Unusual causes of peptic ulcer disease

INTRODUCTION — Peptic ulcers are defects in the gastrointestinal mucosa that extend through the muscularis mucosae. They persist as a function of the acid/peptic activity in gastric juice. Peptic ulcer disease remains an important cause of morbidity and mortality and health care costs [1-3]. Helicobacter pylori and nonsteroidal anti-inflammatory drugs (NSAIDs) account for the large majority of cases of peptic ulcer disease (PUD). (See "Association between Helicobacter pylori infection and duodenal ulcer" and "NSAIDs (including aspirin): Pathogenesis and risk factors for gastroduodenal toxicity".)

This topic will review unusual causes for peptic ulcer disease. The epidemiology, risk factors, clinical manifestations, diagnosis, and management of peptic ulcer disease are discussed in detail, separately. (See "Peptic ulcer disease: Epidemiology, etiology, and pathogenesis" and "Peptic ulcer disease: Clinical manifestations and diagnosis" and "Overview of complications of peptic ulcer disease" and "Peptic ulcer disease: Treatment and secondary prevention" and "Approach to refractory peptic ulcer disease".)

EPIDEMIOLOGY — In a retrospective study that included 386 patients conducted over five years in a large tertiary hospital in the United Kingdom, Helicobacter pylori (H. pylori)-negative, NSAID-negative ulcers accounted for 12 percent of all ulcers [4]. Several studies in the United States have shown that less than 75 percent of patients with duodenal ulcers (DUs) not associated with use of NSAIDs are related to H. pylori infection. In one study, after excluding NSAID use, 61 percent of DUs and 63 percent of gastric ulcers were H. pylori positive [5].

ETIOLOGY

Non-NSAID medications — There are a number of drugs that may cause or exacerbate peptic ulcer disease and/or upper gastrointestinal (GI) bleeding (table 1).

●Acetaminophen – A role for acetaminophen in development of GI complications (including bleeding and perforation) has been suggested in both population-based studies and a randomized controlled trial [6-9]. As a general rule, the risk appears to be increased in doses of 2 to 3 g per day or higher. The risk also appears to be increased with the combination of NSAIDs plus high-dose acetaminophen compared with either alone [6,9]. In a randomized trial of patients with osteoarthritis, co-administration of acetaminophen and aspirin was not associated with a significant difference in endoscopic ulcer rates compared with either drug alone, but there were more endoscopic erosions and ulcers in the combined group compared with either alone [10].

●Bisphosphonates – Damage and acute ulceration have been observed [11,12]. Population-based studies show that use of bisphosphonates such as alendronate are associated with a higher risk of upper and lower GI bleeding [13]. The risk appears to be increased substantially with co-administration of NSAIDs. (See "Risks of bisphosphonate therapy in patients with osteoporosis", section on 'Gastrointestinal'.)

●Glucocorticoids – The association between corticosteroids and peptic ulcer disease (PUD) and its complications is controversial with wide variations in estimates of the risk of PUD. However, the combination of glucocorticoids and NSAIDs results in a synergistic increase in the incidence of gastrointestinal events. (See "Major adverse effects of systemic glucocorticoids", section on 'Gastrointestinal effects'.)

●Clopidogrel – The antiplatelet agent clopidogrel is a significant risk factor for GI bleeding, particularly in patients with a prior risk of bleeding or on cotherapy with low-dose aspirin or NSAIDs [14]. The risk may also be increased with ticlopidine, but data are limited. (See "Acute ST-elevation myocardial infarction: Antiplatelet therapy", section on 'Possible early CABG'.)

●Sirolimus – Sirolimus has been associated with aggressive ulcer disease in patients undergoing liver transplantation [15]. Sirolimus is known to inhibit wound healing and has been associated with small bowel ulceration [16]. This warrants cautious use of this agent in patients with a history of PUD and aggressive management of patients on the drug who develop symptoms or complications suggestive of PUD. (See "Pharmacology of mammalian (mechanistic) target of rapamycin (mTOR) inhibitors", section on 'Gastrointestinal system'.)

