case study on peptic ulcer disease

Case Report: Peptic ulcer disease following short-term use of nonsteroidal anti-inflammatory drugs in a 3-year-old child

Alin Dumitru Ciubotaru Roles: Conceptualization, Project Administration, Resources, Supervision, Writing – Original Draft Preparation Carmen-Ecaterina Leferman Roles: Conceptualization, Writing – Original Draft Preparation, Writing – Review & Editing

peptic ulcer disease, upper gastrointestinal bleeding, nonsteroidal anti-inflammatory drugs, proton pump inhibitors, children

Revised Amendments from Version 1

In the new version, revisions in various sections have been made following the reviewers recommendations. Introduction  – As suggested by the reviewers, regarding clarity of information related to epidemiology, we elaborated more about the indications for endoscopies mentioned in the two studies to which we referred in the second paragraph of the first version. Case presentation – Following the reviewers recommendation, we added hemodynamic parameters at admission (first paragraph), we gave more details of drugs administration (first and second paragraphs), family history and relevant medical history (second paragraph) and nutritional status of the patient (third paragraph). Discussion- We expanded on the accumulation of risk factors (third and fourth paragraphs), including family history, NSAIDs and paracetamol administration in the presented case, referring to the data found in published literature.

See the authors' detailed response to the review by Vera L. Sdepanian See the authors' detailed response to the review by Parijat Ram Tripathi

Introduction

Peptic ulcer disease (PUD) affects 1–2/1000 people annually in the USA, UK and Europe and has been gradually decreasing 1 . An explanation could be the declining prevalence of Helicobacter pylori infection. While the rate of infections is decreasing, the rate of complications remains static, likely due to an aging population which has an elevated usage of ulcerogenic medication 1 .

PUD occurs less frequently in children than adults. Epidemiological data are limited due to the rareness of the disease. A prospective European multicenter study aimed at determining frequency and risk factors of gastric and duodenal ulcers in children who underwent upper gastrointestinal endoscopies for different indications (epigastric or abdominal pain, gastroesophageal reflux disease) 2 . The study showed a frequency of 8.1% of ulcers and/or erosions, occurring mainly during the second decade of development 2 . In the USA, another study reported 17.4% of insured pediatric patients diagnosed as having any upper gastrointestinal ulcer developed peptic ulcer bleeding 3 .

PUD is a heterogenous disease defined by an imbalance between mucosa-protective and aggressive factors in the presence of risk factors including: H. pylori infection, chronic disease (inflammatory bowel disease, rheumatic diseases) and drug use, particularly nonsteroidal anti-inflammatory drugs (NSAIDs) 2 . In practice, NSAIDs are commonly used to manage acute febrile illness or pain in healthy children. One adverse reaction is acute gastrointestinal bleeding associated with short-term NSAIDs use, with a high rate of hospitalization and mortality in developed countries 4 . The adverse effect of short-term utilization of NSAIDs among children and their association with PUD are less clear.

We present a rare case of upper gastrointestinal bleeding following a low dose of ibuprofen in a 3-year-old to underline potentially severe side-effects of short-term NSAIDs use at appropriate doses in children.

Case presentation

A 3-year-old-female, with a family history of peptic ulcers, was admitted with fever, coffee-ground vomiting and abdominal pain, hemodynamically stable (heart rate 128 beats per minute, blood pressure 108/71 mmHg, respiratory rate 28 breaths per minute). The mother stated the patient received two weight-appropriate doses of ibuprofen (two doses of 100 mg -6.66 mg/kg- by mouth, 8 hours apart) and a dose of paracetamol (250 mg - 16.66 mg/kg- by mouth), both administered within an appropriate time interval in the previous 24 hours for fever control.

The patient had a positive medical history of upper respiratory tract infections with febrile seizures and interstitial pneumonia treated with antypiretics and clarithromycin, respectively. In the first days of the upper respiratory infection (5 weeks prior to the bleeding episode) ibuprofen 100 mg -6.66 mg/kg- was administered by mouth every 8 hours for three days and in the next two days two doses a day within an appropriate time interval. For the convulsion episode no antiseizure medication was needed. Also, clarithromycin 7.5 mg/kg/day was administered by mouth for 10 days. The duration of the symptoms was 2 weeks.

The patient is allergic to cephalosporin and amoxicillin/clavulanic acid. No immune deficiency disease was documented.

Clinical examination revealed general malaise, pallor, fever, pharyngotonsillar congestion and productive cough, normal breath sound, a distended and mildly tender abdomen moving normally with respiration and normal stool. The patient weighed 15 Kg (z-score 0.65) at the 72nd percentile and measured 88 cm tall (z-score -1.63) at the 5th percentile for stature. She has a body mass index (BMI) of 19.4 (z-score 2.15), placing the BMI-for-age at the 98th percentile.

Initial laboratory tests indicated anemia with reticulocytosis (Hematocrit 29.7%, Hemoglobin 9.6 g/dl, reticulocytes 3.6%, corrected reticulocyte count 3.24) and lower total protein (5.52 g/dL). Remaining laboratory results were normal, including coagulation tests.

Soon after hospitalization, the patient had a second episode of coffee-ground vomiting.

An upper digestive endoscopy with biopsy was performed revealing a non-bleeding gastric ulcer at 2 cm from pylorus ( Figure 1 ). H. pylori gastric biopsy testing was negative.

Figure 1. Endoscopic imaging.

This shows a non-bleeding gastric ulceration measuring 2.5 × 2 cm with edematous rim located 2 cm from the pyloric ring; pale gastric mucosa, fluid stasis and food debris; snake skin appearance of gastric mucosa in the fundus.

Based on this data, a diagnosis was made of NSAID-induced gastric ulcer, causing upper gastrointestinal bleeding.

During hospitalization, perfusion with glucose and electrolytes was administered in order to compensate for fluid loss. The patient was treated with a proton pump inhibitor (esomeprazole 10 mg/day - 0.66 mg/kg/day) for 2 months.

There were no further gastrointestinal symptoms. Hemoglobin values returned to normal, indicating resolution of gastrointestinal bleeding and the report of the endoscopy performed at the end of the treatment period confirmed the healing of the gastric ulceration area.

Upper gastrointestinal bleeding in a 3-year-old following short-term NSAIDs use is an uncommon presentation. Similar cases 5 have been reported in literature, but the adverse effects of short-term NSAIDs use among children and their association with PUD is not completely understood. However, some studies offer compelling data indicating certain risk factors, primarily: the child’s age 2 , NSAIDs consumption 2 , 4 , 6 , 7 and H. pylori infection 2 , 6 – 8 .

PUD seems to primarily affect patients between 10–20 years old 2 . A retrospective cohort study reported a lower median age for those with gastric ulcers, than those with duodenal ulcers 8 .

The second important factor is NSAIDs consumption. The probability of PUD increases with the duration of therapy, dose and presence of risk factors, including positive familial history or drugs coadministration 7 , 9 . Thus, despite a low dose of ibuprofen, the gastric ulcer (GU) in this case can be explained in part by a positive family history and association with a dose of paracetamol. A joint effect of paracetamol (a dosage higher than 2g) combined with NSAIDs was reported in adults that had both compounds prescribed together 10 . Conversely, the risk for gastrointestinal ulcers and ulcer complications due to normal paracetamol intake has not been yet supported by available biological and clinical data.

The accumulation of more risk factors, like positive family history, NSAID administration or H. Pylori infection in pediatric population affected by PUD, has been well documented. The father of the patient was diagnosed with PUD, but was unable to confirm whether he was H. Pylori positive.

Moreover, some studies conclude that short-term NSAIDs use is highly correlated with GU 6 . The association between short-term NSAIDs use and proton pump inhibitors (PPIs) can theoretically reduce the risk of upper gastrointestinal bleeding in children. Although coadministration of NSAIDs and PPIs is considered safe to reduce adverse gastrointestinal effects in adults 11 , there is not sufficient data about this drugs association in the prevention of short-term NSAIDs-PUDs in children.

The third important risk factor in PUD, H. pylori infection, was negative in our case. Some studies suggest a weaker association between H. pylori and PUD in children as compared with adults 2 , 12 . However, this infection is a well-recognized cause of chronic gastritis and plays an important role in the pathogenesis of PUD in children 13 .

