Topic Editor: Grant E. Fraser, M.D., FRACGP, FACRRM, ASTEM
Review Date: 10/17/2012
Definition
Peptic ulcer disease (PUD) is defined as a 5 mm or greater diameter ulceration of the mucosal lining of the stomach or duodenum. PUD occurs due to an imbalance between various mucosal protective factors (prostaglandins, mucus, bicarbonate, mucosal blood flow) and various mucosal damaging factors (gastric acid, pepsin, Helicobacter pylori infection, NSAIDs, etc.).
Description
- The most common causes of damage are infection of the stomach by Helicobacter pylori (H .pylori) and long-term use of nonsteroidal anti-inflammatory drugs (NSAIDs) such as aspirin, ibuprofen, or naproxen
- Symptoms of peptic ulcer may include the inability to drink as much fluid, changes in appetite and an empty feeling in the stomach, pain in the upper abdomen, bloody or dark tarry stools, chest pain, fatigue, or mild nausea
- Complications of ulcers include bleeding, gastric or duodenal perforation, gastric outlet obstruction, and cancer
- Depending on their location, peptic ulcers may be classified as follows:
- Gastric ulcers:
- Located along the lesser curvature of the antrum of stomach at or around the incisura angularis
- Occurs less commonly than duodenal ulcer
- Usually have normal or even higher than normal stomach pH
- Such ulcers are commonly pre-malignant
- Associated with abdominal pain, usually immediately after meals. There may be additional symptoms such as vomiting to relieve pain, fear of eating food, and weight loss
- Upper GI bleed more commonly presenting with hematemesis rather than melena
- Duodenal ulcers:
- The most common form of peptic ulcer, usually occurs in the proximal part of the duodenum
- Multiple ulcers located distal to the second portion of duodenum (D2) may increase the risk of Zollinger-Ellison syndrome [pancreatic tumor producing large amounts of gastrin which stimulates gastric parietal cells resulting in hypersecretion of acid]
- Gastric hyperacidity
- Almost never malignant
- Associated with pain around 2 hours after a meal, normal or increased appetite, normal or increased weight
- Upper GI bleed more commonly presenting with melena rather than hematemesis
- Esophageal ulcers:
- Located in the distal esophagus, usually secondary to Gastroesophageal Reflux Disease (GERD), which can lead to Barrett's esophagus
- Ectopic gastric mucosal ulcers:
- May develop in patients with Meckel's diverticulum
Epidemiology
Incidence/Prevalence
- Estimated to affect 4.5 million people/year, worldwide
- At least 10% of the U.S. experience symptoms of, or are diagnosed with duodenal ulcer in their lifetime
- Recurrence rate is nearly 4 million/year)
- Global incidence rate is 0.1-0.2%
- Mortality is approximately one death per 10,000 cases
Age
- Patients between 25 and 64 years of age account for 70% of PUD cases, but it may occur at any age
- Incidence of peptic ulcers increases with age
Gender
- Affects both genders, but has a male predominance
- Approximately 11%-14% of men and 8%-11% of women develop PUD in their lifetime
Risk Factors- Family history of peptic ulcers
- History of intestinal bleeding
- H. pylori infection
- Lifestyle factors including smoking and excessive alcohol intake may make the patient more susceptible to damage from NSAIDs or H. pylori
- Long term use of aspirin, ibuprofen, or other NSAIDs cause irritation of the gastric mucosa and inhibit prostaglandins which protect gut mucosa
- Medications: Corticosteroids (high-dose and/or prolonged therapy), bisphosphonates, potassium chloride, chemotherapeutic agents (e.g., IV fluorouracil)
- Older age
- Radiation therapy
- Spicy food
- Stress ulcers
- Zollinger-Ellison syndrome
Etiology
Peptic ulcer disease is felt to be caused by multiple factors such as:
- Genetics
- H. pylori infection
- Lifestyle factors
- Other hypersecretory factors
- Physiological stress
- Rare causes
- Ulcerogenic drugs (e.g., NSAIDs, glucocorticoids)
- H. pylori infection:
- H. pylori is responsible for 90% of ulcers (almost all duodenal ulcers and 70% of gastric ulcers). This organism secretes urease, proteases and phospholipases, which results in disruption of the gastric and/or duodenal mucosa.
