View source for Medicine:Peptic ulcer disease

{{short description|Ulcer of an area of the gastrointestinal tract}}
{{Infobox medical condition (new)
| name            = Peptic ulcer disease
| synonyms        = Peptic ulcer, stomach ulcer, gastric ulcer, duodenal ulcer
| field           = [[Medicine:Gastroenterology|Gastroenterology]]<br>General surgery
| symptoms        = Heartburn, upper abdominal pain,  nausea, belching, [[Medicine:Hematemesis|vomiting]], [[Medicine:Melena|blood in the stool]], weight loss, weight gain, [[Medicine:Bloating|bloating]], loss of appetite,<ref name=Na2011/>  [[Medicine:Jaundice|yellowing of the skin and whites of the eyes]], difficulty swallowing
| complications   = [[Medicine:Gastrointestinal bleeding|Bleeding]], [[Medicine:Gastrointestinal perforation|perforation]], ulcer perforation, blockage of the stomach<ref name=Mil2011/>
| onset           =
| duration        =
| causes          = ''Helicobacter pylori'' bacteria, non-steroidal anti-inflammatory drugs (NSAIDs), [[Chemistry:Tobacco smoking|tobacco smoking]], [[Medicine:Crohn's disease|Crohn's disease]]<ref name=Na2011/><ref name=St2002/>
| risks           =
| diagnosis       = Based on symptoms, confirmed by endoscopy or barium swallow<ref name=Na2011/>
| differential    = Stomach cancer, coronary heart disease, [[Medicine:Gastritis|inflammation of the stomach lining]], gallbladder inflammation<ref name=Na2011/>
| prevention      =
| treatment       = Medications,<ref name=Na2011/> stopping NSAIDs, stopping smoking, stopping [[Chemistry:Alcohol (drug)|alcohol consumption]]
| medication      = Proton pump inhibitor, H2 blocker, antibiotics<ref name=Na2011/><ref name=Wang2011/>
| prognosis       =
| frequency       = 87.4 million (2015)<ref name=GBD2015Pre/>
| deaths          = 267,500 (2015)<ref name=GBD2015De/>
}}

'''Peptic ulcer disease''' is a break in the inner [[Biology:Gastric mucosa|lining of the stomach]], the first part of the [[Biology:Small intestine|small intestine]], or sometimes the lower [[Biology:Esophagus|esophagus]].<ref name=Na2011>{{cite journal | vauthors = Najm WI | title = Peptic ulcer disease | journal = Primary Care | volume = 38 | issue = 3 | pages = 383–94, vii | date = September 2011 | pmid = 21872087 | doi = 10.1016/j.pop.2011.05.001 }}</ref><ref>{{cite web|title=Definition and Facts for Peptic Ulcer Disease|url=http://www.niddk.nih.gov/health-information/health-topics/digestive-diseases/peptic-ulcer/Pages/definition-facts.aspx|website=National Institute of Diabetes and Digestive and Kidney Diseases|access-date=28 February 2015|url-status=dead|archive-url=https://web.archive.org/web/20150402194304/http://www.niddk.nih.gov/health-information/health-topics/digestive-diseases/peptic-ulcer/Pages/definition-facts.aspx|archive-date=2 April 2015|df=dmy-all}}</ref> An ulcer in the stomach is called a '''gastric ulcer''', while one in the first part of the intestines is a '''duodenal ulcer'''.<ref name=Na2011/> The most common symptoms of a duodenal ulcer are waking at night with upper abdominal pain, and upper abdominal pain that improves with eating.<ref name=Na2011/> With a gastric ulcer, the pain may worsen with eating.<ref>{{cite book|last1=Rao|first1=S. Devaji|title=Clinical Manual of Surgery|date=2014|publisher=Elsevier Health Sciences|isbn=9788131238714|page=526|url=https://books.google.com/books?id=qTwHBgAAQBAJ&pg=PA526|language=en|df=dmy-all}}</ref> The pain is often described as a burning or dull ache.<ref name=Na2011/> Other symptoms include belching, vomiting, weight loss, or poor appetite.<ref name=Na2011/> About a third of older people with peptic ulcers have no symptoms.<ref name=Na2011/> Complications may include [[Medicine:Gastrointestinal bleeding|bleeding]], [[Medicine:Gastrointestinal perforation|perforation]], and blockage of the stomach.<ref name=Mil2011/> Bleeding occurs in as many as 15% of cases.<ref name=Mil2011/>

Common causes include the bacteria ''Helicobacter pylori'' and non-steroidal anti-inflammatory drugs (NSAIDs).<ref name=Na2011/> Other, less common causes include [[Chemistry:Tobacco smoking|tobacco smoking]], stress as a result of other serious health conditions, [[Medicine:Behçet's disease|Behçet's disease]], [[Medicine:Zollinger–Ellison syndrome|Zollinger–Ellison syndrome]], [[Medicine:Crohn's disease|Crohn's disease]], and liver cirrhosis.<ref name="Na2011" /><ref name="St2002">{{cite journal | vauthors = Steinberg KP | title = Stress-related mucosal disease in the critically ill patient: risk factors and strategies to prevent stress-related bleeding in the intensive care unit | journal = Critical Care Medicine | volume = 30 | issue = 6 Suppl | pages = S362–4 | date = June 2002 | pmid = 12072662 | doi = 10.1097/00003246-200206001-00005 }}</ref> Older people are more sensitive to the ulcer-causing effects of NSAIDs.<ref name="Na2011" /> The diagnosis is typically suspected due to the presenting symptoms with confirmation by either endoscopy or barium swallow.<ref name="Na2011" /> ''H. pylori'' can be diagnosed by testing the blood for [[Biology:Antibodies|antibodies]], a urea breath test, testing the stool for signs of the bacteria, or a [[Medicine:Biopsy|biopsy]] of the stomach.<ref name="Na2011" /> Other conditions that produce similar symptoms include stomach cancer, coronary heart disease, and [[Medicine:Gastritis|inflammation of the stomach lining]] or gallbladder inflammation.<ref name=Na2011/>

Diet does not play an important role in either causing or preventing ulcers.<ref>{{cite web|title=Eating, Diet, and Nutrition for Peptic Ulcer Disease|url=http://www.niddk.nih.gov/health-information/health-topics/digestive-diseases/peptic-ulcer/Pages/eating-diet-nutrition.aspx|website=National Institute of Diabetes and Digestive and Kidney Diseases|access-date=28 February 2015|url-status=dead|archive-url=https://web.archive.org/web/20150320061357/http://www.niddk.nih.gov/health-information/health-topics/digestive-diseases/peptic-ulcer/Pages/eating-diet-nutrition.aspx|archive-date=20 March 2015|df=dmy-all}}</ref> Treatment includes stopping smoking, stopping use of NSAIDs, stopping [[Chemistry:Alcohol (drug)|alcohol]], and taking medications to decrease stomach acid.<ref name=Na2011/> The medication used to decrease acid is usually either a proton pump inhibitor (PPI) or an H2 blocker, with four weeks of treatment initially recommended.<ref name=Na2011/> Ulcers due to ''H. pylori'' are treated with a combination of medications, such as [[Chemistry:Amoxicillin|amoxicillin]], [[Chemistry:Clarithromycin|clarithromycin]], and a PPI.<ref name=Wang2011/> Antibiotic resistance is increasing and thus treatment may not always be effective.<ref name=Wang2011>{{cite journal | vauthors = Wang AY, Peura DA | title = The prevalence and incidence of Helicobacter pylori-associated peptic ulcer disease and upper gastrointestinal bleeding throughout the world | journal = Gastrointestinal Endoscopy Clinics of North America | volume = 21 | issue = 4 | pages = 613–35 | date = October 2011 | pmid = 21944414 | doi = 10.1016/j.giec.2011.07.011 }}</ref> Bleeding ulcers may be treated by endoscopy, with open surgery typically only used in cases in which it is not successful.<ref name=Mil2011/>

