U.S. flag

An official website of the United States government

NCBI Bookshelf. A service of the National Library of Medicine, National Institutes of Health.

StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2024 Jan-.

Cover of StatPearls

StatPearls [Internet].

Show details

Reflux Esophagitis

; .

Author Information and Affiliations

Last Update: April 17, 2023.

Continuing Education Activity

Reflux esophagitis is considered one of the most common diseases encountered by gastroenterologists and contributes to a large proportion of cases treated by primary care providers. It is defined as a condition in which the stomach contents reflux into the esophagus or beyond (oral cavity, larynx, or the lungs), causing troublesome symptoms and complications. This activity reviews the evaluation and management of esophageal reflux and highlights the role of the interprofessional team in evaluating and improving care for patients suffering from esophageal reflux.

Objectives:

  • Identify the etiology of reflux esophagitis.
  • Describe the options to diagnose reflux esophagitis.
  • Outline the current management options used in reflux esophagitis.
  • Identify interprofessional team strategies for improving care coordination and outcomes in patients with reflux esophagitis.
Access free multiple choice questions on this topic.

Introduction

Reflux esophagitis is considered one of the commonest diseases encountered by gastroenterologists and primary care providers. Reflux esophagitis is defined as inflammation of the esophageal mucosa secondary to gastroesophageal reflux disease (GERD), a condition in which the stomach contents reflux into the esophagus or beyond (oral cavity, larynx, or the lungs), causing troublesome symptoms and complications.

The American College of Gastroenterology defines GERD as “chronic symptoms or mucosal damage incurred by the abnormal reflux of gastric contents into the esophagus.”[1][2] It contributes to a large proportion of cases treated by primary care providers. In Western countries, the prevalence of the disease is approximately 10% to 20%, and severe disease is observed in 6% of the population; in Asian countries, the prevalence is approximately 5%.[3][4] Risk factors contributing to the development of esophageal reflux include age over 50, body mass index above 30, smoking, anxiety, depression, and decreased physical activity. Medicines that modulate the lower esophageal sphincter pressure, including nitrates, calcium channel blocker agents, and anticholinergics, play a role. Recently, non-alcoholic fatty liver disease has been reported to increase the risk of developing reflux esophagitis.

The disease is primarily a disorder of the lower esophageal sphincter. It can be classified based on the presence of symptoms without erosions on endoscopic examination (non-erosive disease, NERD) or symptoms plus esophageal erosions (erosive reflux disease, ERD). While the disease is particularly more common in men, it is more likely to be NERD when it occurs in women. The diagnosis is usually established based on a combination of presenting symptoms, objective testing with endoscopy, ambulatory reflux monitoring, and response to a proton pump inhibitor (PPI) therapy.[5] Based on the clinical picture, particularly when patients are presenting with typical symptoms, investigations are not needed in these patients. Investigations are usually recommended in patients presenting with atypical symptoms and patients developing complications.

Esophageal reflux may result in several complications, including esophagitis, upper gastrointestinal bleeding, anemia, peptic ulcer, peptic stricture, dysphagia, cancer of gastric cardia, and Barrett esophagus.[6] The reflux may also result in extra-gastrointestinal complications, including dental erosions, laryngitis, cough, asthma, sinusitis, and idiopathic pulmonary fibrosis.[7] Reflux esophagitis frequently occurs during pregnancy at any trimester. Usually, these patients do not have heartburn before pregnancy, and in these patients, reflux and heartburn usually resolve after the delivery. The management goals are:

  • Reduction of weight in patients with obesity and changes in dietary habits to decrease the effects of reflux
  • Treatment of reflux with PPI
  • Exploring alternative management plans for patients not responding to PPI
  • Management of esophageal reflux complications

Etiology

To understand the etiology of reflux esophagitis, the physiological mechanisms that regulate esophageal functions and minimize esophageal reflux should be understood first. These factors can be summarized as follows:

  1. The complex valvular mechanism at the esophagogastric junction antagonizes the positive abdominal pressure and the negative thoracic pressure and acts together to prevent the reflux of gastric acid contents into the esophagus. This complex valvular mechanism comprises the following components:[8][9]
    • The lower esophageal sphincter: This physiological sphincter is composed of different muscle fibers spinning 3 to 5 cm in length and coordinating the passage of food into the stomach and preventing the regurgitation of gastric contents into the esophagus.
    • Diaphragm: The diaphragm plays an essential role as the esophagus enters the abdomen through the hiatus. The diaphragm works as an extrinsic component to support the lower esophageal sphincter function.[10]
    • Abdominal part of the esophagus: This part of the esophagus is exposed to the positive intra-abdominal pressure causing a collapse of this part of the esophagus and thus supporting the lower esophageal sphincter.
    • The angle of His: This is the acute angle between the esophagus and the gastric fundus. Such design enhances the function of the lower esophageal sphincter.
    • Phreno-esophageal membrane: This is a fibroelastic ligament that is a continuation of the transversalis fascia that leaves the diaphragm and surrounds the esophagus.
  2. Protective physiological mechanisms include:
    • Esophageal motility: The peristaltic movement of the esophagus enables the movement of any regurgitated acid to return to the stomach.[11][12]
    • Saliva production: Swallowed saliva (alkaline) helps neutralize any acids at the lower esophagus.
    • Esophageal epithelial protection: This mechanism comprises pre-epithelial, epithelial, and post epithelial mechanisms (the three mechanisms are discussed later).

