How should I manage a patient presenting with fever and cough of unknown etiology?

Management of Fever and Cough

The first critical step is to immediately determine whether this represents a life-threatening condition requiring urgent intervention—specifically pneumonia or pulmonary embolism—versus a common self-limited viral respiratory infection. 1

Immediate Assessment Priority

Rule out pneumonia first by examining for:

• Fever lasting >4 days 2
• New focal chest signs, dyspnea, or tachypnea 2
• Tachycardia, respiratory rate >20, or oxygen desaturation 2, 3
• Crackles or asymmetric breath sounds on lung examination 4

If any of these features are present, obtain a chest radiograph immediately to confirm or exclude pneumonia. 2, 4, 3

Consider pulmonary embolism if the patient has risk factors including recent immobilization, history of deep vein thrombosis, or malignancy. 2

Duration-Based Diagnostic Approach

Acute Cough (<3 weeks duration)

For acute viral bronchitis without pneumonia, prescribe first-generation antihistamine-decongestant combinations (brompheniramine/pseudoephedrine or chlorpheniramine/phenylephrine) taken regularly for symptomatic relief. 4, 1

Do NOT prescribe antibiotics unless there is clear evidence of bacterial infection—antibiotics provide minimal benefit (reducing cough by only half a day) while causing adverse effects and promoting antimicrobial resistance. 4, 5

Alternative symptomatic measures include guaifenesin 200-400 mg every 4 hours, honey and lemon, adequate hydration, and rest. 4

Subacute Cough (3-8 weeks duration)

Determine if this is post-infectious cough versus another etiology:

• Post-infectious causes: upper airway cough syndrome, transient bronchial hyperresponsiveness, asthma, pertussis, or acute exacerbation of chronic bronchitis 1
• If non-infectious, evaluate as chronic cough 1

Chronic Cough (>8 weeks duration)

Systematically evaluate and treat the four most common causes sequentially and additively (multiple causes frequently coexist): 1, 2

1. Upper airway cough syndrome (UACS): Most common cause (61-67% of cases). Treat with first-generation antihistamine-decongestant plus intranasal corticosteroid. 2, 4

2. Asthma/Non-asthmatic eosinophilic bronchitis (NAEB): Consider when patient has ≥2 of: wheezing, prolonged expiration, smoking history, or allergy symptoms. Treat with inhaled corticosteroids ± bronchodilators. 2, 4

3. Gastroesophageal reflux disease (GERD): Initiate high-dose proton pump inhibitor therapy even without typical GI symptoms. 2, 4

4. ACE inhibitor-induced cough: Immediately inquire about ACE inhibitor use and switch to another drug class if identified. 2, 6

Critical Medication History

Ask specifically about:

• ACE inhibitors (common reversible cause) 2, 6
• β-adrenergic blocking medications (may exacerbate asthma) 6
• Any other drugs that could induce cough 1, 6

Initial Diagnostic Testing

For chronic or unclear cases:

• Chest radiograph to rule out pneumonia, malignancy, structural abnormalities 6, 7
• Spirometry with bronchodilator testing for asthma/obstructive disease 6
• If cough persists after treating common causes, obtain chest CT scan and consider bronchoscopy 1

Red Flags Requiring Advanced Evaluation

Instruct patients to return immediately for:

• Hemoptysis 4, 7
• Fever with worsening dyspnea 4
• Weight loss 7
• Recurrent pneumonia 7
• Symptoms persisting beyond 3 weeks without improvement 4

Critical Pitfalls to Avoid

Multiple causes frequently coexist—use sequential and additive therapy rather than stopping after identifying one etiology. 2 Continue partially effective treatments while adding new interventions. 1

Do not overlook cardiac causes in elderly patients (>65 years)—cardiac failure can present with cough and chest tightness mimicking respiratory infections, especially with orthopnea or history of myocardial infarction. 2

Elderly patients may present with atypical pneumonia features and warrant chest imaging despite normal vital signs. 2