Guideline for the Diagnosis and Treatment of Chronic Undiagnosed

Dyspepsia in Adults

Introduction Goals Definition Exclusions

This guideline was adapted from Sander J, Van Zanten V, Flook N, et al. An evidence-based approach to the management of uninvestigated dyspepsia in the era of Helicobacter pylori. CMAJ, June 2000; 162(12) Suppl. To position health care professionals in Alberta to optimize the diagnosis and management of Chronic Undiagnosed Dyspepsia in Adults.

Dyspepsia is a group of symptoms which alert clinicians to consider disease of the upper gastrointestinal tract.1 It is not a diagnosis and includes symptoms of upper abdominal discomfort, nausea, bloating, fullness and early satiety amongst others. The recommendations contained in this guideline do not apply to: Pregnant or lactating women Patients under the age of 18 years (see Algorithm) Consider organ pathologies other than upper gastrointestinal (UGI) tract (i.e., cardiac, hepatobiliary, colonic, musculoskeletal) Patients over age 50 with new onset of symptoms or those with alarm features or those who fail repeated trials of therapy warrant careful assessment and timely investigation, preferably including endoscopy*
* Upper GI barium X-ray may be considered as an alternative, however, diagnostic accuracy for X-ray is about 70%.2-6

Recommendations

Vomiting Bleeding/anemia Abdominal mass/unexplained weight loss Dysphagia/odynophagia

AlArm FeAtures

Search for precipitating factors: - advise necessary changes to correct precipitating factor(s) PreciPitAting FActors Dietary indiscretion (caffeine, high fat) NSAID/ASA use Some prescription medications (i.e., calcium channel blockers, bisphosphonates) Excessive alcohol use Smoking

The above recommendations are systematically developed statements to assist practitioner and patient decisions about appropriate health care for specific clinical circumstances. They should be used as an adjunct to sound clinical decision making.

Dyspepsia

If patient less than 50 years of age has signs/symptoms suggestive of gastroesophageal reflux disease (GERD), (i.e., restrosternal burning, regurgitation), refer to the Guideline for Treatment of Gastroesophageal Reflux Disease If patient less than 50 years of age, does not have alarm features, is not using NSAIDs/ ASA, and symptoms do not suggest GERD consider testing for H. pylori. - The test and treat option is preferable in populations with a prevalence of H. pylori > 10%.a Prevalence in Canada is 30%. - Urea Breath Test (UBT)* is the recommended investigation to test for H. pylori infection - If UBT positive, refer to the guideline for treatment of Helicobacter Pylori infection in Adults

* Note: Prior to testing for H. pylori with UBT, a 2-week washout period is recommended following PPI use and 4 weeks following antibiotic use. If UBT negative, consider trial of empiric therapy (see Empiric Therapy below)

empiric therapy Proton pump inhibitor (PPI) for 4 weeksb or H2 receptor antagonist (H2RA) for 4 weeksb Reassess at 2-4 weeks - Success: stop treatment - Partial success: repeat treatment one time - Failure: Reassess and consider further investigation or referral Notes a. Recommended options for treatment include PPI or H2RA. There is little evidence to guide therapeutic choice b. A 4-week trial of empiric therapy has been recommended by expert panels c Prescribe for 4 weeks followed by reassessment

There are very limited data to support the use of low-dose tricyclic antidepressants in functional dyspepsia. a

Background

introduction

Dyspepsia is a common complaint. Treatments can be very effective and investigations sophisticated. More is spent on drugs for dyspepsia than any other treatment for a symptom group. Dyspepsia is a group of symptoms that alerts the physician to consider disease of the upper gastrointestinal tract.1 It is not a diagnosis and includes symptoms of upper abdominal discomfort, retrosternal pain, nausea, bloating, fullness, early satiety and heartburn amongst others. A firm clinical diagnosis can be difficult on the basis of these symptoms, as few symptoms are discriminatory. Many diseases cause dyspepsia and these include peptic ulcers, GERD, cancer of the stomach or pancreas, and gallstones. In a large proportion of cases no clear pathological cause for a patients symptoms is identified. Clinicians can avoid missing serious disease by careful assessment of patients over 50, searching for alarm features and testing selected patients for H. pylori.

