What blood tests should be ordered for a patient with neuropathic pain in extremities?

Blood Tests for Patients with Neuropathic Pain in Extremities

For patients with neuropathic pain in the extremities, a comprehensive laboratory workup should include blood glucose, serum B12 with metabolites (methylmalonic acid with or without homocysteine), and serum protein immunofixation electrophoresis as these tests have the highest yield for identifying treatable causes of neuropathy. 1

Primary Laboratory Tests (First-Line)

• Blood glucose/HbA1c: Diabetes is a common cause of neuropathic pain, and patients with distal symmetric sensory polyneuropathy have a relatively high prevalence of diabetes or pre-diabetes 1
• Glucose tolerance test (GTT): When routine blood glucose testing is not clearly abnormal, GTT should be considered, especially in patients with painful neuropathy 1
• Vitamin B12 with metabolites (methylmalonic acid with or without homocysteine): B12 deficiency is a reversible cause of neuropathy 1
• Serum protein immunofixation electrophoresis (IFE): More sensitive than serum protein electrophoresis (SPEP) for detecting monoclonal gammopathies, which are more common in patients with polyneuropathy 1
• Thyroid function tests (TSH): Hypothyroidism can cause neuropathy 1

Additional Tests Based on Clinical Suspicion

• Complete blood count: To evaluate for anemia, infection, or malignancy 1
• Renal function tests: Renal disease can cause neuropathy 1
• Liver function tests: To assess for liver disease that may contribute to neuropathy 1
• ESR/CRP: To screen for inflammatory conditions 1
• ANA, ANCA: For suspected autoimmune or vasculitic neuropathies 1

Specialized Tests for Specific Clinical Scenarios

• Antiganglioside antibodies: When Guillain-Barré syndrome or its variants are suspected 1
• Anti-MAG antibodies: For suspected paraproteinemic neuropathy 1
• HIV, Hepatitis B/C testing: When infectious causes are suspected 1
• Lyme disease serology: In endemic areas or with relevant exposure history 1
• Paraneoplastic antibody panel (including anti-Hu/ANNA-1): When paraneoplastic neuropathy is suspected 1

Algorithm for Laboratory Testing

1. Initial evaluation: Order blood glucose/HbA1c, vitamin B12 with metabolites, serum protein immunofixation electrophoresis, and TSH for all patients with neuropathic pain 1

2. If initial tests are normal but symptoms persist:

   • Consider glucose tolerance test, especially with painful neuropathy 1
   • Add ESR/CRP, complete blood count, and renal/liver function tests 1

3. If clinical features suggest specific etiology:

   • Asymmetric symptoms: Consider specialized antibody testing 1
   • Rapid progression: Consider paraneoplastic antibodies, antiganglioside antibodies 1
   • Systemic symptoms: Add ANA, ANCA, HIV, hepatitis testing 1

Important Considerations

• Diabetic neuropathy is a diagnosis of exclusion, and other causes of neuropathy should be considered even in patients with known diabetes 1
• Up to 50% of diabetic peripheral neuropathy may be asymptomatic, so laboratory testing is essential even when symptoms are minimal 1
• The yield of laboratory testing varies depending on the particular test, with blood glucose, B12 with metabolites, and serum protein immunofixation having the highest yield 1

Common Pitfalls to Avoid

• Failing to test for glucose intolerance when fasting glucose is normal - impaired glucose tolerance can cause neuropathy even without frank diabetes 1
• Using only SPEP instead of IFE - IFE is more sensitive for detecting monoclonal gammopathies 1
• Overlooking B12 deficiency - always check B12 with metabolites as normal B12 levels can still be associated with functional deficiency 1
• Assuming all neuropathic pain in a diabetic patient is due to diabetes - other treatable causes should still be investigated 1