A 64-year-old woman is diagnosed with rheumatoid arthritis after coming to the office with symmetrical joint pain, swelling, and morning stiffness. The patient has a remote history of peptic ulcer disease and was treated with multidrug therapy for Helicobacter pylori eradication; a follow-up H pylori stool antigen test was negative and she had no recurrent symptoms. The patient is started on methotrexate and high-dose ibuprofen therapy. In addition, daily lansoprazole is prescribed for protection against the adverse gastrointestinal effects of ibuprofen. Three months later, joint symptoms were greatly improved. Ibuprofen and lansoprazole were discontinued. However, 2 weeks later, she begins experiencing heartburn after meals. Which of the following is the most likely cause of this patient's new gastrointestinal symptoms?

Question

A 64-year-old woman is diagnosed with rheumatoid arthritis after coming to the office with symmetrical joint pain, swelling, and morning stiffness.  The patient has a remote history of peptic ulcer disease and was treated with multidrug therapy for Helicobacter pylori eradication; a follow-up H pylori stool antigen test was negative and she had no recurrent symptoms.  The patient is started on methotrexate and high-dose ibuprofen therapy.  In addition, daily lansoprazole is prescribed for protection against the adverse gastrointestinal effects of ibuprofen.  Three months later, joint symptoms were greatly improved.  Ibuprofen and lansoprazole were discontinued.  However, 2 weeks later, she begins experiencing heartburn after meals.  Which of the following is the most likely cause of this patient's new gastrointestinal symptoms?

Quizplus · Accepted Answer

11ec160b_3bd5_c750_9249_2d17662ca398_MD0001_00 Release of gastrin, a hormone produced by G cells in the gastric antrum, is stimulated by dietary protein intake, gastrin-releasing peptide (released in response to vagal stimuli), and increased gastric pH. Gastrin induces acid production directly by binding parietal cells and indirectly by binding enterochromaffin-like (ECL) cells and inducing histamine release. Proton pump inhibitors (PPIs) (eg, omeprazole, lansoprazole) inhibit the hydrogen-potassium-ATPase pump and decrease hydrochloric acid production regardless of stimuli. The resultant increase in gastric pH leads to increased gastrin formation, which induces hypertrophy of the ECL and parietal cells. Withdrawal of the PPI results in overstimulation of the parietal cells with hyperfunctioning of the unblocked ATPase, leading to rebound gastric acid hypersecretion and reflux symptoms. PPIs can be slowly tapered to help prevent this adverse effect. (Choice A) Acetylcholine (released with vagal stimulation) binds to parietal cell muscarinic (M3) receptors and promotes the secretion of hydrochloric acid. Downregulation of vagal tone would likely relieve, rather than cause, the patient's symptoms. (Choice C) Prostaglandins decrease acid production by inhibiting the downstream messenger of histamine and increases bicarbonate formation from gastric epithelial cells. Nonsteroidal anti-inflammatory drugs (eg ibuprofen) inhibit prostaglandin formation and increase the risk of gastritis and peptic ulcer formation. Increased prostaglandin formation after drug withdrawal would be protective against gastritis. (Choice D) Chronic Helicobacter pylori infection causes atrophic gastritis with parietal cell destruction. The effects of hypergastrinemia are masked in these patients due to the inability of the remaining parietal cells to create large volumes of acid. Reinfection is very rare, and the correlation with PPI withdrawal makes rebound hypersecretion more likely. (Choice E) Somatostatin inhibits histamine and gastrin release; upregulation would lead to reduced gastric acid formation. Educational objective: Elevated gastric pH stimulates secretion of gastrin, a polypeptide hormone that increases gastric acid production. Proton pump inhibitors block gastric acid production by parietal cells; the resultant increase in pH leads to hypergastrinemia, which can cause rebound hypersecretion of gastric acid when the drug is withdrawn.

A 64-Year-Old Woman Is Diagnosed with Rheumatoid Arthritis After Coming