In an 83-year-old woman with sudden onset of back pain, severe anemia and markedly elevated erythrocyte sedimentation rate, what are the differential diagnoses and appropriate laboratory and imaging investigations?

Differential Diagnosis and Diagnostic Work-Up for an 83-Year-Old Woman with Sudden Back Pain, Severe Anemia, and Markedly Elevated ESR

Most Likely Differential Diagnoses

The combination of sudden back pain, severe anemia (Hb 7.4 g/dL), and markedly elevated ESR (100 mm/hr) in an elderly woman strongly suggests vertebral osteomyelitis/discitis, spinal metastatic disease, or multiple myeloma as the primary diagnostic considerations. 1, 2

High-Priority Diagnoses Requiring Urgent Evaluation:

• Vertebral osteomyelitis/discitis: Infection presents with back pain, elevated inflammatory markers (ESR/CRP), and can cause anemia of chronic disease; CRP >100 mg/L strongly suggests active spinal infection 1
• Spinal metastatic disease: Prior cancer history raises probability from 0.7% to 9%; age >50 years is a red flag, and metastatic disease can cause pathologic fractures and anemia 2, 3
• Multiple myeloma: Classic triad of back pain (from lytic lesions/compression fractures), anemia (from marrow infiltration), and elevated ESR; particularly common in elderly patients 4
• Compression fracture with underlying malignancy: Advanced age and osteoporosis increase fracture risk; sudden onset suggests acute vertebral collapse 5
• Epidural abscess with spinal cord compression: Requires emergent neurosurgical evaluation if neurologic deficits present 1

Lower-Priority but Important Considerations:

• Giant cell arteritis (temporal arteritis): Can present with elevated ESR in elderly; check for scalp tenderness, jaw claudication, or visual symptoms 5
• Severe anemia from occult gastrointestinal bleeding: Though less likely to cause sudden back pain, chronic blood loss can present with severe anemia and elevated ESR 6, 7

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Immediate Laboratory Investigations

Draw blood cultures and obtain inflammatory markers before starting any antimicrobial therapy to maximize diagnostic yield. 1

Essential First-Line Laboratory Tests:

• Two sets of blood cultures from separate sites (before antibiotics): Mandatory for suspected infection; premature antibiotics markedly reduce diagnostic yield 1
• Complete blood count with peripheral smear: Evaluate for schistocytes (microangiopathic hemolysis), rouleaux formation (myeloma), or leukoerythroblastic picture (marrow infiltration) 7, 4
• C-reactive protein (CRP): More sensitive than ESR for infection; CRP >100 mg/L strongly suggests active spinal infection, and CRP is more responsive than ESR for monitoring 1
• Erythrocyte sedimentation rate (ESR): Already elevated at 100 mm/hr; useful for temporal arteritis diagnosis (though less specific for infection than CRP) 5, 8
• Serum protein electrophoresis (SPEP) with immunofixation: Screen for monoclonal gammopathy in suspected multiple myeloma 4
• Serum calcium and creatinine: Hypercalcemia and renal dysfunction suggest myeloma 4
• Reticulocyte count: Distinguish between hypoproliferative anemia (marrow infiltration, chronic disease) versus hemolysis or blood loss 4
• Iron studies, vitamin B12, and folate: One-third of anemia in elderly is nutritional deficiency 4

Additional Tests Based on Clinical Suspicion:

• Serum lactate dehydrogenase (LDH) and haptoglobin: If hemolysis suspected from peripheral smear 7
• HIV, diabetes screening: Major risk factors for infectious myelitis 1
• Tuberculosis testing (QuantiFERON or PPD): If endemic exposure, immunocompromise, or imaging shows large paraspinal abscess 1

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Imaging Strategy

Obtain urgent MRI of the entire spine with and without IV contrast as the first-line imaging study; this is mandatory to differentiate infection, malignancy, compression fracture, and epidural abscess. 1, 2

Primary Imaging Recommendation:

• MRI complete spine (cervical, thoracic, lumbar) without and with IV contrast:
  • Preferred modality with 96% sensitivity and 94% specificity for spinal infection 2
  • Whole-spine coverage is essential because multilevel involvement occurs in ~51% of spinal infections and skip lesions in ~8% 1
  • Contrast enhancement is mandatory to reveal abscess formation, meningeal involvement, epidural collections, and characteristic infection/tumor enhancement patterns 1, 2
  • Superior soft-tissue resolution compared to CT; visualizes bone marrow edema, disc space, spinal cord, and nerve roots 5
  • Identifies epidural abscess or spinal cord compression requiring emergent neurosurgical intervention 1

Alternative or Complementary Imaging:

• Plain radiographs of the spine (AP and lateral views): May be appropriate if MRI unavailable or contraindicated; can identify compression fractures, lytic lesions, or bone destruction, but cannot visualize discs or soft tissues 5
• CT spine without IV contrast: Useful if MRI contraindicated (pacemaker, severe claustrophobia); superior for detecting mineralized matrix, nondisplaced fractures, and cortical bone destruction, but inferior for soft-tissue and marrow evaluation 5
• CT-guided biopsy: If tuberculosis suspected (large paraspinal abscess disproportionate to bone destruction) or if diagnosis remains unclear after initial imaging; obtain before starting anti-tubercular therapy 1

Critical Imaging Pitfalls to Avoid:

• Do not postpone MRI while awaiting laboratory results; timely imaging is essential to rule out surgical emergencies like epidural abscess or cord compression 1
• Avoid single-level MRI; whole-spine imaging is required to detect multilevel or skip lesions 1
• Do not order MRI without contrast alone; contrast is mandatory for infection and malignancy evaluation 1, 2

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Red Flags Requiring Immediate Neurosurgical Consultation

Any of the following findings mandate urgent neurosurgical evaluation: 1, 2, 3

• New or worsening motor weakness, sensory level change, or bowel/bladder dysfunction (cauda equina syndrome has ~90% sensitivity for urinary retention) 2, 3
• MRI evidence of epidural abscess or significant spinal cord compression 1
• Spinal instability or pronounced kyphotic deformity 1
• Rapidly progressive or severe neurologic deficits at multiple levels 2, 3

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Empiric Management Considerations

Delay empiric antimicrobial therapy until after blood cultures and any planned diagnostic procedures (lumbar puncture, biopsy) are completed, unless the patient is hemodynamically unstable, septic, or has rapid neurologic decline. 1

If Empiric Antibiotics Are Required:

• Vancomycin (MRSA coverage) plus third- or fourth-generation cephalosporin (gram-negative coverage) plus acyclovir (HSV/VZV coverage) for suspected infectious myelitis 1
• If tuberculosis suspected: Obtain image-guided biopsy before starting anti-tubercular therapy (2 months isoniazid, rifampicin, pyrazinamide, ethambutol followed by 4 months isoniazid and rifampicin) 1

Critical Pitfall:

• A normal white blood cell count does not exclude infection; up to 40% of spinal infections present with normal WBC 1

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Monitoring and Follow-Up

• Serial CRP measurements are more responsive than ESR; CRP >2.75 mg/dL after 4 weeks suggests treatment failure 1
• Repeat MRI at intervals to assess disease response and detect complications 1
• Monitor for drug toxicity: Liver function tests for anti-tubercular agents, visual acuity for ethambutol, renal function for vancomycin and acyclovir 1