Patients who develop gastrointestinal bleeding caused by NSAIDs-associated ulcers should discontinue use. Therapeutic strategies in these cases depend on the severity of presentation. Pharmacologic, endoscopic and surgical techniques have been developed to achieve hemostasis. In cases of massive bleeding, immediate endoscopic or surgical intervention is required. Scoring systems for upper gastrointestinal bleeding in children, laboratory tests and blood transfusion requirements are still under development 14 – 16 . In the present case, clinical presentation with two episodes of isolated hematemesis (coffee-ground vomiting) and endoscopic examination findings (non-bleeding gastric ulcer) correlated with laboratory tests indicated pharmacologic management.

Short term NSAIDs use in appropriate doses, commonly prescribed to control fever in children, can lead to PUD. Before administration, risk factors such as other antipyretic medication use, or a suggestive familial history must be considered. Doctors should inform caregivers of the risks involved and encouraging limited NSAIDs use.

Data availability

All data underlying the results are available as part of the article and no additional source data are required.

Written informed consent for the publication of this case report was obtained from the parents of the patient.

• 1.   Sverdén E, Agréus L, Dunn JM, et al. : Peptic ulcer disease. BMJ. 2019; 367 : l5495. PubMed Abstract | Publisher Full Text
• 2.   Kalach N, Bontems P, Koletzko S, et al. : Frequency and risk factors of gastric and duodenal ulcers or erosions in children: a prospective 1-month European multicenter study. Eur J Gastroenterol Hepatol. 2010; 22 (10): 1174–1181. PubMed Abstract | Publisher Full Text
• 3.   Brown K, Lundborg P, Levinson J, et al. : Incidence of peptic ulcer bleeding in the US pediatric population. J Pediatr Gastroenterol Nutr. 2012; 54 (6): 733–736. PubMed Abstract | Publisher Full Text
• 4.   Grimaldi-Bensouda L, Abenhaim L, Michaud L, et al. : Clinical features and risk factors for upper gastrointestinal bleeding in children: a case-crossover study. Eur J Clin Pharmacol. 2010; 66 (8): 831–837. PubMed Abstract | Publisher Full Text
• 5.   Berezin SH, Bostwick HE, Halata MS, et al. : Gastrointestinal bleeding in children following ingestion of low-dose ibuprofen. J Pediatr Gastroenterol Nutr. 2007; 44 (4): 506–508. PubMed Abstract | Publisher Full Text
• 6.   Huang SC, Sheu BS, Lee SC, et al. : Etiology and treatment of childhood peptic ulcer disease in taiwan: a single center 9-year experience. J Formos Med Assoc. 2010; 109 (1): 75–81. PubMed Abstract | Publisher Full Text
• 7.   Cardile S, Martinelli M, Barabino A, et al. : Italian survey on non-steroidal anti-inflammatory drugs and gastrointestinal bleeding in children. World J Gastroenterol. 2016; 22 (5): 1877–1883. PubMed Abstract | Publisher Full Text | Free Full Text
• 8.   Roma E, Kafritsa Y, Panayiotou J, et al. : Is peptic ulcer a common cause of upper gastrointestinal symptoms? Eur J Pediatr. 2001; 160 (8): 497–500. PubMed Abstract | Publisher Full Text
• 9.   Autret-Leca E, Bensouda-Grimaldi L, Maurage C, et al. : Upper gastrointestinal complications associated with NSAIDs in children. Therapie. 2007; 62 (2): 173–176. PubMed Abstract | Publisher Full Text
• 10.   García Rodríguez LA, Hernández-Díaz S: Relative Risk of Upper Gastrointestinal Complications among Users of Acetaminophen and Nonsteroidal Anti-Inflammatory Drugs. Epidemiology. 2001; 12 (5): 570–6. PubMed Abstract | Publisher Full Text
• 11.   Gwee KA, Goh V, Lima G, et al. : Coprescribing proton-pump inhibitors with nonsteroidal anti-inflammatory drugs: risks versus benefits. J Pain Res. 2018; 11 : 361–374. PubMed Abstract | Publisher Full Text | Free Full Text
• 12.   Elitsur Y, Lawrence Z: Non- Helicobacter pylori related duodenal ulcer disease in children. Helicobacter. 2001; 6 (3): 239–243. PubMed Abstract | Publisher Full Text
• 13.   Blecker U, Gold BD: Gastritis and peptic ulcer disease in childhood. Eur J Pediatr. 1999; 158 (7): 541–546. PubMed Abstract | Publisher Full Text
• 14.   Nasher O, Devadason D, Stewart RJ: Upper Gastrointestinal Bleeding in Children: A Tertiary United Kingdom Children’s Hospital Experience. Children (Basel). 2017; 4 (11): 95. PubMed Abstract | Publisher Full Text | Free Full Text
• 15.   Thomson MA, Leton N, Belsha D: Acute upper gastrointestinal bleeding in childhood: development of the Sheffield scoring system to predict need for endoscopic therapy. J Pediatr Gastroenterol Nutr. 2015; 60 (5): 632–636. PubMed Abstract | Publisher Full Text
• 16.   Garber A, Jang S: Novel Therapeutic Strategies in the Management of Non-Variceal Upper Gastrointestinal Bleeding. Clin Endosc. 2016; 49 (5): 421–424. PubMed Abstract | Publisher Full Text | Free Full Text

Comments on this article Comments (0)

Open peer review.

• In paragraph 3 of the Discussion section, the authors pointed out that positive family history of peptic ulcer and association with a dose of paracetamol could explain the gastric ulcer. First of all, the positive family history should be clarified, and secondly what should be the importance of using one dose of paracetamol.  
• The authors should emphasize all drugs used during at least in the last month because the patient “had a positive medical history of upper respiratory tract infections with febrile seizures and interstitial pneumonia treated with antipyretics and clarithromycin, respectively”.  
• The patient was treated with a proton pump inhibitor (esomeprazole 10 mg/day) for two months. Although there were no further gastrointestinal symptoms, and hemoglobin values returned to normal, there is no assurance that the ulcer improved. Therefore, the authors have to explain if another upper endoscopy was done and justify the reason do not perform it.

Is the background of the case’s history and progression described in sufficient detail?

Are enough details provided of any physical examination and diagnostic tests, treatment given and outcomes?

Is sufficient discussion included of the importance of the findings and their relevance to future understanding of disease processes, diagnosis or treatment?

Is the case presented with sufficient detail to be useful for other practitioners?

Competing Interests: No competing interests were disclosed.

Reviewer Expertise: Pediatric Gastroenterologist

• In paragraph 3 of the Discussion section, the authors pointed out that positive family history of peptic ulcer and association with a dose of paracetamol could explain the gastric ulcer. First of all, the positive family history should be clarified, and secondly what should be the importance of using one dose of paracetamol.
• The authors should emphasize all drugs used during at least in the last month because the patient “had a positive medical history of upper respiratory tract infections with febrile seizures and interstitial pneumonia treated with antipyretics and clarithromycin, respectively”.
• The patient was treated with a proton pump inhibitor (esomeprazole 10 mg/day) for two months. Although there were no further gastrointestinal symptoms, and hemoglobin values returned to normal, there is no assurance that the ulcer improved. Therefore, the authors have to explain if another upper endoscopy was done and justify the reason do not perform it.  
• Respond or Comment
• COMMENT ON THIS REPORT
• In the introduction, the second paragraph, “An extensive study estimated the prevalence of ulcers and/or erosions in European children at 8.1%, occurring mainly during the second decade of development. In the USA, 17.4% of pediatric patients are diagnosed with upper gastrointestinal ulcers each year.” In both the studies endoscopies were performed for specific indications rather than in the general pediatric population. Please mention the indications for better clarity of information.  
• What were the hemodynamic parameters of the patient at admission?  
• What tests were performed for H. pylori in the patient?  
• Please give details of family history of peptic ulcer disease (PUD) and how was it diagnosed? Was that person H. pylori -positive?  
• In the discussion, the second paragraph, “A retrospective cohort study reported a lower median age for those with gastric ulcers, than those with duodenal ulcers. Our patient confirms this ratio.” This is not right to say that this case report confirms this ratio. Please change or remove it.  
• How do authors think that the presence of positive family history (in absence of H. pylori ) and paracetamol intake can explain the presence of gastric ulcer even with a low dose of NSAID? Please explain in more detail.  
• Why a repeat endoscopy was not performed to confirm the healing of gastric ulcer?
• Please mention doses (in per kg) and interval of ibuprofen used in the patient.  
• Please do not write the brand name until significant or important (e.g. Augmentin).  
• Duration and severity of respiratory tract infection are not mentioned. Please give details.  
• The patient’s weight and height interpretation should be mentioned as per Z score.  
• Mention corrected reticulocyte count.  
• How laboratory reports (hemoglobin, hematocrit, total protein, and reticulocyte count) are suggesting bleeding characteristics? Please explain.  
• Please mention the dose of esomeprazole in mg/kg/day along with the dose written in case details.  

