What is the differential diagnosis and treatment approach for pharyngitis?

Differential Diagnosis for Pharyngitis

Primary Etiologic Categories

Viral pathogens cause the majority of acute pharyngitis cases and do not require antibiotic therapy, while Group A Streptococcus (GAS) is the only common bacterial cause that definitively requires treatment to prevent acute rheumatic fever and suppurative complications. 1, 2

Viral Causes (Most Common)

• Respiratory viruses account for the largest proportion of pharyngitis cases, including adenovirus, parainfluenza virus, rhinovirus, and respiratory syncytial virus 2, 3
• Enteroviruses (coxsackievirus and ECHO viruses) are common viral pathogens 2
• Herpes simplex virus can cause pharyngitis 2
• Epstein-Barr virus presents distinctively with generalized lymphadenopathy, splenomegaly, and atypical lymphocytes on peripheral smear 4, 2
• Influenza virus should be considered during seasonal outbreaks 3

Clinical features suggesting viral etiology include conjunctivitis, coryza (rhinorrhea/nasal congestion), cough, hoarseness, discrete ulcerative stomatitis, diarrhea, and viral exanthem 4, 2

Bacterial Causes

• Group A Streptococcus (Streptococcus pyogenes) accounts for 15-30% of pharyngitis cases in children aged 5-15 years and 5-15% in adults, with peak incidence in winter and early spring 4, 2, 5
• Groups C and G Streptococci can cause severe or recurrent pharyngitis with exudative tonsillitis and anterior cervical adenopathy, though antibiotic benefit is unproven 3
• Rare bacterial pathogens include Neisseria gonorrhoeae, Fusobacterium necrophorum, and Corynebacterium diphtheriae in specific clinical contexts 1, 3
• Chlamydophila pneumoniae and Mycoplasma pneumoniae have been detected in pharyngitis patients, though routine diagnostic methods are limited 6

Clinical features suggesting GAS pharyngitis include sudden onset of sore throat, fever (temperature >100.4°F/38°C), tonsillopharyngeal erythema with or without exudates, tender and enlarged anterior cervical lymph nodes, palatal petechiae, scarlatiniform rash, and notably the absence of cough 4, 2, 7, 5

Diagnostic Approach Algorithm

Step 1: Clinical Assessment Using Modified Centor Criteria

Assign one point for each of the following 4, 2:

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

Interpretation:

• Score <3 points: Low probability of GAS—testing not recommended 4
• Score 3-4 points: Moderate probability—proceed to microbiological testing 2

Step 2: Microbiological Testing

• Rapid Antigen Detection Test (RADT) is the initial test of choice 4, 2
• Positive RADT is diagnostic for GAS pharyngitis and requires treatment 4, 2
• Negative RADT in children and adolescents requires backup throat culture due to lower sensitivity 4
• Negative RADT in adults does not require backup culture due to lower disease prevalence and complication risk 4

Critical pitfall: The signs and symptoms of bacterial and viral pharyngitis overlap so broadly that accurate diagnosis on clinical grounds alone is impossible—microbiological testing is essential 1, 3

Special Clinical Scenarios

Chronic GAS Carriers

• Up to 20% of young adults may be chronic pharyngeal carriers of GAS during winter/spring months 3
• These patients experience repeated viral pharyngitis episodes that test positive for strep but have no active immunologic response 3
• Carriers are at very low risk for complications and do not require antimicrobial therapy 3, 7
• Differentiation from true GAS infection may be difficult when multiple episodes occur over months or years 1

Red Flags Requiring Urgent Evaluation

• Peritonsillar abscess: Unilateral throat pain with trismus, uvular deviation, and "hot potato" voice—particularly in male patients aged 21-40 who smoke 3
• Airway compromise: Stridor or inability to swallow secretions 3
• Progressive symptoms despite treatment 3

Treatment Recommendations

For Confirmed GAS Pharyngitis

Penicillin remains the treatment of choice due to proven efficacy, safety, narrow spectrum, and low cost. 4, 2

First-line options:

• Oral penicillin V for 10 days 4, 2, 8
• Oral amoxicillin for 10 days (equally effective and more palatable) 7, 5
• Intramuscular benzathine penicillin G (single dose) for patients unlikely to complete oral therapy 4, 2

For penicillin-allergic patients without immediate hypersensitivity:

• First-generation cephalosporins (e.g., cephalexin) 4, 2

For immediate hypersensitivity to β-lactams:

• Erythromycin 4, 2
• Azithromycin 2
• Clindamycin 5

Treatment duration: At least 10 days for any GAS infection to prevent acute rheumatic fever 8

For Viral Pharyngitis

• No antibiotic therapy is indicated 2, 3
• Symptomatic treatment only: Antipyretics (NSAIDs are more effective than acetaminophen), cough suppressants, expectorants, first-generation antihistamines, and decongestants 4, 5
• Medicated throat lozenges used every two hours are effective 5

For Recurrent Episodes

• Consider retreatment with the same antimicrobial agent 4
• If compliance with oral therapy is questionable, use intramuscular benzathine penicillin G 1, 4
• For multiple recurrences over months/years (suggesting carrier state with repeated viral infections), consider clindamycin or amoxicillin/clavulanate for high pharyngeal eradication rates 1, 4

Key Clinical Pitfalls to Avoid

• Do not diagnose GAS pharyngitis on clinical grounds alone—the overlap with viral pharyngitis is too extensive 1, 3
• Do not test patients with clear viral features (cough, rhinorrhea, conjunctivitis, diarrhea) 4
• Do not routinely test or treat asymptomatic household contacts 1
• Do not perform repeated testing after successful treatment completion unless new symptoms develop 1
• Do not treat chronic GAS carriers who are experiencing viral pharyngitis episodes 3, 7