What workup is needed for an adult or child with no significant medical history and a persistent sore throat, but a negative streptococcal (strep) test?

Management of Persistent Sore Throat with Negative Strep Test

Immediate Management: Symptomatic Treatment Only

For both adults and children with a negative strep test, withhold antibiotics and provide symptomatic treatment with ibuprofen or acetaminophen, as the vast majority of these cases are viral and self-limiting. 1

Key Distinction Between Adults and Children

Adults:

• A negative rapid antigen detection test (RADT) alone is sufficient to rule out streptococcal pharyngitis—no backup throat culture is needed 1, 2
• The specificity of RADT is ≥95%, making false positives rare, while sensitivity is 80-90% 1
• Adults have only 5-10% prevalence of group A streptococcal pharyngitis and extremely low risk of acute rheumatic fever 1

Children (ages 5-15):

• A negative RADT should be confirmed with a throat culture before making final treatment decisions 1
• RADTs have only 80-90% sensitivity in children, missing 10-20% of true infections 1
• If the culture returns positive, antibiotics can be initiated at that time—treatment within 9 days of symptom onset still prevents acute rheumatic fever 1

Workup Algorithm for Persistent Symptoms

Define "Persistent"

If symptoms last >3-5 days or worsen significantly, consider alternative diagnoses rather than repeat strep testing. 2

Red Flags Requiring Urgent Evaluation

Assess for the following warning signs that necessitate immediate further workup 2, 3:

• Dysphagia or odynophagia (difficulty/painful swallowing)
• Unilateral throat pain or swelling (suggests peritonsillar abscess)
• Respiratory distress or stridor
• Inability to swallow secretions
• Weight loss
• Severe systemic symptoms

Alternative Diagnoses to Consider

For symptoms persisting >1-2 weeks without improvement: 2, 3

Viral causes (most common):

• Epstein-Barr virus (infectious mononucleosis)—consider monospot test if severe pharyngitis with tonsillar exudate, fatigue, and posterior cervical lymphadenopathy 3
• Adenovirus, rhinovirus, coronavirus, influenza 3
• Herpes simplex virus (look for oral ulcers) 1

Non-infectious causes:

• Gastroesophageal reflux disease (GERD)—especially if burning quality, worse at night or after meals 2
• Chronic irritant exposure (smoking, pollution, dry air) 2
• Allergic pharyngitis (associated with rhinorrhea, sneezing, itchy eyes) 2

Less common bacterial causes:

• Groups C and G β-hemolytic streptococci (not detected by standard strep tests, not associated with rheumatic fever) 3
• Arcanobacterium haemolyticum, Mycoplasma pneumoniae, Chlamydia pneumoniae 3

Specific Workup Based on Clinical Presentation

If severe pharyngitis with fatigue and posterior cervical adenopathy:

• Order monospot or EBV serology to evaluate for infectious mononucleosis 3

If burning throat pain >2 weeks, especially worse at night:

• Consider trial of proton pump inhibitor for presumed GERD 2
• No additional testing needed initially

If unilateral throat pain with fever:

• Perform careful oropharyngeal examination for peritonsillar abscess 2
• Consider CT neck with contrast if abscess suspected

If systemic symptoms (fever, malaise) persist >1 week:

• Consider complete blood count to evaluate for atypical infection 3

Critical Pitfall to Avoid

Do not repeat strep testing in patients with prolonged symptoms (>1 week), as this will likely identify asymptomatic GAS carriers (approximately 25% of the population) rather than acute infection, leading to unnecessary antibiotic prescriptions. 2

• Neither throat culture nor RADT can accurately differentiate acutely infected persons from asymptomatic streptococcal carriers with intercurrent viral pharyngitis 2
• Testing patients with prolonged symptoms leads to treating carrier states rather than true infections 2

Symptomatic Management Recommendations

First-line analgesics: 4, 1

• Ibuprofen or acetaminophen for pain and fever relief
• NSAIDs are more effective than acetaminophen for pharyngitis symptoms 5

Adjunctive measures: 1

• Throat lozenges for comfort
• Reassurance that viral pharyngitis typically resolves in <1 week

Avoid: 2

• Aspirin in children due to Reye syndrome risk
• Antibiotics without confirmed bacterial infection

When to Reassess

Return for re-evaluation if 3:

• Symptoms worsen after 3-5 days
• Development of fever, difficulty swallowing, or new systemic symptoms
• Development of respiratory distress or stridor
• No improvement after 7-10 days