case study on peptic ulcer disease

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 disease

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• Emma Sverdén , upper gastrointestinal surgeon 1 2 ,
• Lars Agréus , general practitioner , professor 3 4 ,
• Jason M Dunn , gastroenterologist 5 ,
• Jesper Lagergren , upper gastrointestinal surgeon, professor 1 5
• 1 Upper Gastrointestinal Surgery, Department of Molecular Medicine and Surgery, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden
• 2 Department of Upper Gastrointestinal Surgery, South Hospital, Stockholm, Sweden
• 3 Division of Family Medicine and Primary Care, Department of Neurobiology, Care Sciences and Society, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden
• 4 The University of Newcastle, Australia
• 5 School of Cancer and Pharmaceutical Sciences, King’s College London, and Guy’s and St Thomas’ NHS Foundation Trust, UK
• Correspondence to emma.s.eklund{at}gmail.com

What you need to know

More than 90% of duodenal ulcers are linked to H pylori infection; eradication therapy with antibiotics and proton pump inhibitors is the mainstay of treatment

A “test and treat” strategy for H pylori infection is appropriate in patients under 60 with suspected peptic ulcer disease who have no complications

Proton pump inhibitors are important in the prevention and treatment of peptic ulcer disease, but avoid their use without clear indications, and re-evaluate patients on long-term treatment

Gastric ulcers are followed up with endoscopy until healed to rule out malignancy

Urgently refer patients with complications such as bleeding, perforation, or penetration to an emergency unit

Peptic ulcer disease presents with gastrointestinal symptoms similar to dyspepsia and can be difficult to distinguish clinically. It can have potentially serious complications such as bleeding or perforation, with a high risk of mortality. 1 Optimal treatment with proton pump inhibitors (PPIs) facilitates healing and can prevent complications and recurrence.

Observational studies and surveys among healthcare providers report that adherence to evidence based treatment guidelines is often poor. 2 3 4 5 6 7 8 9 This results in inadequate treatment and overuse of PPIs. Increasingly, antibiotic resistance has affected the choice of eradication regimen for Helicobacter pylori infection, the main risk factor. In this Clinical Update, we review the epidemiology and management of peptic ulcer disease for non-specialists to guide prompt diagnosis and appropriate treatment.

What is peptic ulcer disease?

Peptic ulcer disease is often defined as a mucosal break greater than 3-5 mm in the stomach or duodenum with a visible depth. It is therefore an endoscopic diagnosis in contrast to dyspepsia, which is a clinical diagnosis based on symptoms alone. Peptic ulcer disease results from an imbalance between factors that protect the mucosa of the stomach and duodenum, and factors that cause damage to it ( fig 1 ).

Factors that protect or harm the gastroduodenal mucosa

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Patients with gastric and duodenal ulcers present similarly. They may report epigastric or retrosternal pain, early satiety, nausea, bloating, belching, or postprandial distress. These symptoms are non-specific and may be difficult to distinguish clinically from functional dyspepsia. Studies have shown low correlation between symptoms and endoscopic findings. 10 Conversely, patients may be asymptomatic until a complication occurs, or an ulcer may be diagnosed incidentally during endoscopy performed for other reasons.

How common is it?

Peptic ulcer disease affects 1-2 per 1000 people annually as per a systematic review with data from the USA, UK, and Europe. 1 11 12 The incidence is declining, possibly due to decreasing prevalence of H pylori infection. 1 13 A time trend study from Asia (12 612 patients) showed similar incidence and declining trend. 14

Complications from peptic ulcer disease have not fallen, however, according to a systematic review and meta-analysis (18 studies from Europe, USA, and Israel, more than 1000 individuals per study). 1 An ageing population that has more comorbidities and more frequently uses ulcerogenic medications may be contributing to this.

What are the risk factors?

Previous studies suggest that 90% of duodenal ulcers and 70% of gastric ulcers are associated with H pylori infection. 15 16 Although these percentages are now considered to be lower, H pylori is also an important risk factor for gastric cancer, which further emphasises the importance of its eradication. 17 18

Medications such as aspirin and non-steroidal anti-inflammatory drugs (NSAIDs) cause approximately 10% of peptic ulcers. NSAIDs are more strongly linked to gastric ulcers than duodenal ulcers. 19 20 21 22 The combination of aspirin with NSAIDs further increases the risk. 23 Use of these drugs has increased over the last few decades. In the USA, self-reported use of aspirin and NSAIDs increased by 57% and 43%, respectively, between 2005 and 2010. Nearly 46% of all people over 70 were regular aspirin users in 2010, according to a national survey (27 157 people). 24 Selective COX-2 (cyclo-oxygenase-2) inhibitors have a lower risk of peptic ulcer disease compared with non-selective NSAIDs. 25

Marginal ulcer is seen in approximately 5% of patients who have undergone gastric bypass surgery for obesity. 26 The incidence can be as high as 27-36% in patients with upper gastrointestinal symptoms after gastric bypass surgery. 27

Box 1 lists other risk factors for peptic ulcer disease. The proportion of idiopathic ulcers has been increasing in recent years. 36 A multicentre study based in France (713 patients) found that 22% of patients with duodenal or gastric ulcer were neither infected by H pylori , nor using ulcerogenic drugs. 37 Between 20% and 50% of duodenal ulcers in the USA and 3-12% in Europe are negative for H pylori . 38 Before defining an ulcer as idiopathic, all other risk factors ( box 1 ) should be excluded.

Risk factors and causes of ulcers in the stomach and duodenum

• Gastric bypass surgery

Cigarette smoking 28

Selective serotonin reuptake inhibitors 29 30

Zollinger-Ellison syndrome (uncommon, gastrin producing tumour usually located in the pancreas)

Physiological stress associated with serious trauma and critical illness 31 (eg, septicaemia)

Gastric tumours mistaken for peptic ulcers

Autoimmune diseases, eg, vasculitis, sarcoidosis, and Crohn’s disease

Infections, mainly in immunocompromised patients, eg, cytomegalovirus, tuberculosis, and syphilis 32

Psychological stress is not an established risk factor for peptic ulcer disease, although some research has suggested an association 33

Consumption of alcohol or coffee does not seem to increase the risk of peptic ulcer disease 34 35

What are the complications?

Bleeding, perforation, penetration to a surrounding organ, and obstruction from fibrotic stricturing (usually in the pyloric region) are important complications. Box 2 lists signs suggestive of acute bleeding. Perforation usually presents with acute onset of severe abdominal pain. Penetration can cause secondary pancreatitis if the pancreas is involved. Obstruction causes nausea and vomiting.

Red flags for referral to a specialist

Signs of acute bleeding 39 40 :

Melaena, self-reported or found on digital rectal examination

Blood in vomit (haematemesis)

Abnormally high pulse or low blood pressure

Severe anaemia

Signs of perforation or penetration such as severe abdominal pain and peritonitis

Symptoms suggestive of malignancy in patients over 50:

o Dysphagia 41

o Unexplained weight loss with upper abdominal pain or gastro-oesophageal reflux

o Loss of appetite

o Recurrent vomiting

Second line eradication therapy fails

Symptoms persist despite successful eradication

Bleeding peptic ulcer occurs in 19 to 57 per 100 000 individuals each year, as per a systematic review (93 studies). Perforation or penetration is relatively less common, occurring in 4 to 14 per 100 000 individuals each year. 42 The risk of recurrence and complications from idiopathic ulcers is higher than for ulcers with known aetiology, as reported in prospective cohort studies. 43 44 Mortality is high with these complications. About 8.6% of patients with peptic ulcer bleeding and 23.5% of patients with perforation die within 30 days. 42

What to cover on initial assessment?

Ask about the nature of symptoms and risk factors such as previous ulcer disease, other medical conditions, medications, and smoking. Inquire about symptoms suggestive of complications listed in box 2 .

On examination, record pulse and blood pressure. Severe peptic ulcer bleeding may affect the patient’s haemodynamic status. Palpate the abdomen. Pronounced tenderness may suggest perforation or penetration, indicating the need for emergency referral. Assess for any palpable mass which may represent malignancy. Digital rectal examination is useful to detect melaena when bleeding from a peptic ulcer is suspected.

When to refer?

Box 2 lists features that prompt referral. Immediately transfer patients with signs of bleeding or perforation to an emergency unit. Refer patients with symptoms suggestive of malignancy to a specialist gastroenterology unit for urgent endoscopy within two weeks.

What investigations can be done?

Request a blood test to detect anaemia. Endoscopy is required to confirm ulcer diagnosis, but may be avoided in patients under 55 with no complications.

Testing for H pylori

Current guidelines recommend a “test and treat” strategy for H pylori in patients with symptoms suggestive of peptic ulcer disease and ≤55 years (National Institute for Health and Care Excellence) 39 or ≤60 years (American College of Gastroenterology). 45 46 Non-invasive tests include urea breath test, stool antigen test, or serology. The urea breath test delivers an immediate result and can be performed at home with the necessary equipment. A stool antigen test is equally reliable, and the stool sample can be collected at home. Serology testing for antibodies has high sensitivity but low specificity, ie, a negative test excludes infection, but a positive result needs to be confirmed by another test. It cannot be used to confirm eradication.

Unlike the serology test, a single negative urea breath test or stool antigen test does not exclude H pylori infection. Bleeding or use of PPIs and antibiotics might cause false negative results. Discontinue PPIs for two weeks 47 and antibiotics for at least four weeks before testing. 48 If no other probable cause of the ulcer is identified, repeat testing a few weeks later.

Endoscopy is advised in older people with dyspepsia, in patients with red flag symptoms ( box 2 ), 39 and in patients whose dyspeptic symptoms do not resolve after 4-8 weeks of PPI. Whether endoscopy should be used more liberally in patients with diffuse upper gastrointestinal symptoms is debated. 49 At endoscopy, H pylori can be diagnosed by rapid urease test or on histology, both of which are invasive tests.

Additional specialist tests can include platelet cyclo-oxygenase activity or blood salicylic acid to establish any link to the use of NSAIDs or aspirin, and fasting gastrin to exclude Zollinger-Ellison syndrome, before determining an ulcer as idiopathic.

How is it managed?

The initial management is usually acid suppressing treatment along with elimination of risk factors.

Acid suppression

Endoscopically confirmed peptic ulcers without H pylori infection are treated with a PPI until healed, along with elimination of any other known risk factors. Systematic reviews have shown that PPIs accelerate the healing process and facilitate eradication of H pylori . 50 51 52 The odds of ulcer healing were three times higher with PPIs compared with control group (odds ratio 3.49, 95% confidence interval 3.28 to 3.72) in a recent meta-analysis (847 randomised trials, 142 485 participants). 50 For duodenal ulcers, when H pylori is the predominant cause, acid suppression included in the eradication therapy for 7-14 days is usually sufficient for healing. Gastric ulcers are treated with acid suppression until healing is confirmed on repeat endoscopy.

The duration of acid suppression for the test and treat recommendation (without prior endoscopy) differs between guidelines, but no more than eight weeks is recommended. Reassess the patient after 4-8 weeks for resolution of symptoms. 45

We advise caution against overuse of PPIs. Ensure that the treatment is clearly indicated with adequate dosage. Re-evaluate the indication for any continued treatment. Observational studies in different settings suggest that between 27 and 81% of PPI use in primary care and 36-63% of use in hospitals could be inappropriate, 2 53 54 ie, having no documented indication for its use or prescribed without re-evaluation. Approximately half of older patients in primary care using NSAIDs were prescribed higher than therapeutic doses or double dose regimens of PPIs in a national audit in Bahrain. 55 This overuse results in unnecessary healthcare costs and an increased risk of adverse effects, such as hip fracture, 56 cardiovascular events, 57 Clostridium difficile infection, pneumonia, dementia, 58 and gastric cancer in long term users. 59 60 The evidence regarding these side effects is largely derived from observational studies, with a risk of confounding, 61 but the potential harms need to be considered in the scenario of overuse and long term use.

Consider alternatives such as histamine 2 receptor antagonists if patients experience side effects. Misoprostol, a prostaglandin analogue, is effective in treating and preventing ulcer recurrence, but compliance is poor owing to side effects such as diarrhoea, nausea, and abdominal pain. 62

H pylori eradication

Patients testing positive for H pylori should receive eradication therapy. 39 45 63 64 The choice of antibiotics is determined by antibiotic resistance patterns in any geographical region. Figure 2 describes typical eradication regimens. Patients can find eradication regimens challenging to follow because they involve talking multiple drugs at the same time. Offer clear written explanation if they would prefer.

