This presentation covers gastrointestinal issues, which are commonly experienced by those living with scleroderma. This session is set to be an invaluable resource for patients and caregivers, as it will provide crucial insights and approaches to managing GI issues effectively. Dr. Khanna's vast knowledge and experience make this talk a must-attend event for anyone seeking to enhance their understanding and management of GI symptoms in scleroderma.

1. Gastrointestinal Tract or Gut in
Systemic Sclerosis
Dinesh Khanna, MD, MS
Frederick G. L. Huetwell Professor of Rheumatology
Professor of Medicine
University of Michigan
khannad@umich.edu
Twitter: @sclerodermaUM

2. Gastrointestinal in Systemic Sclerosis (SSc)
• Approximately 90-95% of patients have gastrointestinal tract (GI)
involvement1,2
• A major impact on their quality of life3
• Involvement of GIT occurs with equal frequency in diffuse and
limited cutaneous subtypes of SSc
• Objective of the presentation is to provide a practical management
for pts with scleroderma
1. Sallam H, et al. Aliment Pharmacol Ther. 2006 Mar;23(6):691-712
2. Sjogren. Arthritis Rheum. 1994 Sep;37(9):1265-82.
3. Khanna D, et al. Arthritis Rheum. 2007 Oct;57(7):1280-6.

3. Vascular Hypothesis
Neural dysfunction Asymptomatic Prokinetics ++
Smooth muscle atrophy Symptomatic Prokinetics +/-
Smooth muscle fibrosis Symptomatic Prokinetics --
Sjogren. Arthritis Rheum. 1994 Sep;37(9):1265-82.
Axonal degeneration
Collagenous cuffing of nerves

4. 4

5. Oropharyngeal Manifestations
• Facial involvement interferes with
mastication
• 20% Sjogren’s syndrome
TREATMENT
• Liberal fluid intake
• Regular dental appointments
• Sugar free gums
• Trial of pilocarpine and cevimeline
therapy

6. Oral Moistures & Protection
• Xylitol containing products
• Caphosol- super saturated calcium phosphate
• Fluoride based products
• Calcium phosphate paste

7. Adaptive devices
7

8. Minimize Enamel Erosion
• Dental appointments and fluoride varnish to prevent enamel erosion
• Treat GERD

9. Esophageal involvement
• 50 to 90% of patients with SSc1,2
• Esophageal dysmotility1,2
― Decrease or complete absence of lower esophageal sphincter pressures
― Decreased amplitude of distal esophageal peristalsis
• SSc primarily affects the distal two-thirds of the esophagus1,2
• Motility of upper esophageal sphincter and proximal esophagus is
generally normal
1. Sjogren. Curr. Opin. Rheumatol 1996 Nov;8(6):569-75.
2. Sjogren. Arthritis Rheum. 1994 Sep;37(9):1265-82.

10. 3 sec
UES
LES
19
24
29
39
34
44
49
54
Cm
from
Nares
0
20
40
60
80
100
120
140
mmHg
*
**
Striated Muscle
Transition Zone
Smooth
Muscle
Courtesy: Jeffrey Conklin, MD
Normal esophageal motility

11. 0
10
20
30
40
50
60
70
90
80
MmHg
10 sec
15
20
25
35
30
40
45
50
Cm
from
Nares
UES
LES
Diaphragm
Courtesy: Jeffrey Conklin, MD
SSc esophageal motility
UES

12. Symptoms of Reflux Disease
• Heartburn
• Difficulty Swallowing
• Chest Pain
• Mouth ulcers/burning
• Change in voice
• Chronic cough
• Asthma

13. Anti-Reflux Measures
• Head of the bed elevated (i.e. wedge pillow, blocks under head
of bed, electric bed.) NOT extra pillows
• Biggest meal at noon, small meals otherwise
• Do not eat late (after 6pm); do not drink fluids late (after 8pm)
• Frequent small meals (5-6 per day)
• No tight garments around waist

14. Wedge Pillow / Blocks

15. How to use PPI?
• PPI blockers 30 to 60 minutes before each meal
• May require higher dose
• Start PPI agent once a day
• Increase to twice a day*
• Add H2 blocker at bedtime*
• Continuing symptoms– refer to GI for w/u.
― R/O stricture
― R/O candida esophagitis
― Further studies such as manometry and ph impedance (can tell about both acidic and non-
acidic reflux)
* If the heartburn or other symptoms continue for 2 weeks

16. Possible Underlying Mechanisms for PPI Failure
Persistent acid reflux
• Patient noncompliance
• Inadequate dose PPI
• Rapid PPI metabolism
Non-Acid Reflux
• Weakly acidic or alkaline reflux
• Visceral hypersensitivity
Non-GERD
• Functional dyspepsia
• Delayed gastric emptying
• Psychological comorbidity
• Achalasia
Hemmink, et al. Am J Gastroenterol 2008 Oct;103(10):2446-53.
Galmiche. Gut 2006 Oct;55(10):1379-81.

