ARE THE PERSISTENT SYMPTOMS TO PROTON PUMP INHIBITOR THERAPY DUE TO REFRACTORY GASTROESOPHAGEAL REFLUX DISEASE OR TO OTHER DISORDERS?

Initially, the management of PPI refractoriness consists in correcting low adherence to PPI therapy, adjusting the PPI dosage and emphasizing the recommendations on lifestyle modification change, avoiding food and activities that trigger symptoms. PPI decreases the number of episodes of acid reflux; however, the number of "non-acid" reflux increases and the patient continues to have reflux despite PPI. In this way, it is possible to greatly reduce greatly the occurrence of symptoms, especially those dependent on the acidity of the refluxed material. Response to PPI therapy can be evaluated through clinical, endoscopic, and reflux monitoring parameters. In the persistence of the symptoms and/or complications, other causes of Refractory GERD should be suspected. Then, diagnostic investigation must be initiated, which is supported by clinical parameters and complementary exams such as upper digestive endoscopy, esophageal manometry and ambulatory reflux monitoring (esophageal pH monitoring or esophageal impedance-pH monitoring). Causes of refractoriness to PPI therapy may be due to the true Refractory GERD, or even to other non-reflux diseases, which can generate symptoms similar to GERD. There are several causes contributing to PPI refractoriness, such as inappropriate use of the drug (lack of patient adherence to PPI therapy, inadequate dosage of PPI), residual acid reflux due to inadequate acid suppression, nocturnal acid escape, "non-acid" reflux, rapid metabolism of PPI, slow gastric emptying, and misdiagnosis of GERD. This is a common cause of failure of the clinical treatment and, in this case, the problem is not the treatment but the diagnosis. Causes of misdiagnosis of GERD are functional heartburn, achalasia, megaesophagus, eosinophilic esophagitis, other types of esophagitis, and other causes. The diagnosis and treatment are specific to each of these causes of refractoriness to clinical therapy with PPI.