IBS - cb

Irritable Bowel Syndrome

Christopher Betts (PGY I)

IBS• IBS definition: three days per month in the last three

months of abdominal pain w/ altered bowel habits (or changes in frequency of normal BM schedule) due to no organic disease

• Clinical picture: Abdominal pain, diarrhea, constipation, an alternating combination of diarrhea with constipation.

• Prevalence of 5-10% in North America; peak prevalence among ages 20-39 yo

• F:M ratio 1.5:1• Lower socioeconomic populations

IBS

Altered Bowel-habits:• Diarrhea predominant– Possible correlation w/ incr plasma serotonin

levels• Constipation predominant– Possible correlation w/ decr plasma serotonin

levels• Mixed pattern of diarrhea and constipation

IBS: Etiology & Epidemiology

• IBS is a functional disorder.• Threefold incr risk of IBS in persons w/ an immediate

family member who has had the condition.• Disturbances in GI motility• Mucosal barrier disruption• Visceral hypersensitivity• Dysfunction of the gut-brain axis• Stress response w/ involvement of neurotransmitters

IBS: Etiology & Epidemiology

• Association w/ psychological disorders– i.e. Anxiety, depression, PTSD– up to two-thirds of patients w/ IBS in tertiary care

centers having a concurrent psychological disorder– A study of 257 patients w/ severe IBS; 12%

reported a h/o rape; these patients showed improved quality of life following psychological treatment and antidepressant therapy.

• Enteric nervous system: Intrinsic innervation of the GI tract; coordinates and relays information from the parasympathetic and sympathetic nervous system to the GI tract. Uses local reflexes to relay information w/in the GI tract.

• Myenteric/Auerbach's plexus: primarily controls motility of the GI smooth muscle

• Submucosal/Meissner's plexus: primarily controls secretion and blood flow; receives sensory info from chemoreceptors and mechanoreceptors in the GI tract.

• Segmentation contractions: mix intestinal contents by sectional contraction of small intestine expelling chyme in orad and caudad directions; a back-and-forth movement produced by segmentation contractions causes mixing w/o any net forward movement of the chyme.

• Emotional factors strongly influence large intestinal motility via the extrinsic ANS. IBS may occur during periods of stress and may result in constipation (increased segmentation contractions) or diarrhea (decreased segmentation contractions).

IBS: Clinical Presentation

• Most common symptoms with high sensitivity– Lower abdominal pain– Feeling of incomplete evacuation

• Less common symptoms with high specificity– Passage of looser stools at the very onset of abdominal pain– Passage of more frequent stools at the very onset of

abdominal pain– Abdominal pain relieved by defecation– Passage of mucus per rectum– Patient-reported abdominal distention

IBS: Clinical Presentation• Recurrent, episodic abdominal pain

– Most common symptom– Cramping-like sensation– Worse w/ food and/or emotional stress– Improved w/ defecation (higher in specificity)– Onset of pain associated with more frequent passage of stools and

passage of looser stool (higher in specificity)• Negative pertinent factors: not progressive, pain not disruptive

of sleep, no associated anorexia, no malnutrition, no weight changes

• The onset of altered bowel habits is consistent w/ the onset of abd pain

IBS: Clinical Presentation• Diarrhea

– Frequent and loose– Preceded by abd pain – Relieves the abd pain– Sensation of urgency and incomplete relief after defecation– Mucus in stool

• Negative pertinent factors: not large in volume, no blood, does not occur at night, no recent abx use

• Constipation: lasting for few days, alternating w/ normal BM or diarrheic episodes, hard pellet-shaped stools, incomplete relief after defecation.

IBS: Clinical Presentation• Other noted symptoms of even lesser frequency:

– lump in throat– belching– acid reflux– dysphagia– early satiety– intermittent dyspepsia– nausea– non-cardiac CP– abdominal bloating– dysmenorrhea– dyspareunia– urinary urgency/frequency– fibromyalgia

IBS: Clinical Presentation

• The negative predictive value of IBS is high with the absence of abdominal pain and presence of other IBS symptoms such as pain relieved by defecation and feeling of incomplete evacuation.

IBS: Diagnosis & Tests• A combination of H&P, Rome III criteria, and statistical criteria.

