Scottish Intercollegiate Guidelines Network

68 Dyspepsia
A national clinical guideline

1 Introduction 1
2 Dyspepsia in the community 5
3 Management of uncomplicated dyspepsia 8
4 H. pylori tests 10
5 Management of functional dyspepsia 12
6 Implementation and audit 17
7 Patient information 19
8 Development of the guideline 20
References 25

March 2003
KEY TO EVIDENCE STATEMENTS AND GRADES OF RECOMMENDATIONS

LEVELS OF EVIDENCE

1++ High quality meta-analyses, systematic reviews of randomised controlled trials (RCTs),
or RCTs with a very low risk of bias
1+ Well-conducted meta-analyses, systematic reviews of RCTs, or RCTs with a low
risk of bias
1- Meta-analyses, systematic reviews of RCTs, or RCTs with a high risk of bias
2 ++
High quality systematic reviews of case control or cohort studies
High quality case control or cohort studies with a very low risk of confounding or bias
and a high probability that the relationship is causal
2+ Well-conducted case control or cohort studies with a low risk of confounding or bias
and a moderate probability that the relationship is causal
2- Case control or cohort studies with a high risk of confounding or bias
and a significant risk that the relationship is not causal
3 Non-analytic studies, e.g. case reports, case series
4 Expert opinion

GRADES OF RECOMMENDATION

Note: The grade of recommendation relates to the strength of the evidence on which the
recommendation is based. It does not reflect the clinical importance of the
recommendation.

A At least one meta-analysis, systematic review of RCTs, or RCT rated as 1++

and directly applicable to the target population; or
A body of evidence consisting principally of studies rated as 1+, directly applicable to
the target population, and demonstrating overall consistency of results

B A body of evidence including studies rated as 2++, directly applicable to the target
population, and demonstrating overall consistency of results; or
Extrapolated evidence from studies rated as 1++ or 1+

C A body of evidence including studies rated as 2+, directly applicable to the target
population and demonstrating overall consistency of results; or
Extrapolated evidence from studies rated as 2++

D Evidence level 3 or 4; or
Extrapolated evidence from studies rated as 2+

GOOD PRACTICE POINTS

þ Recommended best practice based on the clinical experience of the guideline

development group

© Scottish Intercollegiate Guidelines Network

ISBN 1 899893 68 7
First published 2003
SIGN consents to the photocopying of this guideline for the
purpose of implementation in NHSScotland
Scottish Intercollegiate Guidelines Network
Royal College of Physicians
9 Queen Street
Edinburgh EH2 1JQ

www.sign.ac.uk
 1 INTRODUCTION

1 Introduction
1.1 BACKGROUND
This guideline builds on the work already undertaken by SIGN on dyspepsia and incorporates
new evidence in controversial areas. In August 1996, SIGN published a national clinical guideline
on Helicobacter pylori (H. pylori) eradication therapy in dyspeptic disease.1 A single sheet update
of this guideline was issued in October 1999.2 Both publications provided evidence-based
recommendations on which patients with H. pylori should receive eradication therapy and which
eradication regimens to use. These SIGN Guidelines on H. pylori eradication therapy raised the
issue of how H. pylori infection may alter the way in which we investigate patients presenting
with dyspepsia.
This guideline specifically addresses the investigation and management of dyspepsia and updates
the evidence base for the key indications for H. pylori eradication in duodenal ulcer, gastric ulcer
and low grade gastric MALT lymphoma (see Annex 1).

1.2 THE NEED FOR A GUIDELINE

Upper gastrointestinal symptoms affect up to 40% of adults in any one year.3-5 Some 50% of
sufferers self-medicate, perhaps with advice from community pharmacists, with only about one
in four sufferers consulting their general practitioner.3-5
Scottish prescribing data revealed a 27% increase in the number of prescriptions for ulcer healing
drugs between 1996 and 2001.6 Despite the significant increase in the volume of prescribing, the
cost in absolute terms has reduced, from £72.5 m per annum to £71 m over the same period.
This is partly due to price reductions of Proton Pump Inhibitors (PPIs) and the generic tariff
prices for those H2 receptor antagonists (H2RA) available on the Scottish Drug Tariff, and partly
due to increasing use of maintenance doses of PPIs. Upper gastrointestinal symptoms nonetheless
impose a substantial burden on the Scottish healthcare system3,7 as well as causing significant
quality of life impairment for the individuals who suffer them.8,9

1.3 TERMINOLOGY

1.3.1 DYSPEPSIA
The term dyspepsia has been used inconsistently by healthcare professionals to describe differing
patterns of upper gastrointestinal (GI) symptoms. The consequent lack of comparability between
published studies of dyspepsia has been a major barrier to resolving clinical uncertainty about
best practice for investigation and treatment of patients. Clarity about the terminology is thus an
essential preliminary to formulating an up to date guideline on clinical practice. Dyspepsia
denotes symptoms and is not itself a disease. The guideline development group accepted the
Rome II definition:10 Dyspepsia refers to pain or discomfort centred in the upper abdomen.
“Centred” refers to pain or discomfort in or around the midline. Pain in the right or left
hypochondrium is not considered to constitute dyspepsia. “Discomfort” refers to a subjective
negative sensation that the patient does not interpret as pain, which may be characterised by or
associated with upper abdominal fullness, early satiety, bloating, belching, nausea, retching
and/or vomiting.
On investigation, organic disease (eg duodenal or gastric ulcers) thought likely to explain the
dyspepsia will be found in some patients. In others, no such causal pathology or disease is
identified: these patients are said to have functional dyspepsia. The older synonym “non-ulcer
dyspepsia”, though still widely used, is not recommended because some of the patients have
symptoms typical of ulcer disease while others have symptoms not at all like an ulcer. Furthermore,
peptic ulcer is not the only organic disease to be excluded before the diagnosis of functional
dyspepsia is appropriate.

1
DYSPEPSIA

Patients with functional dyspepsia who identify pain as their predominant symptom may be said
to have ulcer-like dyspepsia whereas patients with discomfort as their predominant symptom
may be said to have dysmotility-like dyspepsia.10

1.3.2 HEARTBURN, DYSPEPSIA AND GASTRO-OESOPHAGEAL REFLUX DISEASE (GORD)

Confusion often accompanies consideration of the relationship between heartburn, dyspepsia
and GORD. A first step towards minimising this confusion is to recognise that heartburn and
dyspepsia describe symptoms, whereas GORD is a collective term embracing all diseases caused
by gastro-oesophageal reflux.
Retrosternal heartburn, the classical symptom of GORD, is not included within the Rome II
definition of dyspepsia because it is not an upper abdominal symptom. A diagnosis of GORD
may be made with high confidence for patients who describe retrosternal heartburn and/or acid
regurgitation as their principal complaints. This diagnosis is less certain when pain or discomfort
centred in the upper abdomen (Rome II dyspepsia) is accompanied by heartburn as a secondary,
subordinate symptom, hence the emphasis given to the predominant symptom as the basis for
diagnosis.
Not all patients with GORD present with classical heartburn. A minority of patients describe
upper abdominal pain or discomfort (Rome II dyspepsia) as their principal symptom: other
recognised “atypical” presentations of GORD include asthma and non-cardiac chest pain.
Distinguishing dyspepsia from heartburn potentially allows appropriate diagnostic significance
to be attached to each of these symptoms. Recognition that heartburn is the classical, but not the
only, clinical presentation of GORD serves as a reminder that heartburn and GORD should not
be equated.

þ A diagnosis of gastro-oesophageal reflux disease (GORD) is likely if retrosternal heartburn

and acid regurgitation are a patient’s principal complaints. The term “reflux-like dyspepsia”
is no longer recommended to describe these symptoms.

1.3.3 OESOPHAGEAL AND GASTRIC CANCER

A minority of patients with dyspepsia will have major organic pathology, e.g oesophageal or
gastric cancer. This guideline highlights the alarm features (see sections 2.2 and 2.4) that would
identify patients who require early referral to a hospital specialist.

1.4 REMIT OF THE GUIDELINE

This guideline provides recommendations based on current evidence for best practice in the
management of dyspepsia in adults. It includes guidance on investigation and treatment of
dyspepsia, but does not specifically address the clinical management of:
n Diagnosed gastro-oesophageal reflux disease (GORD) (this may be addressed by a future
SIGN guideline)
n diagnosed gastric or duodenal ulcers (but see Annex 1 for an update on H. pylori eradication)
n dyspepsia associated with the use of non-steroidal anti-inflammatory drugs (NSAIDs).
This guideline is likely to be of particular interest to general practitioners, community pharmacists,
gastroenterologists, upper GI surgeons, general surgeons, nurse endoscopists, public health
physicians, radiologists and clinicians who specialise in the care of the elderly.

