What is the differential diagnosis for numbness and burning in the feet?

Differential Diagnosis of Numbness and Burning in Feet

The differential diagnosis for numbness and burning in the feet includes diabetic peripheral neuropathy (most common), alcohol-related neuropathy, vitamin B12 deficiency, medication-induced neuropathy (especially chemotherapy agents), hypothyroidism, chronic kidney disease, monoclonal gammopathies, hepatitis C-related neuropathy, rheumatoid neuropathy, and idiopathic small fiber neuropathy. 1, 2

Most Common Etiologies

Diabetic Peripheral Neuropathy

• Diabetes is the single most common cause of peripheral neuropathy worldwide, accounting for more than 50% of cases in Western populations and affecting approximately 206 million people globally. 1
• Presents as length-dependent, symmetric sensory symptoms including burning, tingling, numbness, and pain in a "stocking and glove" distribution starting distally in the toes. 3, 1, 2
• Small fiber involvement causes the burning and dysesthesias, while large fiber involvement causes numbness and loss of protective sensation. 3

Alcohol-Related Neuropathy

• Total lifetime ethanol dose is the most important risk factor, followed by duration of alcoholic disease. 4
• Presents with similar burning and numbness symptoms as diabetic neuropathy, often with coexisting nutritional deficiencies (especially thiamine and B vitamins). 4
• Recovery is possible over several months to years with absolute alcohol abstinence. 4

Vitamin B12 Deficiency

• Must be screened in all patients with neuropathy symptoms, especially those taking metformin. 3, 5
• Can compound neuropathy risk and is a treatable cause that should never be overlooked. 5

Less Common but Important Causes

Medication-Induced Neuropathy

• Chemotherapy agents (cisplatin, paclitaxel, vincristine), amiodarone, and HIV medications (stavudine, zalcitabine) are common culprits. 1
• Nitrofurantoin significantly increases neuropathy risk and should be avoided in diabetic patients. 5

Hepatitis C-Related Neuropathy

• Up to 50% of HCV-infected patients develop peripheral neuropathy, presenting with sensory loss, paresthesias, numbness, cramps, burning feet, and tingling. 3
• Can be associated with cryoglobulinemia and may present as asymmetric mononeuritis in severe cases. 3

Monoclonal Gammopathies

• Should be screened with serum protein electrophoresis with immunofixation in all patients with unexplained neuropathy. 1, 2

Rheumatoid Neuropathy

• Presents with stiffness in hands and feet, burning and tingling, stabbing pain, occasional weakness, and numbness. 6
• Greater predilection in females, with direct relation between rheumatoid factor levels and neuropathy occurrence. 6

Hypothyroidism and Chronic Kidney Disease

• Both are treatable causes that must be excluded in the initial workup. 3, 2

Idiopathic Neuropathy

• Accounts for 25% to 46% of peripheral neuropathy cases after comprehensive evaluation. 2
• Up to 27% of adults have no identifiable etiology despite thorough diagnostic testing. 1

Critical Diagnostic Approach

Initial Laboratory Testing

Order the following tests immediately to identify treatable causes: 2

• Fasting blood glucose or HbA1c (diabetes screening)
• Vitamin B12 with methylmalonic acid ± homocysteine
• Serum protein electrophoresis with immunofixation
• Complete blood count
• Comprehensive metabolic profile (kidney function, electrolytes)
• Thyroid-stimulating hormone

Clinical Examination

• Assess pinprick sensation and temperature (small fiber function). 3
• Test vibration perception with 128-Hz tuning fork (large fiber function). 3
• Perform 10-g monofilament testing at multiple plantar sites to assess loss of protective sensation. 3, 4
• Evaluate ankle reflexes. 3

Additional Considerations

• Obtain detailed medication history, including chemotherapy, antibiotics, and cardiac medications. 1
• Assess alcohol consumption history and total lifetime exposure. 4
• Screen for HIV if risk factors present. 1
• Consider hepatitis C testing if other risk factors or systemic symptoms present. 3

Common Pitfalls to Avoid

• Peripheral neuropathy is a diagnosis of exclusion—always rule out treatable causes before attributing symptoms solely to diabetes. 3, 5, 4
• Do not overlook vitamin B12 deficiency, especially in patients on metformin. 5
• Do not prescribe nitrofurantoin for urinary tract infections in patients with or at risk for neuropathy. 5
• Electrodiagnostic studies are rarely needed for initial diagnosis and should not delay treatment. 3, 5