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Asian consensus on irritable bowel syndrome

Asian consensus on irritable bowel syndrome
Kok-Ann Gwee,1 Young-Tae Bak,2 Uday Chand Ghoshal,3 Sutep Gonlachanvit,4 Oh Young Lee,5
Kwong Ming Fock,6 Andrew Seng Boon Chua,7 Ching-Liang Lu,8 Khean-Lee Goh,9
Chomsri Kositchaiwat,10 Govind Makharia,11 Hyo-Jin Park,12 Full-Young Chang,13 Shin Fukudo,14
Myung-Gyu Choi,15 Shobna Bhatia,16 Meiyun Ke,17 Xiaohua Hou18 and Michio Hongo19
1Stomach Liver and Bowel Clinic, Gleneagles Hospital, Singapore; 2Department of Internal Medicine, Korea University College of Medicine, Seoul,South Korea; 3Department of Gastroenterology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, India; 4Department of Internal Medicine, Chulalongkorn University, Bangkok, Thailand; 5Department of Gastroenterology, College of Medicine, Hanyang University, Seoul, South Korea; 6Division of Gastroenterology, Changi General Hospital, Singapore; 7Ipoh Gastro Centre, Ipoh, Malaysia; 8Division of Gastroenterology, Taipei Veterans General Hospital, Taipei, Taiwan; 9Department of Medicine, University of Malaya, Kuala Lumpur, Malaysia;10Ramathibodi Hospital, Mahidol University, Bangkok, Thailand; 11Department of Gastroenterology and Human Nutrition, All India Institute ofMedical Sciences, New Delhi, India; 12Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul, Korea; 13Division of Gastroenterology, Taipei Veterans General Hospital, and National Yang-Ming University School of Medicine, Taipei, Taiwan; 14Department of Behavioral Medicine, Tohoku University Graduate School of Medicine, Aoba Sendai, Japan; 15Seoul St Mary's Hospital, The Catholic University of Korea, Seoul, South Korea; 16Seth Gordhandas Sunderdas Medical College and King Edward Memorial Hospital, Parel, Mumbai, India;17Department of Gastroenterology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union MedicalCollege, Beijing, 18Union Hospital of Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China; and 19Department of Comprehensive Medicine, Tohoku University Hospital, Aoba Sendai, Japan Key words
Asia, diagnosis, diet, epidemiology, irritable Background and Aims: Many of the ideas on irritable bowel syndrome (IBS) are derived
bowel syndrome, pathophysiology, symptom.
from studies conducted in Western societies. Their relevance to Asian societies has not beencritically examined. Our objectives were to bring to attention important data from Asian Accepted for publication 18 April 2010.
studies, articulate the experience and views of our Asian experts, and provide a relevant guide on this poorly understood condition for doctors and scientists working in Asia.
Associate Professor Kok-Ann Gwee, Methods: A multinational group of physicians from Asia with special interest in IBS
Gleneagles Hospital, Annexe Block no. 05-37, raised statements on IBS pertaining to symptoms, diagnosis, epidemiology, infection, 6A Napier Road, Singapore 258500. Email: pathophysiology, motility, management, and diet. A modified Delphi approach was employed to present and grade the quality of evidence, and determine the level of
agreement.
Results: We observed that bloating and symptoms associated with meals were prominent
complaints among our IBS patients. In the majority of our countries, we did not observe a
female predominance. In some Asian populations, the intestinal transit times in healthy and
IBS patients appear to be faster than those reported in the West. High consultation rates
were observed, particularly in the more affluent countries. There was only weak evidence
to support the perception that psychological distress determines health-care seeking.
Dietary factors, in particular, chili consumption and the high prevalence of lactose malab-
sorption, were perceived to be aggravating factors, but the evidence was weak.
Conclusions: This detailed compilation of studies from different parts of Asia, draws
attention to Asian patients' experiences of IBS.
disseminate information pertaining to GI functional and motilitydisorders in Asia, with the ultimate aim of improving the care of On 15 October 2007, 18 active researchers in the field of gas- those suffering from these highly-prevalent conditions. On 21 trointestinal (GI) functional and motility disorders from different March 2008, ANMA was officially launched in Bangkok, Thai- Asian countries met on the sidelines of the Asia–Pacific Digestive land, and the development of an Asian Consensus on irritable Disease Week held in Kobe, Japan. The formation of the Asian bowel syndrome (IBS) was initiated.
Neurogastroenterology and Motility Association (ANMA) was While IBS is one of the most common conditions encountered proposed to promote research into, exchange knowledge of, and in gastroenterology and primary care practices, we believe that it Journal of Gastroenterology and Hepatology 25 (2010) 1189–1205
2010 Journal of Gastroenterology and Hepatology Foundation and Blackwell Publishing Asia Pty Ltd Asian consensus on irritable bowel syndrome K-A Gwee et al.
represents one of the least understood conditions for medical Grade of evidence and level of agreement doctors in Asia. The reason for this could be partly attributed to the nature of IBS as a condition defined only by its symptoms in theabsence of an objective marker, and partly because of the domi- Grade of evidence nance of Western studies and ideas in the available scientific lit- Further research is unlikely to change our erature. As the perception of symptoms (such as abdominal pain confidence in the estimate of effect and discomfort) and bowel function is inevitably influenced by the Further research is likely to have an important individual's psychosocial background, there is a need to question impact on our confidence in the estimate of the relevance of the commonly perpetuated ideas of IBS based effect and might change the estimate predominantly on studies from Western societies, and their socio- Further research is very likely to have an important impact on our confidence in the cultural expectations, to Asian patients. To address this, we felt it estimate of effect and is likely to change was important to review in detail the available Asian literature on IBS, bring the data from these studies to attention, and where data Any estimate of effect is very uncertain are lacking, to articulate the collective experience of our expert Level of agreement† members practicing in different parts of Asia.
Accept completely Accept with minor reservation Accept with major reservation Reject with major reservation A multinational group of physicians from Asia was selected based Reject with minor reservation on the strength of their interests in the study of IBS. Participants Reject completely were organized into four groups and tasked with raising statements †Statements were accepted when 80% or more of participants voted a on IBS pertaining to symptoms and diagnosis, epidemiology and infection, pathophysiology and motility, and management anddiet. The consensus development process was carried out in amodified Delphi method.1 Each team collected reference papers onIBS, published not only from Asia, but also from rest of the world with disturbed bowel pattern in the absence of organic causes
through online literature searching systems. Papers in English and that can be detected by routine medical tests.
local languages not available online were searched manually. Each Grade of evidence: high.
team had to present evidence in support of their statements.
Agreement: a. 11 (68.8%), b. 4 (25%), c. 1 (6.2%).
Through a series of intrateam and interteam discussions, email In this definition, we have intentionally qualified the term ‘organic voting, and round table discussions held between 3 September causes' as those that can be detected by routine medical tests. This 2008 and 10–11 January 2009, the statements were debated and is to take into account recent research employing more sensitive modified to achieve consensus. The grade of the evidence and the methods that have demonstrated differences in inflammatory level of agreement were based on the method of the GRADE markers, gut microbial flora, and genotypic expressions of inflam- Working Group (see Table 1).2 When the proportion of those who matory and neurotransmitter receptor molecules between IBS voted either to accept completely or with minor reservation was patients and controls.3–8 Thus, the traditionally accepted markers 80% or higher, the statement was regarded as acceptable and a of an organic disease—inflammation, infection and biochemical consensus as being reached. Finally consensus was achieved on alterations—might not be strictly applied to the current under- the following 37 statements.
standing of IBS.
