Diagnostic Considerations

Gastroesophageal reflux may be classified into three categories, as follows:

Physiologic (or functional) gastroesophageal reflux: These patients have no underlying predisposing factors or conditions; growth and development are normal; and pharmacologic treatment is typically not necessary, though it may be needed to relieve symptoms if lifestyle changes are unsuccessful.^[7]
Pathologic gastroesophageal reflux or GERD: Patients frequently experience complications noted above, requiring careful evaluation and treatment^[26]
Secondary gastroesophageal reflux: This refers to a case in which an underlying condition may predispose to gastroesophageal reflux, with examples including asthma (a condition that may also be, in part, caused by or exacerbated by reflux) and gastric outlet obstruction

The diagnosis of GERD in patients with atypical symptoms can be difficult. When patients present with atypical complaints, the diagnosis of GERD must be kept in mind. Patients with recurrent aspiration can have asthma, history of pneumonias, and progressive pulmonary fibrosis. Additionally, hoarseness can be present due to chronic laryngeal irritation. Chest pain is another presenting symptom that can be difficult to evaluate. In these patients, excluding cardiac etiology is important prior to labeling the pain as noncardiac chest pain secondary to GERD.

The clinical presentation of GERD in pregnant women is similar to that for the general population. Heartburn and regurgitation are the cardinal symptoms. The diagnostic evaluation consists of a thorough history and physical examination.

