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CHAPTER 78: Peptic Ulcer Disease and Gastritis 505 Ingestion Hotline (National Capital Poison Center, Washington, DC) at 202-625-3333 is a 24-hour/7-day-a-week resource for help in manage ment decisions.  INGESTION OF SHARP OBJECTS Sharp objects in the esophagus need immediate removal. Sharp objects may pass into the stomach spontaneously. Because intestinal perforation from ingested sharp objects that pass distal to the stomach is common, the American Society for Gastrointestinal Endoscopy guidelines recommend removal of sharp objects by endoscopy while they are in the stomach or duodenum. If intestinal perforation occurs, it is usually at the ileocecal valve. If the object is distal to the duodenum at presentation and the patient is asymptomatic, the object’s passage should be documented with daily plain films. Surgical removal should be considered if 3 days elapse without passage. The development of symptoms or signs of intestinal injury (e.g., pain, emesis, fever, GI bleeding) requires immediate surgical consultation.  NARCOTICS INGESTION Narcotic couriers (body packers) ingest multiple small packets of a drug in order to conceal transport. A favored packet is the condom, which may hold up to 5 grams of narcotic. These packets are often visible on plain films. Rupture of even one such packet may be fatal, and endos copy is contraindicated because of the risk of iatrogenic packet rupture. If the packet(s) appears to be passing intact through the intestinal tract, observation until the packet reaches the rectum is the favored treat ment. Some authors advocate the use of whole-bowel irrigation to aid the process. Acknowledgment: We wish to acknowledge the work of Moss Mendelson, MD, for his authorship of this chapter in the previous edition. REFERENCES The complete reference list is available online at www.TintinalliEM.com. Peptic Ulcer Disease and Gastritis Angela M. Bogle Matthew C. Gratton INTRODUCTION AND EPIDEMIOLOGY Peptic ulcer disease is a chronic illness manifested by recurrent ulcer ations in the stomach and proximal duodenum. Acid and pepsin are thought to be crucial to ulcer development, but the great majority of peptic ulcers are directly related to infection with Helicobacter pylori or NSAID use. 1,2 Gastritis is acute or chronic inflammation of the gastric mucosa and has various etiologies. Dyspepsia is continuous or recurrent upper abdominal pain or discomfort and may be caused by a number of diseases or may be functional. 3 Uncomplicated peptic ulcer disease has an estimated incidence of 0.1% to 0.3% per year, and about 5% to 10% of people living in the Western world will experience a peptic ulcer at some point during their lives. 2 H. pylori infection, one of the main risk factors for peptic ulcer disease, is one of the most prevalent human infections in the world, affecting at least 50% of the world’s population. 4 The ageadjusted prevalence of H. pylori infection is decreasing in industrialized countries, likely due to an improved standard of living and to the increased use of proton pump inhibitors and antimicrobial therapy. 2,3 CHAPTER This may explain the decreasing incidence of peptic ulcer disease in the United States, but this may be partially offset by the widespread use of low-dose aspirin and NSAIDs. 2 Currently, at least a fifth of peptic ulcer disease cases have been found to be H. pylori–negative, NSAID-negative, and aspirin-negative.

