Peptic Ulcer Disease & Gastritis Michel-Jose Charles, MD

Transcription

1 Peptic Ulcer Disease & Gastritis Michel-Jose Charles, MD Internal Medicine Gastroenterology Board Certified Assistant Professor 2016

2 Peptic Ulcer Disease and Gastritis Michel-Jose Charles, MD Gastroenterology Assistant Professor SUNY Brookdale University Hospital & Medical Center NYU Langone Medical Center NOAH 2016

3 Overview Peptic ulcer disease (PUD) Definition Pathophysiology H. pylori-induced PUD NSAID-induced PUD Gastritis Definition Types of gastritis

4 Defining Peptic Ulcer Disease Peptic ulcer (PUD) Persistent 5-mm or larger break in the GI mucosa of the stomach or duodenum that penetrates through the muscularis mucosa to the submucosa Erosion Smaller and more shallow mucosal breaks PUD refers to ulceration that depends in part on acid and peptic activity of gastric juice

5 Key Point Most PUD involves the stomach or duodenal bulb Post-bulbar ulcerations think of other etiologies Zollinger-Ellison syndrome (ZES) Crohn disease Ischemia Malignancy

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7 Gastroduodenal Mucosal Integrity Protective (defensive) and Damaging (aggressive) Factors

8 Pathophysiology of PUD

9 Gastroduodenal mucosal barrier Mucus, bicarbonate, and phospholipid are secreted by surface mucous and mucous neck cells Creating a physical barrier and ph gradient to help protect the mucosa These processes are prostaglandin dependent, and can be inhibited by administration of aspirin (ASA) or other prostaglandin synthesis inhibitors

10 Damaging Processes Acid (ZES, systemic mastocytosis) Infection (HP, CMV, syphilis) Drugs (NSAIDs, ASA, antiplatelet drugs, sirolimus, bisphosphonates) Ischemia/stress gastritis/ulceration Chemotherapy/Radiation Gastric outlet obstruction Infiltrative disorders (malignancy, Crohn disease, sarcoidosis) Vasculitis Cigarette smoking Cirrhosis/COPD

11 Helicobacter pylori

12 Helicobacter pylori Commonest chronic bacterial infection worldwide Over half of all persons in world are infected with Hp, with only 5-20% developing ulcers Over 70% of children in developing countries are infected before age 10, and over 90% by age 50 US born pre-1945, 60% infected by age 60 US born pre-1980, 30% infected by age 30 Prevalence is falling due to increase hygiene awareness and use of antibiotics

13 Transmission Person-to-person Oral-oral (organism load 100X in vomit c/w saliva or stool Also detected in aerosolized vomit 1.2 m away!) Fecal-oral Risk factors for H. pylori Lower SES (socioeconomic status) Household overcrowing/sharing beds Vomiting Contaminated water

14 Living in the Stomach Gram-negative, spiral-shaped, microaerophilic, multiple flagella, survives only on gastric mucosa with a narrow ph optimum ph for growth: 6 to 8.5 How does it live in the stomach? Fights acid with urease (forms ammonia to buffer acid) Converts urea into bicarbonate and ammonia (a strong bases) ph: 4 to 6 Creates cloud of acid-neutralizing chemicals Induction of local immune response Chemotactic for neutrophils and monocytes Host T-cell response Remember: Hp doesn t often survive after gastroenterostomy environment becomes too alkaline

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16 Timing of Infection Early in Life Multifocal and pan-gastric gastritis Parietal cell damage Deceased production of acid Increase risk of gastric ulcer Later in life Higher levels of gastrin Antral-predominance active chronic gastritis Decreases number antral D-cells and somatostatin» Increased gastric acid secretion Increase risk duodenal ulcer in areas of gastric metaplasia in the duodenum

17 Pathogenesis Most people infected with Hp are asymptomatic PATHOLOGY (OF PUD) DEPENDS ON 3 FACTORS: (1) Bacteria factors GAG-cytotoxic associated gene products pathogenicity island cat PAI that produce proteins with varying secretory apparatus to allow translocation into host cell (caga) Cag PAI can lead to different Interleukin expression and lead to varying damage with mucosal cell All Hp possess vaca (vacuolating cytotoxin) genes and and >50% express vacuolating cytotoxin that cause epithelial cell injury

