Transcript University of Maryland GI Grand Rounds

IRRITABLE BOWEL
SYNDROME-DIARRHEA
A NEW LOOK AT AN OLD
PROBLEM
Meritus Medical Center
Community Education Seminars
August 18, 2011
M. E. Money, M.D., FACP
Clinical Associate Professor Department of Medicine
University of Maryland School of Medicine
Meritus Medical Staff
IRRITABLE BOWEL
SYNDROME-DIARRHEA
What is the irritable bowel syndrome?
What are the symptoms?
Why does it occur?
What are the treatments?
Are there any tests that can definitely “prove”
a person's symptoms are IBS-D?
M. E. Money. M.D.
Definition of IBS
IBS is a functional bowel disorder in
which abdominal pain or discomfort is
associated with defecation or a change in
bowel habit. Bloating, distension, and
disordered defecation are commonly
associated features.
Irritable bowel syndrome: a global perspective. World
Gastroenterology Organizational Global Guideline. April 20, 2009
M. E. Money. M.D.
Mainstream concepts about IBS
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Exact cause of irritable bowel syndrome not
known.
Multiple factors thought to contribute to etiology.
To date an 'IBS gene' has not been identified.
The concept of IBS as a diagnosis of exclusion is
not acceptable any more.
The treatment of IBS is targeted at symptom relief.
Cognitive behavioral therapy is very beneficial.
M. E. Money. M.D.
Diagnostic criteria (Rome III)
• Onset of symptoms at least 6 months before
diagnosis
• Recurrent abdominal pain or discomfort for >3
days per month during the past 3 months
• At least two of the following features:
– Improvement with defecation
– Association with a change in frequency of stool
– Association with a change in stool form
NB: What precedes the symptoms is not included.
WGO Practice Guidelines Irritable bowel syndrome 2009
M. E. Money. M.D.
Accuracy of symptom-based criteria for
diagnosis of IBS in primary care1
Reviewed 25 primary diagnostic studies.
2 research questions:
Performance of symptom-based criteria in
excluding organic GI disease.
Performance of signs and symptoms in identifying
IBS
Conclusion: “organic disease cannot be accurately
excluded by symptom-based IBS criteria alone.”
1Jellema,
P. et al. Systematic review: accuracy of symptom-based criteria for diagnosis
of irritable bowel syndrome in primary care. Alimentary Pharmacology &
Therapeutics. 7-3-09. DOI: 10.1111/j.1365-2036
M. E. Money, MD
Irritable bowel syndrome impact
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Estimated: 15 Million people in the U.S.
Prevalence 10-20% of adults
$2 Billion in direct annual costs
$20 Billion in indirect annual costs
Estimated only 1/3 patients seek medical
attention for condition.
Laudanum, U. Irritable Bowel Syndrome. Advanced Studies in Medicine. Vol.
4, No. 3. March 2004. Pages 128-134.
Executive Summary: IBS in Women: The Unmet Needs. Society for Women’s
Health Research.2003.
M. E. Money. M.D.
Sub types of IBS
IBS-Constipation
32%
IBS-Diarrhea
33%
IBS-diarrhea and constipation 35%
Executive Summary: IBS in Women: The Unmet Needs. Society for
Women’s Health Research. 2003
M. E. Money. M.D.
Patient #1
Has had intermittent increased loose stools after meals
for 11 yrs, sometimes at night if eats late. She wonders
if she has IBS. Symptoms may last for weeks once it
gets started, otherwise only when eats out in
restaurants. Worse with spicy foods, onions, garlicky
Italian meals and tomatoes.
• Exam entirely normal. 64” tall, 161#
• Chronic medical problems other than above: Asthma
• Current meds: Zyrtec, Advair Diskus, Ventolin inhaler
• Mother has similar digestion problem.
• Patient had never had a colonoscopy.
M. E. Money. M.D.
9
Patient #1 continued
• Patient referred to gastroenterologist who wrote:
“Patient states she has cramping, watery diarrhea
alternating with constipation, up to 10x/day, mild in
nature…..symptoms are suggestive of IBS.”
• Investigation by gastroenterologist:
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Colonoscopy negative
X-rays for the stomach and small intestine were normal
Blood tests for Celiac disease was normal
Biopsy of colon negative for pathology
• Treatment: Patient encouraged to try probiotics by
gastroenterologist.