Reflux of gastric contents into the esophagus occurs in healthy individuals, but the amounts refluxed are normally cleared through two main mechanisms:

  1. Clearance by esophageal peristaltic movement
  2. Neutralization of the small acidic residue by weakly alkaline swallowed saliva

Therefore, the causes of reflux esophagitis could be discussed as follows:[8][9][13][14][15]

  • Transient relaxation of the lower esophageal sphincter or a low resting lower esophageal sphincter pressure
  • Presence of a hiatus hernia
  • Increased intra-abdominal fat, as is the case in obesity, and increased intra-abdominal pressure, such as in pregnancy and patients with ascites
  • Impairment of the normal defense mechanisms, including esophageal peristalsis (dysregulation of esophageal peristalsis)
  • Impairment of saliva production due to several causes, including chronic inflammation of the salivary glands
  • Impairment of esophageal mural defense mechanisms

 The factors that increase the risk of development of esophageal reflux include:[16][17][18][19]

  • White males over the age of 50 and a family history of reflux esophagitis
  • Central obesity: This is associated with ERD and complications, including Barrett esophagus and adenocarcinoma[18]
  • Tobacco smoking is considered an etiological factor of reflux esophagitis, while alcohol consumption is considered a triggering factor of reflux[20]
  • Delayed gastric emptying
  • Esophageal dysmotility
  • Increased abdominal pressure
  • Hiatus hernia
  • Non-alcoholic fatty liver disease[19]
  • Decreased thoracic pressure, such as in chronic chest problems
  • Psychosocial stress and the severity of reflux esophagitis correlate with the degree of stress[21]

Epidemiology

There are geographical variations in the distribution of reflux esophagitis. In Western countries, the prevalence of the disease is approximately 10% to 20%, and severe disease is observed in 6% of the population, while in Asian countries, the prevalence is approximately 5%.[15][22] Reflux esophagitis is equally prevalent among men and women.[23] However, the predominance of esophagitis and Barrett esophagitis in men compared to women is 3:1 and 10:1, respectively. Some studies report a higher frequency of reflux esophagitis in men, whereas others report an increased frequency in women.[24][25] The incidence of reflux esophagitis is greatest at the age of 60 to 70 years and decreases slightly thereafter. As observed in adults, GERD is also increasingly seen in the pediatric population. Nelson et al. reported incidence of GERD ranging between 12% and 50% in children aged 0-18 years from the year 2000 to 2005.[26] Gastroesophageal reflux exists universally in preterm infants.[27] Genetic variations, environmental factors, and lifestyle play a role in developing esophageal reflux.

Approximately half of the pregnant women complain of reflux during pregnancy: 20% to 30% in the first trimester, 40% to 45% in the second trimester, and 60% in the third trimester.[28] Usually, these patients do not have symptoms such as heartburn before their pregnancy. Only 14% may have infrequent mild heartburn.

Reflux esophagitis and Barrett esophagus are associated with higher body mass index: The association with overweight has an odds ratio of 1.33, 95% confidence intervals of 1.07-1.64, and the association with obesity has an odds ratio of 1.70, 95% confidence intervals 1.36 to 2.12.[29]

Several medications have been associated with reflux esophagitis symptoms, including drugs acting by modulating the lower esophageal sphincter pressure, including nitrates, calcium channel blocker agents, anticholinergics, alpha-adrenergic agonists, theophylline, and morphine.

Patients with nonalcoholic fatty liver disease exhibit an increased incidence of reflux esophagitis independent of any confounders.[19]

Pathophysiology

The pathophysiological mechanisms underlying reflux esophagitis are related to the etiological causes and will be discussed in more detail below.[30][31][32][33]

  • Transient relaxation of the lower esophageal sphincter: This change results in regurgitation of the gastric acid, peptic enzymes, and bile acids into the esophagus. In patients with increased intra-abdominal pressure (patients with ascites and pregnant women), this effect is enhanced.
  • Hiatus hernia: The presence of a hernia disturbs the anatomical relationship between the crural diaphragm and the lower esophageal sphincter function. Also, hernias act as a reservoir for gastric contents, which can reflux into the esophagus during swallowing (relaxation of the lower esophageal sphincter).
  • Increased intra-abdominal fat: The change increases the gastroesophageal pressure gradient and increases the frequency of transient lower esophageal sphincter relaxation phase. These changes result in the reflux of the stomach contents into the esophagus.[34][35]
  • Impairment of the physiological defense mechanisms: For example, dysregulation of esophageal peristalsis could result in ineffective clearance of acids from the lower esophagus.
  • Impairment of saliva production could impair the role of saliva in neutralizing the acids refluxed into the esophagus.
  • Impairment of esophageal mural defense mechanisms: This comprises three different mechanisms:
    • A pre-epithelial barrier (unstirred water layer combined with bicarbonate from swallowed saliva and the secretion of submucous glands).
    • Epithelial defense mechanisms include tight intercellular junctions, cellular, intercellular buffers, and cell membrane transporters.
    • Post-epithelial line of defense, including blood supply to the esophagus.
  • The pathogenesis of reflux esophagitis and the development of complications such as Barrett esophagus are mediated by cytokines rather than the results of chemical injury. Reflux esophagitis activates hypoxia-inducible factor (HIF)-2 alpha and nuclear factor kappa-light-chain-enhancer of activated b cells (NF), causing increased pro-inflammatory cytokines and migration of T cells inflammatory cells, causing damage to the esophagus.[36][37][38]