1.5 STATEMENT OF INTENT

This guideline is not intended to be construed or to serve as a standard of medical care. Standards
of care are determined on the basis of all clinical data available for an individual case and are
subject to change as scientific knowledge and technology advance and patterns of care evolve.
These parameters of practice should be considered guidelines only. Adherence to them will not
ensure a successful outcome in every case, nor should they be construed as including all proper

2
 1 INTRODUCTION

methods of care or excluding other acceptable methods of care aimed at the same results. The
ultimate judgement regarding a particular clinical procedure or treatment plan must be made by
the doctor, following discussion of the options with the patient, in light of the diagnostic and
treatment choices available. However, it is advised that significant departures from the national
guideline or any local guidelines derived from it should be fully documented in the patient’s
case notes at the time the relevant decision is taken.

1.6 REVIEW AND UPDATING

This guideline will be issued in 2003 and will be considered for review as new evidence becomes
available. Any updates to the guideline will be noted on the SIGN website: www.sign.ac.uk

3
DYSPEPSIA

Figure 1

"INDIGESTION"

Consider PREDOMINANT
HEARTBURN
n Heart
n Liver
DYSPEPSIA* Yes
n Gall bladder No
n Pancreas
n Bowel
n NSAIDs etc MANAGE
AS GORD
ALARM FEATURES
REFER TO Yes n Dysphagia
HOSPITAL n Evidence of GI blood loss
SPECIALIST n Persistent vomiting
n Unexplained weight loss
n Upper abdominal mass

No

UNCOMPLICATED DYSPEPSIA
Consider
n Lifestyle
n Antacids / H2RA

Persistent / recurrent symptoms

Hp test + ve Hp test Hp test -ve

Eradicate Hp Persistent / recurrent symptoms

despite confirmed eradication

Age

Asymptomatic
≥55
<55

Manage as Consider referral to

functional dyspepsia hospital specialist

* Rome II definition

4
 2 DYSPEPSIA IN THE COMMUNITY

2 Dyspepsia in the community

People with dyspepsia may choose several routes for the initial management of the condition.
Some people purchase antacids or H2RA medicines over the counter, some consult with a
community pharmacist and others will consult their general practitioner. Figure 1 on page 4
describes an evidence-based approach to investigation and management.

2.1 THE ROLE OF THE COMMUNITY PHARMACIST

The UK market for over the counter indigestion remedies was £88.5m in 1999 and £93.7m in
2000.11 In the UK, antacids are categorised under the Medicines Act, Section 3 1978, as general
sales list (GSL) items and may be bought at a variety of sales outlets such as supermarkets, petrol
stations and corner shops without the supervision of a pharmacist. Antacids may also be purchased
from pharmacies. H2RAs are categorised as either GSL for 6 to 12 tablets of ranitidine or as
pharmacy supervised sale (P), for larger quantities of ranitidine or other H2RAs. The dose of over
the counter H2RA is usually 50% of the standard prescribed maintenance dose and the quantity
is limited to 24 tablets in a pack. Users are advised they should not be taken for prolonged
periods without seeking medical advice.
Pharmacists are well placed to provide an early intervention for people suffering from symptoms
of dyspepsia. It has been demonstrated that advice on self-medication and counselling by
pharmacists has a measurable impact on health-related quality of life and that patients value the 2+
information that pharmacists provide.12 Patients advised to visit their general practitioner (GP) by
their pharmacist may not present to their GP. This could be important if their symptoms include
alarm features that may be suggestive of a more serious pathology.13

D Community pharmacists should advise patients suffering from dyspepsia associated with Extrapolated
from studies
alarm symptoms to consult their general practitioner (see section 2.4).
rated 2+

2.2 PRESENTATION IN GENERAL PRACTICE

The general practitioner, faced with the patient complaining of “indigestion” will consider all
possible sources including the oesophagus, stomach, heart, liver, gall bladder, pancreas, bowel,
NSAIDs and other drugs.
Alarm features such as dysphagia, evidence of GI blood loss, persistent vomiting, unexplained
significant weight loss or an upper abdominal mass should be identified (see section 2.4). Patients
with these findings merit early referral to a hospital specialist. The management strategy for
uncomplicated dyspepsia given in this guideline should only be used if pathology outwith the
stomach and proximal duodenum is thought unlikely and alarm features are not present. It
should again be emphasised that this guideline does not address dyspepsia associated with
NSAID use.

2.3 SYMPTOMS OF DYSPEPSIA

Dyspepsia refers to pain or discomfort centred in the upper abdomen.10
The presence of pain or discomfort in the upper abdomen is often accompanied by a combination
of several symptoms including bloating, early satiety, heartburn, and nausea or vomiting. It is
helpful to inquire about the predominant symptom, such as upper abdominal discomfort, pain,
heartburn or reflux in order to distinguish dyspepsia from GORD.
The value of dyspepsia symptom subgroups to reflect underlying pathophysiology is limited.14,15
Unaided clinical diagnosis in dyspeptic patients in primary care is unreliable and the specificity
of individual symptoms have been shown to be low.14 A clinical diagnosis of peptic ulcer will 2+
miss approximately half of all ulcer cases and a provisional diagnosis of ulcer will be confirmed
in only one-third. Symptom assessment cannot be used to make a reliable diagnosis in patients
with dyspepsia.

5
DYSPEPSIA

Computerised models have been developed using multiple clinical and demographic criteria to
try to identify patients at low risk of organic dyspepsia and hence improve the likelihood of an 2-
accurate diagnosis.16,17 Computerised models are rarely validated and cannot therefore be generally
recommended.16

C Symptom assessment cannot be relied upon to make a diagnosis of the cause of dyspepsia.

2.4 ALARM FEATURES AND RISK OF CANCER

Many guidelines recommend that alarm features such as dysphagia, recurrent vomiting, significant
unintentional weight loss, anaemia from gastrointestinal haemorrhage or upper abdominal mass,
are used as predictors for major pathology (eg ulcer with complications or oesophageal cancer) in 4
patients with dyspepsia. 18,19 They further recommend that patients of any age with these features
should have early investigation.18,19 These recommendations tend to be based on expert opinion
rather than published evidence.18,19
The evidence concerning alarm features such as dysphagia, recurrent vomiting, significant
unintentional weight loss, anaemia from gastrointestinal haemorrhage or upper abdominal mass
does not allow clear conclusions. In some studies 20-23 alarm features are seen to be predictive of
major pathology, but in others this association is not found.24 A recent American multicentre
2++
database study of 3815 patients having first endoscopy for dyspepsia, showed that male sex, age
over 45 years and anaemia were significant but weak predictors for major upper GI pathology. 25
In this study, weight loss and dysphagia were not found to be significant predictors. It was
demonstrated that age and alarm features are not effective predictors of endoscopic findings
among patients with dyspepsia and that better clinical prediction strategies are required.
Several cohort studies show that up to 95% of younger patients (age ranges used in studies vary
between under 45 years to under 55 years) with upper GI cancer have more than one alarm
feature. 20,21,25,26 The Scottish Audit of Gastric and Oesophageal Cancer (SAGOC) data show that 2++
9% of patients with upper GI cancer in Scotland are under 55 years of age and 93% of them have
an alarm feature at the time of presentation.27
In the dyspeptic population, some alarm features (age over 45 years, anaemia, male sex) are weak
predictors for upper GI cancer.25 However, in populations of patients with dyspepsia and upper
GI cancer, alarm features are almost always present.20,21

B Patients with dyspepsia and alarm features should be referred to a hospital specialist for
assessment.

