Extraesophageal manifestations of gastroesophageal reflux disease

Gastroesophageal reflux disease often presents as heartburn and acid reflux, the so-called "typical" symptoms. However, a subgroup of patients presents a collection of signs and symptoms that are not directly related to esophageal damage. These are known collectively as the extraesophageal manifestations of gastroesophageal reflux disease. Principal among such manifestations are bronchospasm, chronic cough and laryngitis, which are classified as atypical symptoms. These manifestations comprise a heterogeneous group. However, some generalizations can be made regarding all of the subgroups. First, although the correlation between gastroesophageal reflux disease and the extraesophageal manifestations has been well established, a cause-and-effect relationship has yet to be definitively elucidated. In addition, the main proposed pathogenic mechanisms of extraesophageal reflux are direct injury of the extraesophageal tissue (caused by contact with gastric acid) and the esophagobronchial reflex, which is mediated by the vagus nerve. Furthermore, gastroesophageal reflux disease might not be considered in the differential diagnosis of patients presenting only the atypical symptoms. In this article, we review the extraesophageal manifestations of gastroesophageal reflux disease, discussing its epidemiology, pathogenesis, diagnosis and treatment. We focus on the most extensively studied and well-established presentations.