WGO GUIDELINE

World Gastroenterology Organisation Global Guidelines

Irritable Bowel Syndrome
A Global Perspective
Update September 2015

Review Team: Eamonn M.M. Quigley, MD, FRCP, FACP, MACG,

FRCPI (USA, Chair), Michael Fried, MD (Switzerland), Kok-Ann Gwee, MD (Singapore), Igor Khalif,
MD (Russia), A.P.S. Hungin, MD (United Kingdom),
Greger Lindberg, MD (Sweden), Zaigham Abbas, MD (Pakistan), Luis B. Fernandez, MD (Argentina),
Shobna J. Bhatia, MD (India), Max Schmulson, MD (Mexico), Carolina Olano, MD (Uruguay), and Anton
LeMair, MD (The Netherlands)

WGO IRRITABLE BOWEL SYNDROME (IBS) Tissue transglutaminase antibody to screen for celiac
CASCADES disease.
Esophagogastroduodenoscopy and distal duodenal biopsy
Cascade Options for Resource-sensitive IBS in patients with diarrhea, to rule out celiac disease, tropical
Diagnosis sprue, giardiasis, and in patients in whom abdominal pain
High Resource Levels and discomfort is located more in the upper abdomen.
History, physical examination, exclusion of alarm Colonoscopy and biopsy.
symptoms, consideration of psychological factors.
Fecal inflammation marker (eg, calprotectin or lactofer-rin)
Full blood count (FBC), erythrocyte sedimentation rate to distinguish IBS from inflammatory bowel disease (IBD)
(ESR) or C-reactive protein (CRP), stool studies (white where the latter is prevalent.
blood cells, ova, parasites, occult blood).
Hydrogen breath test for lactose intolerance and small-
Selenium homocholic acid taurine (tauroselcholic acid) test intestinal bacterial overgrowth (SIBO).
(SeHCAT; incorporating selenium-75) for the investigation
of bile acid malabsorption (BAM) and measurement of bile
acid pool loss. This test may have limited availability, even
Medium Resource Levels
in areas with high resources. History, physical examination, exclusion of alarm
Thyroid function. symptoms, consideration of psychological factors.
FBC, ESR or CRP, stool studies, thyroid function.
Sigmoidoscopy.
From the World Gastroenterology Organisation, Milwaukee, WI. Eamonn
M.M. Quigley is supported by Alimentary Health (stock, Low Resource Levels
consultant), Proctor & Gamble (speakers’ bureau); Allergan, Bio- History, physical examination, exclusion of alarm
codex, Commonwealth Labs, Ironwood, Rhythm, Shire, Synergy symptoms, consideration of psychological factors.
(advisor); and Rhythm, Theravance, Vibrant (research support). FBC, ESR, and stool examination.
Address correspondence to: Eamonn M.M. Quigley, MD, FRCP, FACP,
MACG, FRCPI, Chief, Division of Gastroenterology and Hepatology, Note: Even in “wealthy” countries, not all patients need
The Methodist Hospital Weill Cornell Medical Col-lege, Division of colonoscopy, which should be reserved in particular for those
Gastroenterology, 6550 Fannin, Suite SM1201, Houston, TX 77030 (e- with alarm symptoms or signs and those over the age of 50.
mail: equigley@houstonmethodist.org).
The need for investigations and for sigmoidoscopy and colo-
r
Copyright 2016 World Gastroenterology Organisation. All rights reserved. noscopy, in particular, should also be dictated by the charac-
DOI: 10.1097/MCG.0000000000000653 teristics of the patient (presenting features, age, etc.) and the

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J Clin Gastroenterol Volume 50, Number 9, October 2016 WGO Global Guidelines: IBS