Differential Diagnoses

Workup

Giannini EG, Zentilin P, Dulbecco P, Vigneri S, Scarlata P, Savarino V. Management strategy for patients with gastroesophageal reflux disease: a comparison between empirical treatment with esomeprazole and endoscopy-oriented treatment. Am J Gastroenterol. 2008 Feb. 103(2):267-75. [QxMD MEDLINE Link].
Katz PO. Medical therapy for gastroesophageal reflux disease in 2007. Rev Gastroenterol Disord. 2007 Fall. 7(4):193-203. [QxMD MEDLINE Link].
Fass R, Sifrim D. Management of heartburn not responding to proton pump inhibitors. Gut. 2009 Feb. 58(2):295-309. [QxMD MEDLINE Link].
Fass R. Proton pump inhibitor failure--what are the therapeutic options?. Am J Gastroenterol. 2009 Mar. 104 suppl 2:S33-8. [QxMD MEDLINE Link].
Heidelbaugh JJ, Goldberg KL, Inadomi JM. Overutilization of proton pump inhibitors: a review of cost-effectiveness and risk [corrected]. Am J Gastroenterol. 2009 Mar. 104 suppl 2:S27-32. [QxMD MEDLINE Link].
Dial MS. Proton pump inhibitor use and enteric infections. Am J Gastroenterol. 2009 Mar. 104 suppl 2:S10-6. [QxMD MEDLINE Link].
DeVault KR, Castell DO. Updated guidelines for the diagnosis and treatment of gastroesophageal reflux disease. Am J Gastroenterol. 2005 Jan. 100(1):190-200. [QxMD MEDLINE Link].
Gallup Organization. Heartburn Across America: A Gallup Organization National Survey. Princeton, NJ: Gallup Organization; 1988.
Richter JE. Surgery for reflux disease: reflections of a gastroenterologist. N Engl J Med. 1992 Mar 19. 326(12):825-7. [QxMD MEDLINE Link].
Chen CL, Robert JJ, Orr WC. Sleep symptoms and gastroesophageal reflux. J Clin Gastroenterol. 2008 Jan. 42(1):13-7. [QxMD MEDLINE Link].
Sveen S. Symptom check: is it GERD?. J Contin Educ Nurs. 2009 Mar. 40(3):103-4. [QxMD MEDLINE Link].
Mittal RK, Rochester DF, McCallum RW. Sphincteric action of the diaphragm during a relaxed lower esophageal sphincter in humans. Am J Physiol. 1989 Jan. 256(1 Pt 1):G139-44. [QxMD MEDLINE Link].
Mittal RK, McCallum RW. Characteristics of transient lower esophageal sphincter relaxation in humans. Am J Physiol. 1987 May. 252(5 Pt 1):G636-41. [QxMD MEDLINE Link].
Mittal RK, Rochester DF, McCallum RW. Effect of the diaphragmatic contraction on lower oesophageal sphincter pressure in man. Gut. 1987 Dec. 28(12):1564-8. [QxMD MEDLINE Link]. [Full Text].
Stein HJ, DeMeester TR. Outpatient physiologic testing and surgical management of foregut motility disorders. Curr Probl Surg. 1992 Jul. 29(7):413-555. [QxMD MEDLINE Link].
Kahrilas PJ, Dodds WJ, Hogan WJ, Kern M, Arndorfer RC, Reece A. Esophageal peristaltic dysfunction in peptic esophagitis. Gastroenterology. 1986 Oct. 91(4):897-904. [QxMD MEDLINE Link].
Buttar NS, Falk GW. Pathogenesis of gastroesophageal reflux and Barrett esophagus. Mayo Clin Proc. 2001 Feb. 76(2):226-34. [QxMD MEDLINE Link].
Hampel H, Abraham NS, El-Serag HB. Meta-analysis: obesity and the risk for gastroesophageal reflux disease and its complications. Ann Intern Med. 2005 Aug 2. 143(3):199-211. [QxMD MEDLINE Link]. [Full Text].
Herbella FA, Sweet MP, Tedesco P, Nipomnick I, Patti MG. Gastroesophageal reflux disease and obesity. Pathophysiology and implications for treatment. J Gastrointest Surg. 2007 Mar. 11(3):286-90. [QxMD MEDLINE Link].
Merrouche M, Sabate JM, Jouet P, et al. Gastro-esophageal reflux and esophageal motility disorders in morbidly obese patients before and after bariatric surgery. Obes Surg. 2007 Jul. 17(7):894-900. [QxMD MEDLINE Link].
Murray L, Johnston B, Lane A, et al. Relationship between body mass and gastro-oesophageal reflux symptoms: The Bristol Helicobacter Project. Int J Epidemiol. 2003 Aug. 32(4):645-50. [QxMD MEDLINE Link]. [Full Text].
Pandolfino JE, El-Serag HB, Zhang Q, Shah N, Ghosh SK, Kahrilas PJ. Obesity: a challenge to esophagogastric junction integrity. Gastroenterology. 2006 Mar. 130(3):639-49. [QxMD MEDLINE Link].
El-Serag HB, Graham DY, Satia JA, Rabeneck L. Obesity is an independent risk factor for GERD symptoms and erosive esophagitis. Am J Gastroenterol. 2005 Jun. 100(6):1243-50. [QxMD MEDLINE Link].
Tutuian R,. Adverse effects of drugs on the esophagus. Best Pract Res Clin Gastroenterol. 2010 Apr. 24(2):91-7. [QxMD MEDLINE Link].
Galmiche JP, Hatlebakk J, Attwood S, et al. Laparoscopic antireflux surgery vs esomeprazole treatment for chronic GERD: the LOTUS randomized clinical trial. JAMA. 2011 May 18. 305(19):1969-77. [QxMD MEDLINE Link].
Bhatia J, Parish A. GERD or not GERD: the fussy infant. J Perinatol. 2009 May. 29 suppl 2:S7-11. [QxMD MEDLINE Link].
Levine MS, Rubesin SE. Diseases of the esophagus: diagnosis with esophagography. Radiology. 2005 Nov. 237(2):414-27. [QxMD MEDLINE Link].
Ponce J, Garrigues V, Agreus L, et al. Structured management strategy based on the Gastro-oesophageal Reflux Disease (GERD) Questionnaire (GerdQ) vs. usual primary care for GERD: pooled analysis of five cluster-randomised European studies. Int J Clin Pract. 2012 Sep. 66(9):897-905. [QxMD MEDLINE Link].
