Dr. Melvyn Letier

Constantiaberg Mediclinic

October 2016

This presentation will enable you to:

Understand the pathophysiology of IBS

Recognize the clinical manifestations of IBS

Make a confident diagnosis of IBS

Be better able to treat your patients with IBS

IRRITABLE BOWEL SYNDROME

“The bowels are at one time constipated, at another lax, in the same person… How the disease has two such different symptoms I do not profess to explain…”

W Cumming, London Medical Gazette, 1849

Recurrent abdominal pain or discomfort for at least 3 days/month in last 3 months, associated with 2 or more of the following:

Improved with

defaecation

Onset associated

with change in stool

frequency

Onset associated

with change in stool

form

Criteria fulfilled for at least 3 months, and symptom onset at least 6 months prior to diagnosis

Longstreth GF Gastroent 2006

The history and physical examination, and where appropriate selected laboratory tests, should exclude alarm symptoms and signs

Anaemia

Fever

Unexplained weight loss

Persistent Diarrhoea

Severe Constipation

Nocturnal symptoms

Coeliac disease

Rectal bleeding

Family history of colorectal cancer or IBD

New onset symptoms > 50

Not Routinely Recommended

May be helpful Recommended

FBC, ESR, CRP Coeliac serology in D-IBS, M-IBS s-tTG

Colonoscopy in patients with family history of CRC; over 50 years

Serum Chemistry H2 Breath testing for lactose intolerance

Thyroid functions H2 Breath test for small bowel bacterial overgrowth

Stool MC+S*

Abdominal imaging *

Am J Gastroenterol 2009; 104; S1

Adapted from Camilleri and Choi. Aliment Pharmacol Ther. 1997;11:3.

Enhanced

Perception

Sympathetic

Vagal

Nuclei

5-HT

Altered

Motility

Visceral

Hypersensitivity

Have analgesic as well as mood improving effects

Modes of action of TCAs and SSRIs are: endogenous endorphin release, blockade of noradrenalin reuptake, and blockade of serotonin

A meta-analysis showed antidepressants more effective than placebo for pain relief and global symptoms, in a 1-3 month period. (NNT=4)

TCAs exert benefit at lower than antidepressant doses e.g. 10-20mg nocte. Treat initially for 3-4 weeks

Post-infectious IBS (PI-IBS)-odds increased six fold after acute gastroenteritis

Risk factors for PI-IBS include young age, prolonged fever, anxiety and depression, longer illness duration

Causes of PI-IBS thought to include malabsorption, increased lymphocytes and entero-endocrine cells, and antibiotic use

Alteration in faecal microflora.

Small intestinal bacterial overgrowth: positive H2- breath test, response to antibiotics

Food sensitivity/food allergy; carbohydrate malabsorption, gluten sensitivity.

FODMAPS (fermentable oligo-, di-, and monosaccharides and polyols) enter distal small bowel and colon and undergo fermentation

Abdominal Pain

Chronic

Variable sites and intensity

Triggers include food and

stress

Nocturnal pain is unusual

HMO group (Kaiser Permanente)

Surgical predisposition in IBS; misdiagnosis important underlying factor

Women undergoing hysterectomy for pain more likely to have IBS

Increased multidisciplinary collaboration may improve diagnosis and reduce surgery

Longstreth, Yao. Gastroent 2004;126

Surgery IBS (%)

N=4587

Non IBS(%)

N=84421

Cholecyst. 12.4 4.1

Appendicec. 21.1 11.7

Hysterect. 33.2 17.0

Back surg 4.4 2.9

CABG 2.8 2.4

Peptic ulcer 0.5 0.3

Diarrhoea Constipation

Small-moderate volume loose stools; more frequent

Hard, pellet-like stools; may have normal or loose stools; less frequent

Crampy pain, relieved after stool Crampy pain, relieved after stool

Sense of incomplete evacuation Sense of incomplete evacuation

Mucus in ± 50%

Reproduced by kind

permission of Dr K W Heaton,

Reader in Medicine at the

University of Bristol. 2000

Norgine Ltd.

Often worse post-prandial

Worse as day goes on

Increased abdominal girth, without increase in total gas content

Mechanism: gas trapping in small intestine

12

88

Family Practice

IBS

OTHER

28

72

Gastroenterology

IBS

OTHER

12% of GP Visits 28% of Gastro Visits

Prevalence – 4 to 30% (average + 20%)

Up to 75% of persons with IBS do not seek medical attention

8 – 15% of primary care and 20 – 40% of referrals to gastroenterologists

Remains common in the elderly (Often misdiagnosed as symptomatic diverticulosis)

Increased health care burden and more days off work

Medical costs - + $8 billion in USA annually

The North-West University (Potchefstroom) study. The purpose of the study:

To investigate the relationship of job burnout and work

engagement with self-reported received treatment for health conditions (Cardiovascular condition, High cholesterol, Depression, Diabetes, Hypertension and Irritable bowel syndrome), while controlling for age, gender, smoking and alcohol use.