M. E. Money. M.D.
Patient #2
11 year old male
Father has trouble eating certain foods: gets abdominal pain
and urgent diarrhea if eats out in restaurant and avoids
onions at any time.
Son observed to get extremely nervous and sweaty (clammy)
when eating out in a restaurant. Would refuse to eat with
the family sometimes. Didn't want to go with friends to
parties. Frequently complained of having cramping
stomach pains.
M. E. Money. M.D.
Patient #3
76 yr old female
Has had “food allergies” for decades. Predominantly if she
eats spagetti will get moderate cramping and has to find
the bathroom really fast. Sometimes will have 3-4 loose
stools (which may become all liquid) within 30-60 minutes
after eating. The episodes will cause her to feel quite
weak, sweaty, and one time she fainted while sitting on the
commode. She rarely has any nausea and has never had
any hives, trouble breathing, or vomiting.
M. E. Money. M.D.
Patient #4
55 year old construction worker.
Has had frequent bowel movements for the last 20-30 years.
May have 4-6 medium soft to loose stools daily. Will have
to be close to a bathroom while on the job. A couple of
times almost didn't make it. Has more bowel movements
after eating rich, fatty foods, or if sometime is fried.
M. E. Money. M.D.
Incidence of diarrhea occurring after
eating
50% of patients suffering with the diarrhea or
mixed form of IBS related symptoms to
eating.
However, the current definition of IBS does not
encourage nor require the physician to inquire
about any precipitating factor such as the
condition occurring ONLY after eating.
M. E. Money. M.D.
Differential diagnosis for IBS
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Celiac Sprue/gluten enteropathy
Lactose intolerance (inherited or 2nd to mucosal damage)
Inflammatory bowel disease
Colorectal carcinoma
Lymphocytic and collagenous colitis
Acute diarrhea due to protozoa or bacteria
Small-intestinal bacterial overgrowth (SIBO)
Diverticulitis
Endometriosis
Pelvic inflammatory disease
Ovarian cancer
• WGO Practice Guideline IBS 2009
M. E. Money. M.D.
What is missing from this
differential diagnosis?
Conditions that cause
MALDIGESTION
M. E. Money. M.D.
Common conditions that cause
maldigestion
1. Diarrhea due to excess bile acids.
2. Diarrhea due to lack of digestive enzymes
from the pancreas.
3. Diarrhea due to insufficient enzymes from
the small intestine that digest starches
and milk.
Alpha glucosidases deficiencies
(disaccharidases)
Beta glucosidase deficiency (lactase)
M. E. Money. M.D.
Bile acid malabsorption
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Bile acid malabsorption can occur in patients with
or without an intact gall bladder
Bile acid malabsorption(BAM) may affect up to
30-50% of patients with chronic diarrhea
Can be treated with bile acid binding agents:
Welchol, Cholestyramine, Questran
A blood test can now prove this problem but is not
currently available for routine testing.
Recent studies now suggest that bile can bind to
starch and prevent its digestion.
M. E. Money. M.D
Pancreatic insufficiency
Pancreatic insufficiency was found in 6.1%
(19/314) patients who had been diagnosed as
having IBS-D by the Rome Criteria. This was
determined by the measurement of the fecal
elastase-1 concentration in the stool. Patients
were then treated with pancreatic enzyme
supplements with a statistical improvement in
stool frequency, consistency, and abdominal pain.
Some Patient With Irritable Bowel Syndrome May Have Exocrine
Pancreatic Insufficiency. Leeds, J et al, Clinical Gastroenterology and
Hepatology 2010; 8:433-438.
M. E. Money. M.D
Carbohydrate malabsorption
“Carbohydrate malabsorption and intolerance is
suggested by the patient’s clinical history. The
relation of symptoms to feeding and the
occurrence of remission while fasting are crucial
to the history. In older children and adults the
symptoms can resemble those of dyspepsia or
irritable bowel syndrome (IBS)…The diagnosis of
functional bowel disease usually is made without
evaluation of carbohydrate digestion… symptoms
from IBS and carbohydrate intolerance can be
confused easily”.
