Gastroesophageal reflux disease (GERD) is a chronic condition in which stomach contents flow back into the esophagus, causing irritation to the mucosa. Reflux is primarily caused by an inappropriate, transient relaxation of the lower esophageal sphincter (LES). Risk factors include obesity, stress, certain eating habits (e.g., heavy meals or lying down shortly after eating), and changes in the anatomy of the esophagogastric junction (e.g., hiatal hernia). Typical symptoms are retrosternal burning pain (heartburn) and regurgitation, but the presentation is variable and may also include symptoms like chest pain and dysphagia. Most patients with suspected GERD should receive empirical treatment with proton pump inhibitors (PPIs). Diagnostic studies, e.g., esophagogastroduodenoscopy (EGD) and/or 24-hour pH test, may be indicated to confirm the diagnosis or to rule out other causes of symptoms. Management involves lifestyle modifications, medication, and, in some cases, surgery. Treating esophagitis is especially important because chronic mucosal damage can cause Barrett esophagus, a premalignant condition that can progress to adenocarcinoma.
- Gastroesophageal reflux: regurgitation of stomach contents into the esophagus (can also occur in healthy individuals, e.g., after consuming greasy foods or wine)
Gastroesophageal reflux disease (GERD)
- A condition in which reflux causes troublesome symptoms (typically including heartburn or regurgitation) and/or esophageal injury/complications
- The most common endoscopic finding associated with esophageal mucosal injury is reflux esophagitis. 
- NERD (non-erosive reflux disease): characteristic symptoms of gastroesophageal reflux disease in the absence of esophageal injury, such as reflux esophagitis, on endoscopy (50–70% of GERD patients) 
- ERD (erosive reflux disease): gastroesophageal reflux with evidence of esophageal injury, such as reflux esophagitis, on endoscopy (30–50% of GERD patients) 
GERD develops when reflux-promoting factors, such as corrosiveness of the gastric juice, overcome protective mechanisms, such as the gastroesophageal junction and esophageal acid clearance.
Gastroesophageal junction dysfunction can occur because of the following factors:
- Increased frequency of transient lower esophageal sphincter relaxations (TLESRs) 
Imbalance between intragastric and lower esophageal sphincter (LES) pressures 
- Reflux occurs when the intragastric pressure is higher than that created by the LES.
- LES tone can be decreased by substances such as caffeine and nitroglycerin, as well as by conditions that cause denervation of the muscle layer, such as scleroderma (see “Risk factors/associations” below).
- Intragastric pressure is increased in pregnancy, delayed gastric emptying, and obesity, among other conditions.
- Anatomic abnormalities of gastroesophageal junction (e.g., hiatal hernia, tumors)
- Impaired esophageal acid clearance 
Risk factors for GERD
- Smoking, caffeine and alcohol consumption 
- Stress 
- Obesity 
- Pregnancy 
- Angle of His enlargement (> 60°) 
- Iatrogenic (e.g., after gastrectomy)
- Inadequate esophageal protective factors (i.e., saliva, peristalsis) 
- Gastrointestinal malformations and tumors: gastric outlet obstruction, gastric cardiac carcinoma
- Scleroderma 
- Sliding hiatal hernia: ≥ 90% of patients with severe GERD 
The histopathological findings include the following (may vary depending on the severity of mucosal damage): 
- Superficial coagulative necrosis in the nonkeratinized squamous epithelium
- Thickening of the basal cell layer
- Elongation of the papillae in the lamina propria and dilation of the vascular channels at the tip of the papillae (leading to hyperemia)
- Inflammatory cells (granulocytes, lymphocytes, macrophages)
- Transformation of squamous into columnar epithelium leads to 
- Retrosternal burning pain (heartburn)
- Dysphagia, odynophagia 
- Water brash: a symptom of excessive salivation triggered by refluxing of stomach acid
- Pressure sensation in the chest/noncardiac chest pain
- Belching, bloating
- Dyspepsia, epigastric pain
- Features of; GERD complications, e.g., aspiration pneumonia or aspiration pneumonitis
Extraesophageal symptoms 
- Lying down shortly after meals
- Certain foods/beverages
Red flags in GERD 
- Dysphagia, odynophagia 
- Anemia and/or evidence of GI bleeding (e.g., hematemesis, hematochezia)
- Unintentional weight loss
- Signs of GI bleeding
- Presence of > 1 risk factor for Barrett esophagus (see below)
Other causes of pain and discomfort
- See “ .”
