Peptic Ulcer Disease a clinical Review Khalid s malik md

Download 114.68 Kb.
Date conversion07.02.2017
Size114.68 Kb.
Peptic Ulcer Disease - a clinical Review

Khalid S Malik MD, Assistant Clinical Professor, Clinical Chief Family Medicine, Erie County Medical Center, University at Buffalo, NY, USA.

Mathew K Philip MD, Assistant Clinical Professor, Family Medicine, University at Buffalo. NY, USA.

Muhammad A Ghazi MD, Clinical Instructor, Family Medicine, University at Buffalo. NY, USA.

Peptic ulcer disease contributes to significant clinical morbidity and healthcare cost. This purpose of this narrative review article is to highlight the important clinical features and the management of Peptic ulcer disease. A Medline search was performed, which included meta-analyses, randomized controlled trials, clinical trials, and systematic reviews. MeSH terms included Peptic ulcer, diagnosis, management, Helicobacter Pylori; Non steroidal anti inflammatory drugs related ulcer. We also reviewed Cochrane Database of Systematic Reviews, American College of Gastroenterology and the Centers for Disease Control and Prevention guidelines.

The most common causes of Peptic Ulcer disease in the United States are infection with Helicobacter pylori and Non steroidal anti inflammatory drugs. Epigastric pain is the most common presenting symptom. Elderly patients and those with alarm symptoms should have a prompt endoscopy as this may indicate a complication or malignancy.

Younger patients with no alarm symptoms should undergo Helicobacter pylori testing and be treated based on results. If Helicobacter pylori infection is detected, it is eradicated and anti-secretory therapy (with a proton pump inhibitor) is given for four weeks. Acute complications like bleeding require quality supportive care and endoscopic intervention while surgical intervention is rarely needed.

Conclusion: We conclude that timely diagnosis and treatment of Peptic ulcer disease prevents the complications like bleeding, anemia, perforations and decrease the mortality and morbidity of the disease.
Key Words: Peptic Ulcer, Helicobacter pylori, ulcer complications, bleeding ulcer

Peptic ulcer disease (PUD) is an important cause of morbidity and the disease related healthcare costs in terms of days of work lost and treatment expenditures are estimated to about 5.65 billion US dollars each year1. Epidemiological studies show that peptic ulcer hospitalizations and mortality remains high in the older patients which will have significant global impact on healthcare delivery, health economics and quality of life in these patients.

According to Sung et al., the incidence ranges from 0.10 to 0.19 % in physician diagnosed group and 0.01 to 0.17% in hospitalized patients 2. In the United States endoscopic point prevalence was reported to be 2% in H pylori positive individuals 3. According to Wang et al., there is around 30 to 40% decrease in the hospitalizations due to peptic ulcer disease between 1993 and 20064. The population with increased probability of H. pylori infection includes; NSAID users, people from developing countries, those with poor socioecomic backgrounds, and those greater than 50 years of age 5.
Peptic ulcer is characterized by defects in gastric and duodenal mucosa that extends through muscularis mucosa and submucosa usually due to the damaging effects of gastric acid and pepsin. Endoscopic diagnosis of peptic ulcer requires an ulcerated surface breach with a diameter of 5 mm or larger covered with fibrin while a mucosal break less than 5 mm is called erosion6. In a recent systemic review of ulcer prevention among non-steroidal anti-inflammatory drug users, a gastric or duodenal lesion ≥3 mm in diameter with significant depth has been defined as a Peptic ulcer.7 Peptic ulcers can be gastric (prepyloric or antral), duodenal or combined (Dragstedt ulcers).8 The healing rates for pre-pyloric ulcers (located within 2-3 cm of pylorus) are significantly lower than duodenal ulcers. This is probably related to the amount of acid secretion and level of gastritis in different parts of the stomach.9
Etiology- The great majority of peptic ulcer disease results from infection with H. pylori or use of NSAIDs. Up to 95% of duodenal and approximately 70% of gastric ulcers are associated with Helicobacter pylori.10 With a recent increase in Bariatric surgery, there has been a rise of marginal ulcers. A marginal ulcer, or stomal ulceration, refers to the development of mucosal erosion at the gastrojejunal anastomosis, typically on the jejunal side. It can be seen in up to 16 % of individuals undergoing Roux-en-Y gastric bypass (RYGB).11 Other causes of peptic ulcer disease are mentioned in Table 1.

Table 1 Etiology of Peptic Ulcer Disease



Helicobacter Pylori infection-

Spiral shaped, microaerophilic, gram negative bacterium and seen in 48% of patients with peptic ulcer disease.