Results: The results showed that job burnout had a positive relationship with self-reported received treatment for Depression, Diabetes, Hypertension and Irritable bowel syndrome.

Reference : Leon T. de Beer1*†, Jaco Pienaar1 & Sebastiaan Rothmann Jr.2 Published online 10 April 2014 in Wiley Online Library (wileyonlinelibrary.com) DOI: 10.1002/smi.2576

Reference : Leon T. de Beer1*†, Jaco Pienaar1 & Sebastiaan Rothmann Jr.2 Published online 10 April 2014 in Wiley Online Library (wileyonlinelibrary.com) DOI: 10.1002/smi.2576

1. Why present now?

2. Establish therapeutic relationship

3. Patient education

4. Dietary modification

5. Physical activity

6. Psychosocial therapy

7. Medication

8. Alternative therapies

Change in symptoms e.g. medication, diet

Concern about serious illness

Stressors

Hidden agenda e.g. disability, request for opiates or tranquillizers

Psychological co-morbidity

Non-judgmental

Establish realistic expectations

Involve patient in treatment decisions

Patients with established, positive physician interactions have fewer IBS related follow-up visits

Education helps validate patients illness experience

www.uptodate.com/patients www.aboutibs.org

Sets the basis for therapeutic intervention

Stress the chronic, benign nature of IBS

The diagnosis of IBS (well validated) is robust and unlikely to change over time

IBS has no effect on lifespan

Take a careful dietary history

Consider Lactose intolerance, trial of Lactose-free diet, FODMAP diet

Reduced intake of gas forming foods in patients with increased gas

Food allergy testing not recommended

Gluten restriction in non-Coeliac patients may be of benefit

Fermentable oligo-di-monosaccharide and polyols (FODMAPs) enter distal small bowel and colon, fermented, and cause symptoms

FODMAPs include Fructans, Galactans, Lactose, Fructose, Sorbitol, Xylitol and Mannitol

Several studies on low FODMAPs diet have been shown to be of benefit in patients with IBS

A trial of low FODMAPs diet is reasonable, provided nutritional status is monitored

Gibson PR APT 2005

30

Modes of action: increased water holding in stool; gel formation to lubricate stool; bulking of stool; bile salt binding

Bulking agents showed no benefit over placebo for reducing IBS global symptoms

Hi-fiber foods e.g. All Bran® may aggravate bloating

Because of safety and placebo effect a trial of therapy is reasonable, especially in C-IBS (<30g/d)

Increased physical activity may help with symptoms of IBS

In a Scandinavian study of 102 IBS patients, moderate to vigorous exercise 3-5 times per week showed

significant benefit over non-exercising.

Active Exercise Group

Non-active Group

Decrease in symptom score

51 5

Worsening Symptoms

8% 23%

Am J Gastroent 2011

Behavioral treatment e.g. Hypnotherapy, Biofeedback, Psychotherapy may be useful

They reduce anxiety levels, encourage health promoting behavior, involve patients in treatment and improve pain tolerance

A 2009 meta-analysis of 20 studies (n=1278) showed Psychological therapy including Antidepressants to be significantly more effective vs. control or standard of care

Ford AC GUT 2009

Medication must be considered an ADJUNCT to IBS treatment

Drug selection will vary with dominant symptoms

Chronic drug use should be minimized: IBS is a lifelong condition; lack of convincing evidence of efficacy

High placebo response rate in IBS

1. Antispasmodics

2. Antidepressants

3. Anti-diarrhoeal agents

4. Anti-constipation agents

5. Probiotics

6. Alternative therapies

Pain and Bloating

Constipation Diarrhoea

Anti-spasmodics Tricyclics SSRIs

Laxatives Prucalopride* Lubiprostone* Linaclotide*

Loperamide 5HT3 Antagonists e.g. Alosetron*

IBS Drug Treatment

IBS

Most widely used drugs in IBS

Should be used “on demand” rather than on a regular basis

May be useful in patients with post-prandial pain, gas, bloating and faecal urgency

Agents available in SA include Mebeverine, Hyoscine, Peppermint oil, Librax ®

Poynard T et al APT 2001

More effective than placebo for pain relief and global symptom improvement; NNT=4

Tricyclics effective at lower than antidepressant doses e.g. amitriptyline 10-25 mg daily. Use with caution in constipated patients. Aim at 3-4 week trial of therapy given delayed onset of action

SSRI treatment data less consistent than TCAs

Reupert L Cochrane Database 2011

Use step-up approach

Osmotic laxatives; Bulking agents

Irritant laxatives + Bulking agent

Irritant Laxatives

Others

Administration of Bifidobacterium Infantis alleviated IBS symptoms including abdominal pain, bloating and normalized bowel movement.

An abnormal IL10/IL12 ratio at baseline was normalized by feeding B. Infantis.

B. Infantis changed a pro-inflammatory ratio to an anti-inflammatory state i.e. Immune modulating effect

A prospective placebo-controlled study found patients with diarrhoea predominant IBS taking Saccharomyces Boulardii, a probiotic yeast, had a significant reduction on the number and improvement in consistency of bowel movements.

