chronic diarrhea and getting over fecal incontinence€¦ · chronic diarrhea and getting over...

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©2018 MFMER | slide-1

Chronic Diarrhea and Getting Over Fecal Incontinence

Amy Foxx-Orenstein, DO, MACG, FACPProfessor of MedicineDivision of Gastroenterology and HepatologyMayo Clinic

AOMA 39th Annual Fall Seminar


Disclosures

• None

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IBS-D Outline

• Evidence-based criteria to diagnose IBS

• Cost-effective evaluation

• Brief review of traditional and newer treatments for patients with IBS-D


Representative Case

• 35 year old female with 8 years of diarrhea, abdominal cramping and bloating on most days. No bloody stools or nocturnal episodes. Has 3-4 loose stools daily with urgency, never had an ‘accident’. LLQ cramping is relieved with movements. Has hypothyroidism and anxiety, on treatment. Weight is stable. No family history of IBD or colon cancer/polyps.

• Does she have IBS?• Are there other diagnosis to consider?• What tests would you do to evaluate cause?

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Recurrent abdominal pain, on average, ≥1 day per week in the last 3 months, associated with ≥ 2 of the following:

• Related to defecation

• Change in frequency of stool

• Change in form (appearance) of stool

Rome IV Criteria for IBS

Bristol Stool Form Scale

Criteria should be fulfilled for the last 3 months with

symptom onset ≥ 6 months before diagnosis

Lacy BE et al. Gastroenterology. 2016;150:1393-1407

IBS-D IBS-M


What Else Could It Be?Differential for diarrhea is broad and the history will divulge many clues

• Infectious

• Medication

• Bile acid

• Microscopic colitis

• Celiac

• Caffeine

• SIBO

• IBD

• Disaccharidase deficiency

• Food related

• Toxins

• Villous adenoma

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Diagnostic Testing for IBS-D and IBS-M symptoms

IBS-DIBS-DIBS-D IBS-MIBS-MIBS-M

•CRP, fecal calprotectin

• IgA ttG ± quantitative IgA

•Colonoscopy with random biopsies and TI exam if appropriate

•Consider EGD with small bowel biopsies

•CRP, fecal calprotectin

• IgA ttG ± quantitative IgA

CRP = C-reactive proteinttg = tissue transglutaminase.

Chey WD, et al. JAMA. 2015;313:949

Limited testing


Prevalence of Structural Abnormalities in IBS Patients Compared with Controls

7.7

0.4 1.5

26.1

00

5

10

15

20

25

30

Microscopic colitis more common in patients aged

≥45 years

Pat

ient

s, %

IBS patients (n=466) Controls (n=451)

Adenomas IBD Microscopic colitis

N/A

Chey WD et al. Am J Gastroenterol. 2010;105:859

Limited testing

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• Onset of symptoms after age 50

• GI bleeding or iron-deficiency anemia

• Nocturnal diarrhea

• Unintended weight loss

• Family history of organic GI disease (colorectal cancer, IBD, celiac)

Alarm Features

Proceed with testing


Celiac is Common in IBS Patients with Diarrhea

Prevalence of biopsy-proven celiac disease in IBS-D vs controls

4.34 (1.78-10.58)

International meta-analysisFord et al. Archives Int Med. 2009;169:651

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Breath Testing in IBS

Carbohdrateload

Colonic fermentation

H2 and/or methane

• Tests for CHO maldigestion and SIBO

• Conditions associated with bloating

• Heterogeneity in test performance, preparation, indications, and interpretation of results

Rezaie A et al. Am J Gastroenterol. 2017;112(775

CHO = carbohydrateSIBO = small intestinal bacterial overgrowth


Food and IBS Symptoms

69 6458 54

0

20

40

60

80

100

Pat

ient

s, %

Small meals Avoiding fat Increasingfiber

Avoiding milk products

IBS Patients Reporting Symptom ImprovementWith Intervention

(N=1,242)

60% of patients report worsening of symptoms after meals

Simren M et al. Digestion. 2001;63:108Halpert et al. Am J Gastroenterol. 2007; 102:1972

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Food and IBS Symptoms: Restriction Diets

