Peptic Ulcer Disease Update

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Peptic Ulcer Disease Update Col Pat Storms RAM 2005

Disclosure Information 84th Annual AsMA Scientific Meeting Col Patrick Storms I have no financial relationships to disclose. I will discuss the following off-label use in my presentation: Use of Tinidazole, Levofloxacin, Moxifloxacin as treatment options in patients with H pylori infection.

Agenda History lesson Causation Clinical presentation Diagnosis Treatment Aeromedical Implications

History Schwartz dictum, 1910, No acid, no ulcer Treatment protocol, circa 1975 (pre-cimetidine) 30cc antacid po 1 and 3 hrs pc and hs Alternate Mg and Al based antacids to prevent raging diarrhea 50% recurrence rate post healing Vagotomy/antrectomy for refractory PUD And then everything changed!

Enter H pylori Scientific American, Feb 1996

H pylori prevalence 50% of world population thought to be infected Most infected are asymptomatic, despite developing chronic histologic gastritis Table from Wang AY, Peura DA. Gastrointest Endoscopy Clin N Am. 2011

Causation Original estimates: 90% DU, 60% GU due to H pylori Table from Feldman: Sleisenger and Fordtran, 9 th ed, 2010

NSAIDs NSAIDs inhibit systemic prostaglandins Decrease epithelial mucus Decrease mucosal blood flow Decrease bicarbonate secretion Decrease mucosal resistance to injury US Survey: 70% of those older than 65 use NSAIDs at least once a week (34% use NSAIDs daily) Demonstrable damage occurs in 30-50% of NSAID users Most are asymptomatic and heal with cessation of NSAIDs Risk of PUD 5 fold higher in NSAID users

NSAID impact Figure from: Lee I, Cryer B. Gastrointest Endoscopy Clin N Am. 2011

Clinical Presentation Episodic gnawing, dull, burning epigastric pain Often occurs when the stomach is empty Pain awakening the pt from sleep reported in 2/3 of DU patients, 1/3 of GU patients (also seen in 1/3 of patients with non-ulcer dyspepsia) Often relieved by food or antacids Symptoms are neither sensitive nor specific! Vomiting and weight loss increase concerns for outlet obstruction/cancer Acute GI bleeding Up to a third of PUD pts may present with GI bleeding as the initial symptom Of those presenting with bleeding, a third have no history of epigastric pain Acute perforation More common in elderly as an initial presentation of PUD

Alarm Features Age > 55 Family history of upper GI cancer GI bleeding, acute or chronic, including unexplained Fe deficiency Jaundice L supraclavicular lymphadenopathy (Virchow s node) Persistent vomiting Progressive dysphagia Unintended weight loss Feldman: Sleisenger and Fordtran, 9 th ed, 2010

EGD Results GUDU ondu gastric angularis (H Pylori pos) with clot Ulcerated GU due Gastric to NSAIDs Cancer GU spectrum of badness

Rebleed Risk Jairath, Gastro Endo Clin N Am (2011)

Treatment Bleeding patient Stabilize with fluids/blood products prior to EGD Endoscopic interventions as needed Sacks, 1990, performed meta-analysis of 25 RCTs comparing endoscopic therapy to standard therapy. Risk of rebleed down by 69%, surgery down by 62%, mortality down by 30% Acid blockade Proton Pump Inhibitors first line for most patients Withhold NSAIDS Treat H pylori when indicated

Who to test for H pylori Clear indications Documented PUD, past history of PUD, gastric MALT (mucosaassociated lymphoid tissue) lymphoma When used as part of a test and treat strategy in those with uninvestigated dyspepsia, younger than 55, with no alarm features Controversial areas Functional dyspepsia (dyspepsia with neg EGD) GERD NSAID users Those with PUD, even in the face of NSAID use, should be tested for H pylori Fe deficiency anemia Prevention of gastric cancer Testing should only occur if the clinician plans to treat a positive result Am Coll Gastroenterol CPG on Mgmt of H pylori infection, 2007

How to Test for H pylori Endoscopic testing Histology is best choice, but is expensive and requires the appropriate infrastructure Urease testing ( CLO Test ) quite good, but sensitivity is reduced post-treatment Non-endoscopic Antibody testing has good neg predictive value (NPV), but PPV depends on background H pylori prevalence Urea breath tests work well, but are variably available Fecal antigen tests have good PPV and NPV, but are linked to the unpleasantness of collecting a stool sample Presenter cites CLO test as one example of a rapid urease test and does not endorse any specific manufacturer

