Differentials

Acute coronary syndrome

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Cardiac aetiology must be ruled out before considering a diagnosis of GORD in people with chest pain.​[1]

Typical chest pain is substernal pressure or heaviness that radiates to the jaw, arm, or neck.

Diaphoresis, dyspnoea, and syncope may also occur.

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ECG may show ST changes or Q waves.

Cardiac biomarkers (e.g., troponin) may be elevated.

Stable angina

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Cardiac aetiology must be ruled out before considering a diagnosis of GORD in people with chest pain.​[1]

Stable angina causes chest pain which is typically substernal, precipitated by exertion, and relieved by rest.

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ECG may show ST changes or Q waves.

Exercise stress testing may show ST-segment elevation and depression.

Cardiac computed tomographic angiography (CCTA) may show >50% luminal narrowing.

Functional oesophageal disorder/functional heartburn

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No reliable differentiating signs or symptoms.

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Functional heartburn denotes endoscopy-negative heartburn by definition. A normal oesophageal pH study differentiates between non-erosive GORD and functional heartburn. An alternative is a normal impedance-pH study. These studies would usually be done in patients who fail to respond to proton-pump inhibitor (PPI) therapy.

Achalasia

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Dysphagia is typically prominent.

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Oesophageal manometry and/or oesophagram are abnormal and consistent with achalasia.

Functional (non-ulcer) dyspepsia

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Dyspepsia symptoms include upper abdominal pain, early satiety, belching, bloating, and nausea.

Symptoms have been investigated with endoscopy and other relevant tests, which have ruled out an organic cause for the symptoms.[54]

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No definitive differentiating tests. Symptoms may overlap.

Oesophagitis and peptic ulcer disease are absent on endoscopy for both non-erosive GORD and functional dyspepsia.

Peptic ulcer disease

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Burning pain in the epigastrium, which occurs hours after meals or with hunger.

The pain often wakes the patient at night and is relieved by food and antacids.

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Endoscopy demonstrates ulcer.

Testing for Helicobacter pylori infection is often positive, although not diagnostic.

Eosinophilic oesophagitis

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Features of GORD and eosinophilic oesophagitis overlap. However, patients with eosinophilic oesophagitis may be younger or have symptoms of dysphagia, food impactions, or documented food allergies.[55]

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Endoscopy may show oesophageal rings, linear furrows, white plaques, exudates, absence of a hiatus hernia, and a narrow-calibre oesophagus.[55]

Maximum peripheral eosinophil count may be higher than typical for GORD.[55]

Eosinophil count may be ≥15 per high power field in sampled oesophageal tissue.

There may be eosinophil degranulation in biopsy specimens.[55]

Proton pump inhibitor-responsive oesophageal eosinophilia

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International consensus criteria conclude that in many cases proton pump inhibitor-responsive oeosophageal eosinophilia is indistinguishable from eosinophilic oesophagitis (EoO), and that PPIs are better classified as a treatment for oesophageal eosinophilia that may be due to EoO than as a diagnostic criteria.[56]

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Therapeutic response to a PPI.

Doses of PPI should be at least similar to treat GORD-related erosive oesophagitis with a duration of 8 weeks continuing until the time of a follow-up endoscopy and biopsy.

Malignancy

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Suspected in older adults presenting with alarm symptoms: anaemia, acute or progressive dysphagia, haematemesis, melaena, persistent vomiting, or involuntary weight loss.[9]

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Laboratory tests may show anaemia or abnormal LFTs.

Oesophageal or gastric malignancy may be seen during endoscopy.

Computed tomography of the abdomen may detect pancreatic and hepatobiliary carcinoma.

Tissue biopsies diagnostic.

Laryngopharyngeal reflux

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Inflammatory condition of the upper aerodigestive tract tissues related to the direct and indirect effects of gastroduodenal content reflux.[57]

Laryngeal symptoms include dysphonia, cough, globus sensation, persistent throat clearing, and/or dysphagia. Less commonly, patients may exhibit vocal cord polyps or granulomas, laryngospasm, or subglottis stenosis.

Fewer than 50% of patients experience heartburn; oesophagitis is present in 25% of patients.[57]

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Diagnosis is mainly clinical, no single test confirms it.

Laryngoscopy is useful to demonstrate varying degrees of laryngeal oedema and erythema.

Dual sensor pH probe is considered the gold standard for diagnosing laryngopharyngeal reflux.

Clinical response to empirical therapy with proton pump inhibitors may be used as a diagnostic tool.[57][58]

Non-acid reflux

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Non-acid (pH >4) reflux typically occurs during the post-prandial period because gastric acid is buffered by ingested food.[59]​ This can also occur in patients treated with acid-suppressive drugs.The main causes of non-acid reflux include transient lower oesophageal sphincter relaxations and the presence of a hiatal hernia. Non-acid reflux should be suspected in patients with persistent reflux symptoms despite adequate pharmacological acid suppression.

Bile reflux may occur in the context of previous surgery, intestinal obstruction, or impaired small intestinal motility.[60]

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Endoscopy typically reveals absence of erosive oesophagitis. Alternative conditions such as eosinophilic oesophagitis must be ruled out with oesophageal biopsies. pH/impedance testing permits accurate diagnosis.​[1]

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