Regimens for eradicating H pylori

Regimens with eradication rates of ≥90% are recommended. In northern Europe, which has a low prevalence of clarithromycin resistant H pylori , “triple therapy” is recommended. This is a combination of two antibiotics and a PPI twice daily for 7-14 days depending on empirical efficacy in the region. In many regions, for example Italy, Japan, Turkey, and China, this provides an unacceptably low eradication rate, often <80%. 65 In populations with higher prevalence of antibiotic resistance, expert consensus suggests that a “quadruple therapy” is appropriate. This can be concomitant (14 days) or sequential (7+7 days) ( fig 2 ). 66 67 Bismuth is a bactericidal salt that can be added to the quadruple regimen. Prolonged triple therapy in higher doses is an alternative to quadruple regimens. 65

Medication related peptic ulcer disease

Along with prescribing PPIs, consider whether NSAIDs can be discontinued in the patient. A COX 2-selective NSAID in combination with a PPI may be preferred in these patients. The risk of cardiovascular complications has long been considered to be more pronounced with the COX-2 selective NSAID, but a recent review reports similar cardiovascular risk across NSAIDs. 25 68 Use of low dose aspirin for prevention of cardiovascular events can be continued in combination with a PPI. 69 70

Some patients may require long term acid suppression if using ulcerogenic drugs for a longer duration ( box 3 ). Patients are often uncertain of the reason for long term treatment with PPIs and may not be aware that NSAIDs and aspirin can cause peptic ulcer disease. Educate patients about these risks so they are compliant with the treatment.

Indications for long term therapy with a PPI in long term users of aspirin or NSAIDs 71

Age >65 years

A history of peptic ulcer disease, especially with complications

NSAID use at high doses or in combination with certain other drugs, ie, aspirin, steroids, selective serotonin reuptake inhibitors, or anticoagulants

Aspirin use, even at low dosage in elderly patients, particularly in combination with drugs listed above

Histamine 2 receptor antagonists are effective in preventing duodenal ulcers among NSAID users, but not gastric ulcers. 72 These have a shorter duration of action and do not completely suppress postprandial secretion of gastric acid, 73 which requires at least twice-daily dosage. Randomised trials and cohort studies have shown that high doses of famotidine (80 g daily) prevent gastric ulcers, although not as effectively as PPIs. 74

Marginal ulcer

There is no evidence based treatment of marginal ulcers, and they are often difficult to heal. 26 Eliminate any risk factor and consider a high dose PPI regimen. 75 Follow up with endoscopy until the ulcer is healed.

Managing complications

In patients with peptic ulcer bleeding, endoscopic treatment reduces the risk of re-bleeding, the need for surgery, and mortality. 40 76 Approximately 10% of patients require urgent angiographic embolisation or surgery for bleeding despite endoscopic intervention. 77

The gold standard treatment of ulcer perforation is surgery. Endoscopic stenting plus drainage is a less invasive alternative, but its role is debated. 78 Pyloric obstruction is typically managed endoscopically with dilatation, although surgery is sometimes required. 79

What to cover at follow-up visits?

Ask the patient about improvement in symptoms. Assess outcome of eradication therapy, preferably non-invasively, eg, by a urea breath test or a stool antigen test, at least 2 weeks after finishing the PPI therapy. More than 85% of patients experience eradication with good compliance to treatment when the prescription is appropriate for the local resistance pattern. Discuss elimination of other risk factors—mainly NSAIDS and smoking.

Patients with a confirmed endoscopic diagnosis of duodenal ulcer do not require follow-up after eradication. Patients with gastric ulcers will need repeat endoscopies and biopsies until confirmed healed, mainly because such ulcers are slower to heal and some may actually be gastric cancers misdiagnosed as an ulcer. Continue PPI treatment after eradication for up to 8 weeks in total or until healing is endoscopically confirmed. 80 Of note, a malignant ulcer can also temporarily heal with PPI treatment, so biopsies must also be sampled from any visible scar tissue. 81 H pylori eradication may not completely eliminate the risk of gastric cancer. Expert consensus is to offer endoscopic and histological surveillance in patients at risk—as defined by the extent and severity of mucosal atrophy on endoscopy. 82

If eradication fails, second line therapy should be tried ( fig 2 ). If there is no response on second line therapy, or if symptoms persist despite successful eradication, refer the patient to a specialist. Culture from a biopsy of the gastric mucosa can determine potential antibiotic resistance.

Education into practice

Think about a patient with dyspeptic symptoms you have seen in your practice recently. How would you alter your management approach based on reading this article?

How many patients at your practice are on long term treatment with NSAIDs or aspirin and PPIs? When has their indication for continued treatment been evaluated?

Questions for future research

What strategies are effective in treating patients with H pylori antibiotic resistance?

What are the adverse effects of PPI, especially potential cancer risk, with long term use or higher doses?

Which is the ideal long term strategy to prevent recurrence of peptic ulcer disease in high-risk individuals?

How can marginal ulcers occurring after gastric bypass surgery for obesity be prevented and treated?

Additional educational resources

The American College of Gastroenterology https://gi.org/guideline/management-of-dyspepsia-2/

The European Society of Gastrointestinal Endoscopy https://www.esge.com/assets/downloads/pdfs/guidelines/2015_s_0034_1393172.pdf

The National Institute for Health and Care Excellence (NICE)

https://www.nice.org.uk/guidance/cg184 https://www.nice.org.uk/guidance/ng12/chapter/1-Recommendations-organised-by-site-of-cancer#upper-gastrointestinal-tract-cancers

Information resources for patients

National Institute for Health and Care Excellence (NICE) public information. https://www.nice.org.uk/guidance/cg141/ifp/chapter/About-this-information

How patients were involved in the creation of this article

No patients were involved in the creation of this article.

How this article was created

We searched PubMed using the term “peptic ulcer.” We prioritised systematic reviews and high quality and recently published original studies on the topic. We excluded animal and paediatric studies. We also reviewed clinical guidelines from the American College of Gastroenterology, the European Society of Gastrointestinal Endoscopy, the National Institute for Health and Care Excellence, and the Japanese Society of Gastroenterology.

Competing interests The BMJ has judged that there are no disqualifying financial ties to commercial companies. The authors declare the following other interests: none.

Further details of The BMJ policy on financial interests is here: https://www.bmj.com/about-bmj/resources-authors/forms-policies-and-checklists/declaration-competing-interests

Provenance and peer review: commissioned; externally peer reviewed.

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• Open access
• Published: 10 February 2022

The global, regional and national burden of peptic ulcer disease from 1990 to 2019: a population-based study

• Xin Xie 1 , 2 ,
• Kaijie Ren 1 ,
• Zhangjian Zhou 3 ,
• Chengxue Dang 1 , 4 &
• Hao Zhang   ORCID: orcid.org/0000-0001-8986-3854 1 , 4  

BMC Gastroenterology volume  22 , Article number:  58 ( 2022 ) Cite this article

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Metrics details

Peptic ulcer disease (PUD) is a common digestive disorder, of which the prevalence decreased in the past few decades. However, the decreasing tendency has plateaued in recent years due to changes in risk factors associated with the etiology of PUD, such as non-steroidal anti-inflammatory drug use. In this study, we investigated the epidemiological and the sociodemographic characteristics of PUD in 204 countries and territories from 1990 to 2019 based on data from the Global Burden of Disease, Injuries and Risk Factors (GBD) Study.

Demographic characteristics and annual prevalence, incidence, mortality, disability-adjusted life years (DALYs) and age-standardized death rate (ASR) data associated with PUD were obtained and analyzed. According to the sociodemographic index (SDI), the numbers of patients, ASRs, estimated annual percentage changes and geographical distributions were assessed with a generalized linear model and presented in world maps. All evaluations of numbers and rates were calculated per 100,000 population with 95% uncertainty intervals (UIs).

In 2019, the global prevalence of PUD was approximately 8.09 [95% UI 6.79–9.58] million, representing a 25.82% increase from 1990. The age-standardized prevalence rate was 99.40 (83.86–117.55) per 100,000 population in 2019, representing a decrease of 143.37 (120.54–170.25) per 100,000 population from 1990. The age-standardized DALY rate in 2019 was decreased by 60.64% [74.40 (68.96–81.95) per 100,000 population] compared to that in 1990. In both sexes, the numbers and ASRs of the prevalence, incidence, deaths and DALYs were higher in males than in females over 29 years. Regionally, South Asia had the highest age-standardized prevalence rate [156.62 (130.58–187.05) per 100,000 population] in 2019. A low age-standardized death rate was found in the high-income super-region. Among nations, Kiribati had the highest age-standardized prevalence rate [330.32 (286.98–379.81) per 100,000 population]. Regarding socioeconomic status, positive associations between the age-standardized prevalence, incidence, death rate, DALYs and SDI were observed globally in 2019.

Conclusions

Morbidity and mortality due to PUD decreased significantly from 1990 to 2019, while a gradual upward inclination has been observed in recent 15 years, which might be associated with changes in risk factors for PUD. Attention and efforts by healthcare administrators and society are needed for PUD prevention and control.

Peer Review reports

Peptic ulcer disease (PUD), a common disorder of the digestive system, is defined as digestive tract injury that results in a mucosal break greater than 3–5 mm, with a visible depth reaching the submucosa [ 1 , 2 ]. Mainly occurring in the stomach and proximal duodenum, PUD accounts for an estimated lifetime prevalence of 5–10% and an annual incidence of 0.1–0.3% in the general population in Western countries [ 2 , 3 ]. Due to nonspecific symptoms, PUD assessment and treatment requires clinical caution due to severe complications such as bleeding, perforation, penetration into adjacent organs and gastrointestinal obstruction, all of which could require acute endoscopic or surgical treatment [ 1 , 4 , 5 ].

Similar to several digestive disorders, the prevalence of PUD initially increased and then subsequently decreased. Jennings et al . analyzed PUD epidemiological data spanning 150 years and found that the incidence of and mortality due to PUD increased markedly during the nineteenth century and then decreased steadily due to improvements in environmental hygiene and medical therapeutic strategies [ 6 ]. During the first 50 years of the twentieth century in the United States, PUD affected approximately 10% of the adult population [ 7 ]. Several studies which were conducted in the past 20–30 years indicated a sharp decreasing tendency in the PUD prevalence, PUD-related hospital admissions and PUD-associated mortality due to new anti-PUD therapies application, such as Helicobacter pylori ( H. pylori ) eradication and proton-pump inhibitors (PPIs) using [ 8 , 9 , 10 , 11 ]. However, the widespread use of nonsteroidal anti-inflammatory drugs (NSAIDs), histamine 2 receptor antagonists, and selective serotonin reuptake inhibitors, as well as increased physiological stress, have been reported as risk factors and have changed the landscape of PUD in recent years [ 12 , 13 ]. The details of the epidemiological changes caused by these relatively new risk factors are still controversial.

In this study, we analyzed PUD burdens in 204 countries or territories from 1990 to 2019 based on data from the Global Burden of Disease, Injuries and Risk Factors (GBD) Study, which is updated in 2020 and contains epidemiological and socioeconomic data of 354 diseases globally, allowing evaluations of the burdens, distributions and trends of PUD in different regions. Our study aims to investigate the current landscape and changes in the epidemiological characteristics of PUD to support healthcare-associated policy makers in developing improved PUD prevention strategies.

Data acquisition

The GBD study provides comprehensive epidemiological estimates of the prevalence of, incidence of, disability-adjusted life years (DALYs) due to, and mortality associated with diseases and injuries across specific groups of countries and territories by sex, age and year. Annual (inclusive dates: Jan 1st, 1990 to Dec 31st, 2019) prevalence rates, incidence rates, DALYs and deaths and the corresponding age-standardized rates (ASRs) were extracted from the Global Health Data Exchange (GHDx) database ( http://ghdx.healthdata.org/ ). These data were socioecologically classified into seven GBD super-regions, 21 GBD regions and 204 countries/territories by sociodemographic index (SDI) quintiles, which is a composite indicator of lag-distributed income per capita, ranging from 0 (less developed) to 1 (most developed). SDI value reflects the degree of social development and correlates with total fertility, per capita income, and average years of education [ 14 ]. All countries and territories were classified into five quintiles based on the SDI ( http://ghdx.healthdata.org/record/ihme-data/gbd-2019-sociodemographic-index-sdi-1950-2019 ). Besides, super-regions and regions in GBD database are groups of countries rather than geological concepts for analysis ( http://www.healthdata.org/sites/default/files/files/Data_viz/GBD_2017_Tools_Overview.pdf ).

Statistical analyses

ASRs and numbers were analyzed to compare PUD prevalence and mortality trends among different cohorts. DALYs refer to the years lived with disability and years of life lost [ 15 ]. Estimated annual percentage changes (EAPCs) indicate ASR trends during a defined period. The specific EAPC was calculated using a generalized linear model (GLM) considering a Gaussian distribution for the ASR. Under the assumption of linearity on the log scale, which is equivalent to a constant change assumption, the EAPC was calculated. An EAPC estimation greater than zero indicates an increasing ASR trend, while an estimation less than zero indicates a decreasing ASR trend. If the 95% confidence interval (CI) of the EAPC crossed zero, the change in ASR was not obvious over time.

