"Gastrointestinal Manifestations of Systemic Sclerosis" presentation by Dr. Harald Schoeppner MD PhD. for the 12th annual Cheri Woo Scleroderma Education Seminar on March 9, 2013 hosted by Oregon Chapter of the Scleroderma Foundation.

1. Gastrointestinal
Manifestations of
Systemic Sclerosis
Harald Schoeppner, MD PhD
Legacy Health Gastroenterology

3. Objectives
 Give an overview of Gastrointestinal
involvement in patients with Systemic
sclerosis
 Review some of the tests performed
 Review treatment options
 Emphasize on GERD (reflux disease)

4. Paul Klee (1879-1949)

5. Organ involvement in SSc
 GI involvement >90%
 Raynauds >90%
 Skin sclerosis >90%
 Arthritis/arthralgias >60%
 Pulmonary fibrosis >30%
 Renal involvement up to 20%
 Cardiac involvement 10%
Literature, EUSTAR, dNSS database

6. Definitions
 Gastrointestinal
(GI) tract:
Several organs in
continuity one-with
the other whose main
function is to digest
food, absorb nutrients
and excrete waste.

7. SSc affects the GI tract
 New theory
 Auto antibodies to
myenteric neurons
 M3R (anti-
muscarinic 3 Ach R)

8. SSc affects the GI tract
 Any site can be affected
 Can affect pt with limited + diffuse SSc
 Can occur at any time
 Not always symptomatic
 Poor correlation with auto-antibodies
 Association between GI symptoms and quality of
life scores
 Severe involvement in up to 6%
DiCiaula A, BMC Gastro 2008; Forbes A, Rheumatol 2008; Thoua NM, Rheumatol 2010

9. SSc and the GI tract
LIVER:
PRIM BILIARY DYSPHAGIA/
SCLEROSIS REFLUX
EARLY SATIETY/ ANEMIA
BLOATING INTESTINAL
BLEEDING
MALABSORPTION/
WEIGHT LOSS
PSEUDO-
OBSTRUCTION
BACTERIAL
OVERGROWTH
DIARRHEA/
CONSTIPATION
FECAL
INCONTINENCE

10. UCLA Scleroderma Clinical Trial Consortium GI
Tract 2.0 Instrument
 Reflux
 Distention/bloating
 Fecal soilage
 Diarrhea
 Social functioning
 Emotional well-being
 Constipation
Khanna. D Arthritis Rheum 2009

11. Mouth & Oropharynx
 Sicca symptoms (Sjogren’s)
 Poor salivary function
 Difficulty swallowing
 Tooth cavities
 Mouth opening
 Minimal tongue involvement

12. Esophagus
 Most commonly affected
organ
 Symptoms:
 Heartburn
 Regurgitation
 Dysphagia
 Chest pain
 Atypical reflux symptoms
 Hoarseness
 Cough
 ILD (interstitial lung disease)
 Breathing problems (apnea)

13. Esophagus
 Poor lubrication
 Poor motility
 Absent sphincter
barrier
Normal Systemic sclerosis

14. Esophagus
 Complexity of GERD
 Sequelae:
 Stricture
 Ulcers
 Barrett’s metaplasia
 Esophageal cancer
 Diverticula

15. Esophagus (treatment)
 Lifestyle modification
 No late meals (>4h)
 Smaller meals
 Elevate head of bed
 Avoid “food stressors”
 Orange, tomato juice
 Spicy foods
 Chocolate, coffee, tea
 Lose weight if high BMI
 Avoid alcohol
 Avoid smoking

16. Esophagus - treatment
PROTON PUMP BLOCKER Other pharmacological tx
 “PPI”s – which is the right  H2 blockers
one?  “Promotility drugs”
 Proper timing  Antacids
 Proper dosing  Avoid:
 Early initiation in all SSc  Calcium blockers
 Long term commitment  NSAIDs
 Bisphonates
 Safety issues?
 Will prevent complications
 May help with ILD

