Dispepsia

An An Evidence-based ApproachEvidence-based Approachto the Management ofto the Management of

Uninvestigated DyspepsiaUninvestigated Dyspepsiain the Primary Care Settings:in the Primary Care Settings:

an an updateupdate

Talley, J Clin Gastroenterol 2001; 32: 286–93.Locke, Ballieres Clin Gastroenterol 1998; 12: 435–42.

Paré, Can J Gastroenterol 1999; 13: 647–54.van Bommel et al., Postgrad Med J 2001; 77: 514–18.

Talley et al., BMJ 2001; 323: 1294–7.

15–25% of the general population experience dyspepsia within a 12-month period

Much more common than peptic ulcer

Up to 5% of primary care visits are due to dyspepsia

Most patients have no detectable abnormality on radiological upper GI series or endoscopy

Endoscopy findings and symptoms do not correlate

Dyspepsia: the size of the problem

Dyspepsia: the size of the problem

ORGANIC

UNINVESTIGATED

FUNCTIONAL(or idiopathic)

(use of the term ‘non-ulcer’ is discouraged)

INVESTIGATED

Talley et al., Gut 1999; 45(Suppl II): II37–42.

Dyspepsia covers a range of symptoms

Dyspepsia covers a range of symptoms

DYSPEPSIAPAIN OR DISCOMFORTcentred in upper abdomen

IBSGERD

Pain or discomfort occurring Pain or discomfort occurring centred in the upper abdomencentred in the upper abdomen

Talley et al., Gut 1999; 45(Suppl II): II37–42.Malfertheiner, Eur J Gastroenterol Hepatol 1999; 11(Suppl 1): S25–9.

Definition of dyspepsia (Rome II)Definition of dyspepsia (Rome II)Definition of dyspepsia (Rome II)Definition of dyspepsia (Rome II)

GastritisGastritis

Peptic ulcer diseasePeptic ulcer disease(Includes NSAID-induced ulcers)(Includes NSAID-induced ulcers)

DuodenitisDuodenitis

Duodenal ulcerDuodenal ulcer

Acid refluxAcid reflux

OesophagitisOesophagitis

StricturesStrictures

Barrett’sBarrett’soesophagusoesophagus

Oesophageal Oesophageal adenocarcinomaadenocarcinoma

NormalNormal

Gastritis/duodenitisGastritis/duodenitis

Reflux esophagitisReflux esophagitis

CancerCancer

Peptic ulcer diseasePeptic ulcer disease

33.6%33.6%23.9%23.9%

2%2%

19.9%19.9%20.8%20.8%

Richter 1991Richter 1991

51(24%)

36(17%)

27(13%)

21(10%)

11(5%)

7 (3%)

10(5%)

Ulcer-likeUlcer-likedyspepsiadyspepsia

Dysmotility-likeDysmotility-likedyspepsiadyspepsia

Reflux-likeReflux-likedyspepsiadyspepsia

UnspecifiedUnspecifieddyspepsiadyspepsia

n=50 (23%)n=50 (23%)Talley et al 1992

Functional Dyspepsia (Rome I)Functional Dyspepsia (Rome I)Functional Dyspepsia (Rome I)Functional Dyspepsia (Rome I)

Twelve weeks or more (within the last 12 Twelve weeks or more (within the last 12 months) of persistent or recurrent dyspepsia months) of persistent or recurrent dyspepsia and evidence that organic disease likely to and evidence that organic disease likely to

explain the symptoms is absent explain the symptoms is absent (including at upper endoscopy)(including at upper endoscopy)

Definition of Functional Dyspepsia Definition of Functional Dyspepsia (Rome II)(Rome II)

Definition of Functional Dyspepsia Definition of Functional Dyspepsia (Rome II)(Rome II)

Talley et al., Gut 1999; 45(Suppl II): II37–42.Malfertheiner, Eur J Gastroenterol Hepatol 1999; 11(Suppl 1): S25–9.

