What are the differential diagnoses and management approaches for a patient with a persistent sore throat?

Differential Diagnoses for Persistent Sore Throat

The vast majority (65-85%) of persistent sore throats are viral in origin, but you must systematically exclude bacterial causes—particularly Group A β-hemolytic streptococcus (GABHS)—chronic carriage states, and life-threatening conditions like peritonsillar abscess, epiglottitis, and retropharyngeal abscess. 1

Infectious Causes

Viral Etiologies (Most Common)

• Respiratory viruses account for the majority of cases, including rhinovirus, coronavirus, adenovirus, influenza, parainfluenza, and respiratory syncytial virus 1
• Epstein-Barr virus (infectious mononucleosis) presents with pharyngitis accompanied by generalized lymphadenopathy and splenomegaly—look for posterior cervical adenopathy and splenomegaly on exam 1
• Viral pharyngitis is strongly suggested by: conjunctivitis, cough, hoarseness, coryza, diarrhea, anterior stomatitis, discrete ulcerative lesions, or viral exanthem 1
• Acute retroviral syndrome (HIV) should be considered in appropriate risk contexts, particularly with associated rash or generalized lymphadenopathy 2
• Herpangina (Coxsackie A virus) presents with characteristic vesicles 3
• Herpes simplex infection shows typical vesicular lesions 3

Bacterial Causes

Group A β-Hemolytic Streptococcus (GABHS)

• GABHS accounts for 15-30% of pharyngitis in children and 5-15% in adults, making it the most common bacterial cause requiring antibiotic therapy 1
• Clinical features suggesting GABHS: sudden-onset sore throat, fever, tonsillar exudates, tender anterior cervical adenopathy, absence of cough, and patient age 5-15 years 1
• Critical distinction: Chronic GABHS carriers (10.9% in children aged ≤14 years, 2.3% in adults 15-44 years) with intercurrent viral infections are difficult to differentiate from acute infection 4
• Carriers show extremely low risk of post-streptococcal complications and low likelihood of transmission 4

Other Bacterial Pathogens

• Groups C and G β-hemolytic streptococci can cause pharyngitis with milder clinical presentation than GABHS, though severe cases and complications (reactive arthritis, subdural empyema, acute glomerulonephritis) have been reported 4, 1
• Neisseria gonorrhoeae pharyngitis may be accompanied by infection at other sites or other sexually transmitted diseases—consider in sexually active patients with appropriate exposure history 3
• Corynebacterium diphtheriae suggested by typical membrane formation 3
• Corynebacterium haemolyticum may present with scarlatiniform rash 3
• Mycoplasma pneumoniae or Chlamydia pneumoniae suggested by associated atypical pneumonia 3

Fungal Causes

• Candidal infection (oral thrush) in the appropriate clinical circumstance should suggest HIV infection or immunosuppression 3

Life-Threatening Suppurative Complications

Immediate Threats Requiring Emergency Management

• Epiglottitis is a medical emergency requiring immediate airway management—look for cherry-red epiglottis, drooling, stridor, and toxic appearance; caused primarily by Haemophilus influenzae type b 5, 3, 6
• Peritonsillar abscess (quinsy) is a polymicrobial infection occurring mainly in young adults, presenting with severe unilateral throat pain, trismus, uvular deviation, and "hot potato voice" 4, 1, 2
• Retropharyngeal abscess presents with severe dysphagia, neck stiffness, and potential airway compromise—requires surgical drainage 5, 3, 6
• Ludwig's angina is a rapidly progressive cellulitis of the floor of the mouth that can compromise the airway 2
• Lemierre's syndrome (suppurative thrombophlebitis of internal jugular vein) is a rare but serious complication of pharyngitis presenting with persistent fever, neck pain, and septic emboli 1, 2

Other Suppurative Complications

• Acute otitis media, cervical lymphadenitis, mastoiditis, and acute sinusitis are uncommon complications that do not routinely require antibiotic prophylaxis 4

Non-Suppurative Complications (Rare in Developed Countries)

