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Introduction

Dyspepsia is a common term used to characterize abdominalpain centered in the epigastrium, sometimes combined

with other gastrointestinal complaints. Historically the worddyspepsia was used for a heterogeneous group of abdominalsymptoms. Functional (previously nonulcer) dyspepsia (FD)is the focus of this review, and usually indicates abdominaldiscomfort or pain with no obvious organic cause that could beidenti ed by endoscopy.

The term dyspepsia originates from the Greek dys andpepse, popularly known as indigestion. It was rst recorded inthe mid 18th century and since then it has been widely used. 1 Inthe 18th century dyspepsia was thought to be one of the nervousdisorders along with hypochondria and hysteria. 2 In additionto the term functional dyspepsia, several other descriptions of

dyspepsia are in use, each of which re ects various amountsof investigation into upper gastrointestinal symptoms of thepatient. Uninvestigated dyspepsia refers to patients with eithernew or possibly recurrent dyspeptic symptoms in whom noinvestigations have previously been undertaken. After thoseinvestigations dyspeptic complaints may be called investigateddyspepsia and should be di erentiated into organic dyspepsiaand FD. 3 Organic dyspepsia means that there is a clear anatomicor pathophysiologic reason for the dyspeptic complaints, suchas an ulcer disease or mass. In contrast, when a diagnosis of FDhas been made, it means that a number of investigations wereperformed including upper gastrointestinal endoscopy, andwere found to be normal.

De nitionThe recommended de nition for functional dyspepsia wasa symptom or a set of symptoms that are considered by mostphysicians to originate from gastroduodenal region.

Rome criteria were developed by a commi ee of experts andmodi ed subsequently. They include Rome I, Rome II and RomeIII. Rome I and Rome II did not include meal related symptomsand this was the fundamental change in Rome III.Rome I

In 1991, the Rome I commi ee considered dyspepsia torepresent persistent or recurrent abdominal pain or abdominaldiscomfort 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 intermi ent or continuous.

Three categories of dyspepsia were identi ed:i. Dyspepsia with identi ed cause that if treated leads to

improvement, such as chronic peptic ulcer disease, re uxesophagitis, malignancy, or pancreaticobiliary disease;

ii. Dyspepsia with an identi ed abnormality of uncertainsignificance , such as H. pylori gastritis, duodenitis,idiopathic gastroparesis, gastric dysrhythmias, or small bowel dysmotility;

iii. Dyspepsia with no explanation identi ed.Of these three categories, the Rome I criteria considered

both dyspepsia with an identi ed abnormality of uncertainsigni cance and dyspepsia with no explanation as functionaldyspepsia.

The symptoms of functional dyspepsia were described aschronic or recurrent abdominal pain or discomfort centered inthe upper abdomen lasting at least three months. Symptoms hadto have been present at least 25% of the time. This classi cationof functional dyspepsia did not include irritable bowel syndrome(IBS), gastroesophageal re ux disease (GERD), biliary tractdisease, or aerophagia.

Functional dyspepsia was further divided in to three sub-groups:i. Ulcer-like functional dyspepsia , wherein there was

predominant pain and three or more of the followingsymptoms were present: pain that was very well localizedto a small area, pain relieved by food, or antacids or anti-secretory therapy, pain before meals or when hungry, nightpain, or periodic pain

ii. Dysmotility- like functional dyspepsia , wherein thesymptoms suggest gastric stasis. Symptoms were describedas three or more of the following in the absence ofpredominant pain: early satiety, post-prandial fullness,nausea, recurrent retching/vomiting, bloating withoutvisible distention, or discomfort often aggravated by food.

iii. Unspeci ed functional dyspepsia that did not t into theulcer like or dysmotility type categories.