- Ulcerogenic drugs:
- Long-term NSAID use is the second most common causative factor for peptic ulcers. These drugs block prostaglandins that help maintain blood flow and protect the stomach from injury
- Corticosteroids increase the risk for peptic ulcer and potentiate ulcer risk in those concurrently taking NSAIDs
- Spironolactone is felt to increase the risk of upper GI bleeding
- Lifestyle factors
- Smoking and excessive alcohol consumption may increase the risk of PUD due to a stimulant effect on gastric emptying which reduces bicarbonate levels
- Smoking has been associated with increased susceptibility to NSAID induced damage and ulcer recurrence among H. pylori carriers
- Evidence regarding the role of smoking and alcohol in PUD is limited
- There is limited evidence to support the role of caffeine increasing the risk of developing duodenal ulcers
- Physiological Stress
- Stressful conditions such as:
- Burns
- Hypotensive insult
- Respiratory failure/ARDs
- Sepsis
- Surgery (major)
- Trauma (head, multiple, spinal)
- Any other severe physiologic stressor
- Other hypersecretory factors:
- Acid is secreted by parietal cells and antral G cells, whereas pepsin is secreted as pepsinogen by chief cells. Excessive acid production due to excessive stimulation can lead to erosion or perforation of the mucosal lining
- Antral G cell hyperplasia
- Bile acids
- Crohn's disease
- Cystic fibrosis
- Decreased blood flow to gastric mucosa
- Hyperparathyroidism
- Impaired proximal duodenal bicarbonate secretion
- Incompetent pylorus or lower esophageal sphincter
- Short bowel syndrome
- Zollinger-Ellison syndrome
- Rare causes
- Other rare causes of peptic ulcers include vascular insufficiency, radiation therapy, or chemotherapy
Blood test findings
- Basic blood evaluation may include:
- CBC to evaluate for anemia and determine if micro or macrocytic (generally microcytic consistent with iron deficiency if chronic losses)
- Comprehensive panel and lipase if indicated and depending upon clinical scenario to evaluate for upper GI bleeding (Urea/Creatinine ratio markedly elevated), concomitant liver disease, or pancreatitis
- INR if advanced liver disease or on warfarin
- Coagulation profile if needing large volume transfusion
- Fasting serum gastrin level
- Fasting serum gastrin level may be useful to screen cases for Zollinger-Ellison syndrome. In peptic ulcers, gastrin level may be mildly raised after meals
- Secretin Stimulation Test
- It includes testing for maximum acid output (MAO) and basal acid output (BAO). Used in diagnosing Zollinger-Ellison syndrome if serum gastrin level alone is insufficient. It is useful in differentiating Zollinger-Ellison syndrome from other conditions involving high serum gastrin level such as renal failure or gastric outlet obstruction
- Antibody testing
- Antibodies to H. pylori can be measured by blood testing. These antibodies can remain elevated for months to years after the infection has cleared
Other laboratory test findings
- H. pylori testing
- In most cases of PUD, routine laboratory tests are not helpful, however, testing for H. pylori infection is essential
- H. pylori testing may be done by endoscopic evaluation, a rapid urease test, histopathology, and cultures
- H. pylori can be detected in gastric mucosa by testing for urease
- Antigen tests can be used to identify active H. pylori infection by detecting their presence in stool
- Helicobacter pylori breath test
- Urea breath tests can detect the presence of H. pylori infection. This test relies on H. pylori's urease enzymatic activity
- Urea that has radioactive carbon is given to the patient to swallow. If H. pylori is present, urease enzymatic activity results in liberation of some of this labeled carbon as carbon dioxide
- If labeled carbon dioxide is exhaled, H. pylori is presumed to be present in the stomach
- Use of proton pump inhibitors (PPI) within 2 weeks of the urea breath test may interfere with test results
- Histopathology testing
- Histopathology is an important tool in diagnosing H. pylori infection
- Histological evaluation may show surfaces covered with slough and inflammatory debris, active granulation with mononuclear leukocytic infiltration and fibrinoid necrosis