●Spironolactone – Spironolactone has been associated with a nearly threefold increased risk of upper GI bleeding [17,18]. The risk appears to be increased with high doses, suggesting dose-related toxicity [18]. The risk was also increased with advancing age and use of concomitant ulcerogenic medications. It is hypothesized that spironolactone, an aldosterone receptor antagonist, may cause ulceration by impairing the healing of gastric or duodenal erosions [18]. Aldosterone promotes the formation of fibrous tissue by binding to mineralocorticosteroid receptors; the effect is modulated by 11 beta hydroxysteroid dehydrogenase enzymes which are expressed in the stomach and to a small extent in the small intestine.

●Selective serotonin reuptake inhibitors – There are increasing data suggesting an impact of selective serotonin reuptake inhibitors (SSRIs) and venlafaxine on the risk of peptic ulcer and upper GI bleeding [19-25]. The risk of both uncomplicated PUD and ulcer-related bleeding is higher in patients taking SSRIs [26]. A concomitant H. pylori infection appears to increase the risk of serious upper GI bleeding in patients on SSRIs [26]. The risk of bleeding is also higher in patients with a history of peptic ulcer, with increasing age and duration of SSRI use, and when SSRIs are combined with antiplatelet therapy (aspirin, clopidogrel) or NSAIDs [26-29]. In a population-based cohort study, the use of SSRIs alone or in combination with NSAIDs was not associated with an increased 30-day mortality following a peptic ulcer bleed [30]. In one large nested case-control study, the risk of upper GI bleeding was only apparent in non-users of acid inhibitors, suggesting that acid suppression attenuates the impact of SSRIs [27]. Short-time use of SSRIs (14 days) has also been associated with an increased risk of bleeding [31]. A systematic review suggested there was an approximate two-fold increase in the risk for upper GI hemorrhage in SSRI users, and the risk appears to be greatest in those using NSAIDs or antiplatelet drugs concomitantly [32]. (See "Selective serotonin reuptake inhibitors: Pharmacology, administration, and side effects", section on 'Upper gastrointestinal bleeding'.)

●Antineoplastic therapy

•Chemotherapy – Some cancer chemotherapeutic agents have been associated with peptic disease. As an example, patients receiving continuous hepatic artery infusion of fluorouracil frequently complain of abdominal pain. In one series, endoscopy usually revealed duodenal, gastric, or pyloric ulcerations and erosions [33]. The mechanisms have not been established; catheter migration with direct gastric infusion of chemotherapy did not explain most cases. These lesions responded to discontinuation of chemotherapy; H2 receptor blockers and proton pump inhibitors (PPIs) appeared to have little efficacy, but have not been formally tested. Thus, these ulcers may not truly be peptic ulcers.

•Molecular targeted therapy – An example of a targeted agent that can cause ulceration include erlotinib, a reversible tyrosine kinase inhibitor of the epidermal growth factor receptor used for cancer treatment. GI bleeding from peptic ulcers and ulcer perforation have been reported; not surprisingly, the risk appears greater when erlotinib is combined with NSAIDs, including cyclooxygenase-2 inhibitors, and in patients with a peptic ulcer history or treated with anticoagulants [34-37].

•Immune checkpoint inhibitors – Immune checkpoint inhibitors have been associated with severe gastritis, gastric ulcers, and GI bleeding. These ulcers and gastritis may not respond to PPI therapy, and corticosteroid therapy is needed in severe cases [38-40].

Infections

Bacteria

●Isolated duodenal H. pylori colonization – In high-prevalence regions for H. pylori, it is important to consider duodenal colonization in patients who lack gastric evidence of H. pylori. In an Italian study 42 of 608 patients (6.9 percent) with duodenal ulcer had no other obvious cause; 18 of these 42 patients had isolated duodenal colonization with H. pylori detected by biopsy [41]. H. pylori eradication therapy was given to these 18 subjects; two had ulcer recurrences compared with 14 out of 20 subjects in the "idiopathic" group. Urea breath tests were positive in only 3 of the 18 patients with isolated duodenal colonization [41].

●Non-pylori helicobacter – Helicobacters other than H. pylori have been associated with peptic ulcer disease. Helicobacter heilmannii is the most frequently described organism and is often associated with antral ulcers [42].