Rome II In 1999, the Rome II made changes to the criteria for

functional dyspepsia. 5Notably, Rome II sought to a ribute eachfunctional dyspepsia subtype with a single predominate (most bothersome) complaint rather than with a cluster of complaintsas was the case in Rome I. For ulcer-like functional dyspepsiathe predominant symptom was epigastric pain. For dysmotility-like functional dyspepsia, the predominant symptom was anon-painful discomfort characterized as abdominal fullness,early satiety, bloating or nausea. Categorizing sub-groups by apredominant symptom sought to be er identify the underlyingpathophysiologic disturbance and to target treatment. 6,7 Thetime course of functional dyspepsia was revised for all criteriasymptoms had to be present for at least 12 weeks over a 12-monthperiod which need not be consecutive, although this de nitionlater proved clumsy and was abandoned by Rome III. It has been di cult to reliably identify distinct groups of patientswithin functional dyspepsia. There were several drawbacks tothe Rome I and II criteria in this regard. Frequently, patientscannot distinguish pain from discomfort. 8 Some patientsthink of mild pain as discomfort while others dont make thisdistinction at all. Not everyone ed into the sub-groups ofthe Rome classi cation. 9 And even those who did t into thesubgroups showed instability in their categorization, even overthe short term. 10,11 There is still no acceptable understandingof the term predominant as used in the Rome II criteria. Tocompound the di culties, subdividing patient groups according

to the predominant symptom failed to identify subgroups with

Non-Ulcer DyspepsiaPiyush Ranjan *

*Consultant Gastroenterologist, Department of Gastroenterology, SirGanga Ram Hospital, New Delhi 110060.

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homogeneous underlying pathophysiological mechanisms. 12

Rome IIIIn 2006, Rome III radically reformulated the functional

dyspepsia classification. Till now this is the most currentde nition of functional dyspepsia.

According to the most recent 2006 Rome III criteria FDmust include one or more of following symptoms: bothersomepostprandial fullness, early satiation, epigastric pain, epigastric burning with no evidence of structural disease, excluded byupper endoscopy, which is likely to explain the symptoms.Criteria should be ful lled for at least 3 months with symptomonset at least 6 months previously (Table 1).

In Rome III, dyspepsia was rede ned; from a description ofsymptoms centered in the upper abdominal area, the Commi eesuggested pain must be in the more precise epigastric area, whileother key symptoms (early satiety and fullness) should be mealrelated. In Rome III, discomfort was replaced by either post-prandial fullness or early satiety. The Rome III criteria movedaway from the use of the predominant symptom to classify sub-types, and recognized that there is no one symptom present in thevast majority of patients previously labeled as having functionaldyspepsia. Finally, and most notably, the very term functionaldyspepsia was abandoned in favor of a new classi cation asdescribed in Table 2.

In Rome III classi cation functional dyspepsia has beenclassi ed as1. Post-Prandial Distress Syndrome2. Epigastric Pain SyndromePost-Prandial Distress Syndrome

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

(Table 3) refers to unexplained regular meal-induced dyspepticsymptoms (namely bothersome post-prandial fullness after an

ordinary sized meal that occurs at least several times per week orearly satiation that prevents the nishing of a regular sized mealat least several times per week. By Rome III, one or both of thesemust have been present for at least the last three months with anonset of symptoms at least six months prior to diagnosis. PDScan also coexist with symptoms of upper abdominal bloating,post-prandial nausea and epigastric pain.Epigastric Pain Syndrome

Epigastric pain syndrome (EPS) (Table 4) refers to pain or burning localized to the epigastrium of at least moderate severityat least once per week. The pain must be intermi ent in naturethough not relieved by defection or passage of atus. Likewise,the pain characteristics should not ful ll criteria for biliarypain that occurs in functional gallbladder or sphincter of Oddidisorders. Again the pain must have been present for at least thelast three months with an onset of symptoms at least six monthsprior to diagnosis. EPS can include burning, though without aretro sternal component distinguishing it from heartburn. Thepain is thought to be commonly precipitated or relieved bymeals, but can also occur during fasting. Symptoms of PDS canalso occur, although the degree of overlap remains currentlyunde ned. EPS is not a new concept.Functional Dyspepsia Post Rome III 14

Under current criteria, the symptoms of dyspepsia arethought to originate in the gastroduodenal region. Dyspepsiais de ned by Rome III to comprise the presence of one or moreof the following symptoms:

Table 1 : Rome III diagnostic criteria for functionaldyspepsia.