This definition also presents bloating as a key symptom among IBS patients in Asia. In our review of Asian IBS series, we have found that bloating occurs almost as commonly as abdominal pain,and is an important reason for patient consultation.9–16 There is a For each grade of evidence, high indicates that further research is common perception among clinicians that bloating is a symptom unlikely to change our confidence in the estimate of effect, mod- of an upper GI disorder. However, bloating is experienced more erate indicates that further research is likely to have an important frequently in IBS patients than dyspeptic patients, and in recogni- impact on our confidence in the estimate of effect and might tion of this, the current Rome III guidelines no longer consider change the estimate, and low indicates that further research is very bloating as a symptom of dyspepsia.17–20 unlikely to have an important impact on our confidence in theestimate of effect and is likely to change the estimate. For each Statement 2: Early and confident diagnosis of IBS is important
level of agreement, a represents accept completely, b represents to minimize excessive investigations, inappropriate treatment,
accept with minor reservation, c represents accept with major and unnecessary surgery.
reservation, d represents reject with major reservation, e represents Grade of evidence: moderate.
reject with minor reservation, and f represents reject completely.
Agreement: a. 16 (100%).
Among some Chinese communities, IBS appears to be underdiag-nosed and underestimated. In Hong Kong, it was reported that only Symptoms and diagnosis
21% of patients with IBS criteria seen by their medical practitio- Statement 1: IBS is a condition characterized by abdominal
ners had received this diagnosis.14 In a study from Taipei, more pain, bloating or other discomfort occurring in association
than half of the 481 patients who were initially classified as having Journal of Gastroenterology and Hepatology 25 (2010) 1189–1205
2010 Journal of Gastroenterology and Hepatology Foundation and Blackwell Publishing Asia Pty Ltd K-A Gwee et al.
Asian consensus on irritable bowel syndrome functional dyspepsia were found to have IBS.21 An interesting frequent stools with pain onset all discriminated best between IBS observation in this study was that women who had consulted for and peptic ulcer. In fact, of the four symptoms, bloating was the dyspepsia had a threefold greater risk of hysterectomy than non- most commonly occurring, and only bloating occurred more fre- consulters. In another study from Taipei, IBS patients were two quently in IBS than IBD.32,33 However, despite their inclusion in times more likely to have had cholecystectomy.22 In a study from the Rome criteria, harder stools and less frequent stools with pain Singapore, 28% of patients referred by their general practitioners onset did not discriminate between IBS and organic disease in the for upper GI endoscopy were found to have IBS.23 original Manning study.32 Similar excess rates of abdominal surgery, in particular, chole- cystectomy and hysterectomy, have been reported in the West.24–26 Statement 5: The patient's bowel pattern should not be
It has been estimated that in the USA, 8% of IBS patients will described only by the stool frequency alone, but should include
undergo unnecessary cholecystectomy in their lifetime.27 One the stool type, according to the Bristol Stool Form Scale, and
study from the UK showed that over half of women who had gone the specific defecation symptoms of straining at stool, feeling of
to see their gynecologists for abdominal pain actually had symp- incomplete defecation, and urgency.
toms of IBS, and yet, the gynecologist only diagnosed IBS in 16% Grade of evidence: high Agreement: a. 16 (100%).
Doctors should not simply ask whether a patient has constipation Statement 3: It is recommended that all patients presenting
or diarrhea, but should enquire about specific defecation symp- with recurrent abdominal pain, bloating, or other discomfort
toms as recommended above. If the patient is not asked about of 3 months or longer duration should be screened for possible
their specific defecation symptoms or to identify their stool form, IBS by asking for bowel-related symptoms and checking for
he or she might not recognize the association with abdominal pain, bloating, or discomfort. In Asia, the constipation and diar- Grade of evidence: low.
rhea symptoms of IBS can be mild, and IBS patients might Agreement: a. 15 (93.8%), b. 1 (6.2%).
appear to have normal bowel habits by Western definitions. In the To promote an earlier diagnosis of IBS, we are introducing a Indian community, less than 1% of patients had stool frequencies broader entry portal. We wish to encourage doctors, in particular, of fewer than three per week, while among IBS patients, the primary care physicians, to consider the possibility of an IBS median stool frequency was twice a day, regardless of whether diagnosis early in their assessment of patients presenting with they had constipation or diarrhea.10 In a community study from abdominal pain, bloating, or other abdominal discomfort. All Singapore, 77% of patients with IBS thought they had normal patients with these symptoms should be asked specifically whether bowel habits, and yet when they were asked specific questions these symptoms are relieved with defecation, or associated with a relating to defecation symptoms, 50% had criteria for constipa- change in stool consistency or frequency. In addition, patients tion, 25% for diarrhea, and 4% for an alternating habit.13 We should be asked about the presence of the alarm features listed in would suggest that change in stool frequency as a symptom of the statement.7 Those who are possible IBS patients should be IBS should be de-emphasized. Consistently across all Asian worked up according to the algorithm in the statement8 (Fig. 1).
studies, a change in stool frequency was only a minor complaint, The 3 months' duration of symptoms is applied to permit differ- whereas difficulty with evacuation and passage of mucus were entiation from acute causes. For clinical practice, we would rec- common reasons for consultation.9,11–14,22 ommend this practice-oriented approach over the use of the Romecriteria. Experience suggests that few clinicians are familiar with Statement 6: IBS patients may complain of meal-related
the Rome criteria, and few, if any, apply it in their clinical symptoms, which include abdominal pain, bloating, sensations
practice.29–31 Furthermore, our recent review suggests that rigid of fullness or gas, and desire to defecate.
application of the Rome II criteria could have led to misclassifi- Grade of evidence: high.
cation of IBS patients as suffering from dyspepsia, and contributed Agreement: a. 12 (75%), b. 3 (18.8%), c. 1 (6.2%).
to inappropriate treatment with proton pump inhibitors, and to the Studies analyzing the relationship of IBS symptoms to meals, and excess surgery that was reported in a number of centers.9 However, studies of sensorimotor physiological responses to meals, provide for the purpose of standardization in clinical trials, we recommend strong evidence that eating a meal is an important trigger for that the current Rome criteria are applied, as well as the require- symptoms in IBS.34–41 One study from Sweden required IBS ments set out in statement 9.
patients to chart in detail the timing of symptoms throughout theday for up to 6 weeks; this revealed that pain was relieved with Statement 4: Bowel-related symptoms consist of abdominal
defecation on only 10% of occasions, whereas 50% of pain epi- pain, bloating, or other discomfort that is either improved by
sodes were brought on within 90 min of eating.42 This suggests passing stool or flatus, or associated with any change in stool
that the pain experienced by IBS patients might actually bear a form or frequency.
stronger temporal relationship to eating than to defecation.
Grade of evidence: low.
