Thursday, January 6, 2022

Internal Medicine Peptic Ulcer Disease Case File

Posted By: Medical Group - 1/06/2022 Post Author : Medical Group Post Date : Thursday, January 6, 2022 Post Time : 1/06/2022
Internal Medicine Peptic Ulcer Disease Case File
Eugene C. Toy, MD, Gabriel M. Aisenberg, MD

Case 20
A 37-year-old executive returns to your clinic for follow-up of recurrent upper abdominal pain. He had been experiencing a “burning” epigastric pain intermittently for more than 2 years but did not seek medical attention until recently, when the pain increased in frequency and severity over the past 2 months. The pain now occurs three to four times per week, is more noticeable “on an empty stomach,” and often awakens him at night. The pain is usually relieved immediately after eating or using over-the-counter antacids, but it recurs within 2 to 3 hours. He admits to experiencing increased stress at work, drinking more caffeine, and frequently eating take-out foods because of his busy schedule. His medical history and review of systems are otherwise unremarkable. He takes no medications besides the occasional use of antacids. His physical examination is normal, including a stool guaiac test, which was negative for occult blood. Results of the laboratory tests performed at his initial visit show no anemia, but his serum Helicobacter pylori antibody test is positive.

What is the most likely diagnosis?
 What are the main risk factors for developing this condition?
 What is your next step?


ANSWERS TO CASE 20:
Peptic Ulcer Disease

Summary: A 37-year-old man presents with
  • “Burning” abdominal pain located in the epigastrium that is relieved with meals but recurs 2 to 3 hours later
  • No evidence of gastrointestinal (GI) bleeding
  • Serologies positive for H. pylori infection

Most likely diagnosis: Peptic ulcer disease (PUD) since the patient has recurrent, burning epigastric pain and positive serologies for H. pylori.

Risk factors: Infection with H. pylori or chronic use of nonsteroidal anti-inflammatory drugs (NSAIDs).

Next step: Triple therapy (PPI, amoxicillin, clarithromycin) for H. pylori.


ANALYSIS
Objectives
  1. Differentiate common causes of abdominal pain by historical clues. (EPA 1, 2)
  2. Recognize clinical features of duodenal ulcers and gastric ulcers and “alarm symptoms” that increase concern for gastric cancer. (EPA 1, 3)
  3. Understand the association between H. pylori infection and the use of NSAIDs in the development of PUD. (EPA 2, 12)
  4. Understand and interpret the laboratory tests used for diagnosing H. pylori infection. (EPA 3)

Considerations
This is a 37-year-old man whose symptoms are suggestive of a duodenal ulcer. He does not demonstrate alarm symptoms, such as weight loss, bleeding, or anemia. Moreover, his young age and chronicity of complaints make gastric malignancy a less likely diagnosis. H. pylori is the most common cause of PUD, requiring eradication to promote ulcer healing and to prevent development of gastric cancers (eg, gastric adenocarcinoma, mucosa-associated lymphoid tissue [MALT] lymphoma).


APPROACH TO:
Peptic Ulcer Disease

DEFINITIONS
DYSPEPSIA: Pain or discomfort located in the upper abdomen (“epigastrium”), which may be associated with fullness, early satiety, bloating, or nausea. Dyspepsia can be intermittent or continuous and may be related to meals.

FUNCTIONAL (NONULCER) DYSPEPSIA: Symptoms as described for dyspepsia, persisting for at least 12 weeks but without evidence of ulcer on endoscopy.

HELICOBACTER PYLORI: A gram-negative microaerophilic bacillus that resides within the gastric mucosa and causes chronic inflammation. It is urease positive, capable of hydrolyzing urea into ammonia carbonate, thus alkalinizing the local pH and allowing it to survive in an acidic environment. H. pylori is associated with 30% to 60% of gastric ulcers and with 50% to 70% of duodenal ulcers.

PEPTIC ULCER DISEASE (PUD): Presence of gastric or duodenal mucosal ulceration, visualized by endoscopy or by upper gastrointestinal barium study.

TRIPLE THERAPY: Treatment for PUD caused by H. pylori; consists of amoxicillin, clarithromycin, and a PPI (replace amoxicillin with metronidazole if penicillin allergy is present).

QUADRUPLE THERAPY: Alternative treatment for PUD caused by H. pylori, in setting of clarithromycin resistance; consists of metronidazole, a tetracycline, a bismuth compound, and a PPI.


CLINICAL APPROACH
Pathophysiology
Upper abdominal pain is one of the most common complaints encountered in primary care. Many patients have benign functional disorders (ie, no specific pathology can be identified after diagnostic testing), but others have potentially more serious conditions, such as PUD or gastric cancer. Historical clues, knowledge of the epidemiology of diseases, and some simple laboratory assessments can help to separate benign from serious causes of pain. However, endoscopy is often necessary to confirm the diagnosis.

