Acute Pharyngitis: Differential Diagnosis and Diagnostic Approaches

Pharyngitis, commonly known as a sore throat, is characterized by inflammation of the mucous membranes lining the oropharynx. While the majority of cases stem from viral or bacterial infections, a range of other factors, including environmental irritants and underlying medical conditions, can also trigger this condition. This article delves into the differential diagnosis of acute pharyngitis, providing a comprehensive overview for healthcare professionals to accurately evaluate and manage patients presenting with this common complaint.

Etiology of Acute Pharyngitis

The causes of acute pharyngitis are diverse, broadly categorized into infectious and non-infectious etiologies. Identifying the underlying cause is crucial for appropriate management and to rule out more serious conditions.

Infectious Causes:

• Viral Infections (50-80% of cases): Numerous viruses can lead to pharyngitis. Common culprits include rhinoviruses, adenoviruses, influenza viruses, coronaviruses, and parainfluenza viruses. Less frequent viral pathogens are herpes simplex virus (HSV), Epstein-Barr virus (EBV), human immunodeficiency virus (HIV), and coxsackieviruses. Viral pharyngitis often accompanies other upper respiratory symptoms like cough and rhinorrhea.

• Bacterial Infections (5-36% of cases): Group A beta-hemolytic streptococcus (Streptococcus pyogenes) is the most significant bacterial cause due to its potential complications, such as rheumatic fever. Other bacterial agents include Group B and C streptococci, Mycoplasma pneumoniae, Chlamydia pneumoniae, Arcanobacterium haemolyticum, Fusobacterium necrophorum, Neisseria gonorrhoeae, Corynebacterium diphtheriae, and Haemophilus influenzae.

• Fungal Infections: Candida species can cause pharyngitis, particularly in immunocompromised individuals or those using inhaled corticosteroids.

Non-Infectious Causes:

• Allergies: Allergic rhinitis can lead to postnasal drip, irritating the pharynx and causing pharyngitis.
• Environmental Irritants: Exposure to smoke, pollutants, dry air, and chemical fumes can irritate the throat.
• Trauma: Direct injury to the pharynx, such as from intubation or foreign body ingestion.
• Gastroesophageal Reflux Disease (GERD): Stomach acid refluxing into the esophagus can irritate the pharynx.
• Neoplasms: Though less common, pharyngeal cancers can present with persistent sore throat.
• Systemic Diseases: Kawasaki disease and other systemic inflammatory conditions can manifest with pharyngitis.

Differential Diagnosis of Acute Pharyngitis

The differential diagnosis of acute pharyngitis is extensive and requires careful consideration of patient history, physical examination findings, and, when necessary, targeted investigations. It is essential to differentiate benign, self-limiting conditions from those requiring specific treatment or indicating a more serious underlying pathology.

Key Considerations in Differential Diagnosis:

1. Viral vs. Bacterial Pharyngitis: Distinguishing between viral and bacterial causes is paramount, especially to guide antibiotic use. Viral pharyngitis is more likely associated with cough, rhinorrhea, conjunctivitis, and generalized malaise. Bacterial pharyngitis, particularly Group A streptococcal (GAS) pharyngitis, often presents with abrupt onset, fever, tonsillar exudates, and tender anterior cervical lymphadenopathy, typically lacking cough. Clinical scoring systems like the Centor criteria (or modified McIsaac score) can aid in risk stratification for GAS pharyngitis.

   Centor Criteria for GAS Pharyngitis:

   • Tonsillar exudates
   • Tender anterior cervical lymph nodes
   • History of fever
   • Absence of cough

   Each criterion scores one point. Scores guide management: low scores suggest viral etiology, intermediate scores warrant rapid antigen detection testing (RADT), and high scores might indicate empiric antibiotic therapy or RADT.

2. Infectious Mononucleosis (EBV): Pharyngitis due to EBV infection, or infectious mononucleosis, can mimic streptococcal pharyngitis but often presents with more pronounced fatigue, posterior cervical lymphadenopathy (in addition to anterior), and potential hepatosplenomegaly. A heterophile antibody test (Monospot) or EBV-specific serology can confirm the diagnosis. Amoxicillin should be avoided in suspected mononucleosis as it can trigger a characteristic morbilliform rash.

3. Peritonsillar Abscess and Retropharyngeal Abscess: These deep neck infections are critical to rule out in patients with severe sore throat, especially if unilateral. Peritonsillar abscess typically presents with severe sore throat, muffled voice (“hot potato voice”), uvular deviation, and trismus. Retropharyngeal abscess may cause neck stiffness, pain with neck extension, and potentially airway compromise. Imaging, such as CT scan, may be necessary for diagnosis.