Peptic ulcers are present in around 4% of the population.<ref name=Na2011/> New ulcers were found in around 87.4 million people worldwide during 2015.<ref name=GBD2015Pre>{{cite journal | author =  GBD 2015 Disease and Injury Incidence and Prevalence Collaborators | title = Global, regional, and national incidence, prevalence, and years lived with disability for 310 diseases and injuries, 1990-2015: a systematic analysis for the Global Burden of Disease Study 2015 | journal = Lancet | volume = 388 | issue = 10053 | pages = 1545–1602 | date = October 2016 | pmid = 27733282 | pmc = 5055577 | doi = 10.1016/S0140-6736(16)31678-6 }}</ref> About 10% of people develop a peptic ulcer at some point in their life.<ref name=Snow2008>{{cite journal | vauthors = Snowden FM | title = Emerging and reemerging diseases: a historical perspective | journal = Immunological Reviews | volume = 225 | issue = 1 | pages = 9–26 | date = October 2008 | pmid = 18837773 | doi = 10.1111/j.1600-065X.2008.00677.x | pmc = 7165909 }}</ref> Peptic ulcers resulted in 267,500 deaths in 2015, down from 327,000 in 1990.<ref name=GBD2015De>{{cite journal | title = Global, regional, and national life expectancy, all-cause mortality, and cause-specific mortality for 249 causes of death, 1980-2015: a systematic analysis for the Global Burden of Disease Study 2015 | journal = Lancet | volume = 388 | issue = 10053 | pages = 1459–1544 | date = October 2016 | pmid = 27733281 | pmc = 5388903 | doi = 10.1016/s0140-6736(16)31012-1 | last1 = Wang | first1 = Haidong | last2 = Naghavi | first2 = Mohsen | last3 = Allen | first3 = Christine | last4 = Barber | first4 = Ryan M. | last5 = Bhutta | first5 = Zulfiqar A. | last6 = Carter | first6 = Austin | last7 = Casey | first7 = Daniel C. | last8 = Charlson | first8 = Fiona J. | last9 = Chen | first9 = Alan Zian | last10 = Coates | first10 = Matthew M. | last11 = Coggeshall | first11 = Megan | last12 = Dandona | first12 = Lalit | last13 = Dicker | first13 = Daniel J. | last14 = Erskine | first14 = Holly E. | last15 = Ferrari | first15 = Alize J. | last16 = Fitzmaurice | first16 = Christina | last17 = Foreman | first17 = Kyle | last18 = Forouzanfar | first18 = Mohammad H. | last19 = Fraser | first19 = Maya S. | last20 = Fullman | first20 = Nancy | last21 = Gething | first21 = Peter W. | last22 = Goldberg | first22 = Ellen M. | last23 = Graetz | first23 = Nicholas | last24 = Haagsma | first24 = Juanita A. | last25 = Hay | first25 = Simon I. | last26 = Huynh | first26 = Chantal | last27 = Johnson | first27 = Catherine O. | last28 = Kassebaum | first28 = Nicholas J. | last29 = Kinfu | first29 = Yohannes | last30 = Kulikoff | first30 = Xie Rachel }}</ref><ref name=GDB2013>{{cite journal | title = Global, regional, and national age-sex specific all-cause and cause-specific mortality for 240 causes of death, 1990-2013: a systematic analysis for the Global Burden of Disease Study 2013 | journal = Lancet | volume = 385 | issue = 9963 | pages = 117–71 | date = January 2015 | pmid = 25530442 | pmc = 4340604 | doi = 10.1016/S0140-6736(14)61682-2 | author1 = GBD 2013 Mortality Causes of Death Collaborators }}</ref> The first description of a perforated peptic ulcer was in 1670, in Princess Henrietta of England.<ref name=Mil2011>{{cite journal | vauthors = Milosavljevic T, Kostić-Milosavljević M, Jovanović I, Krstić M | title = Complications of peptic ulcer disease | journal = Digestive Diseases | volume = 29 | issue = 5 | pages = 491–3 | date = 2011 | pmid = 22095016 | doi = 10.1159/000331517 | s2cid = 25464311 }}</ref> ''H. pylori'' was first identified as causing peptic ulcers by [[Biography:Barry Marshall|Barry Marshall]] and [[Biography:Robin Warren|Robin Warren]] in the late 20th century,<ref name=Wang2011/> a discovery for which they received the Nobel Prize in 2005.<ref name="Nobel">{{cite web|title=The Nobel Prize in Physiology or Medicine 2005|url=https://www.nobelprize.org/nobel_prizes/medicine/laureates/2005/|website=nobelprize.org|publisher=Nobel Media AB|access-date=3 June 2015|url-status=live|archive-url=https://web.archive.org/web/20150512165749/http://www.nobelprize.org/nobel_prizes/medicine/laureates/2005/|archive-date=12 May 2015|df=dmy-all}}</ref>

==Signs and symptoms==
[[File:Gastric Ulcer.png|thumb|upright=1.2|Gastric ulcer]]
[[File:Duodenal ulcer01.jpg|thumb|Duodenal ulcer A2 stage, acute duodenal mucosal lesion(ADML)]]
Signs and symptoms of a peptic ulcer can include one or more of the following:{{cn|date=July 2022}}
* [[Medicine:Abdominal pain|abdominal pain]], classically epigastric, strongly correlated with mealtimes. In case of duodenal ulcers, the pain appears about three hours after taking a meal and wakes the person from sleep;
* [[Medicine:Bloating|bloating]] and abdominal fullness;
* waterbrash (a rush of saliva after an episode of regurgitation to dilute the acid in esophagus, although this is more associated with [[Medicine:Gastroesophageal reflux disease|gastroesophageal reflux disease]]);
* nausea and copious vomiting;
* loss of appetite and weight loss, in gastric ulcer;
* weight gain, in duodenal ulcer, as the pain is relieved by eating;
* [[Medicine:Hematemesis|hematemesis]] (vomiting of blood); this can occur due to bleeding directly from a gastric ulcer or from damage to the esophagus from severe/continuing vomiting.
* [[Medicine:Melena|melena]] (tarry, foul-smelling feces due to presence of oxidized iron from [[Biology:Hemoglobin|hemoglobin]]);
* rarely, an ulcer can lead to a gastric or [[Medicine:Gastrointestinal perforation|duodenal perforation]], which leads to acute peritonitis and extreme, stabbing pain,<ref>{{cite book | last = Bhat | first = Sriram | year = 2013 | title = SRB's Manual of Surgery | page = 364 | publisher = JP Medical | isbn = 9789350259443 }}</ref> and requires immediate surgery.