How to Treat H pylori Drug resistance impacts treatment choices Macrolide (Clarithromycin) resistance noted in 10-13%, Metronidazole resistance in 25-37% Complex treatment regimens negatively impact compliance No perfect treatment regimen has been found Cure rates of 70-85% common with most first-line regimens Attempts to simplify or short regimens often associated with reduced effectiveness Minor treatment side effects are common and impact compliance

Lots of Treatment Choices Sequential therapy PPI plus Amoxicillin 1gm bid X 5 days THEN, PPI plus Clarithromycin 500mg + Tinidazole* 500mg bid for another 5 days Alternatives Bismuth subsalicylate 2 tabs (525mg total) + Tetracycline 500mg qid + Metronidazole 250mg qid + a PPI for 14 days PPI + Amoxicillin 1gm bid + Clarithromycin 500mg bid for 10 days Retreatment/Salvage PPI + Levofloxacin* 500mg qd OR Moxifloxacin* 400mg qd + Amoxicillin 1gm bid X 7-10 days * Not FDA approved for treatment of H pylori The Sanford Guide Mobile App v3.02, 2013

Follow Up No need for maintenance PPIs after successful treatment of H pylori Re-scope GUs in 8 weeks to ensure healing Reassess the need for NSAIDs, consider use of concomitant PPI and/or COX-2 selective NSAID if ongoing NSAID treatment needed

Aeromedical Implications Air Force AFI 48-123, 6.44.19.1.2: Peptic Ulcer Disease, active or refractory 6.44.19.1.1: Gastrointestinal hemorrhage, regardless of cause Army AR 40-501 3-4(l) (retention): Ulcer, duodenal, or gastric with repeated hospitalization, or sick in quarters because of frequent recurrence of symptoms (pain, vomiting, or bleeding) in spite of good medical management and supported by endoscopic evidence of activity. Aviation: para 4-4d: History of gastrointestinal bleeding. This excludes minor bleeding from hemorrhoids or acute rectal fissure.

FAA Initial Airman Certification/ATCS Clearance: Without bleeding, a medical certificate may be issued for any class if airman has documentation of healing (e.g., upper GI series or endoscopy, etc.). With bleeding within the preceding 6 months, a medical certificate should not be issued for any class until documentation of healing is provided (e.g., upper GI series or endoscopy, etc.). Use of prophylactic medications, such as Carafate and H-2 or ion-pump antagonists (Tagamet, Zantac, Prilosec, etc.), are acceptable if there have been no significant side effects after an adequate trial period (at least two weeks). Continued Airman Certification/ATCS Clearance: At least one follow-up in one year is recommended with current status report from treating physician.

Summary Main causes: H pylori, followed by NSAIDs Typical symptom complex not sensitive or specific Empiric therapy for low risk patients is acceptable H pylori testing indicated in every PUD patient, treat when positive using a regimen that reflects your local antibiogram Stop the PPI after an adequate course of therapy in patients treated for H pylori Be aware of the aeromedical consequences, particularly in a patient presenting with an UGI bleed

The First Command Questions?

Question 1 Which of the following is not a common cause of peptic ulcer disease? Helicobacter pylori Emotional stress Zollinger-Ellison Syndrome NSAIDs

Question 1 Which of the following is not a common cause of peptic ulcer disease? Helicobacter pylori Emotional stress Zollinger-Ellison Syndrome NSAIDs

Question 2 Which of the following is not a method used to detect the presence of Helicobacter pylori? Scanning electron microscopy of biopsies from the distal duodenum Histologic examination of gastric biopsy specimens Rapid urease test applied to gastric biopsy specimens Urea breath test

Question 2 Which of the following is not a method used to detect the presence of Helicobacter pylori? Scanning electron microscopy of biopsies from the distal duodenum Histologic examination of gastric biopsy specimens Rapid urease test applied to gastric biopsy specimens Urea breath test

Question 3 Which of the following factors impact the positive predictive value of testing for the presence of Helicobacter pylori in a given dyspeptic patient: Diabetic patient Prevalence of Helicobacter pylori in the local population Patient s blood type History of recent NSAID use

Question 3 Which of the following factors impact the positive predictive value of testing for the presence of Helicobacter pylori in a given dyspeptic patient: Diabetic patient Prevalence of Helicobacter pylori in the local population Patient s blood type History of recent NSAID use