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Approximately 25% of patients with typical gastroesophageal disease (GERD) symptoms do not respond to double dose of proton pump inhibitors (PPI), and might have refractory GERD. The causes of refractory GERD include poor compliance, esophageal motility disorder, duodeno-gastroesophageal reflux, eosinophilic esophagitis, nonacid reflux, functional heartburn, and inadequate acid suppression. when patient compliacne have been confirmed, it is reasonable to escalate to twice dose of PPI. Upper gastrointestinal endoscopy should be performed to rule out other disorders such as esophageal esophagitis, pill induced esophagitis, or esophageal involvement of autoimmune disorders. If symptoms persist despite double dose PPI, 24 hr pH-impedance monitoring, esophageal manometry, and scintigraphic gastric emptying scan may be required.
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