- See “ .”
- See “ .”
Infectious esophagitis (typically seen in immunocompromised patients)
- ; : Endoscopy shows white or yellow adherent plaques (pseudomembranes).
- Herpes esophagitis (mainly HSV-1); : Endoscopy shows superficial, punched-out ulcers in the distal esophagus in the absence of plaques.
- ; : Endoscopy shows mucosal erosions and linear ulcers in the upper or middle esophagus, and viral inclusion bodies in cell nuclei on biopsy.
- Drug-induced esophagitis: Some medications may cause esophageal mucosal irritation, leading to erosions and ulcers. 
- Eosinophilic esophagitis
- Infectious esophagitis (typically seen in immunocompromised patients)
Rule out clinical diagnosis of GERD. in patients with before making a
The differential diagnoses listed here are not exhaustive.
There is no gold standard test for the diagnosis of GERD. The diagnosis is based on clinical presentation, endoscopic evaluation, reflux assessment, and therapeutic response. 
- All patients
- Typical symptoms without red flags in GERD: Initiate treatment for GERD; start an empiric once-daily PPI trial.
- Red flags in GERD: Refer to gastroenterology for EGD before initiating treatment.
- Extraesophageal symptoms: Rule out other diagnoses prior to initiating treatment for GERD.
Refractory symptoms: Optimize PPI therapy.
- If symptoms are relieved: Continue PPI.
- If symptoms persist: Refer to gastroenterology.
GERD is common during pregnancy and usually subsides after delivery; diagnostic workup is rarely necessary.
- Supportive findings (typically in the lowest third of the esophagus) 
> 50% of patients with GERD present with nonerosive reflux and normal endoscopic findings. 
Esophageal pH monitoring 
- Supportive finding: Drops in esophageal pH to 4 or less that correlate with symptoms of acid reflux and precipitating activities. 
Further diagnostic studies 
Not routinely indicated, as they play a limited role in the diagnosis of GERD; useful if endoscopy is inconclusive.
The initial management of GERD consists of implementing lifestyle changes and initiating acid suppression therapy, preferably with PPIs. Surgical therapy is not routinely indicated and should only be considered in select cases, e.g., patients who develop complications despite receiving optimal medical therapy.
Pharmacological therapy 
See “, detailed dosages, and pharmacological considerations.” for agents
PPIs: : standard dose of PPI for 8 weeks
- Continuous management (based on the clinical response after 8 weeks) 
- Good response and no complications: Discontinue PPI.
- Good response in patients with complications : Continue PPI at maintenance dose. 
- Partial response: Increase dose (to twice-daily therapy), adjust timing, or switch to a different PPI.
- Recurrence of symptoms after discontinuation of PPI or during weaning: Consider confirming the diagnosis (e.g., with ambulatory esophageal pH monitoring) prior to continuing maintenance therapy.
- No response: further diagnostic evaluation
- There is controversy surrounding the risks of long-term PPI therapy 
- H2 receptor antagonists: Consider as alternate maintenance therapy for NERD, or in addition to PPIs to control nighttime symptoms
- Maintenance therapy: lowest effective dose of acid suppression medication
- Adjunctive therapy: Consider adding in patients with partial response to PPIs; Not recommended without confirmatory diagnostic studies
A negative response to a PPI trial does not exclude GERD.
Lifestyle changes 
There is conflicting evidence as to which lifestyle modifications confer a significant benefit. The following recommendations are commonly mentioned in the literature but should be approached on a case-by-case basis, as they may offer relief only for some patients.
- Small portions
- Avoid eating at least 2–3 hours before bedtime.
- Avoid foods and beverages that appear to trigger symptoms. 
- Weight loss in patients with obesity
- Elevate the head of the bed (10–20 cm) for patients with nighttime symptoms.