World maps and graphs were generated to display the distribution and change trends in global, regional, and national disease burdens attributable to PUD. Uncertainty was incorporated by sampling 1,000 draws combining uncertainty from a number of sources, including input data, corrections of measurement errors and estimates of residual nonsampling errors. The 2.5th and 97.5th centiles of the ordered draws were defined as uncertainty intervals (UIs). All calculations and figures were performed and made in EXCEL 2019 (Microsoft Corporation) and R software (version 4.0.0) with the “Rcan”, “ggplot2” and other packages.

Global burden and demographic profiles of PUD

Our study indicated that there were approximately 8.09 million (95% UI 6.79 to 9.58 million) prevalent cases of PUD in 2019, which represented an increase of 25.82% from 1990 [6.43 million (95% UI 5.41 to 7.63 million)]. Moreover, the age-standardized prevalence rate in 2019 was 99.40 per 100,000 (95% UI 83.86 to 117.55 per 100,000) population, which represented a decrease from 1990 [143.37 per 100,000 (95% UI 120.54 to 170.25 per 100,000) population](Additional file 1 : Table S1). Between 1990 and 2019, the number of incident cases of PUD increased from 2.82 million (95% UI 2.36 to 3.30 million) to more than 3.59 million (95% UI 3.03 to 4.22), representing an increase of 27.3% in the global incident cases of PUD. However, the global age-standardized incidence rate of PUD showed a decreasing trend, at 63.84 (95% UI 54.09 to 75.54) per 100,000 population in 1990 and 44.26 (95% UI 37.32 to 51.87) per 100,000 population in 2019 (Additional file 1 : Table S2). At the global level, nearly 6.03 (95% UI 5.59 to 6.64) million DALYs were attributable to PUD, with an age-standardized rate of 74.40 (95% UI 68.96 to 81.95) DALYs per 100,000 population in 2019. The age-standardized rate of DALYs decreased by 60.64% from 1990. Similar trends were also found in PUD-related deaths (Additional file 1 : Tables S3, S4).

Both the number of prevalent cases and age-standardized prevalence rate were higher in males than in females in all years from 1990 to 2019. However, the difference between the two groups decreased, mainly because the number of prevalent cases and age-standardized prevalence rate in males decreased faster than those in females. Overall, in 2019, 3.92 (95% UI 3.29 to 4.64) million prevalent cases occurred in females, whereas 4.17 (95% UI 3.49 to 4.97) million prevalent cases occurred in males. The proportion of prevalent cases between males and females was 1:0.94. The age-standardized prevalence rate was 94.23 (95% UI 79.10 to 111.93) per 100,000 population in females and 104.98 (95% UI 88.26 to 124.10) per 100,000 population in males in 2019 (Fig.  1 a).

Prevalence rates and deaths with age-standardized rate changes in all years from 1990 to 2019. a The numbers of prevalent cases and age-standardized prevalence rates in males and females. b The numbers of deaths and age-standardized death rates in males and females

From Jan.1st, 1990 to Dec 31st, 2019, the number of PUD-related deaths has shown a gradual, fluctuating decreasing trend in females and a relatively significant decreasing trend in males. Moreover, the age-standardized death rates in both groups showed downward trends. Among males, there were 127,522.08 (95% UI 115,260.65 to 143,079.71) PUD-related deaths and 3.57 (95% UI 3.23 to 4.00) per 100,000 population PUD-related age-standardized deaths in 2019, whereas there were 164,933.87 (95% UI 146,881.12 to 180,422.89) deaths and 9.58 (95% UI 8.62 to 10.43) age-standardized deaths in 1990. Among females, there were 108,617.41 (95% UI 96,020.68 to 120,954.17) PUD-related deaths and 2.50 (95% UI 2.21 to 2.79) per 100,000 population PUD-related age-standardized deaths in 2019, whereas there were 114,044.63 (95% UI 99,995.18 to 128,749.67) death and 5.56 (95% UI 4.91 to 6.22) age-standardized deaths in 1990. The number of PUD-related deaths was lowest in 2012 [102,041.21 (95% UI 92,732.31 to 111,554.31)]. This may be related to a variety of factors, such as the age distributions of the different sexes and the proportions of aging populations around the world (Fig.  1 b). The patterns of incidence (Additional file 1 : Figure S1) and DALYs (Additional file 1 : Figure S2) by sex and year were relatively similar to those of prevalence and death, respectively.

The global prevalence of PUD was higher in females than in males on both ends of the age spectrum (more than 70 and less than 24 years old). The PUD prevalence rates peaked in 65- to 69-year-old females [330,974.81 (95% UI 223,943.66 to 485,784.86)] and 55- to 59-years-old males [391,973.56 (95% UI 259,447.97 to 569,117.47)] in 2019. In addition, the age-standardized prevalence rates increased with age, peaking at 80–84 years in both males [393.04 (95% UI 275.22 to 537.73)] and females [385.16 (95% UI 270.52 to 525.41)] and then decreased until patients reached the oldest age group in 2019. Age-standardized prevalence rates were also higher in females than in males at both ends of the age spectrum (more than 85 and less than 24 years old) (Fig.  2 a). However, the age-standardized incidence rates were higher in males than in females and increased with age, peaking in the more than 95-year-old group in both males and females in 2019 (Fig.  2 b). For the age-standardized death rates (Additional file 1 : Figure S3), there was a sharp increase in those aged more than 70 years, and the trend in males increased more than that in females; there was a similar trend in DALYs (Additional file 1 : Figure S4). PUD-related deaths peaked in 80- to 84-year old female patients; at this point, the number of deaths in female patients exceeded that in male patients, which peaked in 75- to 79-year-old males.

Prevalent and incident cases with age-standardized rate changes in 2019. a The numbers of prevalent cases and age-standardized prevalence rates in males and females. b The numbers of incident cases and age-standardized death rates in males and females

Regional burden of PUD

For 30 years, the age-standardized prevalence rate in South Asia [156.62 (95% UI 130.58 to 187.05) in 2019] was highest among all the GBD super-regions. However, it showed a sharp decreasing trend. The super-regions with lowest age-standardized prevalence rates were Latin America and the Caribbean [41.77 (95% UI 35.53 to 49.29) in 2019] (Additional file 1 : Figure S5). Moreover, the age-standardized incidence rate trends of the 7 super-regions were similar to the prevalence rate trends from 1990 to 2019 (Additional file 1 : Figure S6). The high-income super-region had the lowest age-standardized death rate from 1990 to 2019 [1.08 (95% UI 0.96 to 1.19) in 2019]. South Asia presented the largest decreasing trend in the age-standardized death rate during the study period. The percent change from 1990 to 2019 was 66.92% (95% UI 59.25% to 73.22%). Central Europe, Eastern Europe, and Central Asia experienced a fluctuating but gradually decreasing trend (Additional file 1 : Figure S7, S8). Among the 21 GBD regions, the prevalence (Additional file 1 : Figure S9) and incidence cases (Additional file 1 : Figure S10) were highest in South Asia [2.52 (95% UI 2.09 to 3.01) million for prevalence in 2019] and East Asia [1.49 (95% UI 1.22 to 1.82) million for prevalence in 2019], with increasing trends. Although the numbers of PUD-related DALYs (Additional file 1 : Figure S11) and deaths (Additional file 1 : Figure S12) in South Asia and East Asia accounted for the largest proportions, the number of DALYs showed a decreasing trend. The number of deaths in East Asia showed a slight but fluctuating decrease.

In 2019, the age-standardized prevalence rates in males were higher than those in females in 16 GBD regions, with the exception of Western sub-Saharan Africa, South Asia, North Africa and the Middle East, High-income North America and Central sub-Saharan Africa. The region with the greatest difference in prevalence between males and females was High-income Asia Pacific (male:female, 2.35:1), followed by Central Asia (male:female, 2.13:1)(Additional file 1 : Figure S13). The age-standardized incidence rate showed almost the same trend (Additional file 1 : Figure S14). The age-standardized DALY rate was slightly higher in females than in males in only South Asia; in the rest of the GBD regions, males had a higher DALY rate than females. The region with the greatest difference in DALYs between males and females was Eastern Europe (male:female, 2.97:1), followed by Central Asia (male:female, 2.46:1)(Additional file 1 : Figure S15). The trend of death was similar to that of DALYs in 2019 (Additional file 1 : Figure S16). From 1990 to 2019, the age-standardized prevalence rate in males in all GBD regions decreased to varying degrees, but among females, four regions showed variable increases: Eastern Europe, Southern sub-Saharan Africa, Western sub-Saharan Africa and Central sub-Saharan Africa. The age-standardized death rates decreased among all 21 GBD regions, except in females in Eastern Europe and Central Asia. After estimating the EAPCs in the age-standardized prevalence and DALY rates, only females in Eastern Europe showed a consistent increasing trend (Additional file 1 : Figure S17, S18, S19, S20).

National burden of PUD

The age-standardized prevalence rate estimated for PUD in 2019 ranged from 15.19 to 330.32 per 100,000 population. Kiribati [330.32 (95% UI 286.98 to 379.81)], Vanuatu [247.62 (95% UI 214.30 to 284.91)] and Greenland [209.77 (95% UI 182.50 to 239.31)] had the highest age-standardized prevalence rates in 2019. Israel [15.19 (95% UI 11.83 to 18.85)], Costa Rica [17.28 (95% UI 14.59 to 20.33)] and Panama [19.95 (95% UI 16.25 to 23.98)] had the lowest rates (Fig.  3 a). The EAPCs in the age-standardized prevalence rates from 1990 to 2019 differed substantially between countries and territories. Turkey [1.39 (95% CI 1.01 to 1.77)], Norway [1.27 (95% CI 0.86 to 1.69)] and Ghana [0.84 (95% CI 0.43 to 1.26)] showed the largest increases, and Bangladesh [-6.80 (95% CI − 7.07 to − 6.53)], Brazil [-4.76 (95% CI − 5.16 to − 4.35)] and Bhutan [-4.24 (95% CI − 4.55 to − 3.94)] showed the largest decreases (Fig.  3 b). The countries and territories with the highest age-standardized PUD prevalence rates in 2019 also had the highest age-standardized incidence rates (Additional file 1 : Figure S21). The country with the highest EAPC in incidence rate was Norway [1.08 (95% CI 0.45 to 1.71)] (Additional file 1 : Figure S22).

Distribution of age-standardized prevalence rates and EAPCs in age-standardized prevalence rates of PUD globally. a The age-standardized prevalence rate (per 100,000 population) in both sexes globally in 2019. b The EAPC in the age-standardized prevalence rate in both sexes globally from 1990 to 2019. Maps in Fig. 3 were designed and plotted by ArcGIS (version 9.0). ATG Antigua and Barbuda, BRB Barbados, COM Comoros, DMA Dominica, FJI Fiji, FSM Federated States of Micronesia, GRD Grenada, KIR Kiribati, LCA Saint Lucia, MDV Maldives, MHL Marshall Islands, MLT Malta, MUS Mauritius, SGP Singapore, SLB Solomon Islands, SYC Seychelles, TLS Timor-Leste, TON Tonga, TTO Trinidad and Tobago, VCT Saint Vincent and the Grenadines, VUT Vanuatu, WSM Samoa

Age-standardized PUD-associated death rates in 2019 varied from 0.46 to 22.48 per 100,000 population. Cambodia [22.48 (95% UI 17.42 to 28.98)], Kiribati [21.78 (95% UI 16.38 to 27.96)] and Laos [19.24 (95% UI 14.04 to 26.14)] had the highest age-standardized death rates in 2019. Sri Lanka [0.46 (95% UI 0.32 to 0.64)], Italy [0.58 (95% UI 0.50 to 0.64)] and Israel [0.60 (95% UI 0.48 to 0.74)] had the lowest rates (Additional file 1 : Figure S23a). Only eight of the 204 countries and territories showed potential increasing EAPCs in age-standardized death rates (red regions in Additional file 1 : Figure S23b). Among them, only one country, Lesotho [1.19 (95% CI 0.04 to 2.36)], showed a definite increase, with all 95% CIs greater than zero. Bangladesh [-10.08 (95% CI − 11.83 to − 8.29)], the Republic of Korea [-7.34 (95% CI − 9.61 to − 5.02)] and Spain [-7.24 (95% CI − 10.46 to − 3.91)] had the largest decreases in age-standardized death rates from 1990 to 2010 (Additional file 1 : Figure S23b).