We believe that it is important to highlight the relationship of Agreement: a. 15 (93.8%), b. 1 (6.2%).
symptoms to meals in IBS. Mistaking meal-related IBS symptoms These characteristics are derived from the original studies by as dyspepsia could lead to excessive investigation with tests, such Manning and by Thompson.32,33 In these pivotal studies, patients as upper GI endoscopy and ultrasound scans, inappropriate treat- with IBS were compared with those who had peptic ulcer disease ments, such as acid suppression, and unnecessary surgery, such as and inflammatory bowel disease (IBD). Bloating, abdominal pain cholecystectomy.22,23 This could be a particular problem in Asia relieved with defecation, looser stools with pain onset, and more because our patients appear to present more frequently with upper Journal of Gastroenterology and Hepatology 25 (2010) 1189–1205
2010 Journal of Gastroenterology and Hepatology Foundation and Blackwell Publishing Asia Pty Ltd Asian consensus on irritable bowel syndrome K-A Gwee et al.
IBS diagnostic algorithm
Possible IBS
Recurrent abdominal pain, bloating, or other discomfort for ≥ 3 months associated with 1 or more of the following: • relief with defecation • change in stool form (show patient the Bristol Stool Scale) • change in stool frequency Alarm features
• patient age 45 years or older • blood in stools • unintended weight loss • nocturnal symptoms • fever • abdominal mass • ascites • family history of colorectal caner Probable IBS
• presence of anemia Explain IBS Treat primary symptoms Repeat visit within 6 weeks alarm features (+) Check for new symptoms Review alarm features Continue treatment as necessary or modify Laboratory results • anemia • leukocytosis • high ESR, CRP • abnormal blood chemistry • fecal occult blood positive alarm features, or Repeat visit within 6 weeks refractory symptoms (+) Check for new symptoms Diagnostic algorithm for irritable gastroenterologist protein; ESR, erythrocyte sedimentation rate.
abdominal pain than in Western series.10,11,13,43 In a number of Grade of evidence: moderate.
studies from Asia, it appeared that patients with IBS might have Agreement: a. 11 (68.8%), b. 4 (25%), c. 1 (6.2%).
been misclassified as suffering from dyspepsia.9,12,21,44 In a study We propose age of 45 years as a cut-off for ethnic groups who are from Taiwan, more than half of patients initially classified as more susceptible to colorectal cancer (Japanese, Koreans, suffering from dyspepsia were reclassified as having IBS when it Chinese), while other ethnic groups (Indians, Thais) can opt for a was clarified that their upper abdominal pain was exclusively cut-off of 50 years. This is a modification of the recent Asia– relieved with defecation.21 Pacific consensus recommendations for colorectal cancer screen-ing.45 We have set a younger cut-off age because IBS patients are Statement 7: Alarm features to check for in IBS include age
symptomatic and would not qualify for screening guidelines, 45 years or older, presence of anemia, blood in the stools, unin-
which are intended for asymptomatic individuals.
tended weight loss, nocturnal symptoms, fever, abdominal
A recent study from Australia has provided data on the diagnos- mass, ascites, and a family history of colorectal cancer (see
tic yield of alarm features in IBS.46 Age over 45 years, blood coating stools, blood mixed with stools, and blood on toilet paper Journal of Gastroenterology and Hepatology 25 (2010) 1189–1205
2010 Journal of Gastroenterology and Hepatology Foundation and Blackwell Publishing Asia Pty Ltd K-A Gwee et al.
Asian consensus on irritable bowel syndrome were found to discriminate significantly between IBS and patients upper GI endoscopy, in view of the high prevalence of severe with organic bowel disease. However, weight loss and nocturnal gastritis, peptic ulcer disease, and gastric cancer in many parts of pain did not significantly discriminate between IBS and organic Asia. The underlying motivation is also based on the expectation disease. It should be noted that this study was based on an Aus- that these studies will be funded by either national research agen- tralian population, and patients in the organic disease group con- cies or pharmaceutical companies. Thus, the costs involved sisted predominantly of those with IBD or diverticular disease, will not impact on the cost-effectiveness of the day-to-day man- both of which are currently uncommon in many Asian countries.
agement of IBS.
Statement 8: At the primary care level, use of a screening
Statement 10: The subclassification of IBS, according to the
algorithm, comprising symptom criteria, a checklist of alarm
bowel pattern, can be based on a modification of the Rome III
features, and guidelines on monitoring procedure, is recom-
criteria, but this needs validation.
mended (see Fig. 1).
Grade of evidence: low.
Grade of evidence: low.
Agreement: a. 10 (50%), b. 10 (50%).
Agreement: a. 13 (81.3%), b. 3 (18.7%).
In the Rome III classification, IBS is subtyped based on stool We believe that it is important for doctors to move away from consistency alone. We believe that this approach is appropriate for seeing IBS as a last resort diagnosis. This algorithm is meant to Asia, given our observations that changes in stool frequency were help the primary care physician make an early diagnosis of IBS only a minor complaint among our patients. In line with this, we (Fig. 1). In this algorithm, doctors are expected to consider a recommend that patients with types 1–3 stools on the Bristol Stool possible diagnosis of IBS the moment a patient presents with the Scale are classified as IBS with constipation (IBS-C), and those main complaint of abdominal pain, or other discomfort. The next with type 5–7 stools are classified as IBS with diarrhea (IBS-D).
step is to ask the patient whether the main complaint is associated Patients with both hard and soft stools over periods of hours or with relief upon defecation, or with a change in stool consistency days are classified as IBS mixed type, while patients whose stools or frequency. We feel it is important to qualify the symptom with change from hard to soft, or vice versa, over weeks or months, are a minimum of 3 months' or 12 weeks' duration of onset, and to classified as IBS alternating type. This subclassification is pres- exclude all the alarm features. Once this has been achieved, the ently adopted because good correlation has been demonstrated patient should then be given the diagnosis of probable IBS. If the between stool form and colonic transit times, and this can be used primary care physician suspects that a patient has lactose intoler- as a guide to selection of treatments according to their effects on ance, then the patient could undertake either a trial of lactose colonic transit. However, the impact of this on treatment response exclusion or a lactose hydrogen breath test, and if this diagnosis is remains to be validated. Furthermore, this approach does not take confirmed, then it should be managed accordingly. In patients with into account other important pathophysiological disturbances, in diarrhea, stool samples should be sent for microscopic examina- particular, visceral sensitivity.
tion to exclude parasitic infection.
We would emphasize that the diagnosis of IBS should also be Epidemiology and infection
put to the test of time, that is, a patient with a diagnosis of probableIBS should be encouraged to return for two consecutive reviews Statement 11: The reported prevalence of IBS in Asian coun-
each to be carried out within 6 weeks of each other. At each visit, tries varies from 2.9% to 15.6%, but the study population and
the patient should be assessed for their response to treatment, new diagnostic criteria have not been consistent.
symptoms, and alarm features. At any stage during this algorithm, Grade of evidence: high.
if the patient is found to have any of the alarm features listed or any Agreement: a. 14 (87.5%), b. 2 (12.5%).
of the abnormal laboratory results, a gastroenterology consult It has been suggested that the prevalence of IBS is lower among should be sought. A gastroenterology consult should also be Asian than Caucasian communities. Early studies employing the sought if the patient is still symptomatic at the end of the 12-week same questionnaire reported a lower prevalence of spastic irritable monitoring period.
colon in the Thai community (4.4%) compared with British(13.6%) and US (22.3%) patients.47 In a study applying the Statement 9: For clinical trials, all patients should have at least
Manning criteria to different ethnic communities in California, full blood counts, erythrocyte sedimentation rate, C-reactive
USA, Asians had a lower prevalence compared with other racial groups.48 In contrast, the prevalence appeared to be higher in Japan than in the Netherlands (25% vs 9%).49 Recent studies applying the Grade of evidence: moderate.
