AUTHOR INFORMATION

Section 1 of 12

Authored by Ludwig Tsoi, MBChB, MRCP, FRCSEd, MPH, Senior Medical Officer, Adjunct Tutor of A&E Academic Unit, Chinese University of Hong Kong, Accident and Emergency Department, North District Hospital

Coauthored by Chin Hung Chung, MBBS, FRCS(Glasg), FHKAM(Surgery), Chief of Service, Department of Accident and Emergency, North District Hospital, Hong Kong

Ludwig Tsoi, MBChB, MRCP, FRCSEd, MPH, is a member of the following medical societies: Royal College of Physicians, and Royal College of Surgeons of Edinburgh

Edited by James Li, MD, Assistant Professor, Division of Emergency Medicine, Harvard Medical School; Consulting Staff, Department of Emergency Medicine, Miles Memorial Hospital; Francisco Talavera, PharmD, PhD, Senior Pharmacy Editor, eMedicine; Eugene Hardin, MD, FACEP, FAAEM, Chair and Associate Professor, Department of Emergency Medicine, Charles R Drew University of Medicine and Science; Chair, Department of Emergency Medicine, Martin Luther King, Jr/Drew Medical Center; John Halamka, MD, Chief Information Officer, CareGroup Healthcare System, Assistant Professor of Medicine, Department of Emergency Medicine, Beth Israel Deaconess Medical Center; Assistant Professor of Medicine, Harvard Medical School; and Steven C Dronen, MD, FAAEM, Director of Emergency Services, Director of Chest Pain Center, Department of Emergency Medicine, Ft Sanders Sevier Medical Center

Author's Email:	Ludwig Tsoi, MBChB, MRCP, FRCSEd, MPH
Editor's Email:	James Li, MD

eMedicine Journal, January 24 2006, VOLUME 7, Number 1

INTRODUCTION

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Background: Esophagitis is a common medical condition usually caused by gastroesophageal reflux. Less frequent causes of esophagitis include infectious esophagitis (in patients who are immunocompromised), radiation esophagitis, and esophagitis from direct erosive effects of ingested medication or corrosive agents.

Pathophysiology: Reflux esophagitis develops when gastric contents are passively regurgitated into the esophagus. Gastric acid, pepsin, and bile irritate the squamous epithelium, leading to erosion and ulceration of esophageal mucosa. Eventually, a columnar epithelial lining may develop. This lining is a premalignant condition termed Barrett esophagus.

Frequency:

• In the US: Esophageal reflux symptoms occur monthly in 33-44% of the general population; up to 7-10% of people have daily symptoms.

Mortality/Morbidity: Minimal morbidity and mortality result from mild symptoms of esophagitis. Pain from moderate-to-severe symptoms may produce anxiety and lost work and may lead to medical evaluations for more serious causes of pain. Serious GI complications of esophagitis include esophageal strictures, Barrett esophagus, and adenocarcinoma. Aspiration of gastric contents is a potentially serious respiratory complication that occurs more often in children. It may be associated with bronchospasm, pneumonitis, and apnea.

Race: No race predilection has been observed.

CLINICAL

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History:

• The most common complaint in patients with esophagitis is heartburn (dyspepsia), a burning sensation in the mid chest caused by contact of stomach acid with inflamed esophageal mucosa. Symptoms often are maximal while the person is supine, bending over, wearing tight clothing, or has eaten a large meal.

• Water brash is a bitter taste of refluxed gastric contents often associated with heartburn.

• Other common symptoms of esophagitis include upper abdominal discomfort, nausea, bloating, and fullness. Less common symptoms of esophagitis include dysphagia, odynophagia, cough, hoarseness, wheezing, and hematemesis.

• The patient may experience chest pain indistinguishable from that of coronary artery disease. Pain is often midsternal with radiation to the neck or arm and may be associated with shortness of breath and diaphoresis. Chest pain may be relieved with nitrates if esophageal spasm is involved, further confounding diagnostic evaluation.

• Infants with gastroesophageal reflux are at greater risk of aspiration. Symptoms include weight loss, regurgitation, excessive crying, backache, respiratory distress, and apnea.

Physical:

• The physical examination usually is not helpful in confirming the diagnosis of uncomplicated esophagitis. However, the examination may reveal other potential sources of chest or abdominal pain.

• Perform a rectal examination to identify the presence of occult bleeding.