Dyspepsia subgroupsDyspepsia subgroups● Ulcer-like (predominantly pain)Ulcer-like (predominantly pain)

● Dysmotility-like (predominantly discomfort)Dysmotility-like (predominantly discomfort)

● Unspecified (non-specific, no predominant symptom)Unspecified (non-specific, no predominant symptom)

At least 3 months, with onset at least 6 months previously, of 1 or more of the following:

• Bothersome postprandial fullness • Early satiation • Epigastric pain • Epigastric burning

And • No evidence of structural disease (including at upper endoscopy) that is likely to explain the symptoms

Definition of Functional Dyspepsia Definition of Functional Dyspepsia (Rome III)(Rome III)

Definition of Functional Dyspepsia Definition of Functional Dyspepsia (Rome III)(Rome III)

Functional dyspepsia: Functional dyspepsia: an exclusion diagnosisan exclusion diagnosis

Patient with new onset or recurrent Patient with new onset or recurrent dyspeptic symptoms in whom no dyspeptic symptoms in whom no

investigation have been conducted investigation have been conducted and no specific diagnosis for the and no specific diagnosis for the

current symptoms existcurrent symptoms exist

Uninvestigated DyspepsiaUninvestigated DyspepsiaUninvestigated DyspepsiaUninvestigated Dyspepsia

Sander et al., CMAJ 2000; 162 (Suppl): S1–23

Uninvestigated dyspepsiaUninvestigated dyspepsia● All symptomatic patients, All symptomatic patients,

regardless of whether a cause regardless of whether a cause has been soughthas been sought

Functional dyspepsiaFunctional dyspepsia● Symptomatic patients in whom Symptomatic patients in whom

an organic cause has been an organic cause has been sought and excludedsought and excluded

Talley Talley et alet al., ., GutGut 1999; 1999; 45(45(Suppl II): II37–42.Suppl II): II37–42.

Uninvestigated dyspepsia Uninvestigated dyspepsia vs functional dyspepsiavs functional dyspepsia

Uninvestigated dyspepsia Uninvestigated dyspepsia vs functional dyspepsiavs functional dyspepsia

Management of Management of uninvestigated dyspepsiauninvestigated dyspepsia

YES

First Visit

(A)

Other possible causes ?

Consider :Consider :- Cardiac- Cardiac

- Hepatobiliary- Hepatobiliary- Medication-induced- Medication-induced- Dietary indiscretion- Dietary indiscretion

- Other- OtherTreat as appropriateTreat as appropriate

Uninvestigated DyspepsiaUninvestigated Dyspepsia


Consider:cardiac and hepatobiliary sources

medication-induced symptoms possible dietary indiscretion lifestyle or other causes

RecommendationRecommendation

Exclude other possible causes of the dyspeptic Exclude other possible causes of the dyspeptic symptoms with thorough history-taking and symptoms with thorough history-taking and

physical examinationphysical examination

(grade C recommendation, consensus)(grade C recommendation, consensus)

No

YES

YES

First Visit

(A)






InvestigateInvestigate(endoscopy (endoscopy

recommended)recommended)

(B)Age >50 or alarm features?

- Vomiting- Bleeding anemia- Abdominal mass/

unexplained weight loss- Dysphagia


Older patients and with alarm featuresOlder patients and with alarm features

America

> 50 years

> 55 years

> 45 years

Canada

Indonesia

Cancer is a rare cause of dyspeptic symptoms< 2 %

Diagnostic test: endoscopy or radiography?Diagnostic test: endoscopy or radiography?

Radiography :

96 %

70 %

Endoscopy :

Dooley Dooley et al.et al., , Ann Intern Med Ann Intern Med 1984; 1984; 101: 538-45101: 538-45

Endoscopy with biopsiesEndoscopy with biopsies

andand

treat accordingly!treat accordingly!

