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Non-Ulcer Dyspepsia
Piyush Ranjan*


yspepsia is a common term used to characterize abdominal

pain centered in the epigastrium, sometimes combined
with other gastrointestinal complaints. Historically the word
dyspepsia was used for a heterogeneous group of abdominal
symptoms. Functional (previously nonulcer) dyspepsia (FD)
is the focus of this review, and usually indicates abdominal
discomfort or pain with no obvious organic cause that could be
identified by endoscopy.
The term dyspepsia originates from the Greek dys and
pepse, popularly known as indigestion. It was first recorded in
the mid 18th century and since then it has been widely used.1 In
the 18th century dyspepsia was thought to be one of the nervous
disorders along with hypochondria and hysteria.2 In addition
to the term functional dyspepsia, several other descriptions of
dyspepsia are in use, each of which reflects various amounts
of investigation into upper gastrointestinal symptoms of the
patient. Uninvestigated dyspepsia refers to patients with either
new or possibly recurrent dyspeptic symptoms in whom no
investigations have previously been undertaken. After those
investigations dyspeptic complaints may be called investigated
dyspepsia and should be differentiated into organic dyspepsia
and FD.3 Organic dyspepsia means that there is a clear anatomic
or pathophysiologic reason for the dyspeptic complaints, such
as an ulcer disease or mass. In contrast, when a diagnosis of FD
has been made, it means that a number of investigations were
performed including upper gastrointestinal endoscopy, and
were found to be normal.

The recommended definition for functional dyspepsia was
a symptom or a set of symptoms that are considered by most
physicians to originate from gastroduodenal region.
Rome criteria were developed by a committee of experts and
modified subsequently. They include Rome I, Rome II and Rome
III. Rome I and Rome II did not include meal related symptoms
and this was the fundamental change in Rome III.
Rome I
In 1991, the Rome I committee considered dyspepsia to
represent persistent or recurrent abdominal pain or abdominal
discomfort centered in the upper abdomen.4
The discomfort could be described as post-prandial fullness,
early satiety, nausea, retching, vomiting, or upper abdominal
bloating, and could be intermittent or continuous.
Three categories of dyspepsia were identified:

Dyspepsia with identified cause that if treated leads to

improvement, such as chronic peptic ulcer disease, reflux
esophagitis, malignancy, or pancreaticobiliary disease;

ii. Dyspepsia with an identified abnormality of uncertain

significance, such as H. pylori gastritis, duodenitis,
idiopathic gastroparesis, gastric dysrhythmias, or small
bowel dysmotility;
Consultant Gastroenterologist, Department of Gastroenterology, Sir
Ganga Ram Hospital, New Delhi 110060.

iii. Dyspepsia with no explanation identified.

Of these three categories, the Rome I criteria considered

both dyspepsia with an identified abnormality of uncertain
significance and dyspepsia with no explanation as functional

The symptoms of functional dyspepsia were described as

chronic or recurrent abdominal pain or discomfort centered in
the upper abdomen lasting at least three months. Symptoms had
to have been present at least 25% of the time. This classification
of functional dyspepsia did not include irritable bowel syndrome
(IBS), gastroesophageal reflux disease (GERD), biliary tract
disease, or aerophagia.
Functional dyspepsia was further divided in to three subgroups:

Ulcer-like functional dyspepsia, wherein there was

predominant pain and three or more of the following
symptoms were present: pain that was very well localized
to a small area, pain relieved by food, or antacids or antisecretory therapy, pain before meals or when hungry, night
pain, or periodic pain