APTER This may explain the decreasing incidence of peptic ulcer disease in the United States, but this may be partially offset by the widespread use of low-dose aspirin and NSAIDs. 2 Currently, at least a fifth of peptic ulcer disease cases have been found to be H. pylori–negative, NSAID-negative, and aspirin-negative. 2 Certain medical conditions such as Helicobacter heilmannii, cytomegalovirus infections, Behçet’s disease, Zollinger- Ellison syndrome, Crohn’s disease, and cirrhosis with portal hyperten sion may contribute to the development of peptic ulcers. 2 Other risk factors include antiplatelet agents, psychological stress, older age, and African-American ethnicity. 2,5 PATHOPHYSIOLOGY Hydrochloric acid and pepsin destroy gastric and duodenal mucosa. Mucus and bicarbonate ion secretions protect mucosa. Prostaglandins protect mucosa by enhancing mucus and bicarbonate production and by enhancing mucosal blood flow, thereby supporting metabolism. The balance between these protective and destructive forces determines whether peptic ulcer disease occurs. H. pylori bacteria or NSAIDs are thought to be the causal agents of peptic ulcer disease in most cases. 1,2 Although traditional treatment of peptic ulcers by various modalities heals most ulcers, eradication of H. pylori has been shown to accelerate healing and decrease both relapse and rebleeding of ulcers that are not associated with the use of NSAIDs. 2,6 H. pylori is a spiral, gram-negative, urease-producing, flagellated bacterium that is found living between the mucous gel and the mucosa. The bacterium’s production of urease, cytotoxins, proteases, and other compounds is thought to disturb the mucous gel and cause tissue injury. In addition, increased gastrin levels and decreased mucus and bicarbonate production are associated with H. pylori infection. Chronic active (usually asymptomatic) gastritis is an almost universal finding with H. pylori infection, but only some infected people develop peptic ulcer disease. 2 It is unclear why most infected persons do not develop symptomatic peptic ulcer disease, but it most likely reflects an interac tion of factors, including characteristics of host and pathogen (different virulence of strains of bacteria). In 2005, Marshal and Warren were awarded the Nobel Prize in Physiology or Medicine for their discovery of H. pylori and its role in gastritis and peptic ulcer disease. H. pylori is a causative agent of mucosa-associated lymphoid tissue lymphoma, and eradication of infection causes a remission in a sizable percentage of patients with low-grade tumors. 3 In addition, H. pylori infection is a risk factor for adenocarcinoma of the stomach. However, because the prevalence of gastric cancer in the United States is very low and the H. pylori infection rate is high, other factors undoubtedly are involved. There is some evidence that eradication of the infection reduces the risk of gastric cancer. 3,7,8 H. pylori infection has been asso ciated with the development of iron deficiency anemia, with possible mechanisms including decreased iron absorption and/or occult blood loss from chronic gastritis. Eradication therapy plus iron improves hemoglobin levels more than iron alone. 3 Improvement in the platelet count in some patients with idiopathic thrombocytopenic purpura has been demonstrated with H. pylori eradication, but more work remains to be done in this regard. NSAIDs inhibit prostaglandin synthesis, thereby decreasing mucus and bicarbonate production and mucosal blood flow, which allows ulcer formation. Gastrin-secreting tumors produce ulceration due to high levels of acid and pepsin production, but acid alone rarely causes ulcer ation. However, inhibition of acid secretion may allow ulcers to heal and is the basis for traditional ulcer treatments.

onate production and mucosal blood flow, which allows ulcer formation. Gastrin-secreting tumors produce ulceration due to high levels of acid and pepsin production, but acid alone rarely causes ulcer ation. However, inhibition of acid secretion may allow ulcers to heal and is the basis for traditional ulcer treatments. Acute gastritis may be related to ischemia from severe illness (e.g., shock, trauma, severe burns, organ failure) or to the direct toxic effects of agents (e.g., NSAIDs, steroids, bile acids). H. pylori infection causes acute and chronic gastritis (both usually asymptomatic). Chronic gas tritis may also be caused by autoimmune factors that destroy gastric parietal cells; this results in the loss of acid production and the loss of intrinsic factor production, which in turn cause malabsorption of vitamin B 12 and, hence, pernicious anemia. Dyspepsia has multiple causes. Endoscopy of patients with dyspep sia demonstrates that less than 10% have peptic ulcer disease and less Tintinalli_Sec09_p0473-0562.indd 505 8/2/19 6:49 PM