18 Pathogenesis (Cont d) PATHOLOGY (OF PUD) DEPENDS ON 3 FACTORS (Cont d): (2) Host factors Polymorphisms in the regions controlling IL-1β control degree of achlorhydria and development of Ca (3) Environment factors Use of NSAIDs making mucus layer even thinner predisposes to increased PUD

19 Diagnosing H. pylori NON-INVASIVE Serum serology Inexpensive Initial diagnosis only Saliva serology Not reliable Stool antigen Relatively inexpensive sensitivity/specificity Response to therapy Urease breath test Expensive sensitivity/specificity Response to therapy INVASIVE Culture Not widely available Useful in guiding therapy in difficult situations Rapid urease test Inexpensive sensitivity/specificity Bacterial overgrowth and Proteus may lead to false (+) result GI bleeding may lead to false ( ) result Histology Expensive sensitivity/specificity

20 Who to Test for H. pylori? People with Active gastric or duodenal ulcer History of gastric or duodenal ulcer Gastric cancer Gastric lymphoma (MALT) First-degree relatives of patients with gastric adenocarcinoma Symptoms of non-ulcer dyspepsia (if pre >20%) Anticipated prolonged use of NSAIDs/ASA

21 Testing Advice Idiopathic PUD Recommend second test to exclude Hp Testing for eradication Stool antigen, breath test, urease test, histology Off antibiotics and bismuth 4 to 6 weeks Off PPI 1 to 2 weeks

22 Issues Regarding Treatment of Hp No eradication therapy guarantees 100% cure Reduced efficacy over time as resistance develops Majority of recent clinical trials are performed in South Europe or Far East Clarithromycin resistance is a major issue 13% resistance between No organized national surveillance has occurred since then Clarithromycin resistance rates vary from regions 17.5% in Europe 58% India 0% Bhutan Sequential therapy has been introduced to address the diminished effects of clarithromycin PPI and Amox X5 days PPI/Clari/Tinid X5 days Good results from Italy but less so in Turkey No RCT done in USA

23 H. pylori Treatment Now Concomitant therapy has been set up (sequential is too complex) PPI/amox/clari/imidazole for 10 days Good results favoring the above sequential tx even in clarithro-resistance areas but no RCT in USA Hybrid therapy combines sequential and concomitant: 14 days sequential but amox is continued for entire period (hybrid part) USA RCT first line regimen LOAD : PPI/levo/nitazoxanide/doxy for 10 to 14 days Errad rates of 88 to 90% Levoflox regimens have mixed results and are reserved to salvage patients with persistent infection

24 H. pylori Treatment (Cont d) First line If Clarithromycin resistance <15% Amoxillin 1000-mg PO bid (or metronid 400-mg bid) Clarithromycin 500-mg PO bid Standard dose PPI PO bid Has anti Hp activity Penicillin allergy metronidazole 500-mg PO bid Penicillin allergy and previous macrolide Bismuth subsalicylate 525- mg PO qid Poorly absorbed and has local action on the stomach Metronidazole 250 mg PO qid Ranitidine 150-mg PO bid or PPI PO bid Length of treatment: 10 to 14 days

25 H. pylori Treatment (Cont d) Second line Quadruple therapy (bismuth, tetracycline, metronidazole, PPI) Third line (not completely validated) Triple therapy (PPI, amoxicillin and levofloxacin or furazolidone) Sequential therapy PPI and amoxicillin bid for 5 days, then PPI, clarithromycin, and metronidazole or tinidazole bid for 5 days Resistance: rare with amoxicillin, tetracycline or bismuth In the US, recurrent infection with Hp is <1 to 3% per year

