Differential Diagnosis of Heartburn Frank Zerbib MD, PhD Gastroenterology and Hepatology Department, Hôpital Saint André, Centre Hospitalier Universitaire de Bordeaux & Université de Bordeaux Bordeaux, France Clinical evaluation Heartburn is characterized by retrosternal burning pain or discomfort that originates high in the epigastrium with intermittent cephalad retrosternal radiation. Although translations and interpretations of the term “heartburn” may vary among countries and languages, typical heartburn is traditionally considered as a specific symptom for gastro-esophageal reflux disease (GERD), thus allowing diagnosis without the need for any further invasive investigation 1. This assumption remains valid in the majority of patients especially in the primary care setting. In clinical practice, many patients are referred for “heartburn” which appears to be, after a careful interview, either epigastric burning or sore throat. In these patients, the probability of GERD-related symptoms and the response rates to PPIs are probably much lower compared than in patients with actual heartburn 2. In patients with heartburn, empirical treatment with PPIs provides symptom relief in 50-70% of cases. In cases of treatment failure, physicians should check for compliance to therapy before embarking for additional investigations. Compliance to once-daily PPI in GORD has been reported to be lower in patients with refractory symptoms (46-55%) as compared to patients with adequate relief (84%)3. In addition to compliance, the time of dosing should also be checked since taking PPIs 15 minutes before a meal results in a better gastric pH control 4 although it has not been clearly demonstrated yet that this is associated with improved clinical efficacy. Physicians have to keep in mind that the failure of therapy in patients with heartburn is often related to the absence of reflux-related symptoms, and that additional investigations are mandatory. Endoscopy Upper GI endoscopy must be performed in patients who have refractory heartburn, despite therapy, or alarm symptoms. Endoscopy can confirm the diagnosis of GERD when erosive esophagitis or Barrett’s esophagus is present. However, the prevalence of erosive esophagitis in patients previously treated with PPIs is below 10% 5 and may reflect poorly-controlled acid reflux. Esophageal biopsies samples should be obtained regardless of the gross appearance of the esophageal mucosa, to rule out eosinophilic esophagitis. Eosinophilic esophagitis is an allergic disorder defined by symptoms related to esophageal dysfunction and characterized by an eosinophil-predominant inflammation on analysis of esophageal biopsy samples 6. Mucosal eosinophilia is usually isolated to the esophagus, characteristically consisting of a peak value of ≥15 eosinophils per high-power field. In adults, dysphagia is the most frequent symptom of this disorder but in case of heartburn not responding to PPI therapy, upper endoscopy with biopsies may diagnose eosinophilic esophagitis in 1 to 4% of patients 5, 7, 8. It is important is to look for endoscopic esophageal features of eosinophilic esophagitis such as concentric rings (trachealisation), exudates (white spots), furrows or edema, but the endoscopic appearance of the esophageal mucosa may be normal in 10–25% of patients 9. Finally, endoscopy can also demonstrate the presence of a severe esophageal motor disorder, such as achalasia, if there is esophageal stasis in a dilated esophagus associated with a ‘tight’ esophagogastric junction 9. Esophageal manometry All patients who have failed empirical management should have esophageal manometry before reflux monitoring to position pH sensors (especially when recordings are performed in patients taking a PPI) and to rule out achalasia or severe esophageal motor disorders. Indeed, the prevalence of heartburn has been reported to be as high as 35% in achalasia 10, 11. Ambulatory monitoring for reflux Once persisting erosive esophagitis, eosinophilic esophagitis and esophageal motility disorders have been ruled out, a patient with refractory heartburn should be investigated for reflux in ambulatory conditions. The aim of reflux testing is to demonstrate the presence of abnormal reflux (either acid or non-acid) and/or the temporal association between symptoms and reflux events. If GERD has never been previously demonstrated (absence of esophagitis or abnormal pH monitoring), a 24-h pH monitoring without treatment is indicated. If investigations have documented GERD (esophagitis or abnormal pH monitoring), reflux testing should be performed on therapy to assess the residual reflux events and their correlation with symptoms. It is now well demonstrated that testing on therapy should be performed by pH-impedance monitoring which allows the detection of both acid and nonacid reflux events 12. These investigations will help to distinguish patients with GERD-associated symptoms from those whose symptoms are not GERD-related. In the first group, patients may have either increased acid exposure (“non-erosive reflux disease” or “true refractory GERD” when performed on PPIs) or normal acid exposure but positive symptom-reflux association (the socalled “reflux hypersensitivity” or “esophageal hypersensitivity”). In the second group, patients have normal acid exposure and reflux events and no association between reflux and symptoms: this is the current definition of “functional heartburn”. Functional heartburn is likely to represent less than 10% of heartburn patients presenting to gastroenterologists 13, but the proportion may vary between primary care settings and tertiary centers. In a population of 100 patients referred to tertiary centers for reflux testing with pH-impedance monitoring off therapy, the reported prevalence of functional heartburn was 21% in patients refractory to PPIs 14. The mechanism of symptom perception in functional heartburn is unclear. The prevailing view considers altered visceral perception as a major determinant, but the trigger stimuli provoking heartburn World Digestive Health Day WDHD May 29, 2015 WGO HANDBOOK HEARTBURN: A GLOBAL PERSPECTIVE 31
WDHD-2015-handbook-final
To see the actual publication please follow the link above