Dyspepsia and Peptic Ulcer Disease Case File

Dyspepsia and Peptic Ulcer Disease Case File

Eugene C. Toy MD, Donald Briscoe, MD, FA  AFP, Bruce Britton, MD, Joel J. Heidelbaugh, MD, FA  AFP, FACG

Case 47

A 52-year-old man presents to the office with approximately 2 weeks of upper abdominal pain. His symptoms are difficult for him to describe, but include some "discomfort" in the epigastric region that comes and goes. He has had some"heartburn" and nausea, but no vomiting or diarrhea. He has noticed that his stools appear darker than they used to be, has not had bloody stools or rectal bleeding, and has recently noticed early satiety. He tried taking an over-the-counter antacid (calcium carbonate), which only minimally helped to relieve his symptoms. He takes an over-the-counter nonsteroidal anti-inflammatory drug (NSAID) "once or twice" a day because of arthritis in his knees. He does not smoke cigarettes or drink alcohol. On examination, he is pale appearing, but in no acute discomfort. He is afebrile, his blood pressure is 120/80 mm Hg, his pulse is 95 beats/min, and his respiratory rate is 14 breaths/min. Head, ears, eyes, nose, and throat (HEENT) examination is notable only for pale conjunctiva. Cardiac and pulmonary examinations are unremarkable. His abdomen has normal bowel sounds and moderate tenderness in the epigastrium with slight guarding but no rebound. Rectal examination reveals normal sphincter tone, no masses, and dark black stool that tests positive on fecal immunochemical (FIT) testing.

⯈ What is the most likely diagnosis?

⯈ What evaluation and treatment are indicated at this point?

⯈ What can be suggested to reduce the risk of recurrence of this problem?

ANSWER TO CASE 47

Dyspepsia and Peptic Ulcer Disease

Summary: A 52-year-old man presents with vague upper abdominal discomfort, nausea, and early satiety. He is a daily NSAID user. He appears pale on examination, suggesting that he may be anemic. He has mild abdominal tenderness and melanotic stool on examination that should raise suspicion for an upper gastrointestinal (GI) bleed.

• Most likely diagnosis: Bleeding peptic ulcer.
• Evaluation and treatment at this point: Given that this patient has a high likelihood of having an upper GI bleed, hemodynamic stability should be ensured immediately. Two large-bore IVs should be placed, IV fluids started, and the patient should be transported to the emergency department. Initial testing should include a STAT complete blood count (CBC), blood type and screen, consultation for an esophagogastroduodenoscopy (EGD; upper GI endoscopy), discontinuation of his NSAID, and testing for Helicobacter pylori. He should be treated with a proton pump inhibitor (PPI) and antibiotics for H pylori, if tests confirm its presence. He may require a blood transfusion if found to be significantly anemic.
• Reduce risk of recurrence by: Discontinuation and avoidance of NSAIDs or aspirin or if unable to completely discontinue, use of a PPI along with the NSAID; eradication of H pylori.

ANALYSIS

Objectives

1. Learn the common presenting signs and symptoms of peptic ulcer disease (PUD), functional dyspepsia, and gastroesophageal reflux disease (GERD).
2. Learn the risk factors for the development of PUD.
3. Learn how to diagnose and treat PUD and GERD, as well as to know the risks of pharmacotherapy.
4. Understand the role of H pylori in PUD, including methods for testing for and treatment of PUD.
5. Know the "alarm symptoms" and "extraesophageal symptoms" for GERD and PUD.

