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peptic ulcer disease (PUD)

Classification: endoscopic classification - grade 1A: pulsatile bleeding - grade 1B: oozing blood - grade 2A: non-bleeding visible vessel (pigmented protruberance) - grade 2B: adherent clot - grade 2C: flat pigmented spot - grade 3: clean ulcer base Etiology: 1) Helicobacter pylori infection* [6] a) associated with 90-95% of duodenal ulcers b) associated with 70-90% of gastric ulcers c) decreasing as cause of peptic ulcer [21] - only 17% of peptic ulcers H pylori positive [22] d) major cause of chronic active gastritis 2) non-steroidal anti-inflammatory drugs (NSAIDs)* [6] a) may cause gastric (antral) or duodenal ulcers b) addition of steroids potentiates risk of PUD c) accounts for majority of PUD not associated with H pylori d) presence of Helicobacter pylori - does not confer additional risk [4] - does confer additional risk [14] e) glucocorticoids also risk factor [2] 3) ethacrynic acid 4) severe physiologic stress a) burns b) CNS trauma c) surgery d) severe medical illness 5) psychosocial stress [13] - low stress resilience is a marker of risk [13] 6) hypersecretory states a) gastrinoma (Zollinger-Ellison syndrome) b) multiple endocrine neoplasia (MEN)-1 c) antral G cell hyperplasia d) systemic mastocytosis e) basophilic leukemia 7) viral infection a) Herpes b) Cytomegalovirus 8) radiation 9) chemotherapy 10) vascular insufficiency: crack cocaine 11) duodenal obstruction 12) diseases associated with peptic ulcer disease (PUD) a) cirrhosis of the liver b) chronic obstructive pulmonary disease c) renal failure d) renal transplantation 13) smoking & alcohol are risk factors 14) anticoagulation is a risl factor for bleeding [2] 15) 50% of peptic ulcer idiopathic [21] * H pylori & NSAIDs cause > 90% of peptic ulcers [2] Pathology: 1) a break in the gastric or duodenal mucosa >= 5 mm [2] 2) imbalance between protective & injurious factors a) protective factors: mucous, bicarbonate (alkaline tide), mucosal blood flow, prostaglandins, hydrophobic mucosal layer, restitution, epithelial renewal b) injurious factors: H. pylori, acid, pepsin, bile acids, smoking, ethanol, NSAIDs, steroids, stress Genetics: - familial tendency - increased frequency in persons with blood group O Clinical manifestations: 1) patients commonly asymptomatic at diagnosis a) up to 20% of patients b) peptic ulcer often detected during evaluation for positive fecal occult blood c) elderly patients are more likely to be asymptomatic & have an increased risk of GI bleeding, especially if taking NSAIDs 2) epigastric pain & tenderness a) gnawing or burning pain b) onset of pain 1-3 hours after meals c) pain relieved by antacids d) pain may occur at night e) pain may radiate to back f) pain is generally intermittent g) duodenal ulcer more likely than gastric ulcer to cause pain that awakens patient at night 3) nausea/vomiting: - vomiting may be related to gastric outlet obstruction 4) dyspepsia: belching, bloating, distension, fatty food intolerance 5) heartburn 6) anorexia/weight loss 7) hematemesis 8) melena Diagnostic criteria: - endoscopic diagnosis - a break in the gastric or duodenal mucosa >= 5 mm [2] Laboratory: 1) fecal occult blood: - guaiac-positive stool may initiate diagnostic workup 2) complete blood count (CBC) 3) INR if anticoagulation 4) serum chemistries a) serum creatinine b) serum calcium, serum albumin c) serum gastrin in recurrent, refractory PUD or in patients with a family history of Zollinger-Ellison (ZE) syndrome 5) diagnostic tests for Helicobacter pylori (test all patients) a) serology for H pylori IgG antibodies b) urease breath test c) H pylori stool antigen assay d) gastric biopsy during upper GI endoscopy e) predictive value of H pylori testing without EGD is low [2] 6) secretin-stimulation test a) used in conjunction with serum gastrin b) distinguish ZE from other hypergastrinemic states - achlorhydria - pharmacologic agents - proton-pump inhibitors - H2 receptor antagonists 7) measurement of gastric acid secretion a) used in conjunction with serum gastrin & secretin-stimulation test b) distinguish ZE from other hypergastrinemic states c) not useful by itself in evaluation of PUD Special laboratory: - esophagogastroduodenoscopy (EGD) is gold standard [2] - indications - patients > 55 years or other alarm features of dyspepsia [2] - upper GI bleed (INR < 2.5) - repeat upper GI endoscopy for treated peptic ulcers not routinely indicated [2] - repeat upper endoscopy reserved for - persistent symptoms after 8-12 weeks of therapy - ulcers of unknown cause - if no gastric biopsy obtained during initial upper GI endoscopy [2] - a break in the gastric or duodenal mucosa >= 5 mm [2] - patients < 55 years of age with dyspepsia may be treated empirically without EGD [2] - procedure - identify gastric ulcers, duodenal ulcers - biopsy all gastric ulcers to rule out malignancy - test for Helicobacter pylori - endoscopic therapy indicated for active bleeding (grade 1) or visible blood vessel within ulcer (grade 2A) [2] - for high-risk peptic ulcers (grade 1A-2B), observe patient in hospital for 72 hours [2] - for low risk peptic ulcers, treat with PPI, refeed within 24 hours, early hospital discharge [2] - no benefit of observing for 24 hours in hospital [2] - duodenal ulcers are low risk for malignancy - biopsy unnecessary unless refractory to therapy Radiology: - upper GI series