A history of heartburn or [[Medicine:Gastroesophageal reflux disease|gastroesophageal reflux disease]] (GERD) and use of certain medications can raise the suspicion for peptic ulcer. Medicines associated with peptic ulcer include NSAIDs (non-steroidal anti-inflammatory drugs) that inhibit [[Biology:Cyclooxygenase|cyclooxygenase]] and most [[Chemistry:Glucocorticoid|glucocorticoid]]s (e.g., [[Biology:Dexamethasone|dexamethasone]] and [[Chemistry:Prednisolone|prednisolone]]).{{cn|date=July 2022}}

In people over the age of 45 with more than two weeks of the above symptoms, the odds for peptic ulceration are high enough to warrant rapid investigation by esophagogastroduodenoscopy.{{cn|date=July 2022}}

The timing of symptoms in relation to the meal may differentiate between gastric and duodenal ulcers. A gastric ulcer would give epigastric pain during the meal, associated with nausea and vomiting, as [[Biology:Gastric acid|gastric acid]] production is increased as food enters the stomach. Pain in duodenal ulcers would be aggravated by hunger and relieved by a meal and is associated with night pain.<ref name="Angel 2017"/>

Also, the symptoms of peptic ulcers may vary with the location of the ulcer and the person's age. Furthermore, typical ulcers tend to heal and recur, and as a result the pain may occur for few days and weeks and then wane or disappear.<ref name="Peptic Ulcer">{{cite web |url=http://www.merckmanuals.com/home/digestive_disorders/peptic_disorders/peptic_ulcer.html |title=Peptic Ulcer |date=October 2006 |work=Home Health Handbook for Patients & Caregivers |publisher=Merck Manuals |url-status=live |archive-url=https://web.archive.org/web/20111228042709/http://www.merckmanuals.com/home/digestive_disorders/peptic_disorders/peptic_ulcer.html |archive-date=28 December 2011 |df=dmy-all }}</ref> Usually, children and the elderly do not develop any symptoms unless complications have arisen.

A burning or gnawing feeling in the stomach area lasting between 30&nbsp;minutes and 3&nbsp;hours commonly accompanies ulcers. This pain can be misinterpreted as [[Philosophy:Hunger|hunger]], indigestion, or heartburn. Pain is usually caused by the ulcer, but it may be aggravated by the stomach acid when it comes into contact with the ulcerated area. The pain caused by peptic ulcers can be felt anywhere from the navel up to the sternum, it may last from few minutes to several hours, and it may be worse when the stomach is empty. Also, sometimes the pain may flare at night, and it can commonly be temporarily relieved by eating foods that buffer stomach acid or by taking anti-acid medication.<ref>{{cite web|url=http://www.mayoclinic.com/health/peptic-ulcer/ds00242/dsection=symptoms|title=Peptic ulcer|access-date=18 June 2010|url-status=live|archive-url=https://web.archive.org/web/20120214221325/http://www.mayoclinic.com/health/peptic-ulcer/DS00242/DSECTION%3Dsymptoms|archive-date=14 February 2012|df=dmy-all}}</ref> However, peptic ulcer disease symptoms may be different for everyone.<ref>{{cite web|url=http://www.ulcerdisease.net/|title=Ulcer Disease Facts and Myths|access-date=18 June 2010|url-status=dead|archive-url=https://web.archive.org/web/20100605040219/http://ulcerdisease.net/|archive-date=5 June 2010|df=dmy-all}}</ref>

===Complications===
* [[Medicine:Upper gastrointestinal bleeding|Gastrointestinal bleeding]] is the most common complication. Sudden large bleeding can be life-threatening.<ref name="pmid9391242">{{cite journal | vauthors = Cullen DJ, Hawkey GM, Greenwood DC, Humphreys H, Shepherd V, Logan RF, Hawkey CJ | title = Peptic ulcer bleeding in the elderly: relative roles of ''Helicobacter pylori'' and non-steroidal anti-inflammatory drugs | journal = Gut | volume = 41 | issue = 4 | pages = 459–62 | date = October 1997 | pmid = 9391242 | pmc = 1891536 | doi = 10.1136/gut.41.4.459 }}</ref><ref>{{cite journal|author=Blackford, John W.|author2=Williams, Robert H.|title=Fatal Hemorrhage from Peptic Ulcer: One Hundred and Sixteen Cases Collected from Vital Statistics of Seattle During the Years 1935-1939 Inclusive|journal=Journal of the American Medical Association|volume=115|issue=21|year=1940|pages=1774–1779|doi=10.1001/jama.1940.02810470018005}}</ref> It is associated with 5% to 10% death rate.<ref name="Angel 2017"/>
* [[Medicine:Gastrointestinal perforation|Perforation]] (a hole in the [[Biology:Gastrointestinal wall|wall of the gastrointestinal tract]]) following a gastric ulcer often leads to catastrophic consequences if left untreated. Erosion of the gastrointestinal wall by the ulcer leads to spillage of the stomach or intestinal contents into the abdominal cavity, leading to an acute chemical [[Medicine:Peritonitis|peritonitis]].<ref>{{cite book |last1=Gossman |first1=William |last2=Tuma |first2=Faiz |last3=Kamel |first3=Bishoy G. |last4=Cassaro |first4=Sebastiano |title=StatPearls |date=2019 |publisher=StatPearls Publishing |url=https://www.ncbi.nlm.nih.gov/books/NBK519554/ |chapter=Gastric Perforation|pmid=30137838 }}</ref> The first sign is often sudden intense abdominal pain,<ref name="Angel 2017"/> as seen in [[Medicine:Valentino's syndrome|Valentino's syndrome]]. Posterior gastric wall perforation may lead to bleeding due to the involvement of gastroduodenal artery that lies posterior to the first part of the duodenum.{{citation needed|date=April 2018}} The death rate in this case is 20%.<ref name="Angel 2017"/>
* Penetration is a form of perforation in which the hole leads to and the ulcer continues into adjacent organs such as the [[Biology:Liver|liver]] and pancreas.<ref name="Peptic Ulcer"/>
* Gastric outlet obstruction (stenosis) is a narrowing of the pyloric canal by scarring and swelling of the gastric antrum and duodenum due to peptic ulcers. The person often presents with severe vomiting.<ref name="Angel 2017"/>
* Cancer is included in the differential diagnosis (elucidated by [[Medicine:Biopsy|biopsy]]), ''Helicobacter pylori'' as the etiological factor making it 3 to 6 times more likely to develop stomach cancer from the ulcer.<ref name="Peptic Ulcer"/> The risk for developing gastrointestinal cancer also appears to be slightly higher with gastric ulcers.<ref>{{cite journal|title=Long-term risk of gastrointestinal cancers in persons with gastric or duodenal ulcers|year=2016|pmc=4924392|last1=Søgaard|first1=K. K.|last2=Farkas|first2=D. K.|last3=Pedersen|first3=L.|last4=Lund|first4=J. L.|last5=Thomsen|first5=R. W.|last6=Sørensen|first6=H. T.|journal=Cancer Medicine|volume=5|issue=6|pages=1341–1351|doi=10.1002/cam4.680|pmid=26923747}}</ref>

==Cause==

===''H. pylori''===
''Helicobacter pylori'' is one of the major causative factors of peptic ulcer disease. It secretes [[Biology:Urease|urease]] to create an alkaline environment, which is suitable for its survival. It expresses blood group antigen-binding adhesin (BabA) and outer inflammatory protein adhesin (OipA), which enables it to attach to the gastric epithelium. The bacterium also expresses virulence factors such as ''CagA'' and ''PicB'', which cause stomach mucosal inflammation. The VacA gene encodes for vacuolating cytotoxin, but its mechanism of causing peptic ulcers is unclear. Such stomach mucosal inflammation can be associated with hyperchlorhydria (increased stomach acid secretion) or hypochlorhydria (reduced stomach acid secretion). Inflammatory [[Biology:Cytokine|cytokine]]s inhibit the [[Biology:Parietal cell|parietal cell]] acid secretion. ''H. pylori'' also secretes certain products that inhibit [[Biology:Hydrogen potassium ATPase|hydrogen potassium ATPase]]; activate [[Biology:Calcitonin gene-related peptide|calcitonin gene-related peptide]] sensory neurons, which increases [[Biology:Somatostatin|somatostatin]] secretion to inhibit acid production by parietal cells; and inhibit [[Biology:Gastrin|gastrin]] secretion. This reduction in acid production causes gastric ulcers.<ref name="Angel 2017"/> On the other hand, increased acid production at the pyloric antrum is associated with duodenal ulcers in 10% to 15% of ''H. pylori'' infection cases. In this case, somatostatin production is reduced and gastrin production is increased, leading to increased [[Chemistry:Histamine|histamine]] secretion from the enterochromaffin cells, thus increasing acid production. An acidic environment at the antrum causes [[Medicine:Metaplasia|metaplasia]] of the duodenal cells, causing duodenal ulcers.<ref name="Angel 2017"/>