Woodcock J. Statement alerting patients and health care professionals of NDMA found in samples of ranitidine [news release]. September 13, 2019. US Food and Drug Administration. Available at https://www.fda.gov/news-events/press-announcements/statement-alerting-patients-and-health-care-professionals-ndma-found-samples-ranitidine. 2019 Jun; Accessed: October 15, 2020.
US Food and Drug Administration. FDA requests removal of all ranitidine products (Zantac) from the market [news release]. April 1, 2020. Available at https://www.fda.gov/news-events/press-announcements/fda-requests-removal-all-ranitidine-products-zantac-market. Accessed: October 15, 2020.
Yang YX, Lewis JD, Epstein S, Metz DC. Long-term proton pump inhibitor therapy and risk of hip fracture. JAMA. 2006 Dec 27. 296(24):2947-53. [QxMD MEDLINE Link]. [Full Text].
Kellerman R, Kintanar T. Gastroesophageal reflux disease. Prim Care. 2017 Dec. 44(4):561-73. [QxMD MEDLINE Link].
US Food and Drug Administration Press Announcements. FDA approves first generic versions of Aciphex delayed-release tablets to treat GERD. US Food and Drug Administration. Available at http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm374329.htm. Accessed: November 12, 2013.
Agency for Healthcare Research and Quality. Comparative effectiveness of management strategies for gastroesophageal reflux disease - executive summary. AHRQ pub. no. 06-EHC003-1. December 2005. Available at http://effectivehealthcare.ahrq.gov/healthInfo.cfm?infotype=rr&ProcessID=1&DocID=42. Accessed: September 27, 2010.
Rassameehiran S, Klomjit S, Hosiriluck N, Nugent K. Meta-analysis of the effect of proton pump inhibitors on obstructive sleep apnea symptoms and indices in patients with gastroesophageal reflux disease. Proc (Bayl Univ Med Cent). 2016 Jan. 29(1):3-6. [QxMD MEDLINE Link].
Phathom Pharmaceuticals. Phathom Pharmaceuticals announces FDA approval of VOQUEZNA (vonoprazan) tablets for the treatment of erosive GERD and relief of heartburn associated with erosive GERD in adults [news release]. Available at https://investors.phathompharma.com/news-releases/news-release-details/phathom-pharmaceuticals-announces-fda-approval-voqueznar. November 1, 2023; Accessed: November 9, 2023.
Phathom Pharmaceuticals announces positive topline results from PHALCON-EE pivotal phase 3 erosive esophagitis trial. Phathom Pharmaceuticals. Available at https://investors.phathompharma.com/news-releases/news-release-details/phathom-pharmaceuticals-announces-positive-topline-results-0. October 18, 2021; Accessed: November 9, 2023.
Laine L, DeVault K, Katz P, Mitev S, Lowe J, Hunt B, et al. Vonoprazan versus lansoprazole for healing and maintenance of healing of erosive esophagitis: a randomized trial. Gastroenterology. 2023 Jan. 164 (1):61-71. [QxMD MEDLINE Link]. [Full Text].
Boerema I. Hiatus hernia: repair by right-sided, subhepatic, anterior gastropexy. Surgery. 1969 Jun. 65(6):884-93. [QxMD MEDLINE Link].
Allison PR. Hiatus hernia: (a 20-year retrospective survey). Ann Surg. 1973 Sep. 178(3):273-6. [QxMD MEDLINE Link]. [Full Text].
Varshney S, Kelly JJ, Branagan G, Somers SS, Kelly JM. Angelchik prosthesis revisited. World J Surg. 2002 Jan. 26(1):129-33. [QxMD MEDLINE Link].
Nissen R, Rossetti M, Siewert R. [20 years in the management of reflux disease using fundoplication]. Chirurg. 1977 Oct. 48(10):634-9. [QxMD MEDLINE Link].
Kazerooni NL, VanCamp J, Hirschl RB, Drongowski RA, Coran AG. Fundoplication in 160 children under 2 years of age. J Pediatr Surg. 1994 May. 29(5):677-81. [QxMD MEDLINE Link].
Dallemagne B, Weerts JM, Jehaes C, Markiewicz S, Lombard R. Laparoscopic Nissen fundoplication: preliminary report. Surg Laparosc Endosc. 1991 Sep. 1(3):138-43. [QxMD MEDLINE Link].
Nilsson G, Larsson S, Johnsson F. Randomized clinical trial of laparoscopic versus open fundoplication: blind evaluation of recovery and discharge period. Br J Surg. 2000 Jul. 87(7):873-8. [QxMD MEDLINE Link].
Wenner J, Nilsson G, Oberg S, Melin T, Larsson S, Johnsson F. Short-term outcome after laparoscopic and open 360 degrees fundoplication. A prospective randomized trial. Surg Endosc. 2001 Oct. 15(10):1124-8. [QxMD MEDLINE Link].
Somme S, Rodriguez JA, Kirsch DG, Liu DC. Laparoscopic versus open fundoplication in infants. Surg Endosc. 2002 Jan. 16(1):54-6. [QxMD MEDLINE Link].
Rangel SJ, Henry MC, Brindle M, Moss RL. Small evidence for small incisions: pediatric laparoscopy and the need for more rigorous evaluation of novel surgical therapies. J Pediatr Surg. 2003 Oct. 38(10):1429-33. [QxMD MEDLINE Link].
Rothenberg SS. The first decade's experience with laparoscopic Nissen fundoplication in infants and children. J Pediatr Surg. 2005 Jan. 40(1):142-6; discussion 147. [QxMD MEDLINE Link].
Pascoe E, Falvey T, Jiwane A, Henry G, Krishnan U. Outcomes of fundoplication for paediatric gastroesophageal reflux disease. Pediatr Surg Int. 2016 Apr. 32(4):353-61. [QxMD MEDLINE Link].
Lundell L, Miettinen P, Myrvold HE, et al. Continued (5-year) followup of a randomized clinical study comparing antireflux surgery and omeprazole in gastroesophageal reflux disease. J Am Coll Surg. 2001 Feb. 192(2):172-9; discussion 179-81. [QxMD MEDLINE Link].