uction and the loss of intrinsic factor production, which in turn cause malabsorption of vitamin B 12 and, hence, pernicious anemia. Dyspepsia has multiple causes. Endoscopy of patients with dyspep sia demonstrates that less than 10% have peptic ulcer disease and less Tintinalli_Sec09_p0473-0562.indd 505 8/2/19 6:49 PM 506 SECTION 9: Gastrointestinal Disorders than 1% have gastroesophageal cancer. More than 70% have no definite findings on endoscopy and are said to have “functional” dyspepsia. 9 Patients with functional dyspepsia may have evidence of abnormal gastric emptying, abnormal sensitivity to distention, abnormal ability of the stomach to distend with a meal, abnormalities in acid clearance, and abnormal duodenal sensitivity to acid. In addition, there appears to be an as yet poorly characterized interaction between the stomach and intestine and the CNS, which may contribute to symptoms. CLINICAL FEATURES Symptoms are nonspecific; however, burning epigastric pain is the most classic symptom of peptic ulcer disease. The pain also may be described as sharp, dull, an ache, or an “empty” or “hungry” feeling. Pain may be relieved by ingestion of milk, food, or antacids, presumably due to buffering and/or dilution of acid. Pain recurs as the gastric contents empty, and the recurrent pain may classically awaken the patient at night. Pain tends to occur daily for weeks, resolve, and then recur in weeks to months. Postprandial pain and nausea may be associated with gastric ulcers; however, food intolerance, retrosternal pain, and belching are not related to peptic ulcer disease. 2 Older patients (>65 years old) frequently will have no symptoms or only mild symptoms or may have more atypical symptoms such as nausea, vomiting, anorexia, weight loss, and bleeding. A change in the character of typical pain may herald a complication. Abrupt onset of severe or generalized pain may indicate perforation with peritoneal spillage of gastric or duodenal contents. Rapid onset of mid-back pain may be due to posterior penetration into the pancreas, resulting in pancreatitis. Nausea and vomiting may indicate gastric outlet obstruction from scarring or edema. Vomiting of bright red blood or coffee-ground emesis or passage of tarry or melanotic stool or hemato chezia may indicate ulcer bleeding. On physical examination, the only positive finding in patients with uncomplicated peptic ulcer disease may be epigastric tenderness. This finding is neither sensitive nor specific for the diagnosis. Other physical findings may be indicative of complications: a rigid abdomen consistent with peritonitis in perforation; abdominal distention or a succussion splash due to obstruction; or occult or gross rectal blood or blood in the nasogastric aspirate signaling ulcer bleeding. Epigastric pain, nausea, and vomiting may be present with acute gastritis, but the most common presentation of gastritis is GI bleeding, ranging from occult blood loss in the stool to massive upper GI hemor rhage. Physical findings may be normal, may reflect only the GI bleeding, or may reflect a severe underlying associated illness (as listed earlier). DIAGNOSIS A definitive diagnosis of peptic ulcer disease cannot be made on clini cal grounds alone. Uncomplicated peptic ulcer disease can be strongly suspected in the presence of a “classic” history, including epigastric burning pain; relief of pain with ingestion of milk, food, or antacids; and night pain accompanied by “benign” physical examination findings, including normal vital signs with or without mild epigastric tenderness.

ptic ulcer disease can be strongly suspected in the presence of a “classic” history, including epigastric burning pain; relief of pain with ingestion of milk, food, or antacids; and night pain accompanied by “benign” physical examination findings, including normal vital signs with or without mild epigastric tenderness. The differential diagnosis of epigastric pain is extensive and, in addition to peptic ulcer disease, includes gastritis, gastroesophageal reflux disease, cholelithiasis, pancreatitis, hepatitis, abdominal aortic aneu rysm, gastroparesis, and functional dyspepsia. Careful history taking may elicit features that point away from peptic ulcer disease: burning pain radiating into the chest, water brash, and belching may suggest gastroesophageal reflux disease; more severe pain radiating to the right upper quadrant and around the right or left side suggests cholelithiasis; radiation through to the back indicates pancreatitis or abdominal aortic aneurysm; chronic pain, anorexia, or weight loss may indicate gastric cancer. Myocardial ischemic pain may also present as epigastric pain and should be strongly considered in the appropriate clinical setting. Physical examination findings may suggest other diagnoses: right upper quadrant tenderness points to cholelithiasis or hepatitis, an epigastric mass to pancreatitis (pseudocyst) or pancreatic or gastric neoplasm, a pulsatile mass to abdominal aortic aneurysm, jaundice to hepatitis, and peritoneal findings to an acute abdomen.  