2.4.1 AGE AND GASTRIC CANCER

In 1998 both the American Gastroenterological Association18 and a working party for the World
Congress of Gastroenterology advised that patients over 45 and 50 years of age respectively
presenting with new onset uncomplicated dyspepsia should undergo early upper GI endoscopy.28 4
This recommendation was not evidence-based but arose from a perception that non-invasive
investigation or empirical therapy for uncomplicated dyspepsia in this group of patients would
delay the diagnosis of gastric cancer and may adversely affect survival.
A recent systematic review however found no evidence to suggest that an initial course of empirical
therapy, rather than endoscopy, adversely affects outcome in patients with underlying gastric
cancer.29 Some patients with uncomplicated dyspepsia will also have gastric cancer but there is
no evidence that early, potentially curable gastric cancer found via endoscopy to investigate
1+
uncomplicated dyspepsia is other than a chance finding. Despite the belief of many clinicians
that uncomplicated dyspepsia may be a symptom of cancer, upper GI cancer may in fact be no
more prevalent than in an age matched non dyspeptic population.
There is no evidence to support the mandatory use of early upper GI endoscopy to investigate
patients over 55 years old who present with new onset uncomplicated dyspepsia.

6
 2 DYSPEPSIA IN THE COMMUNITY

2.4.2 ENDOSCOPY VERSUS BARIUM MEAL FOR PATIENTS WITH ALARM FEATURES
Endoscopy is more sensitive than barium meal at detecting early curable gastric cancer and is
also more likely to detect gastric and duodenal erosions.30,31 Any lesions seen can also be biopsied
immediately. A well conducted barium meal is a useful investigation which will detect most 2+
serious disease in the upper GI tract32 but it does involve a radiation dose (typical effective dose 4
2mSv equivalent to 11 months of background radiation).33 This is particularly relevant now that
the European Union regulations governing the exposure of patients to medical radiation are in
force.34

C Upper GI endoscopy is the investigation of choice when further evaluation is warranted

and should be widely available.

þ Barium meal studies are appropriate where the local endoscopy services are unavailable
or for patients who cannot tolerate endoscopy.

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DYSPEPSIA

3 Management of uncomplicated dyspepsia

Uncomplicated dyspepsia refers to patients whose dyspepsia is not accompanied by alarm features
or associated with NSAID usage. The traditional management of patients in primary care has
been to consider the role of lifestyle, antacids and H2RAs. There are a number of possible
approaches to the management of patients with persisting or recurrent symptoms (see Figure 1,
page 4). Some of these approaches incorporate the role of H. pylori infection in the aetiology of
ulcer disease. Most studies of these approaches have involved patients of less than 55 years of
age.

3.1 PATIENTS LESS THAN 55 YEARS OF AGE

Acid suppression therapy
This has the disadvantage of depriving those with underlying ulcer disease from being cured by
eradication of H. pylori infection.35-37
1+
Early endoscopy
Studies show that early upper GI endoscopy may be more effective than empirical prescribing
but the benefit is small, not significant and unlikely to be cost-effective. 38-40
H. pylori “test and endoscope”
This strategy involves performing a non-invasive H. pylori test and performing endoscopies only
on those patients with a positive result. This approach is no more effective, or less costly, than
selective endoscopy at the general practitioner’s discretion.38,40
H. pylori “test and treat”
This strategy involves performing a non-invasive H. pylori test, eradicating the infection in all
those testing positive and providing symptomatic treatment for those who test negative. Five
randomised trials have compared the non-invasive H. pylori test and treat strategy with upper GI
endoscopy. One of the trials randomised those with a positive non-invasive H. pylori test to
endoscopy versus H. pylori eradication therapy without further investigation 41 and another trial
randomised patients with a negative non-invasive H. pylori test to endoscopy versus symptomatic
treatment.42 A further three trials randomised patients at the point of presentation to endoscopy
versus non-invasive H. pylori testing.43-45 Each of the five trials came to the same general conclusion,
that non-invasive H. pylori testing was as effective as endoscopy in determining the management
1++
of dyspepsia.41-45
The above strategy involves eradicating H. pylori infection in dyspeptic patients without underlying
ulcer disease. There may be advantages and disadvantages related to this.46,47
Advantages include: 46,47
n symptomatic benefit from eradicating the infection in a small subgroup of patients with
functional dyspepsia
n reducing the risk of subsequent ulcer disease
n removing a risk factor for gastric cancer
n removing concerns about potential adverse interactions between the infection and the
subsequent long term use of proton pump inhibitors.
Disadvantages include:48
n potential risks from wider use of antibacterial therapy (eg resistance and complications)
n possibility of inducing reflux oesophagitis following eradication of strains of H. pylori.
One recent cross sectional study proposed that the H. pylori test and treat strategy should be
limited to dyspeptic patients whose history and symptoms indicated a high risk of underlying
ulcer disease.49 This strategy reduces the number of patients receiving H. pylori eradication
therapy without underlying ulcer disease but has the disadvantage of depriving a substantial
proportion of ulcer patients of curative therapy.

8
 3 MANAGEMENT OF UNCOMPLICATED DYSPEPSIA

It is recognised that the balance of advantages over disadvantages for the H. pylori test and treat
strategy will be less in populations with a low prevalence of H. pylori infection and related
ulcer disease. The prevalence of H. pylori infection in the Scottish population with dyspepsia is
approximately 40% at present and more than 20% of these patients have underlying ulcers.45 The
prevalence of H. pylori infection within any population increases with age and with lower socio-
economic status.50 1++

The H. pylori test and treat strategy is as effective and safe as endoscopy in determining the
management of patients less than 55 years old with uncomplicated dyspepsia. In view of the
fact that the H. pylori test and treat strategy is both non-invasive and cheaper than upper GI
endoscopy,38,39,41-49 it is considered to be the preferred strategy. Facilities for non-invasive H.
pylori testing should therefore be widely available.

A A non-invasive H. pylori test and treat strategy is as effective as endoscopy in the initial
management of patients with uncomplicated dyspepsia who are less than 55 years old.

3.2 PATIENTS OVER 55 YEARS OLD

Current guidelines advise that older patients (age ranges used in studies vary between over 45 to
over 55 years) with uncomplicated dyspepsia should be investigated using early upper GI
endoscopy.18,19,28,51,52 The phrase “recent onset” is also frequently used to indicate a need for more
urgent investigation of dyspepsia. An examination of the literature does not produce evidence to
support these claims.

3.2.1 MANAGEMENT
This guideline has cited substantial evidence supporting the use of non-invasive H. pylori testing
in place of upper GI endoscopy in determining the management of patients less than 55 years old
presenting with uncomplicated dyspepsia (see section 3.1). The question as to whether this
recommendation can be extrapolated to include patients presenting with uncomplicated dyspepsia
who are more than 55 years old has not yet been directly addressed by an RCT. There are,
however, recent studies comparing the outcome of non-invasive management versus early upper
GI endoscopy for this group of patients where no upper age limit was defined for inclusion in the
study.
An RCT studied 500 Danish patients between the age of 18 and 88 years with recent onset
uncomplicated dyspepsia with or without concomitant reflux symptoms. The patients were 1+
randomised to either H. pylori test and treat policy or early endoscopy and followed up for one
year. The test and treat policy was as efficient and as safe as prompt endoscopy.43
A Canadian general practice controlled trial randomised 294 H. pylori positive patients with at
least three months of uninvestigated dyspepsia (age range 18 to 82 years) to either H. pylori
eradication therapy or omeprazole 20 mg for seven days.53 The test and treat strategy showed 1+
significant symptomatic benefit after 12 months follow-up. Two patients died of cancer during
the study, one from a brain tumour and one from inoperable oesophageal cancer that presented
with dysphagia three months into follow-up.
A small Dutch study of 80 patients with recent onset uncomplicated dyspepsia (35 were more
than 45 years of age) randomised to empirical omeprazole therapy followed by H. pylori test and 1-
eradicate for symptom relapse versus early endoscopy concluded that after one year the empirical
strategy was just as effective as the prompt endoscopy strategy.54
The available evidence does not justify an age limit for a different management of patients with 2++
uncomplicated dyspepsia.

C A non-invasive H. pylori test and treat policy may be as appropriate as early endoscopy
for the initial investigation and management of patients over the age of 55 years presenting
with uncomplicated dyspepsia.

þ Referral for assessment should be considered for patients over 55 years old with
uncomplicated dyspepsia whose symptoms persist after initial management with the H.
pylori test and treat strategy.

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DYSPEPSIA

4 H. pylori tests
Two aspects about diagnostic testing for H. pylori must be considered to evaluate its accuracy
(that is, the ability of a diagnostic test to produce correct test results). The first is how well the
tests detect H. pylori infection in patients (sensitivity) and the second is how well the test
correctly identifies patients who do not have the infection (specificity). The selection of the
appropriate test for H. pylori infection should also be based on the prevalence of H. pylori
infection in the community (see Annex 2). The major groups of non-invasive tests are breath
tests, serological tests and faecal antigen tests.

