Gastrointestinal Gastrointestinal Manifestations of Manifestations of

Systemic Sclerosis Systemic Sclerosis

Harald Schoeppner, MD PhD

Legacy Health Gastroenterology

ObjectivesObjectives

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)

Paul Klee (1879-1949)Paul Klee (1879-1949)

Organ involvement in SScOrgan 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

DefinitionsDefinitions

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

SSc affects the GI tractSSc affects the GI tract

New theory Auto antibodies to

myenteric neurons M3R (anti-muscarinic

3 Ach R)

SSc affects the GI tractSSc 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

SSc and the GI tractSSc and the GI tract

DYSPHAGIA/REFLUX

EARLY SATIETY/BLOATING

MALABSORPTION/WEIGHT LOSS

DIARRHEA/CONSTIPATION

PSEUDO-OBSTRUCTIONBACTERIALOVERGROWTH

FECALINCONTINENCE

ANEMIAINTESTINALBLEEDING

LIVER: PRIM BILIARYSCLEROSIS

UCLA Scleroderma Clinical Trial Consortium GI UCLA Scleroderma Clinical Trial Consortium GI Tract 2.0 InstrumentTract 2.0 Instrument

Reflux Distention/bloating Fecal soilage Diarrhea Social functioning Emotional well-being Constipation

Khanna. D Arthritis Rheum 2009

Mouth & OropharynxMouth & Oropharynx

Sicca symptoms (Sjogren’s) Poor salivary function Difficulty swallowing Tooth cavities

Mouth opening Minimal tongue involvement

EsophagusEsophagus

Most commonly affected organ

Symptoms: Heartburn Regurgitation Dysphagia Chest pain Atypical reflux symptoms

Hoarseness Cough ILD (interstitial lung disease) Breathing problems (apnea)

EsophagusEsophagus

Poor lubrication Poor motility Absent sphincter

barrier

Normal Systemic sclerosis

EsophagusEsophagus

Complexity of GERD Sequelae:

Stricture Ulcers Barrett’s metaplasia Esophageal cancer Diverticula

Esophagus (treatment)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

Esophagus - treatmentEsophagus - treatment

PROTON PUMP BLOCKER “PPI”s – which is the right

one? Proper timing Proper dosing Early initiation in all SSc Long term commitment Safety issues? Will prevent complications May help with ILD

Other pharmacological tx H2 blockers “Promotility drugs” Antacids Avoid:

Calcium blockers NSAIDs Bisphonates

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80

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Time after cessation of therapy (monthsTime after cessation of therapy (months)

No mucosal breaksNo mucosal breaks

LA Grade ALA Grade A

LA Grade BLA Grade B

LA Grade CLA Grade C

GERD Is a Chronic Condition GERD Is a Chronic Condition Likely to RelapseLikely to Relapse

From Lundell LR, et al. From Lundell LR, et al. Gut.Gut. 1999; 1999;45:172-18045:172-180.

When do we do endoscopy?When do we do endoscopy?

Patient not responding to treatment

Complications Intestinal bleeding Anemia Swallowing difficulties Painful swallowing

Cancer screening Barrett’s

Cancer risk in SSc (Paris data)Cancer risk in SSc (Paris data)

Barrett’s risk in SSc 14/110 (12.7%) Dysplasia 3/14

Wipff, J 2005

Cancer risk 50 individuals with

Barrett’s 3 year follow up 4/46 developed HGD 1/50 developed cancer 18% no sx of GERD

Wipff, J 2011

Opportunities to interveneOpportunities to intervene Lifestyle Medication

Screening

Surveillance

Ablation

Surgery

StomachStomach

Roles: Reservoir Begins digestion Produces acid Allows absorption of iron

and B12 Defense against ingested

germs

SSc affects StomachSSc 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

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

Stomach (treatment)Stomach (treatment)

Goals: Improve symptoms Improve nutritional status

Methods: Dietary changes Medications ?Pacemaker

Stomach (treatment)Stomach (treatment)

Gastroparesis Rx (early) FDA Approved

Metoclopramide (reglan)

Erythromycin

Withdrawn from market Cisapride

Not reviewed Domperidone

Stomach GAVE “watermelon Stomach GAVE “watermelon stomach”stomach”

10% incidence of Gastric Antral Vascular Ectasia

Blood vessel involvement due to SSc

May cause overt bleeding Causes iron deficiency anemia

Stomach GAVE treatmentStomach GAVE treatment

APC (Argon Plasma Coagulation) or other

Cryotherapy Transfusions Iron replacements

Cyclophosphamide Several case reports Indefinite length?