ANCILLARY TESTING Ancillary tests may help exclude peptic ulcer disease complications and narrow the differential diagnosis. Normal results for CBC rule out ane mia from chronic GI bleeding due to peptic ulcer disease, gastritis, or cancer (but do not rule out acute blood loss). Elevated liver function test results may indicate hepatitis, and an elevated lipase level may indicate pancreatitis. An acute abdominal series may show free air associated with perforation. A limited ED US examination may show gallstones or an abdominal aortic aneurysm. An ECG and cardiac enzyme determi nation are indicated if there is a suspicion of myocardial ischemic pain. The gold standard for diagnosis of peptic ulcer disease is visualization of an ulcer by upper GI endoscopy. 2 Although not all patients with undiagnosed dyspepsia require endoscopy, those with “alarm features” do 2,9 (Table 78-1). Alarm features raise the index of suspicion for gastric or esophageal cancer, as well as other potentially serious conditions, but the features are not specific. H. pylori Tests Because many peptic ulcers are caused by H. pylori infection and eradication of H. pylori dramatically decreases the ulcer recurrence rate, it is important to know how to diagnose infection. H. pylori infection can be diagnosed by endoscopic tests, including the rapid urease test, histologic study, and culture, all of which rely on a biopsy of the gastric mucosa. 10 Noninvasive tests include serologic tests, urea breath tests, and stool antigen tests.10,11 The rapid urease test detects the presence of urease in a biopsy specimen (presumptive evidence of H. pylori infection) with >85% to 95% sensitivity and >95% specificity. 10 Histologic studies allow direct assessment of H. pylori infection and culture of the organism, but these tests require highly trained technicians in appropriate facilities and are not widely available. The major disadvantage of all the aforemen tioned tests is the cost in time, dollars, and potential complications of endoscopy. Serologic studies detect immunoglobulin G antibodies to H. pylori and are readily available, but the sensitivity and specificity are not very good.

ate facilities and are not widely available. The major disadvantage of all the aforemen tioned tests is the cost in time, dollars, and potential complications of endoscopy. Serologic studies detect immunoglobulin G antibodies to H. pylori and are readily available, but the sensitivity and specificity are not very good. 11 Serologic studies are not useful as a test of cure, because anti bodies remain for several months to years after eradication of infection. The urea breath test relies on the presence of urease produced by H. pylori. Urea labeled with carbon-13 or carbon-14 instead of carbon-12 is ingested and, in the presence of bacterial urease, is broken down into labeled carbon dioxide and ammonia. The labeled carbon dioxide is detected in the breath later. Sensitivity and specificity are >90%. 11,12 The urea breath test can be used to determine the presence of infection after eradication therapy. 10 H. pylori antigens can be detected in the stool with about 95% sensitivity and specificity.11 Testing performed ≥4 weeks after completion of H. pylori eradication therapy is useful as a test of cure. 10 The sensitivity of all tests that rely on active infection with H. pylori is decreased significantly by recent treatment with proton pump inhibitors, histamine-2 (H 2) antagonists, antibiotics, and bismuth compounds, and most recommend stopping these agents for 2 to 4 weeks before testing.11 TREATMENT Traditional ulcer therapy (proton pump inhibitors, H2 receptor antagonists, sucralfate, and antacids) heals the ulcer, relieves pain, and prevents complications but does not prevent recurrence. Treatment of H. pylori infection dramatically decreases the recurrence rate and accelerates ulcer healing. 2,6 If NSAID-associated ulcers are present, the offending agent should be stopped whenever possible. TABLE 78-1 “Alarm Features” for Endoscopy •  Age  >50 y, with new-onset symptoms •  Unexplained  weight loss •  Persistent  vomiting •  Dysphagia  or odynophagia •  Iron  deficiency anemia or GI bleeding •  Abdominal  mass or lymphadenopathy •  Family  history of upper GI malignancy Tintinalli_Sec09_p0473-0562.indd 506 8/2/19 6:49 PM