17. Long term risks of PPIs
♦ Dementia
♦ Fracture risk/ Osteoporosis
♦ Infections
– C difficle
– Pneumonia
♦ Poor absorption of
minerals/ vitamins
– Calcium, Magnesium, and
B12
• Depression
• Cardiovascular Deaths
Hemmink, et al. Am J Gastroenterol 2008 Oct;103(10):2446-53.
Galmiche. Gut 2006 Oct;55(10):1379-81.

18. MMF [Cellcept] and PPI
♦ MMF requires acidic environment to convert to active drug
♦ PPIs and even H2 blockers can reduce the availability in the
blood
♦ Suggestion
– Take AM PPI
– MMF in the afternoon and evening
18

19. Failure of the PPI
• RCT in SSc patients who had ongoing GERD despite being on PPI
• Domperidone 10 mg po TID vs. alginic acid 1 chewing tablet three
times daily
• Alginic acid acts by precipitating as a gel and creating a relatively
pH neutral mechanical barrier that floats on the surface of gastric
contents.
• Patients were randomized to either domperidone (n = 38) or
algycon (n = 37) therapy
• At 4 weeks the severity of symptoms, frequency scale for
symptoms of GERD and QoL significantly improved in both groups
Foocharoen, et al. Rheumatology (Oxford). 2017 Feb;56(2):214-222.

20. Barrett’s Esophagus
• Barrett’s esophagus is a
complication of long-standing
GERD1-3.
• Present in 13% consecutive people
with SSc receiving chronic therapy
with PPI1.
• Prevalence of 6% in general
population4.
• Barrett’s esophagus is associated
with adenocarcinoma in SSc.
―Incidence is 0.7%/year3
1. Wipff J, et al. Arthritis Rheum 2005 Sep;52(9):2882-8.
2. Derk CT, et al. J Rheumatol 2006 Jun;33(6):1113-6.
3. Wipff J, et al. Rheumatology (Oxford). 2011 Aug;50(8):1440-4.
4. Hayeck TH, et al. Dis Esophagus 2011 Aug;23(6):451-7.

21. ILD and GERD: Association?
• Association between GERD and interstitial lung disease has been proposed 1,2
• Micro aspirations of gastric content -> ?? ILD
1. Marie I, et al. Arthritis Rheum. 2001 Aug;45(4):346-54.
2. Savarino. Am J Respir Crit Care Med. 2009 Mar 1;179(5):408-13.

22. Gastroparesis or delayed emptying study
• 50% involvement
• Symptoms
• Bloating
• Nausea and vomiting
• Early satiety
• Abdominal pain
• Excessive flatulence
• Result in weight loss
• Overlap symptoms with small bowel bacterial overgrowth
Marie I, et al. Am J Gastroenterol .2001 Jan;96(1):77-83.

23. How to Approach This?
• Ensure that symptoms are consistent with gastroparesis
– Early satiety, bloating, distention, no diarrhea
• Small meals and no meal 2-3 hours before bed time
• If continuing symptoms, refer to GI or consider gastric
emptying study
Marie I, et al. Am J Gastroenterol .2001 Jan;96(1):77-83
📌

24. NORMAL EMPTYING STUDY Less than 50% Remaining (or Greater than 50% Emptying) at 90 minutes
Gastric Emptying Study

25. Pro-Motility Agents
Agent Frequency Part of Gut
• Metoclopramide⍏ 10 mg TID-QID Whole
• Erythromycin 100-123 mg TID Stomach
• Domeperidone* 10-20 mg QID Stomach and Small Bowel
• Cisapride *  10-20 mg TID Whole
⍏ Tardive dyskinesia as Black Box Warning
*Domeperidone not approved in USA--can obtain in Canada or Mexico
 US CALL 1-800-JANSSEN (Restricted use)
*Black box warning for prolonged QTc–
Do EKG before prescribing and need to file an IND

26. Gastric Antral Vascular Ectasia
(Watermelon Stomach)
• Cause of iron deficiency anemia
• Prevalence of GAVE in SSc from 9% to 23%1,2
• Presenting symptoms may be fatigue and tiredness
• Repeated blood transfusions may be necessary
1. Duchini A, et al. Am J Gastroenterol. 1998 Sep;93(9):1453-6.
2. Hung E, et al. J Rheumatol. 2013 Apr;40(4):455-60.