The two major risk factors for developing PUD are chronic infection with H. pylori and the use of NSAIDs. Certain virulence factors of H. pylori are important for producing ulcer formation and include urease, adhesins, and cytotoxins. Urease is an enzyme that hydrolyzes urea into ammonium carbonate, thus producing an alkaline environment, and is an essential virulent factor for H. pylori to survive in the stomach. Adhesins (BabA, OipA) facilitate the attachment of H. pylori to the gastric epithelium. Almost all H. pylori contain the vacA gene, which encodes for a vacuolating cytotoxin that causes gastrointestinal inflammation. However, not all H. pylori express the vacA protein. Therefore, the role of this specific gene in the pathogenesis of PUD remains unclear.

Use of NSAIDs is another major risk factor for the development of PUD, primarily mediating ulcer formation by inhibiting the constitutively expressed cyclooxygenase 1 (COX-1)–derived prostaglandins. Inhibition of these prostaglandins is associated with impaired gastric defenses within the host, such as decreased vasodilation of mucosal blood vessels and low secretion of gastric mucus and bicarbonate. The risk of ulcer formation due to NSAIDs is dose dependent and may even occur within days of NSAID use.

Zollinger-Ellison syndrome (ZES) is a rare, yet highly tested, cause of ulceration that involves a gastrin-producing tumor (“gastrinoma”; usually located in the pancreas), resulting in acid hypersecretion. This condition should be suspected if patients have ulcers refractory to standard medical therapy, ulcers in unusual locations (eg, jejunum), or ulcers without a history of NSAID use or H. pylori infection. Endoscopy shows multiple gastric ulcers and prominent rugae of the gastric mucosa. About 25% of gastrinomas occur in patients with multiple endocrine neoplasia I (MEN I) syndrome, an autosomal dominant genetic disorder characterized by parathyroid, pancreatic, and pituitary neoplasms. To diagnose ZES, the first step is to measure a fasting gastrin level, followed by a secretin stimulation test, which paradoxically elevates gastrin levels (> 1000 pg/mL). Once ZES is suspected, an imaging study (eg, abdominal computed tomography [CT]) is used to localize the tumor.

Clinical Presentation
Dyspepsia refers to upper abdominal pain or discomfort, which may be produced by several gastrointestinal disorders, including PUD. Gastroesophageal reflux disease (GERD) typically produces “heartburn,” a burning epigastric or chest pain, associated with regurgitation of gastric content, usually occurring after meals and worsening with recumbency. Patients with GERD may also complain of a chronic dry cough, secondary to aspiration of gastric contents and stimulation of cough receptors in the lower respiratory tract. Biliary colic is characterized by an acute onset of right upper quadrant pain, lasting 30 to 60 minutes, and precipitated by fatty meals. Biliary colic is more common in fertile, middle-aged women. Irritable bowel syndrome (IBS) is a diagnosis of exclusion, characterized by chronic dysmotility symptoms (bloating, cramping) and relieved with defecation. Patients report a mixture of constipation and diarrhea without weight loss or GI bleeding.

PUD manifests when gastric acid erodes the mucosal and muscularis layers of the gastrointestinal tract, leading to the formation of an ulcer. These ulcers are most commonly located in the stomach (gastric ulcer) or duodenum (duodenal ulcer). Patients typically present with a gnawing/burning pain, located in the epigastrium without radiation to the back and relieved by antacids (ie, calcium carbonate, aluminum-magnesium hydroxide). Other associated symptoms may vary, depending on the location of the ulcer. Gastric ulcers typically present with postprandial abdominal pain, leading to an aversion of food, nausea, vomiting, and weight loss. Patients with duodenal ulcers may experience weight gain because the pain associated with these ulcers is initially relieved during meals, when ingestion of food stimulates bicarbonate secretion into the duodenum. The pain, however, worsens 2 to 5 hours later, when acidic gastric contents are emptied from the stomach and enter the duodenum, directly irritating the ulcer. Pain associated with duodenal ulcers may also worsen at night due to circadian stimulation of acid secretion.

Young patients without alarm features may undergo noninvasive testing, such as serology for H. pylori antibody, urea breath test, or fecal H. pylori antigen test. The urea breath test and serology for the H. pylori antibody are the most commonly used noninvasive tests to detect active infection. However, serologic testing for H. pylori is only useful if the patient has never been previously treated for H. pylori since antibodies will be positive for life, even after successful treatment.

