Northwestern University Feinberg School of Medicine

Fecal Incontinence in the Scleroderma Patient:

What We Know and Where We Should Go

Darren M. Brenner, MD

Assistant Professor of Medicine and Surgery

Northwestern University—Feinberg School of Medicine

Prevalence of Fecal Incontinence:

General Population Versus Scleroderma

Overall prevalence of

fecal incontinence: 9.0%1

Prevalence in patients with

scleroderma (SSc) 22-38%2,3

*Data from NHANES 2005/2006 and 2009/2010 surveys. N=52,195.

Ditah I et al. Am J Gastroenterol. 2012;107:S717. Abstract 1762.; Omair and Lee. J Rheumatol 2013;39:992-6.;

Trezza.Scand Jgastroenterol 1999;34;409-13.

Fecal Incontinence Has a Profound Impact

on Quality of Life

1

2

3

4

Lifestyle Coping Depression Embarrassment

FI patients GI patients not affected by FI

P<.01

*Quality of life measured using the Fecal Incontinence Quality of Life Scale, a validated 4 scale, 29-item survey.

Rockwood TH et al. Dis Colon Rectum. 2000;43:9-16.; Mohamed and Lett J Rheumatolo 2012;39:92-6.

Score

*

QoL significantly lower for SSc patients with FI compared to

SSc patients without FI and controls

Anorectal angle

Descent of pelvic floor

Straining to defecate

Symphysis pubis

Anorectal angle

Coccyx

External anal

sphincter

Puborectalis

Rectum

At rest

Modified from AGA slide: IV-9

Normal Defecation

Anatomy of the Anorectum

Welton ML et al. Anorectum. In: Doherty GM, ed. Current Diagnosis & Treatment Surgery. New York, NY:

The McGraw-Hill Companies, Inc.;2010:698-723.

Pathophysiology of Fecal Incontinence

Rao SSC. Gastroenterology. 2004;126:S14-S22.

Structural

Abnormalities

Functional

Abnormalities Stool

Characteristics

Structural Abnormalities

ANS=autonomic nervous system; CNS=central nervous system

Rao SSC et al. Am J Gastroenterol. 2004;99:1585-1604.

Anatomic Structure Cause Mechanistic Effect

Anal sphincter muscle • Obstetric injury

• Hemorrhoidectomy, anal dilation,

secondary to neuropathy

Sphincter weakness

Loss of sampling reflex

Rectum • Inflammation

• IBD

• Radiation

• Rectal prolapse

• Aging

• IBS

Loss of accommodation

Loss of sensation

Hypersensitivity

Puborectalis muscle • Excessive perineal descent

• Aging

• Trauma

Obtuse anorectal angle

Sphincter weakness

Pudendal nerve • Obstetric or surgical injury

• Excessive straining/perineal descent

• Rectal prolapse

Sphincter weakness

Sensory loss, impaired

reflexes

CNS, spinal cord, ANS • Spinal cord, head injury

• Back surgery

• Multiple sclerosis, diabetes, stroke,

avulsion injury

Loss of sensation

Impaired reflexes

Secondary myopathy

Loss of accommodation

Functional Abnormalities

Anorectal sensation impairment1

• May be caused by aging, neurologic damage, mental impairment2

• Impairment in anorectal sensation may lead to:1

- Excessive accumulation of stool

- Fecal overflow

- Impairment of the sampling reflex

Fecal impaction caused by dyssynergic defecation1

• May result in fecal retention with overflow and leakage of liquid stool

1. Rao SSC et al. Am J Gastroenterol. 2004;99:1585-1604; 2. Engel AF et al. Gut. 1994;35:857-859.

Stool Characteristics

Stool consistency, volume, and presence of irritants in the stool may

contribute to fecal incontinence

• Large-volume liquid stools require intact sensation and unimpaired sphincter function to be retained

Stool characteristics may be influenced by:

• Infection (SIBO)Diarrhea

• Inflammatory bowel disease

• Irritable bowel syndrome

• Medications

• Food intolerances

Rao SSC et al. Gastroenterology. 2004;126:S14-S22.