27. Watermelon Stomach

28. Watermelon stomach After argon plasma
coagulation

29. Visceral Hypersensitivity- Fibromyalgia of the gut
• Medications influencing CNS neuronal signaling may also be effective in the
peripheral nervous system1,2
– Visceral analgesia
– Smooth muscle relaxation
• In a 4-week open label trial, buspirone (Buspar) was evaluated in 30 patients
with SSc and esophageal symptoms3
• Manometric parameters and symptom severity were documented at baseline and
after 4 weeks
• The LES resting pressure increased significantly (p=0.00002; N=22)
• Heartburn and regurgitation severity scores significantly improved
• Mirtazapine was effective in improving gastroparesis in non –SSc patients
1. Ford AC et al. Am J Gastroenterol. 2014
2. Grover M, Drossman DA. Gastroenterol Clin N Am. 2011 Mar;40(1):183-206.
3. Karamanolis et al Arthritis Res Ther 2016 Sep;18(1):195.

30. Bacterial Overgrowth Syndrome
• Stasis of the intestinal contents, resulting in migration of bacteria from the
colon
• Symptoms include1,2
– Bloating
– Nausea, vomiting
– Abdominal pain
– Diarrhea (with pale, greasy, foul-smelling stools)
– Excessive flatulence
– Inability to gain weight or weight loss
• Symptoms overlap with gastroparesis
1. Vantrappen et al J Clin Invest 1977 Jun;59(6):1158-66.
2. Sjogren. Arthritis Rheum. 1994 Sep;37(9):1265-82.

31. Clinical Presentations
• Continuing weight loss or inability to gain weight,
steatorrhea, distention/ bloating
• Abdominal pain, intermittent symptoms of distention,
nausea/ vomiting, and inability to pass gas that is relived
in a few days intermittent pseudo-obstruction
📌

32. How to Approach This?
• Refer the patient to GI
―Breath test
―Jejunal aspirate
• Broad-spectrum antibiotic (Augmentin or rifaximin)
―Improvement in symptoms of distention/ bloating
• May require long term rotating antibiotics
• Work with a dietician to replete nutrients and vitamins

33. Antibiotic Dosing schedule
♦ Augmentin 875 mg 2x per day
♦ Cipro 500 mg 2x per day
♦ Flagyl 500 mg 3 x per day
♦ Doxycyline 100 mg 2x per day
♦ Tetracycline 250 mg 4x per day
♦ Rifaximin 400 mg 2x per day
How to Approach This?

34. Colon
• Constipation
– Caused by weakening of the gut muscle and slow contractions
– Use of stimulant laxatives (docusate, lactulose, senna) -acts on
nerve endings in the gut wall that make the muscles in the
intestine contract with more force
– Liberal use of fluids
– Avoid high-fiber diet and bulk-forming laxatives in slow transit
constipation; may make constipation worse
– Take medication every other day to maintain a healthy bowel
regimen

35. 35
Slow transient time Normal transient time

36. Stimulant Laxatives for normal transient time
♦ Laxatives
♦ Colace
♦ Dulcolax
♦ Senna
♦ Milk of Magnesia
♦ Lactulose
♦ Dosage
♦ 100 mg once-
twice/day
♦ 10-15 mg once a day
♦ 2-4 tablets once a day
♦ 30-60 mg/day
♦ 15-30 ml/day
Do not use these laxatives if symptoms of
bowel obstruction!!

37. New Medications approved for
management of idiopathic constipation
Linaclotide
Guanylate cyclase-C (GC-C) agonist
and binds with high affinity to the
GC-C receptor, which is located
almost exclusively in the intestines.
Dosage for IBS-C
290 µg once daily
Take on empty stomach ≥30 minutes
prior to first meal of the day.
Contraindicated in pediatric patients
up to 6 years of age.
Lubiprostone
Locally acting ClC-2 chloride
channel activator.; promotes fluid
secretion into the intestinal lumen.
Dosing for IBS-C
8 μg BID
Contraindicated in patients with
mechanical GI obstruction
Negative pregnancy test and
contraception recommended in
women of childbearing age.
Prucalopride
Stimulates peristalsis.
Dosage for IBS-C
1-2 mg daily
Contraindicated in patients
with mechanical GI
obstruction.