rm Features” for Endoscopy •  Age  >50 y, with new-onset symptoms •  Unexplained  weight loss •  Persistent  vomiting •  Dysphagia  or odynophagia •  Iron  deficiency anemia or GI bleeding •  Abdominal  mass or lymphadenopathy •  Family  history of upper GI malignancy Tintinalli_Sec09_p0473-0562.indd 506 8/2/19 6:49 PM CHAPTER 78: Peptic Ulcer Disease and Gastritis 507 Traditional ED treatment would entail initiating a trial of a proton pump inhibitor or an H 2 receptor antagonist, with antacids for break through pain and referral to a primary care provider to direct evalua tion and subsequent treatment. Current literature supports using proton pump inhibitors as first-line noneradication therapy for peptic ulcers. 6 This usually remains the best option. Practice guidelines and reviews support treatment of known H. pylori–positive dyspeptic patients with antimicrobial and antisecretory therapy followed by endoscopic study only in those with persistent symptoms. 3 It might be reasonable for the ED physician to order a test for H. pylori, begin symptomatic therapy after the H. pylori test is obtained, and refer the patient for early followup with a primary care provider for initiation of antibacterial therapy if the test results are positive. This specific strategy has not been tested. However, there is some evidence that a “test-and-treat” strategy in the ED using the urea breath test to identify patients positive for H. pylori may be both beneficial and feasible in an area with a known high prevalence. Immediate referral for definitive diagnosis is mandated if alarm features are present (Table 78-1). PROTON PUMP INHIBITORS Proton pump inhibitors (e.g., esomeprazole, lansoprazole, omeprazole, pantoprazole) decrease acid production by irreversibly binding with an H +K+ ATPase molecule (proton pump) located on the gastric parietal cell, thus blocking hydrogen ion secretion. 11 Proton pump inhibitors are most effective if taken 30 to 60 minutes prior to a meal. Proton pump inhibitors generally heal ulcers faster than H 2 recep tor antagonists and also have some in vitro inhibitory effect against H. pylori. 11 Proton pump inhibitors are metabolized in the liver by the cytochrome P450 system and therefore may decrease the metabolism of many other drugs. In addition, proton pump inhibitors may inhibit the absorption of drugs that rely on gastric acidity. Proton pump inhibitors are well tolerated by most patients; however, headache and GI upset can occur. 11 Long-term use of proton pump inhibitors may be associated with Clostridium difficile –associated diarrhea, fracture and pneumonia risk, chronic kidney disease, and hypomagnesemia. 11 Discontinuing a proton pump inhibitor may result in rebound acid hyper secretion and dyspeptic symptoms. 11 Symptoms can be minimized by gradually discontinuing the proton pump inhibitor over a few weeks, and replacing it with an H 2 receptor antagonist or antacids. All proton pump inhibitors, even those available over the counter, appear to have similar efficacy in treating peptic ulcer disease and are the treatment of choice in a patient who develops an ulcer while taking NSAIDs and must continue NSAID therapy. 6,13  H2 RECEPTOR ANTAGONISTS H2 receptor antagonists competitively inhibit the actions of histamine on the H 2 receptors of the gastric parietal cells. All four H 2 receptor antagonists (cimetidine, famotidine, nizatidine, and ranitidine) heal ulcers approximately equally and are available in over-the-counter preparations. 11 Because of renal excretion, make dosage adjustments in patients with renal failure.

istamine on the H 2 receptors of the gastric parietal cells. All four H 2 receptor antagonists (cimetidine, famotidine, nizatidine, and ranitidine) heal ulcers approximately equally and are available in over-the-counter preparations. 11 Because of renal excretion, make dosage adjustments in patients with renal failure. Long-term use of H2 receptor antagonists can lead to tolerance, and discontinuation can lead to rebound hypersecretion of acid.11 Side effects are uncommon but can include headache, confusion, lethargy, depression, and hallucinations. 11 Cimetidine has more significant drug interactions than do the other H2 receptor antagonists due to inhibition of cytochrome P450 activity.11  OTHER AGENTS Sucralfate, an aluminum hydroxide complex of sucrose, appears to protect the ulcer from acid exposure by forming a sticky gel that adheres to the ulcer crater and allows healing to occur but does not relieve pain as well as proton pump inhibitors and H 2 receptor antagonists.11 Sucralfate has few side effects but can cause constipation and aluminum toxicity, as well as inhibit absorption of a number of medications. 