NSAIDs and Aspirin. In the elderly, concomitant diseases and multidrug therapy which includes anti-platelet drugs, warfarin, corticosteroids, SSRI and bisphosphonates increase risk of peptic ulcer disease and its complications.


Physical- severe injuries, extensive burns, major surgery, acute severe infections. Emotional- General anxiety disorders, PTSD

Crohn’s disease of stomach and duodenum

Endoscopic finding of mucosal ‘cobblestoning’, ulcers, strictures, ‘ram horn sign’

Eosinophilic gastroduodenitis

In children and adolescent- mimic GERD.

Rare causes

Acid hypersecretory states (e.g.-Zollinger-Ellison syndrome, MEN-1, Systemic mastocytosis, Hyperparathyroidism)

Multiple gastroduodenal, jejunal or esophageal ulcers


Gastric malignancy, lymphoma, Lung cancer

Diagnosis & Management

Clinical evaluation begins with a good medical, social and family history and continues with a thorough physical examination. The most common symptom of PUD is epigastric pain12, 13 associated with increased or decreased appetite, weight loss, nausea, heartburn and bloating. The bleeding peptic ulcer patients are more severely ill, and less likely to present with epigastric pain14. The alarm features which warrant prompt gastroenterology referral include bleeding or anemia, early satiety, unexplained weight loss, progressive dysphagia or odynophagia, recurrent vomiting and family history of gastrointestinal cancer.15

Diagnostic evaluation of Peptic Ulcer disease

The diagnostic evaluation of a peptic ulcer includes laboratory and endoscopic tests.

Initial work up usually includes complete blood count (CBC) to evaluate for anemia due to occult gastrointestinal bleeding and complete metabolic profile to get a baseline of liver and kidney function. H. pylori tests are broadly divided into endoscopic (invasive) and non-endoscopic tests (non-invasive tests). The endoscopic tests include histological examination, rapid urease test, culture and Polymerase chain reaction. The noninvasive tests include serological tests, urea breath test and stool antigen test.

TABLE 2 Diagnostic Tests for H. pylori Infection

Endoscopic tests







Rapid urease



Fast and inexpensive.

False negative in patients with recent use of PPIs




Diagnostically excellent Sensitivity and specificity

Requires trained personnel.


Can be falsely negative if on antibiotics, bismuth or PPI




Excellent specificity; provides opportunity to test

for antibiotic sensitivity

Variable sensitivity; requires trained staff and properly equipped facilities,

Not widely available.

Only marginal sensitivity.6

Polymerase chain reaction



Excellent sensitivity and specificity. Antibiotic sensitivities can be determined.6

Non-standardized across laboratories. Not widely available.6

Non-endoscopic Tests

Antibody testing



Inexpensive and widely available. Good Negative Predictive value.6

Not useful to confirm eradication as it persists even after eradication

Urea breath test



Identifies active H. pylori infection. High negative and positive predictive values; useful before and after treatment

False negative possible in case of PPI use. Requires trained personnel to perform the test.

Reimbursement and availability is inconsistent.6

Stool/Fecal antigen



High negative and positive predictive values with Monoclonal test. Useful before and after the treatment.

High false positive in upper GI bleed

Cumbersome collection process.16

Polyclonal test is less well validated than Urea Breath test.6

Non endoscopic tests

Among the non endoscopic tests, serological testing for IgG antibodies to H pylori is commonly used because it is readily available and cost effective but it is not a good test for confirmation of eradication of H pylori as it cannot differentiate between the active and past infection of H pylori.5,16 A positive serological test can be present as:

  1. True positive, infective (Positive antibody test and recent infection)

  2. True positive, not infective (Positive antibody test but previous infection)

The patients in the later group will not benefit from H. pylori eradication therapy. This can lead to more treatments of the patients without active infection, more antibiotic resistance and burden on healthcare costs.

