What is the next step for a 35-year-old patient with ulcerative colitis (UC) who started on Rituximab (rituximab) and now has constant chest pain for a few weeks with a negative electrocardiogram (EKG) and negative troponin?

Evaluation of Constant Chest Pain in a 35-Year-Old UC Patient on Rituximab

The next step is to obtain a chest X-ray and consider advanced cardiac imaging (echocardiography or cardiac CT) to evaluate for rituximab-associated cardiovascular complications, pericarditis, or other life-threatening causes, while simultaneously assessing for musculoskeletal causes through physical examination with specific palpation of costochondral joints.

Immediate Diagnostic Priorities

Rule Out Life-Threatening Cardiac Causes

While the initial EKG and troponin are negative, this does not exclude all serious cardiac pathology in a patient on rituximab:

• Rituximab carries specific cardiovascular risks including ventricular fibrillation, myocardial infarction, and cardiogenic shock that may not present with typical biomarker elevation initially 1
• Perform transthoracic echocardiography to evaluate for pericarditis (which can present with constant chest pain worsened in supine position), stress cardiomyopathy, or valvular abnormalities 2
• Obtain chest X-ray immediately to evaluate for pneumonia, pneumothorax, pleural effusion, or widened mediastinum suggesting aortic pathology 2

Consider Rituximab-Specific Complications

Rituximab has documented gastrointestinal and cardiovascular toxicities that must be considered:

• Rituximab-associated cardiovascular adverse reactions can manifest as chest pain and irregular heartbeats, requiring immediate evaluation 1
• While rituximab-associated colitis is more common (4% incidence), cardiovascular complications including myocardial infarction have been reported 3, 1
• The median time from rituximab treatment to adverse events is approximately 181 days, making this temporally plausible 3

Systematic Evaluation Algorithm

Step 1: Focused Physical Examination (Perform Immediately)

• Palpate costochondral joints systematically - tenderness here suggests costochondritis, which is the most common cause of nontraumatic musculoskeletal chest wall pain (42%) 4
• Assess for pericardial friction rub - pericarditis presents with constant pain increased in supine position 2
• Check for pulse differentials and blood pressure in both arms - aortic dissection can present with severe constant pain 2
• Auscultate for murmurs - new murmurs may indicate valvular complications 2

Step 2: Laboratory and Imaging Workup

Order the following tests based on initial examination:

• Repeat high-sensitivity troponin at 3 hours if initial presentation was within 6 hours of pain onset, as serial troponins improve sensitivity for acute coronary syndrome 2
• Chest X-ray to evaluate for pneumonia (fever, egophony, dullness to percussion), pneumothorax (unilateral absent breath sounds), or pleural disease 2
• Transthoracic echocardiography if any hemodynamic disturbances, new murmurs, or concern for pericarditis 2
• Consider D-dimer if pulmonary embolism is suspected (tachycardia, dyspnea, pleuritic pain) 2

Step 3: Risk Stratification

For a 35-year-old with constant chest pain for weeks and negative initial workup:

• The duration (weeks) and constant nature makes acute coronary syndrome less likely but does not exclude it 2
• Low-risk features include: reproducible pain with palpation, absence of radiation, no associated dyspnea or diaphoresis 2, 5
• High-risk features requiring urgent evaluation include: ongoing severe pain, hemodynamic instability, new ECG changes, or elevated troponin 2

Differential Diagnosis Priority List

Most Likely Diagnoses to Evaluate:

1. Costochondritis - characterized by tenderness to palpation of costochondral joints, often affects ribs 6-7, pain may be stinging or pressing 4
2. Pericarditis - constant pain worsened supine, may have friction rub, can be associated with inflammatory conditions 2
3. Rituximab-associated cardiovascular toxicity - documented risk of myocardial infarction and chest pain 1
4. Gastroesophageal reflux disease - common cause of constant chest discomfort 2, 5
5. Anxiety/panic disorder - can present with chest pain; screen with two-item questionnaire 6

Less Common but Critical to Exclude:

• Pulmonary embolism - rituximab patients may have increased thrombotic risk; one case of pulmonary embolism was reported in rituximab trials 7
• Pneumonia - rituximab increases infection risk; look for fever, productive cough, focal findings 1
• Aortic dissection - severe constant pain with abrupt onset, pulse differential 2

Management Based on Findings

If Costochondritis is Confirmed:

• Initiate NSAIDs for 1-2 weeks (if no contraindications) 4
• Consider low-dose colchicine if symptoms persist despite NSAID therapy 4
• Apply ice or heat packs as adjunctive therapy 4
• Reassess if symptoms persist to rule out other causes 4

If Cardiac Cause Cannot Be Excluded:

• Refer to emergency department immediately for patients with high-risk features 2
• Consider cardiac stress testing or coronary CT angiography for intermediate-risk patients once acute coronary syndrome is excluded 2, 5
• Admit for observation if ongoing symptoms despite negative initial workup, particularly given rituximab's cardiovascular risks 1

Critical Pitfalls to Avoid

• Do not dismiss constant chest pain lasting weeks as benign without thorough evaluation, especially in a patient on immunosuppressive therapy 1
• Do not rely solely on initial negative troponin - serial troponins and advanced imaging may be needed 2
• Do not overlook rituximab-specific complications including cardiovascular toxicity and increased infection risk 1
• Do not assume musculoskeletal cause without documenting reproducible tenderness on examination 4, 5
• Remember that relief with nitroglycerin is not diagnostic of cardiac ischemia and can occur with esophageal spasm 2