Dyspepsia
Disease Prevalence
Dyspepsia is one of the most common symptoms bringing a patient to the family physician.b,c According to Talley7, dyspepsia is the 4th ranking symptom presenting for diagnosis in primary care. Only headache, fatigue, and irritability exceed it. Surveys in western societies have recorded prevalence between 21 to 45%.8-10 In the United Kingdom, it has been estimated that approximately 40% of the population will, at some time, have dyspepsia, about 20% of the population used medications for symptom relief and 2% lost time from work because of dyspepsia.

Patient History
Dyspepsia symptoms have been classified as reflux-like, ulcer-like or dysmotility-like. The percentage of dyspeptics that fall into these three groups is approximately 21%, 11% and 7%, respectively. Unfortunately it is not possible to predict underlying disease based on these symptom groups and furthermore overlap between these symptoms occurred in 21% of patients, and in 40% of patients, symptoms were non-specific. The cardinal symptoms suggestive of GERD are heartburn and regurgitation. Patient history and physical examination are focused to detect clinical alarm features (vomiting, bleeding/ anemia, abdominal mass/anorexia/weight loss, dysphagia/odynophagia). Important historical features include dietary indiscretion (caffeine, high fat), NSAID/ASA use, some prescription medications (i.e., calcium channel blockers, biophosphonates), a past history of ulcer disease, or a family history of gastric cancer.

Differential Diagnosis
Acid related disorders of the UGI tract are extremely common. Patients often present with non-specific symptoms, a phenomenon which makes diagnosis challenging. A rational and detailed approach to history taking must be undertaken to ensure correct diagnosis. This will allow for appropriate treatment and management. Consideration should be given to non-UGI causes such as (cardiac, hepatobiliary, colonic, musculoskeletal) and other organ pathologies.11 PrActice Points Consider cardiac and other organ diseases in the differential diagnosis.

identifying those needing early endoscopy

In patients whose dyspepsia is assessed as originating in the UGI tract, further differentiation is required to identify high risk patients who will need endoscopy from those who can be safely managed without early endoscopy. It is reasonable to discuss early endoscopy with patients over 50 years of age with new-onset dyspepsia particularly if the symptom is progressively worsening.I Most individuals with alarm features will not have a serious problem but the vast majority of patients with upper gastrointestinal malignancy will have alarm features when they present for investigation. Serious consideration should be given to arranging prompt endoscopy for patients who have alarm features. The British Society of Gastroenterology recommends that if endoscopy cannot be provided promptly, a 2 to 4 week treatment period before investigation may be acceptable.1 The American Gastroenterology Association suggests that referral for early

Dyspepsia
endoscopy is indicated in older patients presenting with new onset dyspepsia.12 This is because the incidence of gastric cancer increases with advancing age. The threshold of 50 years of age was selected because gastric cancer is very uncommon before that age. The American Gastroenterology Association further recommends that patients whose symptoms have failed to respond to empiric therapeutic approaches should undergo endoscopy. PrActice Points Patients with new onset of dyspepsia over the age of 50 and those with evidence of clinical alarm features should have a very careful assessment usually including prompt endoscopy.

those not needing early endoscopy

Selected dyspepsia patients can be managed without referral or early endoscopy. These selected patients are under age 50 years and have symptoms that have been determined to originate in the UGI tract and are not accompanied by alarm features. Once the dyspepsia patients using NSAIDs/ASA and those with reflux-like symptoms have been separated for management (see Guideline for Treatment of Gastroesophageal Reflux Disease) the remainder will be a mixed group of patients. It will include some who have peptic ulcers and others with non-ulcer dyspepsia (NUD).13 According to the 2005 Canadian GERD Consensus Report, 14 not all patients with dyspepsia require a diagnostic endoscopy. Patients whose symptoms respond to PPI treatment and are characteristic of GERD may not need endoscopy until the duration of symptoms approaches 10 years. At this point, endoscopy is reasonable to search for Barretts esophagitis. Young dyspepsia patients who fail to improve with appropriate treatment such as 4 - 8 weeks of PPI or H2RA should have a careful reassessment that often includes endoscopy.The optimal management of a patient who presents with dyspepsia remains controversial. For many persons, the symptoms of dyspepsia are short-lived or of mild severity and are therefore self managed.15 Only 3-5% patients with dyspepsia have peptic ulcers and only a fraction have cancer, and almost all of these had alarm features on initial presentation.16,17