Most Common Deficiencies Identified in SSc

Patients

• Loss of RAIR

• Decreased Anal Sensation

•Thinning of the IAS

• Fibrosis of the IAS

• Decreased Anal Pressure

• Diarrhea/ Constipation

Thoua et al. AJG 1012:107:597-603. Thoua et al. Rheumatology 2011;50(9):1596-602.

Fynne et al. Scand J Rheumatol 2011;40(6):462-66. Koh et al. Dis Colon Rectum 2009;52(2):315-18.

Indicative of

Neuropathy (Functional)

Indicative of

Myopathy (Structural)

Stool Characteristics

Structural and/or

functional

Diagnostic Evaluation

• History

• Physical exam, including digital rectal exam

• Diagnostic tests

Rao SSC et al. Am J Gastroenterol. 2004;99:1585-1604.

Potential Risk Factors and Relevant Coexisting

Medical Conditions

Bharucha AE et al. Gastroenterology. 2010;139:1559-1566.

Variable Odds Ratios (95% CI)

BMI (per unit) 1.1 (1.004, 1.1)

Current smoker 4.7 (1.4, 15)

Diarrhea 53 (6.1, 471)

IBS 4.8 (1.6, 14)

Cholecystectomy 4.2 (1.2, 15)

Rectocele 4.9 (1.3, 19)

Stress urinary incontinence 3.1 (1.4, 6.5)

Obstetric risk factors (grade 1) 0.8 (0.4, 1.9)

Obstetric risk factors (grade 2) 1.1 (0.4, 3.6)

Obstetric risk factors (grade 3) 1.9 (0.7, 5.2)

Assess Diet, Medications, and Lifestyle

Adapted from National Institute for Health and Clinical Excellence (NICE). CG49 Faecal incontinence: tables. Available at:

http://www.nice.org.uk/CG49Tables#table2. Accessed March 30, 2013.

Fiber Fiber supplements, whole-grain cereals or bread, whole-wheat based cereals

Certain fruits and vegetables

Rhubarb, figs, prunes, plums, beans, cabbage, sprouts

Spices Chili powder

Alcohol Especially stouts, beers, or ales

Lactose/fructose Milk, other high-lactose or high-fructose foods

Caffeine Coffee, tea, sodas

Vitamin and mineral supplements

Excessive vitamin C, magnesium, phosphorus, and/or calcium

Olestra fat substitute Can cause loose stools

Assess Diet, Medications, and Lifestyle

Adapted from National Institute for Health and Clinical Excellence (NICE). CG49 Faecal incontinence: tables. Available at:

http://www.nice.org.uk/CG49Tables#table2. Accessed March 30, 2013

Drugs that alter sphincter tone

Nitrates, calcium channel antagonists, beta-blockers, sildenafil, SSRIs

Broad-spectrum antibiotics

Cephalosporins, penicillins, erythromycin

Topical drugs applied to anus

Glyceryl trinitrate ointment, diltiazem gel, bethancechol cream, botulinum toxin A injection

Drugs causing profuse loose stools

Laxatives, metformin, orlistat, SSRIs, magnesium-containing antacids, digoxin

Tranquilizers or hypnotics

Benzodiazepines, SSRIs, antipsychotics

Diagnostic Testing

Physiologic

Test

Measurements Evidence

Anorectal

manometry1

Quantifies sphincter

pressures, sensation, rectal

compliance and recto-anal

reflexes

Good

Endoanal

ultrasound

Assesses IAS and EAS

thickness, integrity Good

Surface

EMG1

Provides information on

normal or weak tone Fair

Adapted from: Rao SSC. Clin Gastroenterol Hepatol. 2010;8:910-919.