Spechler SJ. Epidemiology and natural history of gastro-oesophageal reflux disease. Digestion. 1992. 51 suppl 1:24-9. [QxMD MEDLINE Link].
Anvari M, Allen C, Marshall J, et al. A randomized controlled trial of laparoscopic Nissen fundoplication versus proton pump inhibitors for treatment of patients with chronic gastroesophageal reflux disease: One-year follow-up. Surg Innov. 2006 Dec. 13(4):238-49. [QxMD MEDLINE Link].
Grant AM, Wileman SM, Ramsay CR, et al. Minimal access surgery compared with medical management for chronic gastro-oesophageal reflux disease: UK collaborative randomised trial. BMJ. 2008 Dec 15. 337:a2664. [QxMD MEDLINE Link]. [Full Text].
El-Serag HB. Time trends of gastroesophageal reflux disease: a systematic review. Clin Gastroenterol Hepatol. 2007 Jan. 5(1):17-26. [QxMD MEDLINE Link].
Grant AM, Cotton SC, Boachie C, et al. Minimal access surgery compared with medical management for gastro-oesophageal reflux disease: five year follow-up of a randomised controlled trial (REFLUX). BMJ. 2013 Apr 18. 346:f1908. [QxMD MEDLINE Link]. [Full Text].
Rebecchi F, Allaix ME, Giaccone C, Ugliono E, Scozzari G, Morino M. Gastroesophageal reflux disease and laparoscopic sleeve gastrectomy: a physiopathologic evaluation. Ann Surg. 2014 Nov. 260(5):909-14; discussion 914-5. [QxMD MEDLINE Link].
Oor JE, Roks DJ, Unlu C, Hazebroek EJ. Laparoscopic sleeve gastrectomy and gastroesophageal reflux disease: a systematic review and meta-analysis. Am J Surg. 2016 Jan. 211(1):250-67. [QxMD MEDLINE Link].
US Food and Drug Administration. FDA approves LINX Reflux Management System to treat gastroesophageal reflux disease. Available at http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm296923.htm.
Zhang H, Dong D, Liu Z, He S, Hu L, Lv Y. Revaluation of the efficacy of magnetic sphincter augmentation for treating gastroesophageal reflux disease. Surg Endosc. 2016 Sep. 30(9):3684-90. [QxMD MEDLINE Link].
Schizas D, Mastoraki A, Papoutsi E, et al. LINX^® reflux management system to bridge the "treatment gap" in gastroesophageal reflux disease: a systematic review of 35 studies. World J Clin Cases. 2020 Jan 26. 8(2):294-305. [QxMD MEDLINE Link]. [Full Text].
[Guideline] Katz PO, Dunbar KB, Schnoll-Sussman FH, Greer KB, Yadlapati R, Spechler SJ. ACG Clinical Guideline for the Diagnosis anCG Clinical guideline for the diagnosis and management of gastroesophageal reflux diseased Management of Gastroesophageal Reflux Disease. Am J Gastroenterol. 2022 Jan 1. 117 (1):27-56. [QxMD MEDLINE Link]. [Full Text].
Kramer JR, Shakhatreh MH, Naik AD, Duan Z, El-Serag HB. Use and yield of endoscopy in patients with uncomplicated gastroesophageal reflux disorder. JAMA Intern Med. 2014 Mar. 174(3):462-5. [QxMD MEDLINE Link].
Mattioli S, Lugaresi ML, Di Simone MP, et al. The surgical treatment of the intrathoracic migration of the gastro-oesophageal junction and of short oesophagus in gastro-oesophageal reflux disease. Eur J Cardiothorac Surg. 2004 Jun. 25(6):1079-88. [QxMD MEDLINE Link].
Osterwell N. GERD: high-risk patients get endoscopic short shrift. January 27, 2014. Medscape Medical News by WebMD. Available at http://www.medscape.com/viewarticle/819754. Accessed: February 3, 2014.
Scheffer RC, Samsom M, Haverkamp A, Oors J, Hebbard GS, Gooszen HG. Impaired bolus transit across the esophagogastric junction in postfundoplication dysphagia. Am J Gastroenterol. 2005 Aug. 100(8):1677-84. [QxMD MEDLINE Link].
Talley NJ, Napthali KE. Endoscopy in symptomatic gastroesophageal reflux disease: scoping out whom to target. JAMA Intern Med. 2014 Mar. 174(3):465-6. [QxMD MEDLINE Link].
Telem DA, Altieri M, Gracia G, Pryor AD. Perioperative outcome of esophageal fundoplication for gastroesophageal reflux disease in obese and morbidly obese patients. Am J Surg. 2014 Aug. 208(2):163-8. [QxMD MEDLINE Link].
Liu L, Li S, Zhu K, et al. Relationship between esophageal motility and severity of gastroesophageal reflux disease according to the Los Angeles classification. Medicine (Baltimore). 2019 May. 98(19):e15543. [QxMD MEDLINE Link].
Ratcliffe EG, Jankowski JA. Gastroesophageal reflux disease and Barrett esophagus: an overview of evidence-based guidelines. Pol Arch Intern Med. 2019 Aug 29. 129(7-8):516-25. [QxMD MEDLINE Link]. [Full Text].
Popescu AL, Ionita-Radu F, Jinga M, Gavrila AI, Savulescu FA, Fierbinteanu-Braticevici C. Laparoscopic sleeve gastrectomy and gastroesophageal reflux. Rom J Intern Med. 2018 Dec 1. 56(4):227-32. [QxMD MEDLINE Link]. [Full Text].
[Guideline] Hunt R, Armstrong D, Katelaris P, et al. World Gastroenterology Organisation Global Guidelines: GERD global perspective on gastroesophageal reflux disease. J Clin Gastroenterol. 2017 Jul. 51(6):467-78. [QxMD MEDLINE Link]. [Full Text].
[Guideline] Gyawali CP, Carlson DA, Chen JW, Patel A, Wong RJ, Yadlapati RH. ACG clinical guidelines: clinical use of esophageal physiologic testing. Am J Gastroenterol. 2020 Sep. 115(9):1412-28. [QxMD MEDLINE Link]. [Full Text].