geographical location (ie, whether or not in an area of high and/or a change in bowel habit. Sensations of discomfort
prevalence for IBD, celiac disease, colon cancer, or para- (bloating), distension, and disordered defecation are com-
sitosis). In general, the diagnosis is “safer” in patients with monly associated features. In some languages, the words
constipation, whereas in patients with severe diarrhea, there is “bloating” and “distension” may be represented by the same
a greater need to consider tests to exclude organic pathology. term.
IBS is not known to be associated with an increased risk
Cascade Options for Resource-sensitive IBS for the development of cancer or IBD, or with increased
Management mortality. It generates significant direct and indirect health
care costs. Although visceral hyper-sensitivity is accepted as
High Resource Levels prevalent, no universal patho-physiological substrate has been
Reassurance, dietary and lifestyle review, and counseling. 1
demonstrated in IBS.
Try a quality probiotic with proven efficacy. A transition of IBS to, and overlap with, other
Symptomatic treatment of: symptomatic gastrointestinal disorders (eg, gastro-esophageal
reflux disease, dyspepsia, and functional con-stipation) may
J Pain, with a locally available antispasmodic; for more occur. IBS usually causes long-term symp-toms, which may
severely affected patients, a low-dose tricyclic occur in episodes. Symptoms vary and are often associated
antidepressant (TCA) or selective serotonin reuptake with food intake and, characteristically, with defecation. They
inhibitor (SSRI) should be added.
interfere with daily life and social functioning in many
J Constipation with dietary measures and fiber sup- patients. Symptoms sometimes develop as a consequence of
plementation, progressing to osmotic laxatives such as
an intestinal infection [post-infectious IBS (PI-IBS)] or are
lactulose.
precipitated by major life events, occur during a period of
J Although the evidence to support their use is weak, it
may be worth addressing diarrhea with simple considerable stress, or develop following abdominal and/or
antidiarrheals. pelvic surgery. They may also be precipitated by antibiotic
treatment. In general, there is a lack of recognition of the
Psychological approaches (hypnotherapy, psychother-apy, condition; many patients with IBS symptoms do not consult a
group therapy) should be considered and consulta-tion with physician and are not formally diagnosed.
a dietitian, where indicated.
Add specific pharmacological agents, where approved: IBS Subclassification
J Lubiprostone or linaclotide for IBS with constipa-tion According to the Rome III criteria, IBS may be sub-typed
(IBS-C). or subclassified on the basis of the patient’s stool
J Rifaximin for diarrhea and bloating. characteristics, as defined by the Bristol Stool Scale:
IBS-D:
J Alosetron and eluxadoline for IBS with diarrhea (IBS-D).
J Loose stools >25% of the time and hard stools <25% of
the time.
Medium Resource Levels J Up to one third of cases.
Reassurance, dietary and lifestyle review, and counseling. J More common in men.
Add a quality probiotic with proven efficacy. IBS-C:
Symptomatic treatment of: J Hard stools >25% of the time and loose stools <25% of
J Pain, with a locally available antispasmodic; for more the time.
severely affected patients, a low-dose TCA should be J Up to one third of cases.
added. J More common in women.
J Constipation with dietary measures and fiber IBS with mixed bowel habits or cyclic pattern (IBS-M):
supplementation.
J Although the evidence to support their use is weak, it J Both hard and soft stools >25% of the time.
may be worth addressing diarrhea with bulking agents J One third to one half of cases.
and simple antidiarrheals.
Unsubtyped IBS:
Low Resource Levels J Insufficient abnormality of stool consistency to meet
Reassurance, dietary and lifestyle review, and counseling. criteria IBS-C or IBS-M
It must be remembered, however, that patients com-
Symptomatic treatment of: monly transition between these subtypes and that the
symptoms of diarrhea and constipation are commonly
J Pain, with a locally available antispasmodic.
misinterpreted in IBS patients. Thus, many IBS patients who
J Constipation,with dietary measures and fiber complain of “diarrhea” are referring to the frequent passage of
supplementation.
formed stools and, in the same patient pop-ulation,
J Although the evidence to support their use is weak, it “constipation” may refer to any one of a variety of complaints
may be worth addressing diarrhea with bulking agents associated with the attempted act of defecation and not simply
and simple antidiarrheals. to infrequent bowel movements.
In addition, bowel habit must be evaluated without using
INTRODUCTION antidiarrheals or laxatives.
Definition: IBS is a functional bowel disorder in which On clinical grounds, other subclassifications may be
abdominal pain or discomfort is associated with defecation developed, whether based on symptoms (eg, with predominant

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Quigley et al J Clin Gastroenterol Volume 50, Number 9, October 2016

bowel dysfunction pain or bloating) or on precipitating factors the 30- to 50-year-old age group but in some cases, symp-toms
[PI-IBS, food induced (meal induced), or stress related]. may date back to childhood. Prevalence is higher in women—
However, with the exception of PI-IBS, which is quite well although this result is not reproduced in some studies from
characterized, the relevance of any of these other India, for example. Although the estimated prevalence of IBS
classifications to the prognosis or response to therapy in in children is similar to that in adults its frequency seems to be
patients with IBS remains to be defined. It must also be lower among older individuals.
remembered that the Rome III criteria are not commonly used
in clinical practice. Furthermore, cultural issues may inform IBS Demographics, East-West Differences in
symptom reporting. In India, for example, a patient who Presenting Features
reports straining or passing hard stools (often with a feeling of
incomplete evacu-ation) is likely to complain of constipation Global information regarding presenting features also
even if he or she passes stools more than once daily. Finally, varies, and comparisons of studies based on community data,
there is consid-erable overlap and a tendency to transition outpatient clinic data, and hospital statistics are fraught with
between IBS-C and functional constipation. difficulties. Typical IBS symptoms are com-mon in healthy
population samples, but the majority of sufferers with IBS are
not actually medically diagnosed. This may explain apparent
Global Prevalence and Incidence
differences between countries in the reported prevalence. Most
The global picture of the prevalence of IBS is far from studies only count diagnosed IBS and not community
complete, as no data are available from several regions. In prevalence.
addition, comparisons of data from different regions are often Some studies in non-Western countries indicate a close
problematic due to the use of different diagnostic criteria (in association between marked distress and IBS in men, in a
general, the “looser” the criteria, the higher the prevalence), as manner similar to that found in women in Western studies.
well as the influence of other factors such as population These same studies also indicate a trend to a higher
selection, the inclusion or exclusion of comor-bid disorders frequency of upper abdominal pain and a lower impact of
(eg, anxiety), access to health care, and cul-tural influences. In defecatory symptoms on a patient’s daily life. This may
Mexico, for example, the prevalence of IBS in the general explain why overlap between functional dyspepsia and IBS is
population, measured using the Rome II criteria, was 16%, but very common in China.
the figure increased to 35% among individuals in a university- Several studies suggest that among African Americans,
based community. What is remarkable is that the available in comparison with their white compatriots, stool frequency is
data suggest that the prevalence is quite similar across many lower and the prevalence of constipation is higher.
countries, despite substantial lifestyle differences. In Latin America, except in Argentina, constipation
predominance is more frequent than diarrhea predominance.
The prevalence of IBS in Europe and North America is Stool frequency seems to be greater in the Indian com-
estimated to be 10% to 15%. In Sweden, the most com-monly munity as a whole—99% passed stools once or more per day.
cited figure is 13.5%. The prevalence of IBS is increasing in
In Mexico, 70% of patients have anxiety, 46%
countries in the Asia-Pacific region, partic-ularly in those with
depression, and 40% both and IBS has a significant eco-nomic
developing economies. Estimates of the prevalence of IBS impact, as it leads to high use of medical resources.
(using the Rome II diagnostic criteria) vary widely in the Asia-
Pacific region. Studies from India showed that the Rome I Psychological distress, life events, and negative coping
criteria for IBS identified more patients than the Rome II style may play important roles in the pathogenesis of IBS.
criteria. Reported prevalence rates included 0.82% in Beijing, These factors may also influence the individual’s illness
5.7% in southern China, 6.6% in Hong Kong, 8.6% in behavior and the clinical outcome.
Singapore, 14% in Pakistan, and 22.1% in Taiwan. A study in
China found that the prevalence of IBS, as defined by the
Rome III criteria, in individuals attending outpatient clinics DIAGNOSIS OF
was 15.9%. Gen-erally, data from South America are scarce, IBS Clinical History
but this may be related to a publication bias, as many studies Although it is currently described as a single coherent
2
are not pub-lished in English or are not cited in commonly entity, it is most likely that the disorder termed “IBS”
used search databases (eg, Medline). In Uruguay, for example, comprises a number of discrete pathophysiological entities,
1 study reported an overall prevalence of 10.9% (14.8% in which have not as yet been defined. Thus, a number of
women and 5.4% in men)—58% with IBS-C and 17% with pathologic processes that we now recognize as quite distinct
IBS-D. In 72% of the cases, the age of onset was below 45 entities (eg, microscopic colitis, carbohydrate intolerance, and
years. Also, a study from Venezuela reported an IBS BAM) would formerly have been included within IBS.
prevalence of 16.8%, with 81.6% of those affected being In assessing the patient with IBS, it is important not only
women and to consider the primary presenting symptoms, but also to
3 identify precipitating factors and other associated gas-
18.4% men. Studies on indigenous populations in Latin
America revealed a high prevalence of IBS, which was similar trointestinal and extragastrointestinal symptoms. It is vital also
4 to seek out and directly question for the presence of alarm
to that in the rest of the population. Data from Africa are very
scarce. A study in a Nigerian student pop-ulation found a symptoms and to consider, in the relevant context, other
26.1% prevalence, based on the Rome II criteria. A study explanations for the patient’s symptoms (eg, bile acid diarrhea,
among outpatients in the same country, based on the same carbohydrate intolerance, microscopic colitis). Thus, the
criteria, reported a prevalence of 33%. history is critical and involves both the identi-fication of those
features regarded as typical of IBS and also the recognition of
Other Observations on IBS Epidemiology “red flags,” or other features that suggest alternative
IBS mainly occurs between the ages of 15 and 65 years. diagnoses. Accordingly, the patient should be asked about the
The first presentation of patients to a physician is usually in following:

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J Clin Gastroenterol Volume 50, Number 9, October 2016 WGO Global Guidelines: IBS

The Pattern of Abdominal Pain or Discomfort fears, and catastrophizing. Tools that may assist in the psy-
Pain that is chronic, intermittent rather than con-tinuous, chological assessment include the Hospital Anxiety and
has occurred before and is relieved by defecation or passing of Depression Scale (HADS), the Sense of Coherence (SOC) test,
flatus is suggestive of IBS. In some individu-als, pain may be and the Patient Health Questionnaire (PHQ-15).
well localized (eg, to the lower left quad-rant of the abdomen),
whereas in others the pain location tends to move around. Physical Examination
Nocturnal pain is unusual in IBS and is considered a warning A physical examination reassures the patient and helps
sign. detect possible organic causes and signs of systemic disease.
Particular attention should, of course, be paid to the abdominal
Other Abdominal Symptoms examination and a digital rectal examination including
Bloating and distension are common features of IBS. examination of the perianal region should be performed
Distension can be measured; bloating is a subjective feeling.
As defined in English, bloating and distension may not share
the same pathophysiology and should not be regarded as IBS Diagnostic Algorithm
equivalent and interchangeable terms, although in other Figure 1 provides a general approach to the evaluation of
languages they may be represented by a single word, or there the patient with IBS-type symptoms. Figure 2 attempts to
may be no expression for bloating, as in Spanish. Nor does prioritize evaluation based on regional variations in the
either necessarily imply that intestinal gas production is prevalence of diseases and disorders that may share symp-
increased. Other symptoms, less specific for IBS, include tomatology with IBS.
borborygmi and latulence.

Nature of the Associated Bowel Disturbance EVALUATION OF IBS

(ie, Constipation, Diarrhea, Alternating) and A diagnosis of IBS is usually suspected on the basis of
Abnormalities of Defecation the patient’s history and physical examination, without
Attention needs to be given to such issues as diarrhea for additional tests. Confirmation of the diagnosis of IBS requires
>2 weeks, mucus in the feces, urgency of defecation, and/or a the confident exclusion of organic disease in a manner dictated
feeling of incomplete defecation/evacuation (this symptom has by an individual patient’s presenting
been reported as particularly important in recent studies in
Asian populations—51% in Singapore, 71% in India, 54% in
Taiwan) Patient with recurrent abdominal pain or discomfort for > 3 days per month
during the previous 3 months, associated with two or more of the following:
— Relief with defecation
Other Information From the Patient’s History and — A change in stool frequency
— A change in stool form (show patient the Bristol Stool Scale)
Important Warning Signs — Bloating and/or distension
As well as seeking the usual “red flag” symptoms
(unintended weight loss, blood in the stool or fever), one
should identify if there is a family history of colorectal Check for alarm features
malignancy, celiac disease, or IBD. Furthermore, the rela- — Unintended weight loss — Fever
— Patient aged 50 or older — Loss of appetite — Abdominal mass
tionships of symptoms, such as pain, to menstruation, drug — Blood in stools — Nocturnal symptoms — Ascites
therapy, consumption of foods that are known to cause
intolerance (especially milk), artificial sweeteners, dieting
products, alcohol, or recent travel, such as visiting the Alarm features not present
(sub)tropics, should be defined.
The patient should be questioned about eating habits and Consider laboratory tests (* if appropriate)
a family history of IBS sought. IBS clearly aggregates within — FBC
— ESR, CRP
families, although its genetics are poorly understood and the Alarm features — Thyroid function
mode of transmission is unclear. present — Fecal occult blood*
— Stool studies*
A history of the sudden onset in relation to exposure to — Celiac serology*
gastroenteritis suggests PI-IBS.
Be wary of a history of persistent diarrhea which,
especially if relatively painless, should prompt more extensive Abnormal lab
Normal lab tests
tests
investigations for other causes of diarrhea, such as celiac
disease, microscopic colitis (especially in a middle-aged or
older woman), bile acid diarrhea (due to impaired absorption Investigate Make IBS diagnosis
of bile acids), or carbohydrate intolerance.
Explain IBS and treat primary
Psychological Assessment symptoms
Psychological factors have not been shown to cause or — Plan repeat visit
— Check for new symptoms
influence the onset of IBS. IBS is not a psychiatric or psy- — Review for alarm features
chological disorder. However, psychological factors may play —Continue treatment as
a role in the persistence and perceived severity of abdominal necessary, or modify
symptoms and contribute to impairment of quality of life and
excessive use of health care services. FIGURE 1. Diagnostic and initial approach to the management of
the patient with IBS-type symptoms. As patient anxiety plays a
For these reasons, coexisting psychological conditions significant role, reassurance and education are of key importance.
are common in referral centers and may include: anxiety, CRP indicates C-reactive protein; ESR, erythrocyte sedimentation
depression, somatization, hypochondriasis, symptom-related rate; FBC, full blood count; IBS, irritable bowel syndrome