Causes:

• Factors or conditions that may increase a person’s risk of developing reflux esophagitis include the following:

• Pregnancy

• Obesity

• Scleroderma

• Smoking

• Alcohol, coffee, chocolate, fatty or spicy foods

• Certain medications (eg, beta-blockers, nonsteroidal anti-inflammatory drugs [NSAIDs], theophylline, nitrates, alendronate, calcium channel blockers)

• Mental retardation requiring institutionalization

• Spinal cord injury

• Immunocompromise

• Radiation therapy for chest tumors

• Pill esophagitis, thought to be secondary to chemical irritation of esophageal mucosa from certain medications (eg, iron, potassium, quinidine, aspirin, steroids, tetracyclines, NSAIDs), especially when swallowed with too little fluid

DIFFERENTIALS

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Acute Coronary Syndrome
Cholecystitis and Biliary Colic
Esophageal Perforation, Rupture and Tears
Foreign Bodies, Gastrointestinal
Gastritis and Peptic Ulcer Disease
Myocardial Infarction

WORKUP

Section 5 of 12

Lab Studies:

• Laboratory tests are usually unhelpful unless complications are present (eg, upper GI hemorrhage). Bleeding, a potentially serious complication of esophagitis, may be excluded upon physical examination with stool guaiac.

• ECG and troponin or other cardiac markers are needed when acute coronary syndrome is in the differential diagnosis.

Imaging Studies:

• Routine radiography is not indicated unless complications (eg, perforation, obstruction, bleeding) are suspected.

• Perform a double-contrast esophageal barium study as a first-line test if dysphagia is a primary complaint. A double-contrast esophageal barium study is useful in structural complications such as strictures and tumors.

Other Tests:

• Direct endoscopy allows for the visualization and the biopsy of esophageal mucosa. Endoscopy is a useful procedure in evaluating the degree of mucosal damage and is indicated in patients with hematemesis, heme-positive stools, or suspected esophageal obstruction.

• Endoscopy may be indicated on an emergency basis in cases of upper GI hemorrhage, obstruction, or perforation.

• Endoscopy is indicated in patients older than 50 years with new onset of symptoms, in those with features suggesting more serious disease (eg, abdominal mass, anemia, vomiting, dysphagia), and in patients in whom repeated trials of medical therapy have failed.

TREATMENT

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Prehospital Care:

• No specific prehospital treatment for esophagitis exists. Care is directed toward complications (eg, bleeding, perforation) that require hemodynamic stabilization.

• Chest pain of esophageal origin cannot be differentiated accurately from chest pain associated with coronary artery disease. Therefore, prehospital protocols should be followed for management of chest pain potentially caused by coronary artery disease.

• Oxygen is generally indicated when the cause of the pain is uncertain.

Emergency Department Care:

• Treatment of esophagitis is generally not indicated in an ED setting unless complications, such as bleeding, obstruction, dehydration, or perforation, occur.

Consultations:

• Patients with moderate-to-severe bleeding, perforation, or suspected obstruction should consult a gastroenterologist.

MEDICATION

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Treatment goals include pain relief, decreased acid production, decreased acid reflux, and protection of the esophageal mucosa. Multiple pharmacologic agents are available, including histamine-2 receptor antagonists, proton pump inhibitors, gastroprokinetic agents, and protective agents.

Drug Category: Histamine-2 receptor antagonists -- These agents decrease gastric acid production by blocking histamine-2 receptors in gastric cells. Some authorities recommend using larger doses than those used for peptic ulcer disease.

Drug Name	Ranitidine hydrochloride (Zantac) -- Competitively inhibits histamine at H2 receptor of gastric parietal cells, resulting in reduced gastric acid secretion, gastric volume, and hydrogen ion concentrations.
Adult Dose	150 mg PO bid; alternatively, 300 mg PO bid or 150 mg PO qid; not to exceed 600 mg/d
Pediatric Dose	Not established
Contraindications	Documented hypersensitivity
Interactions	May decrease effects of ketoconazole and itraconazole; also may alter serum levels of ferrous sulfate, diazepam, nondepolarizing muscle relaxants, and oxaprozin
Pregnancy	B - Usually safe but benefits must outweigh the risks.
Precautions	Caution with renal or liver impairment; consider adjusting dose or discontinuing treatment if changes in renal function occur during therapy