Small BowelSmall Bowel

Anatomy 22-23 feet 3 regions

Roles Digestion of

carbohydrates and protein and some fat.

Absorption of all nutrients

Absorption of water

Small BowelSmall Bowel Migrating Motor Complex 120 minute cycle 4 phases

Small BowelSmall 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

Small BowelSmall Bowel Symptoms / pathology mostly due to

impaired motility

Slow transitSlow transit

Increased ‘fermentation’Increased ‘fermentation’Bacterial OvergrowthBacterial Overgrowth

Excess GasExcess GasBile acid breakdownBile acid breakdown

DiarrheaDiarrhea BloatingBloating

++

NormalNormal

Loss of Loss of MMC;MMC;Decreased Decreased amplitudesamplitudes

Bacterial OvergrowthBacterial Overgrowth

Occurs 20% - 55% of patients with PSS Testing

Aspirates and culture Hydrogen breath test

MalnutritionMalnutrition

Screen for ! Questionnaire BMI Weight loss

- 1 – 2% in 1 week > 5% one month > 7.5% 3 months > 10% 1 year

? Depression

Lab tests Hemoglobin Folic acid Carotene level Prealbumin Vit B12, Vit D, zinc

Small Bowel (treatment 1)Small Bowel (treatment 1)

Antibiotics Several effective agents Beware resistance Beware C. Diff colitis Cycle agents Non absorbable

preferred

Types Tetracycline Doxycycline Augmentin Cephalexin + Flagyl Cipro Nitazoxamid Rifaximin

Small Bowel (treatment 2)Small Bowel (treatment 2)

Dietary Less substrate to ferment and for

bacteria (carbs) Small, frequent meals Consider FODMAP diet

Improve motility Domperidone Erythromycin Octreotide

Nutritional supportNutritional support

Dietician Enteral nutrition

Jejunostomy Parenteral nutrition

TPN

ColonColon

3 Feet long

Functions: Absorb water Concentrate feces Excrete

ColonColon

SSc symptoms: Diarrhea Constipation Incontinence

Mostly due to motility abnormalities of the colon and impaired anal sphincter

ColonColonMeasuring transit timeMeasuring transit time

Day 4Day 4 Day 7Day 7

ColonColon

Intestinal ‘pseudo-obstruction’ (IPO)

Often involves small bowel

Signifies advanced stage Avoid surgery (results in

prolonged ileus)

How about colonoscopy?How about colonoscopy?

Colon cancer screening tool

Investigate for intestinal bleeding

Investigate for anemia

Does nothing for constipation

Anal SphincterAnal Sphincter

Lax internal sphincter (neuropathic)

Fibrotic sphincter (myopathic)

Leads to incontinence and interfering with normal defecation.

Anal SphincterAnal Sphincter

Ano-rectal manometryAno-rectal manometry

New options1.) Sacral stimulation2.) Sphincter reconstruction

Colon (treatment)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

Colon (treatment)Colon (treatment)

Diarrhea Investigate cause !

? Overflow diarrhea Infections (C. diff) Bacterial overgrowth Post-obstructive Malabsorption Celiac disease Bile-acid diarrhea

SummarySummary

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

Thank you!Thank you!

Diarrhea - approachDiarrhea - 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

Distention, abdominal painDistention, abdominal pain

Exclude obstruction Consider gastroparesis (GES) Review medications ? DM Empiric trial of antibiotics for SIBO Dietician referral FODMAP Venting gastrostomy

Weight loss, nutritionWeight loss, nutrition

Assess BMI Rule out depression Rule out malignancy Review with dietician Enteral/parenteral nutrition

IncontinenceIncontinence

Assess frequency and stool consistency If lose: trial of Loperamide Testing: EUS, anorectal motility,

defecography Biofeedback Low fiber diet Neuromodulation Sphincter augmentation

ConstipationConstipation

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