What are the differential diagnoses for a patient presenting with sore throat?

Differential Diagnoses of Throat Pain

Infectious Causes

Viral Pharyngitis (Most Common)

• Viral infections account for the majority of acute sore throat cases, presenting with coryza, hoarseness, cough, conjunctivitis, and characteristic viral enanthems or exanthems 1.
• Epstein-Barr virus (infectious mononucleosis) presents with tonsillar exudate plus generalized lymphadenopathy and splenomegaly, distinguishing it from simple bacterial pharyngitis 2.
• Viral pharyngitis typically resolves spontaneously within 7 days regardless of treatment 2.

Bacterial Pharyngitis

• Group A β-hemolytic Streptococcus (Streptococcus pyogenes) is the primary bacterial pathogen, presenting with sudden-onset sore throat, fever (>38°C), tonsillopharyngeal erythema with or without exudates, palatal petechiae, beefy red swollen uvula, tender anterior cervical lymphadenopathy, and absence of cough 1, 3.
• Groups C and G β-hemolytic streptococci can cause exudative tonsillitis with anterior cervical adenopathy 2.
• Arcanobacterium haemolyticum occurs mainly in teenagers and young adults, often presenting with a scarlet fever-like rash 2.
• Mycoplasma pneumoniae and Chlamydia pneumoniae have been suggested as pathogens in acute sore throat 1.

Fungal Pharyngitis

• Consider fungal infections in immunocompromised patients or those with unexplained chronic cough who have resided in areas of endemic infection 1.

Suppurative Complications (Life-Threatening)

Peritonsillar Abscess

• Unilateral tonsillar swelling with foreign-body sensation, uvular deviation away from the affected side, and trismus strongly indicates peritonsillar abscess requiring urgent ENT referral for needle aspiration or incision-and-drainage 2, 4.
• This is the most common deep space infection in young adults, presenting as a polymicrobial infection requiring immediate ENT consultation for drainage and IV antibiotics 4.

Deep Space Infections

• Obtain contrast-enhanced CT of the neck immediately if neck swelling or fullness, severe unilateral neck pain, or trismus are present to rule out retropharyngeal abscess or Lemierre disease 4.
• Lemierre disease (suppurative thrombophlebitis of the internal jugular vein) should be considered in patients with persistent fever, unilateral neck pain or swelling, and septic pulmonary emboli 4.

Acute Epiglottitis

• Acute epiglottitis is a medical emergency requiring treatment with appropriate antibiotics for Hemophilus influenzae type b and intubation 5.

Non-Infectious Inflammatory Causes

Granulomatous Conditions

• Granulomatosis with polyangiitis (GPA) can present with non-specific mucosal thickening in the nose or paranasal sinuses, characterized by granulomatous inflammation, necrosis, and vasculitis 1.
• Sarcoidosis should be considered in the differential of granulomatous conditions affecting the pharynx 1.

Neoplastic Causes

• Tonsillar cancer should be investigated in cases of persistent sore throat, particularly with unilateral presentation 6.
• NK/T cell lymphoma can mimic granulomatous conditions and should be considered in the differential 1.

Diagnostic Algorithm

Step 1: Exclude Life-Threatening Conditions

• Immediately assess for red flags: neck swelling, severe unilateral pain, trismus, respiratory distress, or drooling 4.
• If any red flags present, obtain contrast-enhanced CT neck immediately and arrange urgent ENT consultation 4.

Step 2: Distinguish Viral from Bacterial Etiology

• Viral features (cough, coryza, hoarseness, conjunctivitis, diarrhea) strongly suggest viral pharyngitis—no testing or antibiotics needed 1, 3.
• Bacterial features (sudden onset, fever >38°C, tonsillar exudate, tender anterior cervical nodes, absence of cough) suggest Group A Streptococcus 1, 3.

Step 3: Apply Modified Centor Criteria (if bacterial suspected)

• Tonsillar exudate (1 point)
• Tender anterior cervical lymphadenopathy (1 point)
• Fever >38°C (1 point)
• Absence of cough (1 point)
• Score 3-4 predicts 28-56% probability of Group A Streptococcus 2.

Step 4: Microbiological Confirmation

• Perform rapid antigen detection test (RADT) for Group A Streptococcus (specificity ≥95%); positive result confirms infection 2, 3.
• If RADT negative but clinical suspicion remains high (score 3-4), obtain throat culture as the gold standard 1, 2.
• Never treat based on clinical findings alone without laboratory confirmation 3.

Step 5: Consider Uncommon Causes if Persistent

• If symptoms persist >14 days despite appropriate treatment, consider tuberculosis (in high-prevalence areas), infectious mononucleosis, fungal infections, neoplastic causes, or granulomatous conditions 1.

Critical Pitfalls to Avoid

• Do not dismiss unilateral presentation as "just strep throat"—this demands exclusion of suppurative complications before considering simple pharyngitis 4.
• Do not wait for culture results if red flag features are present; imaging and specialist consultation take priority 4.
• Do not prescribe empiric antibiotics without microbiological confirmation in typical bilateral presentations, as 65-85% of sore throats are viral 4, 3.
• Missing infectious mononucleosis can result in inappropriate ampicillin use (causing rash) and omission of needed supportive care 2.