Viruses

●Herpes simplex virus type I – The possible involvement of herpes simplex virus type 1 (HSV-1) in patients with PUD has been suggested by an increased incidence of anti-HSV-1 antibodies in patients with peptic ulcers [43,44] and the detection of DNA and protein specific for HSV-1 in the mucosa at the ulcer margin in a small proportion of patients with seemingly ordinary ulcers [43,45]. A study using polymerase chain reaction to identify HSV-I and a CLO-test and histology to identify H. pylori found HSV-I in 30 and 32 percent of duodenal and gastric ulcers, respectively [46]. HSV-I was found more frequently in the absence of H. pylori infection. There is some evidence that the pathogenesis may involve infected enteric neurons [43,47]. (See "Epidemiology, clinical manifestations, and diagnosis of herpes simplex virus type 1 infection", section on 'HSV esophagitis'.)

●Cytomegalovirus – Cytomegalovirus (CMV) has been associated with ulcers in immunocompromised patients in whom it can cause multiple, large, shallow ulcerations of the stomach and esophagus [48]. The diagnosis has been made by finding intranuclear inclusion bodies or CMV-DNA in the gastric mucosa in biopsy specimens taken from the ulcerous region. (See "Epidemiology, clinical manifestations, and treatment of cytomegalovirus infection in immunocompetent adults", section on 'Gastrointestinal manifestations' and "AIDS-related cytomegalovirus gastrointestinal disease", section on 'Gastritis' and "Infection in the solid organ transplant recipient", section on 'CMV and EBV'.)

●Epstein Barr virus (EBV) – Gastric ulcers related to EBV infections have been reported in both immunocompromised and immunocompetent patients [49,50]. The endoscopic appearance may resemble malignancy.

Fungi — Fungal infections can also cause gastric ulcers in patients who are immunocompromised or immunocompetent [51]. Candidal infections have been described in isolated patients with perforated peptic ulcers. Transmural infections with the organism may be seen, and a compromised immune status may be a risk factor [52,53]. Mucormycosis can cause extensive ulceration and necrosis of the gastric wall in immunocompromised patients. Mucormycosis can cause extensive ulceration and necrosis of the gastric wall in immunocompromised patients [51].

Mechanical

Obstruction — Unusual cases of duodenal ulcers have been linked to a variety of gastroduodenal abnormalities, including congenital duodenal webs, hypertrophic pyloric stenosis, annular pancreas (a rare congenital disorder in which pancreatic tissue encircles the second portion of the duodenum), and a preduodenal portal vein. Duodenal ulcers in these settings may present in infancy or childhood, but can also occur in adolescence or adulthood [54]. As an example, although annular pancreas can present at birth with high-grade duodenal obstruction, it more commonly presents in the second to seventh decade, with the peak incidence in between the ages of 30 and 40 years [54,55]. Ulcers with annular pancreas are often postbulbar and can be associated with basal acid hypersecretion, although mechanisms linking these various "obstructing" lesions of the pylorus and duodenum to acid hypersecretion and ulcer disease remain undefined. (See "Annular pancreas".)

Foreign body — Peptic ulceration has also been observed in association with foreign bodies. Ingestion of multiple magnets and button batteries has been associated with GI ulceration. Microcoils from previous gastroduodenal artery embolization [56] and surgical clip migration from prior laparoscopic cholecystectomy have been found in ulcer craters [57]. Duodenal extension of a gastric trichobezoar can cause ulcerations in the duodenum (Rapunzel syndrome) [58,59]. (See "Ingested foreign bodies and food impactions in adults", section on 'Disk batteries' and "Ingested foreign bodies and food impactions in adults", section on 'Magnets'.)

Post-surgical — Stomal (marginal) ulcers involving the small intestinal mucosa occur in 1 to 16 percent of patients 3 to 18 months after Roux-en-Y gastric bypass surgery for obesity [60-64]. Patients present with pain, bleeding, or perforation. Ulcers occurring in the immediate postoperative period present with bleeding and pain, and the bleeding site can usually be reached with the standard upper endoscope. Ulcers that occur weeks or months after surgery typically present with abdominal pain after meals and are usually due to marginal ulcerations [65]. A number of causes have been suggested for marginal ulceration, including surgical technique resulting in ischemia at the anastomosis, H. pylori infection, and drug-induced ulceration caused by NSAIDS [60,61]. Antral exclusion (retained gastrin antrum) is a rare cause of peptic ulcers. It has been described in patients after gastric resection when some antral mucosa was retained in the duodenal pouch [66].

