What is the differential diagnosis and management for a patient presenting with unilateral sore throat?

Unilateral Sore Throat: Differential Diagnosis and Management

A unilateral sore throat is a red flag that demands immediate evaluation for life-threatening suppurative complications—particularly peritonsillar abscess, retropharyngeal abscess, and Lemierre disease—which require urgent imaging and intervention to prevent airway compromise, mediastinitis, and death. 1

Critical Red Flags Requiring Immediate Action

The unilateral presentation distinguishes this from typical viral or streptococcal pharyngitis and mandates aggressive evaluation:

Immediate Imaging Indications

• Obtain contrast-enhanced CT of the neck immediately if any of the following are present: 1
  • Neck swelling or fullness (suggests peritonsillar abscess, retropharyngeal abscess, or Lemierre disease)
  • Severe unilateral neck pain (suggests deep space infection or suppurative lymphadenitis)
  • Trismus or difficulty opening the mouth (suggests peritonsillar abscess)
• Do not delay imaging for throat culture results, as these suppurative complications require urgent diagnosis to prevent catastrophic outcomes 1

Urgent Laboratory Workup

• Complete blood count with differential to evaluate for leukocytosis (bacterial infection) and thrombocytopenia (may suggest Lemierre syndrome) 1
• Blood cultures if febrile, as bacteremia from deep space infection or Lemierre disease is a major concern 1
• Inflammatory markers (CRP, ESR) if deep space infection is suspected 1

Life-Threatening Differential Diagnoses

Peritonsillar Abscess (Quinsy)

• Most common deep space infection in young adults, presenting as polymicrobial infection 2
• Classic presentation: severe unilateral throat pain, trismus, "hot potato" voice, uvular deviation away from affected side 1
• Requires immediate ENT consultation for drainage and IV antibiotics 1

Lemierre Disease

• Suppurative thrombophlebitis of the internal jugular vein following pharyngitis, most commonly caused by Fusobacterium necrophorum 2, 3
• Presents with persistent fever, unilateral neck pain/swelling, and septic pulmonary emboli 3
• Rare but catastrophic if missed—requires prolonged IV antibiotics and anticoagulation consideration 3

Retropharyngeal Abscess

• More common in children but can occur in adults 1
• Presents with severe dysphagia, neck stiffness, and potential airway compromise 1
• Can lead to descending mediastinitis if diagnosis is delayed 3

Common Infectious Causes (After Excluding Emergencies)

Group A β-Hemolytic Streptococcus (GABHS)

• While typically bilateral, can present with asymmetric tonsillar involvement 2
• Clinical features: sudden-onset sore throat, fever, tonsillar exudates, tender anterior cervical adenopathy, absence of cough 2
• Diagnosis requires microbiological confirmation with rapid antigen testing or throat culture—clinical features alone are unreliable 2
• Treatment: Penicillin V 250 mg twice or three times daily for 10 days if confirmed 4, 2

Groups C and G Streptococci

• Can cause pharyngitis with milder clinical presentation than GABHS 2
• May cause severe or recurrent pharyngitis in some cases 5

Infectious Mononucleosis (EBV)

• Presents with pharyngitis, generalized lymphadenopathy (not just unilateral), and splenomegaly 2
• Unilateral presentation less typical but possible with asymmetric tonsillar involvement

Non-Infectious Considerations

Neoplastic Causes

• Tonsillar cancer should be considered in persistent unilateral throat pain, especially in patients with tobacco/alcohol use or HPV risk factors 6
• Requires direct laryngoscopy and biopsy if symptoms persist beyond 2 weeks 5

Other Causes

• Thyroiditis (uncommon but can present as unilateral throat pain) 7
• Gastroesophageal reflux disease (chronic throat irritation, typically not acute unilateral presentation) 5

Management Algorithm

Step 1: Assess for Emergency

• If neck swelling, severe unilateral pain, trismus, or respiratory distress → immediate CT neck with contrast 1
• If confirmed abscess or deep space infection → admit for IV antibiotics and ENT consultation 1

Step 2: If No Emergency Features Present

• Perform rapid antigen testing or throat culture if GABHS suspected based on clinical features 2
• Viral features (conjunctivitis, cough, hoarseness, coryza) suggest no antibiotics needed 2
• Do not routinely use biomarkers (CRP, procalcitonin) for uncomplicated presentations 4

Step 3: Symptomatic Management

• Ibuprofen or paracetamol are strongly recommended for pain relief regardless of etiology 4, 2
• Corticosteroids can be considered in adults with severe presentations (3-4 Centor criteria) in conjunction with antibiotics 4

Step 4: Antibiotic Decision

• Do not prescribe antibiotics for 0-2 Centor criteria presentations 4, 2
• Consider antibiotics only if GABHS confirmed AND patient has 3-4 Centor criteria, weighing modest benefits against side effects and resistance 4, 2
• Penicillin V remains first-line if treatment indicated 4, 2

Critical Pitfalls to Avoid

• Never dismiss unilateral presentation as "just strep throat"—the asymmetry demands exclusion of suppurative complications 1
• Do not wait for culture results if any red flag features are present 1
• Avoid empiric antibiotics without considering imaging first in unilateral presentations with concerning features 1
• Remember that most sore throats (65-85%) are viral and do not benefit from antibiotics 2
• Persistent symptoms beyond 14 days require re-evaluation for non-infectious causes and complications 5