O’Mahoney et al Clin Gastroenterol Hepatol 2005

Meta-analysis of 14 probiotic trials:

Small improvement in overall IBS symptoms

Effects on individual symptoms i.e. bloating, pain, flatulence – conflicting evidence

No adverse effects

Systematic review of 18 trials:

Most used combination or Lactobacilli/ Bifidobacteria

Statistically significant effect over placebo wrt Global IBS symptoms, pain & flatulence but not bloating

ACG guidelines give probiotics a weak recommendation due to lack of long term data

Hoveyda et al – Gastroenterology 2009; Moayyedi et al – Gut 2010

Iberogast (German Herbal medication)

Rifaximin (Antibiotic – not available in S.A)

Tranquilizers e.g. Librax

Hypnotherapy

Acupuncture

Recent studies have suggested that Rifaximin, a non-absorbable antibiotic, can be used as an effective treatment for abdominal bloating and flatulence, giving more credibility to the potential role of bacterial overgrowth in some patients with IBS.

A double-blind, randomized, placebo-controlled trial compared the multi-herbal extract Iberogast versus placebo in the treatment of all three forms of irritable bowel syndrome. This multi-target phytopharmaceutical was found to be significantly superior to placebo via both an abdominal pain scale (p value = 0.0009) and an IBS symptom score (p value = 0.001) after four weeks of treatment.

Enteric coated Peppermint oil capsules has been advocated for IBS symptoms in adults and children; however, results from trials have been inconsistent. Peppermint may exacerbate GORD.

There is a strong brain-gut component to IBS, and Cognitive therapy may improve symptoms in a proportion of patients in conjunction with Antidepressants. In a randomized controlled trial of referred patients, Cognitive behavioural therapy helped even though patients in this study did not have any psychiatric diagnoses.

Gut-directed or gut-specific Hypnotherapy or self-hypnosis is one of the most promising areas of IBS treatment. Current research shows that symptom reduction/elimination from IBS hypnotherapy can last at least five years.

Pharmaceutical companies – Financial potential (High prevalence, Affliction of affluence, Lack of effective therapy)

Will these patients ever uniformly benefit from drug treatment?

Animal models for functional disorders do not accurately reflect the human condition

Recent phase 3 trials fundamentally flawed

Only 6/93 trials of IBS intervention found to be scientifically adequate in recent review

Great difficulty in defining end-points in clinical trials to reflect beneficial effect on global well-being & IBS symptoms

Pressure groups – may have +ve or –ve impact on decisions by licensing authorities and politicians

“It’s not life-threatening, after all, it’s not cancer.”

“You need to learn to live with it. Come back and see me if you get a new symptom, but otherwise it’s just IBS.”

“Heck I can't even find a doctor to actually diagnose me for IBS.”

“A virus that needs to work its way out? Has this doctor never heard of the Rome 3 criteria? Don’t they teach this stuff in Medical school?”

Aim to make a positive diagnosis with Rome criteria

history, examination

Beware alarm symptoms: Wt loss, PR bleeding, recent change

in bowel habit, etc

Basic Ix: stool culture, FBC, U&E, LFT, CRP, TFT, anti tTG Ab, glucose, Ca

Refer for further investigation

IBS-C IBS-D Pain/Bloating

Explanation, reassurance, dietary and lifestyle advice

Increase dietary fibre / fluid Bulk forming laxative(s) Consider Citalopram

Dietary modification Anti-diarrhoeal agents Consider Amitriptyline

Reduced fibre intake Increased fluids Antispasmodics Consider TCA’s/Citalopram

In refractory cases consider Counselling, Hypnotherapy, Biofeedback, role of Probiotics

IBS is a chronic medical condition characterized by abdominal pain, diarrhoea or constipation, bloating, passage of mucus and feelings of incomplete evacuation

Precise etiology of IBS is unknown and therefore treatment is focused on relieving symptoms rather that “curing disease”

A complex multifactorial ‘disease’

Huge resource usage

Probably grossly over investigated in many cases

Targeted drug therapy difficult

New therapies but modest results

Although many IBS patients complain of symptoms after eating, true food allergies are uncommon

Specific therapies are determined by individual patient symptoms

Life-style modifications and possible alternative therapies may relieve symptoms

Current drug therapy often provides inadequate relief of IBS symptoms, leading many patients to consider CAM therapies (Complementary and Alternative Medicine).

Aloe barbadensis Miller Extract (AVH200®) is a CAM therapy that is well tolerated, safe and has been shown to be a promising treatment option for patients with IBS.

PROIBS® which contains AVH200®has successfully completed a randomized placebo study at the Sahlgrenska University Hospital in Sweden.

The results from the study showed that symptoms in adults with diagnosed IBS improved significantly when the diet was supplemented with AVH200® compared to the placebo. AVH200® was seen to reduce problems of discomfort and perceived feeling of bloating.

Thus, PROIBS® containing this unique extract is seen as a promising treatment adjunct for the dietary management of IBS.