Rome II criteria also suggest that the prevalence in Japan (9.8%) Agreement: a. 10 (62.4%), b. 3 (18.8%), c. 3 (18.8%).
and Singapore (8.6%) is comparable to Europe (9.6%) and A number of members expressed reservations because of cost Australia (6.9%), although not as high as in Canada and the UK considerations. However, we wish to emphasize that this recom- mendation is specific to clinical trials and is not applied to clinical Variation in the prevalence of IBS in different studies might be practice. The main aim of this statement is to protect our patients related to several factors, such as demographic characteristics of from being entered inappropriately into clinical trials. For the population, willingness to respond to questionnaires, geo- example, an ultrasound scan is recommended if patients present graphical location, and the criteria used to define IBS. For with symptoms of biliary colic, so that patients who might be example, Manning criteria appears to yield higher values com- harboring symptomatic gallstones are not treated as having IBS.
pared to either the Rome I or II criteria.50 When Kang compared Patients with upper abdominal symptoms should also undergo an the prevalence of IBS in the East to that in the West, he reported Journal of Gastroenterology and Hepatology 25 (2010) 1189–1205
2010 Journal of Gastroenterology and Hepatology Foundation and Blackwell Publishing Asia Pty Ltd Asian consensus on irritable bowel syndrome K-A Gwee et al.
respective median values of 12% versus 17% by Manning criteria, where it is 311 g per day, compared to less than 200 g per day in 9.2% versus 10.4% by the Rome I criteria, and 7.6% versus 6% by the West.11,12,57 However, the normal stool frequency reported from the Rome II criteria.50 Furthermore, it is possible that the preva- other parts of Asia appears to be similar to that in the West; over lence of IBS in Asian countries has increased over time, account- 97% of people in Singapore and Thailand report stool frequency ing for the higher median value of more recent studies from Asia between three per day and three per week; 41% and 84% of people employing the Rome II criteria when compared with that from in Korea and China, respectively, report once daily bowel Western studies.43,50 movement.47,58–60 These differences should be taken into accountwhen defining bowel habits in various populations.
Statement 12: IBS is as prevalent in men as in women in some
Asian countries.
Statement 15: IBS can follow bacterial GI infections, although
Grade of evidence: moderate.
data are available only from a few Asian countries.
Agreement: a. 10 (62.5%), b. 5 (31.3%), c. 1 (6.2%).
Grade of evidence: high.
Most studies from the West reported two to three times higher Agreement: a. 13 (81.3%), b. 3 (18.7%).
prevalence of IBS in women than in men.9 However, several recent Studies from the West suggest that an acute GI infection is an studies from Asia have reported an as high, if not higher, preva- important trigger for the development of IBS.61,62 In Asia, there are lence of IBS in men than in women; (in India 7.9% vs 6.9% in one two prospective studies documenting the development of IBS fol- study, 4.3% vs 4% in another study; in Korea 7.1% vs 6%; in Hong lowing Shigella infection. In a cohort study from Beijing, the Kong 6.6% vs 6.5%; in Pakistan 13.1% vs 13.4%).9 Several other incidence of functional bowel disorders and IBS by Rome II cri- studies from Asian countries have reported non-significant differ- teria among 295 patients recovering from dysentery was 22.4% ences in prevalence between men and women (in Taiwan 21.8% vs and 8.1%, respectively, compared with an incidence of 7.4% and 22.8%; in Singapore 7.8% vs 9.4%).9 Only studies from two Asian 0.8%, respectively, in the control cohort.63 In a study from Seoul countries have reported a convincingly higher prevalence of IBS in involving an outbreak of Shigella infection among 181 health-care women than in men (in Bangladesh 15% vs 9.4%; in Japan 15.5% workers, the odds ratio of developing IBS was calculated to be 2.9 vs 10.7%).9 Statement 13: Dyspepsia is not uncommon in patients with IBS
Statement 16: IBS in a proportion of patients can be associated
with small intestinal bacterial overgrowth.
Grade of evidence: high.
Grade of evidence: moderate.
Agreement: a. 13 (81.3%), b. 2 (12.5%), c. 1 (6.2%).
Agreement: a. 13 (81.3%), b. 3 (18.7).
The frequency of dyspeptic symptoms reported among patients One center from the USA has reported a prevalence of small with IBS in various Asian studies was as follows: India (58%), intestinal bacterial overgrowth (SIBO) in their IBS patients of 84% China (25–64%), and South Korea (14%).15,51–53 Misclassification compared with 20% in healthy controls.65 The definition of SIBO of IBS as dyspepsia could be a particular problem in Asia in that study was based on a rise in breath hydrogen concentration because our patients appear to present more frequently with by 20 ppm above basal levels within 90 min following ingestion of upper abdominal pain than in Western series.9–11 In a study from a lactulose load (lactulose hydrogen breath test; LHBT). Using the Singapore, Ho et al. classified all patients with upper abdominal same criterion, a study from Korea reported a SIBO prevalence of symptoms as having dyspepsia; in an earlier study from the same 48.7% in IBS and 26.5% in controls.66 There are issues with the institution, 44% of patients with a functional cause of chronic use of this definition in diagnosing SIBO. First, there is no vali- upper abdominal pain had IBS, and in a later study, it was dation of this criterion against quantitative jejunal aspirate culture, reported that more than 50% of IBS patients localized their pain by which the prevalence of SIBO (defined as > 105 bacteria/mL) in to the upper abdomen.12,13,54 In a study from Taiwan, more than IBS was reported to be only 4%.67 Another method of identifying half of patients who were initially classified as suffering from SIBO employs the glucose hydrogen breath test (GHBT), which is dyspepsia were reclassified as having IBS when it was clarified less influenced by the orocecal transit time (OCTT). Using the that their upper abdominal pain was exclusively relieved with GHBT, the prevalence of SIBO in IBS patients was reported to be 31% in a US study, 46% in a European study, and 8.5–13% inIndian studies.68–72 It is important to take into account the relatively Statement 14: In the population of some south Asian countries,
shorter OCTT that have been reported in Asian patients compared stool frequency is higher than that in the West.
with the West.73–76 The implication of this is that patients and Grade of evidence: moderate.
healthy patients who have short transit times might give a false Agreement: a. 10 (62.5%), b. 6 (37.5%).
positive LHBT.
In the West, the normal stool frequency range is from three perweek to three per day.55,56 However, several studies from India Statement 17: In some endemic countries, a mild form of
have reported a higher stool frequency.10,57 In a recent study from tropical sprue and Giardia infection can mimic IBS.
India involving 4500 patients drawn from the community, defeca- Grade of evidence: low.
tion frequency was on average greater than three stools per day in Agreement: a. 12 (75%), b. 4 (25%).