4.1 BREATH TESTS

Since their introduction, both 13C and 14C urea breath tests (CUBTs) have been used widely in
patients both before and after H. pylori eradication therapy.55 An RCT has shown that, compared
to an accepted gold standard, accuracy was 94.8% before antimicrobial therapy and 95.4% 1++
afterwards.56 False negative results may occur and CUBT should not be performed within two
weeks of proton pump inhibitor (PPI) or within four weeks of antibiotic therapy.57

4.2 SEROLOGICAL TESTS

4.2.1 HOSPITAL BASED TESTS

Enzyme-linked immunosorbent assays (ELISAs) are the most commonly used serological method
for the detection of H. pylori infection, and a large number of commercial ELISA kits are now
available. Evaluation of test kits is usually made by using an appropriate “gold standard” consisting
of a combination of culture, histology, CLO-test and breath testing as no technique is 100%
sensitive or specific for detecting H. pylori infection. Studies of the sensitivity and specificity of
these tests have produced inconsistent results. One meta-analysis of 21 studies showed sensitivity
and specificity of 85% and 79% respectively and concluded that there is little evidence to 1+
suggest that any of the common commercial serological kits is more accurate than another and
that the overall accuracy of these kits may not be adequate for clinical decision-making in all
patient groups. 58
The Medical Devices Agency also evaluated a large number of ELISA tests.59 588 samples of sera
were evaluated with 16 different tests. The overall accuracy of the assays averaged 78% (range
68-82%) for all sera. A further meta-analysis gave broadly similar results but reached no conclusions
as to whether the use of kits was appropriate.60
A large review, using different methodology, contradicted these results. In a comparison of 36
different commercially available H. pylori serology kits on 26,812 patients the median sensitivity
and specificity were 92% and 83%.61 Kits measuring IgA, IgG, and IgM simultaneously or IgA 2+
alone did not perform as well as those measuring only IgG antibodies. This review concluded
that the overall performance of commercially available serology kits is sufficiently accurate as a
means of diagnosing H. pylori infection.

4.2.2 NEAR PATIENT TESTS

Near patient tests are whole blood tests developed to provide a rapid diagnosis of H. pylori
infection in the clinic. They are technically simple to perform, most of those currently used are
one-step tests that require a drop of whole blood, but others require separation of serum. Recent
evidence accumulated from 3,805 patients in eight studies suggests that these tests have
2+
considerably lower sensitivity and specificity than originally assumed. 62 The mean sensitivity
(weighted for number of patients studied) was 71.1% and the specificity was 87.6%. Studies of
the accuracy of several new rapid whole blood test kits have shown a sensitivity and specificity
of 82-95% and 83-94%, respectively, with positive and negative predictive values of 89-91%
and 93-97%.63,64

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 4 H.PYLORI TESTS

4.3 FAECAL ANTIGEN TESTS

Enzymatic immunoassays that detect the H. pylori antigen in stool specimens are available. A
large number of patients have been evaluated using the stool antigen test for the initial diagnosis
of H. pylori infection and the mean sensitivity and specificity has been calculated at 93.1% and 2+
92.8% respectively.62 Caution is needed following eradication therapy as omeprazole significantly
reduces faecal antigen values, resulting in a decreased accuracy.65,66

4.4 CHOOSING A TEST

4.4.1 PRE-TREATMENT DIAGNOSIS

In the primary care setting, the ELISA (hospital based serology) and CUBT have been shown to be
equally effective in excluding the diagnosis of infection with H. pylori in patients who have had
dyspeptic symptoms for at least two weeks.67 Whole blood tests produced inferior results.67 A
multicentre study suggests that the faecal antigen test is comparable with the CUBT in the initial
detection of H. pylori infection.68 2++

In trials that compare the use of endoscopy with H. pylori test and treat, some have used CUBT
and others have used serology testing.43,45 Outcomes from both types of test have been similar. In
clinical practice therefore, the difference in accuracy between the two tests may not be
significant.43,45

4.4.2 POST-ERADICATION TESTING

CUBT has been shown to be effective in detecting eradication of H. pylori infection. Seven
studies using CUBT alone as a comparison found the sensitivity and specificity of both faecal
antigen testing and CUBT was approximately 90%. There has however been some variability in
the results of the faecal antigen test in the post-therapy setting so at present faecal antigen testing
2++
is not comparable to CUBT in the post-therapy setting.68
Serology may be used for monitoring the efficacy of H. pylori eradication therapy but both pre-
and post-treatment samples must be analysed simultaneously and it is necessary to wait a minimum
of three months following eradication therapy before repeating the test.69

B The CUBT or faecal antigen tests are recommended for the pre-treatment diagnosis of H.
pylori infection in the community. Less accurate, hospital-based serology tests have a
place within the non-invasive test and treat strategy.

B CUBT is the recommended test to determine whether H. pylori has been successfully
eradicated.

þ The CUBT should not be performed within two weeks of proton pump inhibitor therapy
or within four weeks of antibiotic therapy as false negative results may occur.

11
DYSPEPSIA

5 Management of functional dyspepsia

5.1 INTRODUCTION
Functional dyspepsia is the recommended term to denote dyspepsia for which no causal organic
disease has been identified (see section 1.3). As it is a diagnosis of exclusion, clinical judgement
must be exercised in the case of each patient to decide how much investigation is appropriate
before the diagnosis may reasonably be applied. However, when taking these decisions, physicians
should bear in mind that functional dyspepsia is more common than dyspepsia caused by underlying
organic disease and that for most patients under 55 years of age, invasive investigation is not
necessary before a working diagnosis of functional dyspepsia may be made.
Having made a diagnosis of functional dyspepsia, the clinician will wish to consider treatment
options. Part of this consideration requires assessment of what has triggered the patient’s
consultation: consultation with dyspepsia is more probable if the patient is anxious, depressed,
stressed, has severe symptoms or is worried that the symptoms are signals of a life threatening
illness.70,71 Such concerns, if present, need to be addressed.
Not all patients with functional dyspepsia seek active treatment: for some, it may be sufficient to
explain the condition and give reassurance that no serious disease has been found. For others,
however, treatment may be warranted. Clinicians should remember that although by definition
the causes and mechanisms responsible for functional dyspepsia symptoms are unknown, there
is reason to believe that several different derangements of upper GI motor and sensory function
may be implicated. This raises the possibility that symptom alleviation will need different
treatments in different patients. Inevitably, clinical trials that have considered functional dyspepsia
as a single entity and assessed the effect of one therapy do not address this possibility.

þ A working diagnosis of functional dyspepsia is likely to be appropriate for most patients

with dyspepsia who have no alarm features and in whom initial investigations are negative.
Repeated or increasingly invasive investigation in pursuit of an organic cause for the
symptoms may be both futile and counter-productive.

5.2 LIFESTYLE ADVICE

Eleven observational studies and surveys which consider functional dyspepsia and lifestyle factors
were identified. Most of the published literature is based upon patients’ self-reported experiences,
and is subject to the methodological criticisms associated with this type of data collection. One
survey indicated that poor diet, stress and caffeine are perceived as the most common causes of
GI symptoms.72 Another survey found that 80% of dyspeptic patients reported that avoidance of
specific foods helped relieve dyspeptic symptoms.73 Irregular eating patterns have been identified
in functional dyspepsia, and this has been linked to stress, but causal effect is not clear.73,74 A
wide variety of food intolerances have been reported,75 many of which patients are able to
identify and self-treat without recourse to professional advice. Caffeine, alcohol and smoking
have been reported as factors in the exacerbation of dyspeptic symptoms. 75-77 Other studies have
found no association between these factors and dyspepsia.78-80
There is no clear evidence to support a recommendation on the role of diet and lifestyle in the
management of functional dyspepsia.

þ Patients with functional dyspepsia should be advised to stop smoking, and to exclude, or
take only moderate amounts of alcohol and caffeine, in line with general healthy lifestyle
recommendations.

þ If patients have adopted extreme dietary measures, they should be encouraged to follow a
balanced diet to minimise the risk of nutritional deficiencies.

12
 5 MANAGEMENT OF FUNCTIONAL DYSPEPSIA

5.3 PSYCHOLOGICAL TREATMENTS

The correlation of psychosocial problems with functional dyspepsia suggests that psychosocial
interventions may have a role in treatment.81 At the present time however there is no strong
generalisable evidence on the benefit of this kind of intervention.82
It is not possible to make a recommendation on the role of psychosocial interventions in the
management of functional dyspepsia.