Human immune response toward the bacteria also determines the emergence of peptic ulcer disease. The human IL1B gene encodes for Interleukin 1 beta, and other genes that encode for tumour necrosis factor (TNF) and [[Biology:Lymphotoxin alpha|Lymphotoxin alpha]] also play a role in gastric inflammation.<ref name="Angel 2017"/>

===NSAIDs===
Taking [[Chemistry:Nonsteroidal anti-inflammatory drug|nonsteroidal anti-inflammatory drug]]s (NSAIDs) such as [[Chemistry:Aspirin|aspirin]]<ref>{{cite journal |last1=Chan |first1=F. K. L. |last2=Graham |first2=D. Y. |title=Review article: prevention of non-steroidal anti-inflammatory drug gastrointestinal complications--review and recommendations based on risk assessment. |journal=Aliment Pharmacol Ther |date=May 15, 2004 |volume=19 |issue=10 |pages=1051–61 |doi=10.1111/j.1365-2036.2004.01935.x |pmid=15142194 |s2cid=24654342 |url=https://onlinelibrary.wiley.com/doi/10.1111/j.1365-2036.2004.01935.x |access-date=27 February 2022}}</ref> can increase the risk of peptic ulcer disease by four times compared to non-users. The risk of getting a peptic ulcer is two times for aspirin users. Risk of bleeding increases if NSAIDs are combined with [[Chemistry:Selective serotonin reuptake inhibitor|selective serotonin reuptake inhibitor]] (SSRI), [[Biology:Corticosteroid|corticosteroid]]s, [[Chemistry:Antimineralocorticoid|antimineralocorticoid]]s, and anticoagulants. The gastric mucosa protects itself from [[Biology:Gastric acid|gastric acid]] with a layer of mucus, the secretion of which is stimulated by certain prostaglandins. NSAIDs block the function of [[Biology:Cyclooxygenase|cyclooxygenase]] 1 (''COX-1''), which is essential for the production of these prostaglandins. Besides this, NSAIDs also inhibit stomach mucosa cells proliferation and mucosal blood flow, reducing [[Chemistry:Bicarbonate|bicarbonate]] and mucus secretion, which reduces the integrity of the mucosa. Another type of NSAIDs, called COX-2 selective anti-inflammatory drugs (such as [[Biology:Celecoxib|celecoxib]]), preferentially inhibit ''COX-2'', which is less essential in the gastric mucosa. This reduces the probability of getting peptic ulcers; however, it can still delay ulcer healing for those who already have a peptic ulcer.<ref name="Angel 2017"/> Peptic ulcers caused by NSAIDs differ from those caused by ''H. pylori'' as the latter's appear as a consequence of inflammation of the mucosa (presence of neutrophil and submucosal edema), the former instead as a consequence of a direct damage of the NSAID molecule against COX enzymes, altering the hydrophobic state of the mucus, the permeability of the lining epithelium and mitochondrial machinery of the cell itself. In this way NSAID's ulcers tend to complicate faster and dig deeper in the tissue causing more complications, often asymptomatically until a great portion of the tissue is involved.{{cn|date=July 2022}}

===Stress===
Stress due to serious health problems, such as those requiring treatment in an intensive care unit, is well described as a cause of peptic ulcers, which are also known as [[Medicine:Stress ulcer|stress ulcer]]s.<ref name=St2002/>

While chronic life stress was once believed to be the main cause of ulcers, this is no longer the case.<ref name=Fink2011>{{cite journal | vauthors = Fink G | title = Stress controversies: post-traumatic stress disorder, hippocampal volume, gastroduodenal ulceration* | journal = Journal of Neuroendocrinology | volume = 23 | issue = 2 | pages = 107–17 | date = February 2011 | pmid = 20973838 | doi = 10.1111/j.1365-2826.2010.02089.x | s2cid = 30231594 }}</ref> It is, however, still occasionally believed to play a role.<ref name=Fink2011/> This may be due to the well-documented effects of stress on gastric physiology, increasing the risk in those with other causes, such as ''H. pylori'' or NSAID use.<ref>{{cite journal | vauthors = Yeomans ND | title = The ulcer sleuths: The search for the cause of peptic ulcers | journal = Journal of Gastroenterology and Hepatology | volume = 26 | pages = 35–41 | date = January 2011 | issue = Suppl 1 | pmid = 21199512 | doi = 10.1111/j.1440-1746.2010.06537.x | s2cid = 42592868 | doi-access = free }}</ref>

===Diet===
Dietary factors, such as spice consumption, were hypothesized to cause ulcers until the late 20th century, but have been shown to be of relatively minor importance.<ref>For nearly 100&nbsp;years, scientists and doctors thought that ulcers were caused by stress, spicy food, and alcohol. Treatment involved [[Medicine:Bed rest|bed rest]] and a bland diet. Later, researchers added stomach acid to the list of causes and began treating ulcers with antacids. [http://digestive.niddk.nih.gov/ddiseases/pubs/hpylori/ National Digestive Diseases Information Clearinghouse] {{webarchive|url=https://web.archive.org/web/20060705194833/http://digestive.niddk.nih.gov/ddiseases/pubs/hpylori/ |date=5 July 2006 }}</ref> Caffeine and coffee, also commonly thought to cause or exacerbate ulcers, appear to have little effect.<ref>{{cite journal | vauthors = Ryan-Harshman M, Aldoori W | title = How diet and lifestyle affect duodenal ulcers. Review of the evidence | journal = Canadian Family Physician | volume = 50 | pages = 727–32 | date = May 2004 | pmid = 15171675 | pmc = 2214597 }}</ref><ref>{{cite book | first1 = Raphael | last1 = Rubin | first2 = David S. | last2 = Strayer | first3 = Emanuel | last3 = Rubin | title = Rubin's pathology : clinicopathologic foundations of medicine | publisher = Wolters Kluwer Health/Lippincott Williams & Wilkins | location = Philadelphia | isbn = 978-1-60547-968-2 | page = 623 | edition = Sixth | date = 2011-02-01 }}</ref> Similarly, while studies have found that alcohol consumption increases risk when associated with ''H. pylori'' infection, it does not seem to independently increase risk. Even when coupled with ''H. pylori'' infection, the increase is modest in comparison to the primary risk factor.<ref name=salih2007>{{cite journal | vauthors = Salih BA, Abasiyanik MF, Bayyurt N, Sander E | title = H pylori infection and other risk factors associated with peptic ulcers in Turkish patients: a retrospective study | journal = World Journal of Gastroenterology | volume = 13 | issue = 23 | pages = 3245–8 | date = June 2007 | pmid = 17589905 | pmc = 4436612 | doi = 10.3748/wjg.v13.i23.3245 | doi-access = free }}</ref><ref name='Sonnenberg1981'>{{cite journal | vauthors = Sonnenberg A, Müller-Lissner SA, Vogel E, Schmid P, Gonvers JJ, Peter P, Strohmeyer G, Blum AL | title = Predictors of duodenal ulcer healing and relapse | journal = Gastroenterology | volume = 81 | issue = 6 | pages = 1061–7 | date = December 1981 | pmid = 7026344 | doi = 10.1016/S0016-5085(81)80012-1 | doi-access = free }}</ref><ref group="nb">Sonnenberg in his study cautiously concludes that, among other potential factors that were found to correlate to ulcer healing, "moderate alcohol intake might [also] favor ulcer healing." (p. 1066)</ref>

