PEPTIC ULCER AND NON ULCER DYSPEPSIA

DR BANU NISA ABDUL HAMIDMASTER IN FAMILY MEDICINE

1ST YEAR POSTGRADUATE , UKM

Objective

• most likely causes of dyspepsia• risk factors of recurrent peptic ulcer disease• role of Helicobacter pylori in the pathogenesis of

peptic ulcer • disease and its relationship to ulcer relapses• manage patients presented with dyspepsia• role of available drugs for the treatment of dyspepsia• recognise the indications for long-term maintenance

therapy• manage patients with PUD and concomitant high CVD

risk needing antiplatelet therapy

DYSPEPSIA• Defination:- having one or more symptoms of epigastric

pain, burning, post-prandial fullness, or early satiation.

5 MAJOR CAUSE

a)Gastro-esophageal reflux (GERD)b)Medicationsc)Functional dyspepsia (FD) – non ulcer

dyspepsiad)Peptic ulcer disease (PUD)e)Malignancy

Some medications that commonly cause dyspepsia

• NSAIDS• Cox-2 inhibitors• Bisphosphonates• Erythromycin• Tetracyclines• Iron• Potassium supplements

• Acarbose• Digitalis• Theophylline• Orlistat• Aspirin

FUNCTIONAL DYSPEPSIA

FUNCTIONAL DYSPEPSIA

• Rome III working group defined FD presence of symptoms thought to originate in

gastro-duodenal region, in the absence of any organic, systemic ,or metabolic disease that is likely to explain them.[Tack et al. 2006].

FUNCTIONAL DYSPEPSIA

Rome III diagnostic criteria for functional dyspepsia

At least 3 months of one or more of thefollowing:• bothersome postprandial fullness• early satiation• epigastric pain• epigastric burningAND• no evidence of structural disease (including upper

endoscopy) that is likely to explain the symptoms.

Pathophysiological mechanism

• Delayed gastric emptying• Impaired gastric accommodation to a meal• hypersensitivity to gastric distention• H. pylori infection• altered duodenal response to lipids or acid• abnormal duodenojejunal motility• central nervous system dysfunction[Tack et al. 2004].

Pathophysiologic mechanisms in functional dyspepsia. H+, acid exposure.

CNS modulation stress,illness

Visceral hypersensitivity (fat, ,wall distension)

Acid hypersensitivity

Decrease fundic accommodation

Duodenal hypersensitivity

Abnormal distribution ofIgastric contents

Gastric dysarrhytmias

Overdistended antrum

Small bowel dysmotility

Vagal neuropathy

Delayed gastric emaptying/Antral hypomotility

Inflammation gastric contents[bacteria (H. pylori), viruses, etc.]

Diagnostic criteria: PDS 1. Bothersome postprandial fullness, occurring after ordinary sized meals, at least several times per week AND/OR 2. Early satiation that prevents finishing a regular mealSupportive criteria 1. Upper abdominal bloating, postprandial nausea or

excessive belching can be present 2. Epigastric Pain Syndrome may coexist

Diagnostic criteria: EPS1. Pain or burning localized to the epigastrium of at

least moderate severity at least once per week AND

2. The pain is intermittent AND3. Not generalized or localized to other abdominal

or chest regions AND4. Not relieved by defecation or passage of flatus

AND5. Not fulfilling criteria for gallbladder and sphincter

of Oddi

Diagnostic criteria: EPS

Supportive criteria1. Upper abdominal bloating, postprandial

nausea or excessive belching can be present2. The pain is commonly induced or relieved by

ingestion of a meal but may occur while fasting

3. Postprandial distress syndrome may coexist

Management of functional dyspepsia. FD

PPI H.pylori eradiacation

Promotility agents

Nonresponders

Alternative therapies Tricyclics

SSRI

Promotilityagents

PEPTIC ULCER DISEASE

PEPTIC ULCER

• Defination: mucosal lesions that penetrate the muscularis

mucosae layer and form a cavity surrounded by acute and chronic inflammation.

