What are the differential diagnoses and treatment options for a 28-year-old patient with a 3-week history of cough and intermittent fevers?

Differential Diagnoses for 3-Week Cough with Intermittent Fevers in a 28-Year-Old

In a 28-year-old with 3 weeks of cough and intermittent fevers, the primary focus must be ruling out pneumonia through vital signs and lung examination, followed by consideration of pertussis, postinfectious cough, and tuberculosis based on specific clinical features. 1

Immediate Assessment: Rule Out Pneumonia First

The most critical initial step is excluding pneumonia, which carries significant morbidity and mortality risk 1:

• Check vital signs immediately: Look for heart rate ≥100 beats/min, respiratory rate ≥24 breaths/min, or temperature ≥38°C 1
• Perform focused lung examination: Listen for asymmetrical lung sounds, focal consolidation, rales, egophony, or fremitus 1
• Obtain chest radiography if: Vital sign abnormalities are present, asymmetrical lung sounds are detected, or the patient appears ill 1
• In healthy young adults without these findings: Pneumonia is uncommon and chest X-ray may not be immediately necessary 1

Key Differential Diagnoses by Priority

1. Pertussis (Whooping Cough)

Suspect when 1, 2:

• Cough lasting ≥2 weeks with paroxysms of coughing
• Post-tussive vomiting present
• Inspiratory whooping sound
• Recent exposure to confirmed pertussis case

Diagnostic approach 1:

• Obtain nasopharyngeal aspirate or Dacron swab for culture (gold standard)
• Order paired acute and convalescent sera for fourfold increase in IgG or IgA antibodies to pertussis toxin
• If confirmed: Initiate macrolide antibiotic (azithromycin, clarithromycin, or erythromycin) within first few weeks to diminish coughing paroxysms and prevent transmission 1

2. Postinfectious Cough

Suspect when 1, 2:

• Cough follows obvious preceding respiratory infection
• Duration 3-8 weeks (subacute cough)
• No vital sign abnormalities or concerning lung findings

Underlying mechanisms 2:

• Postviral airway inflammation (48.4% of cases)
• Upper airway cough syndrome/postnasal drip (33.2% of cases)
• Cough-variant asthma (15.8% of cases)
• Nonasthmatic eosinophilic bronchitis (5.4% of cases)

3. Tuberculosis

Suspect when 1:

• Patient from high TB prevalence area
• Systemic symptoms: fever, night sweats, weight loss
• Cough persisting >3 weeks

Diagnostic approach 1:

• Obtain chest radiograph
• Collect sputum smears and cultures for acid-fast bacilli
• Consider even in low-prevalence areas when common causes ruled out

4. Acute Bronchitis (Less Likely at 3 Weeks)

Consider when 1, 3:

• Cough typically lasts 2-3 weeks
• At 3-week mark, transitioning to subacute/postinfectious category
• Antibiotics NOT indicated unless pertussis suspected 1, 3

5. Cough-Variant Asthma

Suspect when 1:

• Persistent cough >2-3 weeks duration
• Lack of wheezing
• Cough worsens at night or after cold/exercise exposure
• Normal baseline pulmonary function tests

Diagnostic approach 1:

• Trial of bronchodilator treatment
• Consider methacholine challenge test if diagnosis unclear

Critical Red Flags Requiring Immediate Investigation

Obtain chest radiography immediately if 1, 2:

• Hemoptysis present
• Significant unintentional weight loss
• Voice changes
• Vital sign abnormalities (as above)
• Asymmetrical lung sounds or focal consolidation

Medication Review

Always assess for 1, 2:

• ACE inhibitor use (can cause persistent cough)
• Median time to cough resolution after stopping ACE inhibitor: 26 days 1

Common Pitfalls to Avoid

• Failing to consider pertussis in adults: Often underdiagnosed; think of it with prolonged paroxysmal cough 2
• Inappropriate antibiotic use: Acute bronchitis is viral; antibiotics provide minimal benefit (reducing cough by only half a day) with significant adverse effects including C. difficile infection 1, 3
• Missing pneumonia: Always check vital signs and perform lung examination before dismissing as simple bronchitis 1
• Overlooking TB: Especially in patients from endemic areas or with systemic symptoms 1

Diagnostic Algorithm

1. Assess vital signs and lung examination → If abnormal, obtain chest X-ray to rule out pneumonia 1
2. If pneumonia excluded, evaluate for pertussis features → If present, obtain nasopharyngeal culture and start macrolide 1
3. If pertussis unlikely, consider postinfectious cough → Identify predominant mechanism (postnasal drip, bronchial hyperresponsiveness, etc.) 1, 2
4. Screen for TB risk factors → If present, obtain chest X-ray and sputum cultures 1
5. Review medications → Stop ACE inhibitor if present 1, 2
6. If cough persists >8 weeks → Reclassify as chronic cough and pursue comprehensive evaluation including chest CT if needed 1, 2