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Quigley et al J Clin Gastroenterol Volume 50, Number 9, October 2016

IBS symptoms + no alarm features + age under 50 to a minimum is recommended in straightforward cases of
IBS, and especially in younger individuals.
Additional tests or investigations should be considered if
No diarrhea symptoms begin after the age of 50, if warning signs (red
High
Low prevalence of High
intestinal parasitosis prevalence of
prevalence
Persistent diarrhea flags), as listed above, are present, or if any abnormalities are
of intestinal detected on physical exam.
Low prevalence of celiac celiac disease
parasitosis
disease The following tests (although commonly performed) are
indicated only if supported by the clinical history and where
Simple tests should be Serological test for locally relevant: FBC, serum biochemistry, thyroid function
Serological
considered (FBC, ESR,
test for celiac
Stool celiac disease* tests, and stool testing for occult blood and ova and parasites
FOBT) and/or symptom- studies Stool studies*
disease
based diagnosis Colonoscopy*
Additional tests or investigations may also be consid-
ered if the patient has persistent symptoms or is anxious
FIGURE 2. Approach to the diagnosis of IBS based on regional despite treatment, a major qualitative change in chronic
variations in disease prevalence. *Where relevant—that is,
when there is a high prevalence of celiac disease, parasitosis, symptoms has occurred, or a new coexisting condition should
inflam-matory bowel disease, or lymphocytic colitis. ESR be considered.
indicates erythrocyte sedimentation rate; FBC, full blood count;
FOBT, fecal occult blood test; IBS, irritable bowel syndrome. Differential Diagnosis
BAM
features and characteristics. In many instances (eg, in young Adult-onset BAM is now recognized as an important
patients with no alarm features), a secure diagnosis can be 7
made on clinical grounds alone. cause of an IBS-D-type presentation. A recent review study
There is a lack of robust evidence and prospective studies found evidence that >25% of patients with IBS-D have BAM.
regarding the appropriate use of radiologic imaging in patients Etiologic factors that appear to contribute to the onset and
5 persistence of chronic diarrhea symptoms are alterations in the
with IBS-like symptoms.
enterohepatic circulation, accelerated intestinal transit, an
increase in the bile acid pool, and low levels of fibroblast
Diagnostic Criteria 8
growth factor-19. Diagnostic tools that help in diagnosing
In clinical research, the Rome III criteria are those most BAM and differentiating it from IBS-D are assays of fecal bile
commonly used to make a diagnosis of IBS. However, is acid concentration, 23-seleno-25-homo-taurocholic acid
should be noted, firstly, that these are due to be updated in (SeHCAT) testing, and high-performance liquid
2016 and that a systematic review (2012) of the diag-nostic
chromatography for serum 7-a-OH-4-cholesten-3-one (C4)—
criteria for IBS demonstrated low validity and uti-lization of
the Rome III criteria, and suggested that the Manning criteria in addition to the use of therapeutic trials (with the bile acid
were more widely validated and may be more clinically sequestering agents cholestyramine and colesevelam), and
6 9
applicable. heightened awareness of the like-lihood of BAM.
In clinical practice, whether in the setting of primary or
specialist care, clinicians usually base a diagnosis of IBS on Celiac Disease
their evaluation of the whole patient (often over time) and The main symptoms and signs of celiac disease are
consider a multiplicity of features that support the diagnosis chronic diarrhea, failure to thrive (in children), and fatigue. It
(apart from pain and discomfort associated with defecation, or is estimated to affect approximately 1% of all Indo-European
change in stool frequency or form). This approach includes a wheat-eating populations. It must be emphasized that
history of symptoms regarded as common in IBS and nowadays many with celiac disease do not have classic
generally supportive of its diagnosis, as described above features and present with “IBS-type” symptoms, including
combined with the presence of behavioral features considered bloating and constipation, along with iron deficiency. A low
helpful in recognizing IBS in general practice, such as the threshold for investigation should therefore be maintained in
presence of symptoms for >6 months, and their aggravation by 10
high-prevalence (>1%) regions.
stress or meals. A pattern of fre-quent consultations for
nongastrointestinal symptoms, a history of previous medically
unexplained symptoms, or an association with anxiety and/or Lactose Intolerance
depression may also raise suspicion for IBS. It must also be The main symptoms are bloating, flatulence, and diarrhea
remembered that non-colonic complaints, such as dyspepsia acutely related to consumption of milk and dairy products.
(reported in 42% to 87%), nausea, and heartburn often Although genetic testing can now detect lactase deficiency,
accompany IBS. this is not necessarily predictive of intolerance, which is best
Nongastrointestinal symptoms, including lethargy, tested using the lactose hydrogen breath test. Indeed, a
fatigue, backache and other muscle and joint pains, fibro- substantial proportion of individuals who lack lactase can
myalgia, headache, urinary symptoms (eg, nocturia, frequency tolerate oral lactose despite bacterial fermentation.
and urgency of micturition, incomplete bladder emptying),
dyspareunia, insomnia, and a low tolerance to medications in In countries with a high prevalence of lactase defi-
general may also be evident. ciency, inappropriately labeling IBS patients as lactose
intolerant should be avoided, unless they are consuming
substantial amounts of milk and/or milk products, as this could
Additional Tests or Investigations deprive the community of a cheap nutritious source of protein
In the majority of cases of IBS, no additional tests or and nutrition in countries such as India. In all parts of the
investigations are required. An effort to keep investigations world, the prevalence of lactose malabsorption