At least 3 months, with onset at least 6 months previously, of one ormore of the following: bothersome postprandial fullness early satiation epigastric pain

epigastric burningand no evidence of structural disease (including upper endoscopy)

that is likely to explain the symptoms

Table 2 : Rome III criteria for functional gastroduodenaldisorders

B Functional gastroduodenal disordersB1 Functional dyspepsia (for application in clinical practice but nototherwise useful)B1a Postprandial distress syndromeB1b Epigastric pain syndromeB2 Belching disorders

B2a AerophagiaB2b Unspeci ed excessive belchingB3 Nausea and vomiting disordersB3a Chronic idiopathic nauseaB3b Functional vomitingB3c Cyclic vomiting syndromeB4 Rumination syndrome in adults

Table 3 : Rome III diagnostic criteria for epigastric painsyndrome.

At least 3 months, with onset at least 6 months previously, with ALLof the following symptoms:1. Pain or burning localized to the epigastrium of at least moderate

severity, at least once per week.2. Pain is intermi ent.3. Pain is not generalized or localized to other abdominal or chest

regions.4. Pain is not relieved by defecation or passage of atus.5. Pain does not ful ll criteria for gallbladder or sphincter of Oddi

disorders. Supportive criteria 1. Pain may be of a burning quality, but without a

retrosternal component. 2. Pain is commonly induced or relieved by ingestion of a

meal, but may occur while fasting. 3. Pain may coexist with postprandial distress syndrome.

Table 4 : Rome III diagnostic criteria for postprandialdistress syndrome.

At least 3 months, with onset at least 6 months previously, with one or both of the following symptoms.1. Bothersome postprandial fullness, occurring after ordinary-sized

meals, at least several times per week.2. Early satiation that prevents nishing a regular meal, at least

several times per week. Supportive criteria 1. Upper abdominal bloating or postprandial nausea or

excessive belching can be present. 2. May coexist with epigastric pain syndrome.

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1. Post prandial fullness : Bothersome post-prandial fullnessthat can be described as an unpleasant sensation likeprolonged persistence of food in the stomach.

2. Early satiety : Early satiation which can be described as afeeling that the stomach is over lled soon after starting toeat. This feeling is out of proportion to the size of the mealand results in the patient being unable to nish the meal.

3. Epigastric pain : Epigastric pain which is pain located between the umbilicus and lower end of sternum in-betweenthe midclavicular lines. The pain is a subjective and clearlyunpleasant feeling and is di cult otherwise to describe,although it may be akin to a feeling of tissue being damaged.

4. Epigastric burn : Epigastric burning is pain located in theepigastrium that has a burning quality but does not radiateto 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 ofthe art, 15 heartburn is neither necessary nor su cient to diagnosegastroesophageal reflux disease (GERD), and commonlyco-occurs in patients labeled in clinical practice as havingfunctional dyspepsia. 16,17 In clinical practice, frequent, typicalre ux symptoms should be provisionally classi ed as GERD.However, dominant heartburn is a poor predictor for identifyingobjective ndings such as re ux esophagitis. 18 EPS and PDS maystill be diagnosed to be present according to Rome III if there isuncertainty and dyspepsia persists despite a trial of adequateanti-secretory therapy, although the proton pump inhibitor testas a means for identifying GERD remains suboptimal. 19

Conclusions and FutureThere are some obvious limitations to the new Rome III

criteria and these need exploring. Recent literature re ects

controversy about the nature of functional dyspepsia, and therecurrently remains a divide between the symptom experienceand abnormal pathophysiology which may not be addressed by the new classi cation. 20 While much work has looked atputative mechanisms including gastric emptying and gastricaccommodation in functional dyspepsia, it still remains unclearwhether these are a cause or not of symptoms in this broadpatient grouping.

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Functional dyspepsia. A classi cation with guidelines for diagnosisand management. Gastroenterol Int 1991;4:145-160.

5. Talley NJ, Stanghellini V, Heading RC, Koch KL, Malagelada JR,Tytgat GN. Functional gastroduodenal disorders. Gut 1999;45:II37II42.

6. Gilvarry J, Buckley MJM, Bea ie S, Hamilton H, OMorain CA.Eradication of Helicobacter pylori a ects symptoms in non-ulcerdyspepsia. Scand J Gastroenterol 1997;32:535-540.

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18. des Varannes SB, Sacher-Huvelin S, Vavasseur F, Masliah C, LeRhun M, Aygalenq P, Bonnot-Marlier S, Lequeux Y, Galmiche JP. Rabeprazole test for the diagnosis of gast rooesophagealre ux disease: results of a study in a primary care se ing. World JGastroenterol 2006;12:2569-2573.

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