Treatment
Chronic infection with H. pylori is the most common cause for both gastric and duodenal ulcers. Therefore, the standard of care is to test the patient for infection and treat with triple or quadruple therapy if present. Although triple therapy has traditionally been the gold standard for H. pylori eradication, clarithromycin-resistant strains of H. pylori have been identified, resulting in decreased efficacy of triple therapy. Quadruple therapy is preferred if the patient has ever had exposure to macrolides for any reason, if local clarithromycin resistance rates are > 15%, or if eradication rates with triple therapy are < 85%. A follow-up visit within 4 to 8 weeks is recommended to ensure H. pylori eradication. Fecal H. pylori antigen testing may be used to confirm eradication following treatment. If the patient is older (> 45 years) or presents with alarm symptoms, an esophagogastroduodenoscopy (EGD) with or without biopsy, depending on gastric (high risk) versus duodenal (low risk) ulcer, should be performed to rule out malignancy.

Treatment for PUD caused by NSAIDs consists of discontinuing the offending agent and initiating a PPI to reduce acid secretion and promote ulcer healing.

Complications
Approximately 70% of peptic ulcers are asymptomatic and may go unnoticed until complications develop. The most common severe complication of PUD is hemorrhage. Patients may complain of hematemesis (“coffee ground emesis”) or melena. Chronic ulcers may result in gastric outlet obstruction symptoms due to formation of strictures. Similarly, ulcers located near the pyloric channel may also cause obstructive symptoms due to mass effect. Transmural ulcers may cause perforation within the gastrointestinal tract. Ulcers that perforate the lesser curvature of the stomach or posterior wall of the duodenum may cause hemorrhage due to involvement of the left gastric artery and gastroduodenal artery, respectively. Perforation of the anterior wall of the duodenum may lead to peritonitis (eg, rebound tenderness, involuntary guarding) and referred pain to the shoulder due to phrenic nerve irritation caused by free air accumulation below the diaphragm. Perforation near the pancreas may result in pancreatitis. Both obstructive and peritoneal symptoms are indications for surgery.

Moreover, unlike duodenal ulcers, which have a low propensity for malignant transformation, approximately 5% to 10% of gastric ulcers are malignant (eg, gastric adenocarcinoma). Gastric ulcers should be evaluated endoscopically with an EGD and biopsied to exclude gastric cancer, which may also present as nausea/vomiting, dysphagia, and early satiety. Chronic H. pylori infection may also result in the development of a gastric MALT tumor.

In general, patients older than 45 years who present with new-onset dyspepsia should undergo endoscopy since the risk of malignancy increases with age. Furthermore, patients with alarm symptoms (eg, weight loss, recurrent vomiting, dysphagia, evidence of GI bleeding, or iron-deficiency anemia) or who fail to respond to empiric therapy should also be referred for prompt endoscopic evaluation.


CASE CORRELATION
  • See also Case 3 (Acute Coronary Syndrome), Case 5 (Aortic Dissection/Marfan Syndrome), Case 10 (Acute Pericarditis Caused by Systemic Lupus Erythematosus), Case 22 (Acute Diverticulitis), and Case 25 (Pancreatitis/Gallstones).

COMPREHENSION QUESTIONS

20.1 A previously healthy 42-year-old overweight woman presents to the emergency department complaining of sudden, right upper abdominal pain that “comes and goes,” lasting approximately 45 minutes after eating at a fast-food restaurant. The patient has vomited twice since the pain started, and any attempt to eat worsens the pain. She is sexually active with one male partner, uses condoms regularly, and denies drug use. Which of the following is the most likely cause?
A. Gastric ulcer
B. Cholelithiasis
C. Duodenal ulcer
D. Acute hepatitis

20.2 A 34-year-old man is being seen in the office for follow-up for epigastric pain and suspected PUD. Serum antibodies are positive for H. pylori. Which of the following is the most accurate statement regarding this infection?
A. It is more common in North America than in the developing world.
B. It is associated with the development of colon cancer.
C. Eradication of H. pylori eliminates most cases of nonulcer dyspepsia.
D. It is believed to be sexually transmitted.
E. It is a cause of both duodenal and gastric ulcers.