Two types:

In Malaysia• Few reports on the pattern of peptic ulcer in

Malaysia.• Male are more prone than female • In both sexes, GU –older age grp compare to DU• Of the 3 main Malaysian ethnic grp, Chinese of

both sexes had the highest frequency of peptic ulcer.

• Chinese female had the highest frequency of DU. (Source: Profile of PUD in Malaysia,M V Kudva)

Risk factor

• Major risk factor:Helicobacter pylori infectionNSAIDSASA

Etiology and risk factors for peptic ulcer disease

Nonsteroidal anti-inflammatory drugs 3.7

Helicobacter pylori 3.3

Chronic obstructive pulmonary disease Chronic renal insufficiency

2.34 2.29

Current tobacco use 1.99

3 or more doctor visits in a year 1.49

Coronary heart disease 1.46

Former alcohol use 1.29

obesity 1.18

Odds Ratio

Clinical Manifestation

• Night time awakening /episodic epigastric pain relieved following food intake (most specific clinical sign)

• Epigastric pain describe as episodic , dull, burning (dyspepsia) pain.

• 46% of patients had reflux symp (heartburn, acid regurgitation) ~ GERD

Clinical manifestation

Clinical manifestation

• Most common symp of PUD (> 80 yo) :

1) Epigastric pain (74%)2) Nausea (23%)3) Vomiting ( 20%)

• Less common features:- Indigestion- Belching- Vomiting- Associated with

gastric/pyloric stenosis- LOA- Intolerance to fatty foods- Positive FHX

Definitive diagnosis• direct visualization of the ulcer via

radiography (upper GI barium swallow, double contrast) or upper GI endoscopy (EGD).

• Referral to EGD should be considered in all patients:

50 years of age or older, with persistent symptoms, anorexia, weight loss, vomiting,

and in the presence of signs of GI bleeding.

Differential diagnosis of peptic ulcer diseaseCONDITION TEST(s) FINDINGS

Gastritis Upper gastrointestinal endoscopy

Gastric inflammation

Gastroesophagealreflux disease

Symptoms Dyspepsia worse with eatingand upon lying down

Gastroparesis History History of diabetes

Cholelithiasis ExaminationAbdominal ultrasound

Right upper quadranttendernessGallstones

Pancreatitis Amylase/lipase Elevated

Gastric cancer Upper gastrointestinal endoscopyAbdominal CT scan

Biopsy

Abdominal aorticaneurysm

Abdominal ultrasoundAbdominal CT scan

Size of aorta

Hepatitis Liver function tests Elevated

Myocardial ischemia Cardiac enzymesElectrocardiogram

Elevated CPKMBElevated troponinST segment changesDeep symmetric T waveinversion

Mesenteric ischemia SymptomsAbdominal CT

Pain after mealsMesenteric edema; boweldilatation; bowel wallthickening; intramuralgas; mesenteric stranding

Condition Test(s) Findings

Myocardial ischemia Cardiac enzymesElectrocardiogram

Elevated CPKMBElevated troponinST segment changesDeep symmetric T waveinversion

Mesenteric ischemia SymptomsAbdominal CT

Pain after mealsMesenteric edema; boweldilatation; bowel wallthickening; intramuralgas; mesenteric stranding

Common Complication

GI Bleeding• 80 % stop

spontaneously- only supportive Rx required

• Asymptomatic/hemate-mesis,coffee ground emesis,malena,

tachycardia,shock.

• Urgent OGDS –detect cause of bleeding, start on appropriate therapy.

• Shock present- aggressive resuscitation & blood transfusion needed.

• Surgery remains a definate indication and best Rx – OGDS/interventional radiology fails.

Perforation• Lifetime prevelance of

perforation in PUD pts ~5%.• Cause: NSAIDS, H.pylori• Bleeding, sudden onset of

sudden severe, sharp abdominal pain/ epigastric pain

• Abd : generalized tenderness, guarding,

rigidity, rebound tenderness

• S/S of septic shock tacycardia,hypotension,lethargy,anuria,cyanosis

• Simple surgical closures, intensive medical treatment, H pylori eradication, NSAID withdrawal have been reported to result in very low recurrence rates.

