What is the cause of new onset weakness, upper extremity tingling and cramping, feeling chilled, shivers, visual focus problems, and lethargy in a 37-year-old female with a history of Gastroesophageal Reflux Disease (GERD) treated with Proton Pump Inhibitors (PPIs) and Gaviscon (aluminum hydroxide and magnesium carbonate)?

Differential Diagnosis: PPI-Induced Hypomagnesemia with Possible Vitamin B12 Deficiency

This patient's constellation of symptoms—weakness, upper extremity tingling and cramping, chills, shivers, visual focus problems, and lethargy—in the context of chronic PPI use strongly suggests PPI-induced hypomagnesemia, potentially compounded by vitamin B12 deficiency. 1

Primary Concern: PPI-Induced Hypomagnesemia

Hypomagnesemia from chronic PPI use is the most likely culprit and requires immediate evaluation. The FDA explicitly warns that PPIs can cause symptomatic and asymptomatic hypomagnesemia in patients treated for at least three months, with most cases occurring after a year of therapy. 1 Serious adverse events include:

• Tetany and muscle cramping (explains upper extremity cramping) 1
• Arrhythmias (potentially life-threatening) 1
• Seizures 1
• Generalized weakness 1

The FDA recommends that healthcare professionals consider monitoring magnesium levels prior to PPI initiation and periodically in patients expected to be on prolonged treatment. 1 For this patient already on chronic PPIs, immediate serum magnesium level is essential.

Secondary Concern: Vitamin B12 Deficiency

Chronic PPI therapy (longer than 3 years) can lead to cyanocobalamin (vitamin B12) malabsorption due to hypo- or achlorhydria. 1 Clinical manifestations consistent with B12 deficiency include:

• Peripheral neuropathy (tingling in upper extremities) 1
• Weakness and fatigue (lethargy) 1
• Visual disturbances (focus problems) 1

The FDA states this diagnosis should be considered if clinical symptoms consistent with cyanocobalamin deficiency are observed. 1

Additional Differential Considerations

While the above are most likely given the medication history, other serious causes of acute weakness must be excluded:

• Thyrotoxic hypokalemic periodic paralysis: Presents with acute muscle paralysis and weakness, though typically more severe in lower extremities and associated with hypokalemia and hyperthyroidism 2
• Neurologic emergencies: Brain, spinal cord, nerve root, peripheral nerve, or neuromuscular junction pathology should be considered in any acute weakness presentation 3

Immediate Diagnostic Workup

Order the following laboratory tests immediately:

• Serum magnesium level (priority given PPI use and symptom profile) 1
• Serum potassium (to exclude hypokalemia) 2
• Vitamin B12 level (given chronic PPI use) 1
• Thyroid function tests (TSH, free T4) to exclude thyrotoxicosis 2
• Complete metabolic panel (to assess renal function and other electrolytes) 1

Perform a focused neurologic examination looking specifically for:

• Muscle strength grading in all extremities 3
• Deep tendon reflexes (may be diminished in hypomagnesemia or B12 deficiency) 3
• Sensory examination for peripheral neuropathy patterns 3
• Chvostek's and Trousseau's signs (tetany from hypomagnesemia) 1

Management Algorithm

If hypomagnesemia is confirmed:

• Discontinue the PPI immediately 1
• Initiate magnesium replacement (oral or IV depending on severity and symptoms) 1
• Monitor for arrhythmias (obtain ECG, consider telemetry if severe) 1
• Recheck magnesium levels after replacement 1

If vitamin B12 deficiency is confirmed:

• Initiate B12 supplementation (oral or intramuscular depending on severity) 1
• Consider discontinuing or reducing PPI dose to lowest effective dose 1

Regarding PPI continuation: The AGA recommends that if PPI therapy is continued in a patient with unproven GERD, clinicians should evaluate appropriateness and dosing within 12 months after initiation. 4 Given this patient's symptoms are likely medication-related rather than GERD-related, strongly consider PPI discontinuation or de-escalation after addressing the acute electrolyte and nutritional deficiencies. 4

Critical Pitfalls to Avoid

• Do not assume GERD symptoms are causing the neurologic symptoms: Extraesophageal manifestations of GERD do not typically include weakness, tingling, or visual problems 4
• Do not continue PPIs without reassessing indication: The patient may not require ongoing PPI therapy, and continuation risks worsening deficiencies 4, 1
• Do not delay magnesium assessment: Hypomagnesemia can cause fatal arrhythmias 1
• Do not overlook the temporal relationship: These symptoms developing in a patient on chronic PPIs should immediately trigger consideration of medication-related adverse effects 1