ii. Dysmotility-like functional dyspepsia, wherein the

symptoms suggest gastric stasis. Symptoms were described
as three or more of the following in the absence of
predominant pain: early satiety, post-prandial fullness,
nausea, recurrent retching/vomiting, bloating without
visible distention, or discomfort often aggravated by food.
iii. Unspecified functional dyspepsia that did not fit into the
ulcer like or dysmotility type categories.
Rome II
In 1999, the Rome II made changes to the criteria for
functional dyspepsia.5 Notably, Rome II sought to attribute each
functional dyspepsia subtype with a single predominate (most
bothersome) complaint rather than with a cluster of complaints
as was the case in Rome I. For ulcer-like functional dyspepsia
the predominant symptom was epigastric pain. For dysmotilitylike functional dyspepsia, the predominant symptom was a
non-painful discomfort characterized as abdominal fullness,
early satiety, bloating or nausea. Categorizing sub-groups by a
predominant symptom sought to better identify the underlying
pathophysiologic disturbance and to target treatment.6,7 The
time course of functional dyspepsia was revised for all criteria
symptoms had to be present for at least 12 weeks over a 12-month
period which need not be consecutive, although this definition
later proved clumsy and was abandoned by Rome III. It has
been difficult to reliably identify distinct groups of patients
within functional dyspepsia. There were several drawbacks to
the Rome I and II criteria in this regard. Frequently, patients
cannot distinguish pain from discomfort. 8 Some patients
think of mild pain as discomfort while others dont make this
distinction at all. Not everyone fitted into the sub-groups of
the Rome classification.9 And even those who did fit into the
subgroups showed instability in their categorization, even over
the short term.10,11 There is still no acceptable understanding
of the term predominant as used in the Rome II criteria. To
compound the difficulties, subdividing patient groups according
to the predominant symptom failed to identify subgroups with



Table 1 : Rome III diagnostic criteria for functional

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

bothersome postprandial fullness

early satiation

epigastric pain

epigastric burning


no evidence of structural disease (including upper endoscopy)

that is likely to explain the symptoms

Table 2 : Rome III criteria for functional gastroduodenal

B Functional gastroduodenal disorders
B1 Functional dyspepsia (for application in clinical practice but not
otherwise useful)
B1a Postprandial distress syndrome

Table 3 : Rome III diagnostic criteria for epigastric pain

At least 3 months, with onset at least 6 months previously, with ALL
of the following symptoms:

Pain or burning localized to the epigastrium of at least moderate

severity, at least once per week.


Pain is intermittent.


Pain is not generalized or localized to other abdominal or chest



Pain is not relieved by defecation or passage of flatus.


Pain does not fulfill criteria for gallbladder or sphincter of Oddi



Pain may be of a burning quality, but without a

retrosternal component.


Pain is commonly induced or relieved by ingestion of a

meal, but may occur while fasting.


Pain may coexist with postprandial distress syndrome.

B1b Epigastric pain syndrome

Table 4 : Rome III diagnostic criteria for postprandial

distress syndrome.

B2 Belching disorders
B2a Aerophagia

Supportive criteria

B2b Unspecified excessive belching

At least 3 months, with onset at least 6 months previously, with one or

both of the following symptoms.

B3 Nausea and vomiting disorders


Bothersome postprandial fullness, occurring after ordinary-sized

meals, at least several times per week.


Early satiation that prevents finishing a regular meal, at least

several times per week.

B3a Chronic idiopathic nausea

B3b Functional vomiting
B3c Cyclic vomiting syndrome
B4 Rumination syndrome in adults

Supportive criteria


Upper abdominal bloating or postprandial nausea or

excessive belching can be present.

Rome III


May coexist with epigastric pain syndrome.

In 2006, Rome III radically reformulated the functional

dyspepsia classification. Till now this is the most current
definition of functional dyspepsia.

(Table 3) refers to unexplained regular meal-induced dyspeptic

symptoms (namely bothersome post-prandial fullness after an
ordinary sized meal that occurs at least several times per week or
early satiation that prevents the finishing of a regular sized meal
at least several times per week. By Rome III, one or both of these
must have been present for at least the last three months with an
onset of symptoms at least six months prior to diagnosis. PDS
can also coexist with symptoms of upper abdominal bloating,
post-prandial nausea and epigastric pain.

homogeneous underlying pathophysiological mechanisms.12

According to the most recent 2006 Rome III criteria FD

must include one or more of following symptoms: bothersome
postprandial fullness, early satiation, epigastric pain, epigastric
burning with no evidence of structural disease, excluded by
upper endoscopy, which is likely to explain the symptoms.
Criteria should be fulfilled for at least 3 months with symptom
onset at least 6 months previously (Table 1).
In Rome III, dyspepsia was redefined; from a description of
symptoms centered in the upper abdominal area, the Committee
suggested pain must be in the more precise epigastric area, while
other key symptoms (early satiety and fullness) should be meal
related. In Rome III, discomfort was replaced by either postprandial fullness or early satiety. The Rome III criteria moved
away from the use of the predominant symptom to classify subtypes, and recognized that there is no one symptom present in the
vast majority of patients previously labeled as having functional
dyspepsia. Finally, and most notably, the very term functional
dyspepsia was abandoned in favor of a new classification as
described in Table 2.