4. Epiglottitis: Though less common due to Haemophilus influenzae type b (Hib) vaccination, epiglottitis remains a life-threatening condition, particularly in children. It presents with abrupt onset of severe sore throat, dysphagia, drooling, stridor, and potential respiratory distress. Direct visualization of the epiglottis (often in the operating room with airway management readily available) is crucial for diagnosis, but lateral neck X-rays may show the “thumbprint sign” of a swollen epiglottis.

5. Lemierre’s Syndrome (Fusobacterium necrophorum): This rare but serious complication of bacterial pharyngitis involves septic thrombophlebitis of the internal jugular vein. It should be considered in adolescents and young adults with persistent pharyngitis, fever, and septic emboli, often manifesting as pulmonary infiltrates.

6. Gonococcal Pharyngitis (Neisseria gonorrhoeae): In sexually active individuals, particularly those reporting orogenital contact, Neisseria gonorrhoeae should be considered. Symptoms can range from mild sore throat to exudative pharyngitis. Diagnosis requires specific cultures (Thayer-Martin agar).

7. Herpetic Pharyngitis (HSV): Herpes simplex virus can cause pharyngitis, often characterized by vesicular lesions or ulcers in the oral cavity and pharynx, sometimes extending beyond the tonsils.

8. Diphtheria (Corynebacterium diphtheriae): While rare in vaccinated populations, diphtheria should be considered in unvaccinated individuals or those from endemic regions. Hallmark features include a thick, grayish pseudomembrane covering the tonsils and pharynx, potentially causing airway obstruction.

9. Acute Retroviral Syndrome (HIV): Pharyngitis can be a symptom of acute HIV infection, often accompanied by fever, rash, lymphadenopathy, and fatigue.

10. Non-Infectious Pharyngitis: Consider non-infectious causes in patients with chronic or recurrent pharyngitis, or when infectious etiologies are less likely based on clinical presentation. GERD-related pharyngitis may present with hoarseness and symptoms worsening at night. Allergic pharyngitis often coexists with other allergic symptoms like sneezing and nasal congestion.

Image: Examination of a patient’s throat reveals tonsillitis characterized by inflammation, redness, and white exudates, key signs for differential diagnosis of acute pharyngitis.

Diagnostic Evaluation

The diagnostic approach to acute pharyngitis is guided by the clinical suspicion of the underlying etiology.

Initial Assessment:

• History: Detailed history should include symptom onset, duration, associated symptoms (cough, rhinorrhea, fever, rash, fatigue), past medical history (allergies, GERD, immunocompromised status), medication history, and social history (sexual activity, travel, vaccination status).
• Physical Examination: Thorough examination includes assessment of the oropharynx for erythema, exudates, vesicles, ulcers, pseudomembranes, and uvular deviation. Palpate for anterior and posterior cervical lymphadenopathy, tonsillar size, and tenderness. Assess for signs of airway obstruction (stridor, drooling, respiratory distress), trismus, and neck stiffness. Examine for hepatosplenomegaly and rash.

Specific Diagnostic Tests:

• Rapid Antigen Detection Test (RADT) for GAS: Highly specific for Streptococcus pyogenes. Positive results are generally considered diagnostic. Negative results in children, especially with intermediate or high Centor scores, should be followed by throat culture due to variable sensitivity of RADT.
• Throat Culture: Gold standard for GAS diagnosis, especially when RADT is negative in children. Also useful for identifying other bacterial pathogens.
• Heterophile Antibody Test (Monospot): Screening test for infectious mononucleosis. High specificity but lower sensitivity in early illness and young children.
• EBV Serology: More sensitive and specific for EBV infection, particularly useful if Monospot is negative but clinical suspicion is high.
• Gonococcal Culture: Thayer-Martin agar culture of throat swabs for suspected gonococcal pharyngitis.
• HSV PCR or Viral Culture: May be considered for suspected herpetic pharyngitis, especially if atypical presentation.
• Complete Blood Count (CBC) with Differential: May be helpful in suspected mononucleosis (lymphocytosis, atypical lymphocytes) but not specific for bacterial vs. viral pharyngitis in general.
• Lateral Neck X-ray: To evaluate for epiglottitis or retropharyngeal abscess in cases of suspected airway compromise.
• CT Scan of Neck: For suspected peritonsillar or retropharyngeal abscess when physical exam is inconclusive.

Conclusion

Accurate differential diagnosis of acute pharyngitis is crucial for effective patient management. A thorough clinical evaluation, utilizing scoring systems, and judicious use of diagnostic testing allows clinicians to differentiate between viral, bacterial, and non-infectious causes, rule out serious conditions, and guide appropriate treatment strategies, ultimately optimizing patient outcomes and minimizing antibiotic overuse. Continuous updates on local epidemiology and antibiotic resistance patterns are essential for best practices in managing acute pharyngitis.

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