrhoeae in sexually active individuals with pharyngeal exposure 1
• Corynebacterium diphtheriae (rare, presents with characteristic membrane) 1, 4
• Arcanobacterium haemolyticum particularly in adolescents and young adults, often with scarlatiniform rash 1

Life-Threatening Conditions Requiring Urgent Evaluation

Patients with severe signs including difficulty swallowing, drooling, neck tenderness, or swelling must be evaluated immediately for:

• Peritonsillar abscess 1
• Parapharyngeal abscess 1
• Epiglottitis (cherry-red epiglottis suggests Haemophilus influenzae type b) 1, 4
• Lemierre syndrome (suspect in adolescents/young adults with severe pharyngitis and systemic toxicity) 1

Non-Infectious Causes

• Thyroiditis (uncommon but should be considered in appropriate clinical context) 4
• Tonsillar cancer (consider with persistent unilateral symptoms) 5

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Clinical Differentiation Strategy

Features Strongly Suggesting Viral Etiology

Do NOT test or treat with antibiotics when these features are present: 1

• Cough 1, 2
• Rhinorrhea/nasal congestion 1, 2
• Conjunctivitis 1, 2
• Hoarseness 1, 2
• Diarrhea 1, 3
• Oropharyngeal ulcers or vesicles 1, 2

Features Suggesting Bacterial (GAS) Infection

Use Modified Centor Criteria to determine testing threshold: 1

• Fever by history 1, 2
• Tonsillar exudates 1, 2
• Tender anterior cervical adenopathy 1, 2
• Absence of cough 1, 2

Additional suspicious features include:

• Persistent fever, rigors, night sweats 1
• Scarlatiniform rash 1, 2
• Palatal petechiae 1, 2
• Swollen tonsils 1

Critical Limitation

Clinical features alone cannot reliably differentiate bacterial from viral pharyngitis—even experienced physicians achieve only 35-50% accuracy when all clinical features suggest streptococcal infection. 1, 2

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Diagnostic Algorithm

Step 1: Initial Clinical Assessment

If obvious viral features present (cough, rhinorrhea, conjunctivitis, oral ulcers): No testing needed, provide symptomatic treatment only 1, 2

Step 2: Apply Modified Centor Criteria

Patients meeting <3 Centor criteria: Do not test—probability of GAS is too low 1

Patients meeting ≥3 Centor criteria: Proceed to microbiological testing 1

Step 3: Microbiological Confirmation

Rapid Antigen Detection Test (RADT):

• Specificity 90-96%, sensitivity 79-88% 2
• Positive RADT is diagnostic—no backup culture needed 1, 2
• In children and adolescents, negative RADT MUST be confirmed with throat culture due to low sensitivity and higher risk of rheumatic fever 1, 2

In adults:

• Backup throat culture for negative RADT is optional given low incidence of GAS and exceptionally low risk of rheumatic fever 1
• Physicians seeking maximal sensitivity may continue backup cultures 1

Step 4: Red Flag Assessment

Immediately evaluate for life-threatening conditions if:

• Difficulty swallowing or drooling 1
• Neck tenderness or swelling 1
• Severe pharyngitis in adolescent/young adult (consider Lemierre syndrome) 1
• Stridor or respiratory distress (epiglottitis) 6

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Treatment Approach

For Confirmed GAS Pharyngitis

Penicillin V remains first-line treatment due to proven efficacy, narrow spectrum, safety, low cost, and absence of resistance 2, 7

• Penicillin V: 250 mg three times daily for 10 days 8, 7
• Alternative: Amoxicillin (especially in younger children who prefer once-daily dosing) 2
• For penicillin allergy: First-generation cephalosporins or macrolides 1
• 10-day duration is mandatory for bacterial eradication and rheumatic fever prevention 1, 2

Caution: Avoid amoxicillin in adolescents/young adults with possible EBV due to severe rash risk 2

For Viral Pharyngitis

Antibiotics provide NO benefit and should NOT be prescribed 1

Symptomatic management:

• Analgesics: aspirin, acetaminophen, NSAIDs, or throat lozenges 1, 2
• Salt water gargles 1, 2
• Adequate hydration 2
• Reassurance that typical course is <1 week 1

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Common Pitfalls to Avoid

• Prescribing antibiotics based on clinical impression alone without microbiological confirmation leads to massive antibiotic overuse—over 60% of adults with sore throat receive unnecessary antibiotics 1
• Failing to recognize GAS carriers with concurrent viral pharyngitis—positive throat culture doesn't always mean GAS is the cause 2
• Not backing up negative RADT with culture in children/adolescents misses true GAS cases at higher risk for rheumatic fever 1, 2
• Routine testing for Fusobacterium necrophorum is not recommended, but maintain high suspicion for Lemierre syndrome in severely ill adolescents/young adults 1
• Treating chronic GAS carriers with antibiotics—they are unlikely to spread infection and at minimal risk for complications 1
• Relying on laboratory values (WBC, differential) alone—these have poor sensitivity and specificity for distinguishing bacterial from viral pharyngitis 2