A 33-year-old female presents with 15 years of abdominal pain, diarrhea, and bloating. Her family history is notable for celiac disease in her mother. While irritable bowel syndrome (IBS) is likely, celiac disease must be excluded given her family history. Screening the patient for celiac disease serologically while on a normal diet is the most appropriate next step, rather than colonoscopy or other invasive tests, as her symptoms are classic for IBS and she has no alarm features. If celiac screening is negative, empiric treatment for IBS symptoms is reasonable.

1. Kurdistan Board GEH/GIT SurgeryKurdistan Board GEH/GIT Surgery
Weekly J ClubWeekly J Club
Supervised by:Supervised by:
Dr. Mohamed AlshekhaniDr. Mohamed Alshekhani
Board Review Vignette: Irritable Bowel Syndrome
Am J Gastroenterol 2016

2. The case:The case:
 A 33-year-old female sales manager presents for management ofA 33-year-old female sales manager presents for management of
uninvestigated crampy lower abd pain, diarrhea&bloating that haveuninvestigated crampy lower abd pain, diarrhea&bloating that have
been troubling her for 15 years.been troubling her for 15 years.
 The pain occurs frequently after meals often relieved for a fewThe pain occurs frequently after meals often relieved for a few
minutes by defecation; loose stools are common with pain.minutes by defecation; loose stools are common with pain.
 No family H/O CRC but there is a family H/O celiac dis in her motherNo family H/O CRC but there is a family H/O celiac dis in her mother
 No other red flags (no wt loss, vomiting, bleeding, or otherNo other red flags (no wt loss, vomiting, bleeding, or other
worrying symptoms).worrying symptoms).
 She is well nourished & weighs 77 kg; physical exam is normal.She is well nourished & weighs 77 kg; physical exam is normal.
 What should be done next:What should be done next:
 A: Perform a colonoscopy?A: Perform a colonoscopy?
 B: Screen for CD serologically on a normal diet?B: Screen for CD serologically on a normal diet?
 C: Perform an OGD with biopsies?C: Perform an OGD with biopsies?
 D: treat the symptoms empirically & reassess?D: treat the symptoms empirically & reassess?

3. Commentary:Commentary:
 The diagnosis here is most likely IBS, but the DD includes CD (asThe diagnosis here is most likely IBS, but the DD includes CD (as
the clinical features can mimic IBS) &family history indicates a highthe clinical features can mimic IBS) &family history indicates a high
pre-test probability—so excluding CD serologically is important inpre-test probability—so excluding CD serologically is important in
this case.this case.
 If celiac screening is negative, empiric therapy for IBS would beIf celiac screening is negative, empiric therapy for IBS would be
the most reasonable next step, rather than colonoscopy (young notthe most reasonable next step, rather than colonoscopy (young not
in screening age, no alarm features & long history of symptoms).in screening age, no alarm features & long history of symptoms).

4. IBS:epidemiologyIBS:epidemiology
 Affects 10% of Americans.Affects 10% of Americans.
 It is unusual for IBS to present for the first time in a patient >50 ys.It is unusual for IBS to present for the first time in a patient >50 ys.
 The exact pathophysiology is unknown.The exact pathophysiology is unknown.
 IBS can run in families.IBS can run in families.
 Postinfection IBS is well recognized after bacterial or otherPostinfection IBS is well recognized after bacterial or other
gastroenteritis specially those with severe infection, or are alreadygastroenteritis specially those with severe infection, or are already
anxious or depressed are more at risk.anxious or depressed are more at risk.
 In some patients with IBS, subtle intestinal inflammation (e.g., withIn some patients with IBS, subtle intestinal inflammation (e.g., with
mast cell infiltration) observed & cytokines may be elevated.mast cell infiltration) observed & cytokines may be elevated.
 The gut microbiome may be altered too, producing excess gasThe gut microbiome may be altered too, producing excess gas
from food substrates.from food substrates.
 Anxiety / depression commonly accompany IBS.Anxiety / depression commonly accompany IBS.
 Brain-gut dysregulation through the stress & autonomic pathwaysBrain-gut dysregulation through the stress & autonomic pathways
may alter gut sensation & motility in IBS.may alter gut sensation & motility in IBS.