167 (3.7%), three per day in 242 (5.4%), two per day in 1535 In some Asian populations, parasitic infestation, SIBO, and tropi- (34%), one per day in 2520 (56%), and less than three per week in cal sprue are common causes of malabsorption syndrome.77 Such 43 (1%).10 In addition to higher stool frequency, the average stool conditions, when mild, might not present with weight loss or weight also appears to be greater in the Indian adult population, nutritional deficiency, and could thus mimic IBS. In fact, there are Journal of Gastroenterology and Hepatology 25 (2010) 1189–1205
2010 Journal of Gastroenterology and Hepatology Foundation and Blackwell Publishing Asia Pty Ltd K-A Gwee et al.
Asian consensus on irritable bowel syndrome several reasons to suspect that there might be considerable overlap time according to dyspeptic symptoms.92 Studies from Taiwan and between post-infectious IBS and post-infectious malabsorption India recorded slower orocecal transit times in constipation- predominant IBS patients compared with healthy controls, whilediarrhea-predominant IBS patients recorded faster times than Statement 18: Perception of symptoms of IBS can vary in Asia;
healthy controls.73,74 Enhanced colonic motility response to injec- thus, a questionnaire including relevant socioeconomic and
tion with corticotropin-releasing hormone (CRH) has been cultural factors in Asia should be developed and validated for
reported in a Japanese study.93 Studies from Korea have reported that diarrhea-predominant IBS patients demonstrate differences in Grade of evidence: low.
anorectal manometry findings from constipation-predominant IBS Agreement: a. 8 (50%), b. 6 (37.5%), c. 2 (12.5%).
patients, as well as showing a significant post-prandial decrease in Several lines of evidence suggest that the perception of symp- rectal compliance.94,95 However, the association of motility distur- toms by IBS patients in Asia could be different from those in the bances with specific symptoms has been inconsistent, and differ- West. Patients in Asia appear to be bothered more by upper ences in motility measurements between IBS and healthy controls abdominal symptoms and bloating, and it appears that IBS could appear to be quantitative rather than qualitative.96,97 be misdiagnosed as dyspepsia.9 Many IBS patients in Asia mightnot perceive their bowel pattern to be abnormal; in one study, Statement 21: GI motility disturbances in IBS patients can
58% of patients who had criteria for constipation, diarrhea, or arise from an exaggerated physiological response to environ-
alternating pattern, perceived their bowel habit to be normal.13 In mental stimuli, such as meals and stressors.
India, the median stool frequency was twice a day, whether the Grade of evidence: moderate.
patients considered themselves to have diarrhea or constipa- Agreement: a. 11 (64.71%), b. 5 (29.41%), c. 1 (5.88%).
tion.10 Asian patients appear to be bothered less by the fre- When IBS patients were compared with healthy controls, meal quency of their stools and bothered more by the feeling of ingestion produced a greater increase in the pressure amplitude incomplete defecation.9 A high rate of consultation for IBS has generated in the sigmoid colon, and also a longer increase in been reported from many Asian communities (Singapore, 84%; colonic motility.37,38,98 The response to meals can vary depending Japan, 59%; Taiwan, 55%; Hong Kong, 47–57%.9 With such a on the bowel habit. In one study from Korea, diarrhea- high rate, the role of psychological disturbance in driving con- predominant IBS patients demonstrated a greater increase in sultation behavior is questioned.
colonic motor activity than constipation-predominant IBS.99 Inexamining experimentally-induced stressors, such as criticism, hypnotically- Pathophysiology and motility
induced anger, dichotomous listening, and cold water hand immer-sion.100,101 These studies reported differences between IBS and Statement 19: IBS is a multifactorial disorder where a variable
non-IBS patients in motor and sensory responses, such as combination of genetic factors, gut infections, brain–gut inter-
increased colon motor activity and pressure wave amplitudes, as actions, and psychological disturbance can interact in the
well as decreased antral motor activity, more intense and un- pleasant sensation, and decreased rectal perception and pain Grade of evidence: low.
thresholds.100,101 A series of studies from a center in Japan has Agreement: a. 11 (64.71%), b. 6 (35.29%).
demonstrated that IBS patients have a greater colonic motor The factors listed above have been implicated in the pathophysi- response than healthy patients to experimentally-induced stress, ology of IBS. In any given patient, it is likely that more than one and suggests that CRH is a possible mediator of this response.102,103 factor might be present. For example, in post-infectious IBS, stress Furthermore, in these studies, CRH infusion produced abdominal from major life events predicts the development of IBS in patients pain or discomfort that lasted longer in IBS patients than in healthy with higher anxiety levels who also demonstrate more severe controls, as well as higher plasma adrenocorticotropic hormone inflammatory changes and greater immune activation during the levels in IBS patients than in controls.104 infection.3,62,79 However, the type of factors present can vary fromone patient to another. Although studies are more limited in non- Statement 22: Some diarrhea-predominant IBS patients have
post-infectious IBS, other factors, such as genotypic variations, been shown to have rapid GI transit, while some constipation-
differences in gut microbial flora, and altered brain activation predominant IBS patients have slow GI transit.
patterns, have been implicated.7,80–85 Grade of evidence: low.
Agreement: a. 14 (82.35%), b. 3 (17.65%).
Statement 20: Altered GI motility can be found in IBS
In general, Asian studies have reported similar observations as patients, although it does not always correlate with IBS
those from the West, where IBS patients with diarrhea have rela- tively shorter orocecal and colonic transit times, while those with Grade of evidence: low.
constipation have relatively longer transit times. However, these Agreement: a. 15 (88.24%), b. 1 (5.88%), c. 1 (5.88%).
differences in intestinal transit times are not invariable. Further- Differences between IBS patients and healthy controls have been more, studies from the West suggest that intestinal transit times reported when motility measurements have been studied in every demonstrate a closer correlation with stool form than with stool region of the GI tract.36,86–91 One study from Korea reported that frequency.105 The colonic transit times reported both for healthy gastric emptying time in patients with IBS was delayed compared volunteers and IBS patients from studies in India and Hong to that of controls, but there was no difference in gastric emptying Kong appear to be faster than those reported from the West.57,106 Journal of Gastroenterology and Hepatology 25 (2010) 1189–1205
2010 Journal of Gastroenterology and Hepatology Foundation and Blackwell Publishing Asia Pty Ltd Asian consensus on irritable bowel syndrome K-A Gwee et al.
Statement 23: Visceral hypersensitivity plays an important
Recent studies suggest that the measurement of serum immu- role in the development of symptoms in IBS patients.
noglobulin (Ig)G antibodies to food can help to identify specific Grade of evidence: high.
food intolerance.127–131 Zuo et al., from Shandong province in Agreement: a. 15 (88.24%), b. 2 (11.76%).