26 Eradication Therapies In response to decreasing efficacy, new combinations (e.g. sequential therapies) work in some countries not in others: Sequential therapy is effective in Italy and poor in Korea due to low clarithromycin resistance in Italy A regimen is effective ONLY if eradication is >90% in treated population In US, resistance to combination clarithromycin and MTZ is uncommon (2014), making concomitant therapy first choice and if this fails, bismuth quadruple therapy is given If this fails, culture

27 Treatment of H. pylori in the USA A Final Thought Clarithromycin-based triple therapy and bismuth-based quadruple therapy are commonly prescribed for 10 to 14 days ASA first-line in the US Alternatives: 10 to 14 days conconmittant: PPI/Clar/Amox/Imidazole 10 to 14 days sequential: PPI/Amox X5 days PPI/Clar/Trinid X5 days 10 to 14 days hybrid: 14-day seq + amox 10 to 14 days quadruple: Levoflo/omepr/nitazoxani de/doxyc

28 Benefits of H. pylori Caveat: A lot of data on associations that may be unrelated H. pylori can promote or reduce acid reflux depending on site astral infection increase acid secretion, while corpus infection decrease acid Esophageal adeno ca is increasing by despite the decrease in gastric ca in US, the risk of developing gastric ca is 2 to 3X that of esophageal adeno ca

29 Miscellaneous H. pylori Issues Clarithromycin resistance is increasing 80 to 90% in Japan Ask pts about prior Clarith use Probiotics (S. boullardii and Lactobacillus sp.) reduced diarrhea but not improve efficacy In RCT eradication of H. pylori improves hemoglobin and ferritin levels Can improve platelet counts in those with chronic ITP H. pylori infection is inversely correlated with Barrett esophagus

30 NSAIDs

31 Truth about NSAIDs Can We Handle it? Jack Nicholson Nearly 20 million users each day in US 70% people age 65+ use NSADs at least once per week Up to 200,000 serious complications each year 40 to 50% bleeding PU inked to ASA or NSAIDs Approximately 16,00death each year Between 5 and 30% of persons chronically ingesting full-dose NSAIDs will have an ulcer

32 How Do NSAIDs Products Lead to PUD

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34 Topical Route of Injury In non-ionized form, NSAIDs freely penetrate gastric cells Inside cell, ph neutral so H+ dissociated leaving NSAID negatively charged and unable to leave cell NSAID concentration within mucosal cells leads to superficial injury

35 Systemic Route of Injury Healthy gastric and duodenal mucosa use COX-1 to produce mucosal protective prostaglandin (PG) NSAIDs inhibit synthesis of PG epithelial secretion of mucus and HCO3 blood flow mucosal proliferation Impaired resistance to peptic injury

36 Non-Selective vs. Selective NSAIDs Non-selective NSAIDs Block COX-1 and COX-2 Impaired gastric PG production at low concentrations Aspirin, indomethacin, Ibuprofen, naproxen Selective NSAIDs Spare COX-1 and selectively inhibit COX-2 Less suppressive effects on gastric PG synthesis Celecoxib, etodolac At HIGH DOSES selective inhibitors of COX-2 lose their specificity for COX-2 and can lead to GI damage

37 NSAIDs Risk Factors/Complications Age (over 60 to 70) Previous hx of PUD (esp. if complicated) First 30 to 90 days of therapy High-dose NSAIDs Use of multiple NSAIDs Concomitant corticosteroids, aspirin, antiplatelet drugs, anticoagulants, alendronate Hp infection Comorbid conditions (esp cardiovascular disease)

38 Risk of NSAID-Induced GI Toxicity A Recap High Risk Moderate Risk (1 to 2 risk factors) Low Risk Hx of complicated ulcer, especially recent Multiple (>2 risk factors) Ages >65 years High dose NSAIDs Previous uncomplicated ulcer Concurrent aspirin, clopidogrel, steroids or anticoagulants No risk factors

39 Additive Effect Hp-induced persons who start NSAIDs are at greater risk of PUD/complications Recommend Hp eradication prior to NSAID use decreases risk Studies suggest that risk of bleeding peptic ulcer is 8X greater if Hp and NSAIDs are present together Low dose ASA has no additive effect on bleeding PU if co-infected with Hp

