Michael F. Vaezi - Diagnosis and Treatment of Gastroesophageal Reflux Disease

Department of Medicine, Division of Gastroenterology, Barnes-Jewish Hospital/Washington University School of Medicine, Campus Box 8124, 660 S. Euclid Avenue, 63110 St. Louis, MO, USA

Amit Patel

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Gastroesophageal reflux (GER), or the retrograde flow of gastric content across the esophagogastric junction (EGJ) and the lower esophageal sphincter (LES) , can be physiologic, especially in the postprandial setting. Inherent mechanisms are in place for the LES to relax transiently in response to distension of the fundus of the stomach, resulting in venting of air (belching) [].

GER becomes pathologic (GERD) when associated with symptoms (typically heartburn or regurgitation) or mucosal injury (typically esophagitis or BE) []. Beyond symptom assessment and inspection of the esophageal mucosa at upper endoscopy , the availability of diagnostic tests to quantify reflux and to assess the association of symptoms with reflux episodes affords further insight into the definition of GERD.

The clinical presentation of GERD is predominantly symptom based, as the vast majority of patients present to their physicians with typical symptoms of heartburn and regurgitation . However, there is a significant and growing recognition of atypical symptoms defining GERD, particularly when these atypical symptoms occur in the absence of typical symptoms or endoscopic evidence of mucosal damage. Given the diagnostic challenges associated with the spectrum of clinical symptoms that may be related to GERD with varying definitions across geographic regions, the Montreal classification International Consensus Group was formed to develop a global definition for GERD [].

Symptomatically, the Montreal classification suggested that reflux symptoms must be troublesome to meet the definition of GERD. Specifically, this threshold required adverse effects on patient well-being; population-based studies have suggested mild symptoms occurring at least 2 days weekly or moderate-to-severe symptoms occurring at least 1 day weekly may approximate this threshold [].

The Montreal classification concluded that heartburn and regurgitation constitute the characteristic symptoms of the typical reflux syndrome, allowing suspicion of GERD based on presence of these symptoms alone, a position adopted by the American Gastroenterological Association in 2008 []. The addition of a further step, the proton pump inhibitor (PPI) test, adds additional confidence in the symptomatic diagnosis of GERD with typical symptoms, as discussed below.

A significant advance in defining GERD over the past two decades consists of the distinction between esophageal and extra-esophageal syndromes. In the Montreal classification , esophageal syndromes were further subdivided into symptomatic syndromes (typical reflux syndrome, reflux chest pain syndrome), and syndromes with esophageal injury (reflux esophagitis, reflux stricture, BE, and esophageal adenocarcinoma) [] . Extra-esophageal syndromes were subdivided into established associations (reflux cough, reflux laryngitis, reflux asthma, and reflux dental erosion syndromes) and proposed associations (pharyngitis, sinusitis, idiopathic pulmonary fibrosis, and recurrent otitis media).

With extra-esophageal reflux symptoms, the diagnostic yield of documentation of GERD on endoscopy and ambulatory reflux monitoring is lower than that established for typical GERD. The accuracy of available diagnostic tests, including laryngoscopy, upper endoscopy , pH-metry, and pH-impedance testing, for the evaluation of suspected extra-esophageal reflux symptoms is suboptimal [].

At initial presentation, an empiric therapeutic trial of PPI constitutes a commonly employed approach to diagnosis , with symptomatic response to this trial confirming clinical suspicion of GERD. Initial reports of this approach used omeprazole 40 mg before breakfast and 20 mg before dinner for 7 days, and 80 % of GERD patients with heartburn reported symptom improvement, compared to 42 % of patients with heartburn in the absence of GERD [].

Response to PPI trials in non-GERD heartburn has to be interpreted with caution, since there is overlap with other processes that may also improve with antisecretory therapy (such as eosinophilic esophagitis, EoE) or as a placebo effect (such as functional heartburn). Further, antisecretory therapy may not be as effective at improving GERD symptoms in nonerosive disease compared to erosive esophagitis, and PPI nonresponders could still have reflux-triggered symptoms [].

The diagnostic yield of empiric PPI therapy for most atypical symptoms, apart from NCCP, is worse than for typical symptoms. Two meta-analyses assessing the accuracy of PPI treatment as a diagnostic test for NCCP (with pH monitoring and/or endoscopy serving as reference standards) found a sensitivity of 80 % and specificity of 74 % []. These data highlight the fact that extra-esophageal symptoms often have multifactorial etiologies; GERD may represent a cofactor rather than the sole etiology for symptom generation.

Endoscopic definitions of GERD hinge on identification of esophageal mucosal injury visible to the endoscopist. The Montreal classification defined esophageal complications of GERD to include reflux esophagitis, hemorrhage, stricture , BE , and adenocarcinoma. Reflux esophagitis, the most common form of mucosal injury, may be seen as breaks in the distal esophageal mucosa immediately proximal to the squamocolumnar junction on upper endoscopy. Developed by the International Working Group for the Classification of Oesophagitis (IWGCO), the Los Angeles (LA) classification (named for an initial presentation at the 1994 World Congress of Gastroenterology in Los Angeles) is widely used to grade the severity of reflux esophagitis, with its definitive form published in 1999 []. The LA classification describes increasing endoscopic grades of severity of esophagitis as follows: grade A, mucosal break(s) < 5 mm in length and not extending between the tops of two mucosal folds; grade B, mucosal break(s) > 5 mm in length, extending across the tops of two mucosal folds; grade C, mucosal break(s) continuous between tops of at least two mucosal folds but not involving > 75 % of esophageal circumference; and grade D, mucosal break(s) involving > 75 % of the esophageal circumference.

There are limited data to suggest that LA grade A esophagitis may rarely be encountered in healthy asymptomatic individuations (e.g., in as many as 8 % of control subjects in one study [].