China, examined food antigen-specific serum IgG and IgE anti- Studies employing distension of the colon to the study sensory bodies in IBS patients.127 Similar to the data from Western coun- threshold have demonstrated enhanced visceral sensitivity in IBS tries, Zuo et al. found no increase in IgE levels to various foods, patients compared with controls.107,108 Furthermore, using this para- but found increased IgG levels to wheat (but not to rice), and in digm, it is possible to reproduce the patient's usual abdominal addition, reported increased IgG levels to egg, soybean, shrimp, pain.109,110 It has also been suggested that visceral hypersensitivity and crab. One Korean study reported higher rates of positive skin could be a marker of IBS.107 In one study, nearly all patients (94%) prick tests to certain food antigens.132 with IBS had altered rectal perception, and there was a correlationbetween this altered perception and lower abdominal pain, rectal Statement 25: IBS patients can show altered brain activations
fullness, and urgency.107 It also appears that visceral hypersensitiv- in specific regions, which might be involved in the perception of
ity in IBS patients is not confined to the colon, but has also been pain or discomfort.
reported in the esophagus, stomach, duodenum, and ileum, corre- Grade of evidence: moderate.
lating with symptoms arising from these anatomical regions.36,111–113 Agreement: a. 13 (76.47%), b. 4 (23.53%).
As with Western studies, several studies from Korea, Japan, Advanced brain imaging techniques, such as positron emission and China support the presence of enhanced visceral perception tomography (PET) and functional magnetic resonance imaging in IBS patients.95,114–119 One study from Korea has shown that (fMRI), have made it possible to study brain–gut interactions.
patients with constipation-predominant IBS show more rectal Functional brain imaging studies have shown how the brain pro- hypersensitivity than patients with functional (painless) constipa- cesses visceral sensation. Like somatic sensation, visceral sensa- tion.118 One study from China demonstrated that cold water tion is presented to somatosensory cortices, and also to the limbic intake lowered the visceral perception threshold.117 In one study system and paralimbic structures, which modulate emotional from Singapore, it was possible to reproduce the usual abdomi- changes via the autonomic nervous system. Only a few signals nal pain in up to 78% of IBS patients when air was insufflated delivered to the brainstem and thalamus from visceral organs are into the rectum.120 In one study from Korea, lower abdominal consciously perceived in the cortex. Several brain imaging studies pain, rectal fullness, and urgency were reproduced by rectal using PET and fMRI have demonstrated that experimental rectal balloon distension in 69% of IBS patients.107 In another study, pain produced altered or greater activation of pain processing there was a significant correlation of post-prandial rectal hyper- regions in the brain, such as the anterior cingulated cortex, thala- sensitivity with a sense of incomplete evacuation and increased mus, insula, and prefrontal cortex.133–137 bowel movements.95 Asian studies showed good agreement with Western studies, However, enhanced visceral perception was not observed in all regarding the activated cerebral regions during colon distension.
IBS patients, and as many as one-third of IBS patients do not One Japanese study using PET has reported that colonic disten- demonstrate a lower threshold to bowel distension.95,107 One study sion, especially descending colon distension, produced enhanced from Korea has reported that the visceral sensory threshold in visceral perception and activation of specific regions in the brain, response to rectal balloon distension did not correlate with the including the limbic system and prefrontal cortex.135 Another reported severity of symptoms, such as bloating, straining, mucus, Chinese study using fMRI has reported that in most cases, rectal incomplete evacuation, urgency, stool form, and defecation distension increased the activity of the anterior cingulate cortex, insula, prefrontal cortex, and thalamus in most cases.138 In addi-tion, they have demonstrated that the activated areas at the insular, Statement 24: Certain foods can aggravate symptoms in some
prefrontal cortex, and thalamus regions were significantly greater in patients with IBS than that in control patients during rectal Grade of evidence: low.
balloon distension. A study from Singapore indicated that there Agreement: a. 13 (76.47%), b. 4 (23.53%).
was abnormal activation of the brain areas observed in fMRI Studies from the West suggest that the two main food groups that associated with the anticipation of rectal pain in IBS patients can aggravate symptoms in IBS are dairy products and cere- during rectal stimulation.139 als.121,122 Studies from Asia suggest chili and curry are possiblefood triggers for dyspepsia-like upper abdominal pain in IBS Statement 26: Psychological disturbances occur commonly in
patients.54,123 Lactose intolerance is common in Asia, and it could be a contributing factor for symptoms, such as bloating, flatulence, Grade of evidence: high.
and diarrhea. However, studies from both the West and Asia gen- Agreement: a. 11 (64.71%), b. 4 (23.53%), c. 2 (11.76%).
erally report similar prevalence of lactose malabsorption between Psychiatric diagnoses, such as anxiety, depression, neuroticism, controls and IBS patients, and the avoidance of lactose has yielded hypochondriasis, and abnormal illness behavior were commonly mixed results in studies from the West.72,99–101,124 Fructose malab- reported in studies from tertiary centers in the West.140,141 Studies sorption has also been implicated in IBS.125 However, the effect of from Hong Kong, Japan, and India have reported higher anxiety fructose on IBS patients without fructose malabsorption is uncer- and depression scores in IBS patients compared to non-IBS tain. Fructose tolerance has been less well studied in Asia, but patients.15,142–147 However, a psychological basis should not be limited studies suggests that this might be more prevalent in Asian generalized to all IBS patients. It is difficult to determine the cause women than men.126 and effect relationship of psychological disturbance with IBS. As Journal of Gastroenterology and Hepatology 25 (2010) 1189–1205
2010 Journal of Gastroenterology and Hepatology Foundation and Blackwell Publishing Asia Pty Ltd K-A Gwee et al.
Asian consensus on irritable bowel syndrome IBS is a chronic disease, the possibility remains that the poor Statement 29: Genetic factors can contribute to the develop-
quality of life, reduced productivity, and work absenteeism arising ment of IBS, and gene–environmental interactions need to be
from symptoms could result in secondary anxiety, depression, and disturbed sleep.
Grade of evidence: low.
Lifetime and daily stressful events were also reported to be Agreement: a. 12 (70.59%), b. 4 (23.53%), c. 1 (5.88%).
more common in IBS patients than non-IBS patients and healthy It has been suggested that genetic factors can predispose to the controls.148–153 Adverse lifetime stressors include physical, emo- development of IBS. This hypothesis has been based largely on tional, or sexual abuse. Several studies from Japan have sought findings of a higher prevalence of family history of IBS in patients to ascertain the contribution of stress and other psychological than in non-IBS controls, and a higher concordance rate of monozy- factors to the development of IBS. In one study, significantly gotic twins for IBS than that of dizygotic twins. However, familial more IBS than non-IBS patients met the criteria for agoraphobia aggregations can be due to both similar environments in families and panic disorder.154 In another study, IBS patients reported and genetic influences. The contributions of these factors have not more perceived stress than asymptomatic controls.143 In another clearly been distinguished by studies evaluating genetic influence, study, perceived stress was reported in 55% of patients with IBS such as twin studies. Studies from Asia are limited and have by Rome II criteria.155 However, the role of perceived stress produced conflicting results. One study from China reported that could have been overestimated in these Japanese studies because the 5-HTTLPR allele L/L genotype occurred with greater frequency of a selection bias arising from the recruitment of these patients in constipation-predominant IBS, although this could not be con- from psychosomatic medicine clinics rather than from general firmed in another Chinese study.165,166 One study from Korea reported that there was no relationship between serotonin trans-porter gene polymorphisms and IBS, but in another Korean study, Statement 27: Psychosocial factors have significant role in the
which had a larger sample size, a significant association was development and aggravation of IBS symptoms.
observed between the serotonin transporter (SERT) polymorphisms Grade of evidence: moderate.
and IBS, and in particular with diarrhea-predominant IBS.167,168 Agreement: a. 12 (70.59%), b. 5 (29.41%).