For the Urea breath test, the patient drinks C 13-labeled or C 14-labeled urea, which is converted to labeled carbon dioxide by the urease in H. pylori. The labeled gas is measured in a breath sample. Another test to detect H pylori infection, which has been available more recently, is fecal stool antigen test. Disadvantages include distasteful stool collection process and false negative results in patients who have used PPIs, Bismuth or antibiotics recently.16 In low to intermediate prevalence areas of H. pylori infection, it is recommended to use Urea breath test or stool antigen test instead of serological tests because of their higher level of accuracy with modest incremental cost.5

Endoscopic Tests

Upper gastrointestinal endoscopy is the most accurate diagnostic test for a peptic ulcer. The sensitivity of the endoscopy depends on the experience of the endoscopist (up to 90% in experienced hands) and the location of the ulcer.17 The patient with alarming signs, age more than 55 years and those who have failed empiric treatment should be referred for endoscopy.18 Benign lesions usually appear smooth and round with flat base. Malignant lesions are irregular, clubbed or ulcerated mass protruding into the lumen. Gastric ulcers must be biopsied to rule out gastric cancer.19 Endoscopic tests to diagnose H. pylori infection require biopsies from pre-pyloric and fundic area of gastric mucosa. The biopsy specimen can be tested with a rapid urease test which is rapid and inexpensive. Other methods include histology and cultures which have good sensitivity and specificity but require trained personnel.16 (see Table 2)

Most of these tests (especially, histology, urea breath test and rapid urease test) have limitation that their sensitivity falls abruptly with recent PPI, antibiotic and bismuth use. It is recommended that these tests are done 2-4 weeks after discontinuation of the above medications.15, 16, 20

According to Malfertheiner et al., all patients should be offered a repeat testing after H. pylori eradication to confirm that the infection has been cured 21. The post treatment testing is recommended because one out of four patients fail the eradication therapy, antibiotic resistance is on the rise and many patients do not adhere to full antibiotic treatment.5

Management of Peptic ulcer Disease

Symptomatic therapy for dyspepsia due to peptic ulcer disease includes antacids and GI cocktail (an antacid with an anesthetic such as viscous lidocaine and/or an antispasmodic). Proton pump inhibitors and H2 receptor blockers are anti-secretory therapies with good symptom relief. A “Test and treat” approach is recommended for suspected H. Pylori infections. It has been shown that antibiotic treatment against H. pylori not only promotes ulcer healing but also prevents recurrence of ulcers.6,10 All patients with peptic ulcer bleeding should be tested for H. pylori infection, and eradication therapy should be prescribed to H. pylori-positive patients.10

H. pylori eradication has been shown to reduce the incidence of recurrence in about 60% of cases with duodenal ulcers and up to 50% in patients with gastric ulcers19. H. pylori eradication is superior to anti-secretory therapy in the prevention of rebleeding in peptic ulcers.10

The established indications for the diagnosis and treatment of H. pylori include 18:

Uninvestigated dyspepsia, high prevalence of H. pylori in the population, active peptic ulcer disease, confirmed history of peptic ulcer disease with no previous H. pylori treatment, gastric MALT (Mucosa associated lymphoid tissue) lymphoma and after endoscopic resection of early gastric cancer. There is a growing evidence that H. pylori is associated with Iron deficiency anemia and eliminating H. pylori can sometimes improve Iron deficiency anemia as well18.

Advanced age is an independent risk factor for mortality and bleeding from peptic ulcer disease is more in elderly22.

Primary Treatment of H. pylori Infection

• In the United States, the recommended primary therapies for H. pylori infection include: a PPI (Proton Pump Inhibitors), Clarithromycin, and amoxicillin, or metronidazole (Clarithromycin-based triple therapy) for 14 days or a PPI or H2RA (H2 receptor antagonists), bismuth, metronidazole, and tetracycline (bismuth quadruple therapy) for10–14 days.

• Sequential therapy consisting of a PPI and amoxicillin for 5 days followed by a PPI, Clarithromycin, and Tinidazole for an additional 5 days may provide an alternative to Clarithromycin-based triple or bismuth quadruple therapy but requires validation within the United States before it can be recommended as a first-line therapy.18

Amoxicillin should be replaced with metronidazole in penicillin-allergic patients only, because of the high rate of metronidazole resistance.23

Number needed to treat (NNT) for Sequential therapy for H pylori is 6 and for triple therapy are 8. 24 Testing after eradication is recommended in the following cases: H. pylori-associated ulcer, persistent dyspeptic symptoms despite the test-and-treat strategy, H. pylori-associated MALT (Mucosa Associated lymphoid tissue) lymphoma, and resection of early gastric cancer.25

A Cochrane data base review comparing antibiotics vs. acid suppression therapy (with or without long-term maintenance acid suppression therapy) for the prevention of recurrent bleeding from peptic ulcer has shown that in people who have had a bleeding peptic ulcer caused by Helicobacter pylori, treatment with antibiotics is more effective and prevents gastrointestinal re-bleeding better than acid-suppressing drugs. It has shown that H. Pylori eradication therapy group has up to 3% rebleeding rate, while non eradication group has re-bleeding rate as high as 20%.10 In conclusion the use of antibiotics, when H. pylori infection is present, is cheaper and more convenient than the long term acid suppressant therapy. See (Table 3)