17. GERD Is a Chronic Condition
Likely to Relapse
Patients in symptomatic remission (%)
100 No mucosal breaks
LA Grade A
80
LA Grade B
LA Grade C
60
40
20
0
0 1 2 3 4 5 6
Time after cessation of therapy (months)
(months
From Lundell LR, et al. Gut. 1999;45:172-180.
45:172-180

18. When do we do endoscopy?
 Patient not responding
to treatment
 Complications
 Intestinal bleeding
 Anemia
 Swallowing difficulties
 Painful swallowing
 Cancer screening
 Barrett’s

19. Cancer risk in SSc (Paris data)
 Barrett’s risk in SSc  Cancer risk
 14/110 (12.7%)  50 individuals with
 Dysplasia 3/14 Barrett’s
 3 year follow up
 4/46 developed HGD
 1/50 developed cancer
 18% no sx of GERD
 Wipff, J 2005
 Wipff, J 2011

20. Opportunities to intervene
 Lifestyle
 Medication
 Screening
 Surveillance
 Ablation
 Surgery

21. Stomach
 Roles:
 Reservoir
 Begins digestion
 Produces acid
 Allows absorption of iron
and B12
 Defense against ingested
germs

22. SSc affects Stomach
 Impaired motility/contraction
 Symptoms related primarily to impaired
emptying
 Early satiety, bloating, regurgitation, belching,
nausea, vomiting, ?pain
 50% of patients with SSc have gastroparesis as
measured, but fewer have symptoms

23. Scintigraphic frames at 0, 60, 120, and 180 min during infusion of saline (A) and GLP-1 (B) in
one study subject during gastric emptying of solid meal.
Näslund E et al. Am J Physiol Regul Integr Comp Physiol
1999;277:R910-R916
©1999 by American Physiological Society

24. Stomach (treatment)
 Goals:
 Improve symptoms
 Improve nutritional status
 Methods:
 Dietary changes
 Medications
 ?Pacemaker

25. Stomach (treatment)
 Gastroparesis Rx (early)
 FDA Approved
 Metoclopramide (reglan)
 Erythromycin
 Withdrawn from market
 Cisapride
 Not reviewed
 Domperidone

26. Stomach GAVE “watermelon
stomach”
 10% incidence of
Gastric Antral Vascular Ectasia
 Blood vessel involvement due to
SSc
 May cause overt bleeding
 Causes iron deficiency anemia

27. Stomach GAVE treatment
 APC (Argon Plasma
Coagulation) or other
 Cryotherapy
 Transfusions
 Iron replacements
 Cyclophosphamide
 Several case reports
 Indefinite length?

28. Small Bowel
 Anatomy
 22-23 feet
 3 regions
 Roles
 Digestion of
carbohydrates and
protein and some fat.
 Absorption of all
nutrients
 Absorption of water

29. Small Bowel
 Migrating Motor Complex
 120 minute cycle
 4 phases

30. Small Bowel
 SSc involves small bowel in 50-88% of pts
 Only 6% have severe manifestations
 Symptoms vary (length of dz, extent dz)
 Mild: bloating, fullness, belching
 Severe: diarrhea, weight loss, malnutrition

31. Small Bowel
 Symptoms / pathology mostly due to
impaired motility
Slow transit
Bacterial Overgrowth + Increased ‘fermentation’
Bile acid breakdown Excess Gas
Diarrhea Bloating

32. Normal
Loss of MMC;
Decreased
amplitudes

33. Bacterial Overgrowth
 Occurs 20% - 55% of patients with PSS
 Testing
 Aspirates and culture
 Hydrogen breath test

34. Malnutrition
 Screen for !  Lab tests
 Questionnaire  Hemoglobin
 BMI
 Folic acid
 Carotene level
 Weight loss  Prealbumin
 - 1 – 2% in 1 week
 Vit B12, Vit D, zinc
 > 5% one month
 > 7.5% 3 months
 > 10% 1 year
 ? Depression