Prospective studies in post-infectious IBS have clearly demon- Management and diet
strated that psychosocial stress factors, such as major life events,anxiety, neuroticism, and somatization, predict the development of Statement 30: The aims of IBS management are symptom
IBS following an episode of acute gastroenteritis.3,62,79 Further- relief and improvement in quality of life.
more, stress can provoke GI symptoms and exacerbate symptoms Grade of evidence: high.
in IBS patients.150,152,156,157 Although these phenomena are also Agreement: a. 16 (94.12%), b. 1 (5.88%).
observed in healthy patients, the response to stress was reported to As IBS is a chronic, non-life-threatening disorder, its largest be far greater and more persistent in IBS patients.158 impact is expected to be on quality of life.169–174 Studies from both One study from Korea has shown that depressed women com- the East and the West suggest that regardless of whether they seek plained of GI symptoms more frequently according to the severity professional medical advice or not, individuals with IBS report of depression.146 Two Japanese studies suggest that psychosocial poorer quality of life than controls.143,175,176 A number of studies stress can aggravate GI symptoms in IBS.155,159 from Asia provide additional evidence that quality-of-life scores inIBS patients are lower than in controls.143,161,175,177–179 We recom- Statement 28: Psychosocial factors are important determi-
mend that the aims of IBS management should be to relieve nants of health-care seeking in those with moderate to severe
symptoms as much as possible and to improve quality of life.
IBS.
Grade of evidence: low.
Statement 31: A good doctor–patient relationship is important
Agreement: a. 11 (64.71%), b. 6 (35.29%).
in the management of IBS. Physicians should try to identify
It has been suggested that psychosocial factors are important deter- contributing factors and address the patient's concerns.
minants of consultation behavior in IBS.160 In one study from Grade of evidence: moderate.
Hong Kong, anxiety proved to be the only independent predictor Agreement: a. 16 (94.12%), b. 1 (5.88%).
for health-care seeking.142 In Pakistan, a high psychological dis- Several studies support the notion that a strong doctor–patient tress score was a strong predictor of IBS in men, but not in women, while in India, there appeared to be more consulters in the higher ment.169,171,180,181 Based on an analysis of these studies, we recom- socioeconomic classes.10,161 However, in Japan and Korea, psycho- mend that the physician should strive to achieve the following: (i) logical distress did not appear to predict consultation for IBS.155,162 identify, as far as possible, contributing factors, including GI infec- Thus, there is only weak evidence to support the consensus tions, psychosocial stressors, use of medications (especially anti- group's perception that psychological distress is an important biotics and analgesics), previous abdominal or pelvic surgery, and determinant of health-care seeking. Furthermore, consultation recent dietary changes; (ii) develop appropriate analogies to help rates were reported to be as high as 84%, 57%, and 55% in the patient understand the pathophysiological disturbances associ- Singapore, Hong Kong, and Taipei, respectively, and were gener- ated with IBS symptoms; (iii) provide reasonable evidence to ally higher than reported in certain Western countries.9,12,22,142,163,164 reassure the patient that he or she does not have a life-threatening Taking into account the high medical consultation rates, sociocul- condition; and (iv) involve the patient in setting reasonable lif- tural factors might prove to be more important determinants of estyle, drug treatment, and behavioral goals. One of the anticipated health-care seeking than psychological factors.
outcomes of this approach is that if they can be confidently Journal of Gastroenterology and Hepatology 25 (2010) 1189–1205
2010 Journal of Gastroenterology and Hepatology Foundation and Blackwell Publishing Asia Pty Ltd Asian consensus on irritable bowel syndrome K-A Gwee et al.
reassured, it might be possible to manage patients with minimal Japan, marked improvement in IBS symptoms was reported after symptoms (i.e. symptoms that are not bothersome), who might be 10 days of fasting with only water intake.190 Many suspected food consulting a doctor because of anxiety as an implication of their intolerances might not be substantiated when subjected to a symptoms, without medications.
double-blind food challenge.122,185,191 In many instances, psycho-logical factors appear to be important. There is very little evidence Statement 32: Management of IBS should be individualized
to support IgE food allergy testing in IBS.186 Tests which employ and should target all bothersome symptoms, while taking into
electrodermal devices or a hair analysis to identify food allergy account specific IBS subtypes, symptom severity, and contrib-
and intolerance are unproven, and consumer advocacy testing uting factors (including psychosocial issues).
has shown several commercial allergy tests to be unreliable.192 A Grade of evidence: moderate.
small number of recent studies suggests a potential role for food- Level of agreement: a. 13 (76.47%), b. 3 (17.65%), c. 1 (5.88%).
specific IgG antibody testing, but the clinical benefits are The management approach propounded within statements 32–35 is based on a model proposed by Thompson and Drossman, whichpredicts that the majority of patients (estimated to account for 95% Statement 34: Suggested initial treatments for patients with
of all IBS patients) who are seen in primary and secondary care IBS include various combinations of antispasmodic, laxative,
settings, will present with mild to moderate symptoms, for which prokinetic, antidiarrheal, and probiotic agents.
physiological disturbances play an important role, and in whom Grade of evidence: moderate.
psychological factors are not thought to be dominant.182 The expe- Agreement: a. 6 (37.50%), b. 8 (50%), c. 1 (6.25%), d. 1 (6.25%).
rience reviewed in statement 31 provides support that this In line with statement 32, we suggest the use of combination approach can be reasonably expected to produce a favorable treatment to target all bothersome symptoms, as well as contrib- outcome. This approach is also consistent with the guidelines from uting factors. This suggestion is supported by a number of studies other major professional organizations.97,183 This statement is that have reported good treatment outcomes in as many as 90% of qualified by the premise that for patients with a major psychiatric patients in response to a holistic approach (as outlined in statement diagnosis, it is important that the patient is co-managed by a 31) together with a combination of pharmacological treatments psychiatrist (see statement 36).
comprising antispasmodic agents, laxatives, and anxiolytic or anti-depressant agents.169,180,194,195 A critique published in 1988 of 43 Statement 33: The taking of dietary history and dietary modi-
controlled clinical trials, of which 39 involved only single agents, fication could be helpful in the management of some IBS
concluded that there was no convincing evidence that any therapy was effective in treating the IBS symptom complex. One study Grade of evidence: low.
which compared the response to variable combinations of antis- Level of agreement: a. 5 (31.25%), b. 9 (56.25%), c. 2 (12.50%).
