Widespread Numbness, Burning, and Increased Sensitivity to Touch
Diagnosis: Length-Dependent Peripheral Neuropathy
This clinical presentation—widespread numbness, burning sensation, and increased sensitivity to touch (allodynia/hyperalgesia)—is characteristic of distal symmetric polyneuropathy, most commonly caused by diabetes mellitus, which must be ruled out immediately along with vitamin B12 deficiency and other metabolic causes. 1, 2, 3
The symptom pattern described represents both "plus" symptoms (burning pain, increased sensitivity) and "minus" symptoms (numbness), typically affecting feet more than hands in a stocking-and-glove distribution, indicating small and large fiber involvement. 1
Immediate Diagnostic Workup
Essential Testing to Identify Underlying Cause
Screen for diabetes immediately with fasting glucose, HbA1c, and consider oral glucose tolerance test if prediabetes is suspected, as diabetes is the most common cause and impaired glucose tolerance can cause neuropathy even before overt diabetes develops. 2, 3
Check vitamin B12 levels (with methylmalonic acid and homocysteine if B12 is borderline 150-220 pg/mL), as B12 deficiency causes identical symptoms and is frequently overlooked, especially in patients taking metformin or proton pump inhibitors. 3, 4, 5, 6
Rule out other metabolic causes: thyroid function tests (hypothyroidism), comprehensive metabolic panel (renal disease), complete blood count, and erythrocyte sedimentation rate. 3, 4
Screen for nutritional deficiencies: vitamin E, thiamine, folate, and copper levels, particularly if malabsorption history exists. 3
Check for monoclonal gammopathy: serum protein electrophoresis with immunofixation and serum free light chains, as plasma cell dyscrasias cause neuropathy. 3
Assess medication history for neurotoxic drugs: chemotherapy agents (bortezomib, thalidomide, vincristine, taxanes, platinum compounds), metronidazole, and anti-TNF agents. 1, 3
Hepatitis C screening if risk factors present, as HCV-associated neuropathy occurs in up to 50% of infected patients. 1
Clinical Examination Specifics
Test small fiber function: pinprick sensation and temperature perception (cold/warm discrimination) on toes and fingers—decreased sensation in painful areas confirms small fiber neuropathy. 1, 2
Test large fiber function: 128-Hz tuning fork vibration sense at great toe dorsum and 10-g monofilament testing at multiple plantar sites—inability to perceive indicates loss of protective sensation. 1, 2
Assess deep tendon reflexes: ankle reflexes are typically diminished or absent in length-dependent neuropathy. 1, 2
Examine for foot deformities, skin integrity, calluses, and pre-ulcerative lesions, as these increase amputation risk. 1, 2
Check for autonomic involvement: orthostatic blood pressure (drop >20 mmHg systolic suggests autonomic neuropathy), resting tachycardia >100 bpm, and inquire about constipation, bladder dysfunction, or erectile dysfunction. 1
Electrophysiological testing (nerve conduction studies/EMG) is NOT routinely needed unless the pattern is atypical, asymmetric, or predominantly motor, as clinical examination is sufficient for typical length-dependent sensory neuropathy. 1, 2
Treatment Algorithm
Step 1: Address Underlying Cause Immediately
If diabetes is confirmed: Optimize glycemic control gradually (target individualized HbA1c, typically 6-7%) to prevent progression, but avoid rapid HbA1c reduction if severely elevated as this paradoxically worsens neuropathic pain temporarily. 1, 2, 4
If vitamin B12 deficiency confirmed (<150 pg/mL definite, <220 pg/mL possible): Initiate intramuscular cyanocobalamin 1000 mcg weekly for 4-8 weeks, then monthly indefinitely, or high-dose oral B12 1000-2000 mcg daily—symptoms may stabilize but objective findings rarely improve once established. 5, 6, 7, 8
If metformin use identified: Continue metformin but add calcium 500 mg with meals and vitamin B12 supplementation, as metformin blocks B12 absorption and accelerates neuropathy development after 5+ years of use. 6, 7