Socioeconomic profiles of PUD

A lower SDI was associated with higher age-standardized prevalence rates, incidence rates, DALYs and deaths associated with PUD, with values that were higher than the global rate in the two highest SDI quintiles and lower than the global rate in the three lowest SDI quintiles. The age-standardized prevalence rates in the high-SDI and low-SDI quintiles were 80.98 (95% UI 68.19 to 95.81) and 145.35 (95% UI 123.83 to 169.90) per 100,000 population in 2019, respectively (Additional file 1 : Figure S24). The high-SDI quintile [1.18 (95% UI 1.04 to 1.29)] was associated with the lowest age-standardized death rate in 2019, while the low-SDI quintile [6.15 (95% UI 5.31 to 7.04)] had the second-highest rate, which was just slightly lower than that of the low-middle-SDI quintile (Additional file 1 : Figure S25). In contrast, the largest decreases in age-standardized prevalence, incidence, DALY and death rates from 1990 to 2019 occurred in the low-SDI and low-middle-SDI quintiles. For the 21 GBD regions, positive associations were found between the age-standardized prevalence (Fig.  4 a), incidence (Additional file 1 : Figure S26), DALY (Additional file 1 : Figure S27) and death (Fig.  4 b) rates and SDI between 1990 and 2019. However, in the Saharan African regions, the downward trend of the prevalence rate associated with increasing SDI was not obvious. In the Southern sub-Saharan African region, the death rate showed an inverted U-shaped pattern; the death rate and SDI were positively correlated when the SDI was < 0.59 and negatively correlated when the SDI > 0.59. Positive associations between age-standardized prevalence, incidence, DALY and death rates and SDI for 204 countries and territories in 2019 were observed. The age-standardized prevalence rate was higher than the expected level in some countries such as Kiribati, Vanuatu and Greenland (Fig.  5 ). The estimated age-standardized DALY rate decreased when the SDI improved. Some countries and territories also had DALY rates that were significantly higher than expected, such as Kiribati, Cambodia and Laos (Additional file 1 : Figure S28).

Trends of age-standardized prevalence and death rates (per 100,000 population) in 21 GBD regions by SDI from 1990 to 2019. a Trends of age-standardized prevalence rates; b trends of age-standardized death rates by SDI

Age-standardized prevalence rates (per 100,000 population) of PUD in 204 countries globally by SDI in 2019. The gray line represents the expected age-standardized prevalence rate based on the SDI in 2019

PUD is usually defined as a greater than 3- to 5-mm rupture of the gastric or duodenal mucosa, which is caused by an imbalance in factors that protect the gastric and duodenal mucosa and factors that can cause damage. In this study, we analyzed the prevalence trends of PUD at the global, regional and national levels from 1990 to 2019, along with PPIs medication use over the span of thirty years. The prevalence of PUD in 2019 was approximately 8.09 million worldwide, and this study exhibited continues increasing tendency in the number of prevalent. Similar to the results of other research reports [ 16 , 17 ], the incidence of PUD showed a slight increase from 2006 to 2019, but the ASR showed a decreasing trend. However, in recent years, this downward trend has plateaued, which may be related to the fact that the main ulcer etiology has shifted in many countries from H. pylori infection to non-steroidal anti-inflammatory drug (NSAIDs) use [ 1 ]. For PUD, which is a chronic disease, it is often necessary to take appropriate drugs for a long period of time, and its recurrent characteristics and potentially serious complications have a significant impact on the social economy and medical and health costs.

PUD may be attributed to many etiologies, such as H. pylori infection, NSAIDs use, gastric bypass surgery, smoking, selective serotonin reuptake inhibitor use, stress, lifestyle habits and genetic characteristics, which have been identified as the main risk factors [ 1 , 2 ]. During the study period, especially in the first 20 years, the incidence of and mortality due to PUD showed significant decreasing trends, which were closely related to PPIs use and the widespread administration of anti- H. pylori treatment, which started in the late 1980s. In the last 10 years of the study period, the incidence of and mortality due to PUD showed relatively stable trends that did not decline with the further promotion of anti- H. pylori treatment. However, there was an increase in the use of NSAIDs, especially aspirin and other drugs, and these drugs often lead to serious complications in patients with PUD. In previous studies, especially in Australia, a country with an inexplicable history of H. pylori , H. pylori infection was associated with 70% to 90% of PUD cases [ 18 , 19 ]. Although these values are lower in some other studies, H. pylori infection is still a key factor in the pathogenesis of PUD [ 20 ]. Despite anti-inflammatory effect, NSAIDs are always used in antipyrexia and analgesic therapy, which makes NSAIDs as most commonly prescribed medicine [ 21 ]. Targeting cyclooxygenases enzymes (COXs), NSAIDs are divided into non-selective NSAIDs and selective COX-2 inhibitors, such as aspirin and celecoxib repectively [ 22 ]. However, NSAIDs could cause gastrointestinal adverse effects including ulcers, bleeding or perforation [ 21 , 23 ]. Drugs such as aspirin and other NSAIDs account for approximately 10% of PUD cases. NSAIDs have a stronger correlation with duodenal ulcers than with gastric ulcers. In recent decades, the use of these drugs has increased dramatically [ 24 , 25 ]. They account for approximately 5% to 10% of all prescription drugs each year and have shown an increasing trend [ 26 ]. In general practice, the prevalence of NSAIDs use in patients over 65 years old is as high as 96% [ 27 ]. A study from Norway indicated that approximately 7.3% of elderly patients over 60 years old took at least one NSAIDs prescription within one year period [ 28 ]. Differ from aspirin, selective COX-2 inhibitors have a weaker association with PUD than nonselective NSAIDs, which suppress COX-1 activity to inhibit gastric mucosa repair [ 29 , 30 ].

For sever obesity patients, bariatric surgery, such as Roux-en-Y gastric bypass (RYGBP) surgery and duodenal switch (DS) surgery, could be a proper therapy to reduce weight and comorbidities [ 31 ]. Due to well-established procedure and nearly 70 years of surgical experience, RYGBP is considered as gold standard for bariatric surgery [ 32 ]. Although overweight and related metabolic symptoms would be reduced after gastric bypass surgery, several complications still might influence the recovery of operated patients, such as marginal ulcer (MU). MU developed at or distal to gastroenteral anastomosis and occurs in approximately 5% of obese patients undergoing gastric bypass surgery [ 31 , 33 ]. In patients with upper gastrointestinal symptoms after gastric bypass surgery, the incidence can reach 27% to 36%, indicating gastric bypass surgery history might contribute to the development of PUD [ 1 , 34 ].

In the vast majority of GBD regions, the incidence of and mortality due to PUD showed significant downward trends with increasing SDI; this is closely related to the awareness of H. pylori treatment and the appropriate management of other chronic diseases. However, in some areas, this relationship is questionable, especially in the southern sub-Saharan African region. The cause of this phenomenon is still controversial and may be related to the epidemiological characteristics and risk factors for PUD in such countries and territories. Although the incidence of H. pylori infection had decreased as SDIs increased in these areas, in some countries, the infection rate remains very high. NSAIDs use rates in these areas were significantly lower than those in developed countries [ 35 , 36 ]. Studies have also shown that the rates of severe PUD-related complications, such as perforation of the digestive tract, are high in these countries and territories and appear to be associated with Khat intake [ 37 ]. When stratified by SDI, the incidence of PUD showed decreasing trends in different groups over time. The decrease was more obvious in low- and low-middle-SDI regions than in high-SDI regions, and the incidence of PUD tended to plateau in high-SDI regions; however, it was still far lower than those in low-SDI regions. PUD-related deaths decreased in all groups. In 2019, in different countries and regions, the prevalence of PUD generally decreased with increasing SDI, but in some Pacific islands, such as Kiribati and Vanuatu, the prevalence of PUD remained abnormally high. This may be related to the high H. pylori infection rate among and the ethnic characteristics of Pacific islanders. Some studies found that Maori and Pacific Island adults and children living in South Auckland had a high rate of infection with H. pylori compared to Europeans from the same area [ 38 ]. Data showed that household crowding involving children in New Zealand contributed to 44% of H. pylori infections in Pacific Islanders, 36% in Maori people and 14% in Europeans [ 39 , 40 ].

The age-standardized incidence rate showed an increasing annual trend with increasing age. This is different from the incidence rate of H. pylori . A multicenter cross-sectional study showed that the positive rate of H. pylori serum antibody increased linearly from the 30- to 39-year-old age group to the 60- to 69-year-old group, while the infection rates of H. pylori in people aged 20 to 29 and over 70 years old were low. The change in the H. pylori infection rate showed a trend of initially increasing and then decreasing with age [ 41 ]. The consistent increase in the age-standardized incidence rate may be associated with an increased incidence of drug-related PUD in older people who are more likely to suffer from other chronic diseases and require other medications, such as NSAIDs. Studies have shown that the use of NSAIDs peaks at approximately 50 years old, and after 70 years old, the use of NSAIDs, especially aspirin, decreases, which is related to the increased incidence of NSAID-related adverse reactions in the elderly population [ 42 , 43 ]. Estrogen can prevent ulcers by inhibiting the synthesis and release of gastrin and reducing the secretion of gastric acid. The decrease in estrogen levels in elderly females may be a protective factor for PUD [ 44 ] and may also cause a slight decrease in the growth trend of the age-standardized incidence rate in elderly women over 80 years old.

Regarding sex, at the end of the twentieth century, the incidence of and mortality due to PUD showed significant decreases, and the trends in males were more obvious than those in females. Over time, the decreasing trends of the age-standardized incidence and mortality rates became less steep, but the rates in males remained higher than those in females. PUD-related deaths and DALYs were significantly lower in females than in males. However, further analysis of PUD-related factors revealed that the incidence in females was slightly higher than that in males aged less than 20 years. In 2019, among the different GBD regions, the incidence rates of PUD in the Oceania, High-income Asia Pacific, Eastern Europe, East Asia and Central Asia regions were significantly higher in males than in females, while in other regions, there was no significant difference in the incidence between the sexes. In some regions, such as Western sub-Saharan Africa, the rate in females was significantly higher than that in males. However, the PUD-related death rate was higher in males than in females, except in Central sub-Saharan Africa. In West African countries, such as Ghana and Nigeria, the incidence of PUD in females accounted for approximately 54–57% [ 35 ]. Research results have shown that there is a sex difference in the influence of acetic acid-induced gastric ulcer formation in rats. After the administration of certain interventions, the natural defensive mechanism in the gastric mucosa was adversely disturbed in male rats but activated in female rats [ 45 ]. This phenomenon is similar to previous clinical and the current research results, although the specific mechanism is not completely clear.

There were increasing trends in the EAPCs in the age-standardized prevalence and DALY rates among only female patients in Eastern Europe (marginally increasing incidence and death rate trends) from 1990 to 2019, mainly due to the increase in the number of females in Russia and the Ukraine. In these two countries, especially in Siberia, the H. pylori infection rates were significantly higher than those in other regions. However, there were no differences in H. pylori infection rates between the sexes and among ethnicities [ 46 , 47 ]. Therefore, the consistently increased risk of PUD among females in these areas may be related to factors such as drugs or bypass surgery [ 48 , 49 ]. These reasons require further study to produce high-level evidence-based medical evidence.

The roles of anti- H. pylori therapy and acid suppression therapy in the treatment and prevention of PUD are clear. Identifying high-risk populations and preventing drug-related complications are particularly important at this stage. Anti- H. pylori treatment can reduce the incidence of PUD and reduce the risk of gastric cancer in high-risk groups. Similar to acid suppression therapy, it will not increase the economic burden of disease treatment. However, there is still some controversy regarding whether to administer anti- H. pylori treatment in all positive patients considering the extensive administration of antibiotics, as it may promote the production of other resistant bacteria, leading to the occurrence of Clostridium difficile -associated diarrhea, and increase the potential risk of cardiovascular disease [ 50 , 51 ]. Acid suppressant drugs, mainly PPIs, seem to be the most effective class of gastroprotectants for the management of PUD [ 52 ]. Especially in recent years, the risk factors for PUD have gradually changed from H. pylori infection to drug-related PUD, so treatment with PPIs has gradually increased in importance. Especially in patients with gastrointestinal bleeding, PPIs can significantly reduce the incidence of adverse outcomes. However, PPIs also have certain medication risks, such as an increased risk of fracture and the development of other infections. These risks still lack strong evidence, and the benefits of PPIs greatly outweigh their associated risks. The current controversy mainly concerns the durations and doses of PPIs and whether oral PPIs have the same effect as intravenous medication in maintenance treatment [ 53 ].

The study has some limitations. First, critical information about disease burden in some countries does not exist or was unavailable, making it difficult to illustrate and understand health trends. Second, compared with other chronic noncommunicable diseases with high mortality rates, the mortality rate associated with PUD is relatively low, but PUD has the characteristic of recurrence. The high prevalence rate also results in a high disease burden. However, compared with that of malignant tumors, diabetes, and cardiovascular and cerebrovascular diseases, evidence indicating that PUD should be considered a high-priority disease is lacking [ 54 ].

In conclusion, this study focused on the epidemiological characteristics of PUD in different countries and territories, different age groups and different sexes. Overall, the risk of morbidity and mortality due to PUD decreased significantly, but with the passage of time for H. pylori eradication, the downward trend gradually weakened, which might be related to the gradual shift in the main risk factors for PUD from H. pylori infection to wide use of NSAIDs. Therefore, additional medical and health-related attention is needed to control the incidence of PUD and the occurrence of adverse events.