• FODMAPS are an important trigger of meal-related symptoms in IBS

• Gluten-free diet found to be beneficial in some patients with IBS-D

• Wheat contains fructans and other proteins that may also cause symptoms in IBS patients

• Food antigens may cause changes in the intestinal mucosa of IBS patients

Shepherd SJ et al. Am J Gastroenterol. 2013;108:707;Biesiekierski JR et al. Gastroenterology. 2011;106:508;Vazquez-Roque MI et al. Gastroenterology. 2013;144:903;Chey WD, et al. JAMA. 2015;313:949


Low FODMAP vs mNICE Diet:Adequate Relief

41

52

0

10

20

30

40

50

60

Proportion of patients that answered “Yes” for ≥50% of weeks 3 and 4

N=45

mNICE Low FODMAP

N=38

Pat

ien

ts w

ith

A

deq

uat

e R

elie

f, %

P=0.3055

“In the last week, have you had adequate relief of your GI symptoms?”

mNICE, modified National Institute for Health and Care Excellence. Patients were instructed to eat small frequent meals, avoid trigger foods, and avoid excess alcohol and caffeine

Eswaran SL, et al. Am J Gastroenterol. 2016;111:1824-1832.

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mNICE vs FODMAPWeekly Pain and Bloating Scores

○

§§

§

1

2

3

4

5

6

Baseline Week 1 Week 2 Week 3 Week 4

Ave

rag

e D

aily

Ab

do

min

al P

ain

S

core

s (0

-10)

m-NICE Low FODMAP

#

§§

§

1

2

3

4

5

6

Baseline Week 1 Week 2 Week 3 Week 4

Ave

rag

e D

aily

Ab

do

min

al

Blo

atin

g S

core

(0-

10)

m-NICE Low FODMAP

Abdominal Pain Scores Bloating Scores

mNICE, modified National Institute for Health and Care Excellence. Patients were instructed to eat small frequent meals, avoid trigger foods, and avoid excess alcohol and caffeine

Eswaran SL, et al. Am J Gastroenterol. 2016;111:1824-1832.


Overview of IBS-D Therapies: MOA*

• Modulation of gut flora• Antibiotics, Probiotics, gastric acidity, diet

• 5-HT3 antagonists• Alosetron

• Antidepressants/antianxiety agents• TCA’s, SSRI’s

• Opioid receptor modulators• Loperamide, diphenoxylate, Eluxadoline

• Antispasmodics/Peppermint Oil

• Bile acid binding agents• Colestid, Cholestyramine

*MOA = Mechanisms of action

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Loperamide and Antispasmodics for IBS

Loperamide

Antispasmodics Clinical trials

Patients treated

23

2,154

Clinical trials

Patients treated

2

42

Recommendation

Strong*

Quality of evidence

Very LowRecommendation

Weak

Quality of evidence

Low

Ford AC, et al. Am J Gastroenterol. 2014;109:S2-S26

*FOR DIARRHEA


Probiotics for IBS

Clinical trials Patients treatedRecommendation

WeakQuality of evidence

LowRecommendations regarding individual species, preparations, or strains cannot be made because of insufficient and conflicting data

