What are the primary differential diagnoses for a patient with suspected strep throat?

Differential Diagnoses for Strep Throat

When evaluating a patient with suspected strep throat, the primary differential diagnoses include viral pharyngitis (which accounts for the majority of cases), other bacterial causes, and infectious mononucleosis, with clinical features being insufficient to distinguish between them without laboratory confirmation. 1

Viral Causes (Most Common)

Viruses cause the majority of acute pharyngitis cases and do not require antibiotic therapy 1:

• Respiratory viruses are the most frequent culprits, including adenovirus, influenza virus, parainfluenza virus, rhinovirus, and respiratory syncytial virus 1
• Enteroviruses such as coxsackievirus and echoviruses commonly cause pharyngitis 1
• Herpes simplex virus can present with pharyngitis 1
• Epstein-Barr virus (EBV) causes infectious mononucleosis, typically presenting with pharyngitis accompanied by generalized lymphadenopathy, splenomegaly, posterior cervical adenopathy, and significant fatigue 1, 2
• Other systemic viral infections including cytomegalovirus, rubella virus, and measles virus may be associated with pharyngitis 1

Critical clinical clue: The presence of cough, rhinorrhea, conjunctivitis, hoarseness, coryza, anterior stomatitis, discrete ulcerative lesions, viral exanthem, or diarrhea strongly suggests a viral rather than streptococcal etiology 1, 2

Bacterial Causes

Group A β-hemolytic Streptococcus (Streptococcus pyogenes) is the most common bacterial cause and the only one that definitively requires antibiotic therapy to prevent acute rheumatic fever and suppurative complications 1, 3:

• Accounts for 15-30% of pharyngitis cases in children aged 5-15 years and 5-15% in adults 3, 4
• Primarily occurs in children between 5-15 years of age, typically in winter and early spring 1

Other bacterial causes (rare and generally do not require routine antibiotic therapy) 1:

• Groups C and G β-hemolytic streptococci 1
• Neisseria gonorrhoeae - consider in sexually active individuals with pharyngitis 1
• Corynebacterium diphtheriae - extremely rare but serious 1
• Arcanobacterium haemolyticum - particularly in teenagers and young adults, often associated with a scarlet fever-like rash 1
• Fusobacterium necrophorum - implicated in approximately 10-20% of endemic pharyngitis cases in adolescents and can lead to Lemierre syndrome 1
• Mycoplasma pneumoniae and Chlamydophila pneumoniae - uncommon causes 1
• Mixed anaerobic infections (Vincent's angina), Francisella tularensis, and Yersinia enterocolitica - rare causes 1

Clinical Differentiation Strategy

The modified Centor criteria help stratify risk but cannot definitively diagnose strep throat 1, 2, 5:

• 1 point each for: fever by history, tonsillar exudates, tender anterior cervical adenopathy, and absence of cough 1, 2
• Score interpretation: <3 points = low probability (no testing needed); 3-4 points = moderate probability (perform RADT) 2, 5
• Important limitation: Even with all clinical features present, streptococcal pharyngitis is confirmed only 35-50% of the time 1

Key physical examination findings suggestive of Group A Streptococcus include sudden onset sore throat, fever, tonsillopharyngeal erythema with or without exudates, tender enlarged anterior cervical lymph nodes, beefy red swollen uvula, palatal petechiae, and scarlatiniform rash 1, 3

Diagnostic Approach

Laboratory confirmation is essential because clinical features alone cannot reliably distinguish between streptococcal and viral pharyngitis 1:

• Rapid Antigen Detection Test (RADT) is the initial test of choice with high specificity 1, 3
• Positive RADT is diagnostic and does not require backup culture 1
• Negative RADT in children and adolescents requires backup throat culture due to lower sensitivity and higher risk of rheumatic fever 1, 2
• Negative RADT in adults generally does not require backup culture given low incidence and exceptionally low risk of acute rheumatic fever 1

Critical Pitfalls to Avoid

• Never prescribe amoxicillin or ampicillin if EBV/infectious mononucleosis is suspected due to risk of severe maculopapular rash 2
• Do not perform testing in patients with obvious viral features (cough, rhinorrhea, conjunctivitis, hoarseness) 2
• Remain vigilant for Lemierre syndrome in adolescents and young adults with severe pharyngitis, as urgent diagnosis and treatment is necessary 1
• Avoid routine antibiotic use without confirmed Group A Streptococcus, as this contributes to antibiotic resistance and unnecessary adverse effects 1