What are the potential causes of a prolonged sore throat in a patient of unknown age and sex with no specified past medical history?

Prolonged Sore Throat: Causes and Diagnostic Approach

When a sore throat persists beyond 14 days, you must expand your differential diagnosis beyond typical acute viral and bacterial pharyngitis to include chronic infections, non-infectious inflammatory conditions, and malignancy.

Key Distinction: Acute vs. Prolonged Duration

The guidelines specifically define acute sore throat as symptoms lasting less than 14 days 1. Prolonged sore throat (≥14 days) falls outside standard acute pharyngitis guidelines and requires a different diagnostic approach 1.

Causes of Prolonged Sore Throat

Infectious Causes

Bacterial Pathogens:

• Fusobacterium necrophorum - Recent evidence suggests this organism plays a role in recurrent or persistent pharyngitis in adolescents and young adults, with or without bacteremia or Lemierre's syndrome, which requires urgent antibiotic therapy 1
• Groups C and G β-hemolytic streptococci - Can cause persistent pharyngitis, particularly in college students and adults 1
• Mycoplasma pneumoniae and Chlamydophila pneumoniae - Uncommon but recognized causes of persistent pharyngitis, often associated with atypical pneumonia 1, 2
• Arcanobacterium haemolyticum - Rare cause that may present with scarlet fever-like rash, particularly in teenagers and young adults 1
• Neisseria gonorrhoeae - Consider in sexually active individuals with persistent pharyngitis 1

Viral Pathogens:

• Epstein-Barr virus (EBV) - Infectious mononucleosis can cause prolonged pharyngitis with generalized lymphadenopathy and splenomegaly 1
• Cytomegalovirus (CMV) - Can cause persistent pharyngitis as part of systemic infection 1
• HIV infection - Should be considered, especially if associated with candidal pharyngitis 1, 2
• Herpes simplex virus - Can cause recurrent or persistent pharyngeal symptoms 1

Fungal Infection:

• Candida species - Particularly in immunocompromised patients; presence should prompt HIV testing 2

Non-Infectious Causes

Neoplastic:

• Tonsillar cancer - Must be investigated in prolonged cases, especially with unilateral symptoms 3
• Other pharyngeal malignancies - Consider with persistent unilateral symptoms or mass 3

Inflammatory:

• Thyroiditis - Uncommon but recognized cause of persistent throat pain 2
• Granulomatosis with polyangiitis - Can cause chronic pharyngeal symptoms 1

Mechanical/Structural:

• Peritonsillar or retropharyngeal abscess - Requires surgical drainage 1, 2
• Vincent's angina - Mixed anaerobic infection requiring specific treatment 1

Critical Red Flags Requiring Immediate Investigation

You must exclude these serious conditions in any prolonged sore throat:

• Immunosuppression or HIV infection 1, 2
• Severe systemic infection or sepsis 1
• History of acute rheumatic fever 1
• Unilateral symptoms suggesting abscess or malignancy 2, 3
• Difficulty breathing or stridor suggesting supraglottitis 3
• Persistent fever despite treatment 3

Diagnostic Approach for Prolonged Sore Throat

Step 1: Detailed History

• Duration of symptoms (>14 days defines prolonged) 1
• Sexual history (gonorrhea, HIV risk) 1
• Immunosuppression status 1
• Travel history outside usual geographic area 1
• Associated symptoms: generalized lymphadenopathy/splenomegaly (EBV), atypical pneumonia (Mycoplasma/Chlamydophila), rash (Arcanobacterium), oral thrush (HIV/Candida) 1, 2

Step 2: Physical Examination

• Look for unilateral tonsillar enlargement or mass (malignancy, abscess) 2, 3
• Assess for generalized lymphadenopathy and splenomegaly (EBV, HIV) 1
• Examine for oral candidiasis (immunosuppression) 2
• Check for membrane formation (diphtheria, though rare) 1
• Evaluate for cherry-red epiglottis (Haemophilus influenzae type b) 2

Step 3: Laboratory Investigation

• Throat culture - Remains gold standard for bacterial identification 1
• Monospot or EBV serology - If generalized lymphadenopathy present 1
• HIV testing - Especially if candidiasis or other risk factors present 2
• Gonorrhea culture - If sexually active with persistent symptoms 1
• Consider Fusobacterium necrophorum culture - In adolescents/young adults with persistent symptoms 1

Step 4: Specialist Referral

• Otolaryngology consultation - For any persistent unilateral symptoms, suspected malignancy, or failure to respond to appropriate treatment 3
• Infectious disease consultation - For suspected Lemierre's syndrome, HIV, or complex infections 1

Common Pitfalls to Avoid

• Do not assume prolonged symptoms are simply treatment-resistant streptococcal pharyngitis - The differential is much broader 1
• Do not prescribe repeated courses of antibiotics without establishing a bacterial diagnosis - This contributes to resistance and delays proper diagnosis 1
• Do not miss Fusobacterium necrophorum - This emerging pathogen causes persistent pharyngitis in adolescents/young adults and can lead to life-threatening Lemierre's syndrome 1
• Do not overlook malignancy - Unilateral persistent symptoms warrant otolaryngology evaluation 3
• Do not forget to consider HIV - Especially with candidal pharyngitis or other opportunistic findings 2

When Standard Acute Pharyngitis Guidelines Do Not Apply

The ESCMID and IDSA guidelines explicitly exclude prolonged/recurrent cases from their acute pharyngitis recommendations 1. These patients require individualized investigation based on clinical presentation, risk factors, and response to initial therapy 1.