Acid hypersecretory states

●Gastrinoma – The classic tetrad of the Zollinger-Ellison syndrome consists of a non-beta islet cell tumor secreting gastrin in association with acid hypersecretion and severe PUD, which occurs in approximately 90 percent of cases. (See "Zollinger-Ellison syndrome (gastrinoma): Clinical manifestations and diagnosis".)

The majority of Zollinger-Ellison tumors are sporadic. However, 20 to 25 percent occur in association with the multiple endocrine neoplasia syndrome type 1 (MEN1). MEN1 is a familial disorder characterized by an autosomal dominant predisposition to tumors of the parathyroid glands (which occur in nearly all patients by age 50), anterior pituitary, and pancreatic islet cells (gastrinoma or insulinoma). (See "Multiple endocrine neoplasia type 1: Clinical manifestations and diagnosis".)

Although gastrinoma-associated peptic ulcers may be indistinguishable from ordinary peptic ulcers, several distinguishing features should raise the level of suspicion (table 2). (See "Zollinger-Ellison syndrome (gastrinoma): Clinical manifestations and diagnosis".)

●Systemic mastocytosis – Systemic mastocytosis is characterized by mast cell infiltration of many tissues and symptoms of flushing, pruritus, abdominal pain, and diarrhea. Dyspepsia, duodenal ulcers, and severe duodenitis occur in 30 to 50 percent of cases and can be associated with basal acid hypersecretion, a presentation sometimes reminiscent of gastrinoma [67]. While fasting, serum gastrin levels are normal, serum histamine concentrations may be elevated, particularly in the setting of ulcer disease, suggesting that circulating histamine contributes to basal acid hypersecretion [67,68]. (See "Mastocytosis (cutaneous and systemic) in adults: Epidemiology, pathogenesis, clinical manifestations, and diagnosis".)

●Myeloproliferative disorders – Acid hypersecretion, an increased risk of peptic ulcer, and elevated serum histamine concentrations occur in rare myeloproliferative disorders associated with basophilia such as basophilic leukemia and chronic myeloid leukemia with marked basophilia [69]. Acid hypersecretion may only occur when cell lysis occurs during chemotherapy [69].

Polycythemia vera has also been associated with peptic disease. The precipitating cause may be reduced mucosal blood flow due to increased viscosity. A study suggested that patients with polycythemia vera are at greater risk for H. pylori infection and have a higher prevalence of ulcers and erosions in the stomach and duodenum than controls without the disease [70]. (See "Clinical manifestations and diagnosis of polycythemia vera", section on 'Gastrointestinal symptoms'.)

●Antral G-cell hyperfunction – In the pre-H. pylori era, an entity called antral G-cell hyperfunction was reported, characterized by duodenal ulcers, increased basal- and/or meal-stimulated gastrin release, and usually increased basal or maximal acid output [71,72]. It now appears probable that antral G-cell hyperfunction usually reflects an exaggerated response to H. pylori-induced hypergastrinemia, being part of the spectrum of H. pylori-associated duodenal ulcers. In H. pylori-positive patients who appear to have this disorder, anti-H. pylori therapy induces ulcer healing and suppresses serum gastrin levels [72-74]. Although controversial and rare, antral G-cell hyperfunction can probably occur in the absence of H. pylori [72,74]. The pathogenesis of hypergastrinemia in this setting is not known.

Ischemic

Arterial/venous diseases — Mucosal blood flow is critical to mucosal integrity. Although ischemia is rare because of the rich vascularization of the gastroduodenal mucosa, vascular insufficiency syndromes involving arterial supply rarely present with peptic ulceration that is unrelated to H. pylori infection or NSAID use [75-78]. Some patients complain of typical ulcer pain, while others may have symptoms suggestive of mesenteric angina with pain following meals. Endoscopy may reveal multiple gastric or duodenal ulcers. Ulcers related to vascular stenosis often fail PPI therapy, but several reports indicated response to revascularization [75,78]. Gastroduodenal artery pseudoaneurysm is also a rare cause of ulceration [79].

Intestinal ulceration can occur after vascular injury by abdominal radiotherapy, with the second portion of the duodenum being especially sensitive to radiation injury [80]. Gastroduodenal ulceration also occurs following chemoembolization used to treat hepatic tumors with an incidence between 3 and 5 percent; abdominal pain, nausea, vomiting, and anorexia herald this complication [81-83]. Careful attention to protocol may reduce the risks of this complication [82]. (See "Overview of gastrointestinal toxicity of radiation therapy", section on 'Gastritis'.)