5. IBS : Clin featuresIBS : Clin features
 Diagnosis:Diagnosis:
 IBS is not a diagnosis of exclusion, but should be based on theIBS is not a diagnosis of exclusion, but should be based on the
Rome symptom criteria plus a few simple tests.Rome symptom criteria plus a few simple tests.
 The updated Rome IV criteria for IBS released.The updated Rome IV criteria for IBS released.
 A patient who presents with longstanding gut symptoms (6 monthsA patient who presents with longstanding gut symptoms (6 months
or more) including abd pain& constipation&/or diarrhea&who hasor more) including abd pain& constipation&/or diarrhea&who has
two or more of the following has IBS until proven otherwise:two or more of the following has IBS until proven otherwise:
 •• Abdominal pain relieved (or sometimes worsened) by defecation;Abdominal pain relieved (or sometimes worsened) by defecation;
 •• Abdominal pain associated with an increased stool frequency orAbdominal pain associated with an increased stool frequency or
looser stoolslooser stools
 •• Abdominal pain associated with a decreased stool frequencyAbdominal pain associated with a decreased stool frequency oror
harder stools.harder stools.
 The symptoms typically fluctuate over time.The symptoms typically fluctuate over time.

6. Clin features:Clin features:
 Stool form is used to subtype IBS (into diarrhea, constipation,Stool form is used to subtype IBS (into diarrhea, constipation,
mixed, or unclassifiable).mixed, or unclassifiable).
 The IBS subtype can change over time (e.g., from diarrhea toThe IBS subtype can change over time (e.g., from diarrhea to
constipation) &not an indication to commence another workup.constipation) &not an indication to commence another workup.
 Many IBS patients also report bloating & visible abd distention.Many IBS patients also report bloating & visible abd distention.
 This distention is real, not imagined ( may reflect an abnormal gutThis distention is real, not imagined ( may reflect an abnormal gut
visceral-somatic reflex response with failure of the diaphragm tovisceral-somatic reflex response with failure of the diaphragm to
relax).relax).
 Non-gastrointestinal (GI) symptoms are common& may reflectNon-gastrointestinal (GI) symptoms are common& may reflect
brain-gut dysregulation;include headaches, back pain, fatigue,brain-gut dysregulation;include headaches, back pain, fatigue,
myalgia, dyspareunia, urinary frequency, dizziness.myalgia, dyspareunia, urinary frequency, dizziness.
 These features are not diagnostic.These features are not diagnostic.

7. Diagnosis:Diagnosis:
 A positive diagnosis is considered best practice based on a typicalA positive diagnosis is considered best practice based on a typical
history (long-standing symptoms with positive Rome criteria) & anhistory (long-standing symptoms with positive Rome criteria) & an
absence of red flags or alarm features (e.g.,age >50 years, weightabsence of red flags or alarm features (e.g.,age >50 years, weight
loss, bleeding, anemia, family history of GI cancer).loss, bleeding, anemia, family history of GI cancer).
 Of note, all of these red flag features have a low positive predictiveOf note, all of these red flag features have a low positive predictive
value for organic disease (many have IBS despite having a redvalue for organic disease (many have IBS despite having a red
flags).flags).