Reviewer Expertise: Pediatric gastroenterology and hepatology

• In the introduction, the second paragraph, “An extensive study estimated the prevalence of ulcers and/or erosions in European children at 8.1%, occurring mainly during the second decade of development. In the USA, 17.4% of pediatric patients are diagnosed with upper gastrointestinal ulcers each year.” In both the studies endoscopies were performed for specific indications rather than in the general pediatric population. Please mention the indications for better clarity of information.
• What were the hemodynamic parameters of the patient at admission?
• What tests were performed for H. pylori in the patient?
• Please give details of family history of peptic ulcer disease (PUD) and how was it diagnosed? Was that person H. pylori positive?
• In the discussion, the second paragraph, “A retrospective cohort study reported a lower median age for those with gastric ulcers, than those with duodenal ulcers. Our patient confirms this ratio.” This is not right to say that this case report confirms this ratio. Please change or remove it.
• How do authors think that the presence of positive family history in absence of H. pylori ) and paracetamol intake can explain the presence of gastric ulcer even with a low dose of NSAID? Please explain in more detail.
• Please mention doses (in per kg) and interval of ibuprofen used in the patient.
• Please do not write the brand name until significant or important (e.g. Augmentin).
• Duration and severity of respiratory tract infection are not mentioned. Please give details.
• The patient’s weight and height interpretation should be mentioned as per Z score.
• Mention corrected reticulocyte count.
• How laboratory reports (hemoglobin, hematocrit, total protein, and reticulocyte count) are suggesting bleeding characteristics? Please explain.
• Please mention the dose of esomeprazole in mg/kg/day along with the dose written in case details.

Reviewer Status

Alongside their report, reviewers assign a status to the article:

Reviewer Reports

• Parijat Ram Tripathi , Ankura Hospital for Women and Children, Hyderabad, India
• Vera L. Sdepanian , Universidade Federal de São Paulo, São Paulo, Brazil

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Peptic Ulcer

Case Presentation

Harold, a fifty-eight year old grocery store manager, had recently been waking up in the middle of the night with abdominal pain. This was happening several nights a week. He was also experiencing occasional discomfort in the middle of the afternoon. Harold decided to schedule an appointment with his physician.

The doctor listened as Harold described his symptoms and then asked Harold some questions. He noted that Harold's appetite had suffered as a result of the pain he was experiencing and as a result of the fear that what he was eating may be responsible for the pain. Otherwise, Harold seemed fine.

The doctor referred Harold to a physician that specialized in internal medicine and had Harold make an appointment for a procedure called an endoscopy. The endoscopy was performed at a hospital later that week. During the procedure, a long, thin tube was inserted into Harold's mouth and directed into his digestive tract. The end of the tube was equipped with a light source and a small camera which allowed the doctor to observe the interior of Harold's stomach. The endoscope was also equipped with a small claw-like structure that the doctor could use in order to obtain a small tissue sample from the lining of Harold's stomach, if required.

The endoscopy revealed that Harold had a peptic ulcer. Analysis of a tissue sample taken from the site showed that Harold also had an infection that was caused by Helicobacter pylori bacteria. The doctor who performed the endoscopy gave Harold prescriptions for two different antibiotics and a medication that would decrease the secretion of stomach acid. The doctor also instructed Harold to schedule an appointment for another endoscopy procedure in 6 months.

Case Background

A peptic ulcer is a sore that occurs in the lining of a part of the gastrointestinal tract that is exposed to pepsin and acid secretions. Most peptic ulcers occur in the lining of the stomach or duodenum. 90% of all duodenal ulcers and 80% of all gastric ulcers are caused by H. pylori infection. Most of the remaining peptic ulcers are caused by long-term usage of certain anti-inflammatory medications like aspirin.

There is still some question as to how H. pylori is spread. However, H. pylori has been identified in the saliva of infected individuals and may be spread via this fluid. H. pylori bacteria have the ability to survive the acid environment in the stomach because they produce enzymes that neutralize stomach acids. They also have the ability to move through the mucous membrane lining the stomach or duodenum and take up residence in the underlying connective tissue. The damage to the mucous membrane that results from a H. pylori infection allows pepsin and hydrochloric acid to further damage the wall of the stomach or duodenum. The sore that results is the peptic ulcer.

Describe the functions of the following components of gastric juice.

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Peptic Ulcer Case Study

Nursing 7450 Pathophysiology of Altered Health States

Dr. Amy Mackos, Dr. Kelly Casler, and Dr. Lee Cordell

• Hsiaochi (Chi) Chang
• Stephine Burrows

Our rationale for choosing this condition

We chose Peptic Ulcer disease due to the fact that it’s commonly seen among the patients taking NSAIDs and Aspirin; therefore, we anticipate seeing this condition frequently.

(Picture retrieved from https://www.webmd.com/digestive-disorders/ss/slideshow-visual-guide-to-stomach-ulcers)

CASE STUDY IN GASTROENTEROLOGY & HEPATOLOGY: An Uncommon Complication of Peptic Ulcer Disease

Affiliation.

• 1 Department of Internal Medicine, University of Alabama at Birmingham, Montgomery, Alabama.
• PMID: 24987320
• PMCID: PMC4076883

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Peptic Ulcer Disease and Helicobacter pylori infection

Mechu narayanan , md, kavya m reddy , md, elizabeth marsicano , md.

• Author information
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Contact: [email protected]

Corresponding author.

Peptic ulcer disease (PUD) is a common condition that both primary care providers and gastroenterologists encounter. Symptoms of peptic ulcer disease are variable and may include abdominal pain, nausea, vomiting, weight loss and bleeding or perforation with complicated disease. Identifying the risk factors and mechanisms that lead to the development of PUD helps to understand the approach behind diagnostic and treatment strategies.

Peptic ulcers are frequently encountered in the primary care setting and understanding associated risk factors is key to disease prevention and management.

Definition and Epidemiology

Peptic ulcers are acid-induced lesions found in the stomach and duodenum characterized by denuded mucosa with the defect extending into the submucosa or muscularis propria. 1 Lesions that do not reach this depth are called erosions ( Figure 1 ). In the United States, the prevalence of self-reported physician-diagnosed peptic ulcer disease was 10% in 1990, and the approximate incidence is about 500,000 new cases per a year. 2 , 3 Overall, however, the risk of mortality and need for hospitalizations due to PUD has been decreasing worldwide. This is most likely secondary to a decline in Helicobacter pylori (H. pylori) infections due to treatment and improved hygiene. 4 , 5 Increased use of prescription and over-the-counter acid-suppressing medications and greater caution with non-steroidal anti-inflammatory drugs (NSAIDs) may account partially for this trend as well. 5 , 6

Peptic erosions and ulcers in the stomach and duodenum. A. small erosions in the gastric antrum. Mucosal breaks with focal hemorrhage are identified by the arrows. B. Benign peptic ulcer in the body of the stomach (arrow). C. Duodenal erosions identified by focal areas of adherent exudate (arrows). D. Duodenal ulcer. The mucosal defect has depth and the margin is identified by the arrow. The surrounding mucosa is edematous.

Etiology and Pathophysiology

The main risk factors for PUD are H. pylori and NSAID use, however not all individuals infected with H. pylori or taking NSAIDs develop PUD. 1 , 7 Almost half of the world’s population is colonized by H. pylori. 8 The organism is usually acquired in childhood and persists until treated. Risk factors for acquiring the infection include a lower socioeconomic status and unsanitary conditions or crowding. The prevalence of H. pylori is higher in developing countries and more common in certain ethnicities. In the last five years in the United States, there has been a decline in the prevalence of H.pylori in all ages. Yet, there are differences based on ethnicity with rates of infection that are over 60% in Mexican Americans versus 30% in the non-Hispanic white population. 9

H. pylori causes an inflammatory response with neutrophils, lymphocytes, plasma cells, and macrophages within the mucosal layer and causes epithelial cell degeneration and injury. Gastritis is usually more severe in the antrum, with little or no inflammation in the corpus. All patients found to have peptic ulcers should be tested for H. pylori. There are both invasive and noninvasive methods for testing that are summarized in Table 1 . Of all the noninvasive methods, the urea breath test and stool antigen tests are the most feasible and are more accurate than serologic testing. 10 Although invasive, endoscopy allows for biopsy and includes a variety of methods for testing such as histology, culture, or rapid urease test. All methods other than serology are affected by use of acid-suppressing medications such as proton pump inhibitors and may produce false negatives.