TABLE 3 Treatment Options for H. pylori eradication

Drug Regimes


Eradication rates


Standard Triple Therapy

Omeprazole (Prilosec): 20 mg PO bid


Lansoprazole (Prevacid): 30 mg PO bid


Rabeprazole (Aciphex): 20 mg PO bid


Esomeprazole (Nexium): 40 mg PO qd


Clarithromycin (Biaxin): 500 mg PO bid


Amoxicillin (Amoxil): 1 g PO bid

10-14 days


Nonpenicillin allergic patients who have not been treated with clarithromycin in the past.

14 days course are more effective than 7 day course.

Alternative triple-therapy regimens

The alternative triple therapies, also administered for 14 days, are as follows:

Omeprazole (Prilosec): 20 mg PO bid


Lansoprazole (Prevacid): 30 mg PO bid


Rabeprazole (Aciphex): 20 mg PO bid


Esomeprazole (Nexium): 40 mg PO qd


Clarithromycin (Biaxin): 500 mg PO bid


Metronidazole (Flagyl): 500 mg PO bid

10-14 days


Consider in penicillin allergic patients

Quadruple therapy

  • PPI, standard dose, or

  • ranitidine 150 mg, PO bid

  • Bismuth 525 mg PO qid

  • Metronidazole 500 mg PO qid

  • Tetracycline 500 mg PO qid

10-14 days


Penicillin allergic patients who are able to tolerate Bismuth

Sequential Therapy

PPI + amoxicillin 1 g b.i.d. followed by:
PPI, clarithromycin 500 mg, tinidazole 500 mg b.i.d.

5 days

5 days


Requires validation in North America

Adjunct medicines used in the treatment of Peptic Ulcer

Sucralfate (Carafate)

1 g four times daily


200 mcg PO QID

Treatment duration is four weeks blockers

4-8 weeks

Effectiveness similar to H2

Contraindicated in Pregnancy

FDA approved combinations PYLERA (Bismuth subcitrate potassium 140mg+metronidazole 125mg +tetracycline 125mg)

Prevpac (amoxicillin+lansoprazole+clarithromycin)

Salvage” or “rescue” therapy consists of medications used in case of persistent H pylori infection after one or more treatment cycles. Bismuth based quadruple therapy for 7 days is recommended for salvage with eradication rates of about 70% 18. Alternatively Levofloxacin- based triple therapy for 10 days can be used (eradication rates around 90%). Clinicians should avoid antibiotics that have been used previously to prevent antibiotic resistance.15, 16
Maintainence anti-secretory therapy after H. pylori eradication

There are no established guidelines for the maintainence and continuation of anti-secretory medicine after H pylori eradication. However a consensus guideline recommends a follow up endoscopy in 4-12 weeks after the eradication of H pylori to see the ulcer healing and the cure of H pylori infection and then stop the anti secretory therapy. 26

Low risk patients i.e., with ulcers less than 1 cm with adequate eradication of H pylori do not require a prolonged anti-secretory therapy. High risk patients include those with complicated peptic ulcers like ulcer size >2cm, protracted ulcer healing and fibrosed ulcer bed. These high risk patients are the candidates for the anti-secretory therapy at least till the healing and H pylori eradication has been confirmed. Abrupt stopping of PPIs after prolonged therapy may result in rebound acid hyper secretion therefore the PPIs should be tapered off to avoid recurrence of symptoms.
NSAID /Aspirin induced Ulcers

Non steroidal anti-inflammatory drugs (NSAID) induced ulcers develop in as many as 25% of chronic NSAID users and 2-4% of these ulcers will bleed or perforate.23 Patients who are on NSAIDs are at about four fold increased risk of complications such as bleeding compared to non-users. Prophylaxis is required if the patient is on NSAID and/or Aspirin for a long period of time and if a patient has prior Peptic ulcer disease. 23

A Proton Pump Inhibitor is recommended if there is a history of PUD, UGIB (Upper Gastrointestinal Bleed), patients on Aspirin and clopidogrel, age greater than 60, dyspepsia and history of steroids use.23 Caution is advised in patients using Clopidogrel and Proton pump inhibitors as the FDA has issued alerts that PPIs may decrease the effectiveness of clopidogrel (Plavix) for preventing serious cardiovascular events.27 H2RA (H2 receptor antagonists) can be considered in patients with ASA monotherapy. Change to COX 2 (Cyclo - oxygenase 2) inhibitors is associated with decrease in ulcer bleeding but with increase in cardiovascular events. 18