8. IBS mimics:IBS mimics:
 Classic mimics of IBS to consider in the DD:Classic mimics of IBS to consider in the DD:
 ••CD can present with IBS of any subtype but diarrhea is moreCD can present with IBS of any subtype but diarrhea is more
typical .typical .
 A family history if present is helpful (approximately a 10%A family history if present is helpful (approximately a 10%
prevalence of CD is found in first-degree relatives).prevalence of CD is found in first-degree relatives).
 Usually CD patients in the US typically have not lost weight ( mayUsually CD patients in the US typically have not lost weight ( may
even be obese).even be obese).
 The practical way to sort this out is to check the immunoglobulin AThe practical way to sort this out is to check the immunoglobulin A
(IgA) anti-tissue transglutaminase (tTG) & IgA levels to ensure the(IgA) anti-tissue transglutaminase (tTG) & IgA levels to ensure the
patient is not IgA deficient.patient is not IgA deficient.
 If the patient is eating gluten, a normal tTG is usually sufficient toIf the patient is eating gluten, a normal tTG is usually sufficient to
exclude CD& If tTG is positive, do duodenal biopsies.exclude CD& If tTG is positive, do duodenal biopsies.
 It is cost-eff ctive to screen for CD in a patient with IBS if the pre-It is cost-eff ctive to screen for CD in a patient with IBS if the pre-
test likelihood is over 1%.test likelihood is over 1%.

9. IBS mimics:IBDIBS mimics:IBD
 •• IBD can present with similar symptoms&complete blood count &IBD can present with similar symptoms&complete blood count &
C-reactive protein (not ESR) or stool calprotectin canC-reactive protein (not ESR) or stool calprotectin can help screen.help screen.

10. IBS mimics:MCIBS mimics:MC
 •• Microscopic colitis can present with features typical of IBS-DMicroscopic colitis can present with features typical of IBS-D
(usually older women).(usually older women).
 •• Ovarian cancer (constipation), or chronic pancreatitis or carcinoidOvarian cancer (constipation), or chronic pancreatitis or carcinoid
(diarrhea), can present with IBS-like symptoms.(diarrhea), can present with IBS-like symptoms.

11. IBS mimics:PFDIBS mimics:PFD
 •• Pelvic floor outlet obstruction can present with featuresPelvic floor outlet obstruction can present with features
consistent with IBS-C plus excessive straining, a feeling of analconsistent with IBS-C plus excessive straining, a feeling of anal
blockage, or prolonged defecation.blockage, or prolonged defecation.
 An office rectal examination will provide clues, such as onAn office rectal examination will provide clues, such as on
straining the finger is more tightly gripped by the anal sphincter,straining the finger is more tightly gripped by the anal sphincter,
the opposite of normal (useful clinically, plus a rectal examinationthe opposite of normal (useful clinically, plus a rectal examination
may identify a large obstructing rectocele).may identify a large obstructing rectocele).

12. IBS mimics:EndometriosisIBS mimics:Endometriosis
 •• Endometriosis can mimic IBS.Endometriosis can mimic IBS.
 Women with endometriosis * 6 more to be diagnosed with IBS.Women with endometriosis * 6 more to be diagnosed with IBS.
 Symptoms that correlated with endometriosis in women who hadSymptoms that correlated with endometriosis in women who had
IBS &laparoscopically proven endometriosis were:IBS &laparoscopically proven endometriosis were:
 Worsening of symptoms premenstrually.Worsening of symptoms premenstrually.
 Intermenstrual bleeding.Intermenstrual bleeding.
 On physical exam:On physical exam:
 > Vaginal forniceal tenderness.> Vaginal forniceal tenderness.
 The gold standard for diagnosis is laparoscopy with biopsiesThe gold standard for diagnosis is laparoscopy with biopsies
confirmingconfirming endometriosis.endometriosis.

13. Management:overallManagement:overall
 A positive diagnosis (not endless testing), reassurance (asA positive diagnosis (not endless testing), reassurance (as
mortality in IBS is unaffected)&explanation help many patientsmortality in IBS is unaffected)&explanation help many patients
 A negative colonoscopy is not reassuring — hence the importanceA negative colonoscopy is not reassuring — hence the importance
of the doctor-patient relationship.of the doctor-patient relationship.
 If there are no alarm features, screening tests are negative& aIf there are no alarm features, screening tests are negative& a
typical history is provided, a trial of therapy is reasonable.typical history is provided, a trial of therapy is reasonable.