- Detection of H. pylori depends on the site and number of biopsy samples, the method of staining, and the experience of the pathologist
Radiographic findings
- Chest x ray
- An erect chest x-ray is useful if perforation is suspected (evaluate for pneumoperitoneum)
- Angiography
- Angiography may be useful in patients who have upper GI bleeding when endoscopy cannot be performed and bleeding is ongoing
- Angiography, when a bleeding source is identified, can focus attention on the site of bleeding and allow planning for further therapy
Other diagnostic test findings
- GI endoscopy
- Upper GI endoscopy (Gastroduodenoscopy) is recommended as the diagnostic test of choice in cases of suspected PUD
- Endoscopy is highly sensitive in diagnosing or excluding PUD
- As part of this examination, urease testing is usually performed, along with histology on any stomach biopsy specimens obtained
- Direct testing for Helicobacter pylori can also occur
- Endoscopy includes the benefit of direct viewing and documentation of ulcers, masses or other abnormalities, with any suspicious lesions being biopsied
- It is common in cases of PUD to repeat endoscopy in 6-8 weeks after therapy to evaluate for healing and re-evaluate for the presence of malignancy
General treatment items
- The goal of therapy should be to treat complications, address the underlying cause, relieve symptoms, and provide a treatment strategy which results in ulcer healing
- Most patients with PUD are treated successfully with a regimen to eradicate H. pylori, decrease stomach acidity and avoidance of NSAIDs or other contributory causes
- Treatment of PUD depends on the underlying etiology and symptomatology
- Treatment involves a combination of medications, including antibiotics to eliminate H. pylori bacteria (if present), and proton pump inhibitors (PPIs) to reduce stomach acidity
- Avoidance of NSAIDs (unless absolutely necessary)
- Perforated peptic or duodenal ulcer is a surgical emergency and requires urgent surgical intervention
- Active bleeding ulcers:
- Resuscitation of the patient depending upon degree of blood loss and co-morbidities
- May need blood transfusion and/or fluid resuscitation
- May need other blood products if coagulopathic
- May need urgent interventional endoscopy or surgery for life threatening bleeding
- Endoscopy can decrease the duration of hospitalization by identifying patients who are at a low risk for rebleeding and also by allowing endoscopic interventions such as cauterization (laser, electrical), sclerotherapy or endoclipping
- Endoscopic therapy is beneficial as it both decreases recurrent bleeding and the need for surgical management
- Patients with active bleeding ulcers should be admitted to hospital
- Use of proton pump inhibitors reduces bleeding and need for surgery
- As part of treatment, all non-essential NSAIDs, including aspirin, and anticoagulants should be discontinued
- Concomitant H. pylori infection in the setting of a bleeding peptic ulcer should be treated
- Acid secretion can be reduced by two classes of drugs; Histamine-2 receptor antagonists (H2RAs) and proton pump inhibitors (PPIs). PPI's are significantly more effective
- Examples of H2RAs include cimetidine, famotidine, ranitidine and nizatidine
- Examples of PPIs include esomeprazole, lansoprazole, omeprazole, pantoprazole, and rabeprazole
- No active bleeding ulcers
- The primary treatment approach for non-bleeding ulcers includes addressing the underlying cause, prevention of bleeding/rebleeding, and promoting ulcer healing
- NSAIDs should be discontinued as this is the prime cause in these patients
- If H. pylori is present, it should be treated
- Ulcer healing therapy should then be instituted. Proton pump inhibitors are the drugs of choice for treating peptic ulcers
- H2 antagonists may be tried, often in addition to PPI's in patients not responding with PPI's
- H2 blocker antihistamine agents can be used in short-term treatment of active duodenal ulcer
- Ulcers due to H. pylori infection
- PPI-based triple therapy is recommended as the primary therapy for H. pylori infection.
