What is the most likely diagnosis and appropriate initial work‑up and treatment for a 38‑year‑old patient with three days of sharp pleuritic chest pain that worsens when lying flat, improves when sitting up, recent viral prodrome, normal 12‑lead electrocardiogram, normal chest radiograph, and a low‑probability Wells score for pulmonary embolism?

Acute Pericarditis: Most Likely Diagnosis

Based on the clinical presentation of sharp pleuritic chest pain that worsens when lying flat, improves when sitting up, recent viral prodrome, normal ECG, normal chest radiograph, and low Wells score, the most likely diagnosis is acute viral pericarditis. 1, 2, 3

Clinical Reasoning

The constellation of symptoms strongly points toward pericarditis rather than pulmonary embolism or other serious pathology:

• Positional chest pain (worse supine, better sitting forward) is the pathognomonic feature of pericarditis and essentially rules out pulmonary embolism, which does not improve with position changes 1, 2, 3
• The recent viral prodrome is consistent with viral pericarditis, as viruses (Coxsackieviruses, respiratory syncytial virus, influenza, parainfluenza, Epstein-Barr virus) are the most common causative agents 4
• Low Wells score combined with the positional nature of pain makes pulmonary embolism extremely unlikely 1, 3
• Sharp, pleuritic pain occurs in 52% of pericarditis cases, but the positional component distinguishes it from PE-related pleuritic pain 2, 5

Critical Initial Work-Up (First 10 Minutes)

Immediate Testing Required

• 12-lead ECG should show diffuse concave ST-segment elevation with PR-segment depression (the electrocardiographic hallmark of pericarditis), though your patient's ECG is reported as normal 1, 2, 3
• Cardiac troponin must be measured immediately to exclude myocardial injury and assess for myopericarditis 1, 3
• Chest radiograph (already normal) appropriately excludes pneumothorax, pneumonia, and pleural effusion 1, 3

Physical Examination Pearls

• Listen carefully for a pericardial friction rub (biphasic, creaking sound heard during both inspiration and expiration), which confirms the diagnosis but is present in only a minority of cases 2, 3
• Assess vital signs: tachycardia may be present, but hemodynamic instability would suggest a different diagnosis 1

Diagnostic Criteria for Acute Pericarditis

Acute pericarditis is diagnosed when pleuritic chest pain is present PLUS at least one of the following: 3

1. Pericardial friction rub on auscultation
2. ECG changes (PR depression or diffuse concave ST elevation)
3. New or enlarging pericardial effusion on echocardiography

Important Caveat About Normal ECG

• Your patient has a normal ECG, which does not exclude pericarditis—ECG changes may be absent early in the course or in cases of localized inflammation 2, 3
• The positional nature of the pain and viral prodrome are sufficient to pursue this diagnosis despite normal ECG 2, 3

Additional Diagnostic Testing

Transthoracic Echocardiography

• TTE should be performed to evaluate for pericardial effusion, assess ventricular function, and rule out restrictive physiology 3
• Absence of effusion does not exclude pericarditis (many cases are "dry" pericarditis) 3

Cardiac MRI (If Diagnostic Uncertainty Persists)

• CMR with gadolinium contrast is useful to determine the extent of pericardial inflammation and differentiate myopericarditis from other causes when troponin is elevated 3

Treatment Algorithm

First-Line Symptomatic Therapy

• Acetaminophen may be used for early symptomatic relief 3

Anti-Inflammatory Therapy

• High-dose aspirin 500 mg–1 g every 6–8 hours is the recommended first-line anti-inflammatory agent to reduce pain and inflammation 3

Colchicine Therapy (Critical for Preventing Recurrence)

• Colchicine 0.5–0.6 mg once or twice daily for approximately 3 months significantly reduces symptoms and lowers the risk of recurrent pericarditis 3
• For patients weighing less than 70 kg, use a reduced daily dose 3

Medications to AVOID

• Glucocorticoids and non-aspirin NSAIDs are contraindicated because they may increase the risk of recurrent myocardial infarction or impair myocardial healing 3

Common Pitfalls to Avoid

Do Not Assume Normal ECG Excludes Pericarditis

• ECG sensitivity for pericarditis is imperfect; rely on the clinical presentation (positional pain, viral prodrome) as the primary diagnostic clue 2, 3

Do Not Delay Troponin Testing

• Approximately 10% of pericarditis cases have myocardial involvement (myopericarditis), which requires different risk stratification 3
• Elevated troponin necessitates cardiac MRI and closer monitoring 3

Do Not Overlook Pulmonary Embolism Entirely

• While the positional nature of pain makes PE unlikely, 13% of acute coronary syndrome patients present with pleuritic pain, so maintain vigilance 2, 3
• The low Wells score and normal chest X-ray support withholding further PE workup unless clinical suspicion changes 1, 3

Do Not Use Nitroglycerin Response as a Diagnostic Test

• Relief with nitroglycerin does not confirm or exclude any specific diagnosis 1

Disposition and Follow-Up

• Outpatient management is appropriate if hemodynamically stable, no evidence of myocarditis (normal troponin), and no large pericardial effusion on echo 3
• Cardiology consultation is recommended for confirmation of diagnosis and management guidance 2
• Reassess in 1–2 weeks to ensure symptom improvement and monitor for complications (recurrence, effusion development) 3