Diagnostic Tests for H. pylori

PPI, proton pump inhibitor

NSAIDs are widely used for a variety of conditions to help reduce pain and inflammation; however, many users develop gastrointestinal side effects. NSAIDs account for over 90% of all ulcers and approximately 25% of NSAID users will develop peptic ulcer disease. 11 Aspirin users are also twice as likely to develop peptic ulcers as the general population. 12 , 13 Others develop a milder degree of topical injury, which is seen as mucosal hemorrhages and erosions and are referred to as NSAID gastropathy. These multiple small erosions are usually located in the antrum but may also be seen in the body.

NSAIDs induce mucosal injury by several mechanisms. The majority of NSAIDs are weak acids and become protonated and cross lipid membranes to enter epithelial cells when exposed to acidic gastric juice (pH 2). In the epithelial cell (pH 7.4), the NSAID ionizes and releases its H+ and cannot cross the lipid membrane and thus becomes trapped. This leads to uncoupling of oxidative phosphorylation, leading to decreased mitochondrial energy production, reduced cellular integrity, and increased cellular permeability. This can result in a topical injury and rapid epithelial cell death, superficial hemorrhage, and erosions. 14

The other major mechanism by which NSAIDs cause mucosal injury is by inhibition of cyclooxygenase-1 (COX-1), which is responsible for prostaglandin synthesis. Prostaglandins increase secretion of bicarbonate and mucous, increase mucosal blood flow, and inhibit cell proliferation to maintain the mucosal barrier. 5 Aspirin acetylates cyclooxygenase and irreversibly inhibits the enzyme, whereas NSAIDs inhibit the enzyme reversibly in a concentration-dependent manner. Among these pathophysiologic responses, reduction in blood flow is thought to be the primary mechanism responsible for NSAIDs-induced injury. 14

Two isoforms of COX exist: COX-1 is primarily responsible for prostaglandin synthesis in the GI tract, whereas COX-2 is responsible for prostaglandin synthesis at sites of inflammation. NSAIDs such as ibuprofen, naproxen, aspirin, and indomethacin inhibit both COX-1 and COX-2 and are classified as non-selective. COX-2 specific NSAIDs such as celocoxib or rofecoxib inhibit COX-2 without inhibiting COX-1, making them potentially safer in the GI tract. Endoscopic studies of patients taking COX-2 inhibitors have demonstrated lower incidences of ulceration of approximately 3–5% when compared to traditional NSAIDs which have a 20–40% incidence. However, COX-2 selective NSAIDs have been shown to increase risk of cardiac disease and many have been taken off the market.

Those who are at highest risk for NSAID-induced ulcers are patients with a history of peptic ulcers or hemorrhage, those concomitantly using steroids or anticoagulants, anyone over the age of 65 and those taking high doses or combinations of more than one NSAID (including low dose aspirin). If these patients need multiple agents, they should be started on treatment to prevent ulcers. Furthermore, using medications such as selective serotonin-reuptake inhibitors, corticosteroids, aldosterone antagonists, or anticoagulants increases the risk of bleeding. 15 Older age and a greater number of comorbidities also affect the clinical course of patients with H. pylori and NSAIDs. 16 , 17 Interaction between H. pylori and NSAIDs is controversial but current American College of Gastroenterology guidelines recommend testing and treating for H. pylori if an individual is to start long-term NSAIDs and testing could be considered in those taking long term low dose aspirin as well. 5 , 18

About a fifth of PUD cases are not related to H. pylori , NSAIDs or aspirin, but the accuracy of this value has been challenged due to false negative H. pylori testing or accidental (or underreported) NSAID ingestion. 19 , 20 This idiopathic PUD may be due to an imbalance between factors that contribute to mucosal integrity and aggressive insults, including a hypersecretory status. Other etiologies for PUD include ischemia causing stress ulcers, medications (steroids, alendronate, potassium chloride, and chemotherapeutic agents), viral infections (CMV, HSV), gastric bypass surgery, metabolic disturbances, radiotherapy, histamine, eosinophilic infiltration, and basophilia. 5 , 21

Diagnosis begins with clinical suspicion when patients present with symptoms such as epigastric abdominal pain, burning, post-prandial fullness, or early satiety. 1 Classically, patients with duodenal ulcers complain of worsening abdominal pain on an empty stomach and describe hunger or abdominal pain two to three hours after meals or at night. In contrast, patients with gastric ulcers report nausea, vomiting, weight loss and post-prandial abdominal pain. Elderly patients are often minimally symptomatic and some patients with untreated PUD may have intermittent symptoms due to spontaneous healing and then relapse due to persistence of risk factors, such as continued NSAIDs use or H. pylori infection. 5

If clinical symptoms suggest possible peptic ulcer disease and no alarm symptoms are noted, empiric treatment with anti-secretory therapy can be started. Furthermore, since H. pylori is a common cause of PUD, a test and treat strategy with a non-invasive test for H. pylori (stool antigen or urea breath test) is recommended in patients less than 55 years of age without alarm features, in geographic regions were gastric cancer is uncommon and the prevalence of H. pylori is greater than 20%. 22 In older patients and those with alarm symptoms, endoscopy is recommended to establish a diagnosis. Alarm symptoms include GI bleeding, weight loss, early satiety, dysphagia or odynophagia, family history of upper GI malignancy, iron deficiency anemia or new upper GI symptoms in patients older than 55. 23 Esophagogastroduodenoscopy (EGD) or upper endoscopy is the gold standard for the diagnosis of PUD. It is can be used to detect H. pylori with gastric biopsies and can also rule out malignancy.

Treatment is usually directed at identifying the factors that lead to PUD. For H. pylori -associated PUD, eradication alone will lead to ulcer healing and prevent further mucosal injury. However, due to rising antibiotic resistance in H. pylori , treatment has become more difficult ( Figure 2 ). First line therapy for H. pylori eradication includes a proton pump inhibitor (PPI), clarithromycin and amoxicillin or metronidazole (for penicillin-allergic patients) for seven to 14 days. 24 PPIs work synergistically with antibiotics to eradicate H. pylori. 25 Due to increasing antibiotic resistance, the efficacy of triple therapy has fallen below 70% in many countries. 24 As susceptibility testing is often not available in clinical practice, clarithromycin-based regimens should be avoided when local clarithromycin resistance rates are greater than 15%. 24 Clarithromycin resistance rates are high (>20%) across the United States. 26 When using clarithromycin-based triple therapy, eradication rates can be increased with use of high dose PPI and by extending the duration of treatment from seven to 14 days. 5 For areas with high clarithromycin resistance, bismuth-containing quadruple therapy with a PPI, bismuth, tetracycline and a nitroimidazole (metronidazole or tinidazole) for 14 days or PPI, clarithromycin, amoxicillin, and a nitroimidazole for 14 days is the preferred as first line treatment. 18 There have been issues with the cost and availability of tetracycline and the data have been mixed on whether doxycycline can be substituted. The regimens discussed above yield eradication rates greater than 90%. 5

Multiple treatment regimens for H. pylori can be considered and the standard treatment duration is 14 days. The doses of the drugs used are: proton pump inhibitor (PPI, standard or double dose), clarithromycin 500 mg BID, amoxicillin 1 gm BID, bismuth subsalicylate 300 mg QID, metronidazole 500 mg TID, tetracycline 500 mg QID, levofloxacin 500 mg QD, rifabutin 300 mg QD.

All patients treated for H. pylori, should be tested to confirm eradication at least four weeks after completing therapy. Second line therapy should be prescribed if a first line regimen fails ( Figure 2 ) and should not include repeating metronidazole or clarithromycin. 18 Furthermore, susceptibility testing should be considered after two treatment failures or after one treatment failure when endoscopy is performed (for other reasons such as follow up of gastric ulcer). If culture for H. pylori is not available to evaluate for resistance or after three recommended treatments have failed, rifabutin-based triple therapy (PPI, rifabutin, and amoxicillin) for 10 days can be considered. If symptoms do not improve after H. pylori eradication, endoscopy should be pursued if not already performed.