Availability of data and materials

The datasets generated and/or analyzed during the current study are available in the Global Burden of Disease, Injuries and Risk Factors Study ( http://ghdx.healthdata.org/ ).

Abbreviations

• Peptic ulcer disease

Proton-pump inhibitor

Nonsteroidal anti-inflammatory drugs

Global Burden of Disease, Injuries and Risk Factors Study

Disability-adjusted life years

Age-standardized rate

Global Health Data Exchange database

Sociodemographic index

Estimated annual percentage change

Generalized linear model

Confidence interval

Uncertainty interval

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Acknowledgements

We thank the Global Burden of Disease, Injuries and Risk Factors (GBD) Study which provided the free data for this study.

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Department of Surgical Oncology, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, 710061, Shaanxi, China

Xin Xie, Kaijie Ren, Chengxue Dang & Hao Zhang

Department of Nuclear Medicine, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, 710061, Shaanxi, China

Department of Oncology, The Second Affiliated Hospital of Xi’an Jiaotong University, Xi’an, 710004, Shaanxi, China

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XX, KJR and HZ prepared the manuscript. XX, ZJZ and HZ analyzed and managed the data of this study. XX and HZ reviewed the final manuscript. CXD and HZ designed and supervised this study. All authors reviewed the data and agreed the publication of this manuscript.

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1 : Table S1 . PUD prevalence in 1990 and 2019 for both sexes and estimated annual percentage change in age-standardized rates by location; Table S2 . PUD incidence in 1990 and 2019 for both sexes and estimated annual percentage change in age-standardized rates by location; Table S3 . DALYs of PUD in 1990 and 2019 for both sexes and estimated annual percentage change in age-standardized rates by location; Table S4 . PUD death in 1990 and 2019 for both sexes and estimated annual percentage change in age-standardized rates by location; Figure S1 . Incident cases with age-standardized incidence rate (per 100,000 population) changes in all years from 1990 to 2019; Figure S2 . DALYs with age-standardized rate (per 100,000 population) changes in all years from 1990 to 2019; Figure S3 . Deaths with age-standardized death rate (per 100,000 population) changes by age in 2019; Figure S4 . DALYs with age-standardized DALY rate (per 100,000 population) changes by age in 2019; Figure S5 . Age-standardized prevalent rate changes in PUD in seven super-regions in all years from 1990 to 2019; Figure S6 . Trends of age-standardized incidence rates (per 100,000 population) in seven super-regions in all years from 1990 to 2019; Figure S7 . Trends of age-standardized death rates (per 100,000 population) in seven super-regions in all years from 1990 to 2019; Figure S8 . Trends of age-standardized DALY rates (per 100,000 population) in seven super-regions in all years from 1990 to 2019; Figure S9 . Trends of prevalent cases of PUD in 21 GBD regions in all years from 1990 to 2019; Figure S10 . Trends of incident cases of PUD in 21 GBD regions in all years from 1990 to 2019; Figure S11 . Trends of DALYs due to PUD in 21 GBD regions in all years from 1990 to 2019; Figure S12 . Trends of PUD-related deaths in 21 GBD regions in all years from 1990 to 2019; Figure S13 . Age-standardized prevalence rates (per 100,000 population) of PUD in males and females in 21 GBD regions in 2019; Figure S14 . Age-standardized incident rates (per 100,000 population) of PUD in males and females in 21 GBD regions in 2019; Figure S15 . Age-standardized DALY rates (per 100,000 population) due to PUD in males and females in 21 GBD regions in 2019; Figure S16 . Age-standardized death rates (per 100,000 population) due to PUD in males and females in 21 GBD regions in 2019; Figure S17 . Estimated annual percentage changes in age-standardized prevalent rates in different regions between 1990 and 2019; Figure S18 . Estimated annual percentages of age-standardized incident rates (per 100,000 population) in 21 GBD regions between 1999 and 2019; Figure S19 . Estimated annual percentages of age-standardized DALY rates (per 100,000 population) in 21 GBD regions between 1999 and 2019; Figure S20 . Estimated annual percentages of age-standardized death rates (per 100,000 population) in 21 GBD regions between 1999 and 2019; Figure S21 . Distributions of age-standardized incidence rates (per 100,000 population) of PUD in different regions in 2019; Figure S22 . Distributions of age-standardized incidence rates (per 100,000 population) of PUD in different regions from 1999 to 2019; Figure S23 . Distributions of age-standardized death rates and EAPCs in age-standardized prevalence rates of PUD globally; Figure S24 . Trends of age-standardized prevalence rates (per 100,000 population) in different SDI regions from 1990 to 2019; Figure S25 . Age-standardized death rates (per 100,000 population) from 1990 to 2019 in different SDI regions; Figure S26 . Trends of age-standardized incidence rates (per 100,000 population) of PUD in 21 GBD regions by SDI; Figure S27 . Trends of age-standardized DALY rates (per 100,000 population) of PUD in 21 GBD regions by SDI; Figure S28 . Age-standardized DALY rates (per 100,000 population) due to PUD globally in 204 countries and territories by SDI in 2019.

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Xie, X., Ren, K., Zhou, Z. et al. The global, regional and national burden of peptic ulcer disease from 1990 to 2019: a population-based study. BMC Gastroenterol 22 , 58 (2022). https://doi.org/10.1186/s12876-022-02130-2

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DOI : https://doi.org/10.1186/s12876-022-02130-2

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Mrs. Baker is a 54 year old female who presented to the ED complaining of nausea and severe epigastric pain x 3 days. She reports a history of osteoarthritis and reports taking ibuprofen 400 mg 3-4 times a day regularly for the last few months since her “arthritis has gotten really bad”.

What initial nursing assessments should be performed?

• Put the patient on a monitor to assess EKG. A 12-lead EKG should be done to rule out cardiac involvement, request order for cardiac enzymes from provider
• Auscultate heart and lung sounds
• Full abdominal assessment – inspect, auscultate, palpate and percuss. Assess for tenderness over specific areas, feel for masses, and look for guarding.
• Get more detailed history questions – vomiting? Bloody stools? Has this happened before?

Patient demonstrates guarding when palpating epigastric region, no tenderness to palpation over RLQ, LLQ, or LUQ. Some tenderness over RUQ.  Bowel sounds are hyperactive, lungs are clear to auscultation, S1 and S2 heard clearly with no murmurs. As you finish your assessment, Mrs. Baker reports she is going to be sick and vomits approximately 300 mL of coffee-ground emesis.

Explain the significance of coffee-ground emesis.

• Coffee-ground emesis is vomit that looks like it has coffee-grounds in it.
• These black specs are actually hemolyzed blood cells/clots.
• Coffee-ground emesis is indicative of a slow source of bleeding within the stomach or refluxing from the duodenum.

You notify the provider of the coffee-ground emesis, administer Ondansetron 4 mg IV per provider orders, and assist Mrs. Baker with oral care.

What further diagnostic testing do you expect to be performed for this patient?

• Complete Blood Count
• Occult blood testing of stool and emesis
• Patient may need an EGD (esophagogastroduodenoscopy) to check for bleeding ulcers

Mrs. Baker is now weak and drowsy. Her fecal occult test is positive and her CBC shows a Hemoglobin of 10 g/dL and a Hematocrit of 31%.  Per provider orders, you insert an NG tube to evaluate stomach contents and decompress the stomach. You connect the NG tube to intermittent low wall suction.

What is likely going on with Mrs. Baker physiologically?

• Mrs. Bakers chronic heavy use of NSAID’s may have caused ulcers to form in the lining of her stomach and/or duodenum
• It is possible that these ulcers are now bleeding

What is the benefit to decompressing the stomach via NG tube?

• Decompressing the stomach removes the majority of stomach acid, thereby decreasing the irritation on the stomach lining
• The hope is to prevent further irritation to any bleeding ulcers

The UAP notifies you that Mrs. Baker’s blood pressure has dropped to 96/60. You enter the room and see that the suction canister is over halfway full of bright red blood.

What is your priority assessment at this time?

• Assess Mrs. Baker – LOC, heart and lung sounds, confirm the accuracy of vital signs
• Protect airway – suction if needed, minimize risk for aspiration

What may be happening to Mrs. Baker?

• She may have an ulcer that is bleeding more actively than before. With that amount of blood, it could possibly be an arterial bleed.

Mrs. Baker is pale, diaphoretic, and drowsy. Her heart rate is up to 122. You notify the provider who orders to transfuse 2 units of PRBC’s and calls the Gastroenterology team for a STAT EGD. Within 30 minutes the patient is taken to the GI lab for an EGD, where they find two slow-bleeding gastric ulcers, which they cauterize, and 1 arterial bleed which they repair as well.  Mrs. Baker returns to the unit post-procedure for observation.

What are nursing priorities for Mrs. Baker after this procedure?

• Keep NPO until gag reflex returns
• Assess and monitor output from NG tube
• Monitor vital signs closely
• Monitor LOC as she awakens from sedatives used during the procedure
• Ensure the full 2 units of PRBC’s were administered. If not, continue transfusion.

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Clinical presentation and surgical management of perforated peptic ulcer in a tertiary hospital in Mogadishu, Somalia: a 5-year retrospective study

• Abdihamid Mohamed Ali 1 ,
• Abdulkadir Nor Mohamed 1 ,
• Yahye Garad Mohamed 2 &
• Salim İdris Keleşoğlu 3  

World Journal of Emergency Surgery volume  17 , Article number:  23 ( 2022 ) Cite this article

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Perforated peptic ulcer is a common surgical emergency condition worldwide, which is associated with significant morbidity and mortality if early diagnosis and immediate surgical management were not carried out. Perforation occurs in roughly 5% of PUD patients during their lifetime; this study aimed to explore the wide range of clinical presentations, associated risk factors, complications, and surgical management of perforated peptic ulcer patients.

A 5-year retrospective observational study on the clinical presentation and surgical management of perforated peptic ulcer is carried out in a tertiary hospital in Mogadishu, Somalia, Department of General Surgery, from January 2017 to December 2021. We included all patients undergoing operations with an intraoperative confirmed diagnosis of perforated peptic ulcer at the general surgery department. For operated patients, follow-up evaluation was performed in the outpatient department.

Fifty-one patients underwent an emergency operation for perforated peptic ulcer during the study period. The sociodemographic distribution of patients was 45 (88.2%) males and 6 (11.8%) females, giving a male-to-female ratio of 7.5:1. The mean age of patients was 35.5 ± 16.8 years, and the peak frequency was in the third decade. The commonest presenting symptoms were sudden onset of severe epigastric pain in 42 (82.4%) patients. Patients who presented perforated peptic ulcer within 24 h of initiation of symptoms were free from complications. Age-group and delayed presentation > 48 h after onset of symptoms were linked to postoperative complications and were statistically significant (P 0.032 and P 0.005), respectively. Four patients died (mortality rate of 7.8%). Two patients were reoperated because of the failed primary repair, and 4 patients had > 5 cm intra-abdominal abscess image-guided percutaneous drainage, and the rest were given antibiotic therapy according to peritoneal fluid culture and sensitivity results. The most common microorganism isolated was E. coli 22% and Klebsiella 11%. Other rare microorganisms (pseudomonas, Staphylococcus aureus, and Candida spp.) were identified. In half (51%) of the patients with peritoneal fluid culture, no microorganism growth was seen.

The distribution of perforated peptic ulcer is common in the young age-group in the third decades of life. Delayed presentation of the disease is linked because most patients arrived from remote areas where proper facilities of health care and health education are not available and the patient might come to the hospital in an advanced stage of the disease. We suggest conducting further researches, health awareness related to complications over-the-counter drugs self-medication, and bad habit including smoking, and to improve health-seeking behaviors of society.

Peptic ulcer disease (PUD) affects 4 million people globally each year. The incidence of PUD has been estimated to be between 1.5 and 3%. Perforation occurs in roughly 5% of PUD patients during their lifetime. Perforated peptic ulcer is a common surgical emergency condition worldwide, which is associated with significant morbidity and mortality if early diagnosis and immediate surgical management were not carried out, having a mortality rate that ranges from 1.3 to 20% [ 1 ].

PUP is characterized by the classic triad of abrupt abdominal discomfort, tachycardia, and abdominal tenderness. “I hardly believe that anybody can fail in establishing a diagnosis,” Edward Crisp mentioned in 1843 [ 2 ].

Young age-group distribution is commonly seen in the developing world, which is mostly predisposed by smoking. With the advanced age in developed countries, these patients tend to be elderly with multiple comorbidities and associated use of NSAIDs, Helicobacter pylori, physiological stress, corticosteroids, and previous history of PUD are risks factors for PUP [ 3 , 4 ].

Mortality risk was associated with age more than 60 years, shock (systolic pressure < 90 mmHg) at presentation, and delayed presentation (more than 24 h before surgery). Early diagnosis, prompt resuscitation, and urgent surgical intervention are essential to improve outcomes [ 5 ].

According to the diagnostic value of radiological investigation, 75% of patients with perforated peptic ulcer free air under the diaphragm were detected on erect chest/abdominal X-ray.