- PPIs are inhibitors of the gastric Hydrogen/Potassium (H+/K+) –ATPase pump, which allows the exchange of H+ and K+
- Proton pump inhibitors include agents such as esomeprazole, lansoprazole, omeprazole, pantoprazole, and rabeprazole
- 90 % cases of peptic ulcers can be healed with PPI-based triple therapy
- Triple therapy regimens
- PPI-based triple therapies include a 14-day regimen as shown below:
- Esomeprazole: 40 mg PO qd or Lansoprazole: 30 mg PO bid or Omeprazole: 20 mg PO bid or Rabeprazole: 20 mg PO bid Plus
- Amoxicillin: 1000 mg PO bid and Clarithromycin: 500 mg PO bid
- There is also an option to add a fourth agent (Quadruple therapy), usually bismuth sub-salicylate or tetracycline
- Management of patients on NSAIDs
- According to the ACG guidelines, H. pylori testing is indicated in patients who are starting long-term NSAID therapy
- NSAIDs should immediately be discontinued in patients with a positive H. pylori test, except for those who need to remain on these agents. Generally, such patients undergo H. pylori eradication – preferably while not on NSAIDS and thereafter, PPI maintenance is recommended to prevent PUD recurrences in such patients, even if H. pylori has been eradicated
- If NSAIDs must be continued, changing to a COX-2 selective NSAID is an option
- For patients who need to continue therapy with NSAIDs, PPI maintenance is recommended to prevent recurrences of PUD, even if H. pylori has been eradicated
- Use the lowest possible NSAID dose for the shortest duration with adjuvant therapy with a PPI or misoprostol
- Patients at risk for GI ulcers should avoid NSAIDs or COX-2 inhibitors entirely
- Unnecessary use of NSAIDs should be avoided
- Some patients benefit from prophylactic therapy (PPI or prostaglandin analog), if on NSAIDS. A risk assessment should be made on patients taking long term NSAIDS
- Supplementary measures
- High-risk patients who have active bleeding with hemodynamic instability, cardiac, pulmonary or renal diseases should be provided adequate supportive therapy
- Antacids can be useful symptomatically, but have little impact on PUD healing or progression and thus are not a primary therapy
- Patients experiencing significant or potentially significant hemorrhage should be managed in the intensive care unit
Medications indicated with specific doses
Proton pump inhibitors
- Esomeprazole [Oral]
- Lansoprazole
- Omeprazole
- Pantoprazole [IV]
- Pantoprazole [Oral]
- Rabeprazole
H2 Receptor Blockers- Cimetidine
- Famotidine [IV]
- Famotidine [Oral]
- Ranitidine
Antibiotics- Amoxicillin
- Clarithromycin
- Tetracycline [Oral]
Cytoprotective agentsDietary or Activity restrictions
- No special diet is indicated for patients with duodenal ulcers; however, patients should avoid any food or beverages that may aggravate symptoms (eg. spicy, fried, fatty food, etc.)
Disposition
Admission Criteria
- Patients need to be admitted in cases involving gastric obstruction or perforation, active bleeding in the upper GI tract, melena, uncontrolled pain and anemia requiring transfusion
Discharge Criteria
- Glasgow Blatchford Bleeding Score provides a solid background for upper GI bleeding patients who are low risk for outpatient management. If all of the following are PRESENT, then the patient is low risk and can generally be managed as an outpatient:
- Hb >12.0 g/dL (female) or >13.0 g/dL (male)
- BUN18.2 mg/dL
- Initial SBP>109 mmHg
- HR100/min
- Melena not present
- Has not had syncope
- Does not have hepatic disease
- Does not have heart failure
Prevention
- Avoid excessive use of NSAIDs such as aspirin, ibuprofen and naproxen
- Testing for H. pylori infection prior to initiating long-term NSAID therapy
- Taking a proton pump inhibitor or an H-2 blocker as a prophylactic agent along with NSAID therapy
- The following lifestyle changes may help prevent occurrence/recurrence of peptic ulcers:
- Avoiding cigarette smoking
- Avoiding stress
- Limiting alcohol intake
- Regular healthy eating habits
Prognosis
- Peptic ulcers often recur if untreated
- Generally, duodenal ulcers heal in 4 weeks and gastric ulcers in 8 weeks with proton-pump inhibitor (PPI) therapy
- Following treatment instructions and taking all medications as directed, cure most cases of H. pylori. Re-infection can occur. Some H. pylori strains exhibit antibiotic resistance
- Low ulcer relapse rate, re-infection rates 1% per year, low risk of re-bleeding and decreased recurrence of NSAID induced ulcers is observed after H. pylori eradication
Pregnancy/Pediatric effects on condition
- Peptic ulcers during pregnancy may be associated with adverse birth outcomes such as risk of preterm delivery, low birth weight and small size for gestational age
- Use of misoprostol is contraindicated during pregnancy due to risk of spontaneous abortion
Synonyms/Abbreviations
Synonyms
- Peptic ulcer disease
- Gastric ulcer
- Duodenal ulcer
- Dyspepsia ulcer
Abbreviations
ICD-9-CM
- 531.90 Gastric ulcer, unspecified as acute or chronic, without mention of hemorrhage or perforation, without mention of obstruction
- 533.90 Peptic ulcer of unspecified site, unspecified as acute or chronic, without mention of hemorrhage or perforation, without mention of obstruction
- 532.90 Duodenal ulcer, unspecified as acute or chronic, without hemorrhage or perforation, without mention of obstruction
ICD-10-CM
- K27 Peptic ulcer, site unspecified
- K26 Duodenal ulcer
- K25 Gastric ulcer
