Can Multiple Myeloma Cause Non-Cardiac Chest Pain?
Yes, multiple myeloma can cause non-cardiac chest pain, most commonly through rib or sternal bone involvement with lytic lesions or pathologic fractures, and less frequently through chest wall plasmacytomas or pulmonary infiltration.
Primary Mechanisms of Chest Pain in Multiple Myeloma
Bone-Related Chest Pain (Most Common)
Lytic bone lesions of the ribs, sternum, or thoracic spine are the predominant cause of chest pain in myeloma patients, as bone disease occurs in approximately 79% of patients at presentation 1.
The European Myeloma Network explicitly recognizes that pain, especially back pain and chest wall pain, may be directly attributable to myeloma bone involvement 2.
Pathologic fractures of ribs or vertebral compression fractures with anterior chest wall radiation are characteristic presentations 3, 4.
The International Myeloma Society notes that bone lesions, severe osteoporosis, and pathologic fractures are defining features of symptomatic myeloma (CRAB criteria) 3, 4.
Less Common Thoracic Manifestations
Extramedullary plasmacytomas can develop in the chest wall or pleura, causing localized chest pain 2, 5.
Pulmonary parenchymal involvement occurs in approximately 35% of patients with thoracic disease and may present as mass lesions, nodules, or interstitial infiltration causing pleuritic chest pain 5.
Chest wall soft tissue plasmacytomas account for 3-4% of plasma cell disorders and can cause persistent localized pain 2.
Critical Evaluation Approach
Initial Assessment Must Rule Out Cardiac Causes First
Despite myeloma being a potential cause, the 2021 ACC/AHA Chest Pain Guidelines mandate that cardiac evaluation takes precedence in any patient presenting with acute chest pain 2.
The guideline emphasizes that psychological factors, gastroesophageal disease, and musculoskeletal causes each exceed coronary artery disease by almost 10-fold in low-risk patients, but life-threatening cardiac conditions must be excluded first 2.
Myeloma-Specific Diagnostic Workup
Once cardiac causes are excluded, evaluate for myeloma-related chest pain with:
Skeletal survey including dedicated rib and sternal views to identify lytic lesions or fractures 2, 4, 6.
MRI of the thoracic spine and chest wall if skeletal survey is negative but clinical suspicion remains high, as MRI detects focal lesions ≥5mm that may be missed on plain films 4.
Whole-body low-dose CT or PET/CT is now preferred over conventional skeletal survey for detecting osteolytic disease and extramedullary involvement 4.
Serum and urine protein electrophoresis with immunofixation to document or monitor monoclonal protein 4, 6.
Serum free light chain assay with kappa/lambda ratio, particularly important for light chain or non-secretory disease 4, 6.
Physical Examination Findings
Point tenderness over ribs, sternum, or thoracic spine suggests focal bone involvement 3.
Pain that worsens with movement, coughing, or deep breathing is characteristic of rib or chest wall involvement rather than cardiac pain 2.
Absence of radiation to arms, jaw, or association with exertion helps distinguish from angina 2.
Management of Myeloma-Related Chest Pain
Pain Control Algorithm
For mild pain (able to perform activities of daily living):
- Paracetamol up to 1g four times daily as first-line 2.
- Avoid NSAIDs due to renal toxicity risk in myeloma patients 2.
For moderate pain (interfering with function):
- Oral tramadol or codeine 2.
- Consider adding gabapentin (300-900mg three times daily) or pregabalin for neuropathic component 2.
For severe pain (incapacitating):
- Fentanyl or buprenorphine transdermal patches, or oral oxycodone 2.
- Subcutaneous oxycodone or morphine injection for acute severe pain requiring rapid relief 2.
- All patients on opioids must receive prophylactic laxatives 2.
Disease-Directed Interventions
Bisphosphonates (zoledronic acid or pamidronate) or denosumab reduce skeletal-related events and provide pain relief 2.
Radiation therapy (typically 20-30 Gy) achieves pain relief in over 86% of patients with localized bone involvement within a median of 5 months 2.
Vertebroplasty or kyphoplasty for vertebral compression fractures causing chest wall pain 2.
Systemic anti-myeloma therapy (proteasome inhibitors, immunomodulatory drugs, corticosteroids) addresses the underlying disease and reduces bone pain 1, 7.
Important Clinical Pitfalls
Do Not Assume All Chest Pain is Myeloma-Related
The European Myeloma Network explicitly warns that "pain, especially back pain, may be due to other reasons, and not to myeloma itself" 2.
Myeloma patients remain at risk for acute coronary syndrome, pulmonary embolism (VTE risk 8-22/1000 person-years, higher with IMiD therapy), and pneumonia 2.
Thalidomide therapy can cause dangerous bradycardia, requiring monthly Holter monitoring 2.
Recognize High-Risk Presentations
Chest pain with fever suggests infection (pneumonia occurs frequently due to immunosuppression) rather than bone involvement 5.
Acute onset severe chest pain with dyspnea raises concern for pathologic rib fracture with pneumothorax or pulmonary embolism 2.
Progressive chest pain with neurologic symptoms may indicate spinal cord compression requiring emergency MRI and intervention 2.
Treatment-Related Considerations
Patients on lenalidomide or pomalidomide have VTE risk up to 70% without anticoagulation, particularly in the first 4 months of therapy 2.
Aspirin 100mg daily is sufficient for low-risk patients; LMWH or warfarin required for those with additional risk factors 2.
Prognosis and Follow-Up
Pulmonary involvement in myeloma is associated with rapid disease progression, renal failure, and pathologic fractures, indicating advanced disease 5.
Chest pain from bone involvement typically improves with effective anti-myeloma therapy and supportive measures within weeks to months 2.
Solitary plasmacytomas treated with radiation have excellent local control (>80%) but 50% progress to systemic myeloma within 10 years 2.