Considerations

The Rome III Committee defines dyspepsia as one or more of the following symptoms: postprandial fullness, early satiety, and epigastric pain or burning. Approximately 15% to 25% of dyspepsia is caused by peptic ulcer disease, while 70% is attributable to functional (nonulcer) dyspepsia, or dyspepsia without an identifiable organic cause. Reflux esophagitis accounts for 5% to 15% of cases of dyspepsia,

while gastric or esophageal cancer are found in fewer than 2% of cases. Peptic ulcer disease is a condition of the gastrointestinal tract characterized by mucosal damage (eg, from NSAIDs or aspirin), then chronic exposure of the damaged mucosa to pepsin and gastric acid secretion. It usually occurs in the stomach and proximal duodenum. Less commonly, it occurs in the lower esophagus, the distal duodenum, or the jejunum, as in unopposed hypersecretory states including Zollinger-Ellison syndrome, with hiatal hernias (Cameron ulcers), or in ectopic gastric mucosa (eg, Meckel diverticulum). Symptoms of functional dyspepsia are essentially the same as those of PUD, with no evidence of structural disease to explain the symptoms, thus it is a diagnosis of exclusion.

Gastroesophageal reflux disease, the most common gastrointestinal condition, is a chronic digestive condition in which stomach contents and acid leak backwards from the stomach into the esophagus. A presumptive diagnosis can be accurately made in the setting of classic symptoms of heartburn and regurgitation.

Diagnostic endoscopy should be considered for patients with new-onset dyspepsia older than age 50 or who have symptoms that may be associated with upper GI malignancy (Table 47-1). T he cutoff age may be more appropriate at 40 or 45 for Asian or African-American patients. For persons younger than age 50 and without alarm symptoms, testing for H pylori via immunoglobulin G (IgG) serology, rather than the 13-C urea breath test or stool antigen as initial testing, is recommended due to low cost and ease of collection. For those who test positive, treating the H pylori infection via combination antibiotic and acid-suppression therapy is indicated. For persons who test negative, empiric therapy with a PPI for 4 to 8 weeks is a costeffective intervention. Endoscopy or reconsideration of the diagnosis should be considered for those who continue to be symptomatic following these interventions.

Approach To:

Dyspepsia and Peptic Ulcer Disease

DEFINITIONS

H2 ANTAGONIST: Class of medications that are competitive antagonists of histamine binding to gastric parietal cell H2 receptors, which prevent activation of the pathway that mediates release of acid into the gastric lumen.

PROTON PUMP INHIBITOR: Class of medications that suppress gastric acid production by irreversibly inhibiting the H+/1K+ ATPase proton pump in gastric parietal cells.

CLINICAL APPROACH

PUD is a term generally used to describe both duodenal and gastric ulcers. Duodenal ulcers are more prevalent overall, whereas gastric ulcers are more common in NSAID users. Risk factors for the development of PUD include H pylori infection, the use of NSAIDs and aspirin, cigarette smoking, alcohol consumption and personal or family history of PUD. Black and Hispanic populations have a higher likelihood of developing PUD as well. The lifetime risk of developing PUD in the United States is approximately 10%. Table 47-2 summarizes other causes of PUD.

History and Examination

Dyspepsia symptoms are common and there is significant overlap between the symptoms of PUD, GERD, and functional dyspepsia. Patients with symptoms primarily of heartburn or acid regurgitation are more likely to have GERD. Classic symptoms associated with PUD include epigastric abdominal pain that is improved with the ingestion of food, or pain that develops a few hours after eating. Nocturnal symptoms are also common with PUD, when the circadian stimulation of acid secretion is maximal prior to awakening. The symptoms of PUD are often gradual in onset and may present for weeks or months. Patients often self-medicate with over-the-counter acid-suppression medications which usually provide some relief, prior to presenting to the physician.

Data from Kurata JH, Nogawa AN. Meta-analysis of risk factors for peptic ulcer. Nonsteroidal anti-inflammatory drugs,

Helicobacter pylori, and smoking. J Clin Gastroenterol. 7 997;24:2-7 7.