Prolonged use of PPIs is associated with increased risk of community acquired pneumonia and increased risk of fracture (up to 29%, including 31%increased risk of hip fracture and 54%increased risk of vertebral fracture).28 Moreover there is a twofold increased risk of Clostridium Difficile infection. In March 2011, there was an US Food and Drug Administration (FDA) warning about association of hypomagnesaemia with Proton Pump inhibitor usage probably due to decreased intestinal absorption.29 This can potentially cause cardiac arrhythmia, muscle spasms and seizure. Therefore clinicians should check baseline magnesium levels in susceptible patients (e.g., on digoxin or diuretics) and also periodically check it during long term maintainence treatment. A good rule of thumb is to use PPIs only when clearly indicated, and to reassess continued use so that long-term complications can be avoided.

Refractory and non healing ulcers are related to the smoking which not only promotes ulcer formation but also delays healing, large ulcer size >10 mm and prior ulcer history.30 Occasionally refractory healing is related to Gastrinoma and other comorbid illness like end stage renal disease. Such patients may require a prolonged anti-secretory therapy.

Complications related to Peptic Ulcer Disease

  1. Bleeding

Upper gastrointestinal bleeding is the most common cause of death and the most common indication for surgery in the peptic ulcer disease. In older persons, 20 percent of bleeding episodes result from asymptomatic ulcers. Patients with UGIB who have clean-based ulcers and are stable on admission can be safely discharged immediately after endoscopy.31

Algorithm of the management of a bleeding Peptic Ulcer (Figure 1)

Figure 1

The management of Bleeding Peptic Ulcer disease 38-40

Suspected Peptic ulcer Bleeding

  • Assess hemodynamic status (Pulse , Blood pressure and orthostatic changes)

  • Consider CV catheter placement if hemodynamically unstable, secure airway

  • Wide bore IV Access, Obtain complete blood count, electrolytes, BUN and creatinine, international normalizes ratio, blood type and cross match

  • Initiate resuscitation (crystalloid and blood products, if indicated ) and use of supplemental oxygen

  • Consider nasogastric tube placement and aspiration

  • Initiate treatment with Intravenous Proton Pump inhibitors (80mg bolus dose plus continuous infusion at 8mg per hour) while awaiting early endoscopy. No role of H2 Receptor antagonists.

  • Perform early endoscopy (within 24 hours after presentation)

  • Consider a single dose 250 mg of intravenous erythromycin 30 to 60 minutes before endoscopy(To decrease the likelihood of accumulated blood/large clots within the stomach, which will interfere with visualization and/or treatment of lesions)

  • Consider Risk stratification by using a scoring tool (like Blatchford or Clinical Rockall Score) before endoscopy.

Clean based ulcer

No need of endoscopic treatment. Anti-secretory treatment with PPI.Treat H.pylori if indicated

High risk Ulcers

Active hemorrhage

A visible vessel, a fresh clot over the ulcer
Upper GI endoscopy


(See below)

Successful hemostasis

  • Admit the patient to a monitored bed or ICU.

  • Treat with IV Proton Pump Inhibitor (80 mg bolus dose plus continuous infusion at 8mg per hour) for 72 hours after endoscopic hemostasis

  • Initiate oral intake of clear liquids 6 hours after endoscopy in patients with hemodynamic stability.

  • Transition to oral Proton pump inhibitors after completion of intravenous therapy.

  • Perform testing for H. pylori; initiate treatment if the test is positive

*Combination of Injection sclerotherpy and coagulation therapy works better than monotherapy.

*Combination of hemostatic clip and coagulation therapy works better than injection and coagulation therapy.40

Epinephrine injection as a definitive hemostatic therapy is not recommended because of lower efficacy.40Rockall score is used to stratify the patients at risk of recurrent bleeding and to predict the mortality.32 A score of less than 2 on Rockall indicates that the patient can be safely discharged, however another scoring system which is more useful in identifying low risk patients (who do not require interventions like blood transfusions, endoscopy therapy and or surgery) is the Glasgow –Blatchford scoring system.33 Blatchford score offers more prognostic accuracy before the endoscopy in a patient with upper GI Bleed and it has comparable efficacy to Rockall scoring system post endoscopy.34 (See Table 4)

Table 4 Glasgow-Blatchford scoring system for assessing the severity of Upper GI bleed33

Admission Risk Markers


BUN (mmol/dl)









