Boerhaave's syndrome associated with glucagon-like peptide-1 receptor agonist use: a case report

Glucagon-like peptide 1 receptor agonists (GLP-1 RAs) are increasingly prescribed for type 2 diabetes and weight loss, with well known gastrointestinal side effects including nausea, vomiting, and delayed gastric emptying. While mucosal injuries such as Mallory Weiss tears have been reported, full thickness esophageal perforation has not previously been described. We report the first documented case of Boerhaave's syndrome associated with GLP-1 RA use, highlighting the potential for rare but life threatening complications following abrupt reinitiation at high doses.

A previously healthy woman in her 50s presented with vasopressor dependent shock and respiratory failure requiring intubation following severe nausea, emesis, and acute chest pain. She had restarted semaglutide at the maximum 2.4 mg weekly dose the day prior to symptom onset, after several months off therapy and without dose titration. Imaging revealed pneumomediastinum and bilateral pleural effusions. Esophagram confirmed a contained esophageal perforation. She was managed with endoscopic stent placement, nasojejunal feeding, and chest tube drainage, followed by clinical improvement and discharge. Two months later, she was readmitted with necrotizing pneumonia. Imaging and endoscopy revealed an esophagopleural fistula, abscess, and migrated stent. She underwent left thoracotomy, abscess drainage, decortication, and wedge resection of necrotic lung. The perforation site was reinforced with an intercostal muscle flap, and a PEG tube was placed. Postoperatively, at 10-month follow up she was on a regular diet, PEG tube removed, and esophagus was healed on EGD. She was advised to permanently discontinue GLP-1 RAs.

This case underscores a previously unreported but serious complication of GLP-1 RA therapy, transmural esophageal rupture, likely precipitated by drug induced gastroparesis and forceful emesis. Restarting semaglutide at a high dose without titration after a prolonged interruption likely increased vulnerability to injury. Clinicians should maintain a high index of suspicion for esophageal complications in patients presenting with chest pain and vomiting during GLP-1 RA initiation or reinitiation. Early multidisciplinary management is crucial to optimizing outcomes in this rare but life-threatening scenario.