Drug Name	Cimetidine (Tagamet) -- Inhibits histamine at H2 receptors of gastric parietal cells, decreasing gastric acid secretion, gastric volume, and hydrogen ion concentrations.
Adult Dose	400 mg PO bid; alternatively 400 mg PO qid or 800 mg PO bid
Pediatric Dose	Not established
Contraindications	Documented hypersensitivity
Interactions	Can increase blood levels of theophylline, warfarin, tricyclic antidepressants, triamterene, phenytoin, quinidine, propranolol, metronidazole, procainamide, and lidocaine
Pregnancy	B - Usually safe but benefits must outweigh the risks.
Precautions	Slowly administer IV bolus to avoid rare incidents of arrhythmias or hypotension; elderly patients may suffer confusional states; weak antiandrogen properties may cause impotence and gynecomastia in young males; may increase levels of many drugs; if changes in renal function occur during therapy, consider adjusting dose or discontinuing treatment

Drug Name	Famotidine (Pepcid, Pepcidine) -- Competitively inhibits histamine at H2 receptor of gastric parietal cells, resulting in reduced gastric acid secretion, gastric volume, and hydrogen concentrations.
Adult Dose	20 mg PO bid; alternatively 40 mg PO bid
Pediatric Dose	Not established
Contraindications	Documented hypersensitivity
Interactions	May decrease effects of ketoconazole and itraconazole
Pregnancy	B - Usually safe but benefits must outweigh the risks.
Precautions	If changes in renal function occur during therapy, consider adjusting dose or discontinuing treatment

Drug Category: Gastrointestinal coating agents -- These medications coat the ulcerated surfaces and are used mainly for peptic ulcer disease. May be used as a second agent with an H2 antagonist and in radiation esophagitis.

Drug Name	Sucralfate (Carafate) -- Binds to positively charged proteins in exudates and forms a viscous, adhesive substance that protects GI lining against pepsin, peptic acid, and bile salts. Used for short-term ulcer management.
Adult Dose	1 g PO qid
Pediatric Dose	Not established
Contraindications	Documented hypersensitivity
Interactions	May decrease absorption and, thus, effects of ketoconazole, ciprofloxacin, tetracycline, phenytoin, warfarin, quinidine, theophylline, and norfloxacin
Pregnancy	B - Usually safe but benefits must outweigh the risks.
Precautions	Caution in patients diagnosed with renal failure and impaired excretion of absorbed aluminum; risk of aluminum absorption in dialysis patients

Drug Category: Proton pump inhibitors -- These agents inhibit gastric acid secretion by inhibiting the H⁺/K⁺-ATPase enzyme system in gastric parietal cells. Newer products such as pantoprazole, lansoprazole, esomeprazole, and rabeprazole have recently been approved by the FDA and are at least as effective as the time-honored omeprazole.

Drug Name	Omeprazole (Prilosec, Losec) -- Decreases gastric acid secretion by inhibiting parietal cell H+/K+-ATP pump. Used for up to 4 wk to treat and relieve symptoms of active duodenal ulcers. May use up to 8 wk to treat all grades of erosive esophagitis.
Adult Dose	20 mg/d PO ac; not to exceed 40 mg/d
Pediatric Dose	Not established
Contraindications	Documented hypersensitivity
Interactions	May decrease levels of itraconazole, iron, and ketoconazole; also may increase toxicity of warfarin, digoxin, and phenytoin
Pregnancy	C - Safety for use during pregnancy has not been established.
Precautions	Bioavailability of this medication may be increased in elderly patients

Drug Name	Lansoprazole (Prevacid) -- Decreases gastric acid secretion by inhibiting parietal cell H+/K+-ATP pump. Used for up to 4 wk to treat and relieve symptoms of active duodenal ulcers; may be used up to 8 wk to treat all grades of erosive esophagitis.
Adult Dose	30 mg PO qd ac
Pediatric Dose	Not established
Contraindications	Documented hypersensitivity
Interactions	May decrease the effects of ketoconazole and itraconazole; may increase theophylline clearance
Pregnancy	B - Usually safe but benefits must outweigh the risks.
Precautions	Consider dose adjustment in patients with liver impairment

Drug Name	Esomeprazole magnesium (Nexium) -- Decreases gastric acid secretion by inhibiting parietal cell H+/K+-ATP pump. Used for up to 4 wk to treat and relieve symptoms of active duodenal ulcers; may be used up to 8 wk to treat all grades of erosive esophagitis.
Adult Dose	20-40 mg PO qd for 4-8 wk
Pediatric Dose	Not established
Contraindications	Documented hypersensitivity
Interactions	Amoxicillin or clarithromycin may increase plasma levels of esomeprazole when used concurrently; may reduce absorption of dapsone; may increase levels of diazepam and GI absorption of digoxin; may decrease absorption of iron, ketoconazole and itraconazole
Pregnancy	C - Safety for use during pregnancy has not been established.
Precautions	Symptomatic relief with proton pump inhibitors may mask symptoms of gastric malignancy