5.4 PHARMACOLOGICAL TREATMENTS

5.4.1 INTRODUCTION
Not all patients with functional dyspepsia require drug treatment. However, when prescription
of medication is being contemplated, clinicians should appreciate that in functional dyspepsia,
as in all other functional GI disorders, there is a substantial placebo response to therapy that
constrains the interpretation of apparent treatment effectiveness in individual patients. No drug
therapies have been found to have a high success rate in the treatment of functional dyspepsia
though it should also be acknowledged that there is no scientific basis for supposing that all
patients with functional dyspepsia should respond to the same pharmacological approach.
Heterogeneity of presenting symptoms is evident in functional dyspepsia, heterogeneity of
underlying mechanisms is suspected and there is some evidence suggesting different therapies
may be effective for different patients. Conclusive evidence of this is lacking, however. The
available information concerning drug therapy for functional dyspepsia all relates to relatively
short term treatment periods and consequently drug treatment should usually be given on a short
term basis only.

þ Medication is not necessary for all patients with functional dyspepsia. When medication
is given, short term treatment, intermittent if necessary, is likely to be more appropriate
than long term continuous therapy.

5.4.2 H. pylori ERADICATION

Four placebo controlled double blind RCTs compared effective eradication regimens to treatment
regimens ineffective against H. pylori in patients with functional dyspepsia.83-86 All four trials
assessed symptoms using validated symptom scores at 12 months and excluded patients with
confirmed peptic ulcer disease or oesophagitis at time of enrolment. Three of the four studies
recruited patients with predominant symptoms of upper abdominal pain or discomfort (ROME II
definition10).83,84,86 One study also included patients with predominant symptoms of heartburn,
and this was the only trial to demonstrate a significant benefit for H. pylori.85 A significant
benefit remained after heartburn predominant patients were excluded (23% response compared
to 10% in control group; p=0.02). This study was conducted in Glasgow and may therefore be
most relevant to the Scottish population.
Three meta-analyses on the effect of H. pylori eradication on functional dyspepsia have differed
in their conclusions.87-89 1++
The earliest review aggregated the results from the four studies quoted above and concluded that
the results could not confirm or exclude benefit.89 The most recent meta-analysis concluded that
there is no significant benefit for eradication therapy based on the results from trials published
up to December 1999.88
The largest meta-analysis was based on nine trials that evaluated symptoms in 2,541 patients at
three to 12 months.87,90 Trials published up to May 2000 were included in this meta-analysis
although some of these were published in abstract form and authors provided further information.
There was a significant (9%) reduction in the number of patients with functional dyspepsia
remaining dyspeptic after eradication.87,90
On the basis of this last meta-analysis, 9% of functional dyspepsia patients who test positive for
H. pylori benefit from eradication.87,90 This effect can be described in terms of the number
needed to treat (NNT) of 15 (ie 15 H. pylori positive functional dyspepsia patients will need to
be given eradication therapy for benefit to be obtained in one).87,90

13
DYSPEPSIA

Overall because about 50% of patients with functional dyspepsia will be positive for H. pylori,
eradication treatment will be symptomatically beneficial for slightly less than 5% of all functional 1+
dyspepsia patients.

A H. pylori eradication therapy should be considered in the management of functional

dyspepsia.

5.4.3 ACID SUPPRESSION

The true benefit of acid suppression therapy in functional dyspepsia can be difficult to quantify
for the following reasons:
n few trials of medication have defined functional dyspepsia according to the Rome II definition10
and excluded patients with predominant symptoms of acid reflux
1+
n there is a high placebo response to treatment. 91
Acid suppression therapy can be separated into histamine receptor antagonists (H2RAs) and proton
pump inhibitors (PPIs) and the results of treatment with either in functional dyspepsia are broadly
similar.
One high quality RCT has shown a significant benefit from omeprazole over placebo of 10%
(38% compared with 28%).91 This benefit increased in patient groups who had coexistent heartburn
or epigastric pain, while no benefit was obvious in the patients with early satiety and nausea. A 1++
similar beneficial effect was demonstrated with H2RAs in patients with epigastric pain in trials
using cimetidine 92 and ranitidine.93 There are no meaningful trials comparing the effects of PPIs
and H2RAs.
Response to treatment has been associated with decreased health care costs and an improvement
in health related quality of life. It has been suggested that patients who are more likely to gain
longer term benefit may have an identifiable response after only one week of treatment.94,95 1+
A small number of patients with functional dyspepsia (10%) may benefit from acid suppression
therapy. A response is more likely in those with co-existent heartburn.

B A trial of acid suppression therapy may be considered in the management of functional

dyspepsia.

5.4.4 ANTACIDS
No evidence was identified on the efficacy of antacids in the management of functional dyspepsia.

5.4.5 PROKINETICS
Domperidone or metoclopramide are the prokinetic drugs still prescribed for patients with
functional dyspepsia. They have different pharmacological properties from cisapride, the licence
for which has been suspended in the UK.
Four meta-analyses of RCTs have explored the role of prokinetic pharmacological therapies in
functional dyspepsia 96-99 and three of them considered domperidone and metoclopramide.97-99
All three meta-analyses showed significant short term (2 to 12 weeks) improvement in global 1-
symptoms over placebo, but they included only a few trials and the combined number of patients
covered in each meta-analysis is small. Since these trials are few in numbers, small scale and
heterogeneous the positive results should be regarded with caution.
Although the trials of domperidone and metoclopramide showed significant improvement of
global symptoms of dyspepsia over placebo in the short term, this positive effect may stem from
bias due to the small number of patients involved in the trials.96-99
In view of the problems with the quality of the trials involved, the value of prokinetic drugs is
uncertain. It is not possible to make a recommendation on the role of prokinetics in the
management of functional dyspepsia.

14
 5 MANAGEMENT OF FUNCTIONAL DYSPEPSIA

5.4.6 CYTOPROTECTIVES
Cytoprotective agents include chelates and complexes, such as bismuth chelate and sucralfate
and the prostaglandin analogue, misoprostol. Sucralfate acts by protecting the gastric mucosa,
misoprostol has both antisecretory and protective properties.
n Chelates and complexes
Three RCTs were identified however only one study was considered methodologically sound and
this study did not include a placebo group.100 The two methodologically poor studies testing the
efficacy of sucralfate produced conflicting results.101,102 One study showed no effect against
placebo101 whilst the other was suggestive of benefit but no placebo group was included in this 1-
study.102
n Prostaglandin analogues
One study found no difference in efficacy between misoprostol and placebo but did identify
increased side effects in the misoprostol treatment group.103
It is not possible to make a recommendation on the role of cytoprotectives in the management
of functional dyspepsia.

5.4.7 ANTIDEPRESSANTS
A useful role for antidepressants in the management of idiopathic pain syndromes is often assumed.
There is some evidence for the role of antidepressants in functional bowel disorders, but no clear
evidence of benefit in functional dyspepsia.104-106
It is not possible to make a recommendation on the role of antidepressants in the management
of functional dyspepsia.

5.5 INFORMING PATIENTS

When a diagnosis of functional dyspepsia has been made, it may be helpful to explain to patients
that:
n No disease or abnormality has been found and this should be taken as reassuring.
n Functional dyspepsia is very common and is not itself serious, though the discomfort, pain,
distension and fullness which are perfectly genuine, are often unpleasant and bothersome.
n The definitive causes of functional dyspepsia are not known. It is known that, when compared
with asymptomatic individuals, the stomach in many patients with functional dyspepsia
empties more slowly after meals. There is also evidence of heightened visceral sensation in
many functional dyspepsia patients who experience discomfort when the stomach is distended
to a degree that does not cause discomfort in healthy subjects.
n Functional dyspepsia is not a condition caused by gastric hypersecretion: acid secretion is
usually normal.
n Functional dyspepsia is not usually caused by stress, anxiety or depression but these factors
may worsen the symptoms and diminish a patient’s ability to cope with them.
n Functional dyspepsia is not caused by sensitivity or allergy to dietary constituents. However
functional dyspepsia sufferers, like everyone else, should avoid foods that upset them. This
apart, no specific dietary pattern or restriction is required.
n Drug treatment is not very effective in functional dyspepsia but a minority of patients are
helped by some medications.

