Case Presentation: A 64-year-old woman with a history of rheumatoid arthritis (RA) on leflunomide for 4 months presented with a 2-month history of dysphagia, emesis, and epigastric pain with multiple prior outside admissions for the same. Prior upper endoscopy was notable for erythematous duodenopathy, gastritis, and normal esophagus. Biopsies showed chronic duodenitis, reactive gastropathy, and inflamed gastroesophageal junctional mucosa. She was prescribed a proton pump inhibitor (PPI) twice daily. She presented to our hospital with persistent dysphagia to solids, emesis to liquids, and severe post-prandial epigastric pain. Laboratory evaluation showed electrolyte abnormalities, neutropenia, and normocytic anemia. Liver enzymes, lipase, vitamin B12, folate, copper, iron studies, and morning cortisol were normal. Stool H. pylori, HIV, and viral hepatitis panel were negative. CT abdomen/pelvis demonstrated colonic diverticulosis without diverticulitis, post-cholecystectomy, and normal spleen size. Esophagram showed ineffective esophageal motility without stricture, mass, or gastroesophageal reflux. She required enteral feeding for malnutrition. Gastroenterology was consulted and recommended antiemetics, bowel regimen, PPI, and outpatient esophageal clinic follow up. Given persistent neutropenia and ongoing GI symptoms, leflunomide was held and rheumatology was consulted. Serum leflunomide level was elevated; therefore, a leflunomide washout with cholestyramine was recommended. She was switched to low-dose prednisone for management of her RA. On day of discharge (11 days after stopping leflunomide), her leflunomide level was subtherapeutic, her neutropenia and dysphagia had resolved, and she was able to tolerate a regular diet. At her gastroenterology follow-up 3 months later, she remained asymptomatic with normal oral intake.
Discussion: Leflunomide is a disease-modifying antirheumatic drug (DMARD) used to treat rheumatoid and psoriatic arthritis. Leflunomide toxicity is dose-related with common adverse effects including nausea, diarrhea, hypertension, elevated liver enzymes, and rash. Serious adverse effects include fulminant hepatitis, cytopenias, severe rash, angioedema, pneumonitis, and neuropathy. Although leflunomide is known to cause gastrointestinal symptoms such as abdominal pain, nausea, vomiting, and diarrhea, no established association between leflunomide and esophageal dysmotility or dysphagia has been reported in the literature. Patients with rheumatologic diseases have a higher prevalence of esophageal motility disorders, likely related to the underlying disease process rather than medication-induced effects. Notably, our patient’s symptoms resolved after discontinuation of leflunomide and did not recur at her 3-month follow up.Leflunomide is associated with bone marrow suppression which may manifest as leukopenia, neutropenia, pancytopenia, or agranulocytosis. WBC counts should be monitored regularly, and the drug should be discontinued if there is evidence of bone marrow suppression. Due to leflunomide’s prolonged half-life from enterohepatic recirculation, an accelerated drug elimination procedure should be initiated with cholestyramine or, if not tolerated, activated charcoal.
Conclusions: Our case highlights the importance of reassessing clinical cases and staying vigilant against cognitive errors such as anchoring and momentum bias, especially in patients with multiple prior encounters.