The examination of the patient with dyspepsia should both attempt to confirm the suspicion of PUD and to rule out other diagnoses that may present with abdominal pain. Most patients with dyspepsia and GERD will have unremarkable abdominal examinations, while PUD may only have the examination finding of mild-to-moderate epigastric tenderness. The presence of GI bleeding may be documented by fecal occult blood testing; however, the bleeding from PUD may be episodic and a single negative fecal occult blood test does not completely rule out an upper gastrointestinal bleed. Signs of anemia ( eg, pale conjunctiva and skin, tachycardia, orthostatic hypotension) should be evaluated and treated according to severity and underlying risk factors. If a patient with known coronary artery disease becomes symptomatic and has a hemoglobin level less than 7 g/ dL, then blood transfusion should be considered.

Helicobacter pylori

H pylori is a corkscrew-shaped gram-negative bacillus that is the causative agent of most non-NSAID-related ulcers, and is associated with the development of gastric cancer. The presence of the organism is associated with a five to seven times increased risk of the development of PUD. H pylori infection is commonly acquired during childhood and is more common in developing countries. Serologic testing for anti H pylori antibodies (eg, IgG, IgM) is inexpensive, noninvasive, readily available, and is the first test that should be performed in a previously uninvestigated patient. It is a highly sensitive and specific test, yet cannot distinguish an active infection from a treated infection. Once the test is positive, it will almost always stay positive and should not be repeated. Stool antigen testing, has an excellent positive predictive value and is most often used 8 to 14 weeks posttreatment to test for eradication in cases suspected refractory to treatment. For this test to be most accurate, patients must not have been treated with PPIs for at least 2 weeks prior to stool collection. Active H pylori infection can be confirmed by 13-C urea breath testing. This test is performed by having the patient ingest a carbon-labeled urea compound, which is then metabolized by urease from the H pylori organism. The labeled CO2 released by this process is measured in exhaled breath. This test is highly sensitive and specific, is the most expensive option, and should be reserved for patients who have been treated and with inconclusive stool antigen testing.

The gold standard for diagnosis of H pylori is endoscopy with gastric mucosal biopsy. The bacterium can either be visualized microscopically using a variety of staining methods, cultured, or detected by rapid testing of the specimen. Endoscopy also allows for direct visualization of ulcers and evaluation for the presence of malignancy or other pathology in the esophagus, stomach, or duodenum. Endoscopy is invasive, expensive, requires conscious sedation, and should be considered when a patient has high suspicion for esophageal or gastric complications of PUD or GERD, rather than purely for diagnosis of H pylori.

Complications of PUD

Approximately 25% of patients with PUD have a serious complication such as hemorrhage, perforation, or gastric outlet obstruction. Silent ulcers and complications are more common in older patients and in patients taking chronic NSAIDs and aspirin.

Clinically relevant upper gastrointestinal bleeding occurs in 15% to 20% of patients with PUD, is the most common indication for surgical intervention, and is the most common cause of death. The risk of rebleeding in PUD is the greatest within 48 hours of initial bleed and the risk of death increases proportionally with advanced age, medical comorbidities, and hemodynamic status.

Complications of GERD

Up to 40% of patients with chronic GERD will experience heartburn and regurgitation on a monthly basis. Most patients with GERD will have nonerosive reflux disease (NERD), while others will progress to erosive esophagitis. Caucasian men aged 45 or greater who have chronic GERD, smoke cigarettes, and drink alcohol are at the greatest risk of development of Barrett esophagus, which is a precursor for esophageal adenocarcinoma. Patients with Barrett esophagus should be placed on lifelong PPI therapy and should undergo surveillance upper endoscopy to monitor for the development of esophageal adenocarcinoma.