In comparison with a computed tomography scan which reveals superior diagnostic accuracy of 98%, a CT scan can help to distinguish other mimicking differential diagnoses of the acute abdomen like acute pancreatitis that would not require surgical intervention; the utility of this CT scan is justified when the clinical presentation is not specific to upper gastrointestinal pathology or malignancy is suspected and patients’ hemodynamic is not deranged [ 6 ].

Exploratory laparotomy and omental patch repair remain the gold standard. Laparoscopic surgery should be preserved in the early presentation of disease and diminished associated complications. Definitive anti-ulcer surgery is significantly associated with fatal outcomes in these patients, while it increases the length of the operation, exposes the patient to prolonged anesthetic time, and increases the chance of postoperative complications. Gastrectomy is recommended in patients with a large or malignant ulcer [ 7 , 8 ].

The present study aimed to explore the wide range of clinical presentations, associated risk factors, complications, and surgical management among patients with perforated peptic ulcer. There has been no previous research related to this topic in the country, and this research will be a foundational study in the field.

Methods study

Design and study area.

A 5-year retrospective observational study on the clinical presentation and surgical management of perforated peptic ulcer is carried out in a tertiary hospital in Mogadishu, Somalia, Department of General Surgery, from January 2017 to December 2021.

Mogadishu Somali Turkey Recep Tayyip Erdoğan Training and Research Hospital is one of the country's main referral hospitals, located in Mogadishu, the capital city of Somalia. It has a bed capacity of 250, 7 operating rooms, 28 intensive care units, 28 dialysis machines, and 300 dialysis beds, as well as a radiology department with diagnostic facilities (digital X-rays, ultrasounds, CT scanner, 1.5 T MRI, fluoroscopy) capable of performing many interventional procedures, such as ultrasound-guided and CT-guided percutaneous drainages, and serves people seeking health care from all over the country. It is also a teaching and consulting hospital that offers residency programs in 19 different specialties.

The patients were identified and extracted from hospital electronic medical records; 51 patients operated on perforated peptic ulcer for emergency surgery were reviewed, where patient clinical information including patient demographic characteristics, diagnoses, investigative (laboratory and radiological) workup, performed surgical procedure, complications, hospital stay, pathology results, peritoneal fluid culture and sensitivity, and mortality was reviewed.

A comprehensive history and physical examination were performed followed by blood investigations (e.g., CBC, liver and renal function test, electrolytes, viral markers, and blood group). Radiological investigations like X-ray abdomen erect, chest X-ray and, if necessary, an abdominal CT were performed in patients on the suspicion of diagnosis of perforated PUD.

The diagnosis of perforated peptic ulcer was confirmed with laparotomy and simple closure of the perforation by primary closure of the defect by 2.0 vicryl, and then application of the omental flap (modified Graham patch repair/omentopexy) was done.

Intraoperatively, copious saline irrigation was done and all gastric ulcers were taken a biopsy of the border of the ulcer in a systematical manner, and peritoneal fluid samples were taken for culture and sensitivity analysis.

We included all patients undergoing operations with an intraoperative confirmed diagnosis of perforated peptic ulcer at the general surgery department.

Those who operated in another hospital and were later referred to our hospital and those who operated in the pediatric surgery department were excluded from the study.

For operated patients, a 3–6-month follow-up evaluation was performed on an outpatient basis depending on their compliance.

Data analysis

We used the Stata version 15 (StataCorp, College Station, TX) statistical program to perform statistical data analysis. Data were presented in proportions and frequency tables for categorical variables. To summarize the data for continuous variables, we utilized ranges, medians, and inter-quartile ranges (IQRs). We computed P values for categorical variables using the odds ratio (OR) and its 95% confidence interval (CI). We determined the variables associated with the outcome using logistic regression, and to adjust for confounding variables, we used multivariate logistic regression and direct standardization techniques. The significance was defined as a P value of 0.05 or less.

Sociodemographic characteristics

Fifty-one patients underwent an emergency operation for perforated peptic ulcer during the study period. The sociodemographic distribution of patients was 45 (88.2%) males and 6 (11.8%) females, giving a male-to-female ratio of 7.5:1.

According to the age-group of the study population, they ranged from 18 to 70 years, with a mean age of 35.5 ± 16.8 years. The peak frequency was in the third decade (20–30 years).

Clinical presentation and risk factors

The most common presenting symptoms were sudden onset of severe epigastric pain in 42 (82.4%), abdominal tenderness in 41 (80.4%), abdominal distention in 36 (70.6%), and vomiting in 31 (60.8), clinical signs of peritonitis were seen in 38 (74.5%), and < 90 mmHg systolic pressure was observed in 15 (29.4%) patients (Table 1 ).

Two-third of the patients 34 (66.7%) were aged < 40 years; a positive previous history of peptic dyspepsia disease was noted in nearly half of the patients 25 (49%). Twenty-three patients (45.1%) had a positive history of ingestion of painkillers including nonsteroidal anti-inflammatory drugs (NSAIDS). Twenty-four patients (47.1%) had a history of cigarette smoking (Table 3 ).

The duration of symptoms ranged from 1 to 10 days with a mean duration of 3.8 ± 1.9 days; the median was 4 days.

The majority of patients 22 (43.1%) presented after 2–3 days of onset of symptoms. More than one-third of patients 19 (37.3%) presented of onset of symptoms between 4 and 5 days, 7 (13.7%) presented beyond 5 days after symptoms started, and only 3 (5.8%) presented within 24 h of onset symptoms.

Diagnosis and surgical intervention

The total number of patients who performed chest/erect abdominal X-ray was 43; among these, air under diaphragm was detected in 27 (62.8%) patients. And 45 patients performed abdominal CT scan, and perforation signs were observed in 44 (97.7%) patients. Benign tissue inflammation was seen in performed pathological samples.

Modified Graham patch repair was done in nearly all the cases, and only two cases of sealed perforation underwent peritoneal lavage. Two patients were reoperated because of the failed primary repair, and in 4 patients with > 5 cm intra-abdominal abscess image-guided percutaneous drainage was performed, and in the rest antibiotic therapy was performed according to peritoneal fluid culture and sensitivity results.

In half (51%) of the patients with peritoneal fluid culture, no microorganism growth was seen. The most common microorganism isolated was E. coli 22% and Klebsiella 11%. The others are rare microorganisms (pseudomonas, Staphylococcus aureus, and Candida spp.) (Fig.  1 ).

Microorganism detected in culture fluid analysis of peritoneal fluid

Hospitalization duration and complications

A hospital stay of the patients ranged from minimum of 4 days to a maximum of 20 days; the mean average admission day was 8.7 ± 3.4 days.

The most common complication seen in these patients is pleural effusion which accounts for 29 (56.9%); the second foremost complication noticed in this study was acute renal failure which is about half (23 (45%)) of the patients. Surgical site infection was noted in nearly one-third (16 (31.4%)) of the patients, three patients (5.9%) developed an incisional hernia after 1 year of primary surgery, and only two patients encountered repair site leak (Table 2 ).

Pleural effusion was significantly high in those patients with a delayed presentation, i.e., 20 out of 29 patients came beyond 72 h of the onset of symptoms (P value 0.013).

Patients who presented perforated peptic ulcer within 24 h of initiation of symptoms were free from complications (Table 3 ).

Four patients died giving a mortality rate of 7.8%, as mentioned in Table 4 .

Univariate and multivariate analyses of predictors of complications

Table 5 demonstrates the predictors of complications according to bivariate and multivariate logistic regression analyses. Keeping in mind that the majority of our study population was patients less than 40 years of age, complications associated with this group were statistically significant (P 0.032).

Alongside the age-group, also delayed presentation > 48 h after onset of symptoms was linked to postoperative complications and it is statistically significant (P 0.005).

Higher CRP levels were attributed to the progressive inflammation and advanced peritonitis; in the present study, 68% of patients with CRP levels above 150 mg/L developed complications, but it is not statistically significant. In parallel with other examined factors, cigarette smoking, NSAID use, Hxdyspepsia, and perforation site were all found to have a non-statistically significant association with complications (Figs. 2 , 3 , and 4 ).

Chest X-ray showing a large volume of free sub-diaphragmatic gas with air–fluid levels under both hemidiaphragm (arrows)

An axial abdominal CT showing free sub-diaphragmatic with air–fluid levels under right hemidiaphragm (yellow arrow), extensive free intraperitoneal fluid (blue arrow), and left pleural effusion (red arrow)

Intraoperative: perforated peptic ulcer on the anterior wall of the pyloric region in three different patients (arrows)

Despite the fact that perforated peptic ulcer disease is a common surgical emergency and that eradication of Helicobacter pylori has resulted in a vast decline in peptic ulcer prevalence, the number of patients requiring surgery has remained relatively constant [ 9 ].

The distribution of perforated peptic ulcer is common in the young age-group in the third decades of life; similar studies in Africa and around the globe demonstrated comparable results [ 8 , 10 , 11 ].

Our study demonstrated a male predominance of perforated peptic ulcer, where the majority of the patients were 45 (88.2%) males, giving a male-to-female ratio of 7.5:1 related to other studies where the male/female ratio ranged in 1.3:1 in Tanzania, 3.3:1 in Nigeria, 6.5:1 in Ethiopia, 4:1 in Singapore, and 6.8:1 in Saudi Arabia, respectively [ 8 , 9 , 12 , 13 , 14 ].

This study revealed enormous patients with delayed presentation of the disease; this is linked to most patients arriving from remote areas where proper facilities of health care and health education are not available and the patient might come to the hospital in an advanced stage of the disease; related studies agreed these findings [ 15 , 16 ].

Adoption of national Essential Package of Health Services (EPHS) to all the regions of the country to have access in emergency care facility, as well as training the care providers for early identification of common signs and symptoms of abdominal emergencies, might promote preventing the late presentation of the disease.

The mean average of hospital admission days was 8.7. Long-term hospital stay was discovered as long as 20 days which correlates with late presentation of cases superimposed by consequence complications related to perforated peptic ulcer.

The comparable outcome was documented in various studies in the region and around the globe, concluding that hospital stay and related complications of PUP including death increased in delayed (> 24 h) presentation of the disease [ 17 , 18 , 19 ].

Positive previous history of peptic dyspepsia was observed in nearly half (25 (49%)) of the patients with peptic ulcer, this might explain the inaccessibility of good health facilities, and most of them may encounter non-professional health workers and traditional healers in many parts of the regions, and patient will seek proper health care facility when condition gets worse and patient develops severe abdominal pain and peritonism. This finding is common in developing countries as several reports stated [ 8 , 10 , 13 ].

The two most common microorganisms isolated were E. coli 22% and Klebsiella 11%; a comparable result was found in a study done in India [ 20 ].

Patients with age less than 40 years and delayed presentation of disease were found positive predictors of complications with statistically significant according to bivariate and multivariate logistic regression analyses with a p value of 0.032 and 0.005, respectively. Both factors observed a positive association with postoperative complications. This is particularly noteworthy in developing countries, including Africa, where patients often present late with severe generalized peritonitis, which correlates with a similar study in Tanzania and other parts of the world [ 8 , 21 ].

The patient with a perforated peptic ulcer and sepsis should be evaluated and identified as early as possible to avoid subsequent organ failure and death [ 1 ].

There was no significant association between complications and other above-examined factors.

The mortality rate of 7.8% of patients with perforated peptic ulcer was shown in our study; this substantial rate was worldwide reported in numerous studies as 15.5, 14%, 16.7%, and 27% [ 19 , 22 , 23 , 24 ].

This study has some limitations since it is a retrospective cross-sectional study with a single-center-based design. That might limit the generalizability of the findings.

Perforated peptic ulcer is still a common surgical emergency problem in our country predominantly affecting young males and is associated with substantial morbidity and mortality in delayed disease presentation. Early diagnosis, immediate resuscitation, and urgent surgical intervention are warranted.

Simple primary repair with application omental flap (modified Graham patch repair) is the most appropriate and effective surgical approach in the management of perforated peptic ulcer.

It increases the length of the operation, exposes the patient to prolonged anesthetic time, and increases the chance of postoperative complications.

This is particularly noteworthy in developing countries, including Africa, where patients often present late with severe generalized peritonitis.

Implementation of endoscopic assessment in chronic and intractable dyspepsia will improve the early detection and management of non-complicated peptic ulcer disease.

We suggest further research, preferable to a multicenter study, to determine the epidemiology, associated risk factors, and prognostic factors of the disease in our context, and to conduct health awareness related to complications over-the-counter drugs self-medication and bad habit including smoking and to improve health-seeking behaviors of society.

Availability of data and materials

The data that support the findings of this study are available in Mogadishu Somali Turkey, Recep Tayyip Erdogan Training and Research Hospital information system. Data are, however, allowed to the authors upon reasonable request and with permission of the education and research committee.

