Extra-esophageal manifestations of gastro-esophageal reflux disease Urvashi Hooda, MD Department of Gastroenterology and Human Nutrition, All India Institute of Medical Sciences New Delhi, India Varocha Mahachai, MD, FRCPC, FACG, AGAF Division of Gastroenterology, Chulalongkorn University Hospital and Bangkok Medical Center Bangkok, Thailand Govind K Makharia, MD, DM, DNB, MNAMS Department of Gastroenterology and Human Nutrition All India Institute of Medical Sciences New Delhi, India Introduction While heartburn and regurgitation are the classical, esophageal manifestations of gastro-esophageal reflux disease (GERD), some individuals may suffer from extra-esophageal manifestations (EEMs).1 EEMs represent a wide spectrum of symptoms, mainly related to the upper and the lower respiratory tracts, such as laryngitis, chronic cough, chest pain, bronchial asthma, oral ulcers, and sleep disturbances.2-3 Whilst the evidence is sufficient to label some conditions, such as reflux cough syndrome, reflux laryngitis syndrome, reflux asthma syndrome and reflux chest pain syndrome, as established EEMs of GERD, other symptoms, such as pharyngitis, sinusitis, idiopathic pulmonary fibrosis and recurrent otitis media are labeled as proposed EEMs of GERD because there is only weak or limited evidence to suggest that they are caused by GERD. Table: Extra-esophageal manifestations of GERD Established manifestations Proposed manifestations Bronchopulmonary Reflux cough syndrome Pneumonia Reflux asthma Pulmonary fibrosis Oto-rhino-laryngeal Reflux laryngeal syndrome Sinusitis Otitis media Rhinitis Oral cavity Halitosis Mouth ulcers Dysgeusia Glossodynia Water brash Others Non-cardiac chest pain Dental enamel erosion Dental caries Mechanisms of EEMs of GERD There are two proposed mechanisms for the occurrence of EEMs in patients with GERD: i.e direct reflux-induced or indirect reflexinduced. 2-3 In the first case, direct reflux of gastric contents into the proximal esophagus, secondary to disruption of the mechanical barrier for reflux (lower esophageal sphincter) or esophageal dysmotility, may expose the oropharyngeal or tracheobronchial structures to acid and pepsin (reflux theory). Alternatively, more limited reflux of gastric acid and/or pepsin into the esophagus may, also, stimulate the vagus nerve. Because of the common embryological origin of the esophagus and the bronchial tree, stimulation of vagus nerve may lead to reflex bronchoconstriction and other extra-esophageal symptoms (reflex theory). EEMs are more common in erosive than in non-erosive reflux disease. The economic burden of caring for patients with suspected extra-esophageal reflux is almost five times higher than that for patients with typical GERD.4 In this short review, we have summarized both established and proposed EEMs of GERD. Extra-esophageal manifestations of GERD: Established Reflux laryngitis syndrome GERD is one of the important causes of laryngeal inflammation. Patients with reflux laryngitis can present with symptoms such as change in voice, intermittent change in the tone of the voice, loss of strength of voice, hoarseness, persistent cough or foreign body sensation in the throat or repetitive clearance of phlegm. Such symptoms are not specific for reflux-induced laryngitis; laryngeal inflammation can be caused or aggravated by many other factors such as dust, smoking or viral infections. It is, therefore, important for a clinician to judge whether GERD, really, is the cause of the problem when a patient presents with laryngeal symptoms. The symptoms of reflux laryngitis due to GERD are more often present in the day-time and in the upright position. Some other clues, which may help a clinician to attribute laryngeal symptoms to GERD are the presence of concomitant symptoms of GERD such as heartburn or regurgitation, the demonstration of reflux or reflux-induced mucosal changes at upper endoscopy or the confirmation of abnormal esophageal acid exposure by mean of a 24-hour pH study. Surprisingly, not every patient with laryngeal inflammation due to GERD has typical GERD symptoms, endoscopic esophagitis or abnormal reflux on 24-hour pH-metry.5 Furthermore, features of laryngeal inflammation such as erythema and edema of the crico-arytenoid folds and posterior portion of the true vocal cords are not specific for reflux-induced laryngitis; these findings may be seen in healthy volunteers and they may be caused, also, by smoking, alcohol, post-nasal drip, vocal strain and certain medications.2 It has also been proposed that laryngeal inflammation in patients with GERD can be caused by non-acid reflux, detectable by combined esophageal pH-impedance monitoring.6-7 An assay to detect pepsin in sputum or saliva, collected at the time of symptoms, has also been described recently to determine whether laryngeal in- World Digestive Health Day WDHD May 29, 2015 WGO HANDBOOK HEARTBURN: A GLOBAL PERSPECTIVE 21
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