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J Clin Gastroenterol Volume 50, Number 9, October 2016 WGO Global Guidelines: IBS

on breath tests has been consistently similar between IBS and The classic features of SIBO are those of maldigestion and
non-IBS subjects. malabsorption. Some of the symptoms of SIBO (bloating,
diarrhea) overlap with those of IBS, which has led to the
IBD (Crohn’s Disease, Ulcerative Colitis) suggestion that SIBO is related to IBS. However, it is
There are very significant variations in prevalence generally believed that SIBO is not a common cause of IBS-
worldwide. In a high-prevalence area, IBD, should be like symptoms.
considered if diarrhea has persisted for >2 weeks or if rectal
bleeding is reported and/or an inflammatory mass, weight loss, Tropical Sprue
perianal disease, or fever is detected. In areas in which it is Tropical sprue should be considered in returning
endemic, intestinal tuberculosis should also be considered, as travelers with persistent diarrhea. The symptoms and his-
its presentation may be similar to that of IBD. tologic findings of tropical sprue may resemble those of celiac
disease. A diagnosis of celiac disease is unlikely in the
absence of antiendomysium or antitissue transglutaminase
Colorectal Carcinoma antibodies, but conversely their absence increases the like-
Colorectal carcinoma should be considered in older 14
lihood of tropical sprue.
patients who develop IBS-type symptoms for the first time
later in life and/or in the presence of hematochezia or Diverticulitis
unintended weight loss. An obstructive-type pain may be a The relationship between IBS and so-called “painful
feature of the left-sided lesions, whereas anemia or iron diverticular disease” is unclear; is painful diverticular dis-ease
deficiency is common with the right-sided lesions no more than IBS in a patient who has diverticula? In
diverticulitis, the classic symptoms and/or findings are
Microcytic (Lymphocytic and Collagenous) Colitis episodic and acute to subacute during an episode, featuring
This disorder accounts for 20% of unexplained diar-rhea left-sided abdominal pain, fever, and the presence of a tender
in patients over the age of 70, is typically painless, and is most inflammatory mass in the left lower quadrant. However, it is
common in middle-aged females (M:F = 1:15). Diagnosis is now evident that afflicted patients may have more chronic
based on the pathologic examination of colonic biopsies symptoms in between discrete episodes/ attacks, and that left-
sided and bilateral, but not right-sided diverticular disease,
15
Acute or Chronic Diarrhea Due to Protozoa or may increase the risk for IBS.
Bacteria Endometriosis
Here the principal symptom is an acute onset of diarrhea
and the diagnosis is confirmed by stool examina-tion or Endometriosis will be suggested by the presence of
duodenal biopsy. cyclical lower abdominal pain and the detection of enlarged
11 ovaries or nodules dorsal to the cervix on digital vaginal
A review on the role of intestinal protozoa in IBS examination.
concluded that there was “a possible role for protozoan
parasites, such as Blastocystis hominis and Dientamoeba Pelvic Inflammatory Disease
fragilis” in the etiology of IBS. D. fragilis is known to cause
IBS-like symptoms and has a propensity to cause chronic Here the main symptoms and/or findings include: chronic
infections. It can be detected using nested polymerase chain lower abdominal pain, fever and upward pressure pain or
12 adnexal tenderness, and swollen adnexa on digital vaginal
reaction, where available, or alternatively using micro- examination.
scopy. The role of B. hominis as an etiological agent in IBS
remains unclear, due to contradictory reports and the
controversial nature of B. hominis as a human pathogen. The Ovarian Cancer
role of B. hominis may be genotype related.
13
Although In women over the age of 40, ovarian cancer should be
considered in the differential diagnosis. In 1 survey, the
Entamoeba histolytica infections occur predominantly in
developing regions of the world, the clinical diagnosis of following symptoms were more common among women with
amebiasis is often difficult, as symptoms in patients with IBS ovarian cancer: increased abdominal girth, bloating, urinary
may closely mimic those in patients with nondysenteric urgency, and pelvic pain. The combination of bloating,
amebic colitis. Clinical manifestations of Giardia intestinalis increased abdominal girth, and urinary symptoms was found
infection also vary from asymptomatic carriage to acute and in 43% of women with ovarian cancer, but in only 8% of a
chronic diarrhea with abdominal pain. control population.
Although stool testing for Giardia and Amoeba is
recommended in India, self-medication with imidazoles is Enterocolitis Associated With Nonsteroidal Anti-
common, rendering the results difficult to interpret. It is Inflammatory Drugs (NSAIDs)
essential that all patients with IBS in relevant areas should This may account for diarrhea in elderly patients who are
undergo parasitological investigations to rule out the presence receiving treatment from neurologists and rheumatologists.
of protozoan parasites. It is equally important that these tests
are appropriately interpreted and that over-treatment is Comorbidity With Other Diseases
avoided. Patients with overlap syndromes tend to have more
severe IBS. Thus, fibromyalgia has been reported in up to 20%
SIBO to 50% of IBS patients and IBS is common in several other
SIBO is rare unless the patient has a primary or sec- chronic pain disorders, such as chronic fatigue syn-drome
ondary motility disorder, has been operated on (in partic-ular (51%), temporomandibular joint syndrome (64%), chronic
with ileocecal resection or bariatric surgery), or has impaired pelvic pain (50%), as well as nonulcer dyspepsia and so-called
immunity (such as immunoglobulin A deficiency). gall-bladder and biliary dyskinesia

