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60 9
Epidemiology of Functional Dyspepsia
Arvind Kumar*, Jignesh Patel**, Prabha Sawant***
Introduction
D yspepsia is derived from the Greek words dys and pepse
and literally means “difficult digestion.” Dyspepsia can
occur due to organic causes, but the majority of patients suffer
from functional dyspepsia (FD). It is broadly defined as pain or
discomfort centred in the upper abdomen with symptoms such
as epigastric pain, postprandial fullness, early satiety, anorexia,
belching, nausea and vomiting, upper abdominal bloating,
and even heartburn and regurgitation.1 People with functional
dyspepsia have a significantly reduced quality of life when
compared to the general population.2
In a recent community survey of several European and North
American populations, more than 50% of dyspepsia sufferers
were on medication most of the time and approximately 30%
of dyspeptics reported taking days off work or schooling due
to their symptoms.3
Definition
Several consensus definitions of dyspepsia and FD have
been proposed. Earlier definitions considered dyspepsia to
consist of all upper abdominal and retrosternal sensations. With
time, definitions of dyspepsia have evolved to become more
restrictive and more focused on symptoms thought to arise from
the gastroduodenal region and not the esophagus. The Rome I
and II consensus committees both defined dyspepsia as pain or
discomfort centred in the upper abdomen.4
According to Rome II committee consensus if the heartburn
is the predominant symptom, the patient should be considered
to have GERD and not dyspepsia. Rome III a recent consensus,
has defined dyspepsia as the presence of symptoms considered
by the physician to originate from the gastroduodenal region
and only four symptoms (bothersome postprandial fullness,
early satiation, epigastric pain, and epigastric burning) are
now considered to be specific for a gastroduodenal origin,
although many other symptoms are acknowledged to coexist
with dyspepsia. Patients having chronic dyspeptic symptoms for
the past 3 months with onset at least 6 months before diagnosis
in absence of structural abnormality on upper GI endoscopy
and metabolic or systemic causes explaining the symptoms are
classified as FD.5
Prevalence of Dyspepsia
True prevalence of FD is difficult to determine in population
studies. Several studies have been done to provide a reflection
of the prevalence of FD.
The prevalence of dyspepsia varies considerably between
different populations. this difference might be related to, (1)
true difference in frequency of the condition, (2) criteria used to
diagnose it and (3) degree of meticulousness to exclude organic
causes. The annual incidence of dyspepsia is approximately
9–10%, and 15% of patients have chronic (> 3 months in a year),
frequent (> 3 episodes per week) and often severe symptoms.6,7
In studies using “upper abdominal pain” as the definition,
the prevalence of uninvestigated dyspepsia (UD) has varied
between 7%-34.2%.8-10,13-16
Senior Resident, **Assistant Professor, ***Professor, Department of
* the study from urban Mumbai, India found that dyspepsia was
Gastroenterology, Lokmanya Tilak Municipal Medical College &
General Hospital Sion, Mumbai, India 400022
With this definition, the lowest UD prevalence of 7%-8% is
seen in Singapore, South East Asia.14 Slightly higher rates are
seen amongst the Scandinavians (14.5%)17 prevalence rates of
23-25.8% are seen in the US, with 30.4% population in India15 and
New Zealand (34.2%)[36] having the highest rates. Prevalence of
dyspepsia found to be 23%-45% when definition included “upper
gastrointestinal symptoms.” Using this definition, a lower
prevalence is seen in Spain (23.9%).18 a 32% UD prevalence rate
in the US is noted.19 whilst significantly higher rates of 38%-41%
are noted in the UK.(20-23) and 45% in Nigeria.24
Prevalence of FD-IBS (Irritable Bowel
Syndrome) Overlap
In population-based studies, the estimated prevalence of
IBS among dyspeptic subjects, ranges between 13% and 29%,
while the prevalence of FD among IBS subjects ranges between
29% and 87%.8,38,39 While in inpatient-based series, as opposed
to community series, the prevalence of overlap appears to
be even higher, between 26% and 46% of FD patients having
concomitant IBS and as many as 87% of IBS patients having
concomitant FD.40-44
This difference might be due to the coexistence of these two
sets of symptoms increases the likelihood of a subject seeking
medical attention. The studies from Asia shows the similar
figures. In a population-based study from Mumbai, India, the
prevalence of dyspepsia was 30%, while among subjects with IBS,
the prevalence of dyspepsia was 58%.15 In another study from
India, about 50% patients showed a overlap of FD-IBS..Similarly,
the prevalence of IBS,among subjects with dyspepsia at 14% was
greater than in the general population where it was 7.5%. The
frequency of FD, IBS and FD-IBS overlap were found to be 53%,
21% and 1.6%, respectively.45 A study from China reported the
concomitant IBS 22% of 473 FD, whereas the prevalence of IBS
in this population was estimated to be 7%.46 While in other study
from China, reported prevalence of FD among 662 consecutive
IBS patients consulting gastroenterologists, was 64%.47 Due to
this overlapping of symptoms some time patients of IBS may
be misdiagnosed as dyspepsia and is likely to be a greater
problem in Asia than in the west. IBS patients in Asia appear
to present more commonly with upper abdominal pain.48 In
studies from India, more than half of their patients complained
of upper abdominal pain, whereas in western series only about
a quarter do so.