35. Small Bowel (treatment 1)
 Antibiotics  Types
 Several effective agents  Tetracycline
 Beware resistance  Doxycycline
 Beware C. Diff colitis  Augmentin
 Cycle agents
 Non absorbable
 Cephalexin + Flagyl
preferred  Cipro
 Nitazoxamid
 Rifaximin

36. Small Bowel (treatment 2)
 Dietary
 Less substrate to ferment and for
bacteria (carbs)
 Small, frequent meals
 Consider FODMAP diet
 Improve motility
 Domperidone
 Erythromycin
 Octreotide

37. Nutritional support
 Dietician
 Enteral nutrition
 Jejunostomy
 Parenteral
nutrition
 TPN

38. Colon
 3 Feet long
 Functions:
 Absorb water
 Concentrate feces
 Excrete

39. Colon
 SSc symptoms:
 Diarrhea
 Constipation
 Incontinence
 Mostly due to motility abnormalities of the
colon and impaired anal sphincter

40. Colon
Measuring transit time
Day 4 Day 7

41. Colon
 Intestinal ‘pseudo-
obstruction’ (IPO)
 Often involves small
bowel
 Signifies advanced stage
 Avoid surgery (results in
prolonged ileus)

42. How about colonoscopy?
 Colon cancer
screening tool
 Investigate for
intestinal bleeding
 Investigate for
anemia
 Does nothing for
constipation

43. Anal Sphincter
 Lax internal sphincter
(neuropathic)
 Fibrotic sphincter
(myopathic)
 Leads to incontinence
and interfering with
normal defecation.

44. Anal Sphincter
Ano-rectal manometry
New options
1.) Sacral stimulation
2.) Sphincter reconstruction

45. Colon (treatment)
 Constipation
 Bulk-forming agents; fiber!
 Water intake
 Osmotic agents (avoid with IPO)
 eg, PEG solutions
 Stimulants (pro-motility)
 Prunes, bisacodyl
 Avoid narcotics, calcium blockers

46. Colon (treatment)
 Diarrhea
 Investigate cause !
 ? Overflow diarrhea
 Infections (C. diff)
 Bacterial overgrowth
 Post-obstructive
 Malabsorption
 Celiac disease
 Bile-acid diarrhea

47. Summary
 The GI tract may be affected to varying degrees
 Reflux is most commonly seen
 GI manifestations have impact on quality of life
 Treatment and diagnostic tools exist to help our
patients
 Physicians knowledgeable in SSc are your best
partners
 Treatment must be tailored to the patient’s
individual needs

48. Thank you!

49. Diarrhea - approach
 Rule out overflow (Xray)
 Obtain stool tests (pathogens, c. diff)
 Obtain TTG (Sprue)
 Obtain fecal elastase, fecal leucocytes
 Trial of treatment for SIBO
 Cholestyramine if cholecytectomy
 Symptomatic treatment (fibers, loperamide)
 Trial of pancreatic enzymes

50. Distention, abdominal pain
 Exclude obstruction
 Consider gastroparesis (GES)
 Review medications
 ? DM
 Empiric trial of antibiotics for SIBO
 Dietician referral
 FODMAP
 Venting gastrostomy

51. Weight loss, nutrition
 Assess BMI
 Rule out depression
 Rule out malignancy
 Review with dietician
 Enteral/parenteral nutrition

52. Incontinence
 Assess frequency and stool consistency
 If lose: trial of Loperamide
 Testing: EUS, anorectal motility,
defecography
 Biofeedback
 Low fiber diet
 Neuromodulation
 Sphincter augmentation

53. Constipation
 Establish: urge and emptying
 Drugs, thyroid function
 ?Prolapse
 Normal urge, infrequent: increase fiber
 No urge, not frequent: low fiber, supp,
osmotic laxative
 Normal urge + emptying: stimulant
 Studies: colonoscopy, colonic transit
 Biofeed back, dietician, surgery