In NSAID- or aspirin-associated PUD, ulcers heal more than 85% of the time with 6–8 weeks of PPI therapy if the offending agent is discontinued. Ulcer healing is still attainable but delayed with continued NSAIDs use. Anti-secretory therapy can be started for prevention of PUD in patients on aspirin. Although PPIs, H2 blockers, sucralfate, and misoprostol can all be considered to treat NSAID-associated PUD, PPIs are far more effective than other agents. 25 Sucralfate is effective for treating NSAID-associated duodenal ulcers but not for the treatment or prevention of NSAID-associated gastric ulcers. In addition to its poor efficacy, misoprostol is often limited by its side effect profile, which includes gastrointestinal upset and abortifacient reactions. In cases of refractory ulcers, both drug compliance with PPI use and inadvertent use of NSAIDs should be explored. 27 All gastric ulcers require repeat endoscopy in six to eight weeks to evaluate for healing. If a gastric ulcer is not healed, biopsies must be taken at time of repeat endoscopy to rule out gastric cancer. For refractory ulcers, doubling the PPI dose can be recommended for six to eight weeks, although the evidence supporting this is weak. Furthermore, evaluating for false-negative H. pylori testing (via serology), malignancies, infections, Crohn’s disease, vasculitis, upper abdominal radiotherapy, cocaine use, and Zollinger-Ellison syndrome should be considered for ulcers that have been treated appropriately and have not healed. 5

Complications

The complications of PUD include unabated symptoms, bleeding, perforation, penetration, gastric outlet obstruction, and gastric malignancy (adenocarcinoma and MALT lymphoma). Bleeding is the most common complication and occurs in about 15–20% of patients. PUD accounts for a large proportion (about 40–60%) of acute upper GI bleeding. 28 Upper GI bleeding is an emergency which requires patients to be evaluated and triaged immediately. Alerting a GI consultant early in the evaluation of a bleeding patient is helpful to coordinate care for critically ill patients. The Glasgow-Blatchford score and Rockall scores have been used for risk stratification. 29 Appropriate resuscitation with IV fluids and blood products to maintain a goal hemoglobin above 7 is vital in management. 30

Intravenous PPI therapy should be started on all patients considered to have an upper GI bleed immediately on presentation, as IV PPIs reduce the risk of finding high-risk stigmata during endoscopy and in accordance, re-bleeding risk and need for surgery as well. 25 They work by increasing intra-gastric pH, encouraging platelet aggregation and providing clot stability. Prokinetic agents such as erythromycin or metoclopramide can also be considered to improve endoscopic visualization and diagnostic yield. 31 Early endoscopy which is ideally performed within 24 hours provides both prognostic and therapeutic results. After endoscopy, it is recommended to either start or continue PPI (IV if high-risk stigmata of bleeding are found). Studies have shown that IV PPI given twice daily is as efficacious as a continuous PPI drip 32 , 33 with significant cost savings. Recurrent bleeding is associated with high mortality and may require repeat endoscopy, angiographic embolization by interventional radiology, or surgery.

If patients have coagulopathy due to warfarin, reversal agents such as vitamin K, fresh frozen plasma (FFP), prothrombin complex concentrates (PCC) or recombinant factor VIIa should be considered as a part of management. These agents need to be used judiciously however, as they can have adverse effects. For instance, high doses of vitamin K can cause prolongation of the time to achieve therapeutic warfarin levels after bleeding stops and therapeutic anticoagulation needs to be restarted (e.g., in the setting of mechanical heart valves). FFP has a risk of causing volume overload and recombinant factor VIIa has an increased risk of thrombosis and is expensive. Novel oral anticoagulants (NOACs) are being used more commonly and these agents cannot be reversed with vitamin K. Compared to warfarin, the NOACs rivaroxaban and dabigatran increase the risk of GI bleeding although apixaban does not seem to have an increased risk of GI bleeding. 34 Activated charcoal can be given within four hours of ingestion to treat a NOAC overdose. Hemodialysis and idarucizumab can be used for life-threatening bleeding associated with dabigatran. 5 Anticoagulant and antiplatelet agents can be restarted once hemostasis has been achieved with the timing dependent on the urgency to restore anticoagulation. Patients on dual antiplatelet therapy after placement of drug-eluting stents should avoid stopping both agents, as they are at high risk for in-stent thrombosis. For patients on aspirin for cardiovascular disease, aspirin should be resumed soon (between one to three days, within seven days) after hemostasis is achieved. 31 For patients with a high risk of thrombosis (such as mechanical mitral valve) bridging with low molecular weight heparin is recommended while warfarin levels are sub-therapeutic.

Perforation is the next most common complication of PUD, occurring in 2–10% of peptic ulcers, and can present as sudden severe abdominal pain with hemodynamic instability or shock. 35 Physical exam findings may include initially hyperactive bowel sounds that can diminish and progress to a rigid abdomen with rebound, suggesting peritonitis. The presence of free air on imaging is supportive of this diagnosis and endoscopy should be avoided in this setting. Surgery is usually the treatment of choice for a perforated peptic ulcer. 3 In patients who are poor surgical candidates and with perforation for more than 24 hours that is contained (based on water soluble contrast studies), medical treatment with nasogastric (NG) suction, IV fluids, antibiotics and acid suppression is an option. Penetrating ulcers can also erode into nearby organs such as pancreas, liver, bile duct, or colon.

Gastric outlet obstruction (GOO) is another complication of PUD and can present with early satiety, bloating, weight loss, indigestion, nausea and vomiting. On physical exam, a succussion splash may be heard due to trapped air and fluid in the stomach. Ulcers that manifest with GOO are often located in the pyloric channel or duodenal bulb. Medical therapy usually involves NG suction and anti-secretory therapy. Endoscopic balloon dilation of pylorus or surgery are options to relieve chronic obstruction. 35

PUD is a disease with decreasing clinical burden due to the decline in H. pylori infections, as well as increased accessibility to anti-secretory therapy and more judicious use of NSAIDs. However, due to its continued high lifetime prevalence and varied clinical presentation, recognition and appropriate management of PUD are key to avoid and minimize significant complications. Testing and treating H. pylori as well as limiting mucosal injury caused by NSAIDs (via concurrent PPI prophylaxis or choosing COX-2 selective NSAIDs if available) are the strategies to consider when evaluating PUD. Resuscitation, anti-secretory therapy, endoscopy and management of antithrombotic agents are the key steps in treatment of PUD bleeding, which is the most common complication.

Mechu Narayanan, MD, (top left), and Kavya M. Reddy, MD, (top right), are Fellows, and Elizabeth Marsicano, MD, (bottom), is an Assistant Professor of Internal Medicine in the Division of Gastroenterology and Hepatology, Saint Louis University School of Medicine, St. Louis, Mo.

None reported.