• Rome III Criteria:– Improvement w/ defecation– Onset associated w/ change in frequency of stools– Onset associated w/ change in stool form/appearance

• Criteria must have been met in the previous three months, w/ symptom onset at least six months before diagnosis.

• Used mainly in selecting patients for clinical trials and not in the actual clinical setting

• Alarm features not c/w IBS: – Anemia, rectal bleeding, nocturnal symptoms, weight loss, recent abx use, onset after 50

yrs of age, positive FMHx of colorectal cancer/IBD/celiac disease.– Should prompt further investigation for other diseases.

IBS: Diagnosis & Tests

• Testing for celiac disease– For those w/ diarrhea-predominant or mixed presentation

IBS– Systematic review including more than 4000 patients

showed that 4% of those w/ diarrhea-predominant or mixed presentation IBS had biopsy-proven celiac disease

– Gluten sensitivity as a probable etiology in functional bowel syndrome has been poorly supported

• Unnecessary tests: abd imaging, CBC, CMP, thyroid function tests, stool for ova/parasites– The rationale for developing all these types of criteria.

IBS: Diagnosis & TestsJAMA article in Nov 2008 conducted by Ford et al: JAMA. 2008;300(15):1793-1805 (doi:10.1001/jama.300.15.1793) • Systematic review of literature of the accuracy of individual symptoms and

combinations of findings in diagnosing IBS. The search of medical literature went back as far as 1950 to 2008. A total of 16079 studies identified.

• Overall impression from study:– The absence of abdominal pain reduces the likelihood of IBS as the explanation to lower

GI tract symptoms. It is built into most definitions of IBS, thereby maximizing sensitivity.– Other symptoms related to abdominal pain (i.e. its commencement a/w more frequent

and looser stools, and its relief w/ defection) have better positive likelihood ratios than symptoms such as passage of mucus per rectum and feelings of incomplete evacuation.

– Individual symptoms are poor at distinguishing IBS vs. organic disease of the lower GI tract; using combinations of clinical findings with diagnostic criteria, and statistical models are required.

– Using diagnostic criteria over exhaustive investigative studies to exclude organic causes is an approach endorsed by the American College of Gastroenterology and British Society of Gastroenterology.

History of Diagnostic Criteria for IBS

The IBS Severity Scoring System is a validated measure in assessing the severity of IBS symptoms, as well as a way of monitoring response to treatment.

The Bristol Stool Scale can be used to describe stool consistency to differentiate constipation from diarrhea and monitor treatment response.

ConstipationDiarrhea

Norm

al stool

IBS: Diagnosis & Tests

IBS: Treatment & ManagementSUMMARY• Goals include symptom relief and improved quality of life• Symptoms are often recurrent and resistant to therapy• Exercise, antibiotics, antispasmodics, peppermint oil, and

probiotics appear to improve symptoms in IBS of all types. • OTC laxatives and antidiarrheals improve stool frequency but

lack in relieving abdominal pain.• Antidepressants and psycho-therapy have shown to be effective.• Cases of refractory IBS calls for more specialized medications,

including Lubiprostone, Alosetron, and Tegaserod (the latter two having restrictive use).

IBS: Treatment & Management

IBS: Treatment & ManagementAll types of IBS:• Physical activity• Probiotics, Antibiotics• Therapeutic relationship between physician and patient• Antispasmodics (i.e. Hyoscyamine, Dicyclomine)• Antidepressants, Psychological treatments• Contemporary & Alternative therapies

– Hypnotherapy, Acupuncture, Herbal therapies• Peppermint oil• Dietary modification


Physical activity• One RCT involving 102 patients w/ IBS showed that those who

were randomized to physical activity had fewer IBS symptoms compared w/ the control group (8% vs. 23%).

• After 12 weeks, there was a trend toward more patients in the physical activity arm showing clinical improvement in the severity of IBS symptoms compared to those in the control group. The former group had also shown to be less likely to have clinically significant worsening of their IBS symptoms.

• Moderate to vigorous exercise 20-60 min, three to five times per week.