Lifestyle Modifications

Patients should be advised to eat small frequent meals, stop smoking, reduce alcohol and caffeine, avoid irritating foodstuffs and maintain an ideal weight. Medications should be reviewed. These are reasonable general health measures that often help with dyspepsia symptoms.

gerD

When the symptoms appear to originate in the UGI tract, the physician must separate those cases that appear to be caused by GERD. This is done through the key symptoms: heartburn and acid regurgitation. Roughly 1/2 of primary care patients with symptoms of GERD will also have inflammation and/or ulceration of the lower esophagus known as reflux esophagitis. Serious complications of GERD include reflux strictures and Barretts esophagus. Fortunately, GERD complications are rare in primary care. For most patients with GERD, the primary care physician can initiate therapy on clinical grounds without specific diagnostic testing.19,20

Dyspepsia
Peptic ulcers
A peptic ulcer is found in approximately 5% of primary care dyspepsia cases. A chronic duodenal ulcer is usually caused by H. pylori; chronic gastric ulcers also commonly result from H. pylori infection. Most of the remaining ulcers are caused by NSAIDs.21,22 The Canadian Consensus Conference Panel recommends that those who have a past history of proven duodenal ulcer but have not had adequate H. pylori eradication therapy should receive eradication therapy.13

nsAiDs

NSAID induced ulcer disease is a major epidemiologic problem.23 Twenty percent of individuals using NSAIDs longer than 12 weeks have endoscopic evidence of ulceration. It is important to determine if the dyspeptic patient has a history of NSAID use. If there are no alarm symptoms and the patient is on NSAIDs, try to discontinue the NSAID. If symptoms resolve, no further treatment is indicated. If unable to stop the NSAIDs, treat prophylatically with misoprostol or PPI. If the patient becomes symptom free continue treatment for one month. If the symptoms persist, further investigation is indicated. The association between H. pylori infection and NSAIDs in producing peptic ulceration and its complications is becoming clearer. Eradication of H. pylori infection prior to embarking on long term use of NSAIDs is a reasonable strategy. Similarly, searching for and treating H. pylori in patients on NSAIDs who have dyspepsia is also accepted as beneficial.d (See the H. pylori Guideline)

test for H. pylori and treat

Not all experts support a test and treat strategy for dyspepsia. The test and treat approach to dyspepsia is based on the knowledge that some dyspepsia patients have symptoms associated with duodenal or gastric ulcers, while a small proportion of others with non-ulcer dyspepsia improve when their H. pylori infection is treated. If there are no alarm symptoms, this approach involves performing a UBT and, if positive, treating the infection. Patients who test negative for H. pylori should be treated empirically with a PPI or H2RA, for 4 weeks then reassessing for response.e,f