pasmodic, anxiolytic, bulking agents, and placebo reported that the Addressing the dietary aspects of IBS is important, as many IBS percentage of patients who achieved sustained improvement over patients experience symptoms in relation to meals, and many are 3 months rose with the number of active agents prescribed, with interested to know what foods to avoid.184,185 Studies suggest that the highest response (recorded at 58%) observed in patients receiv- 20–67% of IBS patients might have dietary triggers, and a sub- ing three drugs.195 However, in one recent study, only 31% of stantial number report improvement upon dietary management.185 patients achieved satisfactory relief in a treatment protocol com- However, as a very large number (60 or more) of foods have been prising only reassurance, explanation of IBS, and counseling, implicated in IBS, and many patients report intolerance to a large without receiving pharmacotherapy.196 number of foods (40% of patients in one study had intolerance to Combinations of antispasmodic, laxative, antidiarrheal, and six or more foods; in another study the mean number of foods probiotic agents are suggested as first-line therapy, as they are patients were sensitive to was six), it is not possible to recommend generally safe and inexpensive. In various meta-analyses and sys- a standard diet for all IBS patients.121,128 Therefore, we suggest, as tematic reviews, antispasmodics as a class of medications have a first step, taking a detailed dietary history and the use of a food been shown to improve abdominal pain and global symptoms in diary. Dietary modifications can then be suggested if this assess- IBS.197–199 Bulking agents were frequently promoted for IBS in the ment identifies potential dietary factors. Based on our analysis of past, but recent careful re-evaluation has drawn attention to sig- various food intolerance studies (discussed in statement 24), we nificant limitations. While ispaghula could have some benefit for suggest that doctors should look out for excessive consumption of treating mild constipation in IBS, dietary fiber, especially in the dairy- and lactose-rich products, dietary fiber (especially in the form of bran cereals, could aggravate abdominal pain and form of bran or other cereals), and fructose- or fructan-rich foods.
bloating.197,199–201 While there are no placebo-controlled, random- While we believe that this approach could contribute to building ized studies of commonly-available over-the-counter laxatives, the doctor–patient relationship, there is limited information these can be tried for patients with constipation in IBS-C, bearing regarding the effects of dietary treatment on quality of life in in mind that lactulose could increase flatulence, and stimulant laxatives, like senna and bisacodyl, can cause abdominal The doctor should take care that dietary modification does not cramps.202–204 For the control of diarrhea symptoms, like fre- lead to an inadequate diet.186 The tendency to an eating disorder quency, consistency and incontinence, loperamide has the best might be present, particularly among female IBS patients.187–189 It quality of evidence, but has not been shown to improve abdominal is possible that the improvement in IBS from dietary restriction pain or distension.205–209 stems from an overall reduction in food intake with reduced stimu- Probiotics are defined as live microorganisms, which provide lation of post-prandial motility activity. In a recent study from health benefits to the host. A recent meta-analysis suggested that Journal of Gastroenterology and Hepatology 25 (2010) 1189–1205
2010 Journal of Gastroenterology and Hepatology Foundation and Blackwell Publishing Asia Pty Ltd K-A Gwee et al.
Asian consensus on irritable bowel syndrome they are effective for improving abdominal pain and flatulence, Statement 37: In specialist centers, psychotherapy can be
with a trend for bloating, in IBS.210 However, the magnitude of the effective for IBS patients and considered as a treatment for
benefits and the most effective species and strains of probiotic refractory patients who fail medical treatments.
remain to be defined.210 In general, they appear to be safe, but there Grade of evidence: moderate.
have been rare reports of opportunistic infections with the use of Agreement: a. 8 (50%), b. 5 (31.25%), c. 1 (6.25%), d. 2 (12.5%).
probiotic bacteria.211 Several studies, most of which are of poor quality and have been Currently, we see a limited role for prokinetic agents, as there conducted in tertiary centers, have demonstrated the effectiveness are no convincing data for domperidone, mosapride, and itopride.
of psychotherapies, such as hypnotherapy and cognitive- While there are high-quality data that suggest that tegaserod, a behavioral therapy, for patients with IBS.215,227–230 Psychotherapy 5-HT4 partial agonist, is efficacious for IBS with constipation, its can be useful in IBS patients, both with and without psychiatric role is limited by a controversial withdrawal by the US Food and disorders.229,231 However, these psychiatric treatments, including Drug Administration for suspected cardiovascular side-effects.212 hypnotherapy and cognitive-behavioral therapy, require the pres- Non-absorbable antibiotics, including neomycin and rifaximin, ence of well-trained mental health professionals and are not avail- provide reductions in global and bloating symptoms in IBS.213,214 able in most centers.
However, the effects of long-term, intermittent, non-absorbableantibiotic use in IBS are not known.
Statement 35: Low-dose antidepressants, such as tricyclic anti-
We gratefully acknowledge the support of the following organiza- depressants and selective serotonin reuptake inhibitor (SSRI),
tions who provided unconditional sponsorship towards the devel- can be considered in patients who fail to respond to initial treat- opment of this consensus: Dainippon Sumitomo Pharma (Japan), ment, even in the absence of any overt psychological disorders.
Daewoong Pharmaceutical Company (Korea), Dr Reddy's Labo- Grade of evidence: high.
ratories (India), and Abbott Products GmbH (Germany).
Agreement: a. 13 (81.25%), b. 3 (18.75%).
A recent meta-analysis demonstrated that low-dose antidepres-sants (tricyclic anti-depressants (TCA) and SSRI) can be effective in the treatment of IBS, even in patients without concomitant 1 Murphy MK, Black NA, Lamping DL et al. Consensus psychiatric diagnoses.215–217 As TCA, such as amitriptyline, have development methods, and their use in clinical guideline anticholinergic effects and can cause constipation, they are best development. Health Technol. Assess. 1998; 2: i–iv, 1–88.
used for the treatment of IBS-D patients, where they are effective 2 Atkins D, Best D, Briss PA et al. Grading quality of evidence and in reducing the symptoms of incomplete defecation and loose strength of recommendations. Br. Med. J. 2004; 328: 1490.
stool, and in improving abdominal pain.218–220 However, it might be 3 Gwee KA, Leong YL, Graham C et al. The role of psychological more appropriate to use SSRI in IBS-C as they can shorten intes- and biological factors in postinfective gut dysfunction. Gut 1999; tinal transit times. SSRI are effective in reducing global symp- 44: 400–6.
4 Spiller RC, Jenkins D, Thornley JP et al. Increased rectal mucosal toms, bloating, and problematic bowel movements.215,216,221 As enteroendocrine cells, T lymphocytes, and increased gut patients frequently have reservations with regards to the stigma, as permeability following acute Campylobacter enteritis and in well as to the possible side-effects associated with their use, anti- post-dysenteric irritable bowel syndrome. Gut 2000; 47:
depressant agents are expected to be used for IBS patients with moderate to severe symptoms who have failed to respond favor- 5 Chadwick VS, Chen W, Shu D et al. Activation of the mucosal ably to other conventional treatments.
immune system in irritable bowel syndrome. Gastroenterology
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Statement 36: Patients with IBS and co-morbid psychological
6 Gwee KA, Collins SM, Read NW et al. Increased rectal mucosal disorders should be told that their psychiatric symptoms could
expression of interleukin 1beta in recently acquired post-infectious modify the severity of their bowel symptoms and that adequate
irritable bowel syndrome. Gut 2003; 52: 523–6.
7 Kassinen A, Krogius-Kurikka L, Makivuokko H et al. The treatment of co-morbid psychological disorders is strongly
fecal microbiota of irritable bowel syndrome patients differs significantly from that of healthy subjects. Gastroenterology Grade of evidence: high.
2007; 133: 24–33.
Agreement: a. 11 (68.75%), b. 5 (31.25%).
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