Histopathology

In reflux esophagitis, toxic substances (gastric acid, pepsin, and bile salts) are brought in contact with esophageal mucosa causing damage to the distal esophageal mucosa and mucosal breaks that can be detected by endoscopy in 30% to 40% of these patients. The histology of reflux esophagitis is not specific, as the histologic changes may also be present in other pathologic states, such as in adjacent mucosa in esophageal cancer.[39] The histological changes of reflux esophagitis include:[40]

  • Epithelial injury and neutrophilic infiltration of the epithelium
  • Changes confined to the mucosa, lamina propria, and muscularis mucosa
  • Longstanding and untreated patients develop peptic strictures, chronic inflammation, and Barrett metaplasia
  • Papillae proliferation of basal cells in the distal esophagus
  • Dilated intercellular spaces within the squamous epithelium

In patients with NERD, dilatation of the intercellular spaces (the most consistent microscopic finding), basal hyperplasia, and papillary elongation may be present.

Eosinophilic infiltration can be present. However, eosinophilic infiltration, particularly of the proximal esophagus, is present in eosinophilic esophagitis, and these two conditions should be differentiated.[41]

Confocal laser endomicroscopy in patients with NERD is characterized by more intrapapillary capillary loops per image than in control individuals.[42] Also, the diameter of intrapapillary capillary loops and intercellular spaces are greater in reflux esophagitis compared to controls.

History and Physical

Typical Symptoms

The typical symptoms of reflux esophagitis may include heartburn and acid regurgitation. Heartburn is a burning sensation felt behind the sternum within 60 minutes of eating. It is usually precipitated by exercising and lying in a recumbent position. The pain usually starts in the epigastrium and radiates towards the neck. However, some patients with severe esophagitis or Barrett esophagus may be symptom-free and have no heartburn.[43]

Acid regurgitation where the patient may notice a sour or burning fluid in the throat or mouth may be present. Maneuvers increasing intra-abdominal pressure and bending forward could provoke regurgitation of gastric acid.[44]

Some dysphagia may be reported in 30% of patients with reflux esophagitis (usually present in the presence of peptic strictures, Schatzki rings, weak peristalsis, or mucosal inflammation).

Other symptoms include:

  • Globus sensation (a sense of a lump in the throat)
  • Water brash (increased salivary secretions in response to the acidity of the esophagus)[45]

Atypical Symptoms

These include the following:[46]

  • Chest pain: The esophageal reflux may mimic cardiac pain, and patients should be evaluated to exclude cardiac causes.[47] Other causes of esophageal causes of chest pain, including esophageal motility disorders, diffuse esophageal spasms, or hypertensive peristalsis (nutcracker esophagus), may be considered in the evaluation. However, reflux esophagitis is more common than these esophageal disorders.
  • Chronic cough: Reflux esophagitis is one of the causes of chronic cough.[48] Other causes of chronic cough include post-nasal discharge, asthma, and some medications such as angiotensin-converting enzyme inhibitors. The underlying pathogenesis of cough in reflux esophagitis can be explained based on acid stimulation of nerve endings in the lower esophagus causing activation of the cough center and cough response.
  • Asthma: There is an association between asthma and reflux esophagitis.[49] However, it is unclear whether this relationship is an association or a cause-effect change. However, the underlying relationship could be explained based on autonomic dysregulation that usually occurs in patients with asthma, resulting in an increased vagal tone. This change, together with the increased negative intrathoracic pressure during asthma, could enhance the tendency for reflux. Another contributing factor is medications used to manage asthma, such as theophylline, and alpha-2 adrenergic receptor agonists, which may promote reflux by lowering the pressure across the lower esophageal sphincter.
  • Dental erosions, dysphonia (voice disorder), sore throat, and laryngospasm may be present.[50]

Evaluation

The diagnosis of reflux esophagitis is usually made based on a combination of presenting symptoms, objective testing with endoscopy, ambulatory reflux monitoring, and response to a PPI therapy.[51] A good percentage of patients present with typical symptoms of heartburn and gastric regurgitation and do not need investigations to make the diagnosis. Patients presenting with chest pain should be investigated to exclude cardiac causes of chest pain before the commencement of gastrointestinal evaluation.

Patients with atypical symptoms should undergo a diagnostic evaluation with endoscopy and pH monitoring before a PPI trial.[52] Patients presenting with dysphagia should undergo an endoscopic examination to rule out reflux complications (esophageal strictures, peptic ulcerations, malignancy).

Performing endoscopy may be indicated in high-risk groups, particularly overweight, over the age of 50, and with chronic esophageal reflux for more than five years. Also, it is indicated in patients at high risk of complications, including Barrett esophagus, dysphagia, anemia, bleeding, and weight loss. Esophageal biopsies should be an adjunct to endoscopic examination, particularly in patients with non-erosive changes and those suspected to have eosinophilic esophagitis.[53]

Esophageal manometry is of limited value in the primary diagnosis of reflux esophagitis disease.

Neither a decrease in lower esophageal sphincter pressure nor the presence of a motility abnormality is specific for the diagnosis of reflux esophagitis disease. However, manometry is recommended before considering anti-reflux surgery (to rule out achalasia or severe hypomotility as in scleroderma-like esophagus where Nissen fundoplication is contraindicated).