Non-occlusive ischemia — Mucosal vasoconstriction may explain the perforation of gastroduodenal ulcers that have been described with crack cocaine use [84-88]. Enterocolic lymphocytic phlebitis is a rare cause of GI ischemia apparently due to inflammation. It usually involves the intestine, but one case had both gastric and duodenal involvement associated with a chronic non-healing antral ulcer [89].

Hypothermia and hypoxia at high altitudes may also predispose to gastric and duodenal erosions and ulcers [90,91].

Inflammatory and infiltrating disease

●Sarcoidosis – Involvement of the stomach is the most common site of sarcoidosis in the GI tract, almost always occurring in association with pulmonary disease [92,93]. Ulceration resembling PUD can occur with or without enlargement of mucosal folds. (See "Gastrointestinal, hepatic, pancreatic, and peritoneal sarcoidosis".)

●Crohn disease – Crohn disease of the stomach and/or duodenum is not infrequently found [94] but only occasionally causes clinical impact. In the large majority of cases, more distal Crohn disease is also evident. Involvement presents with obstruction, ulceration, fistula formation, or bleeding [95]. (See "Clinical manifestations, diagnosis, and prognosis of Crohn disease in adults", section on 'Other gastrointestinal features'.)

●Other gastroenteritides – Case reports indicate that peptic ulcers, including perforated ulcers, can occur in association with eosinophilic gastroenteritis [96-98] and hypereosinophilic syndromes [99]. Refractory gastric ulcers have also been associated with abundant IgG4-positive plasma cell infiltration and granulomatosis with polyangiitis [100,101]. (See "Eosinophilic gastrointestinal diseases" and "Granulomatosis with polyangiitis and microscopic polyangiitis: Clinical manifestations and diagnosis".)

Other

●Idiopathic hypersecretory duodenal ulcer – Approximately 10 percent of patients with duodenal ulcers have basal acid output above 15 mmol per hour, normal serum gastrin levels, and ulcer disease unrelated to H. pylori infection [102]. These cases appear to represent a form of hypersecretory duodenal ulcer, the mechanisms of which remain to be defined. The acid hypersecretion appears to respond to long-term treatment with a PPI [102,103]. Such patients may require relatively high doses of a PPI, as in gastrinoma.

●Stress ulcers in the intensive care unit – Estimates of the incidence of overt GI bleeding from stress-induced ulceration range from 1.5 to 8.5 percent among all intensive care unit patients, but may be as high as 15 percent among patients who do not receive stress ulcer prophylaxis. Patient selection for prophylaxis is discussed elsewhere. (See "Stress ulcers in the intensive care unit: Diagnosis, management, and prevention".)

EVALUATION OF H. PYLORI AND NSAID NEGATIVE ULCERS — Before considering unusual causes of peptic ulcer disease (PUD), H. pylori and NSAID use should be excluded since these two risk factors still account for the large majority of cases of PUD. False-negative testing for H. pylori and a failure to detect NSAID use are probably the most common causes of apparently H. pylori-negative, NSAID-negative ulcers. For H. pylori, particular caution is needed because many of the patients being evaluated will have been treated with a proton pump inhibitor or antibiotics, rendering tests dependent upon bacterial density less reliable.

History — The initial evaluation for patients with non-H. pylori, non-NSAID related peptic ulcer disease should include an assessment for associated diseases as well as other possible comorbidities.

Some of the key elements of the history include the following:

●Medications (including over-the-counter drugs and supplements).

●Cocaine or methamphetamine use.

●Prior gastric surgery including bariatric procedures or radiation.

●Comorbidities including Crohn disease, sarcoidosis, mastocytosis, multiple endocrine neoplasia type 1 (MEN1).

●Concomitant history of a hematologic disease including chronic myeloid leukemia and polycythemia vera.

●Associated symptoms, especially diarrhea which may be due to Zollinger-Ellison syndrome, Crohn disease, or systemic mastocytosis.

●A history of peptic ulcers that are resistant to medical therapy, recurrent ulcers, multiple ulcers beyond the duodenal bulb, which are suggestive of Zollinger-Ellison Syndrome (ZES) (table 2).

●Family history of peptic ulcer disease or MEN1 may indicate the presence of ZES.

If an unusual cause of a peptic ulcer is suspected based on the history, additional testing should be performed as needed to establish the etiology.

