This document provides an overview of gastrointestinal manifestations and treatment in scleroderma. It discusses how 60-90% of scleroderma patients experience GI involvement, most commonly affecting the esophagus, stomach, small intestine, and colon. For the esophagus, it covers GERD, dysphagia, and their diagnostic tests and treatments like PPIs. For the stomach, it discusses gastroparesis, GAVE, and treatments like prokinetic agents and APC. It reviews SIBO, CIPO, and treatments for the small intestine. For the colon and anus, it covers constipation, fecal incontinence, diagnostic tests, and treatments including laxatives, bio

1. Scleroderma 2019: A Primer on
GI Manifestations & Patient Q&A
Darren M. Brenner, M.D.
Associate Professor of Medicine and Surgery
Irene D. Pritzker Research Scholar
Director—Neurogastromotility, Functional, and Integrated
Bowel Control Programs
Director—Motts Tonelli GI Physiology Laboratory
Division of Gastroenterology
Northwestern University-Feinberg School of Medicine

2. Overview
• General Overview
• Esophagus
• Stomach/Small Intestine
• Colon/Anus
• Nutritional Deficiencies

3. Scleroderma: GI Involvement
• 60-90% of patients have GI involvement
– Recent Study98.9% SSc pts with GI involvement
– Most commonly involved organ
– Presenting ifeature in 10% of SSc.
• Affects CREST, diffuse and limited cutaneous forms
• Can be slow or rapidly progressive
• Occurs at any age
• Esophageal and Anorectal disorders most common
Rossa et al. Ann Rheum Dis 2001;60:585-91; Sallam et al. APT 2006;23:691-712.; Schmeiser et al. Rheumatol Int 2012;32:2471-78.

4. Scleroderma: GI Involvement
• Pathogenesis: Smooth Muscle
– NeuropathyMyopathyFibrosis and Atrophy
• Treatment: “Plug leaks in the dam”
• Treatment is predominately symptom not study-
based
• Most treatment regimens anecdotal
• Therapies most beneficial before extensive
collagen deposition
Tian et al. WJG 2013;19:7062-7068

5. •GERD
•Dysphagia
•Gastroparesis
•GAVE
•SIBO
•CIPO
Constipation
Fecal Incontinence
Sicca Syndrome
(20%)

6. Esophagus

7. Esophagus
• Most common GI organ involved
– Up to 90% of individuals
– 1/3 may be asymptomatic
• Lower 2/3 + LES
• Gastro-esophageal reflux (GERD)
• Regurgiation
• Dysphagia

8. Esophagus: GERD
• Most common GI manifestation
– Up to 96% patients affected
– Reduction in LES pressure/impaired acid clearance
• Classic Symptoms
– Sub-sternal chest burning
– Acid/Food regurgitation
• Supralaryngeal (SLR) Symptoms
– Cough/Hoarseness/Recurrent URIs/Pulmonary
Fibrosis
Weston et al., AJG 1998;93:1085-89; Stern EK……Brenner, DM. Neurogastroenterol Motil 2018;30(2):

9. Esophagus: GERD
• Diagnostics :
– pH <4 >5% over 24 hrs = abnormal
Abnormal acid exposure

10. GERD Treatment:
Non-pharmacological
• Head of Bed Elevation
– 4-6 inches
– Cinder blocks
– Sleep positioning devices
• Diet Modifications: Key is weight loss
– Spicy, Fatty, Tomato based, Caffeine, Chocolate
– ETOH/Tobacco
– Small Meals
– Avoidance of PO intake within 4 hours of bedtime

11. GERD Treatment: Pharamaceutical
Antacids
Histamine
Receptor Blockers
(H2RAs)
Proton Pump Inhibitors
(PPIs)

12. Esophagus: GERD
• Complications
– Erosive esophagitis
– Peptic strictures (29%)
– Barrett’s Esophagus
(6.8-12.7%) w/inc risk
Eso AdenoCa c/t general
population
– Cough, Hoarse voice,
Asthma, Pulmonary
scarring
EGD Findings:
Wipff et al. Arthritis Rheum 2005;52:2882-2888; Carlson DA et al. CGH 2016;14(10):1502-06.

13. Esophagus: Dysphagia
• Difficulty Swallowing
• Feels like food gets stuck (usually at thyroid cartilage)
• Up to 60% patients affected
• Solids >>> Liquids
• Can lead to microaspiration and interstitial lung disease
Frech TM and Mar D. Rheum Dis Clin N Am 2018;44:15-28.

