Refractory Gastroesophageal Reflux Disease: A Review

Gastroesophageal reflux disease (GERD) develops when reflux of the contents of the stomach cause troublesome symptoms or complications. There is a high prevalence of GERD among the world population, including an estimated 12% to 20% of the urban population in Brazil. Patients with GERD often experience significant limitations to their quality of life and incur high direct and indirect healthcare costs.

Because there is no diagnostic marker for GERD, the condition is difficult to diagnose. Definitive diagnosis can be made when esophageal mucosal erosions are observed on upper digestive endoscopy (UDE); however, observation of erosions occurs in only one third of cases, according to researchers.

The introduction of proton pump inhibitors (PPIs) improved clinical treatment outcomes, the researchers continued. PPIs provide effective blockade to gastric secretions and are commonly prescribed at standard doses and given in the morning for a period of 4 to 8 weeks. In spite of the success of PPI therapies, 20% to 40% of cases may not respond to PPI therapy; those patients have persistent reflux symptoms and/or an occurrence of new symptoms and esophagitis.

Researchers recently conducted a review to identify and examine aspects of GERD refractory patients to treatment with PPIs. They noted that the term refractory may not be adequate as it “is not always a true treatment failure, but sometimes a diagnostic error, non-compliance to the proposed treatment, or inadequate dose.” Because treatment failure could be related to those factors, the researchers said, “A careful review of the possible mechanism of treatment failure, including the diagnosis, is required.” They reported results of their review in the Brazilian journal Arquivos de Gastroenterologia [2012;49(4):296-301].

According to the researchers, their review demonstrated that patients with GERD who meet the criteria to be considered refractory should undergo UDE to exclude peptic ulcer disease and cancer; UDE also provides the opportunity to confirm a diagnosis of mucosal erosions that are characteristic of erosive esophagitis.

Clinicians should then consider and include or exclude the possibility of nonadherence to treatment, misdiagnosis, drug-induced esophagitis, skin disorders, or autoimmune eosinophilic esophagitis. When findings on the UDE are normal, the researchers recommend that the investigation be extended and that clinicians should perform the 24-hour pH-metry as well as, when appropriate, the pH-metry/impedance if the 24-hour pH-metry is not enough to characterize acid reflux.

Summarizing the results of the review of refractory GERD, the reviewers identified 9 main causes for treatment failure: (1) functional heartburn; (2) low adherence to PPI therapy; (3) inadequate PPI dosage; (4) incorrect diagnosis; (5) comorbidities and pill-induced esophagitis; (6) genotypic differences; (7) nonacid GERD; (8) autoimmune skin diseases; and (9) eosinophilic esophagitis.

In conclusion, the reviewers commented, “One should not forget to consider the less frequent hypothesis of achalasia and gastroparesis, and more often, functional pyrosis caused by visceral hypersensitivity, which is treated with pain modulators such as tricyclic antidepressants and serotonin reuptake blockers in low doses.”