Ambulatory reflux monitoring is the only test that allows the determination of abnormal esophageal acid reflux and reflux frequency. In patients with PPI-resistant symptoms, ambulatory 24-h pH-impedance monitoring can be used to assess whether there is a relationship between symptoms and reflux episodes. This test can help exclude reflux esophagitis, but the test should be carried out after the cessation of PPI therapy.[54]

Patients with atypical symptoms should undergo a diagnostic evaluation with endoscopy and pH monitoring before a PPI trial. Barium studies to diagnose reflux esophagitis are of limited value. The presence or absence of reflux during barium esophagography does not correlate with the incidence or extent of reflux observed during 24-hour pH impedance monitoring and is of no value in the diagnosis of reflux esophagitis.[55]

Los Angeles classification of severity of reflux esophagitis-four grades:[56]

  • Grade A: One or more esophageal mucosal breaks less than 5 mm in length.
  • Grade B: One or more mucosal breaks greater than 5 mm but with continuity across mucosal folds.
  • Grade C: Continuous mucosal breaks between the tops of two or more mucosal folds but involving less than 75% of the esophageal circumference.
  • Grade D: Mucosal breaks involving more than 75% of the esophageal sphincter.

Response to therapy with PPI (twice daily) in patients suspected of reflux esophagitis confirms the diagnosis. However, the PPI test is sensitive but has less specificity.[57]

Treatment / Management

Recommendations for the management of reflux esophagitis include the following:[58]

  • Weight loss, particularly in overweight patients and patients with obesity, will help in reducing the severity and frequency of symptoms.[59]
  • Elevating the head of the bed during sleep and avoiding meals two to three hours before sleep will reduce reflux at night.[60]
  • Avoiding certain foods such as chocolate, caffeine, alcohol, and spicy food may help.[61]
  • Treatment of patients with a proton pump inhibitor for eight weeks is recommended. Usually, initiated once daily before the first meal of the day. If there is a partial response, the dose should be increased to twice daily. PPIs are safe in pregnant women if clinically indicated.
  • Maintain PPI therapy for patients who continue to have symptoms and patients with erosive esophagitis and Barrett esophagus.
  • Patients who need PPI therapy for longer durations or life because of recurrence of symptoms should be placed on the lowest dose required for maintenance. Chronic use of PPI is associated with complications, including increased risk of bone fractures, electrolyte deficiencies, and renal insufficiency.
  • Patients not responding to PPIs treatment should be evaluated by the provider. In addition, other disorders should be considered, including eosinophilic esophagitis, delayed gastric emptying, irritable bowel syndrome, achalasia, and psychological disorders.
  • Surgical therapy is as effective as medical therapy in patients with chronic reflux esophagitis. It offers long-term treatment. Patients should be investigated (preoperative manometry) for surgery to rule out achalasia and scleroderma-like esophagus.
  • Vonoprazan fumarate tablet (a new synthesized potassium-competitive acid blocker), used on-demand, is an effective alternative maintenance therapy for mild reflux esophagitis.[62]
  • In patients with obesity, bariatric surgery- gastric bypass is usually recommended.
  • Management of reflux complications such as Schatzki rings by esophageal dilatation followed with PPI treatment; esophageal adenocarcinoma; laryngitis; and idiopathic pulmonary fibrosis.

Differential Diagnosis

 The differential diagnoses of reflux esophagitis may include:[63]

  • Coronary artery disease
  • Infectious esophagitis
  • Eosinophilic esophagitis
  • Peptic ulcer disease
  • Biliary colic
  • Esophageal motor disorders
  • Esophageal stricture
  • Esophageal cancer
  • Dyspepsia
  • Dysphagia
  • Rumination syndrome
  • Radiation and chemotherapy-induced esophagitis

Prognosis

Many patients with esophageal reflux do well with medications, but relapse after stopping medical treatment is common and indicates the need for long-term maintenance therapy. In refractory cases or when complications related to reflux disease are identified (e.g., stricture, aspiration, airway disease, Barrett esophagus), surgical treatment (fundoplication) is typically necessary. The prognosis with surgery is considered excellent. The surgical morbidity and mortality are higher in patients who have complex medical problems in addition to esophageal reflux. About 10% of patients with reflux develop Barrett esophagus, a precursor for adenocarcinoma of the esophagus.[64]

Complications

Complications associated with reflux esophagitis include:

  • Esophagitis varies in severity. Patients with Grade C and D in LA classification are characterized by severe reflux. These patients have the lowest healing rate with PPIs. Patients with severe reflux esophagitis usually relapse after treatment and are more likely to develop Barrett esophagus. These patients should undergo endoscopy 8 to 10 weeks after PPI therapy to check on healing and assess for complications.[65][66]
  • Lower esophageal rings (Schatzki)- This complication correlates with reflux esophagitis. Dilatation is the mainstay of management, followed by PPI treatment.
  • Barrett esophagus: This complication presents in 5% to 15% of patients with reflux esophagitis. It is more likely to occur in White male patients with severe reflux esophagitis, who have the symptoms for a longer duration, and are over the age of 50.
  • Peptic stricture tends to occur in older patients who have reflux for a longer duration, with abnormal esophageal motility and not receiving treatment for the reflux symptoms.
  • Esophageal adenocarcinoma (8 to 1 male to a female)
  • Peptic ulceration, gastric cardia cancer, dysphagia, and upper gastrointestinal bleeding.
  • Other complications include anemia (due to chronic blood loss), laryngitis, cough, sinusitis, bronchial asthma, idiopathic pulmonary fibrosis, and dental erosions.

