Differential Diagnoses for Upper Respiratory Infection
When a patient presents with URI symptoms, the key differential diagnoses include viral rhinosinusitis (common cold), acute bacterial rhinosinusitis, acute pharyngitis (viral vs. Group A Streptococcus), acute otitis media, acute bronchitis, exacerbations of asthma/COPD, pneumonia, and less commonly pulmonary embolism. 1
Primary Viral vs. Bacterial Distinction
The most critical initial differentiation is between viral URI (which requires only symptomatic management) and bacterial complications (which may warrant antibiotics):
Viral Rhinosinusitis (Common Cold)
- Symptoms lasting <10 days without worsening strongly suggest viral etiology 2, 1
- Presents with purulent nasal drainage, nasal obstruction, facial pressure/pain, low-grade fever, headache, and malaise 1
- Over 80-90% of acute URIs are viral (rhinoviruses, coronaviruses, parainfluenza, RSV, adenoviruses) 1
- Purulent discharge alone does NOT indicate bacterial infection—this is a normal progression of viral illness 1, 3
Acute Bacterial Rhinosinusitis (ABRS)
Diagnose ABRS when symptoms meet one of these criteria 2:
- Persistent symptoms ≥10 days without improvement (most common pattern)
- "Double worsening": initial improvement followed by worsening within 10 days
- Severe onset: fever ≥39°C (102.2°F) PLUS purulent discharge for ≥3 consecutive days 1, 3
Critical pitfall: Fever alone, purulent discharge alone, or symptom duration <10 days do NOT distinguish bacterial from viral infection 3
Pharyngitis Differential
Viral Pharyngitis
- Most common cause of sore throat 2, 4
- Accompanied by cough, congestion, rhinorrhea 2
- Self-limited, resolves in <1 week 1
Group A Streptococcal (GAS) Pharyngitis
- Requires positive rapid antigen test or culture for diagnosis 2
- Never diagnose clinically without testing (except rare circumstance of symptomatic household contact with confirmed GAS) 2
- Do not test children <3 years (GAS pharyngitis rare in this age group) 2
Lower Respiratory Tract Considerations
Acute Bronchitis vs. Pneumonia
When cough is prominent, distinguish between upper and lower respiratory tract involvement 2:
Suspect pneumonia when 2:
- Acute cough PLUS one of: new focal chest signs, dyspnoea, tachypnoea, or fever >4 days
- Focal auscultatory abnormalities increase pneumonia probability from 5-10% to 39% 2
- Obtain chest radiograph if pneumonia suspected 2
Acute bronchitis/tracheobronchitis 2:
- Cough without focal chest findings
- No radiographic infiltrate
- Predominantly viral; antibiotics not indicated 2
Asthma/COPD Exacerbation
Consider in patients with acute cough when ≥2 of the following present 2:
- Wheezing
- Prolonged expiration
- Smoking history
- History of allergy
- Up to 45% of patients with acute cough >2 weeks have underlying asthma/COPD 2
- Consider lung function testing 2
Less Common but Important Differentials
Pulmonary Embolism
Consider PE in patients with respiratory symptoms PLUS 2:
- History of DVT or prior PE
- Immobilization in past 4 weeks
- Malignancy
Acute Otitis Media
- Part of URI spectrum, particularly in children 4
- Requires otoscopic examination for diagnosis
Diagnostic Approach Algorithm
Duration and pattern assessment 2, 1:
- <10 days, not worsening → Viral URI
- ≥10 days without improvement → Consider ABRS
- Worsening after initial improvement → Consider ABRS
- Fever ≥39°C + purulent discharge ≥3 days → Consider ABRS
- Focal chest findings + dyspnea → Consider pneumonia
Sore throat with URI symptoms 2:
- With cough/congestion → Viral pharyngitis
- Without viral symptoms → Test for GAS if age ≥3 years
Prominent cough 2:
- No focal findings, no dyspnea → Viral bronchitis
- Focal findings or dyspnea → Obtain chest radiograph
Do not obtain imaging for uncomplicated ARS 2
Do not use fever, purulent discharge, or CRP alone to distinguish viral from bacterial infection 3