Gastric outlet obstruction• more commonly due to

malignancy than PUD. • nausea, vomiting, bloating,

indigestion, epigastric pain, and weight loss.

• endoscopy has the advantage of being diagnostic and can rule out possible malignancy.

• Malignant obstruction is reported in 66% of patients.

• Outcomes may be improved with effective ulcer therapy with acid reduction and eradication of H pylori.

• Surgery is associated with significant morbidity and mortality and should be reserved for endoscopic

treatment failures.• Surgical palliation for

malignant disease has poor results and high rates of morbidity and mortality.

HELICOBACTER PYLORI

HELICOBACTER PYLORI (HP)

• Gram negetive spiral bacteria• Transmitted: fecal-oral ,oral-oral, mother to

child routes, iatrogenic.• Highly prevalent in developing country &

lower socioeconomic .• HP +ve subjects have 10-20% lifetime risk of

developing PUD.

PIC of halicobacter

Common Treatment RegimnRegimen Comment

Trile therapy PPI; amoxicillin 1 g BID; clarithromycin500mg BID for 10 -14 days

First line treatment

Sequential therapyPPI and amoxicillin 1 g BID for 5 days followed by PPI,clarithromycin 500mg BID, tinidazole 500mg BID for 5 days

May be first line where macrolideresistance is common

Quadruple therapyPPI; bismuth 525mg QID; metronidazole 500mg QID;and tetracycline 500mg QID for 14 days

Treatment for failure

• Overall ,triple therapy for 14 days has been shown to be more effective at eradication of H pylori than dual therapy.

• A recent meta-analysis did not find a difference in H pylori eradication rate between quadruple (PPI +bismuth +metronidazole + tetracycline for 10–14 days) and triple therapy (PPI+clarithromycin +azithromicin for 7–14

days).

• H. pylori has been found more frequently in dyspeptic patients than in controls and has been shown to affect acid secretion and, to a lesser extent, gastric motility .

• “Test and treat strategy”(< 50YO, no alarming symp)

• In areas of low H. pylori prevalence (< 20%), the empirical use of PPIs alone is considered to be an equal option for symptom relief .

• NICE guidelines recommend initiation of a 4 week trial of full dose PPI therapy in patients with uninvestigated dyspepsia.

Test available for H.pylori:• Blood antibody test (enzyme-linked immunosorbent

assay [ELISA]). This test detects exposure to H pylori but cannot be used to confirm successful treatment.

• Urea breath test. This test is adequate for screening and for confirming cure following treatment. The use of PPIs within 2 weeks of testing can interfere with the results.

• Stool antigen test. This test is adequate for screening and for confirming cure following treatment.

• Stomach biopsy. Gold standard. It is adequate for screening and for confirming cure. Results depend on the number of biopsies and the experience of the pathologist.

RELATIONSHIP WITH ULCER RELAPSES

• Studies showed that the rate of Helicobacter pylori "reappearance" and of duodenal ulcer relapse up to 6 years after eradication of H. pylori.

(Archimandritis A, Balatsos V. 'Bacteriology and epidemiology of Helicobacter pylori infection. J Clin Gastroenterol. 1999;28(4):345.)

• Recent studies have suggested that the eradication of H. pylori affects the natural history of duodenal ulcer disease such that the rate of relapse decreases markedly.

(Asaka M, Ohtaki T, Kato M. Causal role of Helicobacter pylori in peptic ulcer relapse. Gastroenterol. 1994 Jul;29 Suppl 7:134-8.)

• Chronic PUD was almost exclusively due to H. pylori infection with up to 90% of duodenal ulcers and 70% of gastric ulcers attributed to this bacterium.

• However, NSAIDs and aspirin are now responsible for most ulcer disease in developed countries.

(d2- advances in public health, effective H.pylori eradication therapy).

EGD

(Esophagogastroduodenoscopy)

Alarm symptoms that require prompt EGD in dyspeptic patients.• Anemia• Evidence of acute/chronic bleeding• Previous history of peptic ulcer• Odynophagia• Dysphagia• Recurrent or persistent vomiting• Unintentional weight loss

• Prompt endoscopy is recommended in patients with alarm symptoms or patients over a threshold age (35-55 years).