23 2,575


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Alosetron for IBS-D

• Dose• .5-1 mg BID• Females• Not first line treatment

Alosetron is effective in

females with IBS-D

Recommendation

Strong

Quality of evidence

High

Ischemic colitis0.95 cases/1000 patient-years

Difficult constipation0.36 cases/1000 patient-years

Rare Adverse EffectsAssociated with Alosetron



Rifaximin for IBS-D

TARGET 1 TARGET 2 Combined

40.8 40.6 40.731.2 32.2 31.7

0

20

40

60

80

100

Pat

ient

s, %

P=0.01P=0.03 P<0.001

Adequate Relief of Global* IBS Symptoms

Rifaximin Placebo

3336.9

25 29.3

0

20

40

60

80

100

Pat

ient

s, %

First repeat treatment

Second repeat treatment

P=0.04P=0.02

First and Second Retreatments

Urgency, bloating, pain, stool consistency

Pimentel M, et al. N Engl J Med. 2011;364:22

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Rifaximin

• 550 mg TID 2 weeks

• Recurrence of symptoms can be retreated up to two times, same regimen

Schoenfeld P, et al. Aliment Pharmacol Ther. 2014;39:1161


Antidepressant Agents in IBS-D

• Meta-analysis 16 RCT TCA reduced global pain and IBS symptoms

• SSRI’s may increase intestinal transit

• SNRI’s have not been adequately studied

Antidepressant actions in IBS

Antidepressant action

Visceral analgesia

Changes in motility

Smooth muscle relaxation

Ford AC et al. Am J Gastroenterol. 2014;109:1350;Grover M, et al Gastroenterol Clin N Am. 2011;40:183;Chey WD, et al. Gut Liver. 2011;5:253;Gorard DA, et al. Aliment Pharmacol Ther. 1994;8:159

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Prescribing Antidepressants in IBS

Consider specific symptoms

TCA’s in IBS-D

SSRI for anxiety

Consider Side Effects

TCA’s → constipation

SSRI → diarrhea

Start LOW dose and titrate

8 weeks for full response

6-12 months treatment

Sobin WH et al. Am J Gastroenterol. 2017;112:693;Grover M et al. Gastroenterol Clin N Am. 2011;40:183;Dekel R et al. Expert Opin Invest Drugs. 2013;22:329


Eluxadoline for IBS-D

Placebo BID Eluxadoline 75 mg BID Eluxadoline 100 mg BID

0

20

40

60

80

100

0

20

40

60

80

100

P<0.001

Weeks 1–26Weeks 1–12

Res

po

nd

ers,

%

P<0.001

P<0.001

P<0.001

Reduced abdominal pain > 30% compared to baseline and stool consistency < 5/d daily, for >50% of days in trial

Lembo AJ, et al. N Engl J Med. 2016;374:242

Mixed opioid receptor agonist (mu) and antagonist (delta)

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Eluxadoline Adverse Events

Sphincter of Oddispasm events 0.6% (10 /1666) In patients who did not have gall bladders

PancreatitisAlcohol use and biliary sludge increase risk

AdverseEvents

Placebo (n=808)

Eluxadoline75 mg

(n=859)

Eluxadoline100 mg (n=807)

n (%)

Constipation* 20 (2.5) 60 (7.4) 74 (8.6)

Nausea 41 (5.1) 65 (8.1) 64 (7.5)

Abdominal pain† 33 (4.0) 47 (5.9) 62 (7.2)

Vomiting 11 (1.4) 32 (4.0) 36 (4.2)

Gastroenteritis‡ 27 (3.4) 36 (4.4) 19 (2.2)

URI 32 (4.0) 27 (3.3) 47 (5.5)

Nasopharyngitis 27 (3.3) 33 (4.1) 23 (2.7)


Prescribing Eluxadoline

• 100 mg BID with food

• 75 mg BID for patients with hepatic impairment

Contraindications

1. Bile duct disorders

2. NO Gallbladder

3. History of pancreatitis

4. Severe constipation or liver disease

5. ETOH daily

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Peppermint Oil for IBS

• Improved total IBS symptom score, frequency and intensity of symptoms over 4 weeks (p<0.02)

• Adverse events: dyspepsia

• Prescribing • 180 mg tid

0

20

40

60

80

100

AbdominalPain or

Discomfort

AbdominalBloating orDistension

Pain atEvacuation

Sym

pto

m r

edu

ctio

n, %

Placebo TID(n=37)

Peppermint oil 180 mg TID (n=35)

Cash BD, et al. Dig Dis Sci. 2016;61:560


Psychological Therapy is Effective in Many Patients With IBS

• 20 studies• Mindfulness, cognitive behavioral therapy, psychotherapy,

hypnosis

Psychological therapy

(%)

Control therapy

(%)RR symptoms remain

(95% CI)

49.1 27.5 0.67(0.57-0.79)

Ford AC et al. BMJ. 2008;337:a2313.Walter SA et al. Neurogastroenterol Motil 2013;25:741.Halland M, Talley NJ. Nat Rev Gastroenterol Hepatol 2013;10:13.