Drug Name	Rabeprazole (Aciphex) -- Decreases gastric acid secretion by inhibiting the parietal cell H+/K+-ATP pump. Used for up to 4 wk to treat and relieve symptoms of active duodenal ulcers; may be used up to 8 wk to treat all grades of erosive esophagitis.
Adult Dose	20 mg tab PO qd for 4-8 wk
Pediatric Dose	Not established
Contraindications	Documented hypersensitivity
Interactions	May decrease effects of itraconazole and ketoconazole; may increase toxicity of warfarin, digoxin, and phenytoin
Pregnancy	B - Usually safe but benefits must outweigh the risks.
Precautions	Symptomatic relief with proton pump inhibitors may mask symptoms of gastric malignancy

Drug Name	Pantoprazole (Protonix) -- Decreases gastric acid secretion by inhibiting the parietal cell H+/K+-ATP pump. Used for up to 4 wk to treat and relieve symptoms of active duodenal ulcers; may be used up to 8 wk to treat all grades of erosive esophagitis.
Adult Dose	40 mg PO qd
Pediatric Dose	Not established
Contraindications	Documented hypersensitivity
Interactions	May decrease effects of itraconazole and ketoconazole; may increase toxicity of warfarin, digoxin, and phenytoin
Pregnancy	C - Safety for use during pregnancy has not been established.
Precautions	Symptomatic relief with proton pump inhibitors may mask symptoms of gastric malignancy

FOLLOW-UP

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Further Inpatient Care:

• Admit the patient when significant bleeding, perforation, obstruction, or volume depletion occurs. Surgery (fundoplication) is sometimes indicated in patients with severe pain who fail to respond to medical management.

Further Outpatient Care:

• The patient should receive follow-up care from his or her primary care physician. Refer the patient for endoscopy in the presence of suspected complications such as strictures, minor bleeding not requiring admission, and failure of medical therapy.

In/Out Patient Meds:

• Previously, histamine-2 receptor antagonist therapy has been recommended as the initial treatment; however, newer evidence in cost-effectiveness analysis and symptomatic relief suggests proton pump inhibitors (omeprazole 20 mg daily, pantoprazole 40 mg daily, or lansoprazole 30 mg daily for 4-8 wk) to be superior to ranitidine, cimetidine, and placebo.

• Cisapride, a gastroprokinetic agent, and sucralfate, a coating agent, are less effective but may be useful in selected patients or as second-line agents.

• Although no consensus on treatment choice exists, prescribing for 2-4 weeks with reassessment is reasonable. Some patients with relapse may require long-term maintenance therapy.

• Some authorities suggest proton pump inhibitors and histamine-2 receptor antagonists for patients with ulcerlike dominant symptoms (eg, nocturnal symptoms, relief with food) and gastroprokinetic agents for patients with dysmotility dominant symptoms (eg, nausea, bloating).

Transfer:

• Transfer patients with moderate-to-severe bleeding, obstruction, or perforation to a facility with endoscopic capabilities.

Complications:

• Common complications of esophagitis are bleeding and stricture formation.

• Barrett esophagus, which occurs when the normal squamous epithelium of the esophagus is replaced with columnar epithelium, is linked to the development of esophageal cancer. A systematic review of patients with Barrett esophagus and colonic cancer also indicated a link between Barrett esophagus and colonic cancer (7.6% of patients with Barrett esophagus had colonic cancer vs 1.6% in controls).

• Although rare, perforation with mediastinitis is a serious complication.

• Volume depletion and weight loss may occur secondary to inability to swallow.

• Laryngitis, aspiration pneumonitis, and bronchospasm may occur if gastric contents are refluxed to the level of the larynx.

• Esophagitis also has been linked to failure to thrive and apnea in infants.

• Helicobacter pylori (HP) eradication therapy has been inversely related to reflux esophagitis. It is postulated that the ammonia (alkaline) produced by HP reduces the acidity of the stomach and, hence, protects the esophagus from acid spillage.

Prognosis:

• Recurrence is a frequent problem in patients with reflux. Many patients require maintenance therapy for relapse of symptoms.

Patient Education:

• Lifestyle changes recommended to reduce the frequency and amount of gastric contents that may reflux back into the esophagus include the following:

• Elevate the head of the bed with 6-inch blocks. (Sleeping on extra pillows is discouraged because this actually may increase reflux by increasing intra-abdominal pressure caused by the patient bending at the waist.)

• Stand upright for several hours after meals.

• Reduce meal size.

• Lose weight.

• Quit smoking.

• Avoid alcohol and caffeine.