20.3 A 45-year-old man was brought to the emergency department after vomiting bright red blood. He has a blood pressure of 88/46 mm Hg and heart rate of 120 bpm. Which of the following is the best next step?
A. Intravenous fluid resuscitation and preparation for a transfusion
B. Administration of a PPI
C. Guaiac test of the stool
D. Treatment for H. pylori

20.4 Which one of the following patients should be promptly referred for endoscopy?
A. A 65-year-old man with new onset of epigastric pain and weight loss
B. A 32-year-old patient whose symptoms are not relieved with ranitidine
C. A 29-year-old H. pylori–positive patient with dyspeptic symptoms
D. A 49-year-old woman with intermittent right upper quadrant pain following meals


ANSWERS

20.1 B. This patient demonstrates risk factors for biliary colic secondary to cholelithiasis (4 F’s: “fat, fertile, female, forty”). Acute right upper abdominal pain occurring after a fatty meal (“fast food”) and producing nausea/vomiting is most suggestive of biliary colic due to gallstones. Gastric and duodenal ulcers (answers A and C) cause a gradual, “gnawing/burning” pain, most commonly located in the midepigastrium. Moreover, the pain associated with duodenal ulcers is relieved with meals. The patient does not demonstrate risk factors for acute hepatitis (answer D) such as intravenous drug use, recent travel, and risky sexual activity.

20.2 E. Helicobacter pylori infection is more common in developing countries (answer A). It is associated with poor hygiene and transmitted via ingestion of the bacteria (contaminated food or water—not sexually [answer D]). H. pylori is associated with the development of gastric adenocarcinoma and MALT lymphoma, not colon cancer (answer B). The association between H. pylori and nonulcer dyspepsia (answer C) remains unclear. Fewer than 10% of patients with nonulcer dyspepsia improve after H. pylori treatment.

20.3 A. This patient is hemodynamically unstable with hypotension (systolic blood pressure < 90 mm Hg) and tachycardic because of the acute blood loss. Immediate volume resuscitation with crystalloid solution (eg, normal saline), followed by blood transfusion, if necessary, are the best initial steps to prevent irreversible shock and death. Only after the patient is stabilized would it then be appropriate to investigate the cause of instability (eg, hemorrhage or ulcer perforation [answers B, C, and D]).

20.4 A. The patient in answer A has “red flag” symptoms, prompting immediate endoscopic evaluation: He is older than 45 years and has new-onset symptoms suggesting possible malignancy (eg, weight loss). The patient in answer B is young and may benefit from a PPI rather than an H2 blocker. The patient in answer C is also young and may benefit from triple or quadruple therapy for H. pylori eradication. If this initial therapy does not improve symptoms, endoscopic examination would then be appropriate to investigate other causes of dyspepsia. The patient in answer D is most likely experiencing a biliary colic. A right upper quadrant ultrasound would be the best next step in order to evaluate for gallstones.


CLINICAL PEARLS
▶ The most common causes of duodenal and gastric ulcers are H. pylori infection and the use of NSAIDs.

▶ Helicobacter pylori is associated with duodenal and gastric ulcers, chronic active gastritis, gastric adenocarcinoma, and gastric MALT lymphoma.

▶ Treatment of peptic ulcers requires acid suppression with a PPI to heal the ulcer and antibiotic therapy for eradication of H. pylori, if present, to prevent recurrence.

▶ Patients with dyspepsia who have red flag symptoms (new dyspepsia after the age of 45, weight loss, dysphagia, evidence of bleeding, or anemia) should be referred for endoscopic examination.

▶ Patients without red flag symptoms may undergo noninvasive testing for H. pylori first. The urea breath test may demonstrate active infection. Serologies may be used only if the patient has never been treated for H. pylori since antibodies will remain present even after successful treatment.

▶ Triple or quadruple therapy is used for the treatment of PUD secondary to H. pylori. Triple therapy consists of amoxicillin (or metronidazole if penicillin allergy is present), clarithromycin, and a PPI. Quadruple therapy is preferred in the setting of suspected clarithromycin-resistant strains of H. pylori, and it consists of a tetracycline, metronidazole, a bismuth compound, and a PPI.

REFERENCES

Atherton JC, Blaser MJ. Helicobacter pylori infections. In: Jameson JL, Fauci AS, Kasper DL, et al, eds. Harrison’s Principles of Internal Medicine. 20th ed. New York, NY: McGraw Hill Education; 2018:1038-1042. 

Del Valle J. Peptic ulcer disease and related disorders. In: Jameson JL, Fauci AS, Kasper DL, et al, eds. Harrison’s Principles of Internal Medicine. 20th ed. New York, NY: McGraw Hill Education; 2018:1911-1932. 

Lanas A, Chan FKL. Peptic ulcer disease. Lancet. 2017;390(10094):613-624. 

Talley NJ, Vakil N; Practice Parameters Committee of the American College of Gastroenterology. Guidelines for the management of dyspepsia. Am J Gastroenterol. 2005;100:2324-2337. 

Vakil NB. Peptic ulcer disease: Treatment and secondary prevention. Feldman M, ed. UpToDate. Waltham, MA: UpToDate; 2019. https://www.uptodate.com. Accessed July 10, 2019.

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