===Other===
Other causes of peptic ulcer disease include gastric ischaemia, drugs, metabolic disturbances, [[Biology:Cytomegalovirus|cytomegalovirus]] (CMV), upper abdominal radiotherapy, [[Medicine:Crohn's disease|Crohn's disease]], and [[Medicine:Vasculitis|vasculitis]].<ref name="Angel 2017"/> Gastrinomas ([[Medicine:Zollinger–Ellison syndrome|Zollinger–Ellison syndrome]]), or rare gastrin-secreting tumors, also cause multiple and difficult-to-heal ulcers.<ref>{{cite journal | title = Gastrinoma Zollinger-Ellison-Syndrome | journal = Endotext | date = November 28, 2013 | pmid = 25905301 | last1 = Feliberti | first1 = E. | last2 = Hughes | first2 = M. S. | last3 = Perry | first3 = R. R. | last4 = Vinik | first4 = A. | last5 = Feingold | first5 = K. R. | last6 = Anawalt | first6 = B. | last7 = Boyce | first7 = A. | last8 = Chrousos | first8 = G. | last9 = Dungan | first9 = K. | last10 = Grossman | first10 = A. | last11 = Hershman | first11 = J. M. | last12 = Kaltsas | first12 = G. | last13 = Koch | first13 = C. | last14 = Kopp | first14 = P. | last15 = Korbonits | first15 = M. | last16 = McLachlan | first16 = R. | last17 = Morley | first17 = J. E. | last18 = New | first18 = M. | last19 = Perreault | first19 = L. | last20 = Purnell | first20 = J. | last21 = Rebar | first21 = R. | last22 = Singer | first22 = F. | last23 = Trence | first23 = D. L. | last24 = Vinik | first24 = A. | last25 = Wilson | first25 = D. P. }}</ref>

It is still unclear if smoking increases the risk of getting peptic ulcers.<ref name="Angel 2017"/>

==Diagnosis==
[[Image:Gastric ulcer 3.jpg|right|thumb|upright=1.2|Endoscopic image of gastric ulcer, biopsy proven to be gastric cancer.]]
The diagnosis is mainly established based on the characteristic symptoms. Stomach pain is usually the first signal of a peptic ulcer. In some cases, doctors may treat ulcers without diagnosing them with specific tests and observe whether the symptoms resolve, thus indicating that their primary diagnosis was accurate.{{cn|date=July 2022}}

More specifically, peptic ulcers erode the [[Biology:Muscularis mucosae|muscularis mucosae]], at minimum reaching to the level of the submucosa (contrast with erosions, which do not involve the muscularis mucosae).<ref>{{cite web |url=http://www.merckmanuals.com/professional/gastrointestinal-disorders/gastritis-and-peptic-ulcer-disease/peptic-ulcer-disease |title=Peptic Ulcer Disease |access-date=2016-01-17 |url-status=live |archive-url=https://web.archive.org/web/20160113063138/http://www.merckmanuals.com/professional/gastrointestinal-disorders/gastritis-and-peptic-ulcer-disease/peptic-ulcer-disease |archive-date=13 January 2016 |df=dmy-all }}</ref>

Confirmation of the diagnosis is made with the help of tests such as endoscopies or barium contrast [[Physics:X-ray|x-ray]]s. The tests are typically ordered if the symptoms do not resolve after a few weeks of treatment, or when they first appear in a person who is over age 45 or who has other symptoms such as weight loss, because [[Medicine:Stomach cancer|stomach cancer]] can cause similar symptoms. Also, when severe ulcers resist treatment, particularly if a person has several ulcers or the ulcers are in unusual places, a doctor may suspect an underlying condition that causes the stomach to overproduce [[Chemistry:Acid|acid]].<ref name="Peptic Ulcer"/>

An esophagogastroduodenoscopy (EGD), a form of endoscopy, also known as a gastroscopy, is carried out on people in whom a peptic ulcer is suspected. It is also the gold standard of diagnosis for peptic ulcer disease.<ref name="Angel 2017"/> By direct visual identification, the location and severity of an ulcer can be described. Moreover, if no ulcer is present, EGD can often provide an alternative diagnosis.

One of the reasons that [[Medicine:Blood test|blood test]]s are not reliable for accurate peptic ulcer diagnosis on their own is their inability to differentiate between past exposure to the bacteria and current infection. Additionally, a false negative result is possible with a blood test if the person has recently been taking certain drugs, such as antibiotics or [[Medicine:Proton-pump inhibitor|proton-pump inhibitor]]s.<ref>{{cite web|url=http://www.mayoclinic.com/health/peptic-ulcer/DS00242/DSECTION=tests-and-diagnosis|title=Peptic ulcer|access-date=18 June 2010|url-status=live|archive-url=https://web.archive.org/web/20100209072021/http://www.mayoclinic.com/health/peptic-ulcer/DS00242/DSECTION%3Dtests-and-diagnosis|archive-date=9 February 2010|df=dmy-all}}</ref>

The diagnosis of ''Helicobacter pylori'' can be made by:
* Urea breath test (noninvasive and does not require EGD);
* Direct culture from an EGD biopsy specimen; this is difficult and can be expensive. Most labs are not set up to perform ''H. pylori'' cultures;
* Direct detection of [[Biology:Urease|urease]] activity in a biopsy specimen by [[Medicine:Rapid urease test|rapid urease test]];<ref name="Angel 2017"/>
* Measurement of [[Biology:Antibody|antibody]] levels in the blood (does not require EGD). It is still somewhat controversial whether a positive antibody without EGD is enough to warrant eradication therapy;
* Stool [[Biology:Antigen|antigen]] test;<ref name="Stenstrom2008">{{cite journal | vauthors = Stenström B, Mendis A, Marshall B | title = Helicobacter pylori--the latest in diagnosis and treatment | journal = Australian Family Physician | volume = 37 | issue = 8 | pages = 608–12 | date = August 2008 | pmid = 18704207 }}</ref>
* Histological examination and staining of an EGD biopsy.

The breath test uses radioactive [[Chemistry:Carbon|carbon]] to detect H. pylori.<ref>{{cite web|url=http://www.mayoclinic.com/health/peptic-ulcer/DS00242/DSECTION=tests-and-diagnosis|title=Tests and diagnosis|access-date=18 June 2010|url-status=live|archive-url=https://web.archive.org/web/20100209072021/http://www.mayoclinic.com/health/peptic-ulcer/DS00242/DSECTION%3Dtests-and-diagnosis|archive-date=9 February 2010|df=dmy-all}}</ref> To perform this exam, the person is asked to drink a tasteless liquid that contains the carbon as part of the substance that the bacteria breaks down. After an hour, the person is asked to blow into a sealed bag. If the person is infected with ''H. pylori'', the breath sample will contain radioactive [[Chemistry:Carbon dioxide|carbon dioxide]]. This test provides the advantage of being able to monitor the response to treatment used to kill the bacteria.

The possibility of other causes of ulcers, notably [[Medicine:Malignancy|malignancy]] (gastric cancer), needs to be kept in mind. This is especially true in ulcers of the ''greater (large) curvature'' of the [[Biology:Stomach|stomach]]; most are also a consequence of chronic ''H. pylori'' infection.

If a peptic ulcer perforates, air will leak from inside the gastrointestinal tract (which always contains some air) to the peritoneal cavity (which normally never contains air). This leads to "free gas" within the peritoneal cavity. If the person stands, as when having a chest X-ray, the gas will float to a position underneath the diaphragm. Therefore, gas in the peritoneal cavity, shown on an erect chest X-ray or supine lateral abdominal X-ray, is an omen of perforated peptic ulcer disease.