Anorectal Manometry

High-Resolution Manometry Catheter:

• 10 distal sensors

• 2 Proximal sensors

Resting Pressure

Normal Weak

RAIR

Normal

Failed

Internal Anal Sphincter Thinning

Normal IAS Thinned IAS

Management of Fecal Incontinence

• Diet changes

• Lifestyle modification/Non-pharmacological interventions

• Medical therapies

• Surgical interventions

Dietary and Lifestyle Interventions for

Fecal Incontinence

• If stools are frequent and/or loose, evaluate intake of

fermentable, poorly absorbed carbohydrates

• Consider evaluation for lactose maldigestion or

fructose malabsorption

•Evaluate relationship between caffeine intake1 and

symptoms

Behavioral Techniques for Fecal Incontinence

• Avoid rushing to the toilet

•Increases abdominal wall contraction which increases chance of fecal incontinence

•Reduces focus on pelvic floor

• Stop and perform Kegel exercise and proceed to toilet

• Clean, squeeze, reclean

• After bowel movement, clean anus, perform 2-3 Kegel exercises, then re-clean

• If stool present, may have avoided fecal incontinence

• Delay bowel movement after biofeedback therapy

• Start with brief periods, then increase; improves confidence

• Wean off laxatives and anti-diarrheals

.

Non-pharmacologic Management of

Fecal Incontinence

Whitehead WE, Bharucha AE. Gastroenterology. 2010;138:1231-1235.

Intervention Mechanism of Action Side Effects Comments

Incontinence pads

Provides skin protection; prevents soiling; conduct moisture away from skin

Skin irritation

Disposable provides better skin protection than nondisposable

Enemas Evacuates rectum, decreasing likelihood of FI

Inconvenient; side effects from specific preparations

Anorectal biofeedback

Improves rectal sensation; coordinates external anal sphincter contraction; may increase anal sphincter tone

None

Success is more likely if the patient is motivated, with intact cognition, absense of depression, and with some rectal sensation; availability and cost can be problematic

Long-term Results of Biofeedback for

Fecal Incontinence

Lacima G et al. Colorectal Dis. 2010;12(8):742-749.

38

48.1

11.4

2.5

12.5 12.5

22.5

52.5

0

10

20

30

40

50

60

Biofeedback

No treatment

Solid Stool FI Assessed 1,6,36,60 MONTHS

Perc

en

tag

e

Group A Group B Group C Group D

Group A: Continence fully recovered

Group B: >75% reduction in # of incontinence episodes

Group C: <75% reduction in # of incontinence episodes

Group D: No improvement or worse than before therapy

Pharmacologic Management of

Fecal Incontinence

• Antidiarrheals

•Tricyclic antidepressants

• Bile acid binding resins

No pharmacologic treatments have been adequately evaluated in large,

randomized, controlled studies in patients with fecal incontinence

No pharmacologic treatments have been evaluated in controlled studies in

SSc patients with fecal incontinence

Injectable Gel Treatment for FI

• Biocompatible gel of dextranomer

microspheres in hyaluronic acid

• FDA-approved for the treatment of

fecal incontinence in patients aged ≥18

years who have failed conservative

therapy

• Administration

• Done in physician office or hospital

outpatient department

• Four injections through an anoscope

• Injected into submucosal layer of the

anal canal

• No anesthesia required

Solesta [package insert]. Oceana Therapeutics, Edison NJ, 2012. Accessed April 1, 2013 at: http:www.solestainfo.com/pdf/solesta-pi.pdf

Solesta ® Injection Pivotal Trial:

Primary Endpoint Data

*Responder = ≥50% reduction in incontinence episodes as compared with baseline.

Graf W et al on behalf of the NASHA Dx Study Group. Lancet. 2011; 377: 997–1003.

Significantly higher responder rates in injection

group at 6 months (Responder)*

52%

n=136

31%

n=70

0

20

40

60

80

Injection Sham

Median number of

incontinence episodes

during 2 weeks in the

active treatment group

decreased from 15.0

(IQR 9.6–27.5) at baseline

to 6.2 (2.0–15.5) at

12 months (P<.0001)

P=.0089

Secondary Endpoint: Decrease in FI Episodes

After Solesta® Treatment

Graf W et al on behalf of the NASHA Dx Study Group. Lancet. 2011; 377: 997–1003.