Patients often respond to psychological support, including strong physician-patient relationship

N=1278

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Exercise Has a Positive Impact on IBS Symptoms

• Randomized to physical activity* or maintain lifestyle

• Control group had significantly higher IBS symptom scores than patients in physical activity group

• Physical activity improvedIBS symptom scores (p=0.003)

Johannesson E et al. Am J Gastroenterol. 2011;106:915-922.

500

400

300

200

100

0

IBS

Sev

erit

y S

core

Control group Physical activity group

P = 0.001

Start 12 Weeks

*Intervention: 20-60 minutes moderate to vigorous exercise 3-5 times weekly

(N=75)


Summary IBS-D

• Diagnose using symptom-based criteria

• Check TTG, CRP• Consider referral for endoscopy, breath tests

• Educate• Primary role of diet in managing IBS

• Smaller meals, FODMAP, elimination • Medications to achieve a goal: reduce pain and

diarrhea, improve quality of life

• Psychological therapy

• Exercise

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The End

But there’s more…


Evaluation of Chronic Diarrhea (not IBS)

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Why is Chronic Diarrhea Important?

• Diarrhea is common• You will see it!• Affects 5% of the adult population

• $$ There can be considerable expense in the work-up/management.

• Cost effective evaluation

• Differential can be broad• Alarm features are key


Outline

• Stepwise approach to diagnosing and evaluating chronic diarrhea

• Features of chronic diarrhea that warrant increased attention

• What and when tests are warranted

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Representative Case

• 53 y/o woman with diarrhea for 2 years. She has 4-6 watery stools daily, no formed stool. No blood, but she has nocturnal stools, cramps and bloating. Medical history of hypothyroidism and depression (treated). Underwent a hysterectomy and radiation therapy for cervical cancer 5 years ago.

• Does she have IBS?• Are there historical clues in this case?• What testing would you do?


Step-Wise Approach to Chronic Diarrhea

• 1. Does the patient truly have diarrhea?

• 2. Is the diarrhea really chronic?

• 3. Can you categorize the diarrhea?

• 4. Are there historical clues to the diagnosis?

• 5. Is it diet or medication-induced?

• 6. Is there a factitious component?

Schiller LR, et al. CGH 2017;15:182

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Step 1: Does the patient truly have diarrhea?

• Fecal incontinence?

• Overflow from fecal impaction?

• Perception versus reality of volume / frequency?


Definition of diarrhea

• In past, based on volume and time:• >200-250 g liquid per day• >4 weeks

• Current way we diagnose:• >3 unformed BM/day• >25% loose or mushy stools• Bristol stool scale 6 or 7

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Step 2: Does the patient have acute or chronic diarrhea?

• Acute = up to 4 weeks

• Chronic = >4 weeks

OR


Step 3: Can you categorize the diarrhea?

• Large or small bowel intestine source• Often differs in volume and frequency

• Watery• Secretory versus osmotic

• Inflammatory• Bloody stools, abdominal pain, fever, tenesmus

• Fatty• greasy, oily, difficult to flush, floating stools, smelly

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Small bowel:large volume, vitamin andmineral deficiencies

Colon:Smaller volume (not always),frequent, bloody, tenesmuswith rectal involvement


Tests Based on Characteristics

• Watery: Secretory versus Osmotic• Osmotic gap = 290 mOsm/kg-2(stool Na+K)

• Gap < 50 Secretory• Gap > 100 Osmotic

• Stool osmolality:• Should be the same as serum

• Lower - urine or water contamination• Higher - stool collection sitting around

e.g. 2(140+ 4)= 288

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Osmotic Secretory

Daily volume <1L >1L

Effect of Fast Stops continues

Stool osmolality 290 290

Osmotic gap >100 <50

Common causes Malabsorption*PEG**, lactulose, Mg+ antacids, sorbitol/xylitol

Cholera, toxins,bile acid, VIPoma, gastrinoma, diabetic diarrhea, microscopic colitis, factitious, villous adenoma

*Malabsorption e.g . Fructose, lactose, bacterial overgrowth (SIBO)**PEG = polyethylene glycol


Osmotic Secretory

Testing Strategy

Dietary reviewMalabsorption tests (breath tests, avoidance, small bowel biopsy)Stool magnesium

CulturesStructural evaluation: colon biopsies.NeuroendocrineVIP, calcitonin, gastrin