Talley Talley et alet al., ., BMJBMJ 2001; 2001; 323323: 1294–7: 1294–7

Specialist management of Specialist management of uninvestigated dyspepsiauninvestigated dyspepsia

Specialist management of Specialist management of uninvestigated dyspepsiauninvestigated dyspepsia

Prompt investigation is recommended for patients Prompt investigation is recommended for patients over 50 years of age over 50 years of age with uninvestigated dyspepsia and for any patient presenting with with uninvestigated dyspepsia and for any patient presenting with alarm alarm

featuresfeatures

Endoscopy is the recommended method of investigation for Endoscopy is the recommended method of investigation for patients patients

with uninvestigated dyspepsia who are over 50 years of age or with uninvestigated dyspepsia who are over 50 years of age or who have alarm featureswho have alarm features


Alarm features:persistent vomiting

evidence of gastrointestinal bleeding or anemia presence of an abdominal mass

unexplained weight lossdysphagia

(grade B recommendation, level III (grade B recommendation, level III evidence)evidence)

(grade A recommendation, level II (grade A recommendation, level II evidence)evidence)

(C)NSAID and/or Regular ASA

Use?

NSAID Management

No

NO

YES

YES

YES

First Visit

(A)












Patients who use NSAIDsPatients who use NSAIDs

Hp infection is the most common cause ofpeptic ulcers

NSAIDs are responsible for most Hp-negative ulcers

Patients with uninvestigated dyspepsia Patients with uninvestigated dyspepsia who are regular users of NSAIDSwho are regular users of NSAIDS

(including ASA) should be identified, (including ASA) should be identified, and if there are no alarm features,and if there are no alarm features,

they can be managed without initial they can be managed without initial endoscopy endoscopy



NSAID and/or reguler ASA use

Can NSAID/ASAbe stopped?

Treat or investigatea. PPIb. Cytoprotective agentc. High-dose H2-RA

d. Switch to COX-2 inhibitor

Stop therapy

Patient improved? End

NO

YES

YESNO


If possible, NSAID use should be stopped If possible, NSAID use should be stopped and the patient’s response monitored and the patient’s response monitored

Treatment recommendations for patients aged 50 years or Treatment recommendations for patients aged 50 years or less who less who

present with uninvestigated dyspepsia, who no alarm features present with uninvestigated dyspepsia, who no alarm features and and

who need to use NSAIDs (including ASA) are as follows:who need to use NSAIDs (including ASA) are as follows:• PPIPPI• Cytoprotective agentCytoprotective agent• High-dose HHigh-dose H22–RA therapy –RA therapy

(d) Consider switch to COX-2 inhibitor (d) Consider switch to COX-2 inhibitor



(grade C recommendation, level III (grade C recommendation, level III evidence)evidence)

If NSAIDs cannot be stopped the choice is to treat or investigateIf NSAIDs cannot be stopped the choice is to treat or investigate


Use?

(D)Is dominant symptom

heartburn and/orregurgitation ?

NSAID Management

Treat as reflux

No

NO

NO

YES

YES

YES

YES

First Visit

(A)












Patients with dominant symptom of heartburn Patients with dominant symptom of heartburn or acid regurgitation, or bothor acid regurgitation, or both

Heartburn (89 %) or acid regurgitation (95 %) have Heartburn (89 %) or acid regurgitation (95 %) have high specificity for GERDhigh specificity for GERD

Most GERD patients do not have macroscopicMost GERD patients do not have macroscopicesophagitisesophagitis

Initial treatment can be started based on symptoms Initial treatment can be started based on symptoms of reflux in primary careof reflux in primary care

Endoscopy is not a useful diagnostic Endoscopy is not a useful diagnostic gold standard gold standard forforGERD, nor 24-hour pH monitoringGERD, nor 24-hour pH monitoring

A reliable interpretation of the term heartburn is key A reliable interpretation of the term heartburn is key for the diagnosis of GERDfor the diagnosis of GERD

Patients aged 50 years or less with uninvestigated dyspepsia Patients aged 50 years or less with uninvestigated dyspepsia and dominant symptoms of heartburn or acid regurgitation, and dominant symptoms of heartburn or acid regurgitation,

or both should be diagnosed as having GERD or both should be diagnosed as having GERD and be treated accordingly and be treated accordingly

Rather than using the term “heartburn”, describing the sensation of “a burning feeling

rising from your stomach or lower chest toward your neck” increases the diagnostic

accuracy for GERD


(grade B recommendation, level II-2 (grade B recommendation, level II-2 evidence)evidence)

Reflux mini-management schema

Dominant symptom heartburn and/or regurgitation

Treata. PPIb. H2-RAc. ProkineticReassess at 4 weeks

SymptomsResolved?