Media Gallery

Gastroesophageal Reflux Disease. Relationship of the phrenoesophageal ligament to the diaphragm and esophagus.
Gastroesophageal Reflux Disease. Arterial blood supply and lymphatic drainage of the esophagus.
Gastroesophageal Reflux Disease. This image demonstrates peptic esophagitis.
Gastroesophageal Reflux Disease. Reflux esophagitis is demonstrated on barium esophagram.
Gastroesophageal Reflux Disease. Gastroesophageal reflux disease (GERD)/Barrett esophagus/adenocarcinoma sequence.
Gastroesophageal Reflux Disease. Endoscopy demonstrating intraluminal esophageal cancer.
Gastroesophageal Reflux Disease. The image is a representation of concomitant intraesophageal pH and esophageal electrical impedance measurements. The vertical solid arrow indicates commencement of a nonacid gastroesophageal reflux (GER) episode (diagonal arrow). The vertical dashed arrow indicates the onset of a normal swallow.
Gastroesophageal Reflux Disease. Nissen fundoplication.
Gastroesophageal Reflux Disease. Laparoscopic Nissen fundoplication.
Gastroesophageal Reflux Disease. This radiograph shows a hiatal hernia.

of 10

Author

Marco G Patti, MD Surgeon, UNC Hospitals Multispecialty Surgery Clinic

Marco G Patti, MD is a member of the following medical societies: American Association for the Advancement of Science, American College of Surgeons, American Gastroenterological Association, American Medical Association, American Surgical Association, Association for Academic Surgery, Pan-Pacific Surgical Association, Society for Surgery of the Alimentary Tract, Society of American Gastrointestinal and Endoscopic Surgeons, Southwestern Surgical Congress, Western Surgical Association

Disclosure: Nothing to disclose.

Chief Editor

BS Anand, MD Professor, Department of Internal Medicine, Division of Gastroenterology, Baylor College of Medicine

BS Anand, MD is a member of the following medical societies: American Association for the Study of Liver Diseases, American College of Gastroenterology, American Gastroenterological Association, American Society for Gastrointestinal Endoscopy

Disclosure: Nothing to disclose.

Acknowledgements

Piero Marco Fisichella, MD Assistant Professor of Surgery, Stritch School of Medicine, Loyola University; Director, Esophageal Motility Center, Loyola University Medical Center.

Piero Marco Fisichella is a member of the following medical societies: American College of Surgeons, American Medical Association, Association for Academic Surgery, Society for Surgery of the Alimentary Tract, and Society of American Gastrointestinal and Endoscopic Surgeons