Differential diagnosis: 1) gastroesophageal reflux disease (GERD) 2) dyspepsia without ulcer (gastroduodenitis) - pharmacologic agents a) theophylline b) digitalis c) caffeine 3) biliary tract disease 4) pancreatitis 5) musculoskeletal 6) carcinoma a) gastric b) duodenal (rare) c) pancreatic 7) Crohn's disease 8) infectious agents a) giardiasis b) tuberculosis c) Mycobacterium avium-intracellulare 9) sarcoidosis 10) Menetrier's disease 11) lymphoma Complications: - gastrointestinal bleeding (15%) - hematemesis, melena, hematochezia [2] - risk of rebleeding is highest in the 1st 72 hours after endoscopic therapy [2] - risk of rebleeding is higher in idiopathic peptic (30%) than peptic ulcers due to H pylori (7%) or NSAIDs (3%) [15] - oral esomeprazole noninferior to IV esomeprazole after endoscopic treatment of bleeding peptic ulcer [12] - perforated peptic ulcer, gastric perforation, intestinal perforation - sudden severe abdominal pain, peritoneal signs, shock - obstruction: gastric outlet obstruction, intestinal obstruction - nausea/vomiting, early satiety, succussion splash - penetration - gradual increase in abdominal pain frequency & severity - may present as acute pancreatitis Management: 1) test for & treat Helicobacter pylori if positive; then, empiric treatment with proton pump inhibitor (PPI) for patients < 55 years & no alarm features of dyspepsia 2) stop & avoid NSAIDs - aspirin may be continued in combination with proton pump inhibitor in patients with cardiovascular disease (see antiplatelet therapy below) [8] - restart aspirin 1-7 days after initiation of proton pump inhibitor [25] - restart day 1 ok, restart in 10 days is too late [25] - if no alternative to NSAID, use COX-2 inhibitor plus a PPI QD [2] 3) smoking cessation 4) endoscopy as indicated (see Diagnostic-procedures) - patients with low-risk peptic ulcer may be fed within 24 hours, receive daily proton pump inhibitor & discharged from hospital [2] 5) proton pump inhibitors (PPI) a) once daily oral PPI - hemodynamically stable patient with hematemesis & a clean-based gastric ulcer with no active bleeding (low risk) - oral PPI noninferior to IV PPI after endoscopic treatment of bleeding peptic ulcer [12,19] b) duration of therapy - high risk - high-dose PPI IV infusion or IV push BID for 3 days after successful endoscopic therapy (strong recommendation) [23] & BID for 2 weeks (weak recommendation) [23] - low risk: oral QD for 4-8 weeks [2] - idiopathic bleeding ulcers require indefinite duration of PPI therapy due to risk of rebleeding [2] c) 80-100% healing of ulcer after completion of therapy d) omeprazole (Prilosec) 20-40 mg QD e) lansoprazole (Prevacid) 15-30 mg QD f) addition of H2-receptor antagonist may be synergistic (see proton pump inhibitor) 6) H2-receptor antagonist [2] a) duration of therapy 6-8 weeks b) 90-95% healing of ulcer after completion of therapy c) cimetidine (Tagamet) 400 mg BID or 800 mg QHS d) famotidine (Pepcid) 20 mg BID or 40 mg QHS e) nizatidine (Axid) 150 mg BID or 300 mg QHS f) ranitidine (Zantac) 150 mg BID or 300 mg QHS 7) prostaglandins a) inhibit acid secretion by inhibiting activation of adenylate cyclase in gastric parietal cells by histamines b) used primarily as prophylactic agents, not recommended for routine treatment of PUD c) Misoprostol (Cytotec) 200 ug QID 8) antimuscarinic agents: a) pirenzipine b) telenzipine c) not approved for used in the US 9) antacids 10) cytoprotective agents a) sucralfate (Carafate) 1 g QID or 2 g BID for 6-8 weeks b) bismuth subsalicylate 11) nitrates (Isordil, nitroglycerin) may protect against bleeding ulcers [3] 12) avoid excess alcohol 13) stress-reduction 14) surgery for peptic ulcer complications 15) blood transfusion only if blood hemoglobin < 7 g/dL (conditional recommendation) [23] 16) follow-up: a) endoscopy to document healing of gastric ulcer & to rule-out gastric cancer b) repeat endoscopy not needed in the absence of complications [2] - low risk peptic ulcers due to NSAIDs in younger patients < 55 years [2] - duodenal ulcers (low risk of malignancy) c) 1 year recurrence rate < 10% if Helicobacter pylori is eradicated d) follow-up H pylori testing (proof of eradication) - urease breath test [2] or - H pylori stool antigen testing [24] - H pylori serology maintains elevated titers > 1 year after successful eradication 17) antiplatelet therapy - combination aspirin 80 mg + proton pump inhibitor in patients with healed peptic ulcers is safer than clopidogrel (Plavix) [5] - aspirin-related ulcers will heal with proton pump inhibitor regardless of whether aspirin is continued or switched to clopidogrel [7,8] - restarting low-dose aspirin 3-5 days after upper GI bleed reduces 30-day mortality 10-fold in patients with cardiovascular disease, while increasing rebleeding rates only 2-fold [2] - restart aspirin 1-7 days after resolution of bleeding & initiation of proton pump inhibitor if peptic ulcer related to aspirin use for secondary prophylaxis for cardiovascular disease [2] 18) restart anticoagulation after resolution of bleeding [2] - restart anticoagulation in 7 days [2]

Interactions

disease interactions

Related

antiulcer agent dyspepsia (indigestion) Helicobacter pylori NSAID gastropathy

Specific

duodenal ulcer gastric ulcer perforated peptic ulcer

General

gastrointestinal ulcer chronic gastrointestinal disease

References

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