• Avoid citrus, spicy or fatty foods, and chocolate.

• Avoid aggravating medications such as aspirin and other over-the-counter NSAIDs.

• For excellent patient education resources, visit eMedicine's Heartburn/GERD/Reflux Center and Esophagus, Stomach, and Intestine Center. Also, see eMedicine's patient education articles Reflux Disease (GERD), Heartburn, and Understanding Heartburn/GERD Medications.

MISCELLANEOUS

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Medical/Legal Pitfalls:

• Do not misdiagnose cardiac chest pain as esophageal pain. Pain can be similar, particularly in elderly patients and women.

• Always consider cardiac causes of chest discomfort and treat appropriately. If the diagnosis is unclear, admission for further evaluation is suggested.

Special Concerns:

• Infectious esophagitis is primarily seen in patients who are immunocompromised. The most common causes of infectious esophagitis are fungal (Candida species), herpetic (herpes simplex virus), and viral (cytomegalovirus). Odynophagia is a common presenting complaint. Endoscopy with biopsy and cultures is required for diagnosis. Treatment is directed toward the causative organism or organisms.

• Radiation esophagitis may occur with radiation treatment of cancers located in the chest (ie, lung, esophagus, mediastinum). Healing may not occur for several months after cessation of radiation therapy. Treatment is with viscous lidocaine and sucralfate. Stricture formation is a common complication and may require endoscopy for dilation.

• Pill-induced esophagitis is caused by ingesting medication with insufficient liquid and may be prevented by drinking larger quantities of fluid with medication. Certain medications (eg, iron, potassium, quinidine, tetracyclines, NSAIDs, aspirin, steroids) are more likely to cause esophagitis.

TEST QUESTIONS

Section 10 of 12

CME Question 1: In which of the following cases would an endoscopy not be part of the workup for a 35-year-old man with dyspepsia?

A: Physical examination elicits an abdominal mass.
B: Anemia
C: Belching
D: Persistent symptoms despite medical therapy
E: None of the above

The correct answer is C: Elective endoscopy should be arranged for patients with alarm features (eg, abdominal mass, anemia, vomiting, dysphagia) or for patients who fail repeated trials of medication.

CME Question 2: Which of the following lifestyle changes is not included in recommendations to patients with reflux esophagitis?

A: Avoid aspirin and nonsteroidal anti-inflammatory medications.
B: Avoid alcohol.
C: Avoid lying down for several hours after meals.
D: Sleep on extra pillows to elevate the upper body.
E: Avoid large fatty meals.

The correct answer is D: To reduce gastric reflux, use blocks to elevate the head of the bed. Sleeping on extra pillows is discouraged because this actually may increase reflux by increasing intra-abdominal pressure caused by the patient bending at the waist.

Pearl Question 1 (T/F): Chest pain of esophageal origin may closely mimic coronary artery disease, angina, or acute myocardial infarction.

The correct answer is True: Chest pain indistinguishable from that of coronary artery disease may occur. Pain is often midsternal with radiation to the neck or arm and may be associated with shortness of breath and diaphoresis. Chest pain may be relieved with nitrates if esophageal spasm is involved, further confounding diagnostic evaluation.

Pearl Question 2 (T/F): Bleeding, a potentially serious complication of esophagitis, may be excluded on physical examination with stool guaiac.

The correct answer is True: Laboratory tests are usually unhelpful unless complications ensue (eg, upper GI hemorrhage). Bleeding, a potentially serious complication of esophagitis, may be excluded on physical examination with stool guaiac.

Pearl Question 3 (T/F): Patients with reflux esophagitis who do not respond to histamine-2 antagonists should not be treated with proton pump inhibitors.

The correct answer is False: Proton pump inhibitors have a higher efficacy in symptom relief and endoscopic remission than histamine-2 antagonists and placebo.

Pearl Question 4 (T/F): Emergent endoscopy is not indicated if the patient has moderate-to-severe GI bleeding or suspected obstruction of esophagus.

The correct answer is False: Endoscopy may be indicated on an emergency basis in cases of upper GI hemorrhage, obstruction, or perforation.

PICTURES

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Caption: Picture 1. Peptic esophagitis. A rapid urease test (RUT) is performed on the esophageal biopsy sample. The result is positive for esophagitis.
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Caption: Picture 2. Corrosive esophagitis. This is a vinegar-induced esophageal burn. The patient had a fish bone in her throat. She ingested vinegar in an attempt to dissolve the fish bone but to no avail; this led to corrosive esophagitis.
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BIBLIOGRAPHY

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