What is the differential diagnosis for fever, night sweats, and a blood‑tinged cough in a 60‑year‑old man?

Differential Diagnosis for a 60-Year-Old Man with Fever, Night Sweats, and Blood-Tinged Cough

Tuberculosis is the primary diagnosis that must be ruled out immediately in any patient presenting with the classic triad of fever, night sweats, and hemoptysis, regardless of cough duration. 1, 2

Immediate Priority: Tuberculosis Evaluation

You must screen for TB first when fever, night sweats, and hemoptysis occur together, as this combination significantly increases TB probability. 1, 2

Key TB Discriminators to Assess:

• Duration of symptoms ≥2 weeks strongly suggests TB over acute bacterial pneumonia 2
• Risk factors that substantially elevate TB likelihood: foreign-born status from endemic countries, HIV infection, homelessness, incarceration, immunosuppression, diabetes, silicosis, end-stage renal disease, recent TB contact 2
• Weight loss accompanying the triad is highly suggestive of TB 1, 3

Diagnostic Approach for TB:

• Collect three sputum specimens on different days for AFB smear microscopy and mycobacterial culture (culture remains the gold standard) 2
• Perform nucleic acid amplification testing (Xpert MTB/RIF) on at least one specimen to enable diagnosis within 1-2 days 1, 2
• Never exclude TB based on negative AFB smears alone, as smear sensitivity is only ~60% 1, 2
• Obtain chest radiograph looking for: upper lobe cavitary disease, apical posterior segment infiltrates, hilar/mediastinal adenopathy, fibrotic lesions 2

Other Critical Diagnoses to Consider

Bacterial Pneumonia (Community-Acquired)

• More acute onset (days rather than weeks) distinguishes pneumonia from TB's insidious progression 2
• Check vital signs immediately: fever ≥38°C, heart rate ≥100 bpm, respiratory rate ≥24 breaths/min mandate chest radiography 1, 4
• CRP >30 mg/L plus suggestive symptoms increases pneumonia likelihood 1
• CRP <10 mg/L or 10-50 mg/L without dyspnea and daily fever makes pneumonia less likely 1

Lung Cancer

• Must be considered in the differential, particularly with hemoptysis and constitutional symptoms 2
• Blood-tinged cough persisting beyond 3 weeks is a red flag requiring evaluation 3, 4
• Chest radiograph and potentially CT imaging are essential 2

Fungal Infections

• Histoplasmosis, coccidioidomycosis, and blastomycosis can present identically to TB with chronic cough, fever, night sweats, weight loss, and cavitary lung lesions 2
• Geographic exposure history is critical for distinguishing fungal infections 1

Nontuberculous Mycobacterial (NTM) Infections

• Can present with identical symptoms and radiographic findings to TB 2
• Requires mycobacterial culture for definitive differentiation from TB 2

Critical Pitfalls to Avoid

• Do not delay empiric TB treatment in high-risk patients with classic symptoms while awaiting diagnostic confirmation, as this increases mortality and transmission risk 2
• Do not assume all hemoptysis is minor—this is a red flag symptom requiring immediate evaluation 3
• Do not rely on symptom duration alone—in endemic areas or high-risk populations, consider TB regardless of cough duration 3
• Elderly patients may present atypically with less fever and sweating, making diagnosis more challenging 2

Diagnostic Algorithm

1. Immediately assess TB risk factors and obtain three sputum specimens for AFB smear, culture, and Xpert MTB/RIF 1, 2
2. Obtain chest radiograph looking for upper lobe cavitary disease or infiltrates 2
3. Check vital signs and CRP to assess for bacterial pneumonia 1, 4
4. If TB testing is negative and symptoms persist, consider fungal infections, NTM, or malignancy 2
5. Start empiric TB treatment in high-risk patients with classic presentation while awaiting culture results 2