15
DYSPEPSIA

5.6 PROGNOSIS IN FUNCTIONAL DYSPEPSIA

Little information is available that describes the long term outcome of patients with functional
dyspepsia in the United Kingdom. In a study of Swedish patients with functional dyspepsia,
about two thirds still had dyspeptic symptoms after ten years of follow up.107 Many of them had
undergone repeat GI investigations during the ten years, though new organic disease was rarely
found. In common with other studies108,109 many of these patients with functional dyspepsia
exhibited symptoms that overlapped with those of irritable bowel syndrome. In a small proportion
of patients, symptom profiles may actually change with time from the one condition to the
other.110

16
 6 IMPLEMENTATION AND AUDIT

6 Implementation and audit

6.1 LOCAL IMPLEMENTATION
Implementation of national clinical guidelines is the responsibility of local NHS organisations
and is an essential part of clinical governance. It is acknowledged that not every guideline can be
implemented immediately on publication, but mechanisms should be in place to ensure that the
care provided is reviewed against the guideline recommendations and the reasons for any differences
assessed and, where appropriate, addressed. These discussions should involve both clinical staff
and management. Local arrangements may then be made to implement the national guideline in
individual hospitals, units and practices, and to monitor compliance. This may be done by a
variety of means including patient-specific reminders, continuing education and training, and
clinical audit.

6.2 KEY POINTS FOR AUDIT

In order for the audit of this guideline to be efficient the information used should be derived
from routinely collected data. It is recognised that due to gaps in the data available there may be
difficulties doing this. It is recommended that the national systems currently in place, such as
the Scottish Clinical Information Management Programme (http://www.ceppc.org/scimp/), be
used to ensure appropriate diagnostic codes for functional dyspepsia, investigations and treatment.
The use of stand-alone systems is discouraged, as they require double entry of data. Audit could
take place on three levels: national, regional/local and practice level. The following are
recommended areas for audit.
National level
n stage shift in presentation of upper GI cancer
n use of a national referral form
Regional or local level
n the % of patients undergoing H. pylori test and treat before referral
n the % of patients referred for GI endoscopy who are less than 55 years of age without alarm
features
n the % of patients undergoing upper GI endoscopy who are less than 55 years of age with
alarm features
Practice level
n prescribing of acid suppression therapy for functional dyspepsia
n success rate of primary H. pylori eradication
n the number of patients managed with a diagnostic code of functional dyspepsia.

6.3 RECOMMENDATIONS FOR RESEARCH

The literature review integral to the SIGN guideline process enabled the guideline development
group to highlight areas of research need based on the following principles:
n the issues should be related to the guideline and/or its implementation
n information gained should be of value in the management of dyspepsia
n the questions should be answerable
The following areas for further research are listed in order of priority:
n A comparative study of the pathological stage and presenting symptoms of upper GI cancers
before and after the implementation of this guideline. This is required to demonstrate that
early, treatable cancer is not missed by managing patients under 55 years of age presenting
with uncomplicated recent onset dyspepsia without endoscopy. In any research studies the
definition of ‘recent-onset’ should be defined.

17
DYSPEPSIA

n The efficacy and safety of the “test and treat” policy versus early upper GI endoscopy in the
management of patients over 55 years of age presenting with recent onset uncomplicated
dyspepsia.
n The management of functional dyspepsia with reference to lifestyle management, patient
education, psychosocial interventions and pharmacological intervention.
n Definition of the age related risk of having upper GI cancer associated with a presentation of
dyspepsia along with one of the commonly quoted alarm features
n A health economic study exploring whether short term increases in costs and work load
related to tests of H. pylori status and drugs involved in H. pylori eradication are related to
any possible medium to long term savings from reductions in endoscopic investigations and
drugs to manage the symptoms of dyspepsia.
n A study to explore whether wider use of antibacterial therapy and eradication of H. pylori are
associated with adverse effects.

6.4 RESOURCE IMPLICATIONS

The economic consequences of implementing this guideline are likely to include the following:
n an increase in the need for tests of H. pylori status
n an increase in the cost of drugs involved in H. pylori eradication regimes
n a reduction in the need for endoscopic investigation of the GI tract, especially in younger
patients
n a reduction in the use of drugs to manage the symptoms of dyspepsia.
The economic consequences are difficult to quantify precisely at the local level. Impact will
depend on the following factors:
n the age of the population
n the prevalence and incidence of GI problems
n the existing management practice
n the availability of different investigations.
The following points form the suggested background to local budget impact calculations:
n There are short-term work implications for GPs in taking breath test samples, starting treatment
and reviewing progress but these should be offset by medium- to long-term savings as cases
are resolved more quickly.
n Giving a CUBT sample is a straightforward procedure that can be done either at a brief
hospital visit or by sending in a sample to the hospital for analysis. Analysis of the CUBT
requires specialist equipment and staff however and the capacity of local hospitals to manage
CUBT samples should be kept under review.

18
 7 PATIENT INFORMATION

7 Patient information
7.1 EXAMPLE PATIENT INFORMATION LEAFLET
The following points may be incorporated into local information materials for patients with
dyspepsia.
What is Dyspepsia?
Dyspepsia is a general term used to describe discomfort or pain in the upper abdomen. It can be
called indigestion. Usually it disappears quite quickly but sometimes it is more persistent.
What can you do about it?
You can go to your chemist who will advise on something to take to relieve the pain. If it
continues to trouble you, you should go to see your family doctor.
What can the doctor do?
Dyspepsia can sometimes be caused by any one of several diseases so your doctor will try to find
out if you have one of these.
In recent years a bacterium (called Helicobacter pylori) has been shown to contribute to dyspepsia
in some patients and your doctor may decide to check whether it is present. This can be done by
taking a blood or stool sample or, with a breath-test (a simple procedure that involves blowing
into small test tubes). While waiting for results, your doctor may prescribe a drug to relieve the
pain. If the bacterium is found your doctor may prescribe antibiotics to get rid of it.
If you have other symptoms along with the stomach pain your doctor may consider it is best for
you to see a specialist in hospital. At the hospital it may be decided to have a look inside using
an endoscope, a camera that is guided through the mouth to the stomach. Depending on what
the specialist sees, further treatment may be suggested. If there is no bacterium present and/or
nothing untoward can be seen in the stomach this is good news.
In 70% of all patients with dyspepsia no disease can be found. This means it is not a serious
complaint but it can still be painful.
Although no medication has proved to be very effective it may be that your doctor will suggest
and prescribe one which may help. He or she will also discuss your diet and lifestyle with you
and may offer the following suggestions to improve things.
n giving up smoking
n reducing the amount of alcohol and coffee or tea you drink
n avoiding foods which trigger your indigestion
n eating a balanced, healthy diet
n reducing stress in your life.
A copy of the SIGN Dyspepsia guideline and a patient version of the guideline can be downloaded
from the SIGN web site at www.sign.ac.uk, where further information for patients is available.

7.2 SOURCES OF FURTHER INFORMATION

British Society of Gastroenterology
3 St Andrews Place, Regent’s Park, London. NW1 4LB
Tel: 020 7387 3534 Fax: 020 7487 3734
bsg@mailbox.ulcc.ac.uk
www.bsg.org.uk/

19
DYSPEPSIA

8 Development of the guideline

8.1 INTRODUCTION
SIGN is a collaborative network of clinicians, other health care professionals and patient
organisations funded by the Scottish Executive Health Department. SIGN guidelines are developed
by multidisciplinary groups using a standard methodology based on a systematic review of the
evidence. Further details about SIGN and the guideline development methodology are contained
in “SIGN 50: A guideline developer’s handbook”, available at www.sign.ac.uk

