What is the likely diagnosis and further workup for a 39-year-old patient with chronic cervical, thoracic, and lumbar pain, numbness, elevated C-Reactive Protein (CRP), normal vitamin D level, positive Antinuclear Antibody (ANA) screen, and negative Human Leukocyte Antigen B27 (HLA B27), with an upcoming Electromyography (EMG)?

Likely Diagnosis and Immediate Workup

This patient requires urgent MRI of the cervical, thoracic, and lumbar spine with and without IV contrast to rule out spinal infection, which is the most critical diagnosis to exclude given the combination of multilevel spinal pain, neurologic symptoms (numbness), and elevated inflammatory markers (CRP 8.8 mg/L). 1, 2

Critical Red Flag Assessment

This presentation contains multiple red flags that mandate urgent imaging rather than conservative management:

• Elevated CRP (8.8 mg/L) combined with chronic multilevel spinal pain and numbness constitutes a red flag requiring urgent evaluation 1
• The combination of neurologic symptoms with any elevation of inflammatory markers requires urgent imaging to exclude spinal infection, epidural abscess, or vertebral osteomyelitis 2
• Positive ANA screen raises concern for inflammatory/autoimmune etiology affecting the spine 1

Common pitfall: Do not dismiss mildly elevated CRP (8.8 mg/L) as insignificant—while this level is in the "mild" range (10-45 mg/L typically considered mild), the combination with multilevel pain and neurologic symptoms warrants aggressive workup 3, 4

Differential Diagnosis Priority

1. Spinal Infection (Highest Priority)

• Vertebral osteomyelitis or epidural abscess can present with chronic pain and elevated CRP, even without fever 1, 2
• CRP rises within 4-6 hours of inflammatory insult and is highly sensitive for spinal infections 3
• Critical assessment needed: Inquire specifically about fever, night sweats, weight loss, IV drug use, recent spinal procedures, diabetes, immunosuppression, or indwelling catheters 2

2. Inflammatory Spondyloarthropathy

• Despite negative HLA-B27, seronegative spondyloarthropathy remains possible (HLA-B27 is only positive in ~90% of ankylosing spondylitis cases) 5
• Positive ANA with multilevel spinal pain suggests possible inflammatory arthritis 1
• ESR and CRP are commonly used for disease activity assessment in spondyloarthropathies, though both have low sensitivity and specificity 5

3. Rheumatoid Arthritis with Cervical Spine Involvement

• Positive ANA (though more commonly RF/anti-CCP positive) with chronic cervical involvement warrants consideration 6
• RA commonly involves cervical spine with potential for instability and myelopathy 6

4. Multilevel Degenerative Disease with Radiculopathy/Myelopathy

• Numbness suggests nerve root or spinal cord involvement requiring imaging 1
• However, degenerative changes alone would not explain elevated CRP 7

Immediate Workup Algorithm

Step 1: Urgent Imaging (Within 24-48 Hours)

MRI cervical, thoracic, and lumbar spine with and without IV contrast is the single most important test 1, 2:

• Sensitivity 96%, specificity 94% for spinal infection 2
• Superior for detecting epidural abscess, soft tissue abnormalities, disc herniations, and spinal cord compression 1
• IV contrast essential to differentiate infection from other pathology 1, 2

If MRI contraindicated: CT cervical, thoracic, and lumbar spine with IV contrast (sensitivity 79%, specificity 100% for vertebral osteomyelitis, but only 6% sensitive for epidural abscess) 2

Step 2: Laboratory Workup (Before Any Antibiotics)

Obtain immediately:

• Blood cultures (two sets from separate sites) before any antibiotics if infection suspected 2, 4
• ESR (highly sensitive for spine infections including paraspinal abscesses) 2, 4
• Complete blood count with differential (though WBC may be normal in up to 40% of spine infections) 2, 4
• Comprehensive metabolic panel (azotemia artificially elevates ESR) 2

Additional testing based on ANA positivity:

• Rheumatoid factor (RF) and anti-CCP antibodies to evaluate for rheumatoid arthritis 2
• ANA with reflex to specific antibodies (anti-dsDNA, anti-Smith, anti-Ro, anti-La) to characterize autoimmune disease 2

Step 3: Assess for Additional Risk Factors

Specifically document presence or absence of:

• Constitutional symptoms: fever, night sweats, unintentional weight loss 2
• Progressive weakness, bowel/bladder dysfunction (suggests cord compression requiring emergency intervention) 2
• Risk factors for infection: IV drug use, recent procedures, diabetes, immunosuppression 1, 2, 4
• Morning stiffness >45 minutes, bilateral shoulder/hip girdle pain (suggests polymyalgia rheumatica) 2

Management Based on MRI Results

If MRI Shows Spinal Infection:

• Start empiric IV antibiotics (vancomycin plus third-generation cephalosporin like ceftriaxone) immediately after blood cultures obtained 2
• Obtain tissue diagnosis via CT-guided biopsy when feasible to guide antibiotic selection 2
• Surgical consultation for neurologic compromise, vertebral destruction with instability, large epidural abscess, or medical treatment failure 2
• Monitor CRP at 4 weeks (should decline by 25-33%; CRP >27.5 mg/L at 4 weeks suggests treatment failure) 3

If MRI Shows Inflammatory Changes Without Infection:

• Rheumatology referral for comprehensive evaluation of inflammatory arthropathy 2
• Consider trial of NSAIDs if no contraindications 5
• Further serologic workup as guided by rheumatology 2

If MRI Shows Degenerative Disease with Nerve Compression:

• Proceed with planned EMG to characterize radiculopathy 1
• Consider physical therapy and conservative management initially 1
• Neurosurgery/spine surgery referral if progressive neurologic deficits or severe symptoms 1

If MRI Negative:

• Repeat ESR and CRP in 2-4 weeks to determine if elevation is persistent or transitory 2
• Continue rheumatologic workup for inflammatory arthritis given positive ANA 2
• Proceed with EMG as planned to evaluate for peripheral nerve pathology 1

Critical Pitfalls to Avoid

• Do not delay imaging based on "mild" CRP elevation—the combination with multilevel pain and neurologic symptoms mandates urgent evaluation 2, 3
• Do not start antibiotics before obtaining blood cultures if infection is suspected 2, 4
• Do not rely on normal WBC to exclude infection—it may be normal in 40% of spine infections 2, 4
• Do not dismiss negative HLA-B27 as excluding spondyloarthropathy—10% of ankylosing spondylitis patients are HLA-B27 negative 5
• Do not attribute all findings to degenerative disease without excluding infection and inflammatory causes first 1