14. Management:DietManagement:Diet
 •• A diet low in FODMAPs (Fermentable Oligo-Di-MonosaccharidesA diet low in FODMAPs (Fermentable Oligo-Di-Monosaccharides
 and Polyols) reduces IBS symptoms in 50–70% of cases, possiblyand Polyols) reduces IBS symptoms in 50–70% of cases, possibly
by starving microbes so that gas production is reduced.by starving microbes so that gas production is reduced.
 •• Fiber (preferably soluble rather than insoluble) or a fiberFiber (preferably soluble rather than insoluble) or a fiber
supplement(psyllium) can help constipation (start at a low dose&supplement(psyllium) can help constipation (start at a low dose&
build up slowly).build up slowly).

15. Management:DrugsManagement:Drugs
 To prescribe gut-directed pharmacotherapy, consider whichTo prescribe gut-directed pharmacotherapy, consider which
subtype of IBS is currently predominant.subtype of IBS is currently predominant.

16. Management:IBS-CManagement:IBS-C
 Try an osmotic laxative (e.g., polyethylene glycol) first&titrate theTry an osmotic laxative (e.g., polyethylene glycol) first&titrate the
dose as needed; pain is not helped.dose as needed; pain is not helped.
 •• Next consider a locally acting secretagogue; two FDA-approvedNext consider a locally acting secretagogue; two FDA-approved
choices—linaclotide (a guanylate cyclase activator) or lubiprostonechoices—linaclotide (a guanylate cyclase activator) or lubiprostone
(a chloride channel activator),well tolerated & do(a chloride channel activator),well tolerated & do reduce abdominalreduce abdominal
pain.pain.

17. Management:IBS-DManagement:IBS-D
 Loperamide first & titrate dose to prevent symptoms ( not for pain).Loperamide first & titrate dose to prevent symptoms ( not for pain).
 •• Consider a bile salt binder such as cholesytramine (as excess bileConsider a bile salt binder such as cholesytramine (as excess bile
salts drive diarrhea in up to one-third with IBS).salts drive diarrhea in up to one-third with IBS).
 •• Three FDA-approved drugs:Three FDA-approved drugs:
 1 Rifaximin, a safe non-absorbable oral antibiotic, improves1 Rifaximin, a safe non-absorbable oral antibiotic, improves
diarrhea, pain, and to a lesser extent bloating.diarrhea, pain, and to a lesser extent bloating.
 Relapse is the rule in those who respond & re-treatment works in aRelapse is the rule in those who respond & re-treatment works in a
subset of initial responders.subset of initial responders.
 2 Eluxadoline, a mixed μ - & κ -opioid receptor agonist&2 Eluxadoline, a mixed μ - & κ -opioid receptor agonist& δ -opioidδ -opioid
receptor antagonist, is efficacious. Pancreatitis is rare (<1%), butreceptor antagonist, is efficacious. Pancreatitis is rare (<1%), but
avoid if post cholecystectomy or the patient is a heavy drinker.avoid if post cholecystectomy or the patient is a heavy drinker.
 3 Alosetron, a 5-HT3 (serotonin 3) antagonist, slows3 Alosetron, a 5-HT3 (serotonin 3) antagonist, slows int transit ( notint transit ( not
FDA-approved in men). can cause severe constipation & ischemicFDA-approved in men). can cause severe constipation & ischemic
colitis.colitis.

18. Management: BloatingManagement: Bloating
 Consider a probiotic or rifaximin& treat constipation if present.Consider a probiotic or rifaximin& treat constipation if present.
 If available, psychological therapy can help reduce symptoms.If available, psychological therapy can help reduce symptoms.

19. Management: case continuedManagement: case continued
 After negative celiac serological testing a positive diagnosis of IBSAfter negative celiac serological testing a positive diagnosis of IBS
was made.was made.
 A course of rifaxamin 550 mg three times daily for 14 days resultedA course of rifaxamin 550 mg three times daily for 14 days resulted
in no improvement.in no improvement.
 A low-FODMAP diet was commenced, with symptom reduction thatA low-FODMAP diet was commenced, with symptom reduction that
has been maintained.has been maintained.