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Quigley et al J Clin Gastroenterol Volume 50, Number 9, October 2016

In a meta-analysis, the prevalence of biopsy-proven identifying and exploring the patient’s concerns. A positive
celiac disease was found to be >4 times higher in patients who patient-physician relationship should be established, with the
met the diagnostic criteria for IBS than in control individuals patient’s symptoms and distress being accepted as real and
16 appreciating the impact of symptoms. Time should be taken to
without IBS.
There is a significantly higher prevalence of chronic explore the patient’s anxieties related to symptoms and
idiopathic constipation in patients with IBS. Distinguishing possible diagnoses, with the aim being to eliminate
between IBS-C and chronic idiopathic constipation may be unnecessary worries and in so doing to identify and helping to
difficult in clinical practice; several recent studies have called resolve stressful factors. Attempts should be made to reduce
into question the appropriateness and feasibility of creating avoidance behavior. Patients may avoid activities that they
what appears to be an artificial division between these 2 fear are causing the symptoms, but avoidance behavior has a
17 negative influence on the prognosis. General guidance on diet
functional gastrointestinal disorders.
The prevalence of gastroesophageal reflux-type symp- and activity should be provided.
toms in patients with IBS is 4 times higher than in those 20
without IBS. There is an overlap between the 2 conditions in Diet and Dietary Supplements
up to 25% of individuals. It is recommended that when A fiber-rich diet or a bulk-former (eg, psyllium) com-
physicians encounter patients with symptoms of IBS, they bined with sufficient intake of fluids would seem to be a
should routinely screen for coexistent gastroesophageal reflux logical approach in IBS, but the general status of fiber in IBS
18 20
symptoms. is not straightforward. Insoluble fibers may exacer-bate
Symptoms compatible with IBS have been reported to be symptoms and provide little relief—adverse events and
significantly higher in patients with IBD in comparison with bloating, distension, flatulence, and cramping, in particular,
non-IBD controls, even among those thought to be in may limit the use of insoluble fiber, especially if increases in
remission. IBS-type symptoms were also found to be sig- fiber intake are not introduced gradually. Soluble fibers such
nificantly more common in patients with Crohn’s disease than 21
as psyllium (ispaghula), in contrast, provide relief in IBS.
in those with ulcerative colitis (UC), and in those with active Diets low in fermentable oligosaccharides, dis-accharides,
19 monosaccharides, and polyols (FODMAPs) reduce abdominal
disease. Of course, a diagnosis of IBS would not be
appropriate in a patient with active IBD. 21
pain and bloating, and improve the stool pattern, but long-
term outcomes and the safety of low-FODMAP diets remain
MANAGEMENT OF IBS to be demonstrated. It is also still unclear whether the low-
21
FODMAP intervention diet is beneficial to all IBS patients.
Introduction Although they are widely used, especially in North America
Given that there is no general agreement on the cause of and Europe, the status of wheat-free or gluten-free diets in IBS
IBS, it comes as no surprise that no single treatment is is uncertain. Some probiotics provide global relief of
currently regarded throughout the world as being univer-sally symptoms in IBS, and others alleviate individual symptoms
applicable to the management of all IBS patients. 20,22
such as bloating and flatulence. However, the duration of
Given also the common association between IBS these benefits and the nature of the most effective species are
symptoms and such factors as diet, stress, and psycho-logical 23
not clear. The efficacy of probiotics is difficult to interpret,
factors, attention should be given to adopting measures that as different strains, doses, formulations, and methods of
may alleviate, if not eliminate, such precip-itants. Dietary 21
delivery have been used in various studies. Furthermore,
differences between different countries and ethnic groups
most randomized controlled studies of probiotics in IBS have
would be expected to have a significant influence on the been of short duration, have not used an appropriate study
prevalence of symptoms of IBS, but little information is 22
available. design, and have not adequately reported adverse events.
There is at present insufficient evidence for a general rec-
Recent data on disturbances in the intestinal flora ommendation of prebiotics or synbiotics in patients with
(microbiota) in IBS have spurred interest in novel approaches: 20
probiotics, prebiotics, and antibiotics. Recent meta-analyses IBS. A recent consensus statement provides guidance on the
24
confirm a role for probiotics in IBS, but also make it clear that use of specific probiotics in the management of IBS.
the effects of probiotics in IBS, as else-where, are highly strain
Drug Therapy
specific. Variability and the for-mulation of specific strains
vary dramatically around the world. Issues of quality control A variety of agents are used throughout the world for the
treatment of individual symptoms in IBS. These include
also continue to complicate recommendations in this area.
antispasmodics for pain, laxatives, fiber, bulking agents, the
IBS patients commonly have recourse to a variety of chloride-channel agonist lubiprostone, and the guanylate
alternative/complementary therapies throughout the world. In cyclase agonist linaclotide for constipation, fiber, bulking
India (in Ayurvedic medicine) and China, for example, herbal agents, antidiarrheals, the poorly absorbable antibiotic
remedies are widely available and commonly used for IBS. rifaximin and eluxadoline, a mu-opioid receptor agonist, and
However, their efficacy is difficult to assess, as the delta-opioid receptor antagonist for diarrhea.
concentrations of active ingredients vary considerably
depending on the extraction process. Few “alternative” Overall Symptoms—First-Line Therapy
therapies have been subjected to the rigors of a randomized Certain antispasmodics (otilonium, hyoscine, cime-
trial in IBS. tropium, pinaverium, dicyclomine, and mebeverine) provide
Nonpharmacological factors are often ignored, but are of symptomatic short-term relief in IBS. Adverse events are more
20
paramount importance in the management of IBS. The common with antispasmodics than with a placebo.
physician-patient relationship is critical and should include Peppermint oil is superior to placebo in improving IBS
attention to several aspects, both during the initial assess-ment 20,25
symptoms. The risk of adverse events is no greater with
and in the subsequent follow-up. These include 20
peppermint oil than with a placebo.