Management of Suspected PUD

A CBC should be obtained to determine a baseline hemoglobin value and should be repeated every 6 to 8 hours to monitor for anemia and gastrointestinal blood loss, even in the setting of negative fecal occult blood. Liver transaminases and serum amylase and lipase levels should be obtained when biliary or pancreatic disease is suspected. An electrocardiography (ECG) should be performed upon initial evaluation to rule out cardiac ischemia, since upper abdominal pain can be an atypical sign of acute coronary syndrome. A chest x-ray should be obtained to rule out abdominal visceral perforation, characterized by free air under the diaphragm. Abdominal ultrasonography is indicated when cholecystitis is suspected. A pregnancy test should be obtained on all reproductive-age women, and endocervical cultures obtained when suspicion of pelvic inflammatory disease is high. Patients with significant anemia, hemodynamic instability (eg, hypotension, tachycardia, orthostasis), or a suspected acute abdomen should be immediately hospitalized. Urgent surgical evaluation should be obtained if an acute abdomen is present.

Dyspepsia in patients younger than age 50 with no alarm symptoms can be managed with a noninvasive H pylori "test-and-treat" protocol with serologic testing followed by acid suppression using a PPI if symptoms remain. A negative test rules out H pylori infection in dyspeptic patients. If positive, appropriate treatment to eradicate the infection, along with a PPI to suppress acid production, should be prescribed (Table 47-3 lists H pylori treatment regimens).

Management of GERD

Patients who experience classic GERD symptoms often begin self-directed acid suppressive therapy with either an H2 antagonist or a PPI. Over-the-counter formulations of these medications have a 2-week limit on therapy, then physician consultation is advised. The "test and treat" strategy for GERD posits starting with the lowest possible dose of an H2 antagonist once daily to control symptoms, then increasing frequency and potency to a PPI if symptoms are not adequately controlled (step-up therapy). If a patient is on chronic PPI therapy, they should be "stepped down'' to an H2 antagonist if possible.

Data from Del Valle J. Peptic ulcer disease and related disorders. In: Fauci AS, Braunwald E, Kasper DL, et al., eds. Harrison's Principles of Internal Medicine. 17th ed. New York, NY: McGraw-Hill; 2008:7863.

When a patient requires acid-suppressive therapy for 8 weeks to control symptoms and cannot undergo step-down therapy or stop medication, then they should undergo upper endoscopy to rule out potential complications. Patients with heartburn or regurgitation should be advised to avoid smoking, alcohol, spicy foods, citrus foods, fatty foods, large meals, fatty meals, chocolate, peppermint, and should avoid eating or drinking 3 to 4 hours prior to recumbency. Elevation of the head of the bed 6 to 8 inches and avoiding tight clothing around the waist may also help to improve symptoms.

Generally PPIs have greater efficacy in suppressing acid production and hastening ulcer healing than H2 blockers. Those with no evidence of active infection can be treated with acid suppression alone for 4 to 8 weeks. If symptoms resolve, no further testing is indicated. Along with treatment, offending agents, such as NSAIDs and tobacco, should be discontinued. Most patients with H pylori infection who have been treated successfully will require chronic acid suppressive therapy to combat symptoms of dyspepsia. Chronic acid suppressive therapy with PPIs has been associated with increased risk of community-acquired pneumonia; Clostridium difficile-associated diarrhea; demineralization of bone; and decreased absorption of calcium, magnesium, and iron.

Patients older than age 50 or those with alarm symptoms for either PUD or GERD should be referred for upper GI endoscopy to exclude complications of esophageal stricture, erosive disease, or malignancy. Endoscopy is preferred over radiographic procedures such as barium esophagram due to direct visualization and the ability to perform biopsy. Endoscopy also can be therapeutic, as a stricture

could be readily dilated, and a visible source of bleeding can be identified and cauterized. Any patient 50 years or older who has hematemesis, hematochezia, or melena should undergo a colonoscopy regardless of the upper endoscopic findings, to evaluate for a lower gastrointestinal cause of bleeding including diverticulosis, vascular malformation, or malignancy.

Surgical treatment for PUD is rarely indicated, yet may be warranted in cases of severe hemorrhage that cannot be controlled via endoscopy, or in cases of perforation or obstruction.

CASE CORRELATION

• See Case 23 (Lower GI Bleeding) and Case 40 (Irritable Bowel Syndrome).