Hemoglobin (mg/dl) Men







Hemoglobin (mg/dl) Women





Systolic BP mmHg







Other factors

Pulse ≥ 100

Presentation with melena

Presentation with syncope

Hepatic disease

Cardiac failure






A score of zero indicates a low risk patient who should not be admitted and has a sensitivity of 99% in identifying those patient who do not require endoscopy.34

Intravenous PPIs have been proven to reduce rates of re-bleeding and need for surgical intervention, thereby reducing the mortality from peptic ulcer disease 35. Intravenous pantoprazole or omeprazole is administered as an 80-mg bolus followed by a continuous 8-mg/h infusion for 72 hours. Oral PPI can be started after 72 hours if no rebleeding occurs. PPI treatment initiated before endoscopy for upper gastrointestinal bleeding significantly reduces the need for endoscopic therapy. The management of bleeding peptic ulcer is summarized in Figure 1. 38-40

  1. Perforation: Perforation occurs in approximately 2 to 10% of peptic ulcers. 19It usually involves the anterior wall of the duodenum (60%), although it may also occur in antral (20 %) and lesser-curve (20%) gastric ulcers. Perforation of ulcers in children is rare.

  2. Gastric outlet obstruction: Peptic ulcer disease is the underlying cause in less than 5% to 8%of patients presenting with gastric outlet obstruction.

  3. Ulcer penetration: It is the penetration of the ulcer through the bowel wall without free perforation and leakage of luminal contents into the peritoneal cavity.

  4. Mucosa associated lymphoid tissue (MALT) lymphoma: If the cause for peptic ulcer disease is H. pylori then it can also cause MALT (Mucosal Associated Lymphoid Tissue) lymphoma and gastric cancers.

Role of Surgery in Peptic Ulcer Disease

Surgery for peptic ulcer disease is an emergency option only and elective surgery is no longer indicated. Indications for surgery include;

1. Hemodynamic instability due to failure of endoscopic hemostasis.

2. Recurrent bleeding after 2 endoscopic attempts

3. Visible perforation on endoscopy.

Gastric ulcers perforation is treated with omental patch, wedge resection or partial gastrectomy and re-anastomosis. Duodenal ulcer can be treated surgically with Graham’s patch plication.19 Laparoscopic surgery is comparable to open surgery regarding the outcomes but is less painful for the patients.36Open surgery is indicated for large and posterior perforations. The details of these procedures are beyond the scope of this article.

Recommendations for different patient populations

Children: Peptic ulcer disease is rare in children. Most case occurs in age eight to 17 years. Most common etiology is H. pylori infection.19

Elderly: In most cases old age predisposes to worse clinical outcomes in peptic ulcer disease. These patients can present as silent perforation with signs of confusion, restlessness and abdominal distension. Mortality is three times higher as compared to younger adults.19

Pregnancy and Lactation: Symptoms of Peptic ulcer disease may be mild in early pregnancy and may be associated with third trimester vomiting. Diagnostic evaluation by upper GI endoscopy is safe during pregnancy. Proton Pump inhibitors are also considered safe to use. Cytotec (misoprostol) and tetracycline are contraindicated throughout the pregnancy and metronidazole in the first trimester.19 As far as the lactating mothers are concerned medications like Metronidazole and Bismuth are considered unsafe.

Refractory ulcers are mostly associated with poor compliance to medications. Other factors include resistant organism or unrecognized HP infection, continued use of NSAIDS or impaired healing due to dense fibrosis of chronic ulceration. Consider underlying co-morbidities and hypersecretory states such as Gastrinoma, antral G cell hyperplasia and idiopathic hypersecretory duodenal ulcers. Such cases should be referred to a specialist earlier in the course of the disease.

Peptic ulcer disease prevention

NSAID induced ulcers can be prevented by using acid suppressive drugs, misoprostol or COX 2 inhibitors. Lifestyle modifications such as, smoking cessation and alcohol abstinence is recommended.7, 37 H. pylori eradication may prevent NSAID-induced ulcers in NSAID naive patients. In patients receiving long-term NSAID, proton pump inhibitor (PPI) is effective in the prevention of ulcer recurrence and bleeding. 23

Data Source:

A Medline search was performed, which included meta-analyses, randomized controlled trials, clinical trials, and systematic reviews. Key words included Peptic ulcer, diagnosis, management, Helicobacter Pylori; NSAID related ulcer. Cochrane Database of Systematic Reviews, American College of Gastroenterology ACG Site, the Centers for Disease Control and Prevention were also reviewed. Search period: March to June 2012.