Reference List

Dyspepsia

1. British Society of Gastroenterology. Guidelines in Gastroenterology, September 1996. 2. Kiil J, Andersen D. X-ray examination and/or endoscopy in the diagnosis of gastroduodenal ulcer and cancer. Scand J. Gastroenterol 1980; 15: 39-43 3. Sander J, Van Zanten V, Flook N, et al. An evidence-based approach to the management of uninvestigated dyspepsia in the era of Helicobacter pylori. CMAJ, June 13 2000; 162(12) Suppl. 4. Shaw PC, van Romunde LKJ, Griffioen G, Janssens AR, Kreuning J, Eilers GAM. Peptic ulcer and gastric carcinoma: diagnosis and biphasic radiography compared with fiberoptic endoscopy. Radiology 1987; 163: 39-42 5. Martin TR, Vennes JA, Silvis SE, Ansel HJ. A comparison of upper gastrointestinal endoscopy and radiography. J. Clin Gastroenterol 1980; 2: 21-25 6. Greenlaw R, Sheahan DG, DeLuca V, Miller D, Myerson D, Myerson P. Gastroduodenitis. A broader concept of peptic ulcer disease. Dig Dis Sci 1980; 25(9): 660-672 7. Talley N. Non-ulcer dyspepsia: current approaches to diagnosis. American Family Physician, 1993;47:6 8. Locke G. The epidemiology of functional gastrointestinal disorders in North America. Gastroenterology Clinics of North America, 1996; 25: 1-9. 9. Talley N, Zinsmester A, Scheck C. Dyspepsia and dyspepsia subgroups: a population based study. Gastroenterology, 1992; 102: 1259-1268. 10. Jones RH, Lipleard S. Prevalence of symptoms of dyspepsia in the community. British Medical Journal, 1989; 298: 30-32. 11. Talley NJ. Spectrum of chronic dyspepsia in the presence of the irritable bowel syndrome. Scan J Gastro Suppl, 1991; 182:7-10. 12. American Gastroenterology Association. Medical position statement: evaluation of dyspepsia. Gastroenterology, 1998; 114: 579-581. 13. Hunt R, Thompson A. Canadian Helicobacter pylori consensus conference. Canadian Journal of Gastroenterology, 1998 Jan/Feb; 12: 31-41. 14. Beck T, Connon J, Lemere S, Thompson A. Canadian consensus conference on the treatment of gastroesophageal reflux disease. Canadian Journal of Gastroenterology, 1992; 6: 277-289. 15. Talley N, Holtmann G. AGA technical review: evaluation of dyspepsia. Gastroenterology, 1998; 114: 582-595. 16. Health and Public Policy Committee, American College of Physicians. Endoscopy in the evaluation of dyspepsia. Annals of Internal Medicine, 1985; 102: 266-269. 17. Colin-Jones D. Management of dyspepsia: report of a working party. Lancet, 1988; 1: 576-579. 18. A. Thomson. Whats new in Dyspepsia? Parkhurst Exchange, Feb 1999. 19. American Association of Physician Assistants. 24th Annual Conference, 1996. 20. Armstrong D, Marshall J, Chiba N, et al. Canadian Consensus Conference on the Management of Gastroesophageal Reflux Disease in Adults: Update 2004. Canadian Journal of Gastroenterology, Jan 2005; 19(1). 21. Graham D. Treatment of peptic ulcers caused by Helicobacter pylori. New England Journal of Medicine, 1993; 328: 349-350. 22. Soll A. Medical treatment of peptic ulcer disease: practice guidelines. Journal of the American Medical Association, 1996; 275: 622-629.

Reference List

Dyspepsia

23. Young Tae Bak. An approach to the patient with non-ulcer dyspepsia. a. Talley N, Vakil N. Practice Parameters Committee of the American College of Gastroenterology. American Journal of Gastroenterology, 2005 October; 100(10): 23242337. b. Jones RH, Lydeard SE, Hobbs FDR, et al. Dyspepsia in England and Scotland. Gut 1990;31:401-405 c. Penston JG, Pounder RE. A survey of dyspepsia in Great Britain. Aliment Pharm Ther 1996;10:83-89 d. Hunt R, Fallone C, Veldhuyzan van Zanten S, et al. Canadian Helicobacter Study Group Conference: Update on the management of Helicobacter pylori - an evidence-based evaluation of six topics relevant to clinical outcomes n patients evaluated for H. pylori infection. Canadian Journal of Gastroenterology, 2004 Sep; 18(9): 547-554. e. Talley, N. J., N. Vakil, Veldhuyzen van Zanten, S., N. Flook. Randomized-controlled trial of esomeprazole in functional dyspepsia patients with epigastric pain or burning: does a 1-week trial of acid suppression predict symptom response? Aliment Pharmacol Ther 2007, 26(5): 673-82. f. Veldhuyzen van Zanten, S., N. Flook, et al. One-week acid suppression trial in uninvestigated dyspepsia patients with epigastric pain or burning to predict response to 8 weeks treatment with esomeprazole: a randomised, placebo-controlled study. Aliment Pharmacol Ther 2007, 26: 665-672.