• 1. Feldman M, Friedman LS, Brandt LJ. Sleisenger and Fordtran’s gastrointestinal and liver disease : pathophysiology/diagnosis/management. Tenth edition ed. 2 volumes. Philadelphia, PA: Saunders/Elsevier; 2016. p. xxxi.p. 2369.p. 2389. [ Google Scholar ]
• 2. Sonnenberg A, Everhart JE. The prevalence of self-reported peptic ulcer in the United States. Am J Public Health. 1996;86:200–205. doi: 10.2105/ajph.86.2.200. [ DOI ] [ PMC free article ] [ PubMed ] [ Google Scholar ]
• 3. Ramakrishnan K, Salinas RC. Peptic ulcer disease. Am Fam Physician. 2007;76:1005–1012. [ PubMed ] [ Google Scholar ]
• 4. Sonnenberg A. Review article: historic changes of Helicobacter pylori-associated diseases. Aliment Pharmacol Ther. 2013;38:329–342. doi: 10.1111/apt.12380. [ DOI ] [ PubMed ] [ Google Scholar ]
• 5. Lanas A, Chan FKL. Peptic ulcer disease. The Lancet. 2017;390:613–624. doi: 10.1016/S0140-6736(16)32404-7. [ DOI ] [ PubMed ] [ Google Scholar ]
• 6. Lanas-Gimeno A, Lanas A. Risk of gastrointestinal bleeding during anticoagulant treatment. Expert Opinion on Drug Safety. 2017;16:673–685. doi: 10.1080/14740338.2017.1325870. [ DOI ] [ PubMed ] [ Google Scholar ]
• 7. Zhang BB, Li Y, Liu XQ, Wang PJ, Yang B, Bian DL. Association between vacA genotypes and the risk of duodenal ulcer: a meta-analysis. Mol Biol Rep. 2014;41:7241–7254. doi: 10.1007/s11033-014-3610-y. [ DOI ] [ PubMed ] [ Google Scholar ]
• 8. Papatheodoridis GV, Archimandritis AJ. Role of Helicobacter pylori eradication in aspirin or non-steroidal anti-inflammatory drug users. World J Gastroenterol. 2005;11:3811–3816. doi: 10.3748/wjg.v11.i25.3811. [ DOI ] [ PMC free article ] [ PubMed ] [ Google Scholar ]
• 9. Grad YH, Lipsitch M, Aiello AE. Secular trends in Helicobacter pylori seroprevalence in adults in the United States: evidence for sustained race/ethnic disparities. Am J Epidemiol. 2012;175:54–59. doi: 10.1093/aje/kwr288. [ DOI ] [ PMC free article ] [ PubMed ] [ Google Scholar ]
• 10. Chey WD, Wong BC Practice Parameters Committee of the American College of G. American College of Gastroenterology guideline on the management of Helicobacter pylori infection. Am J Gastroenterol. 2007;102:1808–1825. doi: 10.1111/j.1572-0241.2007.01393.x. [ DOI ] [ PubMed ] [ Google Scholar ]
• 11. Lanza FL, Chan FK, Quigley EM Practice Parameters Committee of the American College of G. Guidelines for prevention of NSAID-related ulcer complications. Am J Gastroenterol. 2009;104:728–738. doi: 10.1038/ajg.2009.115. [ DOI ] [ PubMed ] [ Google Scholar ]
• 12. Huang JQ, Sridhar S, Hunt RH. Role of Helicobacter pylori infection and non-steroidal anti-inflammatory drugs in peptic-ulcer disease: a meta-analysis. Lancet. 2002;359:14–22. doi: 10.1016/S0140-6736(02)07273-2. [ DOI ] [ PubMed ] [ Google Scholar ]
• 13. Lanas A, Carrera-Lasfuentes P, Arguedas Y, Garcia S, Bujanda L, Calvet X, et al. Risk of upper and lower gastrointestinal bleeding in patients taking nonsteroidal anti-inflammatory drugs, antiplatelet agents, or anticoagulants. Clin Gastroenterol Hepatol. 2015;13:906–912. e902. doi: 10.1016/j.cgh.2014.11.007. [ DOI ] [ PubMed ] [ Google Scholar ]
• 14. Somasundaram S, Sigthorsson G, Simpson RJ, Watts J, Jacob M, Tavares IA, et al. Uncoupling of intestinal mitochondrial oxidative phosphorylation and inhibition of cyclooxygenase are required for the development of NSAID-enteropathy in the rat. Aliment Pharmacol Ther. 2000;14:639–650. doi: 10.1046/j.1365-2036.2000.00723.x. [ DOI ] [ PubMed ] [ Google Scholar ]
• 15. Masclee GM, Valkhoff VE, Coloma PM, de Ridder M, Romio S, Schuemie MJ, et al. Risk of upper gastrointestinal bleeding from different drug combinations. Gastroenterology. 2014;147:784–792. e789. doi: 10.1053/j.gastro.2014.06.007. quiz e713–784. [ DOI ] [ PubMed ] [ Google Scholar ]
• 16. Crooks CJ, West J, Card TR. Comorbidities affect risk of nonvariceal upper gastrointestinal bleeding. Gastroenterology. 2013;144:1384–1393. e1381–1382. doi: 10.1053/j.gastro.2013.02.040. 1393. quiz e1318–1389. [ DOI ] [ PMC free article ] [ PubMed ] [ Google Scholar ]
• 17. Gonzalez-Perez A, Saez ME, Johansson S, Nagy P, Garcia Rodriguez LA. Risk factors associated with uncomplicated peptic ulcer and changes in medication use after diagnosis. PLoS One. 2014;9:e101768. doi: 10.1371/journal.pone.0101768. [ DOI ] [ PMC free article ] [ PubMed ] [ Google Scholar ]
• 18. Chey WD, Leontiadis GI, Howden CW, Moss SF. ACG Clinical Guideline: Treatment of Helicobacter pylori Infection. Am J Gastroenterol. 2017;112:212–239. doi: 10.1038/ajg.2016.563. [ DOI ] [ PubMed ] [ Google Scholar ]
• 19. Kanno T, Iijima K, Koike T, Abe Y, Shimada N, Hoshi T, et al. Accommodation in a refugee shelter as a risk factor for peptic ulcer bleeding after the Great East Japan Earthquake: a case-control study of 329 patients. J Gastroenterol. 2015;50:31–40. doi: 10.1007/s00535-014-0940-4. [ DOI ] [ PubMed ] [ Google Scholar ]
• 20. Kiss S, Zsikla V, Frank A, Willi N, Cathomas G. Helicobacter-negative gastritis: polymerase chain reaction for Helicobacter DNA is a valuable tool to elucidate the diagnosis. Aliment Pharmacol Ther. 2016;43:924–932. doi: 10.1111/apt.13564. [ DOI ] [ PubMed ] [ Google Scholar ]
• 21. McColl KE. Helicobacter pylori-negative nonsteroidal anti-inflammatory drug-negative ulcer. Gastroenterol Clin North Am. 2009;38:353–361. doi: 10.1016/j.gtc.2009.03.004. [ DOI ] [ PubMed ] [ Google Scholar ]
• 22. Agreus L, Talley NJ, Jones M. Value of the “Test & Treat” Strategy for Uninvestigated Dyspepsia at Low Prevalence Rates of Helicobacter pylori in the Population. Helicobacter. 2016;21:186–191. doi: 10.1111/hel.12267. [ DOI ] [ PubMed ] [ Google Scholar ]
• 23. Talley NJ, Vakil NB, Moayyedi P. American gastroenterological association technical review on the evaluation of dyspepsia. Gastroenterology. 2005;129:1756–1780. doi: 10.1053/j.gastro.2005.09.020. [ DOI ] [ PubMed ] [ Google Scholar ]
• 24. Malfertheiner P, Megraud F, O’Morain CA, Gisbert JP, Kuipers EJ, Axon AT, et al. Management of Helicobacter pylori infection-the Maastricht V/Florence Consensus Report. Gut. 2017;66:6–30. doi: 10.1136/gutjnl-2016-312288. [ DOI ] [ PubMed ] [ Google Scholar ]
• 25. Strand DS, Kim D, Peura DA. 25 Years of Proton Pump Inhibitors: A Comprehensive Review. Gut Liver. 2017;11:27–37. doi: 10.5009/gnl15502. [ DOI ] [ PMC free article ] [ PubMed ] [ Google Scholar ]
• 26. Park JY, Dunbar KB, Mitui M, Arnold CA, Lam-Himlin DM, Valasek MA, et al. Helicobacter pylori Clarithromycin Resistance and Treatment Failure Are Common in the USA. Dig Dis Sci. 2016;61:2373–2380. doi: 10.1007/s10620-016-4091-8. [ DOI ] [ PubMed ] [ Google Scholar ]
• 27. Lanas AI, Remacha B, Esteva F, Sainz R. Risk factors associated with refractory peptic ulcers. Gastroenterology. 1995;109:1124–1133. doi: 10.1016/0016-5085(95)90570-7. [ DOI ] [ PubMed ] [ Google Scholar ]
• 28. Lanas A, Garcia-Rodriguez LA, Polo-Tomas M, Ponce M, Quintero E, Perez-Aisa MA, et al. The changing face of hospitalisation due to gastrointestinal bleeding and perforation. Aliment Pharmacol Ther. 2011;33:585–591. doi: 10.1111/j.1365-2036.2010.04563.x. [ DOI ] [ PubMed ] [ Google Scholar ]
• 29. Stanley AJ, Dalton HR, Blatchford O, Ashley D, Mowat C, Cahill A, et al. Multicentre comparison of the Glasgow Blatchford and Rockall Scores in the prediction of clinical end-points after upper gastrointestinal haemorrhage. Aliment Pharmacol Ther. 2011;34:470–475. doi: 10.1111/j.1365-2036.2011.04747.x. [ DOI ] [ PubMed ] [ Google Scholar ]
• 30. Villanueva C, Colomo A, Bosch A, Concepcion M, Hernandez-Gea V, Aracil C, et al. Transfusion strategies for acute upper gastrointestinal bleeding. N Engl J Med. 2013;368:11–21. doi: 10.1056/NEJMoa1211801. [ DOI ] [ PubMed ] [ Google Scholar ]
• 31. Laine L, Jensen DM. Management of patients with ulcer bleeding. Am J Gastroenterol. 2012;107:345–360. doi: 10.1038/ajg.2011.480. quiz 361. [ DOI ] [ PubMed ] [ Google Scholar ]
• 32. Sachar H, Vaidya K, Laine L. Intermittent vs continuous proton pump inhibitor therapy for high-risk bleeding ulcers: a systematic review and meta-analysis. JAMA Intern Med. 2014;174:1755–1762. doi: 10.1001/jamainternmed.2014.4056. [ DOI ] [ PMC free article ] [ PubMed ] [ Google Scholar ]
• 33. Wang CH, Ma MH, Chou HC, Yen ZS, Yang CW, Fang CC, et al. High-dose vs non-high-dose proton pump inhibitors after endoscopic treatment in patients with bleeding peptic ulcer: a systematic review and meta-analysis of randomized controlled trials. Arch Intern Med. 2010;170:751–758. doi: 10.1001/archinternmed.2010.100. [ DOI ] [ PubMed ] [ Google Scholar ]
• 34. Lanas-Gimeno A, Lanas A. Risk of gastrointestinal bleeding during anticoagulant treatment. Expert Opin Drug Saf. 2017;16:673–685. doi: 10.1080/14740338.2017.1325870. [ DOI ] [ PubMed ] [ Google Scholar ]
• 35. Behrman SW. Management of complicated peptic ulcer disease. Arch Surg. 2005;140:201–208. doi: 10.1001/archsurg.140.2.201. [ DOI ] [ PubMed ] [ Google Scholar ]
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StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2024 Jan-.