Epigastric Pain Syndrome

In Rome III classification functional dyspepsia has been

classified as

Epigastric pain syndrome (EPS) (Table 4) refers to pain or

burning localized to the epigastrium of at least moderate severity
at least once per week. The pain must be intermittent in nature
though not relieved by defection or passage of flatus. Likewise,
the pain characteristics should not fulfill criteria for biliary
pain that occurs in functional gallbladder or sphincter of Oddi
disorders. Again the pain must have been present for at least the
last three months with an onset of symptoms at least six months
prior to diagnosis. EPS can include burning, though without a
retro sternal component distinguishing it from heartburn. The
pain is thought to be commonly precipitated or relieved by
meals, but can also occur during fasting. Symptoms of PDS can
also occur, although the degree of overlap remains currently
undefined. EPS is not a new concept.


Post-Prandial Distress Syndrome

Functional Dyspepsia Post Rome III14


Epigastric Pain Syndrome

Under current criteria, the symptoms of dyspepsia are

thought to originate in the gastroduodenal region. Dyspepsia
is defined by Rome III to comprise the presence of one or more
of the following symptoms:

Post-Prandial Distress Syndrome

This is a new concept. Post-prandial distress syndrome (PDS)



Post prandial fullness: Bothersome post-prandial fullness

that can be described as an unpleasant sensation like
prolonged persistence of food in the stomach.


Early satiety: Early satiation which can be described as a

feeling that the stomach is overfilled soon after starting to
eat. This feeling is out of proportion to the size of the meal
and results in the patient being unable to finish the meal.


Epigastric pain: Epigastric pain which is pain located

between the umbilicus and lower end of sternum in-between
the midclavicular lines. The pain is a subjective and clearly
unpleasant feeling and is difficult otherwise to describe,
although it may be akin to a feeling of tissue being damaged.


Epigastric burn: Epigastric burning is pain located in the

epigastrium that has a burning quality but does not radiate
to the chest.

What about Coexistent Heartburn?

Though past definitions have included heartburn (a
retrosternal burning pain) as a cardinal symptom of dyspepsia,
and while some authorities still insist this should be the state of
the art,15 heartburn is neither necessary nor sufficient to diagnose
gastroesophageal reflux disease (GERD), and commonly
co-occurs in patients labeled in clinical practice as having
functional dyspepsia.16,17 In clinical practice, frequent, typical
reflux symptoms should be provisionally classified as GERD.
However, dominant heartburn is a poor predictor for identifying
objective findings such as reflux esophagitis.18 EPS and PDS may
still be diagnosed to be present according to Rome III if there is
uncertainty and dyspepsia persists despite a trial of adequate
anti-secretory therapy, although the proton pump inhibitor test
as a means for identifying GERD remains suboptimal.19

Conclusions and Future

There are some obvious limitations to the new Rome III
criteria and these need exploring. Recent literature reflects
controversy about the nature of functional dyspepsia, and there
currently remains a divide between the symptom experience
and abnormal pathophysiology which may not be addressed
by the new classification.20 While much work has looked at
putative mechanisms including gastric emptying and gastric
accommodation in functional dyspepsia, it still remains unclear
whether these are a cause or not of symptoms in this broad
patient grouping.


Baron JH, Watson F, Sonnenberg A. Three centuries of stomach

symptoms in Scotland. Aliment Pharmacol Ther 2006;24:821-829.


Hare E. The history of nervous disorders from 1600 to 1840, and

a comparison with modern views. Br J Psychiatry 1991;159: 37-45.


Brun R, Braden K. Functional dyspepsia 2010;3:145-164.


Talley NJ, Colin-Jones D, Koch KL, Koch M, Nyren O, Stanghellini V.

Functional dyspepsia. A classification with guidelines for diagnosis
and management. Gastroenterol Int 1991;4:145-160.


Talley NJ, Stanghellini V, Heading RC, Koch KL, Malagelada JR,

Tytgat GN. Functional gastroduodenal disorders. Gut 1999;45:II37



Gilvarry J, Buckley MJM, Beattie S, Hamilton H, OMorain CA.