8.2 THE GUIDELINE DEVELOPMENT GROUP

Ms Angela Timoney Consultant in Pharmaceutical Public Health,
(Chairman) Kings Cross Hospital, Dundee
Mr Colin MacKay Consultant Surgeon, Victoria Infirmary, Glasgow
(Secretary)
Dr Robin Balfour General Practitioner, Murrayfield Medical Practice, Edinburgh
Mrs Janice Bancroft Staff Nurse, Thoracic Unit,Hairmyres Hospital, East Kilbride
Mr Graham Bell Patient Representative, Penicuik
Ms Anne Crozier GI Specialist Nurse, Ninewells Hospital, Dundee
Dr Michael Gray General Practitioner, Ancrum Medical Centre, Dundee
Dr Bob Heading Consultant Physician, Centre for Liver and Digestive Disorders,
Royal Infirmary, Edinburgh
Mr Robin Harbour Quality and Information Director, SIGN
Dr Stuart Hislop Consultant Gastroenterologist,
Royal Alexandra Hospital, Paisley
Mrs Phoebe Isard Patient Representative, Edinburgh
Ms Moira Kinnear Principal Pharmacist, Western General Hospital, Edinburgh
Professor Kenneth McColl Director of Gastroenterology, Western Infirmary,Glasgow
Dr John Murchison Consultant Radiologist, Royal Infirmary, Edinburgh
Mr William R Murray Consultant Surgeon, Lister Department of Surgery,
Glasgow Royal Infirmary
Dr Stephanie Norris Medical Director, North Cumbria Acute Hospitals, Carlisle
Mrs Fiona Phillips Senior Dietitian, Western General Hospital, Edinburgh
Dr Rita Rigg General Practitioner, Hermitage Medical Practices, Edinburgh
Dr Jack Taylor General Practitioner, Aboyne Medical Practice, Aberdeenshire
Ms Joanne Topalian Programme Manager, SIGN
Dr Craig Williams Consultant Medical Microbiologist,
Yorkhill NHS Trust, Glasgow
The membership of the guideline development group was confirmed following consultation
with the member organisations of SIGN. Declarations of interests were made by all members of
the guideline development group. Further details are available from the SIGN Executive.
SIGN is also grateful to the following for contributing to particular sections of this guideline:

Dr Pablo Alonso General Practitioner Assistance with the algorithm

Iberoamerican Cochrane (see page 4)
Centre, Barcelona

Dr Andrew Walker Senior Lecturer in Health Drafting section 6.4

Economics, Robertson
Centre for Biostatistics,
University of Glasgow.

20
 8 DEVELOPMENT OF THE GUIDELINE

8.3 SYSTEMATIC LITERATURE REVIEW

The evidence base for this guideline was synthesised in accordance with SIGN methodology. A
systematic review of the literature was carried out using an explicit search strategy devised by the
SIGN Information Officer in collaboration with members of the guideline development group.
Searches were restricted to systematic reviews, meta-analyses, RCTs, and longitudinal studies.
Internet searches were carried out on the Web sites of the Canadian Practice Guidelines Infobase,
the New Zealand Guidelines Programme, the UK Health Technology Assessment Programme,
the US National Guidelines Clearinghouse, and the US Agency for Healthcare Research and
Quality. Searches were also carried out using Google and OMNI search engines, and all suitable
links followed up. Database searches were carried out on Cochrane Library, Embase 1990 to
2000, and Medline 1990 to 2000. Embase and Medline searches were later extended back to
1980 in relation to specific questions where more recent evidence was lacking. All searches were
later updated to 2001.
An independent information specialist reviewed the search strategies. The Medline version of the
main search strategies is available on the SIGN Web site, in the section covering supporting
material for published guidelines. The main searches were supplemented by material identified
by individual members of the development group. All selected papers were evaluated using
standard methodological checklists before conclusions were considered as evidence.

8.4 CONSULTATION AND PEER REVIEW

8.4.1 NATIONAL OPEN MEETING

The national open meeting is the main consultative phase of SIGN guideline development, at
which the guideline development group presents their draft recommendations for the first time.
The national open meeting for this guideline was held in October 2001 and was attended by all
of the key specialties relevant to the guideline. The draft guideline was also available on the
SIGN web site for a limited period at this stage to allow those unable to attend the meeting to
contribute to the development of the guideline.

8.4.2 SPECIALIST REVIEW

The guideline was also reviewed in draft form by a panel of independent expert referees, who
were asked to comment primarily on the comprehensiveness and accuracy of interpretation of
the evidence base supporting the recommendations in the guideline. SIGN is very grateful to all
of these experts for their contribution to this guideline.
Dr Pablo Alonso Iberoamerican Cochrane Centre, Barcelona
Professor John Atherton University Hospital, Nottingham
Mr Charles Auld Consultant Surgeon, Dumfries & Galloway NHS Trust
Dr James Beattie Director of Guidelines, Royal College of General Practitioners
Dr Alan Begg General Practitioner, Montrose
Ms Janice Birrell Scottish Executive, Health Planning and Quality Division
Professor Peter Bytzer Department of Medical Gastroenterology,
Glostrup University Hospital, Denmark
Dr Anthony Chapman Consultant Radiologist, St James Hospital, Leeds
Dr Michael Cornbleet Senior Medical Officer, Scottish Executive, Edinburgh
Dr Xavier Emmanuel Medical Microbiologist, University of Edinburgh
Professor David Foreman Coordinating Editor, Cochrane UGPD Group,
University of Leeds
Professor Ian Gilmore Registrar, Royal College of Physicians, London
Dr Barclay Goudie General Practitioner,Westgate Health Centre, Dundee
Dr Colin Hunter National Co-ordinator for Primary Care, Edinburgh
Dr Emily Kennedy Pharmacist, Boots, Dumfries
Dr Alistair Leanord Consultant Microbiologist, Monklands Hospital, Airdrie
Mr Donald MacDonald Nurse Endoscopist, St Johns Hospital, Livingston
Ms Sheena MacGregor Lead Pharmacist, Dundee LHCC

21
DYSPEPSIA

Mr Ron MacLeod Associate Director of Nursing,

Dr George Masterton
Dr Alan Merry
Professor Paul Moayyedi
Mr Kenneth Park
Dr Andrew Power
Ms Patricia Purton
Dr Alan Shepherd
Dr Hamish Simpson
Dr Philip Shorvon
Mr Alistair Thompson
Dr Sander Veldhuyzen
Van Zanten
Dr Marten Walker
Dr Hugh Whyte
Ms Kerry Yuill
Tayside Primary Care NHS Trust
Consultant Psychiatrist, Royal Infirmary of Edinburgh
General Practitioner, Ardrossan
Professor of Gastroenterology Health Services Research,
City Hospital NHS Trust, Birmingham
Consultant Surgeon, Aberdeen Royal Infirmary
Head of Medicines Management Team,
Gartnavel Royal Hospital, Glasgow
Director, Royal College of Midwives, Edinburgh
Consultant Physician and Gastroenterologist,
Perth Royal Infirmary
General Practitioner,West Kilbride, Ayrshire
Consultant Radiologist, Central Middlesex Hospital, London
Consultant Surgeon, Ninewells Hospital, Dundee
Consultant Gastroenterologist, Dalhousie University, Halifax, Canada
General Practitioner, Stornoway
Senior Medical Officer, Primary Care Directorate,
Scottish Executive
Dietitian, Royal Infirmary, Edinburgh

8.4.3 EDITORIAL GROUP

As a final quality control check, the guideline is reviewed by an Editorial Group comprising the
relevant specialty representatives on SIGN Council to ensure that the peer reviewers’ comments
have been addressed adequately and that any risk of bias in the guideline development process as
a whole has been minimised. The Editorial Group for this guideline was as follows:
Dr David Alexander British Medical Association Scottish General Practice Committee
Dr Douglas Harper Royal College of Surgeons of Edinburgh
Professor Gordon Lowe Chairman, SIGN; Co-Editor
Dr Lesley MacDonald Faculty of Public Health Medicine
Ms Fiona McMillan Lead Pharmacist, North Glasgow NHS Trust
Dr Safia Qureshi Programme Director, SIGN
Dr Bill Reith Chairman, Royal College of General Practitioners, Edinburgh
Dr Sara Twaddle Director, SIGN; Co-Editor

22
 ANNEX 1

Annex 1
SIGN guideline number 7 produced in 1997 and the update to this published in 1999 each
contained a table detailing the evidence for H. pylori eradication in duodenal ulcer, gastric ulcer
and gastric lymphoma.1,2 This evidence has been updated by the dyspepsia guideline development
group (see below).

1.1 WHICH PATIENTS WITH H. PYLORI SHOULD RECEIVE ERADICATION THERAPY?

Grade of
Eradicate? Level of Evidence
Recommendation
Duodenal ulcer111 Yes A 1+
Gastric ulcer111
Yes A 1+
Low grade gastric MALT
Yes B 2+
Lymphoma112,113

1.2 H. PYLORI ERADICATION OPTIONS

The evidence base for H. pylori eradication options has also improved since the previous SIGN
guidelines were published. An update of the numbers of medicines to use, the duration of
treatment and the influence of known antimicrobial resistance are given below.
Dual therapies eradicate H. pylori from fewer people than triple therapies114

n Triple therapies including PPIs and two antibiotics give consistently high eradication rates
n Metronidazole or clarithyromycin resistance established by laboratory testing is associated
with reduced eradication of H. pylori by regimens including these antibiotics
n Two weeks of triple therapy versus a one week regimen does not increase the eradication rate.

