What is the initial workup and treatment for a patient presenting with peripheral numbness and tingling?

Initial Workup for Peripheral Numbness and Tingling

Begin with a focused history to determine symptom distribution (distal symmetric "stocking-glove" versus patchy), temporal profile (acute versus chronic), and associated features (pain, burning, weakness, autonomic symptoms), followed by immediate laboratory testing for diabetes, vitamin B12 deficiency, and thyroid dysfunction. 1, 2

Immediate Clinical Assessment

History Taking

• Determine fiber type involvement by asking specifically about burning pain and tingling (small fiber) versus numbness with loss of balance (large fiber) 1, 3
• Assess distribution pattern: distal symmetric suggests metabolic/toxic causes; patchy or asymmetric suggests mononeuropathy multiplex from vasculitis or leprosy 2, 4
• Identify red flags for urgent evaluation: hemibody sensory loss without motor weakness requires stroke evaluation within 48 hours 1
• Medication review focusing on metformin (especially ≥2g daily), chemotherapy agents, and statins as common culprits 1

Physical Examination

• Small fiber testing: pinprick sensation and temperature perception 5, 3
• Large fiber testing: vibration perception with 128-Hz tuning fork, 10-g monofilament testing, and ankle reflexes 1, 5
• Motor examination: assess for distal weakness or atrophy indicating advanced disease 2
• Autonomic signs: check for orthostatic hypotension, resting tachycardia, and skin dryness/cracking 5

Initial Laboratory Workup

Order these tests immediately for all patients with peripheral numbness/tingling: 2, 6

• Complete blood count (anemia, infection, malignancy screening)
• Comprehensive metabolic profile (renal disease, electrolyte abnormalities)
• Fasting blood glucose and HbA1c (diabetes is the most common treatable cause) 1, 5
• Vitamin B12 level (especially critical if patient takes metformin) 1, 2
• Thyroid-stimulating hormone (hypothyroidism is a common treatable cause) 2, 6
• Erythrocyte sedimentation rate (inflammatory/vasculitic causes) 6
• Serum protein electrophoresis with immunofixation (paraproteinemic neuropathy) 2

Additional Testing Based on Clinical Context

• Hepatitis C serology if risk factors present (up to 50% of HCV patients develop neuropathy) 1
• Electrodiagnostic studies (nerve conduction studies and EMG) if diagnosis remains unclear after initial workup to differentiate axonal versus demyelinating patterns 2, 7, 4

Treatment Approach

Address Underlying Causes First

• Optimize glycemic control if diabetic (HbA1c target 6-7%); this is the only proven strategy to prevent or delay diabetic neuropathy progression 1, 5
• Vitamin B12 supplementation at 2500 mcg daily if deficient, particularly in metformin users 1
• Treat hypothyroidism if identified 6

Symptomatic Management for Neuropathic Pain

First-line pharmacologic options: 5, 3

• Duloxetine (preferred for chemotherapy-induced neuropathy and diabetic neuropathy with pain) 8, 1, 5
• Pregabalin (first-line for diabetic peripheral neuropathy) 5, 3
• Gabapentin 300-1200 mg three times daily 5

Alternative options if first-line agents fail: 5

• Tricyclic antidepressants (amitriptyline), but use cautiously in patients ≥65 years due to anticholinergic effects
• Topical capsaicin (8% patch or 0.075% cream) for localized pain

Non-Pharmacologic Interventions

• Physical activity is recommended for both chemotherapy-induced and diabetic neuropathy 8, 5
• Acupuncture may be offered for musculoskeletal-related neuropathic symptoms 8

Common Pitfalls and Monitoring

• Do NOT use acetyl-L-carnitine for prevention of chemotherapy-induced peripheral neuropathy (harms outweigh benefits) 8
• Avoid opioids (tapentadol, tramadol) for chronic neuropathic pain due to addiction risk 5
• Monitor metformin users closely for B12 deficiency, as long-term use causes neuropathy in a stocking-glove distribution 1
• Annual foot examinations with 10-g monofilament testing are mandatory once loss of protective sensation is documented to prevent ulceration 5, 3
• Start medications at lower doses in older patients and titrate slowly to minimize adverse events 5

When to Refer

• Neurology referral if initial workup is inconclusive or if electrodiagnostic studies, specific antibody assays, or nerve biopsy are needed 2
• Reproductive endocrinology referral for chemotherapy patients of childbearing age with fertility concerns 8
• Stroke evaluation within 48 hours for hemibody sensory loss 1