IBS: Treatment & ManagementProbiotics and antibiotics• The probable etiology in IBS of an alteration of the gut

microflora

• Majority of RCT studies on antibiotic use in selected patients w/ IBS showed improvement in symptoms of bloating, abdominal pain, and altered bowel habits.

• One small RCT involving 39 patients w/ constipation-predominant IBS were given Neomycin and ultimately showed improved constipation and global IBS symptoms.

IBS: Treatment & ManagementRifaximin• A non-absorbable bacterial DNA-dep RNA polymerase

inhibitor• Its use in diarrhea-predominant or mixed presentation IBS

showing improved bloating, abd pain, and stool consistency compared to placebo in two RCT studies.

• Two RCT trials (TARGET 1 & 2) of 1260 patients w/ IBS without constipation; use of it led to improvement in global IBS symptoms and bloating; dosage in trials was 550 mg tid for 14 days; most common symptom of relief was less bloating

• unlabeled use in treating C-difficile colitis


Probiotics– Weak evidence due to heterogeneity of studies and the

varied probiotics studied– Systematic review of 10 RCTs involving 918 patients w/ IBS

showed significant benefit for reducing IBS symptoms and decr pain and flatulence.

– Systematic review of 14 RCTs showed a modest improvement in overall symptoms, abd pain, and flatulence in patients taking probiotics vs. placebo.

• Type of probiotic species is irrelevant in difference of improvement.

IBS: Treatment & ManagementAntispasmodics• Short-term relief • Administered on an as needed basis and/or in anticipation of

stressors w/ known exacerbating effects• Hyoscyamine (Levsin) 0.125-0.25 mg PO or sublingual tid or qid prn• Dicyclomine (Bentyl) 20 mg PO qid prn• Anticholinergic properties and hence adverse effects include dry

mouth, dizziness, and blurred vision. • One Cochrane review of 29 RCTs showed antispasmodics being

effective in improving abd pain and symptom score in 2333 patients compared to placebo or no treatment.

IBS: Treatment & ManagementAntidepressants• SSRIs (i.e. Citalopram, Fluoxetine, Paroxetine)• TCAs (i.e. Amitriptyline, desipramine, doxepin, imipramine,

trimipramine)• Analgesic properties independent of their mood improving effects• Possible facilitation of endogenous endorphin release, blockade

of NE reuptake leading to enhancement of descending inhibitory pain pathways, blockade of pain neuromodulator serotonin.

• TCAs have anticholinergic properties, like antispasmodics, and can slow intestinal transit time which can be helpful in diarrheal-predominant IBS patients.


Antidepressants• Cochrane review of 15 studies involving 922 patients

found a beneficial effect w/ antidepressants over placebo for improvement in abdominal pain, global assessment, and symptom score.

• Statistically significant benefit shown with SSRIs for improvement of global assessment, and w/ tricyclic antidepressants for improvement of abdominal pain and symptom score.


Therapeutic Relationship• Establishing from the start a healthy physician-

patient relationship. • Physician should be non-judgmental, involving

patient in management decisions, and establishing realistic expectations w/ consistent limits

• This can lead to fewer IBS-related f/u visits.

IBS: Treatment & ManagementTherapeutic Relationship• Annals of medicine – Prospective study of 112 patients w/ diagnosed IBS

through a median 29-year follow up. The study demonstrated the following findings:– IBS associated with a good prognosis and the dx is unlikely to be changed to

that of an organic disease during f/u– IBS-patients w/ a positive physician-patient relationship resulted in fewer

clinic visits and reduced use of ambulatory health services: included noting psychosocial hx, precipitating factors, and discussion of dx and tx w/ patient.

• Non-pharmacologic approach favored• Presence of IBS did not incr risk of mortality or risk of developing other

GI diseases, e.g. chronic pancreatitis, GI cancers, SBO, and gastric ulcers.• Small caveat: Old study back in 1995


Peppermint Oil• Unclear mechanism (decr intestinal motility and secretion?)• A systematic review of four RCTs involving 392 patients

showed that it was more effective than placebo at reducing IBS symptoms.

• Most common result was freedom of abdominal pain and discomfort.

• Two trials conducted a dosage of 187 mg of peppermint oil PO tid for 4 weeks.