• Men , younger age ↑prevalence at diagnosis of upper GI malignancy

• Once failed a 48 week trial of PPI therapy (in an area of low prevalence of H. pylori)/ failed to respond to eradication of H. pylori (in an H. pylori endemic region) upper endoscopy is indicated.

• Performing upper endoscopy during a symptomatic period especially while the patient is off acid-suppressant

therapy is important to making a diagnosis of functional dyspepsia by excluding other potential causes of symptoms.

• Upper GI barium radiography: inferior to upper endoscopy and is generally

not recommended as part of the work up for dyspepsia.

Management of dyspepsia

Full dose PPI trial

Age>50 oralarm symptoms

EGD

Age<50 and noalarm symptoms

Dyspepsia

Dyspepsiawithout GERD oroffending medication

High or intermediatePrevalenceof H. pylori (>20%)

Trial off medicationor change toan alternate medication

Use of NSAIDsor other probableoffending medication

Typical GERDsymptoms

Continued symptoms despiteadequate PPI trial

Full dose PPI trial

Treat as GERD

Empiric trial of PPI4–6 weeks

Test and treatfor H. pylori(Stool antigen or breathtest off PPI for >2 weeks)

Symptomresolution

NoNegetive

Yes

EGD

Empiric trial of PPI4–6 weeks

Test and treatfor H. pylori(Stool antigen or breathtest off PPI for >2 weeks)

Treatment basedon endoscopic findings

1. Biopsy for H. pylori (unless negativeH. pylori stool antigen or breath testOFF PPI for greater than 2 weeks)

1. Reassurance4. Evaluate and treat for IBS2. Consider alternate causes of abdominal pain3. Consider trial of low dose trycydicantidepressant or antispasmotic

No responseNo respond

Abnormal EGD

Normal EGD

Note: diagnostic algorithm may differ based on regional cancer risk, gender, and age of patient at presentation.

Refractory Functional Dyspepsia

• Patients who do not respond to empiric PPI therapy, have normal upper endoscopy, and who either are negative for H. pylori or have cleared infection following treatment yet continue to have dyspepsia represent a challenging group.

• First, the diagnosis should be re-evaluated, considering other disorders that may be mistaken for dyspepsia.

• In the absence of an alternate disease, reassurance and education of the patient

with functional dyspepsia becomes important.

• Although not validated in the functional dyspepsia population, a positive physician-patient interaction including reassurance can reduce health care seeking behavior.

• Patients are often also educated to eat smaller, more frequent meals to avoid gastric distention and to avoid food that aggravates symptoms.

TREATMENT

• Treatment of PUD consists of healing the ulcer and prevention of complications. All plans should include appropriate management of PUD risk factors.

• discontinue smoking; offered stress management programs and counseled to avoid NSAIDs, aspirin, and alcohol abuse.

• Management of patients with PUD requires detection and eradication of H pylori infection and the administration of antisecretory therapy, preferably PPIs, for a minimum of 4 weeks.

• If patients recover after the first course of treatment, they should be observed.

• If symptoms persist, antisecretory therapy with PPIs / histamine receptor (H2) blockers should be continued for an additional 4 to 8 weeks, and repeat EGD should be considered.

• re-evaluated for H pylori infection

NSAIDS• Economic modeling suggests that Cox-1 NSAIDs + H2

blockers or Cox-1 NSAIDs + PPIs are the most cost-effective strategies for avoiding

endoscopic ulcers in patients requiring long-term NSAID therapy.

• PPIs are more effective than H2-blockers at standard

dosages in reducing the risk of gastric and duodenal ulcer, and are superior to misoprostol in preventing duodenal but not gastric lesions.

ASPIRIN• Aspirin is commonly recommended to reduce the risk of

cardiovascular events.• Several factors have been identified to increase the risk of

patients to develop aspirin-associated GI bleeding. These include a history of previous GI ulcer, ulcer

complications, dyspepsia, H pylori infection, and simultaneous use of aspirin with NSAIDs or clopidogrel.