Treat- If not on PPI, switch to PPI x 4-8 weeks- If on PPI, double dose x 4-8 weeks or

consider investigation

Symptomsresolved?

Investigate

Stop therapy (if symptoms recur,

repeat original therapy)

NO

YES

NO

YES


Management of patients with GERDManagement of patients with GERD

Five treatment possibilities for GERD- lifestyle modification

- antacids- H2RAs

- prokinetic- PPIs

Review of lifestyle modification and antacids concluded that definitive evidence of efficacy is unavailable

Milder symptoms of GERD may derive benefit from lifestyle modification

The effectiveness of lifestyle modifications and antacids for the treatment The effectiveness of lifestyle modifications and antacids for the treatment of GERD is not proven. Patient with mild GERD symptoms may derive of GERD is not proven. Patient with mild GERD symptoms may derive

benefit from these treatment benefit from these treatment

Treatment recommendations for patients with a dominant symptom of

heartburn or acid regurgitation, or both, are as follows : • PPI

(a) H2 – RA (b) Prokinetic agent



Patients should be reassessed after 4 weeks of therapy

(grade A recommendation, level I (grade A recommendation, level I evidence)evidence)



Use?


heartburn and/orRegurgitation ?

NSAID Management

Treat as reflux

Treat as Hp positive

No

NO

NO

NO

YES

YES

YES

YES

YES

First Visit

(A)











(E)

Hp test positive?

1. UBT

2. Serology

Hp test and treat strategyHp test and treat strategy

Hp infection is associated with- duodenal ulcer 90 – 95 %

- gastric ulcer 60 – 80 %- gastric cancer

Option for the treatment of younger patients w/o alarm features:Option for the treatment of younger patients w/o alarm features:- trial of empiric (antisecretory or prokinetic)trial of empiric (antisecretory or prokinetic)

- diagnostic evaluationdiagnostic evaluation- non invasive testing for non invasive testing for HpHp

followed by eradication therapy for patients w/ (+)ve resultsfollowed by eradication therapy for patients w/ (+)ve results- non invasive testing for non invasive testing for HpHp

followed by endoscopy for patients w/ (+)ve results followed by endoscopy for patients w/ (+)ve results

Uncertainty as to whether Hp plays a role in dyspepsia in the absence of ulcers

A test-and-treat strategy for uninvestigated dyspepsia A test-and-treat strategy for uninvestigated dyspepsia in younger patient (aged 50 years or less) in younger patient (aged 50 years or less)

who have no alarm features is recommended who have no alarm features is recommended


(grade B recommendation, level I (grade B recommendation, level I evidence)evidence)

Testing for Hp infectionTesting for Hp infection

Infection can be detected by:Infection can be detected by:- invasive (endoscopy based)invasive (endoscopy based)

- non invasive (UBT, HPSA or serologic non invasive (UBT, HPSA or serologic testing)testing)

Serologic testing cannot be used to determine cure Serologic testing cannot be used to determine cure as the IgG antibodies remain detected for a long as the IgG antibodies remain detected for a long

time after eradicationtime after eradication

UBTUBT has a high (+)ve and (-)ve predictive value has a high (+)ve and (-)ve predictive value (both > 95 %)(both > 95 %)

Gisbert et al. Aliment Pharmacol Ther 2004;20:1001–17

Noninvasive methods are recommended Noninvasive methods are recommended for the detection of H. pylori in patient aged 50 years or less for the detection of H. pylori in patient aged 50 years or less

with uninvestigated dyspepsia who have no alarm featureswith uninvestigated dyspepsia who have no alarm features

Hp stool antigen is the preferred testHp stool antigen is the preferred test


(grade B recommendation, level II-2 (grade B recommendation, level II-2 evidence)evidence)