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J Clin Gastroenterol Volume 50, Number 9, October 2016 WGO Global Guidelines: IBS

Overall Symptoms—Second-Line Therapy formally tested. Lubiprostone and linaclotide have been
TCAs and SSRIs are effective for symptom relief in approved for the treatment of IBS-C.
21
20,21,26
IBS. Adverse effects are common, with drowsiness
26 Specific Symptoms—Diarrhea
and dizziness the most common, and may limit patient
20
tolerance. TCAs are associated with significant adverse Although it is an effective agent for the treatment of
effects in treating IBS-D and should be avoided in IBS-C; diarrhea, because of the lack of effects on pain, the cardinal
clinicians should expect 1 adverse effect for every 3 patients symptom of IBS, there is insufficient evidence to recom-mend
27 20
who benefit from therapy. SSRIs may be considered in loperamide for use in IBS. Alosetron is indicated only for
resistant IBS-C, although it is not currently recommended that women with severe IBS-D with symptoms lasting >6 months
SSRIs should be routinely prescribed for IBS in patients and no response to antidiarrheal agents. Eluxadoline and
without comorbid psychiatric conditions, because of rifaximin have recently been approved in the United States for
conflicting and limited data regarding efficacy, safety, IBS-D; it is difficult, at this early stage, to define their position
28
and long-term outcomes. Rifaximin is effective in reduc-ing overall in IBS management.
20,29
symptoms in IBS-D. Rifaximin may be
21
considered as a second-line therapy. Older patients and women Specific Symptoms—Bloating and Distension
29 Diets that produce less gas, such as the low-FODMAP
were found to have higher response rates. Rifax-imin is well
30 diet, may be helpful in some patients. There is no evidence to
tolerated, but its efficacy and safety have not been established
29 support the use of activated charcoal–containing prod-ucts,
beyond 16 weeks. However, retreatment efficacy and safety has “antiflatulents,” simethicone, and other agents in IBS. Some
31
been recently reported. It has also been reported that 846 specific probiotic strains, such as B. lactis DN-173010 and the
27
patients benefit for each adverse effect. probiotic cocktail VSL#3, have clinical trial evi-dence of
Alosetron is useful for second-line therapy of IBS- efficacy for bloating, distension, and flatulence. Others, such
20,21 as B. infantis 35624, reduce bloating as well as the other
D. However, it has been associated with an increased
risk of ischemic colitis and may cause severe con-stipation.
21 cardinal symptoms of IBS. Antibiotic treatment with rifaximin
Clinicians should expect 1 adverse effect for has been shown to reduce bloating in some IBS patients. Older
27 patients and women have been found to have higher response
every 3 patients who benefit from therapy. Lubiprostone is safe
20,27 29
and effective for treatment of IBS-C. Nausea rates. Rifaximin has been shown to be effective on retreating
has been the major side effect limiting use. Linaclotide is safe patients who have relapsed after a first effective treatment.
31
20,32,33
and effective for treatment of IBS-C. Diar-
rhea is the major adverse effect of linaclotide; further studies Psychological Interventions
are needed to evaluate its long-term efficacy and safety.
33 Apart from the general approaches described above for
governing the conduct of the doctor-patient relationship in
However, there is insufficient evidence to recommend IBS, more formal psychological interventions may be
20 contemplated in certain circumstances and depending on the
loperamide for use in IBS ; mixed 5-HT4 agonists/5-HT3
antagonists are no more effective than placebo at improving availability of appropriate resources and expertise. Such
20 approaches may include:
symptoms of IBS-C and renzapride and cis-apride have no
34 Cognitive behavioral therapy, in group or individual
benefit in IBS. Although there is no evidence that sessions, has shown excellent results, but its limited
polyethylene glycol (PEG) improves overall symptoms in 21,26
20 availability and labor-intensive nature limit routine use.
patients with IBS, it may relieve constipation. Behavioral techniques are aimed at modifying
Ondansetron was found to improve urgency, diarrhea, dysfunctional behaviors through and include: relaxation
and bloating in IBS-D, but did not provide any benefits in techniques, contingency management (by rewarding healthy
relation to pain. Ramosetron, where available, should also be behavior), and assertion training. Gut-directed hypnosis should
considered as second-line therapy in IBS-D; it has also been be recommended for patients with IBS refractory to
shown to be effective in IBS-D and seems to be devoid of 35
conventional (drug) treatment. It has a high level of safety
serious adverse effects such as severe constipation and and tolerability, and there is evidence of sustained efficacy, in
21 35
ischemic colitis. contrast to drug therapy. It should be offered by licensed
35
Specific Symptoms—Pain hypnotherapists with spe-cialist training in the technique.
Group treatment is more time efficient than individual sessions
If an analgesic is required, paracetamol is preferable to 35
NSAIDs. Opiates are to be avoided at all costs, as dependence and at least as effective. Daily practice by patients,
and addiction are a significant risk in such a chronic condition. supported by audiorecordings, boosts efficacy; training and
35
NSAIDs and opiates also have unde-sirable side effects on the experiences should regularly be discussed with patients.
gastrointestinal tract. The pro-biotic strain Bifidobacterium However, there is limited evidence from randomized
infantis 35624 has been shown to reduce pain, bloating, and controlled trials (RCTs). Future RCTs are needed that use
defecatory difficulty and normalize stool habit in IBS, strict diagnostic criteria, have follow-up periods of at least 1
regardless of predominant bowel habit, but is currently year, and include newly diagnosed and treatment-resistant
36
available only in the United States, Canada, the United patients. The limited availability and labor-intensive nature
Kingdom, and Ireland. 21
of hypnotherapy limits routine use.
The American College of Gastroenterology (ACG) Task
Specific Symptoms—Constipation 37
Force concluded that psychological therapies, including
The probiotic strain B. lactis DN-173010 has been shown cognitive therapy, dynamic psychotherapy, and hypnotherapy,
to accelerate gastrointestinal transit and to increase stool but not relaxation therapy, are more effec-tive than usual care
frequency among IBS patients with constipation. Although in relieving global symptoms of IBS.
osmotic laxatives are often useful, few have been
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Copyright r 2016 Wolters Kluwer Health, Inc. All rights reserved.
Quigley et al J Clin Gastroenterol Volume 50, Number 9, October 2016