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Tests based on characteristics

• Inflammatory:• +CRP, fecal calprotectin or lactoferrin

• If positive, these are nonspecific• Differential:

• infection, inflammation, ischemia, radiation

• Often structural evaluation is needed• colonoscopy and/or EGD with biopsies,

CT enterography, MR enterography


Tests based on characteristics

• Fatty / Steatorrhea• Symptoms: malodorous diarrhea, weight

loss, vitamin ADEK deficiencies• Etiology: pancreatic, mucosal (e.g celiac,

Whipple’s disease)• Tests:

• Qualitative fecal fat (Sudan stain) –’meh’!• Fecal elastase ( pancreatic disease)• Quantitative fecal fat (collection 24-72 hr)

normal < 7g/day or <14 if diarrhea

‘meh’ = low sensitivity/specificity

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Step 4: Are There Historical Clues to the Diagnosis?

• Abdominal pain/functional issues - IBS

• Autoimmune, iron deficiency, family history, itchy rash - celiac

• Female, culprit meds - microscopic colitis

• Bariatric surgery (RYGB), radiation, paralytic motility issues - SIBO

• Younger, bloody stool, fever, family history IBD, extra-intestinal features - IBD


Irritable bowel syndrome (IBS) ROME 4

• Recurrent abdominal pain on average at least 1 day/week in the last 3 months with 2 or more features:

• Related to defecation• Change in frequency of stool• Change in form/consistency of stool

• Symptoms present at least 6 months

• In absence of alarm features manage symptoms

Gastroenterology 2016:150:1393

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Important in History/Exam

• If ALARM features are present, further workup is needed:

• Bloody stool, weight loss, family history of IBD or bowel cancer, new onset, older age, immunosuppressed


Step 5: Does the Patient Have Diet-Induced Diarrhea?

• DIET• Caffeine• Soda, fruit/juice (fructose)• Sweeteners (sucrose)• Sugar free anything (xylitol)• Dairy (lactose)• Wheat (celiac, allergy, sensitivity)• Syrups, elixirs (sorbitol)

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Step 5: Does the Patient Have Medication-Induced Diarrhea?

• >700 drugs implicated

• Makes up 7% of medication side effects!

Some to Remember: NSAID

Metformin

Antibiotic

PPI

SSRIs

Mg+

Angiotensin receptor blockers (olmesatan)

Herbal products

Many chemotherapy agents

Rubio-Tapia A, et al. Mayo Clinic Proc 2012;87:732Prieux-Klotz C, et al. Target Oncol 2017;12:301


Step 6: Is there a factitious component?

• Stool osmolality not equal to 290 (diluted)• Munchausen syndrome

• Melanosis coli• Pigment from stimulant laxative use• Benign/reversible• Up to 15% undergoing diarrhea workup

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Evaluation May Include:

Stool Tests

Endoscopy

Imaging

Quantitative Stool Tests

Baseline Labs CBC, TTG, TSH, e-lytes,CRP, vitamin levels

Colonoscopy with TI exam and biopsy,EGD with SB biopsy

CT enterography, MRE

24-72 hour fat or bile acid collection

Infectious panel, parasites (Giardia),elastase, c diff, osm, Calprotectin

Very Individualized!


Summary

• Many causes of diarrhea can be deciphered from a careful history and examination

• A stepwise approach for diarrhea is cost-effective and efficient.

• #1. Does the patient truly have diarrhea?

• #2. Is it chronic?

• #3. How is it characterized (watery, fatty, inflammatory)

• #4. Historical clues to the diagnosis? (travel, illness, medications)

• #5. Diet or medication induced?

• #6. Could it be factitious?

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Seventh Inning Stretch!