Dyspepsia
Toward Optimized Practice (TOP) Program
Arising out of the 2003 Master Agreement, TOP succeeds the former Alberta Clinical Practice Guidelines program, and maintains and distributes Alberta CPGs. TOP is a health quality improvement initiative that fits within the broader health system focus on quality and complements other strategies such as Primary Care Initiative and the Physician Office System Program. The TOP program supports physician practices, and the teams they work with, by fostering the use of evidence-based best practices and quality initiatives in medical care in Alberta. The program offers a variety of tools and out-reach services to help physicians and their colleagues meet the challenge of keeping practices current in an environment of continually emerging evidence.

To Provide Feedback

The Alberta CPG Working Group for Dyspepsia is a multidisciplinary team composed of family physicians, general practitioners, gastroenterologists, pediatric gastroenterologists, a pathologist, radiologist, radiation oncologist, an infectious disease specialist, and representatives from the public and the Alberta Pharmaceutical Association. The team encourages your feedback. If you have difficulty applying this guideline, if you find the recommendations problematic, or if you need more information on this guideline, please contact: toward optimized Practice Program 12230 - 106 Avenue NW EDMONTON, AB T5N 3Z1 T 780. 482.0319 TF 1-866.505.3302 F 780.482.5445 E-mail: cpg@topalbertadoctors.org

Dyspepsia, June 2000 reviewed november 2001 revised Jan 2005 revised 2009

Algorithm: Diagnosis and Treatment of Chronic Undiagnosed Dyspepsia in Adults

Dyspepsia
Investigate: cardiac Pancreatic Hepatobiliary Colonic Musculoskeletal
Refer or investigate with endoscopy preferredb Drugs: - NSAIDs - ASA - Calcium channel blockers - Biophosphonates Diet (caffeine, high fat) Smoking Excessive alcohol

Dyspeptic Symptoms: Consider non-GI organ pathology?

No

Yes

Alarm features or over age 50 or failed empiric therapya

Yes

No

Precipitating factors

Yes

Modification of precipitating factors

No

GERD-like symptomsc heartburn regurgitation No Test for H. pylori positive?d No Manage as Functional (non-ulcer) Dyspepsiaf Symptoms resolved? No Reconsider diagnosis and consider investigation or referral

Yes

See Guideline for the Treatment of Gastroesophageal Reflux Disease (GERD)

Yes

If UBT positive for H. pylori See Guideline for Treatment of Helicobacter Pylori Infection in Adultse

Yes

Stop treatment and monitor for recurrence of symptoms

Algorithm: Diagnosis and Treatment of Chronic Undiagnosed Dyspepsia in Adults

Dyspepsia

notes
a.

Alarm Features Vomiting, Bleeding/anemia Abdominal mass/unexpected weight loss Dysphagia/odynophagia b. endoscopy Upper GI barium X-ray may be considered as an alternative c. Gastroesophageal Reflux Disease (GERD) Symptoms suggestive of GERD: (1) Retrosternal burning, discomfort rising toward the throat; (2) Regurgitation d. Peptic Ulcer disease (PUD)

e.

f.

Helicobacter pylori (H. pylori) testing Test only if patient is willing to be treated if tests positive for H. pylori Do not trial H. pylori eradication therapy without testing If H. pylori is associated with an ulcer, symptoms will improve with H. pylori eradication If symptoms have stopped, there is no need to re-test to prove eradication If there is Functional (non-ulcer) Dyspepsia consider H. pylori eradication UBT is recommended for pre and post-treatment testing Serology is not recommended for post-treatment testing Some potential exists for treatment side effects: allergies, C. difficile colitis, metallic taste Patient compliance is essential to reduce the potential for H. pylori resistance: 12% of Alberta H. pylori resistant to clarithromycin (1998), 29% of Alberta H. pylori resistant to metronidazole (1998) Stop antibiotics 4 weeks before and PPI 2 weeks before re-testing with UBT Functional (non-ulcer) Dyspepsia Two-thirds of dyspepsia patients less than age 50 without alarm features, symptoms not suggesting GERD, not taking ASA or NSAIDs will have Functional Dyspepsia There is limited symptomatic response to treatment for NUD Recommended options for treatment include PPI or H2RA. There is no concensus to guide therapeutic choice, therefore consider symptoms to make a choice and prescribe for 2 to 4 weeks with reassessment

One third of dyspepsia patients under age 50, without alarm features or GERD and not on ASA or NSAIDs will have H. pylori-induced peptic ulcer disease

10