No more serology Stool antigen is the recommended

test Test with stool antigen before

prescribing PPIs do not have alarm symptomsdo not have alarm symptoms have not been using NSAIDShave not been using NSAIDS who are not > 55 yrswho are not > 55 yrs


(AGA guidelines from (AGA guidelines from 2005)2005)

H. Pylori positive mini-management schema

Patient Hp positive

Eradicate Hp:a. PPI + AC or MC or RBC + AC or MC (bid x 7 days)b. Alternative first line therapyc. PPI + BMT (bid x 14 days)(advise patient to return 4 weeks aftertreatment if symptoms recur or

persist)

Symptomsresolved at follow up?

Confirm Hp eradication by UBT or histology (not serology)

Hp eradicated?

Switch regimen and retreator refer for investigation

Treat as Hp negative

NO

YES

NO

No further therapyor investigation

YES


(a) First line therapy(a) First line therapyPPI + AC PPI + AC or or PPI + MC PPI + MC (bid for 7 days)(bid for 7 days)

oror ranitidine bismuth citrate + AC or MC ranitidine bismuth citrate + AC or MC• Alternative first-line therapyAlternative first-line therapy

• PPI + BMT (14-day quadruple regimen)PPI + BMT (14-day quadruple regimen)PPI (bid)PPI (bid)

B (4x2 tablets/day)B (4x2 tablets/day)M (4x250 mg/day)M (4x250 mg/day)T (4x500 mg/day)T (4x500 mg/day)

Hp eradication therapyHp eradication therapy

PPI = Lansoprazole 30 mg; Omeprazole 20 mg; Pantoprazole 40 mg

A = Amoxicillin 1000 mg

B = Bismuth subsalicylate (2 tablets)

C = Clarithromycin 250 (or 500 mg if treatment failure)

M = Metronidazole 500 mg (250 mg in BMT combination therapy)

T = Tetracyclin 500 mg


Eradication therapies recommended for patients Eradication therapies recommended for patients with uninvestigated dyspepsia who are found with uninvestigated dyspepsia who are found to be H. pylori positive are as follow:to be H. pylori positive are as follow:• PPI + AC or MC, PPI + AC or MC, or ranitidine bismuth citrate + AC or MCor ranitidine bismuth citrate + AC or MC• Alternative first-line therapyAlternative first-line therapy(c) PPI + BMT (c) PPI + BMT


(grade A recommendation, level I (grade A recommendation, level I evidence)evidence)

PPI = Lansoprazole 30 mg; Omeprazole 20 mg; Pantoprazole 40 mgA = Amoxicillin 1000 mgB = Bismuth subsalicylate (2 tablets)C = Clarithromycin 250 (or 500 mg if treatment failure)M = Metronidazole 500 mg (250 mg in BMT combination therapy)T = Tetracyclin 500 mg

Calvet et al. Aliment Pharmacol Ther 2000;14:603–609

A meta-analysis of 13 studies:Eradication rate for 14-day therapy vs 10-day therapy

was 81% (95% CI, 77%–85%) vs 72% (95% CI, 68%–76%)

The eradication rate for 10-day therapy vs 7-day therapy:83% (95% CI, 75%–89%) vs 80% (95% CI, 71%–86%)

A meta-analysis of short versus long therapywith a PPI, clarithromycin

and either metronidazole or amoxicillinfor treating Hpinfection

Fuccio et al. Ann Intern Med. 2007;147(8):553-62

Extending triple therapy beyond 7 daysis unlikely to be a clinically useful strategy

Meta-analysis:duration of first-line PPI-based triple therapy

for Helicobacter pylori eradication

Eur J Gastroenterol. 2004;16: 89-99

Pantoprazole achieves similar cure rates tothose of omeprazole and lansoprazolewhen co-prescribed with antibiotics

Pantoprazole based therapies in HP eradication:a systematic review and meta-analysis


Use?


heartburn and/orRegurgitation ?

NSAID Management

Treat as reflux

Treat as Hp positiveTreat as Hp Negative

No

NO

NO

NO

NO

YES

YES

YES

YES

YES

First Visit

(A)











(E)

Hp test positive?