Abbreviations

Peptic ulcer disease

• Peptic ulcer perforation

Acute renal failure

Nonsteroidal anti-inflammatory drugs

Essential Package of Health Services

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A.M.A. and A.N.M. participated in study conception and design, material preparation and data collection. A.M.A. and Y.G.M. performed data analysis and prepared the first draft of the manuscript. A.M.A. and S.İ.K. participated in revising the manuscript and data interpretation. All authors read and approved the final manuscript.

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Ali, A.M., Mohamed, A.N., Mohamed, Y.G. et al. Clinical presentation and surgical management of perforated peptic ulcer in a tertiary hospital in Mogadishu, Somalia: a 5-year retrospective study. World J Emerg Surg 17 , 23 (2022). https://doi.org/10.1186/s13017-022-00428-w

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Analysis of risk factors affecting the development of peptic ulcer perforation: case-control study

Sami akbulut.

1 Department of Surgery and Liver Transplant Institute, Faculty of Medicine, Inonu University, Malatya, Turkey

Ali Riza Caliskan

2 Department of Gastroenterology, Faculty of Medicine, Inonu University, Malatya, Turkey

Hasan Saritas

3 Department of Surgical Nursing, Faculty of Health Sciences, Inonu University, Malatya, Turkey

Khaled Demyati

4 Department of Surgery, An-Najah National University Hospital, An-Najah National University, Nablus, Palestine

Yilmaz Bilgic

Selver unsal.

5 Department of Nursing Service, Inonu University, Malatya, Turkey

Cemalettin Koc

Sezai yilmaz.

The aim of the to determine the risk factors associated with increased risk of peptic ulcer perforation (PUP).

Material and methods

The demographic, clinic, and biochemical parameters of 65 patients (PUP group) who underwent PUP surgery at our clinic between June 2009 and September 2016 were compared with the data of 134 patients (control group) who underwent endoscopy at a gastroenterology clinic for dyspeptic complaints. The control group were matched at random in a 1 : 2 ratio with the PUP group. Univariate analyses were used to compare different variables and variables with clinical significance, and p ≤ 0.05 was used in the backward stepwise logistic regression model.

This study included 65 patients with peptic ulcer perforation aged 17 to 92 years (PUP group) and 134 patients with dyspeptic complaints aged 18 to 87 years (control group). Univariate analysis showed that statistically significant differences were found between groups in terms of non-steroidal anti-inflammatory drugs usage ( p = 0.042; OR = 1.868), smoking ( p < 0.001; OR = 5.124), old age ( p = 0.003), low body mass index (BMI) ( p < 0.001), and low hemoglobin (Hb) ( p = 0.002). However multivariate analysis showed that increasing age ( p = 0.004; OR = 1.035), smoking ( p = 0.007; OR = 3.591), decreasing Hb ( p = 0.042; OR = 1.277), and decreasing BMI ( p < 0.001; OR = 1.669) were independent clinically significant risk factors for development of PUP.

Conclusions

This study showed that decreased BMI, decreased Hb, increased age, and smoking were independent risk factors for development of PUP. Thus, this group of patients needs particular attention paid to suggestive symptoms with early diagnosis and optimal management of peptic ulcer disease.

Introduction

Peptic ulceration is a major public health problem. It is estimated that each year, peptic ulcer disease (PUD) affects 4 million people around the world [ 1 ]. Individuals with PUD are at risk of developing complications such as gastroduodenal haemorrhage, perforation, penetration, and obstruction, and mortality among patients with these complications is high [ 2 ]. Peptic ulcer perforation (PUP) is a frequent emergency condition worldwide associated with high mortality if left untreated. It presents as an acute abdominal condition, with localised or generalised peritonitis and a high risk for developing sepsis and death. PUP is a surgical emergency and carries a mortality ranging from 1.3% to 20%. Thirty-day mortality rates reaching 20% and 90-day mortality rates of up to 30% have been reported [ 3 – 5 ].

Being closely related to advanced age, increased burden of comorbidity may partially explain the higher mortality among elderly patients; however, several other factors affect this high mortality [ 6 ]. While Helicobacter pylori and use of non-steroidal anti-inflammatory drugs (NSAID) are frequent causes of PUP, demographic differences in age, gender, perforation location, and aetiology exist between countries, as do mortality rates, with several risk factors potentially influencing the development of PUP and postoperative mortality.

This study’s primary aim was to determine both the risk factors affecting PUP and the risk factors affecting the mortality in patients who underwent surgery due to PUP. Identifying patients at increased risk with application of optimised management and prophylactic measures is expected to reduce mortality in this group of patients.

Electronic file records of adult patients who underwent surgery with the preliminary diagnosis of PUP at the Department of Surgery, Inonu University Faculty of Medicine between 15 June 2009 and 15 September 2016 were reached. The patient list was obtained by entering the codes “609.710, 609.890, 609.900” into the ENLIL patient information system used in our hospital. A total of 68 patients with PUP, whose demographic (age, gender, height, weight, body mass index (BMI)), clinical (blood group, smoking, alcohol use, diabetes, chronic kidney disease, chronic heart disease, non-steroidal anti-inflammatory drugs (NSAID) use) and biochemical (white blood cell (WBC), mean cell haemoglobin (MCH), mean corpuscular volume (MCV), red cell distribution width (RDW), platelet distribution width (PDW), lymphocyte, neutrophil, PDW, and platelet) parameters were reached, were found suitable for inclusion, and this group was defined as the case group (PUP group). To create a control group, 136 consecutive patients with dyspeptic complaints, who underwent panendoscopy at the Gastroenterology Department of our hospital due to dyspeptic complaints, were selected as the control group. Both groups were compared in terms of the above-mentioned demographic and clinical parameters. All patients were contacted by phone to learn the current status. However, 3 patients in the case group and 2 patients in the control group were excluded because they could not be reached by phone. As a result, 65 patients in the case group and 134 patients in the control group of this study were included in the analysis. After the approval of the Inonu University Institutional Review Board for non-interventional studies (Approval No: 2018/6-4), the patients’ files were retrospectively examined.

Statistical analysis

The statistical analyses were performed using IBM SPSS Statistics v25.0 (Statistical Package for the Social Sciences, Inc., Chicago, IL, USA). The quantitative variables were expressed as mean ± SD, median, and min-max. The qualitative variables were reported as numbers and percentages (%). Kolmogorov-Smirnov test was used to assess normality of quantitative variables’ distribution. Mann Whitney -U test was used to compare quantitative variables. Pearson’s χ 2 and Fisher’s exact tests were used to compare qualitative variables. Variables such as age, smoking, NSAIDs, haemoglobin (Hb), BMI, height, and weight, which were thought to be both clinically and statistically significant were taken into a backward stepwise (likelihood ratio) logistic regression model to determine independent risk factors for PUP. Hosmer-Lemeshow test was used for the goodness of fit of logistic regression models. P ≤ 0.05 was considered statistically significant. This retrospective study was approved by the Inonu University Rectorate Ethics Committee (Approval No. 2018/6-4)

This study included 65 patients with peptic ulcer perforation aged 17 to 92 years (PUP group) and 134 patients with dyspeptic complaints aged 18 to 87 years (control group). A statistically significant difference was found between the groups in terms of age ( p = 0.003), height ( p < 0001), weight ( p < 0001), BMI ( p < 0001), Hb ( p = 0.002), WBC ( p < 0001), neutrophil ( p < 0001), lymphocyte ( p < 0001), MPV ( p < 0001), RDW ( p < 0.001), PDW ( p < 0001), platelets ( p = 0.016), NSAID usage ( p = 0.042, OR = 1.868), and smoking ( p < 0001, OR = 5.124) variables. However, no statistically significant difference was found between the groups in terms of gender ( p = 0.070), blood groups ( p = 0.509), diabetes mellitus ( p = 0.316), alcohol intake ( p = 0.352), cardiovascular disease ( p = 0.290), renal disease ( p = 0.446), and pulmonary disease ( p = 0.215) variables ( Tables I, II ). To demonstrate whether the variables were risk factors for PUP development, seven clinical significant variables (age, smoking, NSAIDs, Hb, BMI, height, and weight), with p ≤ 0.05, were taken into the logistic regression model, and this model showed that increasing age ( p = 0.004; OR = 1.035), smoking ( p = 0.007; OR = 3.591), decreasing Hb ( p = 0.042; OR = 1.277), and decreasing BMI ( p < 0.001; OR = 1.669) were independent risk factors for development of PUP ( Table III ).

Comparison of PUP and Control groups in terms of continuous variables

Determination of factors affecting PUP using backward stepwise logistic regression model

Hosmer and Lemeshow test (p = 0.797), Nagelkerke R 2 (65.4%), Cox and Snell R 2 (47%), Omnibus tests of model coefficients (χ 2 = 125; p < 0.001).

Comparison of PUP and Control groups in terms of categorical variables

A PUD is a defect in the gastric or duodenal wall that extends through the muscularis mucosa into the deeper layers of the wall. PUD remains a major public health problem worldwide, and a recent systemic review showed that the 1-year prevalence of PUD based on physician diagnosis ranged from 0.12% to 1.50%, and that based on hospitalisation data ranged from 0.10% to 0.19% [ 7 ].

PUD can be complicated by haemorrhage, perforation, penetration, or obstruction. These complications represent the most common indications for surgery in PUD. Although there has been a sharp decline in elective surgery for PUD, the rates of emergency surgery for complicated PUD have been stable over time. Patients with gastric ulcers are also at risk of developing gastric malignancy. PUP typically presents with sudden onset of severe abdominal pain but may be less dramatic, particularly in hospitalised, elderly, and immunocompromised patients. The resulting peritonitis is often generalised but can be localised when the perforation is walled off by adjacent viscera and structure. In general, all patients with PUP require prompt resuscitation, intravenous antibiotics, analgesia, proton pump inhibitory medications, nasogastric tube, urinary catheter, and surgical source control. Perforated gastric ulcers are best treated by simple wedge resection to eliminate the perforation and exclude malignancy. If wedge resection of the ulcer cannot be performed due to ulcer location in the juxtapyloric region, multiple biopsies of the ulcer are taken and omental patching is performed. Perforated duodenal ulcers are best managed by simple omental patching and peritoneal debridement followed by Helicobacter pylori eradication. An acid-reducing procedure, which is usually not performed in emergency surgeries for PUP, should be considered in stable patients who have failed medical therapy.

PUP carries a mortality ranging from 1.3% to 20%. Thirty-day mortality rates reaching 20% and 90-day mortality rates of up to 30% have been reported [ 3 – 5 ]. Studies showed that while haemorrhage remained the most common complication, perforation had the highest mortality. PUP had a five-fold higher mortality rate than bleeding ulcers and was the single most important contributor to inpatient mortality [ 8 ]. While there has been a significant decrease in PUD mortality with a significant increase in the use of therapeutic endoscopy for bleeding ulcer [ 8 ], mortality rates for PUP have remained stable, despite progress in perioperative care, imaging techniques, and surgical management [ 3 ]. In the present study the 30-day mortality rate is 12.3%; the results are consistent with the literature.

Despite continuous exposure to several noxious factors, under normal conditions the gastric mucosa is able to maintain structural integrity and function. However, gastric mucosal injuries may occur when harmful factors overcome an intact mucosal defence or when the mucosal defensive mechanisms are impaired. Mucosal injury and, thus, peptic ulcer occur when the balance between the aggressive noxious factors and the defensive mechanisms is disrupted [ 9 ].

Aggressive noxious agents may include injurious factors of endogenous origin such as reflux of alkaline duodenal contents containing bile and pancreatic enzymes. Alcohol, cigarette smoking, drugs – particularly aspirin and aspirin-like drugs, and steroids are among exogenous mucosal irritants that can inflict mucosal injury [ 9 ]. It can alter the mucosal defence by allowing back diffusion of hydrogen ions and subsequent epithelial cell injury. The defensive mechanisms include tight intercellular junctions, mucus, bicarbonate, mucosal blood flow, cellular restitution, and epithelial renewal. PUD occurs mainly in the stomach (gastric ulcer) or proximal duodenum (duodenal ulcer). It was also shown that duodenal ulcers occur in gastric metaplasia mucosa in the duodenum [ 10 ].

It is unclear why some patients perforate and others do not. It might be related to the presence of continuous insult exposure without adequate management. Furthermore, there are geographical differences in the aetiology and variation in risk factors for PUP [ 3 ]. Only about a third of patients with PUP have a known history of peptic ulcer at the time of diagnosis. Furthermore, some patients develop very small (< 5 mm) perforations without large mucosal defects, which suggests that the ulcer size is unrelated to perforation risk, while other patients may develop large mucosal defects with perforation of several centimetres.

The most common causes of PUD are H. pylori infection and use of NSAIDs. We were unable to accurately identify the status of H. pylori infection in patients in this study due to the retrospective nature of the study. However other studies showed a variable prevalence of H. pylori (0–90%) in perforated ulcers, and ulcers may also develop in the absence of H. pylori infection and NSAID use [ 3 , 11 ].

