What are the differential diagnoses and treatment options for a patient presenting with symptoms suggestive of strep pharyngitis?

Differential Diagnoses for Strep Pharyngitis

When evaluating a patient with suspected strep pharyngitis, you must systematically differentiate between viral and bacterial causes, as clinical features alone cannot reliably distinguish them—microbiological confirmation is essential before prescribing antibiotics. 1, 2

Viral Causes (Most Common)

Viruses account for the majority of acute pharyngitis cases, and these do not require antibiotic therapy 1, 3:

• Respiratory viruses: Adenovirus, parainfluenza virus, rhinovirus, respiratory syncytial virus 1
• Enterovirus: Coxsackievirus and ECHO viruses 1
• Herpes simplex virus 1
• Epstein-Barr virus: Often presents with generalized lymphadenopathy, splenomegaly, and atypical lymphocytes 1, 2
• Systemic viral infections: Measles, cytomegalovirus, rubella, influenza 1

Clinical Features Suggesting Viral Etiology:

• Presence of cough, rhinorrhea/nasal congestion 2, 4
• Hoarseness 2
• Conjunctivitis 2
• Discrete ulcerative stomatitis or oral ulcers 2
• Diarrhea 3
• Viral exanthem 3

Bacterial Causes

Group A β-Hemolytic Streptococcus (Most Important)

Group A Streptococcus (Streptococcus pyogenes) is the only commonly occurring bacterial cause that definitively requires antibiotic treatment to prevent acute rheumatic fever and suppurative complications 1:

• Accounts for 15-30% of pharyngitis cases in children aged 5-15 years 2
• Only 10% of adults with sore throat have GAS pharyngitis 4
• Most common in winter and early spring 2

Clinical Features Suggesting GAS Pharyngitis:

• Sudden onset of sore throat 2, 5
• Fever (temperature >100.4°F/38°C) 6, 4
• Tonsillopharyngeal erythema with or without exudates 2, 4
• Tender and enlarged anterior cervical lymph nodes 2, 6, 4
• Palatal petechiae 2
• Scarlatiniform rash 3
• Absence of cough (cough suggests viral etiology) 2, 6, 4

Other Bacterial Causes (Rare)

These organisms rarely cause pharyngitis but should be considered in specific clinical contexts 1:

• Groups C and G β-hemolytic streptococci 1, 7
• Corynebacterium diphtheriae (diphtheria—extremely rare) 1
• Arcanobacterium haemolyticum: Associated with scarlet fever-like rash, particularly in teenagers and young adults; rarely recognized in the United States 1
• Neisseria gonorrhoeae: Consider in sexually active individuals with pharyngitis 1
• Francisella tularensis (tularemia—rare) 1
• Yersinia enterocolitica (rare) 1
• Mixed anaerobic infections (Vincent's angina—rare) 1

Atypical Bacterial Causes

• Mycoplasma pneumoniae: Uncommon cause of acute pharyngitis 1
• Chlamydia pneumoniae: Uncommon cause of acute pharyngitis 1

Diagnostic Approach Algorithm

Step 1: Clinical Assessment Using Modified Centor Criteria 2, 3, 6

Assign one point for each:

• Fever (temperature >100.4°F/38°C)
• Tonsillar exudates
• Tender anterior cervical adenopathy
• Absence of cough

Score interpretation:

• <3 points: Low probability of GAS—no testing or treatment needed 2, 3
• 3-4 points: Moderate probability—proceed to microbiological testing 2, 3

Step 2: Microbiological Confirmation 1, 2, 3

Do not prescribe antibiotics based on clinical features alone 1, 2:

• Rapid Antigen Detection Test (RADT): Initial test of choice 2, 3

  • Positive RADT = diagnostic for GAS pharyngitis 2
  • Negative RADT in children/adolescents = perform backup throat culture 2, 3, 4
  • Negative RADT in adults = no further testing needed (lower prevalence) 4

• Throat culture: Gold standard, but results take 1-2 days 2, 5

Treatment Based on Diagnosis

For Confirmed GAS Pharyngitis

First-line treatment 1, 3, 6, 4:

• Oral penicillin V: 250 mg 2-3 times daily (children) or 250 mg 4 times daily or 500 mg twice daily (adolescents/adults) for 10 days 7, 6
• Intramuscular benzathine penicillin G: Single dose of 600,000 units (<60 lb) or 1,200,000 units (>60 lb) 7, 6
• Amoxicillin: Equally effective and more palatable alternative 6

For penicillin-allergic patients (non-anaphylactic) 7, 6, 4:

• Cephalexin: 20 mg/kg per dose twice daily (maximum 500 mg per dose) for 10 days 7
• First-generation cephalosporins for 10 days 3, 6

For immediate hypersensitivity to penicillin 7, 8:

• Azithromycin: 12 mg/kg once daily (maximum 500 mg) for 5 days 7, 8
• Note: Significant resistance to azithromycin exists in some U.S. regions 4
• Erythromycin: Alternative macrolide option 6

For Viral Pharyngitis

No antibiotic therapy indicated 1, 3:

• Symptomatic treatment only: antipyretics, analgesics 3
• Steroids are not recommended 4

Critical Pitfalls to Avoid

• Do not treat based on clinical impression alone—60% of adults with sore throat receive unnecessary antibiotics 4
• Do not use laboratory values (TLC/DLC) alone to differentiate bacterial from viral pharyngitis—poor sensitivity and specificity 2
• Do not assume all positive throat cultures require treatment—patient may be a GAS carrier with concurrent viral pharyngitis 1, 2
• Do not routinely test asymptomatic household contacts or perform post-treatment testing in asymptomatic patients 1
• Recognize treatment failure vs. carrier state: For recurrent episodes, consider clindamycin or amoxicillin/clavulanate, which achieve higher pharyngeal eradication rates 1, 7
• Complete the full 10-day course of oral antibiotics even if symptoms resolve earlier 7

Special Considerations

For recurrent GAS pharyngitis 1:

• Retreat with same antimicrobial agent initially
• If compliance questionable, use intramuscular benzathine penicillin G
• For multiple recurrences, consider clindamycin or amoxicillin/clavulanate

Tonsillectomy thresholds 4:

• 7 episodes in 1 year, OR
• 5 episodes per year for 2 consecutive years, OR
• 3 episodes per year for 3 consecutive years