Acknowledgments: We thank Oliver Blatchford (National Services Scotland) for the permission to reproduce the Blatchford scoring system.

Conflicts of Interest: None


1. Sonnenberg A., Everhart J.E. , Health impact of peptic ulcer in the United States. Am J Gastroenterol, 1997; 92(4): 614-20.

2. Sung JJ, Kuipers EJ, El-Serag HB. Systematic review: the global incidence and prevalence of peptic ulcer disease. Aliment Pharmacol Ther, 2009; 29(9): 938-46.

3. Anand BS, Raed AK, Malaty HM, Genta RM, Klein PD, Evans DJ Jr., et al. Low point prevalence of peptic ulcer in normal individuals with Helicobacter pylori infection. Am J Gastroenterol, 1996; 91(6): 1112-5.

4. Wang YR, Richter JE, Dempsey DT. Trends and outcomes of hospitalizations for peptic ulcer disease in the United States, 1993 to 2006. Ann Surg, 2010; 251(1): 51-8.

5. Vakil N, Fendrick AM. How to test for Helicobacter pylori in 2005. Cleveland Clinic Journal of Medicine, 2005; 72(2): S8-S13.

6. Malfertheiner P, Chan FK, McColl KE., Peptic ulcer disease. Lancet, 2009; 374(9699): 1449-61.

7. Ma L, Chow JY, Cho CH. Effects of cigarette smoking on gastric ulcer formation and healing: possible mechanisms of action. J Clin Gastroenterol, 1998; 27 Suppl 1: S80-6.

8. Holle GE. Pathophysiology and modern treatment of ulcer disease. Int J Mol Med, 2010; 25(4): 483-91.

9. Ström M, Bodemar G, Gotthard R, Walan A. Duodenal, prepyloric, and combined duodenal/prepyloric ulcer disease: three distinct entities of juxtapyloric ulcer disease? Scand J Gastroenterol, 1986; 21(9): 1105-10.

10. Gisbert JP, Khorrami S, Carballo F, Calvet X, Gene E, Dominguez-Muñoz E. Meta-analysis: Helicobacter pylori eradication therapy vs. antisecretory non-eradication therapy for the prevention of recurrent bleeding from peptic ulcer. Aliment Pharmacol Ther, 2004; 19(6): 617-29.

11. Azagury DE, Abu Dayyeh BK, Greenwalt IT, Thompson CC. Marginal ulceration after Roux-en-Y gastric bypass surgery: characteristics, risk factors, treatment, and outcomes. Endoscopy, 2011; 43(11): 950-4.

12. Ebell MH . Peptic ulcer disease. American family physician, 1992; 46(1): 217-227.

13. Edwards FC, Coghill NF. Clinical manifestations in patients with chronic atrophic gastritis, gastric ulcer, and duodenal ulcer. Q J Med, 1968; 37(146): 337-60.

14. Xia ZW, Ma LL, Yao W. A survey of nonsteroidal anti-inflammatory drugs and aspirin associated peptic ulcer bleeding in hospitals. Zhonghua Nei Ke Za Zhi, 2011. 50(2): 111-5.

15. Chey WD, Wong BC. Practice Parameters Committee of the American College of, American College of Gastroenterology guideline on the management of Helicobacter pylori infection. Am J Gastroenterol, 2007. 102(8): 1808-25.

16. McColl, K.E. Clinical practice. Helicobacter pylori infection. N Engl J Med, 2010; 362(17): 1597-604.

17. Dooley CP, Larson AW, Stace NH, Renner IG, Valenzuela JE, Eliasoph J, et al. Double-contrast barium meal and upper gastrointestinal endoscopy. A comparative study. Ann Intern Med, 1984; 101(4): 538-45.

18. Talley NJ, Vakil N. Practice Parameters Committee of the American College of, Guidelines for the management of dyspepsia. Am J Gastroenterol, 2005; 100(10): 2324-37.

19. Ramakrishnan K, Salinas RC. Peptic ulcer disease. Am Fam Physician, 2007; 76(7):1005-12.

20. Midolo P, Marshall BJ. Accurate diagnosis of Helicobacter pylori. Urease tests. Gastroenterol Clin North Am, 2000; 29(4): 871-8.

21. Malfertheiner P, Mégraud F, O'Morain C, Hungin AP, Jones R, Axon A. et al, Current concepts in the management of Helicobacter pylori infection--the Maastricht 2-2000 Consensus Report. Aliment Pharmacol Ther, 2002; 16(2): 167-80.

