Differential Diagnoses for Persistent Sore Throat

Infectious Causes

The American Academy of Pediatrics suggests that 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
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 2, 3
Carriers show extremely low risk of post-streptococcal complications and low likelihood of transmission 4
Groups C and G β-hemolytic streptococci can cause pharyngitis with milder clinical presentation than GABHS, though severe cases and complications have been reported 4, 1

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
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

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) 5, 4
Acute poststreptococcal glomerulonephritis follows GABHS pharyngitis after a latency period of a few weeks 4

Gastroesophageal reflux disease (GERD) can cause chronic throat irritation 6
Allergic rhinitis with postnasal drip may present as chronic sore throat 7
Chronic irritant exposure from smoking, environmental allergens, or occupational exposures 6

Apply Centor criteria (fever, absence of cough, tonsillar exudates, tender anterior cervical lymphadenopathy) to risk-stratify for GABHS 5, 8
Testing for GABHS should be considered if 2-3 Centor criteria are present, but is not routinely recommended when viral symptoms predominate 8, 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

Either ibuprofen or acetaminophen is strongly recommended for relief of acute sore throat symptoms 5, 8
Adequate hydration with cool liquids should be encouraged 8
Antibiotics should NOT be used in patients with less severe presentation (0-2 Centor criteria) 5, 8
In patients with 3-4 Centor criteria, perform RADT before prescribing antibiotics and discuss modest benefits versus side effects, antimicrobial resistance, and costs 5, 8
If antibiotics are indicated, penicillin V twice or three times daily for 10 days is recommended 5, 8
For penicillin-allergic patients: first-generation cephalosporins, clindamycin, or macrolides can be used 8

Antimicrobial therapy is NOT indicated for the large majority of chronic streptococcal carriers 2, 3
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 2, 3
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 2, 3