14. Esophagus: Dysphagia

15. High Resolution Manometry

16. Dysphagia: Diagnostics
Normal High Resolution Esophageal Manometry
Upper 1/3
Esophagus
Normal Wave
Propagation
Normal LES Relaxation

17. Dysphagia: Diagnostics
Pathognomonic for Scleroderma
Upper 1/3
Esophagus
Lower Esophageal
Sphincter
Lack of
propagation

18. Dysphagia: Treatment
Avoid precipitating foods Chew Vigorously
Follow solids w/liquids Liquid Supplements
PEG

19. Stomach

20. Stomach: Gastroparesis
• “Gastro”  Stomach “Paresis”  Impaired movement
• Disorder of delayed stomach emptying
• Reported in @ least 50% patients
• Develops from loss of neural innervation and fibrosis of smooth
muscle of the stomach
• Symptoms:
– Fullness after a few bits of food
– Nausea +/- vomiting
– Bloating/Belching
– Stomach pain after eating
– Weight loss (sitophobia)
– GERD/Regurgitation
Clements et al., Clin Exp Rheumatol 2003;21:S15-18.

21. Gastroparesis: Diagnostics
• EGD • Gastric Emptying
Study

22. Stomach: Gastroparesis
Treatment
• Dietary Modification
– Small frequent meals (4-5 day)
– Low fat/fiber diet (Phase III MMC)
• Anti-Emetics
• Prokinetic Agents
– Metoclopromide, Domperidone, Erythromycin, Prucalopride,
? Tegaserod
• Botox ??
• G-POEM/PEJ/Venting G-J/TPN

23. Scleroderma : GI Bleeding
• GI bleeding occurs in 15% patients
• Telengiectasias (small superficial vessels) most
common source
• Can be found throughout GI tract
• Stomach most common site
– GAVE (gastric antral vascular ectasias) / Watermelon
stomach
• Presents as iron deficiency anemia
• Overt bleeding less common
• Autoimmune vascular fibrosis presumed etiology
• Colon AVMs
Duchini et al., AJG 1998;93:1453-56

24. Gastric Antral Vascular Ectasias
(GAVE)

25. • Treatment:
–Thermal Therapy (APC q 4 weeks)
–PO/IV Iron supplementation
–Blood Transfusions rare after initial
discovery
Stomach: GAVE

26. Small Intestine

27. Scleroderma: Small Intestine
• Intestinal motility delayed in 40-88% patients
• Fibrosis reduced absorptive surface area
• Stasis:
– Small Intestine Bacterial Overgrowth (SIBO)
– Chronic Intestinal pseudo-obstruction (CIPO)
• 65% asymptomatic
Fynne et al. Scand J Gastroenterol 2011;46:1187-1193; Gyger et al. Curr Rheumatol Rep 2012;14:22-29.

28. SIBO
• SI bacteria colonization primarily limited to the distal
small intestine
– <105 CFU/cc normal in proximal SI
• SIBO  Bacterial colonization of the proximal portion
of the small intestine
– Bloating/Distention (production of H2/CH4)
– Diarrhea
– Malabsorption
• B12
• Fat Soluble Vitamins
• Carbohydrate/Protein Malabsorption
– Pneumatosis Cystoides Intestinalis
• Risk may be increased by concomitant use of PPIs

29. SIBO: Diagnosis
• Endoscopic biopsies
– Villous atrophy/Crypt hyperplasia/Inc IELs
– Not specific and cannot be differentiated from Celiac and other disorders
• Jejunal aspirates
– Gold Standard (> 105 CFU/CC)
– Limited performance
• Hydrogen Breath Tests
– Less invasive and expensive
– Imperfect sensitivity/Specificity
– Glucose and Lactulose
• Empiric Treatment (10-14 days)
– Rifaximin
– Ciprofloxacin/Metronidazole
– Tetracycline/Doxycycline
– Amoxicillin-Clavulanate
– Trimethoprim-Sulfamethoxazole

30. SI: Chronic Intestinal Pseudo-obstruction
(CIPO)
• Signs and Symptoms of obstruction without fixed
lumen-occluding lesion
• Small Intestine appears dilated on radiography
• Predisposes to SIBO
• Symptoms:
– Abdominal pain
– Nausea +/- vomiting
– Bloating/Distention
– Early satiety
– Weight loss

31. CIPO
SBFT: “Hidebound sign”

32. CIPO: Treatment
• Dietary Modification
– Small frequent meals (4-5 day)
– Low fat/fiber diet
– Vitamin Supplements
• Prokinetic Agents
– Similar to gastroparesis
• Octreotide
– Increases SI motility in SSc patients
– Significantly decreases nausea, vomiting, bloating, abdominal pain
• Surgery
– Bypass localized disease
– Provide access to the stomach/SI for venting
Soudah et al., NEJM 1991;325:1461-67;
Nikou et al., J Clin Rheumatol 2007;13:119-23.