Fecal Incontinence

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Objectives: you will be able to

•Understand types of FI and impact of the disorder

•Take a focused history

•Maximize conservative therapy


Fecal incontinence

• FI: involuntary loss of stool or liquid feces

• Anal incontinence: involuntary loss of gas• Prevalence: 18% in the community, 47%

in nursing home residents

Serious, Devastating disorder• Impairs quality of life, limits socialization,

predisposes to institutionalization, higher morbidity

• Patients rarely discuss symptoms• Often misdiagnosed as diarrhea

Gorina Y et al. NCHS Vital Health Stat 2014

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Types of incontinence

• Passive: involuntary discharge without awareness (loss of perception, or impaired rectoanal reflexes)

• Urge: discharge despite active attempts to contain (disruption of sphincter function and/or rectal capacity)

• Fecal seepage: After a movement; incomplete evacuation (Intact mechanisms of function)


Risk Factors of FI

• Diarrhea -

• Rectal urgency -

• Advancing age

• Increased body mass index

• Cholecystectomy

• Anal fistula

• Birth related trauma, multiparity

• Urinary incontinence

• Chronic illness (e.g. DM)

• *Overflow (constipation)

Independent risk factors

Average annual costs per person*treat constipation Salix.com

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Relative Frequencies of Common Mechanisms of FI

0% 20% 40% 60% 80% 100%

Anal spincter dysfunction

Pudendal neuropathy

Impaired rectal sensation

Poor rectal compliance

Other 5%

35%

50%

50%

80%

Frequency


Bristol Stool Form Scale

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Diagnosis: Take a focused history

• Ask directly about the presence of FI

• Identify conditions that predispose to FI

• Determine appearance using BSS*, frequency, volume, urgency

• Bowel diaries are superior to self reports

Strength of recommend-

ation

Quality of evidence

Strong High

Strong High

Strong Moderate

Strong Moderate

ACG Clinical Guidelines: Management of Benign Anorectal Disorders 2014

*Bristol Stool Scale


Recommendation for Physical Examination of FI

• Perform a physical examination to eliminate diseases to which FI is secondary.

• Visually inspect the anorectum.

• Perform digital exam before making a referral for anorectal manometry*.


ation

Quality of evidence

Strong Moderate

Strong Moderate

Strong Moderate

*hard stool = overflow incontinence


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Recommendations for diagnostic testing of FI

• Anorectal manometry in patients who do not respond to conservative measures

• Image anal canal for patients with reduced anal pressures


ation

Quality of evidence

Strong Moderate

Weak Moderate



Treatment

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Recommendations for conservative treatment of FI

• First-line management includes education, bulk stool, diet modification, skin care

• Prescribe anti-diarrheal agents

• Education is more effective and superior to pelvic floor exercises


ation

Quality of evidence

Strong Moderate

Strong Low

Strong Moderate



Minimally invasive treatments• Injectable agents

• Radiofrequency ablation

• Barrier devices

• Neuromodulation • Sacral stimulation

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Recommendations for minimally invasive procedures for FI by GI’s

• Injectable bulking agents

FDA-A 2012

Office procedure

Minimally invasive

• SECCA (radiofrequency ablation)


ation

Quality of evidence

Moderate Moderate

Weak Insufficientevidence



Anal Plugs

Lukacz E, Wexner S. Dis Col Rec 2015;58:892-898

Renew Insert device

soft silicone

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Plugs…

Coloplast Peristeen Anal Plug

Absorbent foam, cup-shaped device.Covered by a dissolvable filmStay in place for 12 hours


Vaginal Plugs..

Pelvalon Eclipse Vaginal insert

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More Plugs……. NO


Sacral Nerve Stimulation: Interstim® • 96% had a greater than 50% improvement in

their ability to defer defecation

• Change battery every 5 years

• Concluded• Improvement in symptoms for up to 10 years

in majority of patients. Some patients will experience deterioration in their symptoms over time.

First line treatment after conservative care

A George, et al. GUT 2011

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FI surgical treatment

• Sacral nerve stimulation

• Anal sphincteroplasty for severe sphincter defect

• Graciloplasty and artificial sphincter

• Colostomy


ation

Quality of evidence

Strong Moderate

Weak Low quality evidence

Weak Insufficientevidence

Strong Moderate



External protection

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For Patients: Management Tips

1. Avoid trigger foods and caffeine

2. Bristol Stool Scale #4

3. Anti-diarrheal AFTER movement

4. Enema prior to activity

5. Have a change of clothes

6. Blot more, wipe less


Thank you!

[email protected]

chronic diarrhea and getting over fecal incontinence€¦ · chronic diarrhea and getting over...

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