23
DYSPEPSIA

Annex 2
Selection of Diagnostic Tests
When considering how useful diagnostic tests are in differentiating people with disease from
healthy people reference is frequently made to the sensitivity, specificity, positive predictive
value, and negative predictive value of a test. These terms are defined as follows:

Test Positive Test Negative

Patient with disease True Positive (TP) False Negative (FN)
Normal patient False Positive (FP) True Negative (TN)

From this the following can be calculated:

Value Calculation
Sensitivity TP/(TP+FN)
Specificity TN/(TN+FP)
Positive predictive value (PPV) TP/(TP+FP)
Negative predictive value (NPV) TN/(TN+FN)
Positive Predictive value (PPV) is a function of the True and False positive values. If there were
no false positives, the PPV would be TP/TP or 100%. In the real world this is rarely the case as
laboratory results usually fall on a continuous scale and a cut off has to be selected to separate
positive from negative results. As such there is some degree of overlap between results from
normal and affected patients.
It is theoretically possible that everyone in the population has a disease. In this case every
positive result would be a true positive and the PPV would be 100%. Conversely, if no one in
the population had the disease, every positive result would be a false positive. There could be no
true positives, and the PPV would be 0%. This makes it clear that the prevalence of a disease in
the population has an important influence on the positive predictive value of a diagnostic test.
With decreasing disease prevalence, the less likely it becomes that a person with a positive test
result has the disease, and the more likely it becomes that the positive result is a false positive.
The diagnostic accuracy of a test therefore depends upon the prevalence of the disease in the
population. The table below outlines how the positive and negative predictive values of all
commonly used diagnostic tests vary by prevalence, using the published sensitivity and specificities
quoted in the text (see section 4) for each test.
Prevalence of Serology tests Laboratory based Faecal
CUBT
H. pylori Primary Care serology tests antigen tests
PPV NPV PPV NPV PPV NPV PPV NPV
0.1% 15% 99% 0.5% 99% 2% 99% 1% 00%
5% 43% 99% 21% 99% 55% 99% 33% 99%
10% 61% 99% 37% 97% 73% 99% 51% 99%
20% 78% 97% 57% 94% 85% 99% 70% 98%
30% 86% 95% 69% 90% 91% 98% 80% 97%
40% 90% 92% 78% 85% 94% 97% 86% 96%
50% 93% 88% 84% 80% 96% 96% 90% 94%
60% 96% 83% 88% 73% 97% 93% 93% 91%

Relating this to testing for H. pylori infection, young people are less likely to have the disease
and in Scotland the prevalence is likely to be less than 20%, in this group the best serological
test only has a PPV of 78%, but the negative predictive value remains high. In this group therefore
serology, even assuming the worst sensitivity and specificity could be used to reliably exclude H.
pylori infection. In an older patient group where between 50-60% could have the disease, CUBT
or faecal antigen testing would be a more appropriate choice of test as both have a PPV of over
90%. The best performing serology in this group has a PPV of over 90% but many studies using
serology show much poorer results in this group.

24

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27
68 Dyspepsia

This Quick Reference Guide provides a summary of the main
recommendations in the SIGN dyspepsia guideline. It specifically
addresses the investigation and management of dyspepsia and also
updates the evidence base for Hp eradication in duodenal ulcer,
gastric ulcer and low grade gastric MALT lymphoma. Dyspepsia
denotes symptoms and is not itself a disease. The guideline
development group accepted the Rome II definition: Dyspepsia
refers to pain or discomfort centred in the upper abdomen. On
investigation, organic disease likely to explain the dyspepsia will
be found in some patients, in others, no causal pathology/disease
is identified: these patients are said to have functional dyspepsia.
DYSPEPSIA IN THE COMMUNITY
People with dyspepsia may choose several routes for the initial management
of the condition. Some people purchase antacids or H2RA medicines over the
counter, some consult with a community pharmacist and others will consult
MANAGEMENT OF FUNCTIONAL DYSPEPSIA RESOURCES FOR PATIENTS
þ A working diagnosis of functional dyspepsia is likely to be A patient version of the guideline and a patient information leaflet are
appropriate for most patients with dyspepsia who have no alarm available from the SIGN website: www.sign.ac.uk
features and in whom initial investigations are negative. Repeated
or increasingly invasive investigation in pursuit of an organic cause ABBREVIATIONS
for the symptoms may be both futile and counter-productive. CUBT 13
C and 14C urea breath tests
H2RA Histamine receptor antagonists
þ Patients with functional dyspepsia should be advised to stop
smoking, and to exclude, or take only moderate amounts of alcohol Hp H. Pylori
and caffeine, in line with general healthy lifestyle recommendations. PPI Proton Pump Inhibitor
þ If patients have adopted extreme dietary measures, they should be
encouraged to follow a balanced diet to minimise the risk of
nutritional deficiencies.
þ Medication is not necessary for all patients with functional dyspepsia.
When medication is given, short term treatment, intermittent if "INDIGESTION"

their general practitioner. necessary, is likely to be more appropriate than long term continuous
therapy.
Consider
D Community pharmacists should advise patients suffering from
A Hp eradication therapy should be considered in the management
PREDOMINANT
HEARTBURN
Heart
dyspepsia associated with alarm symptoms to consult their GP.
n

of functional dyspepsia. n Liver

DYSPEPSIA* Yes
n Gall bladder No
C Symptom assessment cannot be relied upon to make a diagnosis n Pancreas

of the cause of dyspepsia. B A trial of acid suppression therapy may be considered in the n
n
Bowel
NSAIDs etc MANAGE
management of functional dyspepsia. AS GORD
ALARM FEATURES
B Patients with dyspepsia and alarm features should be referred to REFER TO Yes n Dysphagia
a hospital specialist for assessment. It is not possible to make a recommendation on the role of HOSPITAL n Evidence of GI blood loss
SPECIALIST
antidepressants, cytoprotectives, prokinetics or psychosocial n Persistent vomiting
n Unexplained weight loss
C Upper GI endoscopy is the investigation of choice when further interventions in the management of functional dyspepsia. n Upper abdominal mass
evaluation is warrented and should be widely available. No
HP TESTS
þ Barium meal studies are appropriate where the local endoscopy UNCOMPLICATED DYSPEPSIA

services are unavailable or for patients who cannot tolerate B The CUBT or faecal antigen tests are recommended for the pre- Consider
Lifestyle
treatment diagnosis of Hp infection in the community. Less
n

endoscopy. n Antacids / H2RA

accurate, hospital-based serology tests have a place within the non-
There is no evidence to support the mandatory use of early upper GI invasive test and treat strategy.
Persistent / recurrent symptoms
endoscopy to investigate patients over 55 years old who present with new
onset uncomplicated dyspepsia. B CUBT is the recommended test to determine whether Hp has been
successfully eradicated.
Hp test + ve Hp test Hp test -ve
MANAGEMENT OF UNCOMPLICATED DYSPEPSIA þ The CUBT should not be performed within two weeks of PPI therapy
or within four weeks of antibiotic therapy as false negative results
A A non-invasive Hp test and treat strategy is as effective as endoscopy
in the initial management of patients with uncomplicated dyspepsia may occur.
who are less than 55 years old. HP ERADICATION OPTIONS Eradicate Hp Persistent / recurrent symptoms
despite confirmed eradication

C A non-invasive Hp test and treat policy may be as appropriate as n Triple therapies including PPIs and two antibiotics give consistently Age

early endoscopy for the initial investigation and management of high eradication rates
patients over the age of 55 years presenting with uncomplicated n Metronidazole or clarithyromycin resistance established by laboratory
Asymptomatic
≥55
dyspepsia. testing is associated with reduced eradication of Hp by regimes <55
including these antibiotics
þ Referral for assessment should be considered for patients over 55 Manage as Consider referral to
years old with uncomplicated dyspepsia whose symptoms persist n Two weeks of triple therapy versus a one week regimen does not functional dyspepsia hospital specialist
after initial management with the Hp test and treat strategy. increase the eradication rate. * Rome II definition