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 Presented at Scleroderma Patient Education Conference - Saturday, October 19, 2013 Conference hosted by the Scleroderma Foundation, Greater Chicago Chapter and the Northwestern Scleroderma Program

1. 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

2. 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.

3. Fecal Incontinence Has a Profound Impact
on Quality of Life
FI patients
GI patients not affected by FI
4
P<.01
Score*
3
2
1
Lifestyle
Coping
Depression
Embarrassment
QoL significantly lower for SSc patients with FI compared to
SSc patients without FI and controls
*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.

4. Normal Defecation
At rest
Straining to defecate
Symphysis
pubis
Coccyx
Anorectal
angle
Anorectal
angle
Puborectalis
Rectum
External
anal
sphincter
Modified from AGA slide: IV-9
Descent of
pelvic floor

5. 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.

6. Pathophysiology of Fecal Incontinence
Structural
Abnormalities
Functional
Abnormalities
Rao SSC. Gastroenterology. 2004;126:S14-S22.
Stool
Characteristics

7. Structural Abnormalities
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
ANS=autonomic nervous system; CNS=central nervous system
Rao SSC et al. Am J Gastroenterol. 2004;99:1585-1604.

8. 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.

9. 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.

10. 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)
Structural and/or
functional
Stool Characteristics

11. Diagnostic Evaluation
• History
• Physical exam, including digital rectal exam
• Diagnostic tests
Rao SSC et al. Am J Gastroenterol. 2004;99:1585-1604.

12. Potential Risk Factors and Relevant Coexisting
Medical Conditions
Variable
BMI (per unit)
Odds Ratios (95% CI)
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)
Bharucha AE et al. Gastroenterology. 2010;139:1559-1566.

13. Assess Diet, Medications, and Lifestyle
Fiber
Fiber supplements, whole-grain cereals or bread, wholewheat 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
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.

14. Assess Diet, Medications, and Lifestyle
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
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

15. Diagnostic Testing
Physiologic
Test
Measurements
Anorectal
manometry1
Quantifies sphincter
pressures, sensation, rectal
compliance and recto-anal
reflexes
Assesses IAS and EAS
thickness, integrity
Endoanal
ultrasound
Surface
EMG1
Provides information on
normal or weak tone
Adapted from: Rao SSC. Clin Gastroenterol Hepatol. 2010;8:910-919.
Evidence
Good
Good
Fair

16. Anorectal Manometry
High-Resolution Manometry Catheter:
• 10 distal sensors
• 2 Proximal sensors

17. Resting Pressure
Normal
Weak

18. RAIR
Normal
Failed

19. Internal Anal Sphincter Thinning
Normal IAS
Thinned IAS

20. Management of Fecal Incontinence
• Diet changes
• Lifestyle modification/Non-pharmacological interventions
• Medical therapies
• Surgical interventions

21. 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

22. 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
.

23. Non-pharmacologic Management of
Fecal Incontinence
Intervention
Incontinence
pads
Enemas
Anorectal
biofeedback
Mechanism of Action
Side Effects
Provides skin protection;
prevents soiling; conduct
moisture away from skin
Skin irritation
Evacuates rectum, decreasing
likelihood of FI
Comments
Inconvenient; side
effects from
specific
preparations
Improves rectal sensation;
coordinates external anal
sphincter contraction; may
increase anal sphincter tone
None
Whitehead WE, Bharucha AE. Gastroenterology. 2010;138:1231-1235.
Disposable provides better
skin protection than
nondisposable
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

24. Long-term Results of Biofeedback for
Fecal Incontinence
60
Solid Stool FI Assessed
1,6,36,60 MONTHS
48.1
50
Percentage
40
52.5
38
Biofeedback
No treatment
30
22.5
20
12.5
12.5
11.4
10
2.5
0
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
Lacima G et al. Colorectal Dis. 2010;12(8):742-749.

25. 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

26. 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

27. Solesta ® Injection Pivotal Trial:
Primary Endpoint Data
Significantly higher responder rates in injection
group at 6 months (Responder)*
80
P=.0089
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)
60
40
52%
n=136
31%
n=70
20
0
Injection
*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.
Sham

28. 16.0
15.0
14.0
52.2%
54.4%
57.4%
60%
50%
44.1%
12.0
40%
10.0
8.6
30%
7.3
8.0
7.0
6.2
6.0
20%
10%
4.0
2.0
0%
0.0
-10%
Baseline
3 months 6 months 9 months 12 months
Episodes
reduction
Graf W et al on behalf of the NASHA Dx Study Group. Lancet. 2011; 377: 997–1003.
Proportion responders
Median number of episodes/14 days
Secondary Endpoint: Decrease in FI Episodes
After Solesta® Treatment

29. Solesta® Injection: Adverse Events
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%)
—
22 (16%)
5 (7%)
Others
*Serious adverse event
Graf W et al on behalf of the NASHA Dx Study Group. Lancet. 2011; 377: 997–1003.

30. Sacral Nerve Stimulation System
1. Tined lead is placed parallel
to the sacral (S2, S3, or S4)
nerve
3
2. Implantable
neurostimulator generates
mild electrical pulses that
are delivered through the
lead electrodes
2
1
3. Clinician and patient
programmers are used to
set the parameters of the
electrical pulses
InterStim II Neuromodulator [manual]. Medtronic, Inc. Minneapolis, MN. 2012.

31. SNS Placement

32. Sacral Nerve Stimulation System:
Bowel Control Study
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)
Wexner SD, Coller JA et al. Ann Surg. 2010;251:441-449.

33. Sacral Nerve Stimulation In SSc
• 5 women
• All failed conventional
therapy
• Liquid and solid stool
• Median # weekly FI
episodes=15
Weekly Incontinent Episodes
25
20
15
10
5
0
Pre-SNS
Post-SNS
• Duration SSc=13 yrs
• Duration FI=5 years
Kenefick et al. Gut 2002;51:81-83
Patient 5: lead displdged in 1st 24 hours
Max response time 60 months
Improvements in urgency, QoL
Elevations in resting pressures identified

34. 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.

35. Treatment Options for Fecal Incontinence
Conservative
Therapies
Solesta® Injection
• Generally safe
•
Generally safe
• Limited evidence
of benefit
•
Requires in-office
procedure
• Not commonly
successful in SSc
•
Longer-term evidence for
benefit required
Surgical
Therapies
• Invasive
• Potential safety issues
• Long-term benefit may
be limited but initial
data for SNS good