Deterrence and Patient Education

Lifestyle modifications are an important part of treatment for esophageal reflux. Patients are counseled to make the following changes in their lifestyle:

  • Weight loss (if overweight)
  • Avoid alcohol, chocolate, citrus juice, peppermint, and coffee
  • Avoid large meals
  • Wait three hours after a meal before lying down
  • Elevate the head of the bed by 8 inches
  • Avoid bending or stooping

Pearls and Other Issues

The diagnosis of esophageal reflux is usually based on symptoms, objective testing with endoscopy, ambulatory reflux monitoring, and response to a PPI therapy. However, upper endoscopy is not required in patients presenting typical esophagitis symptoms. In addition, patients presenting with chest pain require investigation to exclude cardiac causes of chest pain.

Enhancing Healthcare Team Outcomes

The majority of patients with reflux esophagitis may present to the primary care provider. The public and patients require education about common presenting symptoms of reflux esophagitis and preventive measures. Because patients may present with atypical symptoms or complications, healthcare workers, including providers, gastroenterologists, pulmonologists, otolaryngologists, nurses, and pharmacists, all operating as an interprofessional team, need to be aware of the diagnosis, sequelae, and complications. Dentists should be aware of dental changes associated with reflux esophagitis. Patients presenting with atypical symptoms such as chronic cough, asthma, laryngitis, or dysphonia may seek medical advice from pulmonologists and otolaryngologists, not aware that esophageal reflux is the primary disease. Performing endoscopy may be indicated in high-risk groups, particularly overweight, over 50, with chronic esophageal reflux. Also, it is indicated in patients at high risk of complications, including Barrett esophagus, dysphagia, and weight loss. Using new classifications to stage reflux esophagitis patients should improve patient management.[67][68]

While the providers listed above will drive therapeutic interventions, they should enlist the pharmacist's assistance. Pharmacists can help determine which agents would best suit the patient's presentation and counsel the patient regarding appropriate administration and dosing and what adverse effects might occur. Nursing can answer patient questions, assess compliance, evaluate treatment progress, and inform the provider staff of any concerns they encounter. This type of interprofessional teamwork will improve patient outcomes with reflux esophagitis. [Level 5]