• Acute rheumatic fever has very low incidence in Europe and developed countries; prevention depends on effective control of GABHS pharyngitis in high-risk patients (those with previous rheumatic fever or family history) 4
• Acute poststreptococcal glomerulonephritis follows GABHS pharyngitis after a latency period of a few weeks 4

Non-Infectious Causes

• Thyroiditis is a relatively uncommon consideration in the differential diagnosis of acute febrile pharyngitis 3
• Kawasaki disease should be considered in children with persistent fever, conjunctivitis, rash, and cervical lymphadenopathy 2
• Gastroesophageal reflux disease (GERD) can cause chronic throat irritation 4
• Allergic rhinitis with postnasal drip may present as chronic sore throat 4
• Chronic irritant exposure from smoking, environmental allergens, or occupational exposures 4

Diagnostic Approach for Persistent Sore Throat

Initial Assessment

• Apply Centor criteria (fever, absence of cough, tonsillar exudates, tender anterior cervical lymphadenopathy) to risk-stratify for GABHS 4, 7
• Testing for GABHS should be considered if 2-3 Centor criteria are present, but is not routinely recommended when viral symptoms predominate 7, 1
• Clinical features alone cannot reliably distinguish GABHS from viral pharyngitis—microbiological confirmation with throat culture or rapid antigen detection test (RADT) is required when GABHS is suspected 1

For Persistent or Recurrent Cases

• Distinguish chronic GABHS carriage from recurrent acute infection by evaluating: precise nature of presenting signs and symptoms, clinical response to previous antibiotic therapy, and presence/absence of GABHS in throat swabs during asymptomatic intervals 4
• Chronic carriers have persistence of the same strain over time, whereas recurrent infections show different strains (though serotyping/genotyping is only available in specialized research laboratories) 4
• Most patients with multiple episodes are chronic streptococcal carriers experiencing repeated viral infections 4

Red Flags Requiring Immediate Evaluation

• Drooling, stridor, toxic appearance, or respiratory distress suggest epiglottitis or other airway-threatening conditions 6
• Severe unilateral throat pain with trismus suggests peritonsillar abscess 2
• Neck stiffness with severe dysphagia suggests retropharyngeal abscess 6
• Persistent fever >3 days despite appropriate symptomatic treatment requires re-evaluation 7

Management Principles

Symptomatic Treatment (All Patients)

• Either ibuprofen or acetaminophen is strongly recommended for relief of acute sore throat symptoms 4, 7
• Adequate hydration with cool liquids should be encouraged 7

Antibiotic Decision-Making

• Antibiotics should NOT be used in patients with less severe presentation (0-2 Centor criteria) 4, 7
• In patients with 3-4 Centor criteria, perform RADT before prescribing antibiotics and discuss modest benefits versus side effects, antimicrobial resistance, and costs 4, 7
• If antibiotics are indicated, penicillin V twice or three times daily for 10 days is recommended 4, 7
• For penicillin-allergic patients: first-generation cephalosporins, clindamycin, or macrolides can be used 7

Management of Chronic Carriers

• Antimicrobial therapy is NOT indicated for the large majority of chronic streptococcal carriers 4
• Eradication of carriage may be desirable in special situations: community outbreak of acute rheumatic fever/glomerulonephritis/invasive GAS, outbreak in closed community, family/personal history of acute rheumatic fever, excessive family anxiety, or when tonsillectomy is being considered only because of carriage 4
• For carrier eradication, use: oral clindamycin 20-30 mg/kg/d in 3 doses for 10 days, penicillin V plus rifampin, amoxicillin-clavulanate, or benzathine penicillin G plus rifampin 4

Common Pitfalls to Avoid

• Treating viral pharyngitis with antibiotics provides no benefit and increases risk of side effects and antimicrobial resistance 7
• Failing to recognize life-threatening conditions like epiglottitis or retropharyngeal abscess due to anchoring on common diagnoses 6
• Misinterpreting positive GABHS testing in chronic carriers as acute infection rather than viral pharyngitis in a carrier 4
• Prescribing antibiotics without appropriate testing or clinical criteria leads to overuse and resistance 7
• Inadequate dosing or duration of antibiotics when truly indicated can lead to treatment failure 7