StatPearls [Internet].

Peptic ulcer disease.

Talia F. Malik ; Karthik Gnanapandithan ; Kevin Singh .

Affiliations

Last Update: June 5, 2023 .

• Continuing Education Activity

Peptic ulcer disease is characterized by discontinuation in the inner lining of the gastrointestinal (GI) tract because of gastric acid secretion or pepsin. It extends into the muscularis propria layer of the gastric epithelium. It usually occurs in the stomach and proximal duodenum. It may involve the lower esophagus, distal duodenum, or jejunum. This activity reviews the cause, pathophysiology, and presentation of peptic ulcer disease and highlights the role of the interprofessional team in its management.

• Review the causes of peptic ulcer disease.
• Describe the presentation of a patient with peptic ulcer disease.
• Summarize the treatment options for peptic ulcer disease.
• Review the importance of improving care coordination among interprofessional team members to improve outcomes for patients affected by peptic ulcer disease.
• Introduction

Peptic ulcer disease (PUD) is characterized by discontinuation in the inner lining of the gastrointestinal (GI) tract because of gastric acid secretion or pepsin. It extends into the muscularis propria layer of the gastric epithelium. It usually occurs in the stomach and proximal duodenum. It may involve the lower esophagus, distal duodenum, or jejunum. Epigastric pain usually occurs within 15-30 minutes following a meal in patients with a gastric ulcer; on the other hand, the pain with a duodenal ulcer tends to occur 2-3 hours after a meal. Today, testing for Helicobacter pylori is recommended in all patients with peptic ulcer disease. Endoscopy may be required in some patients to confirm the diagnosis, especially in those patients with sinister symptoms. Today, most patients can be managed with a proton pump inhibitor (PPI) based triple-drug therapy.

Peptic ulcer disease (PUD) has various causes; however, Helicobacter pylori -associated PUD and NSAID-associated PUD account for the majority of the disease etiology. [1]

Causes of Peptic Ulcer Disease

• H. pylori infection

Medications

• Zollinger-Ellison syndrome
• Malignancy (gastric/lung cancer, lymphomas)
• Stress (Acute illness, burns, head injury)
• Viral infection
• Vascular insufficiency
• Radiation therapy
• Crohn disease
• Chemotherapy

Helicobacter Pylori -Associated PUD

H. pylorus is a gram-negative bacillus that is found within the gastric epithelial cells. This bacterium is responsible for 90% of duodenal ulcers and 70% to 90% of gastric ulcers. H. pylori infection is more prevalent among those with lower socioeconomic status and is commonly acquired during childhood. The organism has a wide spectrum of virulence factors allowing it to adhere to and inflame the gastric mucosa. This results in hypochlorhydria or achlorhydria, leading to gastric ulceration.

  Virulence Factors of   Helicobacter Pylori

• Urease: The secretion of urease breaks down urea into ammonia and protects the organism by neutralizing the acidic gastric environment.
• Toxins: CagA/VacA is associated with stomach mucosal inflammation and host tissue damage.
• Flagella: Provides motility and allows movement toward the gastric epithelium.

NSAID-associated PUD

Nonsteroidal anti-inflammatory drugs use is the second most common cause of PUD after H. pylori infection. [2] [3]  The secretion of prostaglandin normally protects the gastric mucosa. NSAIDs block prostaglandin synthesis by inhibiting the COX-1 enzyme, resulting in decreased gastric mucus and bicarbonate production and a decrease in mucosal blood flow.

Apart from NSAIDs, corticosteroids, bisphosphonates, potassium chloride, and fluorouracil have been implicated in the etiology of PUD.

Smoking also appears to play a role in duodenal ulcers, but the correlation is not linear. Alcohol can irritate the gastric mucosa and induce acidity.

Hypersecretory environment occurs in the following conditions.

• Zollinger Ellison syndrome
• Systemic mastocytosis
• Cystic fibrosis
• Hyperparathyroidism
• Antral G cell hyperplasia
• Epidemiology

Peptic ulcer disease (PUD) is a global problem with a lifetime risk of development ranging from 5% to 10%. [4] [5]  Overall, there is a decrease in the incidence of PUD worldwide due to improved hygienic and sanitary conditions combined with effective treatment and judicious use of NSAIDs. [5]  Duodenal ulcers are four times more common than gastric ulcers. Also, duodenal ulcers are more common in men than in the woman.

• Pathophysiology

The peptic ulcer disease (PUD) mechanism results from an imbalance between gastric mucosal protective and destructive factors. Risk factors predisposing to the development of PUD:

• H. pyl ori infection
• First-degree relative with PUD
• Emigrant from a developed nation
• African American/Hispanic ethnicity

With peptic ulcers, there is usually a defect in the mucosa that extends to the muscularis mucosa. Once the protective superficial mucosal layer is damaged, the inner layers are susceptible to acidity. Further, the ability of the mucosal cells to secrete bicarbonate is compromised.

H. pylori is known to colonize the gastric mucosa and causes inflammation. The H. pylori also impairs the secretion of bicarbonate, promoting the development of acidity and gastric metaplasia.

• Histopathology

Gastric ulcers are most commonly located on the lesser curvature, whereas duodenal ulcers are most common at the duodenal bulb. The ulcer is round to oval with a smooth base. Acute ulcers have regular borders, while chronic ulcers have elevated borders with inflammation. An ulcer extends beyond the muscularis mucosa.

• History and Physical

Signs and symptoms of peptic ulcer disease may vary depending upon the location of the disease and age. Gastric and duodenal ulcers can be differentiated from the timing of their symptoms in relation to meals. Nocturnal pain is common with duodenal ulcers. Those with gastric outlet obstruction commonly report a history of abdomen bloating and or fullness.

Common signs and symptoms include:

• Epigastric abdominal pain
• Abdominal fullness
• Nausea and vomiting
• Weight loss/weight gain
• Hematemesis

Warning symptoms or alarm symptoms that should prompt urgent referral include: [6]

• Unintentional weight loss
• Progressive dysphagia
• Overt gastrointestinal bleeding
• Iron deficiency anemia
• Recurrent emesis
• Family history of upper gastrointestinal malignancy

Diagnosis of PUD requires history taking, physical examination, and invasive/non-invasive medical tests. A careful history should be obtained and noted for the presence of any complications. Patient reporting of epigastric abdominal pain, early satiety, and fullness following a meal raise suspicion of PUD. The pain of gastric ulcers increases 2 to 3 hours after a meal and may result in weight loss, whereas the pain of duodenal ulcers decreases with a meal which can result in weight gain. Any patient presenting with anemia, melena, hematemesis, or weight loss should be further investigated for complications of PUD, predominantly bleeding, perforation, or cancer. A physical exam may reveal epigastric abdominal tenderness and signs of anemia.