Review Questions

References

1.
DeVault KR, Castell DO. Updated guidelines for the diagnosis and treatment of gastroesophageal reflux disease. The Practice Parameters Committee of the American College of Gastroenterology. Am J Gastroenterol. 1999 Jun;94(6):1434-42. [PubMed: 10364004]
2.
Vakil N, van Zanten SV, Kahrilas P, Dent J, Jones R., Globale Konsensusgruppe. [The Montreal definition and classification of gastroesophageal reflux disease: a global, evidence-based consensus paper]. Z Gastroenterol. 2007 Nov;45(11):1125-40. [PubMed: 18027314]
3.
Sonnenberg A, El-Serag HB. Clinical epidemiology and natural history of gastroesophageal reflux disease. Yale J Biol Med. 1999 Mar-Jun;72(2-3):81-92. [PMC free article: PMC2579001] [PubMed: 10780569]
4.
Dent J, El-Serag HB, Wallander MA, Johansson S. Epidemiology of gastro-oesophageal reflux disease: a systematic review. Gut. 2005 May;54(5):710-7. [PMC free article: PMC1774487] [PubMed: 15831922]
5.
Weijenborg PW, Cremonini F, Smout AJ, Bredenoord AJ. PPI therapy is equally effective in well-defined non-erosive reflux disease and in reflux esophagitis: a meta-analysis. Neurogastroenterol Motil. 2012 Aug;24(8):747-57, e350. [PubMed: 22309489]
6.
Thrift AP, Kramer JR, Qureshi Z, Richardson PA, El-Serag HB. Age at onset of GERD symptoms predicts risk of Barrett's esophagus. Am J Gastroenterol. 2013 Jun;108(6):915-22. [PMC free article: PMC3972036] [PubMed: 23567358]
7.
Ghisa M, Marinelli C, Savarino V, Savarino E. Idiopathic pulmonary fibrosis and GERD: links and risks. Ther Clin Risk Manag. 2019;15:1081-1093. [PMC free article: PMC6733342] [PubMed: 31564886]
8.
Boeckxstaens GE. The lower oesophageal sphincter. Neurogastroenterol Motil. 2005 Jun;17 Suppl 1:13-21. [PubMed: 15836451]
9.
Boeckxstaens GE. Alterations confined to the gastro-oesophageal junction: the relationship between low LOSP, TLOSRs, hiatus hernia and acid pocket. Best Pract Res Clin Gastroenterol. 2010 Dec;24(6):821-9. [PubMed: 21126696]
10.
E Souza MÂ, Nobre RA, Bezerra PC, Dos Santos AA, Sifrim D. Anatomical and functional deficiencies of the crural diaphragm in patients with esophagitis. Neurogastroenterol Motil. 2017 Jan;29(1) [PubMed: 27418308]
11.
Fouad YM, Katz PO, Hatlebakk JG, Castell DO. Ineffective esophageal motility: the most common motility abnormality in patients with GERD-associated respiratory symptoms. Am J Gastroenterol. 1999 Jun;94(6):1464-7. [PubMed: 10364008]
12.
Gutschow CA, Leers JM, Schröder W, Prenzel KL, Fuchs H, Bollschweiler E, Bludau M, Hölscher AH. Effect of aging on esophageal motility in patients with and without GERD. Ger Med Sci. 2011;9:Doc22. [PMC free article: PMC3159207] [PubMed: 21863136]
13.
Boeckxstaens GE, Rohof WO. Pathophysiology of gastroesophageal reflux disease. Gastroenterol Clin North Am. 2014 Mar;43(1):15-25. [PubMed: 24503356]
14.
Beaumont H, Bennink RJ, de Jong J, Boeckxstaens GE. The position of the acid pocket as a major risk factor for acidic reflux in healthy subjects and patients with GORD. Gut. 2010 Apr;59(4):441-51. [PubMed: 19651625]
15.
Rubenstein JH, Chen JW. Epidemiology of gastroesophageal reflux disease. Gastroenterol Clin North Am. 2014 Mar;43(1):1-14. [PubMed: 24503355]
16.
Emerenziani S, Rescio MP, Guarino MP, Cicala M. Gastro-esophageal reflux disease and obesity, where is the link? World J Gastroenterol. 2013 Oct 21;19(39):6536-9. [PMC free article: PMC3801365] [PubMed: 24151378]
17.
Asanuma K, Iijima K, Shimosegawa T. Gender difference in gastro-esophageal reflux diseases. World J Gastroenterol. 2016 Feb 07;22(5):1800-10. [PMC free article: PMC4724611] [PubMed: 26855539]
18.
Chang P, Friedenberg F. Obesity and GERD. Gastroenterol Clin North Am. 2014 Mar;43(1):161-73. [PMC free article: PMC3920303] [PubMed: 24503366]
19.
Yang HJ, Chang Y, Park SK, Jung YS, Park JH, Park DI, Cho YK, Ryu S, Sohn CI. Nonalcoholic Fatty Liver Disease Is Associated with Increased Risk of Reflux Esophagitis. Dig Dis Sci. 2017 Dec;62(12):3605-3613. [PubMed: 29063416]
20.
Ness-Jensen E, Lagergren J. Tobacco smoking, alcohol consumption and gastro-oesophageal reflux disease. Best Pract Res Clin Gastroenterol. 2017 Oct;31(5):501-508. [PubMed: 29195669]
21.
Song EM, Jung HK, Jung JM. The association between reflux esophagitis and psychosocial stress. Dig Dis Sci. 2013 Feb;58(2):471-7. [PMC free article: PMC3576549] [PubMed: 23001402]
22.
Savarino E, Marabotto E, Bodini G, Pellegatta G, Coppo C, Giambruno E, Brunacci M, Zentilin P, Savarino V. Epidemiology and natural history of gastroesophageal reflux disease. Minerva Gastroenterol Dietol. 2017 Sep;63(3):175-183. [PubMed: 28215067]
23.
Nebel OT, Fornes MF, Castell DO. Symptomatic gastroesophageal reflux: incidence and precipitating factors. Am J Dig Dis. 1976 Nov;21(11):953-6. [PubMed: 984016]
24.
Loffeld RJ, van der Putten AB. Rising incidence of reflux oesophagitis in patients undergoing upper gastrointestinal endoscopy. Digestion. 2003;68(2-3):141-4. [PubMed: 14646335]
25.