Most patients with PUD are treated successfully with cure of H. pylori infection and avoidance of NSAIDs, along with the appropriate use of antisecretory therapy. When H. pylorus colonises the gastric mucosa, inflammation usually results. The causal association between H. pylori gastritis and duodenal ulceration is now well established in the adult and paediatric literature. In patients infected with H. pylori , high levels of gastrin and pepsinogen and reduced levels of somatostatin have been measured. In infected patients, exposure of the duodenum to acid is increased. Virulence factors produced by H. pylori , including urease, catalase, vacuolating cytotoxin, and lipopolysaccharide, are well described.

Patients with PUD should be tested for infection with H. pylori and treated accordingly [ 12 ]. Eradication of H. pylori in patients with PUD is associated with higher healing rates in patients with duodenal and gastric ulcers. A meta-analysis of 24 randomised trials showed that the 12-month ulcer remission rates for gastric and duodenal ulcers were significantly higher in patients successfully eradicated of H. pylori infection as compared with those with a persistent infection [ 13 ]. Furthermore, eradication of H. pylori infection is associated with lower recurrence rates in patients with ulcers, who are not placed on maintenance antisecretory therapy [ 14 ].

Decreased BMI and increased age are found to be independent risk factors for the development of PUP on multivariate analysis in this study. There are conflicting data about the association between obesity and risk of PUD [ 15 , 16 ]. However, to our knowledge the association between low BMI and increased risk of PUP has not been described before. Further studies are needed to confirm these results. Old age was also found in other studies to be associated with increased risk of PUP and increased mortality in PUP [ 6 , 17 ]. The proportions of patients with comorbidities and taking NSAIDs were reported to be significantly higher in the old age group; a higher proportion of patients in the old age group had PUP over 1 cm in size [ 17 ].

NSAIDs are one of the most widely used therapeutic agents, both prescribed and over the counter. NSAIDs are a broad class of non-glucocorticoid drugs, which are extensively used in anti-inflammatory, analgesic, and antipyretic therapies. However, NSAIDs are a leading cause of drug-related morbidity, especially in the elderly and patients with comorbidities. It may cause many side effects, most commonly in the gastrointestinal (GI) tract, cardiovascular system, kidney, liver, central nervous system, and haematopoietic system. About a quarter of chronic NSAID users will develop PUD, and 2–4% will bleed or perforate. In NSAID users the size of the PUP was described as larger than in other groups, and hospital stays were relatively longer than for the H. pylori infected group, although statistically insignificant [ 17 – 19 ]. Proton-pump inhibitors have been proven efficacious in healing NSAID-associated ulcers because they provide potent and long-lasting inhibition of gastric acid secretion. Co-administration of NSAIDs and proton-pump inhibitors has been used to decrease upper-GI tract adverse events [ 19 ]. In the present study NSAID use was shown to increase PUP risk 1.8 fold with univariate analysis, but the results could not be confirmed with multivariate analysis. One of the limiting factors of the present study is that the patients with PUP were not given adequate information about the size of PUP in the operation report. Therefore, we cannot comment on whether the size of PUP of patients using NSAIDs are different from others.

Smoking and chronic nicotine treatment play a role in the pathogenesis of PUD in several ways. They stimulate basal acid output, which is more pronounced in smokers having duodenal ulcers, by increasing histamine release and pepsinogen secretion. Long-term nicotine treatment in rats also significantly decreases total mucus neck cell population and neck-cell mucus volume. Smoking also increases the bile salt reflux rate and gastric bile salt concentration. Nicotine not only induces ulceration, but also potentiates ulceration caused by H. pylori , alcohol, nonsteroidal anti-inflammatory drugs, or cold restrain stress [ 20 ]. Variable results are reported with regard to its clinical significance and association with PUP in the literature [ 17 , 18 , 21 ]. Multivariate analysis in the present study showed that smoking ( p = 0.007; OR = 3.591) is an independent risk factor for development of PUP.

PUP is a serious disease complication. This study showed that decreased BMI, decreased Hb, increased age, and smoking were independent risk factors for development of PUP. This group of patients needs particular attention regarding suggestive symptoms with early diagnosis and optimal management of their PUD.

Conflict of interest

The authors declare no conflict of interest.

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Parkinson’s Disease & End of Life

End-Stage Parkinson’s Disease & Risk of Death

It’s hard to think about the tough stuff. The what ifs, the worst-case scenarios, the unknowns.

Parkinson’s disease (PD) is a progressive condition, which means that it gets worse with time. However, for many people, the worsening is gradual, maybe even imperceptible at times. This affords you many years of good living – exercising, spending time with family, maybe even working. But we would be remiss if we did not educate you about the full spectrum of possibilities, since many of you want to know what obstacles you may face down the road and how to prepare for them.

Over time, for some people with PD, symptoms can become advanced and much more difficult to navigate. To help you, we created a special set of blog posts about advanced PD to address many of the What If’s of Parkinson’s Disease (authored together with Dr. Pravin Khemani, a Movement Disorders specialist in Seattle, WA).

A question we often get asked is – can advanced Parkinson’s disease lead to death and if so, how? When a person is first diagnosed with PD, they are often told “You will die with Parkinson’s disease, not of Parkinson’s disease”. This means that PD is not a fatal disease per se and end of life often occurs at an old age from another medical illness entirely. But is that true in all cases?

This week we will try to answer this important question.

Relationship between Parkinson’s disease and mortality

Multiple studies have investigated the connection between PD and mortality. Results are not consistent across studies, and some conclude that PD does not increase mortality over the general population. Other studies conclude that people with PD have a mortality ratio of about 1.5 as compared with the general population. This means that the rate of observed deaths among all people with PD is about 1.5 times higher than would be expected in the general population.

However, even studies that conclude that PD overall does not confer an increase in mortality over the general population, find that people with PD who have certain characteristics are at an increased risk of dying. These characteristics are associated with advanced PD and include:

• Longer duration of disease
• A higher Hoehn and Yahr motor stage with increased level of motor disability
• Cognitive dysfunction
• Hallucinations
• Presence of comorbid medical conditions

How can certain symptoms of advanced PD increase risk of dying?

Advanced PD symptoms can contribute to an increased risk of dying in several ways. At this point we are not able to stop the progression of PD, however there are some steps you can take that may minimize certain risks, so it is important to understand the symptoms of advanced PD and how they can be managed.

• Falls – Due to increased balance problems as well as the presence of neurogenic orthostatic hypotension (NOH) , people with advanced PD are at an increased risk of falls. Falls are one of the major causes of emergency room visits and hospitalizations for people with PD. Falls in turn can cause life-threatening injuries such as traumatic brain injury. More commonly, falls can cause fractures which are also linked to an increased risk of mortality. Although not every fall can be prevented, physical therapy to improve balance and assess for the appropriate walking aid can be very helpful. Assessing bone density on a regular basis is also important to prevent fractures in the case of a fall. In addition, NOH should be routinely assessed for and treated, to minimize the chance of falls.
• Pressure ulcers – Due to increased immobility , people with advanced PD are at more of a risk of developing pressure ulcers, a breakdown of skin and underlying tissue resulting from prolonged pressure on a particular part of the body. If not promptly recognized and treated, pressure ulcers can lead to infections of the underlying tissues and even result in sepsis (a life-threatening illness caused by your body’s response to an infection). The chance of pressure ulcers can be minimized by frequent repositioning, protection of bony prominences that are in contact with resting surfaces, and maintenance of good nutrition.
• Pneumonia – People with advanced PD may have progressive difficulty with swallowing , which can lead to aspiration. Aspiration occurs when saliva or food enters the lungs instead of the gastrointestinal tract and can cause pneumonia. In addition, people with advanced PD often have a weak cough which means they can’t cough up what they aspirated, and also can’t clear their airways of secretions once pneumonia has started. Pneumonia has been found to be a more common cause of death among people with PD than the general population, highlighting the contribution of swallowing difficulties in mortality in PD. In addition, those with PD can die from choking accidents. In order to prevent these problems, talk with the neurologist about a swallow assessment that can determine which foods are safe for the person with advanced PD to eat. For some, swallowing therapy can also be instituted to improve swallow function.
• Other infections – Increased frailty is linked to advanced PD. In general, the frail elderly have less reserve to fight infection and withstand new medical problems. Therefore, in the advanced PD population, a minor medical problem such as a urinary tract infection can spiral into a bigger problem that can lead to more widespread infection and even death. A hospitalization for a seemingly treatable cause can disrupt the delicately balanced equilibrium at which the frail elderly lives.

A minor hospitalization, that in a less frail person would be easily weathered, can unfortunately spiral into permanently increased disability and death in the following ways:

• Increased confusion – with the abrupt change in his/her surroundings, the person with advanced PD may get more confused. Increased hallucinations and agitation are common. The person may pull at their IV and increase their risk of infection. Medications to control hallucinations and agitation may be introduced to help but can also cause problematic side effects.
• Increased risk of falls – with increased confusion, the person with advanced PD may try to get out of bed and fall. Often, the nursing staff will identify the person with advanced PD as a fall risk and not allow the person to get out of bed without help. This is important to prevent falls, however, can lead to much more immobility than is typical for the person with advanced PD, causing further disability.
• With increased agitation and the nursing staff’s desire to prevent falls, restraints may be ordered to ensure the person stays safe in bed. These can further increase confusion, immobility, and disability.
• With an inability to get out of bed, the person with advanced PD may have a urinary catheter placed. This increases the risk of a urinary tract infection, which in turn can lead to a larger infection
• In a hospital setting, the person with PD may not get their medications on time, which will invariably lead to more immobility and disability. It can also impact swallow and increase the chance of aspiration in the hospital.

These are just some of the ways in which a medical event can lead to death much more easily in someone who is already frail from PD than in someone who is not.

How will the person with advanced PD experience death?

The journey for every person with PD will be different. Their symptoms, disease progression, access to medical care, and their concurrent medical issues (among other things) may vary widely and play a role in their life and their death with PD. As described above, the person with advanced PD typically dies from an event that occurs on top of the increasing levels of frailty and disability that build up over time. That event may be a fall, an infection, a choking event, or another medical issue that leads to a hospitalization and causes a more precipitous decline.

Regardless of the cause, when a neurologist assesses that the possibility of death within a particular time frame is likely, hospice care can be initiated. This is different from palliative care , which is a clinical approach that focuses on improving quality of life for people with complex diseases. Palliative care can begin at any point during the disease progression and work in conjunction with the treatment plan. Hospice care, on the other hand, is provided to improve the quality of life when end of life is near.

In summary, while it is true that PD in and of itself is not fatal in the same way that a rupture of a brain aneurysm or a massive heart attack may be (although both of these disorders can be survived under the right conditions), the disability caused by PD can contribute to death in a variety of ways as outlined above.  Educating yourself on the various possibilities and areas of concern may help you better prepare for the future, minimize some risks, and possibly enhance or prolong quality of life.

Tips and Takeaways

• Some studies show that the rate of deaths among all people with PD is about 1.5 times higher than would be expected in the general population
• Although PD is not fatal in and of itself, certain characteristics of advanced PD are associated with an increased risk of death including cognitive decline, hallucinations, and an increased level of motor disability
• Advanced PD can cause falls, pressure ulcers, swallowing difficulties and general frailty, which are all linked to death
• Proactive steps can help minimize certain risks, and possibly prolong quality of life
• View our other blog articles about advanced PD to learn more and help you navigate these challenging issues

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Quiz Questions

Q1. Which pathogen is strongly associated with peptic ulcer?

(a) Bifidobacterium bifidum (b) Escherichia coli (c) Helicobacter pylori (d) Faecalibacterium prausnitzii

Q2. Gastric ulcers are most common in younger patients

(a) True (b) False

Q3. How do NSAIDs contribute to peptic ulcer formation?

(a) By burning holes directly in the gastric mucosa when they hit the stomach. (b)Increasing acid production (c) Decreasing prostaglandin synthesis

Q4. Your patient who has been diagnosed with Chronic Gastritis for 3 years presents to your primary care office complaining of worsening epigastric pain, stating “I’m still taking Protonix every day, but my symptoms have been getting worse.” How would you explain the main difference between Gastritis and Peptic Ulcer disease?

(a) You have actually had Peptic Ulcer disease this whole time. (b) With your worsening symptoms, I think you may have developed a peptic ulcer in addition to Gastritis. I’m ordering a scope to see what’s going on. (c) I wouldn’t worry about it, sometimes symptoms worsen during periods of stress (d) Have you ingested any foreign objects recently?

Q5. An obese woman with chief complaints of heartburn, upper abdominal pain within one hour of eating came into the clinic without having the sighs of active bleeding. The Esophageal endoscopy shows that she is having the Barrett’s Esophagus. Which of the following disease do you suspect that cause her discomfort?

(a) Stress Ulcer (b) Gastric Cancer (c) Gastroesophageal reflux disease (GERD) (d) None of the above