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Gastrointestinal
 Manifestations of
Systemic Sclerosis
 Harald Schoeppner, MD PhD
Legacy Health Gastroenterology
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)
Paul Klee (1879-1949)
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
Definitions
   Gastrointestinal
    (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 tract




                 New theory
                 Auto antibodies to
                  myenteric neurons
                 M3R (anti-
                  muscarinic 3 Ach R)
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
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
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
Mouth & Oropharynx
   Sicca symptoms (Sjogren’s)
       Poor salivary function
       Difficulty swallowing
       Tooth cavities
   Mouth opening
   Minimal tongue involvement
Esophagus
   Most commonly affected
    organ
   Symptoms:
       Heartburn
       Regurgitation
       Dysphagia
       Chest pain
       Atypical reflux symptoms
            Hoarseness
            Cough
            ILD (interstitial lung disease)
            Breathing problems (apnea)
Esophagus

   Poor lubrication
   Poor motility
   Absent sphincter
    barrier




     Normal               Systemic sclerosis
Esophagus
   Complexity of GERD
   Sequelae:
       Stricture
       Ulcers
       Barrett’s metaplasia
       Esophageal cancer
       Diverticula
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 - 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
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
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)
   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
Opportunities to intervene
                    Lifestyle
                    Medication

                    Screening

                    Surveillance


                    Ablation

                    Surgery
Stomach

   Roles:
       Reservoir
       Begins digestion
       Produces acid
       Allows absorption of iron
        and B12
       Defense against ingested
        germs
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
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)
   Goals:
     Improve symptoms
     Improve nutritional status

   Methods:
     Dietary changes
     Medications

     ?Pacemaker
Stomach (treatment)
   Gastroparesis Rx (early)
       FDA Approved
            Metoclopramide (reglan)

            Erythromycin
       Withdrawn from market
            Cisapride
       Not reviewed
            Domperidone
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
Stomach GAVE treatment
   APC (Argon Plasma
    Coagulation) or other
   Cryotherapy
   Transfusions
   Iron replacements

   Cyclophosphamide
       Several case reports
       Indefinite length?
Small Bowel
   Anatomy
       22-23 feet
       3 regions
   Roles
       Digestion of
        carbohydrates and
        protein and some fat.
       Absorption of all
        nutrients
       Absorption of water
Small Bowel
   Migrating Motor Complex
   120 minute cycle
   4 phases
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
Small Bowel
   Symptoms / pathology mostly due to
    impaired motility
                              Slow transit



     Bacterial Overgrowth + Increased ‘fermentation’



        Bile acid breakdown      Excess Gas


              Diarrhea            Bloating
Normal

         Loss of MMC;
         Decreased
         amplitudes
Bacterial Overgrowth
   Occurs 20% - 55% of patients with PSS
   Testing
       Aspirates and culture
       Hydrogen breath test
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
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
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 support
   Dietician
   Enteral nutrition
       Jejunostomy
   Parenteral
    nutrition
       TPN
Colon

   3 Feet long

   Functions:
     Absorb water
     Concentrate feces

     Excrete
Colon
   SSc symptoms:
     Diarrhea
     Constipation

     Incontinence



   Mostly due to motility abnormalities of the
    colon and impaired anal sphincter
Colon
 Measuring transit time




Day 4                     Day 7
Colon
   Intestinal ‘pseudo-
    obstruction’ (IPO)

       Often involves small
        bowel
       Signifies advanced stage
       Avoid surgery (results in
        prolonged ileus)
How about colonoscopy?
   Colon cancer
    screening tool
   Investigate for
    intestinal bleeding
   Investigate for
    anemia
   Does nothing for
    constipation
Anal Sphincter
   Lax internal sphincter
    (neuropathic)
   Fibrotic sphincter
    (myopathic)

   Leads to incontinence
    and interfering with
    normal defecation.
Anal Sphincter

Ano-rectal manometry




                       New options
                       1.) Sacral stimulation
                       2.) Sphincter reconstruction
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)
   Diarrhea
       Investigate cause !
          ? Overflow diarrhea
          Infections (C. diff)

          Bacterial overgrowth

          Post-obstructive

          Malabsorption

          Celiac disease

          Bile-acid diarrhea
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
Thank you!
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
Distention, abdominal pain
   Exclude obstruction
   Consider gastroparesis (GES)
   Review medications
   ? DM
   Empiric trial of antibiotics for SIBO
   Dietician referral
   FODMAP
   Venting gastrostomy
Weight loss, nutrition
   Assess BMI
   Rule out depression
   Rule out malignancy
   Review with dietician
   Enteral/parenteral nutrition
Incontinence
   Assess frequency and stool consistency
   If lose: trial of Loperamide
   Testing: EUS, anorectal motility,
    defecography
   Biofeedback
   Low fiber diet
   Neuromodulation
   Sphincter augmentation
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

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1 gastrointestinal manifestations of systemic sclerosis

  • 1. Gastrointestinal Manifestations of Systemic Sclerosis Harald Schoeppner, MD PhD Legacy Health Gastroenterology
  • 2.
  • 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)
  • 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
  • 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

Editor's Notes

  1. 1.) behind every disease there is a patient 2.) hope: most productive period of his life 3.) one cannot be defined by the disease
  2. We T
  3. Dr. Lundell and colleagues conducted a study of patients who were diagnosed with reflux disease. Their symptoms were relieved and erosive esophagitis (if present) was healed with a course of PPI therapy. 1 Six months following treatment, symptomatic relapse occurred in an average of 83% of patients regardless of the status of their esophageal mucosa at the time of relapse. It is also important to note that the majority of patients who relapse do so within three months of stopping therapy. 2 References: 1. Lundell LR, et al. Gut . 1999;45:172-180. 2. Vakil NB, et al. Aliment.Pharmacol Ther. 2001;15:927-935.
  4. Most of the threat in SSc are relaed to smoking, lung cancer
  5. Lifestyle: prevent obesity, avoid tobacco exposure. Medication: PPI, NSAIDS
  6. 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.
  7. Initial treatment: 14 days course of antibiotics, if relapse then 1 st 10 days every month, then add prokinetics (reglan avoid, Dom 10-20 Q6, Emycin at night 200mg at night, Octreotide 50-100yg qhs, long acting 2omg q month, octreotide + emcyin)
  8. FODMAP