Kotzan J, Wade W, Yu HH. Assessing NSAID prescription use as a predisposing factor for gastroesophageal reflux disease in a Medicaid population. Pharm Res. 2001 Sep;18(9):1367-72. [PubMed: 11683254]
26.
Nelson SP, Kothari S, Wu EQ, Beaulieu N, McHale JM, Dabbous OH. Pediatric gastroesophageal reflux disease and acid-related conditions: trends in incidence of diagnosis and acid suppression therapy. J Med Econ. 2009;12(4):348-55. [PubMed: 19827992]
27.
Eichenwald EC., COMMITTEE ON FETUS AND NEWBORN. Diagnosis and Management of Gastroesophageal Reflux in Preterm Infants. Pediatrics. 2018 Jul;142(1) [PubMed: 29915158]
28.
Vazquez JC. Heartburn in pregnancy. BMJ Clin Evid. 2015 Sep 08;2015 [PMC free article: PMC4562453] [PubMed: 26348641]
29.
Stein DJ, El-Serag HB, Kuczynski J, Kramer JR, Sampliner RE. The association of body mass index with Barrett's oesophagus. Aliment Pharmacol Ther. 2005 Nov 15;22(10):1005-10. [PubMed: 16268976]
30.
Herregods TV, Bredenoord AJ, Smout AJ. Pathophysiology of gastroesophageal reflux disease: new understanding in a new era. Neurogastroenterol Motil. 2015 Sep;27(9):1202-13. [PubMed: 26053301]
31.
Boeckxstaens GE. Review article: the pathophysiology of gastro-oesophageal reflux disease. Aliment Pharmacol Ther. 2007 Jul 15;26(2):149-60. [PubMed: 17593062]
32.
Castell DO, Murray JA, Tutuian R, Orlando RC, Arnold R. Review article: the pathophysiology of gastro-oesophageal reflux disease - oesophageal manifestations. Aliment Pharmacol Ther. 2004 Dec;20 Suppl 9:14-25. [PubMed: 15527461]
33.
Usai Satta P, Oppia F, Cabras F. Overview of pathophysiological features of GERD. Minerva Gastroenterol Dietol. 2017 Sep;63(3):184-197. [PubMed: 28251844]
34.
Niigaki M, Adachi K, Hirakawa K, Furuta K, Kinoshita Y. Association between metabolic syndrome and prevalence of gastroesophageal reflux disease in a health screening facility in Japan. J Gastroenterol. 2013 Apr;48(4):463-72. [PubMed: 22976934]
35.
Corley DA, Kubo A, Levin TR, Block G, Habel L, Zhao W, Leighton P, Quesenberry C, Rumore GJ, Buffler PA. Abdominal obesity and body mass index as risk factors for Barrett's esophagus. Gastroenterology. 2007 Jul;133(1):34-41; quiz 311. [PubMed: 17631128]
36.
Souza RF. Reflux esophagitis and its role in the pathogenesis of Barrett's metaplasia. J Gastroenterol. 2017 Jul;52(7):767-776. [PMC free article: PMC5488728] [PubMed: 28451845]
37.
Souza RF, Bayeh L, Spechler SJ, Tambar UK, Bruick RK. A new paradigm for GERD pathogenesis. Not acid injury, but cytokine-mediated inflammation driven by HIF-2α: a potential role for targeting HIF-2α to prevent and treat reflux esophagitis. Curr Opin Pharmacol. 2017 Dec;37:93-99. [PMC free article: PMC5922421] [PubMed: 29112883]
38.
Dunbar KB, Agoston AT, Odze RD, Huo X, Pham TH, Cipher DJ, Castell DO, Genta RM, Souza RF, Spechler SJ. Association of Acute Gastroesophageal Reflux Disease With Esophageal Histologic Changes. JAMA. 2016 May 17;315(19):2104-12. [PMC free article: PMC5030713] [PubMed: 27187303]
39.
Takubo K, Honma N, Aryal G, Sawabe M, Arai T, Tanaka Y, Mafune K, Iwakiri K. Is there a set of histologic changes that are invariably reflux associated? Arch Pathol Lab Med. 2005 Feb;129(2):159-63. [PubMed: 15679411]
40.
Genta RM, Spechler SJ, Kielhorn AF. The Los Angeles and Savary-Miller systems for grading esophagitis: utilization and correlation with histology. Dis Esophagus. 2011 Jan;24(1):10-7. [PubMed: 20659145]
41.
Straumann A, Katzka DA. Diagnosis and Treatment of Eosinophilic Esophagitis. Gastroenterology. 2018 Jan;154(2):346-359. [PubMed: 28756235]
42.
Chu CL, Zhen YB, Lv GP, Li CQ, Li Z, Qi QQ, Gu XM, Yu T, Zhang TG, Zhou CJ, Rui-Ji, Li YQ. Microalterations of esophagus in patients with non-erosive reflux disease: in-vivo diagnosis by confocal laser endomicroscopy and its relationship with gastroesophageal reflux. Am J Gastroenterol. 2012 Jun;107(6):864-74. [PubMed: 22415199]
43.
Nagahara A, Hojo M, Asaoka D, Sasaki H, Oguro M, Mori H, Matsumoto K, Osada T, Yoshizawa T, Watanabe S. Clinical feature of asymptomatic reflux esophagitis in patients who underwent upper gastrointestinal endoscopy. J Gastroenterol Hepatol. 2012 Apr;27 Suppl 3:53-7. [PubMed: 22486872]
44.
Kellerman R, Kintanar T. Gastroesophageal Reflux Disease. Prim Care. 2017 Dec;44(4):561-573. [PubMed: 29132520]
45.
Helm JF, Dodds WJ, Hogan WJ. Salivary response to esophageal acid in normal subjects and patients with reflux esophagitis. Gastroenterology. 1987 Dec;93(6):1393-7. [PubMed: 3678754]
46.
Naik RD, Vaezi MF. Extra-esophageal gastroesophageal reflux disease and asthma: understanding this interplay. Expert Rev Gastroenterol Hepatol. 2015 Jul;9(7):969-82. [PubMed: 26067887]
47.
Garza JM, Kaul A. Gastroesophageal reflux, eosinophilic esophagitis, and foreign body. Pediatr Clin North Am. 2010 Dec;57(6):1331-45. [PubMed: 21111120]
48.