20 utilization of Rome III. Neurogastroenterol Motil.

However, Ford et al found that the quality of evidence was
2012;24:853–e397.
very low and that the results were only slightly superior to
usual care or waiting-list control. With the exception of a 7. Slattery SA, Niaz O, Aziz Q, et al. Systematic review with meta-
analysis: the prevalence of bile acid malabsorption in the irritable
single study, these therapies have not been shown to be
bowel syndrome with diarrhoea. Aliment Pharmacol Ther.
superior to placebo. The sustainability of their effect is 2015;42:3–11.
questionable.
8. Barkun AN, Love J, Gould M, et al. Bile acid malabsorption in
With regard to herbal therapies and acupuncture, the chronic diarrhea: pathophysiology and treatment. Can J
ACG Task Force concluded that the available RCTs, mostly Gastroenterol. 2013;27:653–659.
testing unique Chinese herbal mixtures, seemed to show a 9. Wedlake L, A’Hern R, Russell D, et al. Systematic review: the
benefit. It was not possible to combine these studies into a prevalence of idiopathic bile acid malabsorption as diagnosed by
meaningful meta-analysis, however, and overall, any benefit SeHCAT scanning in patients with diarrhoea-predominant
of Chinese herbal therapy in IBS continues to be potentially irritable bowel syndrome. Aliment Pharmacol Ther. 2009;30:
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liver failure, with the use of any Chinese herbal mixture. A gastrointestinal disorders (FD/IBS/etc.). Symptoms of irritable
systematic review of trials of acupuncture was inconclusive bowel syndrome in celiac patients; relationship to disease activity
[poster presentation]. J Gastroenterol Hepatol. 2013;28(suppl
due to heterogenous outcomes. Further research is needed 3):574.
before any recommendations on acu-puncture or herbal
11. Stark D, Van Hal S, Marriott D, et al. Irritable bowel syndrome: a
therapy can be made. review on the role of intestinal protozoa and the importance of
their detection and diagnosis. Int J Parasitol. 2007;37:11–20.
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For most patients with IBS, symptoms are likely to 12. Sarafraz S, Farajnia S, Jamali J, et al. Detection of Dientamoeba
persist, but not worsen. Symptoms will deteriorate in a smaller fragilis among diarrheal patients referred to Tabriz health care
centers by nested PCR. Trop Biomed. 2013;30:113–118.
proportion, and some patients will recover completely.
13. Yakoob J, Jafri W, Beg MA, et al. Irritable bowel syndrome: is it
Factors that may negatively affect the prognosis include: associated with genotypes of Blastocystis hominis?. Parasitol Res.
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certain medical conditions, impaired function as a result of 14. Langenberg MCC, Wismans PJ, Van Genderen PJJ. Distin-
symptoms, a long history of symptoms, chronic ongoing life guishing tropical sprue from celiac disease in returning travellers
stress, and psychiatric comorbidity. In contrast, the physician with chronic diarrhoea: a diagnostic challenge? Travel Med Infect
can positively affect treatment out-come by acknowledging the Dis. 2014;12:401–405.
15. Yamada E, Inamori M, Uchida E, et al. Association between the
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location of diverticular disease and the irritable bowel syndrome:
a multicenter study in Japan. Am J Gastroenterol. 2014;109:1900–
1905.
Follow-up
16. Ford AC, Chey WD, Talley NJ, et al. Yield of diagnostic tests for
In mild cases, there is generally no medical need for celiac disease in individuals with symptoms suggestive of irritable
follow-up consultations in the long term, unless symptoms bowel syndrome: systematic review and meta-analysis. Arch
persist and/or are accompanied by considerable incon- Intern Med. 2009;169:651–658.
venience or dysfunction, diarrhea, or constipation do not 17. Suares NC, Ford AC. Prevalence of, and risk factors for, chronic
respond to therapy or warning signs emerge. idiopathic constipation in the community: systematic review and
One should beware of possibility that an eating dis-order meta-analysis. Am J Gastroenterol. 2011;106: 1582–1591. Quiz
might develop. Many patients with IBS try some form of 1581, 1592.
dietary manipulation and this can lead to nutri-tionally 18. Lovell RM, Ford AC. Prevalence of gastro-esophageal reflux-type
inadequate diets or ingestion of abnormal amounts of fruit, symptoms in individuals with irritable bowel syndrome in the
community: a meta-analysis. Am J Gastroenterol. 2012;107:
caffeine, dairy products, and dietary fiber. The tendency for 1793–1801. Quiz 1802.
eating disorders to develop is more common in female IBS
19. Halpin SJ, Ford AC. Prevalence of symptoms meeting criteria for
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