22. Bardhan KD, Royston C. Time, change and peptic ulcer disease in Rotherham, UK. Dig Liver Dis, 2008; 40(7): 540-6.

23. Lanza FL, Chan FK, Quigley EM. Guidelines for prevention of NSAID-related ulcer complications. Am J Gastroenterol, 2009; 104(3): 728-38.

24. Gatta L, Vakil N, Leandro G, Di Mario F, Vaira D. Sequential therapy or triple therapy for Helicobacter pylori infection: systematic review and meta-analysis of randomized controlled trials in adults and children. Am J Gastroenterol, 2009; 104(12): 3069-79; quiz 1080.

25. O'Connor HJ, Stewart C, Walsh R, McGee CN, Flynn B. Six-year follow-up after Helicobacter pylori eradication in peptic ulcer disease. Ir J Med Sci, 2001; 170(1):24-7.

26. Buckley M, Culhane A, Drumm B, Keane C, Moran AP, O'Connor HJ et al. Guidelines for the management of Helicobacter pylori-related upper gastrointestinal diseases. Irish Helicobacter Pylori Study Group. Ir J Med Sci, 1996; 165 Suppl 5: 1-11.

27. Food and Drug Administration (FDA) [homepage on internet]. Information for Healthcare Professionals: Update to the labeling of Clopidogrel Bisulfate (marketed as Plavix) to alert healthcare professionals about a drug interaction with omeprazole (marketed as Prilosec and Prilosec OTC) [updated 11/17/2009; cited 2011 June 12]. Available from:

28. Gill JM, Player MS, Metz DC. Balancing the risks and benefits of proton pump inhibitors. Ann Fam Med, 2011; 9(3): 200-2.

29. Food and Drug Administration (FDA) [homepage on internet]. Proton Pump Inhibitor drugs (PPIs): Drug Safety Communication - Low Magnesium Levels Can Be Associated With Long-Term Use. [updated 03/02/2011; cited 2011 June 12]. Available from:

30. Reynolds JC, Schoen RE, Maislin G, Zangari GG. Risk factors for delayed healing of duodenal ulcers treated with famotidine and ranitidine. Am J Gastroenterol, 1994; 89(4): 571-80.
31. Chaparro M, Barbero A, Martín L, Esteban C, Espinosa L, de la Morena F., et al. Prospective evaluation of a clinical guideline recommending early patients discharge in bleeding peptic ulcer. J Gastroenterol Hepatol, 2010; 25(9):1525-9.
32. Rockall TA, Logan RF, Devlin HB, Northfield TC. Risk assessment after acute upper gastrointestinal haemorrhage. Gut, 1996; 38(3):316-21.
33. Blatchford O, Murray WR, Blatchford M. A risk score to predict need for treatment for upper-gastrointestinal haemorrhage. Lancet, 2000; 356(9238): 1318-21.
34. Chandra S, Hess EP, Agarwal D, Nestler DM, Montori VM, Song LM, et al. External validation of the Glasgow-Blatchford Bleeding Score and the Rockall Score in the US setting. Am J Emerg Med, 2012;30(5): 673-9.

35. Tajima A, Koizumi K, Suzuki K, Higashi N, Takahashi M, Shimada T, et al. Proton pump inhibitors and recurrent bleeding in peptic ulcer disease. J Gastroenterol Hepatol, 2008. 23 Suppl 2: p. S237-41.

36. Siu WT, Leong HT, Law BK, Chau CH, Li AC, Fung KH, et al. Laparoscopic repair for perforated peptic ulcer: a randomized controlled trial. Ann Surg, 2002; 235(3):313-9.
37. Ko JK, Cho CH. Alcohol drinking and cigarette smoking: a "partner" for gastric ulceration. Zhonghua Yi Xue Za Zhi (Taipei), 2000;63(12):845-54.
38. Gralnek IM, Barkun AN, Bardou M. Management of Acute Bleeding from a Peptic Ulcer. New England Journal of Medicine, 2008; 359(9): 928-937.

39. Larssen L, Moger T, Bjørnbeth BA, Lygren I, Kløw NE. Transcatheter arterial embolization in the management of bleeding duodenal ulcers: a 5.5-year retrospective study of treatment and outcome. Scand J Gastroenterol, 2008; 43(2): 217-22.

40. Wang HM, Hsu PI, Lo GH, Chen TA, Cheng LC, Chen WC, et al. Comparison of hemostatic efficacy for argon plasma coagulation and distilled water injection in treating high-risk bleeding ulcers. J Clin Gastroenterol, 2009; 43(10):941-5.

The database is protected by copyright © 2016
send message

    Main page