What is the differential diagnosis, work‑up and initial management for a 63‑year‑old man with generalized peripheral numbness from arms to feet, no focal neurological deficits, mild diastolic hypertension and mild hypothermia, and a history of allergy treated with cetirizine?

Approach to Generalized Peripheral Numbness in a 63-Year-Old Man

This patient most likely has a length-dependent sensory polyneuropathy requiring systematic evaluation for metabolic, toxic, and inflammatory causes, with initial management focused on identifying treatable etiologies through targeted laboratory testing and symptomatic treatment if needed. 1

Differential Diagnosis

Most Likely: Length-Dependent Sensory Polyneuropathy

• The "connected sensation from arms to feet" with bilateral involvement suggests a symmetric, length-dependent polyneuropathy presenting in the classic "stocking-and-glove" distribution 1
• This pattern is characteristic of metabolic, toxic, or nutritional neuropathies rather than focal nerve lesions 1
• The absence of focal deficits (no facial drooping, slurred speech, or unilateral weakness) effectively rules out acute stroke or focal CNS pathology 1

Key Differential Considerations

Metabolic causes:

• Diabetes mellitus – the most common identifiable cause of peripheral neuropathy, accounting for a significant proportion of cases 1
• Hypothyroidism – can present with peripheral neuropathy and may explain the mild hypothermia (35.9°C) 2
• Vitamin B12 deficiency – a treatable cause that must be excluded early 2, 1

Medication-related:

• Cetirizine is not known to cause peripheral neuropathy based on extensive safety data 3, 4
• However, chronic medication use warrants review for other potential neurotoxic agents 2

Inflammatory/Autoimmune:

• Chronic Inflammatory Demyelinating Polyneuropathy (CIDP) – presents with progressive symmetric sensorimotor deficits over at least 2 months, affecting both proximal and distal regions 5
• MADSAM variant would present asymmetrically, which does not match this patient's symmetric presentation 5, 6

Idiopathic:

• 25-46% of peripheral neuropathies remain idiopathic despite thorough evaluation 1

Essential Workup

Initial Laboratory Evaluation (All Patients)

The following tests should be obtained immediately to identify treatable causes: 1

• Complete blood count – to assess for anemia, infection, or hematologic disorders 1
• Comprehensive metabolic profile – to evaluate renal function and electrolyte abnormalities 1
• Fasting blood glucose and HbA1c – diabetes is the leading identifiable cause 1
• Vitamin B12 level – a readily treatable deficiency 2, 1
• Thyroid-stimulating hormone (TSH) – hypothyroidism can cause neuropathy and may explain the hypothermia 2, 1
• Serum protein electrophoresis with immunofixation – to screen for paraproteinemia and monoclonal gammopathies 1

Physical Examination Priorities

Focus the neurologic examination on these specific findings: 2, 1

• Sensory testing:
  • Light touch and vibration sense (large-fiber function) 2
  • Pin-prick and temperature sensation (small-fiber function) 2
  • Proprioception testing 2
• Motor examination:
  • Distal muscle strength in hands and feet 1
  • Look for distal muscle atrophy in later stages 1
• Deep tendon reflexes – diminished or absent reflexes support peripheral nerve pathology 2, 5
• Autonomic assessment:
  • Orthostatic vital signs (10-12% of some neuropathies have orthostatic hypotension) 2
  • Assess for constipation or bladder dysfunction 2

When to Order Electrodiagnostic Studies

EMG and nerve conduction studies are indicated if: 2

• The clinical pattern is asymmetric (suggesting focal nerve lesions or MADSAM variant) 2
• The neurological exam is normal despite symptoms 2
• Differentiation between axonal versus demyelinating neuropathy is needed for diagnosis (e.g., CIDP) 2
• There is suspicion of hereditary neuropathy (e.g., Charcot-Marie-Tooth disease) 2

Important caveat: EMG may be normal in small-fiber neuropathy, so normal studies do not exclude the diagnosis 2

Referral to Neurology

Consider neurologist referral if: 1

• Initial laboratory evaluation is inconclusive 1
• Specific antibody assays are needed 1
• Nerve biopsy is being considered 1
• CIDP or other inflammatory neuropathy is suspected (requires specialized treatment) 5

Initial Management

Address Underlying Etiology

• Treatment focuses on managing the identified underlying cause – this is the cornerstone of peripheral neuropathy management 1
• Optimize glycemic control if diabetic 1
• Replace vitamin B12 if deficient 1
• Treat hypothyroidism if present 1

Symptomatic Pain Management (If Needed)

If the patient develops painful neuropathy: 2, 7

• Duloxetine is first-line therapy with moderate-strength evidence for neuropathic pain 2, 7
• Gabapentin or pregabalin have insufficient evidence for routine use but may be tried individually 2
• Topical combination gels (baclofen, amitriptyline ± ketamine) may be reasonable for selected patients, though evidence is limited 2, 7
• Tricyclic antidepressants and oral cannabinoids lack sufficient evidence for recommendation 2

Ongoing Monitoring

• Perform comprehensive neurologic examination at each visit to track severity and progression 2
• Recognize that some neuropathies may persist or become irreversible despite treatment 2

Critical Pitfalls to Avoid

• Do not assume cetirizine is causing the neuropathy – it is not associated with peripheral nerve toxicity 3, 4
• Do not miss treatable causes – diabetes, B12 deficiency, and hypothyroidism must be excluded early 1
• Do not order EMG reflexively – it is not needed for typical symmetric length-dependent neuropathy with clear metabolic risk factors 2
• Do not overlook the mild hypothermia (35.9°C) – this may indicate hypothyroidism, which is a treatable cause of neuropathy 2
• Do not confuse this with acute limb ischemia – the bilateral symmetric nature, absence of pain at rest, and normal temperature (not cold limbs) argue against vascular steal or acute arterial occlusion 8