Eradication of Helicobacter pylori affects symptoms in non-ulcer
dyspepsia. Scand J Gastroenterol 1997;32:535-540.


Talley NJ, Meineche-Schmidt V, Pare P, Duckworth M, Raisanen P,

Pap A, Kordecki H, Schmid V. Efficacy of omeprazole in functional
dyspepsia: double-blind, randomized, placebo-controlled trials (the
Bond and Opera studies). Aliment Pharmacol Ther 1998;12:1055-1065.


Holtmann G, Stanghellini V, Talley NJ. Nomenclature of dyspepsia,

dyspepsia subgroups and functional dyspepsia: clarifying the
concepts. Baillires Clin Gastroenterol 1998;12:417-433.


Camilleri M, Dubois D, Coulie B, Jones M, Kahrilas PJ, Rentz

AM, Sonnenberg A, Stanghellini V, Stewart WF, Tack J, Talley NJ,
Whitehead W, Revicki DA. Prevalence and socioeconomic impact
of upper gastrointestinal disorders in the United States: results of
the US Upper Gastrointestinal Study. Clin Gastroenterol Hepatol

10. Laheij RJ, De Koning RW, Horrevorts AM, Rongen RJ, Rossum
LG, Witteman EM, Hermsen JT, Jansen JB. Predominant symptom
behavior in patients with persistent dyspepsia during treatment. J
Clin Gastroenterol 2004;38:490-495.
11. Meineche-Schmidt V, Jorgensen T. Fluctuation in dyspepsia
subgroups over time. A three-year follow-up of patients consulting
general practice for dyspepsia. Dig Liver Dis 2002;34:332-338.
12. Karamanolis G, Caenepeel P, Arts J, Tack J: Association of
the predominant symptom with clinical characteristics and
pathophysiological mechanisms in functional dyspepsia.
Gastroenterology 2006;130:296-303.
13. Armstrong D, Veldhuyzen van Zanten SJ, Barkun AN, Chiba N,
Thomson AB, Smyth S, Sinclair P, Chakraborty B, White RJ. The
CADET-HR Study Group. Heartburn-dominant, uninvestigated
dyspepsia: a comparison of PPI-start and H2-RA-start
management strategies in primary care the CADET-HR Study.
Aliment Pharmacol Ther 2005;21:1189-1202.
14. Tally JN, Ruff K, Jung X, Jung HK. The Rome III classification of
dyspepsia: Will it help research. Dig Dis 2008;26:203-209.
15. Ford AC, Forman D, Bailey AG, Cook MB, Axon AT, Moayyedi P:
Who consults with dyspepsia? Results from a longitudinal 10-yr
follow-up study. Am J Gastroenterol 2007;102:957-965.
16. Locke GR 3rd, Zinsmeister AR, Fett SL, Melton LJ 3rd, Talley NJ.
Overlap of gastrointestinal symptom complexes in a US community.
Neurogastroenterol Motil 2005;17:29-34.
17. Thomson AB, Barkun AN, Armstrong D, Chiba N, White RJ,
Daniels S, Escobedo S, Chakraborty B, Sinclair P, Van Zanten SJ: The
prevalence of clinically significant endoscopic findings in primary
care patients with uninvestigated dyspepsia: the Canadian Adult
Dyspepsia Empiric Treatment Prompt Endoscopy (CADET-PE)
study. Aliment Pharmacol Ther 2003;17:1481-1491.
18. des Varannes SB, Sacher-Huvelin S, Vavasseur F, Masliah C, Le
Rhun M, Aygalenq P, Bonnot-Marlier S, Lequeux Y, Galmiche
JP. Rabeprazole test for the diagnosis of gastrooesophageal
reflux disease: results of a study in a primary care setting. World J
Gastroenterol 2006;12:2569-2573.
19. Talley NJ, Locke GR 3rd, Lahr BD, Zinsmeister AR, Tougas G,
Ligozio G, Rojavin MA, Tack J: Functional dyspepsia, delayed
gastric emptying, and impaired quality of life. Gut 2006;55:933-939.
20. Talley NJ, Verlinden M, Jones M. Can symptoms discriminate among
those with delayed or normal gastric emptying in dysmotilitylike
dyspepsia? Am J Gastroenterol 2001;96:1422-1428.