Manage cardiovascular risk factors aggressively: blood pressure target <130/80 mmHg, statin therapy for lipid control, and mandatory smoking cessation as smoking significantly increases amputation risk. 1, 2, 4
Step 2: Initiate First-Line Neuropathic Pain Medication Immediately
Do not delay pharmacologic treatment while waiting for diagnostic results or attempting glycemic optimization alone, as pain significantly impairs quality of life. 1, 4
Choose ONE of the following based on patient comorbidities:
Pregabalin 75 mg twice daily, titrate to 300-600 mg/day divided twice daily (FDA-approved for diabetic neuropathy, NNT 7.7)—preferred if patient has anxiety or insomnia as side effects. 1, 4
Duloxetine 30 mg daily, titrate to 60-120 mg/day (FDA-approved for diabetic neuropathy, NNT 6.4)—preferred if patient has comorbid depression or urinary incontinence. 1, 4
Gabapentin 300 mg at bedtime, titrate to 900-3600 mg/day divided three times daily (NNT 6.3)—preferred if cost is a barrier, as generic is inexpensive. 1, 4
If first-line agent fails after 4-6 weeks at therapeutic dose, switch to alternative first-line agent rather than adding second drug. 1
Step 3: Consider Second-Line Options if First-Line Fails
Tricyclic antidepressants (amitriptyline 10-75 mg at bedtime, NNT 1.5-3.5) are highly effective but have significant anticholinergic side effects and cardiac risk >100 mg/day—avoid in elderly or those with cardiac disease. 1
Tramadol 50 mg twice daily, titrate to 200-400 mg/day if opioid therapy necessary, but use cautiously due to addiction potential. 1
Step 4: Critical Preventive Foot Care (Non-Negotiable)
Refer to podiatry immediately for ongoing preventive care, therapeutic footwear prescription with adequate cushioning and depth, and regular nail care. 1, 2, 4
Educate patient on daily foot self-examination using mirror to inspect plantar surfaces for cuts, blisters, redness, or calluses—any skin break requires immediate medical attention. 1, 2, 4
Never walk barefoot, even indoors; check inside shoes before wearing for foreign objects; test bath water with elbow, not foot. 2, 4
Inspect feet at every clinical visit (every 3-6 months minimum depending on risk category) with comprehensive vascular assessment including pedal pulses, capillary refill, and assessment for dependent rubor or pallor on elevation. 1, 2
Critical Pitfalls to Avoid
Do not attribute all neuropathy to diabetes without checking B12 levels, as metformin-induced B12 deficiency compounds diabetic neuropathy and is reversible if caught early. 4, 6, 7
Do not prescribe nitrofurantoin for urinary tract infections in patients with neuropathy, as it significantly worsens nerve damage. 4
Do not give folic acid >0.1 mg/day without confirming B12 adequacy, as folic acid masks B12 deficiency anemia while allowing irreversible spinal cord degeneration to progress. 5
Do not rely solely on nerve conduction studies, as small fiber neuropathy (70-90% of peripheral nerve fibers) shows normal conventional electrophysiology and will be missed. 3
Do not delay treatment waiting for "optimal" glucose control, as neuropathic pain management and foot care are independent of glycemic optimization and prevent catastrophic outcomes. 1, 4
Monitoring and Follow-Up
Reassess neuropathy severity every 3-6 months with 10-g monofilament testing, vibration sense, and symptom scoring to monitor progression. 1, 2, 4
Monitor for Charcot neuroarthropathy (unilateral red, warm, swollen foot with intact skin)—requires immediate immobilization and imaging if suspected. 2
Screen annually for cardiac autonomic neuropathy with resting heart rate and orthostatic vital signs, as this often coexists with peripheral neuropathy and increases mortality risk. 1, 4
Recheck vitamin B12 levels every 6-12 months if on metformin or if initially deficient, with continued supplementation as needed. 4, 6