Disaccharide Digestion: Clinical and Molecular Aspects. Robayo-Torres, C. et
al; Clinical Gastroenterology and Hepatology. 2006;4:276-287
M. E. Money. M.D.
Digestion of starches:
alpha-glucosidases
Starch digestion begins in the mouth by salivary
amylase, which breaks the starch into smaller units
called disaccharides. These are then broken down to
glucose by enzymes in the small intestine known as
“alpha-glucosidases:”
•Maltase
•Isomaltase
•Sucrase
•Trehalase
•Gluco-amylase
M. E. Money. M.D.
Carbohydrate malabsorption
syndromes
Milk-Lactose Maldigestion
• Due to Lactase deficiency,
(a beta-glucosidase)
• Symptoms after the
ingestion of milk
products:
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Abdominal pain
Cramps
Urgent diarrhea
Time of onset: variable
depending upon quantity
and sensitivity of
patient
M. E. Money. M.D.
Starch Maldigestion
• Due to alphaglucosidase(s) deficiency
• Symptoms after the
ingestion of carbohydrates
(lettuce, beans, corn, etc)
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Abdominal pain
Cramps
Urgent diarrhea
Time of onset: variable
depending upon quantity
and sensitivity of patient
What is the current evidence for
maldigestion due to alphaglucosidases deficiency or
inhibition?
M. E. Money. M.D.
Inherited alpha-glucosidase deficiency in
children
1-2% of children with severe diarrhea from birth are
found to have an inherited sucrase-isomaltase
disaccarhidase deficiency
Recent research by Dr. Buford Nichols (Baylor College,
Houston, Texas) in collaboration with Dr. Susan Baker
( Woman and Children Hospital of Buffalo, NY ) have
found 26% of children with digestion symptoms have
difficulty digesting starch due to a deficiency of
glucoamylase.
M. E. Money. M.D.
Alpha-glucosidase deficiency in
adults
4 papers from 1964-1985 reported the
identification of sucrase-isomaltase enzyme
deficiency in adults. Symptoms were quite
variable from none to constant diarrhea.
Sonntag, W. M. et al, 1964, Gastroenterology 47:18.
McNair, et al. 1972, Sucrose malabsorption in Greenland, Br. Med J. 2:19.
Ringrose (1980) Dig. Dis. Sci. 25:384
Gudmand-Høyer E.Sucrose malabsorption in children: a report of thirtyone Greenlanders.J Pediatr Gastroenterol Nutr. 1985 Dec;4(6):873-7.
M. E. Money. M.D.
Alpha-Glucosidases deficiency in patients
with chronic diarrhea compared to those with
indigestion
In Indonesia, biopsies taken from the small intestine
were examined for concentration of Lactase,
Sucrase, and Maltase from 13 patients with
chronic diarrhea, and compared to biopsies from
34 patients with “dyspepsia”.
Results: All of enzyme concentrations from the
patients with chronic diarrhea were statistically
lower than those with dypepsia.
Examination of small bowel enzymes in chronic diarrhea. J
Gastroenterol Hepatol. Simadibrata, m., et al.18(1): 53-6. 2003.
M. E. Money. M.D.
Low carbohydrate diet and
diarrhea symptoms
A very low-carbohydrate diet improves symptoms
and quality of life in IBS-D patients. 2009
Prospective Study
17 enrolled with moderate to severe IBS-D
Initially had 2 weeks of standard diet, then 4 weeks of
very low (20gm carbohydrate/day).
13 completed the study. 10 (77%) reported adequate relief
for all 4 weeks on the low carb diet; stool number
decreased, QOL improved, and decrease in pain.
Clin Gastroenterol Hepatol. Austin, GL; Dalton, CB; et.al. 2009 June;
7(6) 706-708.el.doi:10.10167/j.cgh.2009.02.023
M. E. Money. M.D.
Alpha-glucosidase inhibition by foods
and spices
Laboratory studies have demonstrated glucosidase
inhibition with common food substances such as
cinnamon extract , certain tropical pepper spices , basil
extract , certain strains of maize , certain Indian spices
, the Welch onion , the Maitake mushroom, (Grifola
frondosa) and chamomile tea . A consequence of
glucosidase inhibition may be abdominal symptoms
such as bloating and postprandial diarrhea.