• The use of enteric-coated or buffered aspirin does not significantly decrease the risk of ulcer complications due to its systemic effect.

• PPI + aspirin significantly reduces the risk recurrent ulcer bleeding.

MEDICATION

CLASS Medication Typical dose Precautions

Histamine -2 Receptor blocker

Cimetidine (Tagamet)

Ranitidine (Zantac)

Famotidine (Pepcid)

400 mg BID

150mg BD

20 mg BD

High incidence of sideeffects and potential fordrug interactions due toinhibition of CYP450

Proton pump inhibitors

Omeprazole

Lansoprazole

Pantoprazole

20-40 mg daily

15-30 mg daily

40mg BD

Altered metabolism ofmedications throughCYP450

Prostaglandins

Misoprostol 200 mg QID Dose-dependent diarrheaand abdominal painAvoid in fertile women andduring pregnancy

Other medications

Sucralfate 1 g QID Contains aluminum, shouldbe avoided in patientswith renal failureCan prevent absorption ofother medications

INTERACTIONS H2 RECP ANTAGO• Cimetidine (Tagamet) will inhibit drug metabolizing

enzymes and increase plasma concentrations for:

• Benzodiazepines Coumadin• Theophylline Caffeine• Oral hypoglycemics Dilantin• Tricyclic antidepressants Flagyl• Propranolol• Tegretol

PROTON PUMP INHIBITORS• Omeprazole (Prilosec)• Lansoprazole (Prevacid)

• In a cost-simulation model, PPI therapy was calculated as the most cost effective strategy in dyspeptic patients at 30 years of age and in areas of low H. pylori prevalence.

• For 60-year-old patients, H. pylori test and treat was the most cost-effective strategy .

• Significantly better response rate for omeprazole (31%) than for ranitidine (21%), cisapride (13%) and placebo (14%).

MISOPROSTIL• Prostaglandin analog that replaces

prostaglandins lost in stomach as result of NSAID therapy

• Only indicated for NSAID induced ulceration• Side effects : diarrhea and abdominal pain

SULCRALFATE - CARAFATE• Viscous gel• Adheres to ulcerated tissue and protects it

from acid / pepsin• Minor side effect is constipation• No major side effects• May impede absorption of some drugs

NON-DRUG THERAPY• Diet plays only a minor role in ulcer management.• No conclusive evidence that caffeine containing

beverages promote ulcer formation or interfere with recovery.

• Thought that alcohol can be harmful to lining of stomach

• Beneficial to eat 5-6 small meals a day instead of 3 large ones to decrease fluctuations in gastric pH.

When to refer• Patient ≤ 55 yo presenting with dyspepsia

without red flags, routine endoscopy is unnecessary ( chances of devp GIT cancer is 1 in a million).

• Older than 55yo with new onset persistant dyspepsia despite lifestyle & drug modification & 4/52 Rx.

• Younger than 55 & symp unresponsive to full dose PPI ,HP eradication,& lifestyle modification where concern exists about diagnosis.

Case Scenario

Case scenario:

• A 60 year old man • k/o :Diabetes Mellitus and Hypertension for 10 years • c/o: epigastric discomfort for 1 month duration. • The pain worsened at night and would awaken him from

sleep. • He denied of other GIT symptoms such as malena, lost of

weight or anorexia.• He also suffered Left hemiparesis from Ischaemic Stroke

since 3 months ago. • His current treatment is metformin 1gm bd, perindopril

4mg od, aspirin 150mg od and Simvastatin 20mg ON. Currently, his vital signs are stable and examination including abdomen was unremarkable.

• Proceed with management

• This history is typical of dyspepsia.• Non-pharmacology :stop aspirinExplain that dyspepsia is a common condition

that usually responds well to treatmentOffer lifestyle advice, including smoking

cessation, weight loss, reduced alcohol and caffeine intake, and regular exercise.

• Pharmacological: Aspirin + PPICaspirin + PPITiclid