38. PROGRASS trial
• Prucalopride is a 5-HT4 receptor agonist
―Increasing peristalsis
―Approved for chronic idiopathic constipation
• Open-label cross-over study
―40 SSc patients with self-reported mild-to-moderately-severe constipation
―Randomized 1:1; prucalopride 2 mg/day vs no Rx for one month
• UCLA GIT 2.0 and the number of spontaneous bowel movements was
recorded
• Prucalopride was associated with:
– Significantly more spontaneous bowel evacuations (p < 0.001)
– Improvement of UCLA GIT constipation, reflux and bloating (p< 0.05) scores
Vigone B, et al. Arthritis Res Ther. 2017 Jun;19(1):145.

39. Rectum
• Stool incontinence occurs in up to 1/3 of patients
• Weakening of the rectal muscle and poor control over rectal sphincter
• Biofeedback therapy
―Strengthen the rectal muscle by volunteer squeezing of the muscle
• Bulk agents such as Citrucel
• Anti-diarrheal agents such as Imodium

40. Sacral Nerve Stimulation
• Electrical stimulation of the sacral nerve, which is thought to normalize
neural communication between the bladder and brain and between the
bowel and brain
• Using electrodes to stimulate sacral in the sacrum
• May be effective in a subset of patients

41. Primary Biliary Cirrhosis
• 8% of PBC patients have SSc1
• Royal Free Hospital2
– 43 patients with SSc
– 93% had limited cutaneous SSc
– Median PBC diagnosis after SSc: 4.9 (range 0.1- 26.7)
– Majority: 39% no symptoms
– Pruritus (32%), fatigue (16%), and diarrhea (13%)
1. Watt FE et al Q J Med 2004 Jul;97(7):397-406.
2. Rigamonti C et al Gut 2006 Mar;55(3):388-94.

42. UCLA SCTC Gastrointestinal Tract 2.0 Instrument
• Captures GIT involvement in patients with SSc
• 34-item instrument for clinical care and clinical trials
• Feasible: Takes approximately 7-9 minutes to complete
• UCLA SCTC GIT 2.0 has 7 scales:
– Reflux
– Bloating/indigestion
– Diarrhea
– Constipation
– Fecal Soilage
– Emotional well-being
– Social functioning Khanna D et al. Arthritis Rheum 2009 Sep;61(9):1257-63.

43. UCLA SCTC 2.0 – How do I use it? 5-minute
screen and Rx plan
Symptoms Management
↑Reflux • Anti-reflux
• PPIs
• ?Promotility agent
↑Distention/Bloating
PLUS Diarrhea • Trial of antibiotics
No Diarrhea • Small meals
• Trial of promotility agents
↑Constipation • Stimulant laxatives
• Good bowel regimen
↑Fecal soilage • Referral to physical therapist and
colorectal surgeon (resistant cases)
↑Out of proportion emotional sym • Irritable bowel disease
43

44. Hand out for our patients
Digestive system (Gut)
involvement in scleroderma
Eating well with scleroderma
Linda Kaminski and
Dinesh Khanna
Dinesh Khanna

45. Conclusion
• GIT involvement in SSc is very common
• Has a major impact on quality of life
• Proactive approach in diagnosing GIT involvement
– Cornerstones of GIT examination are imaging studies and
laboratory tests
– Motility disorders: barium contrast study is the preferred
radiographic procedure
– For assessment of mucosal disease, endoscopy is the preferred
test

46. New
Partnerships
SF California, SF Greater
Chicago and F-WSF are official
partners and mutually support
each organization’s goals and
mission.

47. CME Update:
Early Detection
and Diagnosis
of Scleroderma

48. Continuin
g Medical
Education
Early Detection and Diagnosis
of Scleroderma (SSc)
CME Outline
Introduction
•Dinesh Khanna, MD, MSc
Patient Voices – Journey to Diagnosis
•Tina Burger – Scleroderma Foundation of California
•Beverly Townsley – Michigan resident
SSc – Differential Diagnosis, Screening & Diagnosis for PCPs
•Philip Clements, MD and Suzanne Kafaja, MD
Pathogenesis for Primary Care Physicians
•John Varga, MD
Non-Pharmacologic Management of Early SSc
•Susan Murphy, MD
Current Treatment for SSc
•Dan Furst, MD