===Classification===
[[File:Peptic ulcer.svg|thumb|upright=1.2|{{olist
    |Esophagus
    |Stomach
    |Ulcers
    |Duodenum
    |Mucosa
    |Submucosa
    |Muscle
}}]]

Peptic ulcers are a form of acid–peptic disorder. Peptic ulcers can be classified according to their location and other factors.

====By location====
* [[Biology:Duodenum|Duodenum]] (called duodenal ulcer)
* [[Biology:Esophagus|Esophagus]] (called esophageal ulcer)
* [[Biology:Stomach|Stomach]] (called gastric ulcer)
* [[Medicine:Meckel's diverticulum|Meckel's diverticulum]] (called Meckel's diverticulum ulcer; is very tender with palpation)

====Modified Johnson====
* Type '''I''': Ulcer along the body of the stomach, most often along the lesser curve at incisura angularis along the locus minoris resistantiae. Not associated with acid hypersecretion.
* Type '''II''': Ulcer in the body in combination with duodenal ulcers. Associated with acid oversecretion.
* Type '''III''': In the pyloric channel within 3&nbsp;cm of pylorus. Associated with acid oversecretion.
* Type '''IV''': Proximal gastroesophageal ulcer.
* Type '''V''': Can occur throughout the stomach. Associated with the chronic use of NSAIDs (such as [[Chemistry:Ibuprofen|ibuprofen]]).

===Macroscopic appearance===
[[Image:Benign gastric ulcer 1.jpg|thumb|upright=1.2|A benign gastric ulcer (from the antrum) of a [[Medicine:Gastrectomy|gastrectomy]] specimen.]]

Gastric ulcers are most often localized on the lesser curvature of the stomach. The ulcer is a round to oval parietal defect ("hole"), 2–4&nbsp;cm diameter, with a smooth base and perpendicular borders. These borders are not elevated or irregular in the acute form of peptic ulcer, and regular but with elevated borders and inflammatory surrounding in the chronic form. In the ulcerative form of gastric cancer, the borders are irregular. Surrounding mucosa may present radial folds, as a consequence of the parietal scarring.{{cn|date=July 2022}}

===Microscopic appearance===
[[File:Erosive gastric ulcer.jpg|thumb|upright=1.2|Micrograph showing erosive gastric ulcer. (H&E stain)]]
A gastric peptic ulcer is a mucosal perforation that penetrates the [[Biology:Muscularis mucosae|muscularis mucosae]] and lamina propria, usually produced by acid-pepsin aggression. Ulcer margins are perpendicular and present chronic gastritis. During the active phase, the base of the ulcer shows four zones: fibrinoid necrosis, inflammatory exudate, granulation tissue and fibrous tissue. The fibrous base of the ulcer may contain vessels with thickened wall or with thrombosis.<ref name="pathologyatlas">{{cite web| url= http://www.pathologyatlas.ro/chronic-peptic-ulcer.php| title= ATLAS OF PATHOLOGY| access-date= 26 August 2007| url-status= live| archive-url= https://web.archive.org/web/20090209051200/http://www.pathologyatlas.ro/chronic-peptic-ulcer.php| archive-date= 9 February 2009| df= dmy-all}}</ref>

===Differential diagnosis===
Conditions that may appear similar include:
{{div col|colwidth=30em}}
* [[Medicine:Gastritis|Gastritis]]
* [[Medicine:Stomach cancer|Stomach cancer]]
* [[Medicine:Gastroesophageal reflux disease|Gastroesophageal reflux disease]]
* [[Medicine:Pancreatitis|Pancreatitis]]
* Hepatic congestion
* [[Medicine:Cholecystitis|Cholecystitis]]
* Biliary colic
* [[Medicine:Myocardial infarction|Inferior myocardial infarction]]
* Referred pain ([[Medicine:Pleurisy|pleurisy]], [[Medicine:Pericarditis|pericarditis]])
* [[Medicine:Superior mesenteric artery syndrome|Superior mesenteric artery syndrome]]
{{div col end}}

==Prevention==
Prevention of peptic ulcer disease for those who are taking NSAIDs (with low cardiovascular risk) can be achieved by adding a proton pump inhibitor (PPI), an [[Chemistry:H2 antagonist|H2 antagonist]], or [[Chemistry:Misoprostol|misoprostol]].<ref name="Angel 2017"/> NSAIDs of the COX-2 inhibitors type may reduce the rate of ulcers when compared to non-selective NSAIDs.<ref name="Angel 2017"/> PPI is the most popular agent in peptic ulcer prevention.<ref name="Angel 2017"/> However, there is no evidence that H2 antagonists can prevent stomach bleeding for those taking NSAIDs.<ref name="Angel 2017"/> Although misoprostol is effective in preventing peptic ulcer, its properties of promoting abortion and causing gastrointestinal distress limit its use.<ref name="Angel 2017"/> For those with high cardiovascular risk, naproxen with PPI can be a useful choice.<ref name="Angel 2017"/> Otherwise, low-dose aspirin, celecoxib, and PPI can also be used.<ref name="Angel 2017"/>

==Management==
[[File:Antisectetory drugs.jpg|thumb|Peptic ulcer treatment: pharmacology of drugs]]

===Eradication therapy===
Once the diagnosis of ''H. pylori'' is confirmed, the first-line treatment would be a triple regimen in which [[Chemistry:Pantoprazole|pantoprazole]] and [[Chemistry:Clarithromycin|clarithromycin]] are combined with either [[Chemistry:Amoxicillin|amoxicillin]] or [[Chemistry:Metronidazole|metronidazole]]. This treatment regimen can be given for 7–14 days. However, its effectiveness in eradicating ''H. pylori'' has been reducing from 90% to 70%. However, the rate of eradication can be increased by doubling the dosage of pantoprazole or increasing the duration of treatment to 14 days. Quadruple therapy (pantoprazole, clarithromycin, amoxicillin, and metronidazole) can also be used. The quadruple therapy can achieve an eradication rate of 90%. If the clarithromycin resistance rate is higher than 15% in an area, the usage of clarithromycin should be abandoned. Instead, [[Chemistry:Bismuth|bismuth]]-containing quadruple therapy can be used (pantoprazole, bismuth citrate, [[Chemistry:Tetracycline|tetracycline]], and metronidazole) for 14 days. The bismuth therapy can also achieve an eradication rate of 90% and can be used as second-line therapy when the first-line triple-regimen therapy has failed.

===NSAIDs-induced ulcers===
NSAID-associated ulcers heal in six to eight weeks provided the NSAIDs are withdrawn with the introduction of proton pump inhibitors (PPI).<ref name="Angel 2017"/>

===Bleeding===
For those with bleeding peptic ulcers, [[Medicine:Fluid replacement|fluid replacement]] with crystalloids is sometimes given to maintain volume in the blood vessels. Maintaining haemoglobin at greater than 7 g/dL (70 g/L) through restrictive blood transfusion has been associated with reduced rate of death. [[Medicine:Glasgow-Blatchford score|Glasgow-Blatchford score]] is used to determine whether a person should be treated inside a hospital or as an outpatient. Intravenous PPIs can suppress stomach bleeding more quickly than oral ones. A neutral stomach pH is required to keep platelets in place and prevent clot lysis. [[Chemistry:Tranexamic acid|Tranexamic acid]] and [[Medicine:Antifibrinolytic|antifibrinolytic]] agents are not useful in treating peptic ulcer disease.<ref name="Angel 2017"/>

