What is the most likely diagnosis and differential for a 68‑year‑old woman with joint pain and burning skin sensation, history of gastric bypass, bipolar disorder, depression, and taking amlodipine, zolpidem (Ambien), escitalopram, gabapentin, tirzepatide (Mounjaro), and hydroxyzine?

Diagnosis: Post-Gastric Bypass Nutritional Neuropathy

The most likely diagnosis is peripheral neuropathy secondary to nutritional deficiencies following gastric bypass surgery, specifically thiamine (B1) and other B-vitamin deficiencies, which occur in 16% of bariatric surgery patients and present with burning sensations and joint pain. 1

Primary Diagnosis

• Nutritional peripheral neuropathy is the leading diagnosis given the combination of burning skin sensation, joint pain, and history of gastric bypass surgery 2, 1
• Peripheral neuropathy develops in 16% of bariatric surgery patients compared to only 3% after other abdominal surgeries, establishing a clear causal relationship 1
• The median time to onset of neurologic manifestations after bariatric surgery is 12 months, though symptoms can appear as early as 3.5 months post-operatively 3, 4
• Thiamine (B1) deficiency is the most common clinically relevant micronutrient deficiency after gastric bypass, followed by B12, vitamin D, iron, and copper 5
• The burning sensation described is characteristic of sensory-predominant polyneuropathy, the most common pattern (27/71 patients) following bariatric surgery 1

Critical Differential Diagnoses to Exclude

Wernicke-Korsakoff Syndrome (WKS)

• Must be ruled out urgently as it occurs in bariatric patients and causes irreversible neurologic damage if untreated 4
• Look specifically for the triad: confusion/altered mental status, ataxia/gait abnormality, and ophthalmoplegia 4
• Her current medications (escitalopram for depression, gabapentin) may mask early cognitive symptoms
• WKS is not reversible and all four patients in one series had residual ataxia and nystagmus despite treatment 4

Diabetic Neuropathy

• Consider if patient has diabetes or prediabetes (Mounjaro suggests possible diabetes history) 6
• Diabetic neuropathy presents with similar burning sensations and can coexist with nutritional deficiency 6
• Check HbA1c and fasting glucose to assess glycemic control 6

Medication-Induced Neuropathy

• Gabapentin is prescribed for neuropathic pain but does not cause neuropathy 6
• Amlodipine can cause peripheral edema mimicking neuropathy but does not cause burning sensations 6

Fibromyalgia

• Can present with widespread pain and burning sensations 6
• However, fibromyalgia does not explain the post-gastric bypass context and typically has normal inflammatory markers 6
• The presence of objective nutritional risk factors makes primary fibromyalgia less likely 6

IBD-Associated Type 2 Peripheral Arthropathy

• Presents with symmetric polyarthritis affecting >5 joints, independent of bowel inflammation 7, 8
• Less likely without gastrointestinal symptoms (diarrhea, blood in stool, abdominal pain) 7
• Would require elevated ESR/CRP and negative RF/anti-CCP for confirmation 7, 8

Immediate Diagnostic Workup (Order Today)

Essential Laboratory Tests

• Thiamine (B1) level - most critical, as deficiency causes acute neurologic deterioration 5, 4
• Vitamin B12 level - second most common deficiency causing neuropathy post-bypass 5, 4
• Vitamin B6 (pyridoxine) level - reported in 12/47 patients with neurologic symptoms 4
• Folate level - part of B-vitamin complex assessment 3
• Complete blood count with MCV - macrocytic anemia suggests B12/folate deficiency 5
• Serum albumin and transferrin - reduced levels are risk factors for neuropathy development 1
• Copper and ceruloplasmin - copper deficiency causes myeloneuropathy after gastric bypass 5
• Vitamin D (25-OH) level - common deficiency affecting bone and muscle pain 5
• Iron studies (ferritin, TIBC, serum iron) - iron deficiency is highly prevalent post-bypass 5

Additional Metabolic Assessment

• HbA1c and fasting glucose - to evaluate for diabetic neuropathy contribution 6
• TSH - hypothyroidism causes neuropathy and is common in this demographic 6
• Creatinine and eGFR - renal disease causes uremic neuropathy 6
• ESR and CRP - if elevated with joint symptoms, consider inflammatory arthropathy 7, 8

Neurologic Examination Priorities

• Assess for ataxia, nystagmus, and confusion to rule out Wernicke-Korsakoff syndrome 4
• Document distal sensory loss in stocking-glove distribution characteristic of polyneuropathy 1
• Test for proximal muscle weakness which suggests myopathy rather than pure neuropathy 9
• Check deep tendon reflexes - typically reduced or absent in peripheral neuropathy 1
• Evaluate for orthostatic hypotension if autonomic neuropathy is suspected 6

Immediate Management (Start Today, Before Lab Results)

Empiric Vitamin Replacement

• Thiamine 100 mg IV or IM daily for 3-7 days, then 100 mg oral daily - start immediately given high risk of Wernicke's encephalopathy 4
• Vitamin B-complex oral supplement containing B1, B2, B6, and B12 daily 3, 4
• Vitamin B12 1000 mcg IM weekly for 4 weeks, then monthly if deficiency confirmed 5
• Do not wait for laboratory confirmation before starting thiamine in symptomatic post-bariatric patients 4

Symptomatic Pain Management

• Continue gabapentin at current dose - it is FDA-approved for neuropathic pain 6
• Consider adding duloxetine 30-60 mg daily if gabapentin provides insufficient relief (FDA-approved for neuropathic pain) 6
• Avoid opioids as first-line therapy for chronic neuropathic pain 6

Nutritional Clinic Referral

• Urgent referral to bariatric nutritional clinic - not attending nutritional follow-up is a significant risk factor for neuropathy development 1
• Patients require lifelong monitoring and supplementation after gastric bypass 5

Risk Factors Present in This Patient

• History of gastric bypass - 16% develop neuropathy vs 3% after other surgeries 1
• Potential rapid weight loss - rate and absolute amount of weight loss are risk factors 1
• Possible non-adherence to supplementation - diet and standard multivitamins are insufficient to prevent deficiency 5
• Psychiatric medications - may mask early cognitive symptoms of severe deficiency 4

Follow-Up Strategy

Week 2-4 After Initial Presentation

• Review all vitamin levels and adjust supplementation accordingly 5
• Reassess neurologic symptoms - 85% of patients show resolution with vitamin replacement 4
• If no improvement, consider EMG/nerve conduction studies to characterize neuropathy pattern 1

Month 3

• Repeat thiamine, B12, B6, copper, and vitamin D levels to confirm repletion 5
• If symptoms persist despite normal vitamin levels, consider neurology referral for atypical presentations 6
• Evaluate for diabetic neuropathy if glycemic control is suboptimal 6

Ongoing Monitoring

• Lifelong quarterly to annual vitamin level monitoring is required after gastric bypass 5
• Continue high-dose vitamin supplementation indefinitely, as standard multivitamins are inadequate 5

Critical Pitfalls to Avoid

• Do not delay thiamine replacement while awaiting laboratory results - Wernicke-Korsakoff syndrome is irreversible once established 4
• Do not assume standard multivitamins are sufficient - they do not consistently prevent deficiency after gastric bypass 5
• Do not attribute all symptoms to fibromyalgia or psychiatric conditions when objective risk factors (gastric bypass) indicate organic pathology 6
• Do not overlook copper deficiency - it causes myeloneuropathy that mimics B12 deficiency but requires different treatment 5
• Do not stop vitamin replacement once symptoms improve - lifelong supplementation is required to prevent recurrence 5