40 Gastritis

41 Gastritis vs. Gastropathy Gastritis Inflammation with or without endoscopic features Gastropathy Epithelial damage with little or no inflammation

42 Gastritis Inflammation of the gastric mucosa Classified and diagnosed histologically as endoscopic appearance (redness) is misleading Seldom symptomatic Can have sequelae in some patients 3 important causes: (1) H. pylori-antral or corpus predominant (2) Aspirin/NSAIDchemical gastritis (3) Autoimmuneconfined to the body/corpus

43 Acute Gastritis Neutrophilic infiltrate With or without intramucosal hemorrhage and/or superficial mucosal sloughing infection H. pylori, CMV Drugs or toxins NSAIDs, excessive alcohol, chemotherapy Ischemia Trauma, shock, sepsis, burns

44 Chronic Gastritis Non-atrophic Chronic Hp infection Antral predominance Mixed infiltrate Neutrophils Lymphocytes Plasma cells Eosinophils Atrophy, metaplasia, dysplasia NOT seen Atrophic Multifocal Autoimmune auto Ab to parietal cells and IF

45 Multifocal Atrophic Gastritis Chronic Hp infection (85%) Loss of glands and metaplastic change in body and antrum Increased risk for GU and gastric adenocarcinoma

46 Autoimmune Atrophic Gastritis Less than 5% Hypo- or achlorhydria, iron deficiency, hypergastrinemia, pernicious anemia Associated with Hashimoto, Grave, Addison, diabetes, vitiligo Loss of gastric folds and prominent submucosal vasculature in body and fondus Autoantibodies to parietal cells, intrinsic factor, and H+, K+ ATPase Microcarcinoid tumors or gastric adenocarcinoma may be seen

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48 Biopsies for Atrophic Gastritis 2 antrum + 2 incisura in one bottle 2 body + 2 fundus in separate bottle

49 Gastropathy and Gastritis Special Forms Chemical Vascular Hypertrophic Infectious Autoimmune Non-infectious Granulomatous Eosinophilic Lymphocytic

50 Chemical & Vascular Gastropathy Chemical Gastropathy NSAIDs, alcohol, bite salts Bile reflux gastropathy may respond to UDCA or surgical Roux-en-Y revision Vascular Gastropathy Congestive Congestive heart failure, portal hypertension, gastric vascular ectasia Iron deficiency anemia, melena

51 Hypertrophic Gastropathies H. pylori Lymphocytic gastritis ZES Malignancy Sarcoidosis Ménétrier disease

52 Infectious Gastritis Most common is H. pylori Less common bacteria, including syphilis and mycoplasma CMV is the most common viral (immunosuppressed) Fever, abdominal pain, nausea, vomiting, bleeding

53 Noninfectious Granulomatous Gastritis Crohn disease Antrum Sarcoidosis Collagen vascular disease Vasculitis (Wegener disease) Drug reaction Foreign bodies Gastric malignancies

54 Eosinophilic Gastritis Eosinophilic gastroenteritis Peripheral eosinophilia and increased serum IgE Mucosa, serosa-, or muscularis-predominant Collagen vascular disease Drug, food, allergy Vasculitis Hypereosinophilic syndrome Anisakis infection

55 Lymphocytic Gastritis Asymptomatic or dyspepsia, iron deficiency anemia, diarrhea Celiac disease (antral) 38% Hp infection (body) 29% Microscopic colitis Ménétrier syndrome

56 Lymphocytic Infiltration Treat Hp if present Gluten-free diet A Few More Words If no response, consider looking for colonic involvement with colon biopsies If refractory to gluten-free diet, consider steroid therapy (budesonide)

57 Conclusion Importance of protective influences in the stomach H. pylori importance of resistance exp. Clarithromycin and Metronidazole NSAIDs Don t forget about autoimmune gastritis as a cause of an elevated gastrin good catch question and commoner than Zollinger-Ellison

58 Thank You! Any Questions or Comments