15.0

8.6

7.3 7.0 6.2

44.1%

52.2% 54.4% 57.4%

-10%

0%

10%

20%

30%

40%

50%

60%

0.0

2.0

4.0

6.0

8.0

10.0

12.0

14.0

16.0

Baseline 3 months 6 months 9 months 12 months

Episodes reduction

Med

ian

nu

mb

er

of

ep

iso

des

/14 d

ays

Pro

po

rtio

n r

es

po

nd

ers

Solesta® Injection: Adverse Events

*Serious adverse event

Graf W et al on behalf of the NASHA Dx Study Group. Lancet. 2011; 377: 997–1003.

Dextranomer

Microspheres

(n=136)

Sham

(n=70)

Proctalgia 19 (14%) 2 (3%)

Rectal hemorrhage 10 (7%) 1 (1%)

Diarrhea 7 (5%) 3 (4%)

Injection site bleeding 7 (5%) 12 (17%)

Rectal discharge 5 (4%) —

Anal pruritis 2 (2%) —

Proctitis 4 (3%) —

Painful defecation 2 (2%) —

Fever 11 (8%) —

Rectal abscess* 1 (1%) —

Prostate abscess* 1 (1%) —

Others 22 (16%) 5 (7%)

Sacral Nerve Stimulation System

1. Tined lead is placed parallel

to the sacral (S2, S3, or S4)

nerve

2. Implantable

neurostimulator generates

mild electrical pulses that

are delivered through the

lead electrodes

3. Clinician and patient

programmers are used to

set the parameters of the

electrical pulses

1

2

3

InterStim II Neuromodulator [manual]. Medtronic, Inc. Minneapolis, MN. 2012.

SNS Placement

Sacral Nerve Stimulation System:

Bowel Control Study

Wexner SD, Coller JA et al. Ann Surg. 2010;251:441-449.

Most common adverse events (≥5%) reported during the implant phase:1

Adverse Event Frequency (%)

Implant site pain 25.8%

Paresthesia 12.5%

Implant site infection 10.8%2

Change in sensation of stimulation 8.3%

Urinary incontinence 6.7%

Diarrhea 5.0%

26 SAEs: 13 (10.8%) experienced implant site infection. 5 infections treated with medication; 7 (5.8%)

required surgical intervention (5 device explants and 2 device replacements)

Sacral Nerve Stimulation In SSc

0

5

10

15

20

25

Pre-SNS

Post-SNS

• 5 women

• All failed conventional

therapy

• Liquid and solid stool

• Median # weekly FI

episodes=15

• Duration SSc=13 yrs

• Duration FI=5 years

Kenefick et al. Gut 2002;51:81-83

Weekly Incontinent Episodes

Patient 5: lead displdged in 1st 24 hours

Max response time 60 months

Improvements in urgency, QoL

Elevations in resting pressures identified

Artificial Anal Sphincter

Cuff placed around upper anal canal1

Tubing from cuff is directed along

perineum and connected to pump

implanted just below skin of scrotum or

labia

Limited clinical experience1

• In a post-hoc analysis (n=37), normal

continence for liquid stool was 78.9%; normal

continence for gas was 63.1%1

• ~12% failure rate1

• No data in Scleroderma patients

1. Michot F et al. Ann Surg. 2003;1:52-56.

Treatment Options for Fecal Incontinence

Conservative

Therapies Solesta® Injection

Surgical

Therapies

• Generally safe

• Limited evidence

of benefit

• Not commonly

successful in SSc

• Generally safe

• Requires in-office

procedure

• Longer-term evidence for

benefit required

• Invasive

• Potential safety issues

• Long-term benefit may

be limited but initial

data for SNS good