• One trial conducted a dosage of 225 mg PO bid for 8 weeks.

IBS: Treatment & ManagementOther complementary & Alternative therapies• Although the mechanism is unclear, the general purpose of this form of

therapy includes decr anxiety in the patient, encouraging a health-promoting behavior in the patient, and increasing patient responsibility and involvement in managing disease.

• Psycho-therapy: CBT, Interpersonal psychotherapy, relaxation and stress management; effective in improving IBS symptoms compared w/ usual care.

• Therapies that had inadequate results from RCT studies: – Hypnotherapy

• Quality in the RCT trials was inadequate to determine its effectiveness– Acupuncture

• No significant difference from sham therapy in a review of 6 trials involving 109 patients.– Herbal therapies

• Some improvement in a Cochrane review of 75 RCTs but inadequate methodology and small sample size.


Dietary modification• Fiber

– No clear beneficial effect compared to placebo in improving global symptoms of IBS in various studies.

• Exclusion of gas-producing foods– i.e. beans, onions, celery, carrots, raisins, bananas, apricots,

prunes, brussel sprouts, wheat germ, pretzels, bagels• Food allergies• Gluten sensitivity• Carbohydrate malabsorption

– Lactose, Fructose, Sorbitol, Xylitol, Mannitol, Galactans, Fructans


Constipation-predominant IBS:• OTC laxatives• Lubiprostone • Neomycin • Tegaserod (Zelnorm)– Withdrawn in 2007


OTC laxatives (i.e. Polyethlyene glycol – Miralax)• Supportive evidence of its use in people w/ IBS is

poor• One small study comparing polyethylene glycol

w/ placebo in 48 adolescents w/ constipation-predominant IBS showed improved stool frequency but no alleviation of abdominal pain

• Miralax is FDA approved for treatment of chronic constipation, but not for IBS

IBS: Treatment & ManagementLubiprostone (Amitiza)• Intestinal chloride-channel activator which enhances chlorine-rich

intestinal fluid• FDA approved for treatment of IBS w/ constipation in women 18 yr

or older.• Best reserved for those w/ IBS and severe constipation refractory to

initial therapies.• Two RCTs of 1171 patients w/ constipation-predominant IBS showed

significantly higher overall symptom relief in those treated w/ lubiprostone than those treated w/ placebo.

• Common adverse reactions included diarrhea and nausea.• Caveats: Long-term safety remains to be established and is expensive


Tegaserod (Zelnorm)• 5-HT4 agonist: stimulate release of NTs and

incr colonic activity• Removed from market in March 2007; due to

cardiovascular side-effects: MI, unstable angina, and stroke

• only available in emergency settings as per FDA


Diarrhea-predominant IBS:• Antidiarrheals• Rifaximin • Alosetron (Lotronex)


Loperamide (Imodium): synthetic opioid decr intestinal transit and incr intestinal absorption of water and ions• Three RCTs involving 126 patients w/ IBS showed that

loperamide was effective at decr stool frequency and increasing stool consistency but did not improve abdominal pain and incr nocturnal pain.

• Preferred use on an as needed basis, but patients who consistently get diarrhea following meals may benefit from its usage just prior to a meal.

IBS: Treatment & ManagementAlosetron (Lotronex)• 5-HT3 antagonist: modulate visceral afferent activity from the GI tract• Meta-analysis that included 14 RCTs in IBS found a benefit in global

improvement in IBS and relief of abd pain and discomfort. • Most effective in female patients with severe diarrheal-predominant

IBS refractory to initial therapies and complementary therapies. • Uncommon but major adverse events include associations w/

ischemic colitis, severe constipation, and death. • FDA pulled it from the market but replaced it back after post-

marketing data and major demand from the small population of patients responsive to its therapeutic effects; under restrictive use.

Resources

• AAFP article: Diagnosis and Management of IBS in Adults: Wilkins, Pepitone, Alex, Schade (2012)

• JAMA article: Will the history and Physical Examination Help Establish That IBS is causing This Patient's Lower Gastrointestinal Tract Symptoms?: Ford, Talley, van Zaten et al. (2008)

• Up To Date: Treatment of IBS

Documents

IBS - cb