Epidemiological Factors
Age
In various surveys age does not appear to be related to any
particular age. Although most of the studies have included
population above the age of 18 years or older. the references
regarding dyspepsia in children are limited, it appears that
dyspepsia represents a common situation (60%-80%) under the
broad spectrum of recurrent abdominal pain.49 In studies of Asia,
FD is more common in younger age group. A study from Japan
reported that prevalence of FD was 13% and 8% in age groups
below and above 50 years, respectively.31 Peak prevalences of
FD appeared to peak in Chinese subjects 41-50 years.25-26 While
more prevalent in adults > 40 years.15 The studies from Britain,18
Taiwan29 and Denmark show a decreasing trend of FD with age.
10 © SUPPLEMENT TO JAPI • march 2012 • VOL. 60
In the latter survey, there was a significantly lower prevalence
of UD in adults > 70 years (10%) compared to those < 60 years
(18.4%).17
Gender
Majority of population-based studies do not show any
gender difference in dyspepsia prevalence. While few studies
from different populations, have noted a consistent female
preponderance with dyspepsia.17-19,27,29,32,50
Ethnicity
The role of ethnicity for dyspepsia has not been established
and it requires more data to conclude the role of ethinicity.
In most of the population based studies role of ethnicity in
dyspepsia has not been examined. Most surveys have been
done on populations of single/similar ethnic groups, mostly of
Caucasian or Oriental background. Few studies from Asia also
reflect the prevalence of dyspepsia in different populations. Two
studies from Malaysia on about 2000 patients on applying Rome
II criteria showed a prevalence of dyspepsia in Malay, Chinese
and Indian populations is 231 (14.6%), 30 (19.7%) and 28 (11.2%)
respectively.51-52
Infections
Does the Helicobacter Pylori (H pylori) have any role to play in
FD? The evidence is still unclear and most H pylori eradication
trials in FD have been badly designed and gave conflicting
results. The reviews by both O’Morain and Malfertheiner
evidence were provided of well conducted randomized control
trials and meta-analysis, showing a small but significant effect
in eradicating H pylori in dyspeptic patients.53-54 A recent well
done meta-analysis and Cochrane Database systematic reviews
show that there is a small but significant benefit of eliminating
H pylori in patients with dyspepsia.55-56
There is some evidence though data is less that enteric
infection caused by bacteria and protozoa such as Giardia lamblia
may be followed by development of post-infectious irritable
bowel syndrome (IBS) and FD.58 A study in an area which is not
endemic for Giardia, demonstrated Giardia in 15.5% of patients
presenting with dyspepsia and its prevalence is similar with or
without obvious lesions at endoscopy.59 While in other study
from Giardia endemic area, 44% patients of dyspepsia were
found Giardia positive.60 In another study of 522 patients from
China, 35 (6.7%) patients developed FD on follow-up after acute
gastroenteritis.61
However in a recent large prospective study of a well
documented single source out-break of salmonella gastroenteritis
demonstrated the development not only of IBS, but also for
the first time,of dyspepsia.The three most common dyspeptic
symptoms were pain, bloating and fullness. Prolonged
abdominal pain and vomiting during the acute episode were
found to be positive predictors. In patients who developed IBS,
there was a 62% overlap with FD at 12 month post-infection. In
patients who developed FD, there was a 46% overlap with IBS.62
Dietary Factors
Due to the diversity of dietary habits within individual
populations the role of diet in dyspepsia has not been established.
Some western studies have reported that excessive coffee or
tea intake has not been shown to be related to the presence
of dyspepsia/UD.17,19,23,36,62,63 However one Canadian survey
showed that heavy intake of cola was associated with markedly
increased prevalence of dyspepsia.62 Study from Mumbai India
have shown that vegetarians or non vegetarian diet have no
effect on dyspeptic symptoms, and spicy, fried or food prepared
outside the home contributed insignificantly to worsening of
symptoms.15 While a population-based study from Malaysia
showed that high chilly intake was an independent risk factor
for dyspepsia (OR, 2.35; 95% CI, 1.15-4.80).52 Rice-based diet,
popular among many Asian population may be better tolerated
than Western wheat-based diet by many patients with functional
bowel disorders.64 However this data on diet and dyspepsia
seems to be insufficient and more studies on the role of diet in
dyspepsia are needed.