Investigations

• Esophagogastroduodenoscopy (EGD): Gold standard and most accurate diagnostic test with sensitivity and specificity up to 90% in diagnosing gastric and duodenal ulcers. The American Society of Gastrointestinal Endoscopy has published guidelines on the role of endoscopy in patients presenting with upper abdominal pain or dyspeptic symptoms suggestive of PUD. [6]  Patients over 50 years of age and new onset of dyspeptic symptoms should get evaluated by an EGD. Anyone with the presence of alarm symptoms should undergo EGD irrespective of age.
• Barium swallow: It is indicated when EGD is contraindicated.
• Complete blood work, liver function, and levels of amylase and lipase.
• Serum gastric is ordered if Zollinger Ellison syndrome is suspected.
• Helicobacter pylori testing:
• Serologic testing
• Urea breath test: High sensitivity and specificity. It may be used to confirm eradication after 4 to 6 weeks of stopping treatment. In the presence of urease, an enzyme produced by H.pylori, the radiolabeled carbon dioxide produced by the stomach is exhaled by the lungs.
• Antibodies to H.pylori can also be measured.
• Stool antigen test
• Urine-based ELISA and rapid urine test
• Endoscopic biopsy: Culture is not generally recommended as it is expensive, time-consuming, and invasive. It is indicated if eradication treatment fails or there is suspicion about antibiotic resistance. Biopsies from at least 4-6 sites are necessary to increase sensitivity. Gastric ulcers are commonly located on the lesser curvature between the antrum and fundus. The majority of duodenal ulcers are located in the first part of the duodenum.

     6. Computerized tomography of the abdomen with contrast is of limited value in the diagnosis of PUD itself but is helpful in the diagnosis of its complications like perforation and gastric outlet obstruction.

• Treatment / Management

Medical Treatment

Antisecretory drugs used for peptic ulcer disease (PUD) include H2-receptor antagonists and the proton pump inhibitor (PPIs). PPIs have largely replaced H2 receptor blockers due to their superior healing and efficacy. PPIs block acid production in the stomach, providing relief of symptoms and promote healing. Treatment may be incorporated with calcium supplements as long-term use of the PPIs can increase the risk of bone fractures. NSAIDs induced PUD can be treated by stopping the use of NSAIDs or switching to a lower dose. Corticosteroids, bisphosphonates, and anticoagulants should also be discontinued if possible. Prostaglandin analogs (misoprostol) are sometimes used as prophylaxis for NSAID-induced peptic ulcers. First-line treatment for H. pylori-induced PUD is a triple regimen comprising two antibiotics and a proton pump inhibitor. Pantoprazole, clarithromycin, and metronidazole, or amoxicillin are used for 7 to 14 days. [7]  Antibiotics and PPIs work synergistically to eradicate H. pylori . [8] The antibiotic selected should take into consideration the presence of antibiotic resistance in the environment. If first-line therapy fails, quadruple therapy with bismuth and different antibiotics is used.

Refractory Disease and Surgical Treatment

Surgical treatment is indicated if the patient is unresponsive to medical treatment, noncompliant, or at high risk of complications. A refractory peptic ulcer is one over 5 mm in diameter that does not heal despite 8-12 weeks of PPI therapy. The common causes are persistent H.pylori infection, continued use of NSAIDs, or significant comorbidities that impair ulcer healing or other conditions like gastrinoma or gastric cancer. If the ulcer persists despite addressing the above risk factors, patients can be candidates for surgical treatment. Surgical options include vagotomy or partial gastrectomy. [9]

• Differential Diagnosis

The following conditions can present with symptoms similar to peptic ulcer disease and it is important to be familiar with their clinical presentation in order to make the correct diagnosis.

• Gastritis - an inflammatory process of the gastric mucosa from immune-mediated or infectious etiology presenting with upper abdominal pain and nausea. Clinical presentation is very similar to that of peptic ulcer disease.
• Gastroesophageal reflux disease (GERD) - patients usually describe a burning sensation in the epigastrium and lower retrosternal area, excessive salivation, or intermittent regurgitation of food material.
• Gastric cancer - apart from abdominal pain, patients usually describe alarm symptoms like weight loss, melena, recurrent vomiting, or evidence of malignancy elsewhere in case of metastasis.
• Pancreatitis - epigastric or right upper quadrant pain that is more persistent and severe, worse in the supine position, and patients usually have a history of alcoholism or gallstones. [10]  Elevated serum amylase and lipase are useful in the diagnosis.
• Biliary colic - intermittent, severe deep pain in the right upper quadrant or epigastrium precipitated by fatty meals.
• Cholecystitis - right upper quadrant or epigastric pain that usually lasts for hours and is exacerbated by fatty meals and is associated with nausea and vomiting. Fever, tachycardia, positive Murphy sign, leukocytosis, and abnormal liver functions help further distinguish this from biliary colic. [11]

These are some potentially life-threatening conditions that can also have similar presentations.

• Myocardial infarction - especially in the inferior wall and right ventricular involvement, sometimes patients can present with epigastric pain with nausea and vomiting. [12]  The presence of other symptoms like dizziness, shortness of breath, and abnormal vital signs in a high-risk patient should alert the clinician to look for this. 
• Mesenteric ischemia - while acute mesenteric ischemia presents with severe, acute onset abdominal pain; the chronic variant usually presents with ongoing post-prandial epigastric pain [13] and can be mistaken for peptic ulcer disease. Older age, presence of risk factors for atherosclerosis, and weight loss should prompt a workup for the same.
• Mesenteric vasculitis - unexplained abdominal symptoms with or without lower gastrointestinal bleeding in a patient with other features from underlying systemic vasculitis should raise the suspicion of mesenteric vasculitis. [14]

The prognosis of peptic ulcer disease (PUD) is excellent after the underlying cause is successfully treated. Recurrence of the ulcer may be prevented by maintaining good hygiene and avoiding alcohol, smoking, and NSAIDs. Unfortunately, recurrence is common with rates exceeding 60% in most series. NSAID-induced gastric perforation occurs at a rate of 0.3% per patient per year. However, unlike in the past, mortality rates for peptic ulcer disease have decreased significantly.

• Complications

Peptic ulcer disease (PUD) if not diagnosed and treated promptly can lead to serious complications. Following complications can occur in PUD:

• Upper gastrointestinal bleeding
• Gastric outlet obstruction
• Perforation
• Penetration
• Gastric cancer
• Deterrence and Patient Education

Patients with peptic ulcer disease (PUD) should be counseled about potentially injurious agents like nonsteroidal anti-inflammatory drugs (NSAIDs), aspirin, alcohol, tobacco, and caffeine. If it is necessary to use NSAIDs use the lowest possible dose and also consider prophylaxis for patients who use NSAIDs. Obesity has a strong association with peptic ulcer disease, and patients should be asked to lose weight. Stress reduction counseling can be helpful in some cases.

• Pearls and Other Issues

Ulcers are differentiated from erosions based on size. Lesions less than 5 mm in diameter are termed erosions, whereas lesions greater than 5 mm in diameter are termed ulcers. COX-2 selective NSAIDs are less likely to cause PUD as COX-2 is not expressed on the gastric mucosa. Therefore, in patients with a history of PUD, COX-2 selective NSAIDs are preferred. A gastrin-producing endocrine tumor causes Zollinger-Ellison syndrome or gastrinoma usually arises from the pancreas or duodenum. It results in multiple ulcers in the duodenum and jejunum. It can be diagnosed by measuring serum gastrin levels.

• Enhancing Healthcare Team Outcomes

An evidence-based approach to peptic ulcer disease is recommended. PUD is a very common disorder that affects millions of people. When left untreated, it has significant morbidity. The majority of patients with PUD present to their primary caregiver, but others may present to the emergency department, urgent care clinic, or an outpatient clinic. Because the presentation of PUD is often vague, healthcare workers, including nurses, need to be aware of this diagnosis. The abdominal pain can mimic a number of other pathologies and consequently lead to a delay in treatment.

Once the diagnosis is made, the key is to educate the patient on lifestyle changes, which include discontinuation of smoking, abstaining from alcohol and caffeinated beverages, and avoid consumption of too many NSAIDs. Gastroenterology nurses monitor patients, provide education, and keep the team updated on the patient's condition. The pharmacist should educate the patient on medication compliance to obtain symptom relief and a cure. A dietary consult should be sought as there is evidence that obesity may be a trigger factor for peptic ulcer disease. Only through a team approach can the morbidity of peptic ulcer disease be decreased. For most patients with PUD who are treated with the triple regimen or PPI, the outcomes are excellent, but recurrence of symptoms is not uncommon. [15] [16]  (Level 2)

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Disclosure: Talia Malik declares no relevant financial relationships with ineligible companies.

Disclosure: Karthik Gnanapandithan declares no relevant financial relationships with ineligible companies.

Disclosure: Kevin Singh declares no relevant financial relationships with ineligible companies.

This book is distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0) ( http://creativecommons.org/licenses/by-nc-nd/4.0/ ), which permits others to distribute the work, provided that the article is not altered or used commercially. You are not required to obtain permission to distribute this article, provided that you credit the author and journal.

• Cite this Page Malik TF, Gnanapandithan K, Singh K. Peptic Ulcer Disease. [Updated 2023 Jun 5]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2024 Jan-.

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