What are the differential diagnoses for an adult presenting with acute dyspnea, pleuritic chest pain, tachycardia, hypoxemia, or unexplained syncope suggestive of pulmonary embolism?

Differential Diagnosis for Pulmonary Embolism

When evaluating a patient with suspected pulmonary embolism, the key differential diagnoses include acute coronary syndrome, pneumonia, acute heart failure, pneumothorax, pericarditis, aortic dissection, musculoskeletal chest pain, and acute exacerbation of COPD—each requiring specific clinical features and diagnostic tests to distinguish from PE. 1

Cardiovascular Differentials

Acute Coronary Syndrome (ACS)

• Central PE can present with substernal angina-like chest pain reflecting right ventricular ischemia, making ACS a critical differential. 1
• ACS typically presents with exertional chest pain, radiation to arm/jaw, and diaphoresis, whereas PE more commonly causes pleuritic pain and dyspnea at rest. 1
• Troponin elevation occurs in both conditions; ECG showing ST-segment elevation or depression favors ACS, while T-wave inversion in V1-V4 or S1Q3T3 pattern suggests PE. 2, 3

Aortic Dissection

• Must be differentiated from central PE, as both can present with sudden severe chest pain and hemodynamic instability. 1
• Dissection classically presents with tearing chest pain radiating to the back, pulse differentials between extremities, and widened mediastinum on chest X-ray. 1

Acute Heart Failure

• In patients with pre-existing heart failure, worsening dyspnea may be the only symptom indicative of PE, making this a challenging differential. 1
• Heart failure typically shows pulmonary edema on chest X-ray (bilateral infiltrates, Kerley B lines), elevated BNP, and responds to diuretics. 1
• PE more commonly presents with sudden onset dyspnea, pleuritic pain, and normal or mildly elevated BNP unless massive PE with right ventricular strain. 1

Pericarditis

• Presents with pleuritic chest pain that improves when leaning forward, friction rub on auscultation, and diffuse ST-segment elevation on ECG. 3
• Unlike PE, pericarditis typically has gradual onset and lacks risk factors for venous thromboembolism. 3

Pulmonary Differentials

Pneumonia

• Fever >38.5°C occurs in only 7% of PE cases versus 17% in non-PE patients, making fever a useful distinguishing feature. 1
• Pneumonia presents with productive cough, fever, focal consolidation on chest X-ray, and elevated white blood cell count. 4
• Pleuritic chest pain occurs in 52% of PE cases and 43% of non-PE cases, limiting its discriminatory value. 1
• Ground glass opacities following recent pneumonia represent post-infectious changes, but recurrent PE must be actively excluded in patients with prior PE history. 5

Pneumothorax

• Presents with sudden pleuritic chest pain and dyspnea, but physical examination reveals decreased breath sounds and hyperresonance on the affected side. 3
• Chest X-ray shows visceral pleural line and absent lung markings peripherally, definitively distinguishing it from PE. 3

Acute Exacerbation of COPD

• PE prevalence in unexplained acute COPD exacerbations is 16.1%, making this a critical differential in COPD patients. 6
• Pleuritic chest pain and cardiac failure are more frequently reported in COPD patients with PE, while signs of respiratory tract infection are less frequently related to PE. 6
• COPD exacerbation typically presents with increased sputum production, wheezing, and responds to bronchodilators and corticosteroids. 6

Pulmonary Infarction Syndrome

• This is actually a presentation of PE itself, not a true differential—caused by distal emboli creating alveolar hemorrhage with pleuritic pain, hemoptysis, and wedge-shaped pleural-based opacity (Hampton's hump) on imaging. 1

Other Important Differentials

Musculoskeletal Chest Pain

• Reproducible chest wall tenderness on palpation distinguishes this from PE. 3
• Pain is typically positional and worsens with specific movements, unlike PE which causes constant pleuritic pain. 3

Anxiety/Panic Attack

• Can present with dyspnea, chest tightness, and tachycardia, but lacks objective findings of hypoxemia or tachypnea. 4
• Approximately 30% of first-episode PE patients have no identifiable risk factors, so absence of risk factors does not rule out PE. 4

Key Distinguishing Clinical Features

Features More Suggestive of PE

• Sudden onset dyspnea and pleuritic chest pain are the most typical symptoms of PE. 2
• Syncope occurs in 19% of PE cases versus 11% in non-PE patients, and is associated with higher prevalence of right ventricular dysfunction. 1, 7
• Hemoptysis occurs in 11% of PE cases versus 7% in non-PE patients. 1
• Signs of deep vein thrombosis (unilateral leg swelling) present in 15% of PE cases versus 10% in non-PE patients. 1

Chest Imaging Findings

• Chest X-ray is abnormal in >80% of PE cases, though findings are non-specific. 7, 2
• Decreased pulmonary vascularity (Westermark sign) appears in 36% of PE cases versus 6% in non-PE patients. 1
• Amputation of hilar artery occurs in 36% of PE cases versus 1% in non-PE patients. 1
• Pleural effusion occurs in 46% of PE cases versus 33% in non-PE patients. 1

Critical Pitfalls to Avoid

• Up to 40% of PE patients have normal arterial oxygen saturation, making the absence of hypoxia unreliable for excluding PE. 5, 7
• Do not use normal oxygen saturation to rule out PE, as normal SaO₂ occurs in approximately 40% of cases. 7
• Patients with obvious alternative diagnoses such as acute left heart failure, pneumonia, or acute coronary syndrome should not be investigated for PE. 4
• However, in patients with pre-existing cardiopulmonary disease, worsening symptoms may represent PE superimposed on chronic disease. 1
• Tachypnea >20 breaths/min is present in 70% of PE cases and 68% of non-PE cases, limiting its discriminatory value but making its absence useful for reducing suspicion. 1, 7