Laboratory testing in selected patients — Initial evaluation in a patient with suspected ZES is with measurement of fasting serum gastrin concentration and measurement of gastric pH (table 2). In patients with elevated serum gastrin levels/low gastric pH that are not diagnostic for ZES, we perform a secretin stimulation test. Laboratory evaluation for ZES is discussed in detail separately. (See 'History' above and 'Acid hypersecretory states' above and "Zollinger-Ellison syndrome (gastrinoma): Clinical manifestations and diagnosis", section on 'Clinical manifestations'.)

Repeat upper endoscopy in ulcers without a clear etiology — In patients with gastric or duodenal ulcers without a clear etiology, we perform an upper endoscopy 8 to 12 weeks after initiating medical therapy (with biopsies of the ulcer if still present) in order to exclude a malignancy. This upper endoscopy allows for additional biopsies of the ulcer to exclude neoplastic, infiltrative, or infectious causes of ulceration. We biopsy both the ulcers and the surrounding mucosa. In addition, we biopsy the duodenum to detect isolated duodenal colonization by H. pylori. (See 'Bacteria' above and 'Inflammatory and infiltrating disease' above.)

SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Peptic ulcer disease".)

SUMMARY AND RECOMMENDATIONS

●Peptic ulcers are defects in the gastrointestinal mucosa that extend through the muscularis mucosae. They persist as a function of the acid/peptic activity in gastric juice. Peptic ulcer disease (PUD) is an important cause of morbidity and health care costs. Helicobacter pylori and NSAIDs account for the large majority of cases of peptic ulcer disease. (See 'Introduction' above and 'Epidemiology' above.)

●Several medications have been implicated in the development of peptic ulcers either alone or synergistically with other ulcerogenic or antithrombotic agents. Drugs implicated include acetaminophen (in doses greater than 2 or 3 g daily), bisphosphonates, cocaine, glucocorticoids, selective serotonin reuptake inhibitors, clopidogrel, and erlotinib. The risk of some agents may only be evident in patients with an ulcer or bleeding diathesis, such as those with a prior history of PUD or bleeding complications. (See 'Non-NSAID medications' above.)

●Other causes of peptic ulcer disease include infections (eg, non-pylori Helicobacter, Cytomegalovirus), mechanical (eg, post-obstructive, foreign body, surgery), ischemia, inflammatory and infiltrating diseases of the stomach (eg, Crohn disease), and acid hypersecretory states (eg, Zollinger-Ellison syndrome). (See 'Etiology' above.)

●Before considering unusual causes of peptic ulcer disease, H. pylori and NSAID use should be excluded since these two risk factors still account for the large majority of cases of PUD. False-negative testing for H. pylori and a failure to detect NSAID use are probably the most common causes of apparently H. pylori-negative, NSAID-negative ulcers. For H. pylori, particular caution is needed because many of the patients being evaluated will have been treated with a proton pump inhibitor or antibiotics, rendering tests dependent upon bacterial density less reliable. (See 'Evaluation of H. pylori and NSAID negative ulcers' above.)

●The initial evaluation for patients with non-H. pylori, non-NSAID related peptic ulcer disease should include an assessment for associated diseases as well as other possible comorbidities. Zollinger-Ellison Syndrome should be suspected in patients with multiple or refractory peptic ulcers; ulcers distal to the duodenum; peptic ulcer disease and diarrhea, enlarged gastric folds, or multiple endocrine neoplasia type 1 (MEN1). ZES should also be suspected in patients with peptic ulcer disease and a family history of peptic ulcer disease or MEN1. (See 'History' above.)

●In patients with gastric or duodenal ulcers without a clear etiology, we perform an upper endoscopy 8 to 12 weeks after initiating medical therapy (with biopsies of the ulcer if still present) in order to exclude a malignancy. This upper endoscopy allows for additional biopsies of the ulcer to exclude neoplastic, infiltrative, or infectious causes of ulceration. We biopsy both the ulcers and the surrounding mucosa. In addition, we biopsy the duodenum to detect isolated duodenal colonization by H. pylori. (See 'Repeat upper endoscopy in ulcers without a clear etiology' above.)

ACKNOWLEDGMENT — The UpToDate editorial staff acknowledges Andrew H. Soll, MD, who contributed to an earlier version of this topic review.