11 Antacids heal ulcers by buffering gastric acid. Magnesium- and aluminum-con taining antacids can inhibit absorption of drugs and should be avoided in patients with renal insufficiency or renal failure. In renal failure, aluminum can accumulate and cause osteoporosis and encephalopathy, and hypermagnesemia can also result. Due to the simplicity of proton pump inhibitor and H 2 receptor antagonists dosing requirements, antacids currently are used mainly on an as-needed basis for ulcer pain until healing occurs. Although NSAIDs should be stopped in patients with peptic ulcer disease whenever possible, misoprostol may prevent ulcer formation in those concurrently receiving NSAID therapy but has not been proven to heal ulcers. 11 Misoprostol is a prostaglandin analogue that may act by increasing mucus and bicarbonate production and by increasing mucosal blood flow. Because it is an abortifacient, do not use misoprostol in women who could become pregnant.  H. PYLORI ERADICATION If H. pylori infection is diagnosed in the presence of peptic ulcer disease, eradication is clearly indicated but has become more challenging due to increasing antibiotic resistance. 3,6,8 Multiple regimens have been proposed and studied, and most commonly, “triple therapy” with a proton pump inhibitor, clarithromycin, and either amoxicillin or metronidazole has been prescribed. 3,6,8,11 Authorities in the United States recommend 10- to 14-day regimens for the best cure rates, and tailoring decisions regarding first-line therapy on local antibiotic resistance. 3,6,8,11,14 In areas where clarithromycin resistance is high, quadruple therapy or sequential therapy may be preferred. 11 If H. pylori is not eradicated after treatment with two different regimens, resistance testing should be considered.11 Patients generally do not present to the ED with a definitive diagnosis of H. pylori–positive peptic ulcer disease but rather with a symptom, such as epigastric pain. If appropriate history, physical examination, and laboratory evaluation result in a physician’s impression of “possible peptic ulcer disease” or “dyspepsia, ” the physician is left with three main options: empiric treatment with conventional antiulcer medication, immediate referral for definite diagnosis (endoscopic study), or non invasive testing for H. pylori followed by antibiotic therapy for patients with positive test results. COMPLICATIONS  HEMORRHAGE Upper GI bleeding is the most common cause of GI-related hospital admissions, and of those, peptic ulcer disease is the most common underlying etiology.

diagnosis (endoscopic study), or non invasive testing for H. pylori followed by antibiotic therapy for patients with positive test results. COMPLICATIONS  HEMORRHAGE Upper GI bleeding is the most common cause of GI-related hospital admissions, and of those, peptic ulcer disease is the most common underlying etiology. 1,15,16 Due to advances in endoscopic and medical management of peptic ulcer disease, the overall incidence of upper GI bleeding is decreasing; however, the mortality rate has remained the same at 10% to 14%. 2,15 Bleeding from peptic ulcers is most commonly seen in the elderly. ED treatment for ulcer bleeding focuses on restoring hemodynamic stability by IV administration of isotonic saline solution and packed red blood cells (see Chapter 75, “Upper Gastrointestinal Bleeding” for details of treatment). Transfusion of red cells is recommended for hemoglobin levels less than 7 grams/dL or in patients who are hypotensive with severe GI bleeding before the hemoglobin level is known or if it falls below that threshold. 1 Early upper endoscopy is recommended in most patients to confirm the diagnosis and target endoscopic treatment. 1,15 Before endoscopy, a bolus dose of a proton pump inhibitor followed by a continuous infusion can be considered, as can use of a prokinetic agent, such as erythromycin, given IV . Neither has been consistently shown to improve clinical outcomes; however, erythromycin administered 30 minutes prior to endoscopy may improve visualization of the gastric mucosa. 1 There is no clinical benefit to either a nasogastric or orogastric tube.1 Most patients should undergo upper GI endoscopy within 24 hours for diagnostic, prognostic, and treatment purposes. 1,15,16 Lesions can be described using the Forrest classification to predict risk of rebleeding. 15 Ranging from highest to lowest risk, the classification is as follows: active spurting of blood (Ia); active oozing (Ib); nonbleeding visible vessel (IIa); adherent clot (IIb); flat pigmented spot (IIc); and an ulcer with a clean base (III). 15 Endoscopic management is indicated for those ulcers at high risk for rebleeding. Treatment through endoscopy Tintinalli_Sec09_p0473-0562.indd 507 8/2/19 6:49 PM