Quercetin (found in onions and garlic, 5x more potent
than acarbose)
M. E. Money. M.D.
Examples of food triggers among 49
“users”
Food Trigger
#
%
Food Trigger
#
%
Mexican Food
36
74%
Green Peppers
18
37%
Cajun
33
67%
Oranges
16
33%
Iceberg Lettuce 27
55%
Onion
16
33%
Italian
27
55%
Broccoli
16
33%
Chinese
27
55%
Garlic
13
27%
Ice Cream
26
53%
Beans
13
27%
Milk
20
41%
Apples
13
27%
Corn
19
39%
Tomatoes
2912
25%
Alpha-glucosidase inhibition by drugs
Drugs: Acarbose ( a diabetic medication to reduce absorption of
carbohydrates by preventing absorption).
Side effect: >30% patients experience diarrhea
The STOP-Noninsulin Dependent Diabetes Mellitus
international trial from 1995 to 2001 clearly demonstrated the
benefits of α-glucosidase inhibition in patients with impaired
fasting blood sugar, by demonstrating a 49% relative risk
reduction in the development of cardiovascular events among
the acarbose users compared to the placebo group. However,
29.5% of patients assigned to acarbose, compared to 18.2%
using placebo, discontinued the drug because of adverse
gastrointestinal tract effects: flatulence, diarrhea, and
abdominal pain .
M. E. Money. M.D.
Mainstream treatment options for
IBS-Diarrhea
• Antidepressants
• Anticholinergics
(Bentyl, Levsin, etc)
• Bulking agents
(metamucil, etc)
• Chinese Herbal
therapies
• Cholestyramine
M. E. Money. M.D.
• Antispasmodics
• Lactase
supplementation
• Antibiotics
• Serotonin modulators
• Antidiarrheals drugs
(Lomotil, etc)
• Deodorized tincture of
opium
Potential treatment options for
patients with diarrhea after meals
Over the counter agents:
Fiber capsules (which absorbs extra liquids)
Calcium (which slows down the motility naturally),
Enzyme supplement: Essential Enzymes 500 mg (by Source
Natural), an over the counter supplement (1-3) before eating any
“trigger meal” or daily as needed.
Prescription medications from a physician:
Pancreatic enzymes: examples: ZenPep 20,000 lipase, Creon 24
(1-3capsules) before eating any “trigger meal” or daily as
needed.
Bile acid binding drugs: Questran 1-2 packages/day; Welchol
625 mg (1-3) before eating any trigger meal or daily as needed.
M. E. Money. M.D.
Effectiveness of pancreatic enzymes
A retrospective review was recently completed of all of the
patients in my practice who had the diagnosis of IBS
and had been treated by me from 2001-2010 to evaluate
the effectiveness of the enzymes.
278 patients had received a diagnosis of spastic colon or
IBS
– 134 excluded since they had been treated by
another practitioner
– 144 seen by me, and 104 had been offered PEZ
• 86/104 patients returned for follow-up,
and 82.5% (71) reported positive
improvement
M. E. Money. M.D.
Diarrhea predominant IBS (IBS-D):
fact or fiction
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Dr. Saad Habba, gastroenterologist in NY,
analyzed all patients seen by him over the
last 8 yrs for “IBS-D”.
575 patients seen, only 303 patients
completed all of the studies. Of these 303
patients, 204 (68%) responded to bile acid
binding agents with resolution of diarrhea.
Diarrhea Predominant Irritable Bowel Syndrome-Diarrhea: Fact or
Fiction. Habba,S., Medical Hypotheses 76(2011) 97-99.
M. E. Money. M.D
Working hypothesis
Diarrhea occurring after meals may
actually be a subclinical form of
inherited or acquired maldigestion,
possibly related to a bile acid
malabsorption or a mild deficiency,
relative ineffectiveness or suppression
of one or more enzymes: amylase,
lipase, the alpha-glucosidases, or
others.
M. E. Money. M.D.
Summary
• The current Rome Criteria may be limiting
appropriate research and treatment for a subset of
IBS-D patients who recognize the direct
association of symptoms with meals or triggering
foods. The relationship to meals should be sought
in obtaining the history from patients.
• A high percentage of these patients probably have a
subclinical form of maldigestion which may be
substantially improved by the use of enzymes or
bile acid binding agents when taken immediately
before eating the “triggering meal.”
M. E. Money. M.D.