Kahrilas PJ, Altman KW, Chang AB, Field SK, Harding SM, Lane AP, Lim K, McGarvey L, Smith J, Irwin RS., CHEST Expert Cough Panel. Chronic Cough Due to Gastroesophageal Reflux in Adults: CHEST Guideline and Expert Panel Report. Chest. 2016 Dec;150(6):1341-1360. [PMC free article: PMC6026249] [PubMed: 27614002]
49.
Parsons JP, Mastronarde JG. Gastroesophageal reflux disease and asthma. Curr Opin Pulm Med. 2010 Jan;16(1):60-3. [PubMed: 19887939]
50.
Marsicano JA, de Moura-Grec PG, Bonato RC, Sales-Peres Mde C, Sales-Peres A, Sales-Peres SH. Gastroesophageal reflux, dental erosion, and halitosis in epidemiological surveys: a systematic review. Eur J Gastroenterol Hepatol. 2013 Feb;25(2):135-41. [PubMed: 23111415]
51.
Badillo R, Francis D. Diagnosis and treatment of gastroesophageal reflux disease. World J Gastrointest Pharmacol Ther. 2014 Aug 06;5(3):105-12. [PMC free article: PMC4133436] [PubMed: 25133039]
52.
Mattox HE, Richter JE. Prolonged ambulatory esophageal pH monitoring in the evaluation of gastroesophageal reflux disease. Am J Med. 1990 Sep;89(3):345-56. [PubMed: 2203264]
53.
Dent J. Endoscopic grading of reflux oesophagitis: the past, present and future. Best Pract Res Clin Gastroenterol. 2008;22(4):585-99. [PubMed: 18656818]
54.
Hemmink GJ, Bredenoord AJ, Weusten BL, Monkelbaan JF, Timmer R, Smout AJ. Esophageal pH-impedance monitoring in patients with therapy-resistant reflux symptoms: 'on' or 'off' proton pump inhibitor? Am J Gastroenterol. 2008 Oct;103(10):2446-53. [PubMed: 18684197]
55.
Saleh CM, Smout AJ, Bredenoord AJ. The diagnosis of gastro-esophageal reflux disease cannot be made with barium esophagograms. Neurogastroenterol Motil. 2015 Feb;27(2):195-200. [PubMed: 25327284]
56.
Lundell LR, Dent J, Bennett JR, Blum AL, Armstrong D, Galmiche JP, Johnson F, Hongo M, Richter JE, Spechler SJ, Tytgat GN, Wallin L. Endoscopic assessment of oesophagitis: clinical and functional correlates and further validation of the Los Angeles classification. Gut. 1999 Aug;45(2):172-80. [PMC free article: PMC1727604] [PubMed: 10403727]
57.
Pace F, Pace M. The proton pump inhibitor test and the diagnosis of gastroesophageal reflux disease. Expert Rev Gastroenterol Hepatol. 2010 Aug;4(4):423-7. [PubMed: 20678016]
58.
Gyawali CP, Fass R. Management of Gastroesophageal Reflux Disease. Gastroenterology. 2018 Jan;154(2):302-318. [PubMed: 28827081]
59.
Heidelbaugh JJ, Nostrant TT, Kim C, Van Harrison R. Management of gastroesophageal reflux disease. Am Fam Physician. 2003 Oct 01;68(7):1311-8. [PubMed: 14567485]
60.
Kaltenbach T, Crockett S, Gerson LB. Are lifestyle measures effective in patients with gastroesophageal reflux disease? An evidence-based approach. Arch Intern Med. 2006 May 08;166(9):965-71. [PubMed: 16682569]
61.
Surdea-Blaga T, Negrutiu DE, Palage M, Dumitrascu DL. Food and Gastroesophageal Reflux Disease. Curr Med Chem. 2019;26(19):3497-3511. [PubMed: 28521699]
62.
Umezawa M, Kawami N, Hoshino S, Hoshikawa Y, Koizumi E, Takenouchi N, Hanada Y, Kaise M, Iwakiri K. Efficacy of On-Demand Therapy Using 20-mg Vonoprazan for Mild Reflux Esophagitis. Digestion. 2018;97(4):309-315. [PubMed: 29514137]
63.
Spechler SJ. Eosinophilic esophagitis: novel concepts regarding pathogenesis and clinical manifestations. J Gastroenterol. 2019 Oct;54(10):837-844. [PMC free article: PMC6759606] [PubMed: 31342146]
64.
Zhang HY, Spechler SJ, Souza RF. Esophageal adenocarcinoma arising in Barrett esophagus. Cancer Lett. 2009 Mar 18;275(2):170-7. [PMC free article: PMC2673195] [PubMed: 18703277]
65.
DeMeester SR. Barrett's oesophagus: treatment with surgery. Best Pract Res Clin Gastroenterol. 2015 Feb;29(1):211-7. [PubMed: 25743467]
66.
Parasa S, Sharma P. Complications of gastro-oesophageal reflux disease. Best Pract Res Clin Gastroenterol. 2013 Jun;27(3):433-42. [PubMed: 23998980]
67.
Ribolsi M, Giordano A, Guarino MPL, Tullio A, Cicala M. New classifications of gastroesophageal reflux disease: an improvement for patient management? Expert Rev Gastroenterol Hepatol. 2019 Aug;13(8):761-769. [PubMed: 31327288]
68.
Hopper AD. Improving the diagnosis and management of GORD in adults. Practitioner. 2015 Apr;259(1781):27-32, 3. [PubMed: 26529827]

Disclosure: Samy Azer declares no relevant financial relationships with ineligible companies.

Disclosure: Anil Kumar Reddy Reddivari declares no relevant financial relationships with ineligible companies.

Copyright © 2024, StatPearls Publishing LLC.

This book is distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0) ( http://creativecommons.org/licenses/by-nc-nd/4.0/ ), which permits others to distribute the work, provided that the article is not altered or used commercially. You are not required to obtain permission to distribute this article, provided that you credit the author and journal.

Bookshelf ID: NBK554462PMID: 32119349

Views

  • PubReader
  • Print View
  • Cite this Page

Related information

  • PMC
    PubMed Central citations
  • PubMed
    Links to PubMed

Similar articles in PubMed

See reviews...See all...

Recent Activity

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...