COMPREHENSION QUESTIONS

47.1 A 30-year-old woman with no significant medical history presents asking for advice. She recently attended a health fair where she tested positive for H pylori on a blood test. She denies any recent abdominal discomfort, nausea, vomiting, diarrhea, or melena. Occasionally, she uses over-the-counter acidsuppressive therapy after eating spicy foods or drinking alcohol when she develops dyspepsia and heartburn, and her symptoms resolve within a week. Which of the following is the most appropriate advice to give this patient regarding H pylori?

A. Based on this test result, it is not possible to tell if she has an active infection.

B. She should undergo stool antigen testing to prove infection.

C. She should undergo upper endoscopy to prove infection.

D. She should be prescribed a PPI for 8 weeks.

E. She should be prescribed triple therapy to treat infection.

47.2 A 62-year-old man presents to clinic with increasing shortness of breath and fatigue over the last several days. Cardiac examination reveals regular rate and rhythm and lungs are clear to auscultation bilaterally. No jaundice, jugular venous distention (JVD), or peripheral edema is noted. Mucous membranes are pink with no evidence of cyanosis and capillary refill is brisk. CBC reveals a microcytic anemia and a gastric ulcer is diagnosed on upper GI endoscopy. Gastric mucosa biopsy confirms an H pylori infection. His last colonoscopy was 10 years ago and was unremarkable. Which of the following is the next most appropriate step in the workup of this patient?

A. Barium esophagram

B. Abdominal ultrasound

C. Colonoscopy

D. Urea breath test

E. Stool antigen test

47.3 A 41-year-old man presents for evaluation of upper GI discomfort present over the last 2 months. He says that he has a "full" sensation in the epigastric region. He recently began smoking again due to increased stress at work. He denies blood in his stool, denies vomiting, and has had no dysphagia. He has lost 10 lb in the last few weeks unintentionally, which he attributes to not eating. His mother has hemorrhoids, and no family member has ever had colon cancer. He has never had a colonoscopy. Which of the following is the most appropriate next step in workup of this patient?

A. H pylori "test-and-treat"

B. PPI therapy for 8 weeks

C. Fecal occult blood test

D. Upper endoscopy

E. Colonoscopy

47.4 A 19-year-old woman arrives at the emergency room with a 15-hour history of nausea, vomiting, and severe epigastric abdominal pain that awoke her from sleep. She admits to heavy alcohol consumption the prior evening that is common for her on the weekends. She takes no medications and does not take NSAIDs regularly. Her blood pressure is 100/60 mm Hg, pulse rate is 130 beats/min, respiratory rate is 14 breaths/min, and her temperature is 39°C (102.2°F). An acute abdominal series upon admission displayed a substantial amount of free air under the right hemidiaphragm. Which of the following is the most likely diagnosis?

A. Perforated peptic ulcer

B. Alcohol-related gastritis

C. Appendicitis

D. Gastroenteritis

E. Kidney stones

47.5 A 36-year-old man presents to your office for follow-up after having been recently admitted to the hospital for hypoxia due to an acute asthma attack. A chest x-ray performed on admission was unremarkable. Upon admission, he was given intravenous corticosteroids and started on a PPI for stress ulcer prophylaxis. He was discharged home on a tapering course of oral corticosteroids and advised to continue the PPI until steroid therapy was completed. Which of the following complications from PPI therapy is most likely to occur in this patient?

A. Community-acquired pneumonia

B. Osteoporosis

C. Hypermagnesemia

D. Elevated ferritin

E. C difficile-associate diarrhea

ANSWERS

47.1 A. H pylori serologic testing cannot distinguish active infections from old infections nor can they diagnose the presence of ulcers. Treating a positive serum test in an asymptomatic person is not indicated. Stool antigen testing, upper endoscopy, daily PPI therapy, or triple therapy is not indicated.