Early endoscopic therapy can help to stop bleeding by using cautery, [[Medicine:Endoclip|endoclip]], or epinephrine injection. Treatment is indicated if there is active bleeding in the stomach, visible vessels, or an adherent clot. Endoscopy is also helpful in identifying people who are suitable for hospital discharge. Prokinetic agents such as [[Chemistry:Erythromycin|erythromycin]] and [[Chemistry:Metoclopramide|metoclopramide]] can be given before endoscopy to improve endoscopic view. Either high- or low-dose PPIs are equally effective in reducing bleeding after endoscopy. High-dose intravenous PPI is defined as a bolus dose of 80&nbsp;mg followed by an infusion of 8&nbsp;mg per hour for 72 hours—in other words, the continuous infusion of PPI of greater than 192&nbsp;mg per day. Intravenous PPI can be changed to oral once there is no high risk of rebleeding from peptic ulcer.<ref name="Angel 2017"/>

For those with [[Medicine:Hypovolemic shock|hypovolemic shock]] and ulcer size of greater than 2&nbsp;cm, there is a high chance that the endoscopic treatment would fail. Therefore, surgery and angiographic embolism are reserved for these complicated cases. However, there is a higher rate of complication for those who underwent surgery to patch the stomach bleeding site when compared to repeated endoscopy. Angiographic embolisation has a higher rebleeding rate but a similar rate of death to surgery.<ref name="Angel 2017"/>

===Anticoagulants===
According to expert opinion, for those who are already on anticoagulants, the international normalized ratio (INR) should be kept at 1.5. For aspirin users who required endoscopic treatment for bleeding peptic ulcer, there is two times increased risk of rebleeding but with ten times reduced risk of death at eight weeks following the resumption of aspirin. For those who were on double antiplatelet agents for indwelling stent in blood vessels, both antiplatelet agents should not be stopped because there is a high risk of stent thrombosis. For those who were under [[Chemistry:Warfarin|warfarin]] treatment, [[Medicine:Fresh frozen plasma|fresh frozen plasma]] (FFP), vitamin K, prothrombin complex concentrates, or recombinant factor VIIa can be given to reverse the effect of warfarin. High doses of vitamin K should be avoided to reduce the time for rewarfarinisation once the stomach bleeding has stopped. Prothrombin complex concentrates are preferred for severe bleeding. Recombinant factor VIIa is reserved for life-threatening bleeding because of its high risk of thromboembolism.<ref name="Angel 2017"/> [[Medicine:Anticoagulant#Directly acting oral anticoagulants|Direct oral anticoagulants]] (DOAC) are recommended instead of warfarin as they are more effective in preventing thromboembolism. In case of bleeding caused by DOAC, [[Physics:Activated carbon|activated charcoal]] within four hours is the antidote of choice.

==Epidemiology==
[[File:Peptic ulcer disease world map-Deaths per million persons-WHO2012.svg|thumb|upright=1.3|Deaths from peptic ulcer disease per million persons in 2012 {{Div col|small=yes|colwidth=10em}}{{legend|#ffff20|0-7}}{{legend|#ffe820|8-11}}{{legend|#ffd820|12-16}}{{legend|#ffc020|17-19}}{{legend|#ffa020|20-25}}{{legend|#ff9a20|26-32}}{{legend|#f08015|33-40}}{{legend|#e06815|41-53}}{{legend|#d85010|54-72}}{{legend|#d02010|73-132}}{{div col end}}]]
[[File:peptic ulcer disease world map - DALY - WHO2004.svg|thumb|upright=1.3|[[Disability-adjusted life year]] for peptic ulcer disease per 100,000&nbsp;inhabitants in 2004.<ref>{{cite web |url=https://www.who.int/healthinfo/global_burden_disease/estimates_country/en/index.html |title=WHO Disease and injury country estimates |year=2009 |work=World Health Organization |access-date=11 November 2009 |url-status=live |archive-url=https://web.archive.org/web/20091111101009/http://www.who.int/healthinfo/global_burden_disease/estimates_country/en/index.html |archive-date=11 November 2009 |df=dmy-all }}</ref>{{Div col|small=yes|colwidth=10em}}
{{legend|#b3b3b3|no data}}
{{legend|#ffff65|less than 20}}
{{legend|#fff200|20–40}}
{{legend|#ffdc00|40–60}}
{{legend|#ffc600|60–80}}
{{legend|#ffb000|80–100}}
{{legend|#ff9a00|100–120}}
{{legend|#ff8400|120–140}}
{{legend|#ff6e00|140–160}}
{{legend|#ff5800|160–180}}
{{legend|#ff4200|180–200}}
{{legend|#ff2c00|200–220}}
{{legend|#cb0000|more than 220}}
{{div col end}}]]
The lifetime risk for developing a peptic ulcer is approximately 5% to 10%<ref name=Snow2008/><ref name="Angel 2017"/> with the rate of 0.1% to 0.3% per year.<ref name="Angel 2017">{{cite journal | vauthors = Lanas A, Chan FK | title = Peptic ulcer disease | journal = Lancet | volume = 390 | issue = 10094 | pages = 613–624 | date = August 2017 | pmid = 28242110 | doi = 10.1016/S0140-6736(16)32404-7 | s2cid = 4547048 }}</ref> Peptic ulcers resulted in 301,000 deaths in 2013, down from 327,000 in 1990.<ref name="GDB2013"/>

In Western countries, the percentage of people with ''H. pylori'' infections roughly matches age (i.e., 20% at age 20, 30% at age 30, 80% at age 80, etc.). Prevalence is higher in third world countries, where it is estimated at 70% of the population, whereas developed countries show a maximum of a 40% ratio. Overall, ''H. pylori'' infections show a worldwide decrease, more so in developed countries. Transmission occurs via food, contaminated groundwater, or human saliva (such as from kissing or sharing food utensils).<ref name="pmid11218379">{{cite journal | vauthors = Brown LM | title = Helicobacter pylori: epidemiology and routes of transmission | journal = Epidemiologic Reviews | volume = 22 | issue = 2 | pages = 283–97 | year = 2000 | pmid = 11218379 | doi = 10.1093/oxfordjournals.epirev.a018040 | df = dmy-all | doi-access = free }}</ref>

Peptic ulcer disease had a tremendous effect on morbidity and mortality until the last decades of the 20th century when epidemiological trends started to point to an impressive fall in its incidence. The reason that the rates of peptic ulcer disease decreased is thought to be the development of new effective medication and acid suppressants and the rational use of [[Chemistry:Nonsteroidal anti-inflammatory drug|nonsteroidal anti-inflammatory drug]]s (NSAIDs).<ref name="Angel 2017"/>

==History==

John Lykoudis, a general practitioner in Greece, treated people for peptic ulcer disease with antibiotics beginning in 1958, long before it was commonly recognized that bacteria were a dominant cause for the disease.<ref name=Lykoudis>{{cite book |first1=Basil |last1=Rigas |first2=Efstathios D. |last2=Papavasassiliou |chapter=Ch. 7 John Lykoudis. The general practitioner in Greece who in 1958 discovered the etiology of, and a treatment for, peptic ulcer disease. |chapter-url=https://books.google.com/books?id=lK4ATW-lQZQC&pg=PA75 |editor-first=Barry J. |editor-last=Marshall |title=Helicobacter pioneers: firsthand accounts from the scientists who discovered helicobacters, 1892–1982 |url=https://books.google.com/books?id=lK4ATW-lQZQC&pg=PR4 |date=22 May 2002 |publisher=John Wiley & Sons |isbn=978-0-86793-035-1 |pages=74–88 |url-status=live |archive-url=https://web.archive.org/web/20160521063535/https://books.google.com/books?id=lK4ATW-lQZQC&pg=PR4 |archive-date=21 May 2016 |df=dmy-all }}</ref>