- Reduce or avoid triggering substances
Surgical therapy 
Antireflux surgery may be considered for select patients after careful evaluation. Predictors of successful outcomes include: 
- Symptoms that correlate objectively with reflux episodes using ambulatory esophageal pH monitoring
- Prior good response to PPIs
- Discontinuation of medical therapy (e.g., due to nonadherence or side effects)
- Symptoms refractory to medical therapy
- Complications despite optimal medical therapy, e.g., severe esophagitis, strictures, recurrent aspiration
- Large hiatal hernia
- Definition: an antireflux procedure in which the gastric fundus is wrapped around the lower esophagus and secured with stitches to form a cuff; results in a narrowing of the distal esophagus and the gastroesophageal junction (GEJ), preventing reflux
- Approach: Laparoscopic and open fundoplication are possible.
- Techniques 
- Complications 
- Considerations for patients with comorbidities
Barrett esophagus 
- Definition: intestinal metaplasia of the esophageal mucosa induced by chronic reflux.
- Incidence: up to 15% of patients with GERD
Risk factors for Barrett esophagus 
- Male sex
- European descent
- Age ≥ 50 years
- Symptoms ≥ 5 years
- Reflux esophagitis → stomach acid damages mucosa of distal esophagus → nonkeratinized stratified squamous epithelium is replaced by nonciliated columnar epithelium and goblet cells (intestinal metaplasia, Barrett metaplasia) 
- The physiological transformation zone (Z line) between squamous and columnar epithelium is shifted upwards.
- Complications: esophageal adenocarcinoma (see “ )
Management and surveillance
PPI therapy 
- Consider if asymptomatic.
- Continue maintenance therapy long-term if symptomatic.
Endoscopy with four-quadrant biopsies at every 2 cm of the suspicious area (salmon-colored mucosa)
- If no dysplasia: Repeat endoscopy every 3–5 years.
- If indefinite for dysplasia: Repeat endoscopy with biopsies after 3–6 months of optimized PPI therapy.
- If low-grade dysplasia:
- If high-grade dysplasia: endoscopic treatment of mucosal irregularities, e.g., radiofrequency ablation
- Consider antireflux surgery or resection of the segment based on a specialist's evaluation. 
- PPI therapy 
Endoscopic examination of the esophagus is indicated to screen for Barrett esophagus in men with chronic (> 5 years) and/or frequent (occurring at least weekly) GERD symptoms and ≥ 2 of the following risk factors: age > 50 years, white ethnicity, obesity, current or past history of smoking, family history of Barrett esophagus or esophageal adenocarcinoma.
- Reflux esophagitis: most common complication of GERD 
- Erosive esophagitis
- Iron deficiency anemia: mucosal erosions and ulcerations → chronic bleeding → anemia
- Clinical features: solid food dysphagia
- Recurrence occurs in the majority of patients; multiple treatment attempts are often necessary.
- Esophageal rings: e.g., Schatzki rings
- Complications due to aspiration of gastric contents
- Reflux laryngitis: hoarseness (due to laryngopharyngeal reflux)
We list the most important complications. The selection is not exhaustive.
Special patient groups
Gastroesophageal reflux disease in infants
- Etiology: persistent lower esophageal sphincter insufficiency
- Clinical features
Diagnostics: based on clinical findings
- H&P (e.g., presence of , nutritional assessment, cow's milk and/or soy protein intolerance)
- Imaging: may be indicated if symptoms after initiation of empirical treatment persist
- Differential diagnoses: See .
Conservative measures: lifestyle and dietary changes should be re-evaluated every 2–4 weeks
- Positioning therapy: maintain the infant in an upright position for 20–30 minutes after feeding
- If there is suspicion of cow's milk and/or soy protein intolerance:
- Using food thickeners
- Avoid exposure to tobacco smoke 
- Pharmacological treatment
- Surgical treatment (complete or partial Nissen fundoplication): indicated in infants with complications from severe GERD who did not respond to conservative and pharmacological treatment
- Conservative measures: lifestyle and dietary changes should be re-evaluated every 2–4 weeks
- : 2022 updated American College of Gastroenterology (ACG) guidelines for GERD
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