Smoking, alcohol and Non-steroidal anti-inflammatory
drugs (NSAIDs)
Association of regular smoking and dyspepsia has not
been consistent. In the few population-based studies that
have examined FD, smoking has not been shown to be a risk
factor.26,27,36,37 In surveys from US,19 Canada,63 UK23 and India15
of patients with UD have showed regular smoking as an
identifiable risk factor. The relationship of regular alcohol intake
and dyspepsia, has been not proven in various studies. Two
studies from India15 and New Zealand16 have showed definite
associations between alcohol and UD. Two population based
studies have revealed a relationship of dyspepsia and NSAIDs.
In a British study of 4982 adults, NSAID usage was identified as
an independent risk factor for UD and thought to be responsible
solely for 4% of dyspepsia in the community.23 In a study of
American adults from a single institution, regular usage of
NSAIDs and Aspirin, bought over the counter, were strongly
associated with UD than in controls without dyspepsia.19
Socio-economic associations
In majority of population-based studies prevalence of
dyspepsia have not been found to be linked with social class.
However studies examining details of socio-economic status
were able to elicit associations with dyspepsia. In study of
Drossman et al in the US noted a strong relationship between
lower household income and larger household membership
with increased functional GI diseases, including FD.35 Similarly
in a British survey, factors including rented accommodation,
no central heating, low educational level and sharing a bed
with siblings (surrogate for crowded household) were found
to be predictive of UD in adults.23 Other study from China
on dyspepsia have shown that “dissatisfaction with financial
income” was associated with FD.26
Psychological Associations
A biopsychosocial model to explain FD has been proposed,
whereby biological, psychological and social factors interact
to account for patient’s symptoms, behavioural response and
disease outcome. FD can then be seen as a result of dysregulation
of intestinal motor, sensory and CNS activity, resulting from
interruptions at some level of the brain gut axis. Early life stress
and acute life threatening situations are strong risk factors
for developing FD in the genetically predisposed individual,
later on in life. The most common psychiatric comorbidities
in patients with functional dyspepsia are anxiety disorders,
depressive disorders, somatoform disorders, and a recent or
remote history of physical or sexual abuse. Talley et al had
reported in an American adult population that sexual, emotional
and verbal abuse either in childhood or adulthood were
significantly associated with dyspepsia.9 In an Australian survey
where adults with FD scored highly on anxiety and depression
scales.37 A population-based study from Hong Kong revealed
that anxiety was associated medical consultation and sick leave
among patients with dyspepsia and IBS and degree of anxiety
was an independent factor associated with health care seeking
behaviour in dyspeptic patients.65
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Quality of Life in Patients with Dyspepsia
Dyspepsia is rarely fatal, with a majority of patients suffering
from significant levels of abdominal pain that interrupt daily
activities and treatment remains unsatisfactory in this chronic
condition. It poses significant burden to the society due to
work absenteeism, reduced productivity and use of health care
resources. The impact of dyspepsia has therefore been largely
assessed by its impact on health-related quality of life (HRQOL)
in several Western populations. Two studies were ‘positive’ in
showing a significant reduction at least in some domains of
HRQOL among patients with functional dyspepsia compared
to controls,66,67 while one study was negative.68 In general, the
decline in scores of physical domains was similar to those on
mental domains. However, data on QOL of patients with FD
from Asia are scanty. Health-related QOL scores, evaluated
by Korean version of SF-36, were worse for all 8 domains in
patients with dyspepsia and IBS compared with those not having
chronic GI symptoms.69 Two other studies from Asia one on
rural and other on urban populations showed that subjects with
dyspepsia(Rome II and III criteria) had lower health-related QOL
using EuroQOL (EQ-5D) instrument.51,52,70
Summary
Functional dyspepsia (FD) is the most common cause of
dyspeptic symptoms. It refers to a heterogeneous group of
symptoms located in the upper abdomen. The prevalence of
dyspepsia is variable in different populations and is related
to the different definitions of dyspepsia as inclusion criterias,
variation in survey population and environmental factors.
Epidemiologically some risk factors have been identified and
underlying psychological disturbances have been shown to be
important factors in FD. Age and ethnicity do not appear to be
predictive of dyspepsia. A majority of patients suffering from
significant levels of abdominal pain that interrupt daily activities
and treatment remains unsatisfactory in this chronic condition.
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