1. UBT

2. Serology Sander et al., CMAJ 2000; 162 (Suppl): S1–23

H. Pylori negative mini-management schema

Patient Hp negative

Treat x 4 weeksa. PPIb. H2-RAc. Prokinetic

Symptomsresolved?

Modify therapy(increase dose or switch to another

therapy)

Symptomsresolved?

Reassess or investigate/refer

Stop therapy

NO

YES

NO

YES


There is good evidence that antacids are ineffective There is good evidence that antacids are ineffective for functional dyspepsia, and they are not recommended for functional dyspepsia, and they are not recommended

for the treatment of uninvestigated dyspepsia for the treatment of uninvestigated dyspepsia in patients subsequently found to be H. Pylori negativein patients subsequently found to be H. Pylori negative



Treatment recommendation for patients who presentTreatment recommendation for patients who present

with uninvestigated dyspepsia and who subsequentlywith uninvestigated dyspepsia and who subsequently

have negative results of testing for H. Pylori are as follows:have negative results of testing for H. Pylori are as follows:

(a)(a) PPIPPI

(b)(b) HH22-RA-RA

(c)(c) Prokinetic agentProkinetic agent



SummariesSummaries

Clinical management tool consists of 5 key steps in the evaluation of patients with uninvestigated dyspepsia

The tool is practical, easy to use, explicit and concise, and it reflects the realities of the primary care setting

Adoption of this tool will optimize the treatment of patients with dyspepsia, improve quality of care and be cost-effective

The tool includes 4 mini-management schemata

SPECIALIST REFFERAL :SPECIALIST REFFERAL :

PRIMARY MANAGEMENT OF NEW ONSET PRIMARY MANAGEMENT OF NEW ONSET UNINVESTIGATED DYSPEPSIA IN INDONESIAUNINVESTIGATED DYSPEPSIA IN INDONESIA

IF < 2 – 4 WKS.IF < 2 – 4 WKS.DIETARY ADVICE, OBSERVEDIETARY ADVICE, OBSERVE

REVIEW CURRENT MEDS.REVIEW CURRENT MEDS.

EXCLUDE BY HISTORY :EXCLUDE BY HISTORY :BILLIARY PAIN, BILLIARY PAIN,

IRRITABLE BOWEL, REFLUXIRRITABLE BOWEL, REFLUX

FAILURE OR FAILURE OR EARLY RELAPSEEARLY RELAPSE

FINAL EVALUATION AFTER 8 WKSFINAL EVALUATION AFTER 8 WKS> 3 X RELAPSE> 3 X RELAPSE

RELAPSERELAPSE

FOLLOW UPFOLLOW UP

SUCCESSSUCCESS

POS.POS.

AGE > 55 YRSAGE > 55 YRS WITH ALARM FEATURES :WITH ALARM FEATURES :

NEG.NEG.

SEROLOGIC Hp TESTINGSEROLOGIC Hp TESTING

ANTACIDSANTACIDS ANTISECRETORYANTISECRETORY

PROKINETICSPROKINETICS

GASTROENTEROLOGISTGASTROENTEROLOGIST

INTERNAL MED./PED. WITHINTERNAL MED./PED. WITH ENDOSCOPIC FACILITIESENDOSCOPIC FACILITIES

TREATMENT TRIAL : 2 WKSTREATMENT TRIAL : 2 WKS

AGE > 55 YRSAGE > 55 YRSWITHOUT ALARM FEATURESWITHOUT ALARM FEATURES

DYSPEPSIADYSPEPSIA

FEVERFEVER HEMATEMESIS / MELENA HEMATEMESIS / MELENA ICTERUSICTERUS ↓↓BWBW NSAIDsNSAIDs STRONG FEAR OF SERIOUS DIS. STRONG FEAR OF SERIOUS DIS. FAMILY HISTORY : GASTRIC CA. FAMILY HISTORY : GASTRIC CA.

SEVERE VOMITINGSEVERE VOMITING

Dispepsia

Health & Medicine

Transcript of Dispepsia