''Helicobacter pylori'' was identified in 1982 by two {{wipe|Australia}}n scientists, [[Biography:Robin Warren|Robin Warren]] and [[Biography:Barry Marshall|Barry J. Marshall]], as a causative factor for ulcers.<ref>{{cite journal | vauthors = Warren JR, Marshall B | title = Unidentified curved bacilli on gastric epithelium in active chronic gastritis | journal = Lancet | volume = 1 | issue = 8336 | pages = 1273–5 | date = June 1983 | pmid = 6134060 | doi = 10.1016/S0140-6736(83)92719-8 | s2cid = 1641856 }}</ref> In their original paper, Warren and Marshall contended that most gastric ulcers and gastritis were caused by colonization with this bacterium, not by stress or spicy food, as had been assumed before.<ref>{{cite journal | vauthors = Marshall BJ, Warren JR | title = Unidentified curved bacilli in the stomach of patients with gastritis and peptic ulceration | journal = Lancet | volume = 1 | issue = 8390 | pages = 1311–5 | date = June 1984 | pmid = 6145023 | doi = 10.1016/S0140-6736(84)91816-6 | s2cid = 10066001 }}</ref>

The ''H. pylori'' hypothesis was still poorly received,<ref>{{cite magazine |url=http://www.slate.com/content/slate/blogs/thewrongstuff/2010/09/09/stress_doesn_t_cause_ulers_or_how_to_win_a_nobel_prize_in_one_easy_lesson_barry_marshall_on_being_right.html |title=Stress Doesn't Cause Ulcers! Or, How To Win a Nobel Prize in One Easy Lesson: Barry Marshall on Being ... Right | first = Kathryn | last = Schulz | date=9 September 2010 |magazine=The Wrong Stuff |publisher=Slate |access-date=17 July 2011 |url-status=live |archive-url=https://web.archive.org/web/20110805082007/http://www.slate.com/content/slate/blogs/thewrongstuff/2010/09/09/stress_doesn_t_cause_ulers_or_how_to_win_a_nobel_prize_in_one_easy_lesson_barry_marshall_on_being_right.html |archive-date=5 August 2011 |df=dmy-all }}</ref> so in an act of [[Self-experimentation|self-experimentation]] Marshall drank a Petri dish containing a culture of organisms extracted from a person with an ulcer and five days later developed gastritis. His symptoms disappeared after two weeks, but he took antibiotics to kill the remaining bacteria at the urging of his wife, since halitosis is one of the symptoms of infection.<ref name="mja">{{cite journal | vauthors = Van Der Weyden MB, Armstrong RM, Gregory AT | title = The 2005 Nobel Prize in physiology or medicine | journal = The Medical Journal of Australia | volume = 183 | issue = 11–12 | pages = 612–4 | year = 2005 | pmid = 16336147 | url = http://www.mja.com.au/public/issues/183_11_051205/van11000_fm.html#0_i1091639 | archive-url = https://web.archive.org/web/20090627035448/http://www.mja.com.au/public/issues/183_11_051205/van11000_fm.html#0_i1091639 | df = dmy-all | url-status = live | archive-date = 27 June 2009 | doi=10.5694/j.1326-5377.2005.tb00052.x| s2cid = 45487832 }}</ref> This experiment was published in 1984 in the ''Australian Medical Journal'' and is among the most cited articles from the journal.

In 1997, the Centers for Disease Control and Prevention, with other government agencies, academic institutions, and industry, launched a national education campaign to inform health care providers and consumers about the link between ''H. pylori'' and ulcers. This campaign reinforced the news that ulcers are a curable infection and that health can be greatly improved and money saved by disseminating information about ''H. pylori''.<ref>{{cite web |url=https://www.cdc.gov/ulcer/history.htm |title=Ulcer, Diagnosis and Treatment - CDC Bacterial, Mycotic Diseases |publisher=Cdc.gov |access-date=27 February 2014 |url-status=live |archive-url=https://web.archive.org/web/20131203231313/http://www.cdc.gov/ulcer/history.htm |archive-date=3 December 2013 |df=dmy-all }}</ref>

In 2005, the Karolinska Institute in Stockholm awarded the Nobel Prize in Physiology or Medicine to Marshall and his long-time collaborator Warren "for their discovery of the bacterium ''Helicobacter pylori'' and its role in [[Medicine:Gastritis|gastritis]] and peptic ulcer disease." Marshall continues research related to ''H. pylori'' and runs a molecular biology lab at UWA in Perth, Western Australia.

Some believed that mastic gum, a tree resin extract, actively eliminates the ''H. pylori'' bacteria.<ref name="pmid9874617">{{cite journal | vauthors = Huwez FU, Thirlwell D, Cockayne A, Ala'Aldeen DA | title = Mastic gum kills Helicobacter pylori | journal = The New England Journal of Medicine | volume = 339 | issue = 26 | pages = 1946 | date = December 1998 | pmid = 9874617 | doi = 10.1056/NEJM199812243392618 | url = http://content.nejm.org/cgi/content/extract/339/26/1946 | archive-url = https://web.archive.org/web/20080915121329/http://content.nejm.org/cgi/content/extract/339/26/1946 | df = dmy-all | url-status = live | archive-date = 15 September 2008 | doi-access = free }} See also [http://content.nejm.org/cgi/content/extract/340/7/576 their corrections in the next volume] {{webarchive|url=https://web.archive.org/web/20081005120756/http://content.nejm.org/cgi/content/extract/340/7/576 |date=5 October 2008 }}.</ref> However, multiple subsequent studies have found no effect of using mastic gum on reducing ''H. pylori'' levels.<ref name="pmid12562704">{{cite journal | vauthors = Loughlin MF, Ala'Aldeen DA, Jenks PJ | title = Monotherapy with mastic does not eradicate Helicobacter pylori infection from mice | journal = The Journal of Antimicrobial Chemotherapy | volume = 51 | issue = 2 | pages = 367–71 | date = February 2003 | pmid = 12562704 | doi = 10.1093/jac/dkg057 | doi-access = free }}</ref><ref name="pmid12888582">{{cite journal | vauthors = Bebb JR, Bailey-Flitter N, Ala'Aldeen D, Atherton JC | title = Mastic gum has no effect on Helicobacter pylori load in vivo | journal = The Journal of Antimicrobial Chemotherapy | volume = 52 | issue = 3 | pages = 522–3 | date = September 2003 | pmid = 12888582 | doi = 10.1093/jac/dkg366 | doi-access = free }}</ref>

==Notes==
<references group="nb" />

== References ==
{{Reflist}}

== External links ==
{{Medical condition classification and resources
| DiseasesDB = 9819
| ICD10 = {{ICD10|K|25||k|20}}–{{ICD10|K|27||k|20}}
| ICD9 = {{ICD9|531}}–{{ICD9|533}}
| ICDO =
| OMIM =
| MedlinePlus = 000206
| eMedicineSubj = med
| eMedicineTopic = 1776
| eMedicine_mult = {{eMedicine2|ped|2341}}
| MeshID = D010437
}}
* [https://web.archive.org/web/20120719000141/http://rad.usuhs.edu/medpix/parent.php3?mode=pt_finder&srchstr=gastric%20ulcer#top Gastric ulcer images]
* {{cite web | url = https://medlineplus.gov/pepticulcer.html | publisher = U.S. National Library of Medicine | work = MedlinePlus | title = Peptic Ulcer | access-date = 20 May 2020 | archive-url = https://web.archive.org/web/20200416082316/https://medlineplus.gov/pepticulcer.html | archive-date = 16 April 2020 | url-status = dead }}

{{Gram-negative bacterial diseases}}
{{Gastroenterology}}

{{DEFAULTSORT:Peptic Ulcer}}
[[Category:Wikipedia medicine articles ready to translate]]
[[Category:Acute pain]]

{{Sourceattribution|Peptic ulcer disease}}