47.2 C. The presence of blood in the stool or anemia in a patient older than age 50, even when an ulcer is found, is an indication for colonoscopy, as this may also represent a presentation of a concomitant colon cancer. The urea breath test may be beneficial after completion of treatment to confirm eradication of the infection.

47.3 D. This patient presents with the alarm symptom of weight loss. He should be referred for early endoscopy.

47.4 A. The acute abdomen and free air under the diaphragm indicates a perforated viscus. This patient has perforated ulcer with hemodynamic instability. Additional workup includes a chemistry panel, CBC, and urgent laparotomy.

47.5 E. Given that this patient was recently admitted to the hospital and started on PPI therapy, his greatest immediate risk is of the development of C difficile-associate diarrhea. While community-acquired pneumonia can be seen concomitantly with asthma exacerbations, and is associated with

PPI use, the patient had a negative chest x-ray on admission. If he developed pneumonia subsequently, it would be classified as a health-care-associated pneumonia. PPIs can cause hypomagnesemia, hypocalcemia, hypophosphatemia, and decreased iron absorption. While chronic steroids and PPIs can lead to osteoporosis, the time course is likely too short in this case to develop these complications.

CLINICAL PEARLS

⯈ Persons who require long-term NSAID therapy and/or aspirin should be monitored for signs and symptoms of dyspepsia and peptic ulcer disease.

⯈ Persons with chronic symptoms of dyspepsia who have not been taking NSAIDs or aspirin, or those from Mexico, Central America, Africa, or other endemic areas should be tested for H pylori infection via lgG serologic testing and treated if positive.

⯈ Commonly held beliefs, such as ulcers being caused by stress or spicy foods, are incorrect. The vast majority of ulcers are caused by H pylori and NSAIDs.

⯈ Patients who experience heartburn and regurgitation should be treated with acid-suppressive therapy in a step-up fashion, with attempts at step-down therapy when symptoms are controlled.

⯈ Acid-suppression therapy carries long-term risks of community-acquired pneumonia; C difficile-associated diarrhea; demineralization of bone; decreased absorption of calcium, magnesium, and iron; and interaction with the metabolism of clopidogrel.

REFERENCES

Chey WD, Wong BCY. The Practice Parameters Committee of the American College of Gastroenterology. Management of Helicobacter pylori infection. Am J Gastroenterol. 2007; 102:1808-1825. 

Del Valle J. Peptic ulcer disease and related disorders. In: Kasper D, Fauci A, Hauser S, et al., eds. Harrison's Principles of Internal Medicine. 19th ed. New York, NY: McGraw-Hill Education; 2015. Available at: http://accessmedicine.mhmedical.com. Accessed May 25, 2015. 

Fashner J, Gitu AC. Diagnosis and treatment of peptic ulcer disease and H. pylori infection. Am Fam Physician. 2015; 91( 4):236-242. 

Heidelbaugh JJ, Gill AS, Harrison RV, Nostrant TT. Atypical presentations of gastroesophageal reflux disease. Am Fam Physician. 2008; 78( 4):483-488. 

Heidelbaugh JJ, Kim AH, Chang R, Walker PC. Overutilization of proton pump inhibitors: what the clinician needs to know. Ther Adv Gastroenterol. 2012; 5( 4):219-232. 

Katz PO, Gerson LB, Vela MF. Guidelines for the diagnosis and management of gastroesophageal reflux disease. Am J Gastroenterol. 2013; 108(3):308-328. 

Lanza FL, Chan FKL, Quigley EMM. The Practice Parameters Committee of the American College of Gastroenterology. Prevention of NSAID-related ulcer complications. Am J Gastroenterol. 2009; 104:728-738. 

Loyd RA, McClellan DA. Update on the evaluation and management of functional dyspepsia. Am Fam Physician. 2011; 83(5):547-552. 

Talley NJ, Vakil N. Guidelines for the management of dyspepsia. Am ] Gastroenterol. 2005; 100:2324-2337.

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