33. Octreotide for CIPO
Soudah et al. NEJM 1991:325(21):1461-1467.

34. Colon (Large Intestine)

35. Scleroderma: Colon & Anus
• Involvement affects 20-50% of SSc patients
• Prevalence likely underreported
• 2 major manifestations
– Constipation
– Fecal Incontinence (40%)
Trezza et al., Scand J Gastroenterol 1999;34:409-13
Clements et al., Clin Exp Rheumatol 2003;21(S29) S15-18

36. What is Constipation?
• Historically it depends on who you ask:
Infrequent bowel
movements

37. What is Constipation?
straining
Digital Maneuvers
Incomplete evacuation

38. Diagnostic Criteria for Functional Constipation
includes 2 or more of the following*
< 3 spontaneous bowel movements (SBM) per
week
Lumpy or hard stools (BSFS I-II) ≥ 25% BM
Straining ≥ 25% of BM
Sense of incomplete evac ≥ 25% BM
Sense of blockage ≥ 25% BM
Manual maneuvers to assist ≥ 25% BM
+
Loose stools rarely present w/o laxatives
Insufficient criteria for IBS
Rome IV—Functional Constipation
Criteria fulfilled for 3 months w/sx onset > 6 months prior to diagnosis
Lacy B et al. Gastroenterology 2016;150:1393-1407.

39. Radio-opaque Marker Testing
• Numerous markers throughout the
colon
•Colon Contractions Reduced/Absent
•Numerous markers in the
rectumoutlet obstruction
•Atrophy and fibrosis of Internal
Anal Sphincter (IAS)

40. ACG Recommendations:Constipation
Fordet al. AJG 2014;109:S2-26.;Guyattet al. J Clin Epidemiol2011;64:383-94.
Agent Recommendation Quality of Evidence
Fiber Strong Low
Osmotic Laxatives:
PEG
Lactulose
Strong
Strong
High
Low
Stimulant Laxatives:
Bisacodyl
Sodium Picosulfate
Strong
Strong
Moderate
Moderate
5-HT4 agonists:
Prucalopride Strong Moderate
Secretagogues:
Linaclotide
Plecanatide#
Lubiprostone
Strong
NR
Strong
High
NR
High
*StrengthorrecommendationsandqualityofevidencedeterminedusingGRADE(GradingofRecommendationsAssessmentDevelopmentandEvaluation)
##Plecanatidenotavailableattimeofassessment

41. AGA Technical Review on Constipation
BharuchaAE et al. Gastroenterology. 2013;144:218-238.
Agent
NNT
(95% CI)
Number of
patients
Quality of
Evidence
Soluble fiber NR due to
low quality
evidence
368 Very low
Osmotic and
stimulant laxatives
3 (2-4) 1411 High
PEG 2.4 573 High
Lubiprostone 4 (3-7) 610 Moderate
Linaclotide 6 (5-8) 2858 Moderate
Prucalopride 6 (5-9) 2639 Moderate

42. Fecal Incontinence Subtypes
FI
Passive
Overflow
Urge
Stress
• Unconscious loss of stool
• Primarily related to IAS
dysfunction
Passive FI
• Secondary to constipation/fecal
impaction
• ImpactionInhibition of IAS tone
Overflow
FI
• Conscious knowledge of stool loss
with inability to control
• Primarily related to EAS
dysfunction
Urge FI
• Uncommon and a/w (+) recto-anal
gradientStress FI

43. FI: 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

44. High-Resolution Anorectal
Manometry
•

45. Passive Fecal Incontinence
High Resolution Anorectal Manometry
High pressure
zone 10-20mmHg:
Normal 40-60mm
Hg

46. Fecal Incontinence:
• Treatment:
– Laxatives/Anti-diarrheals
– Physical Therapy/Biofeedback
– Removable continence devices
– Injectables
– Surgical Interventions
• Sacral Nerve Stimulator
• Sphincteroplasty/Dynamic graciloplasty
• Artificial sphincters/Magnets
Kenefick et al., Gut 2002;51:881-83.

47. 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 dislodged in 1st 24 hours
Max response time 60 months
Improvements in urgency, QoL
Elevations in resting pressures identified

48. Summary
Organ Involved Disorder Primary Diagnostic
Test
Primary Treatment
Mouth Tight skin
Cavities
Trouble Swallowing
Skin exam
Dental exam
Swallowing exam
Stretching exercises
Oral hygiene
Speech exercises
Bilateral
Commissurotomy
Esophagus GERD
Dysphagia
pH study
Manometry
PPIs
Supportive
Stomach Gastroparesis
GAVE
4-hr solid gastric
emptying study
EGD
Pro-motility agents
APC
Small Intestine SIBO
CIPO
Breath tests
SBFT
Antibiotics
Pro-motility agents
Colon Constipation ROM tests
Manometry
Laxatives
PT/Biofeedback
Anus Fecal Incontinence Manometry PT/Biofeeback
SNS

49. Thanks For Your Time