Approach to the Patient with Chronic Diarrhea and A Few Interesting IBS Cases

1. Approach to the Patient with Chronic Diarrhea and A Few Interesting IBS Cases Christina Surawicz, MD, MACG Professor of Medicine University of Washington McCall, Idaho January 2014

2. Alarm Symptoms • Weight loss “Beware the diet that works” • Blood in stool • Nocturnal diarrhea • Anemia

3. Diagnostic Approach to Chronic Diarrhea • Bloody – gross or occult • Fatty • Watery

4. Diarrhea with Blood → Colitis • Infection • IBD • Ischemia • Some drugs • NSAIDS • Isotretinoin • SCAD – Segmental Colitis Associated with Diverticular Disease • Radiation • Diversion colitis

5. Work – upChronic Bloody Diarrhea Stool culture for enteric pathogens, Yersinia, Aeromonas, Plesiomonas, C. difficile Stool O + P – Ameba, Trichuris Stool WBC, lactoferrin--nonspecific Colonoscopy/biopsy= helpful to distinguish IBD vs. infection

6. Colonoscopic Appearances Infections – often patchy Ulcerative Colitis – typical Crohn’s - segmental Ischemia – Rectal sparing Location, location, location Can be multifocal

7. Chronic Bloody Diarrhea • History + exam • Stool cultures, O + P, in some • Colonoscopy and colorectal biopsy - mainstay of diagnosis

8. Colonoscopy in Any Diarrhea Work Up • Age > 50 years old • Family history colon cancer at an early age (<60)

9. Infection Uncommon Stool CultureO + P • Salmonella• Ameba • Campylobacter • Trichuris • Yersinia • Aeromonas • Plesiomonas • C. difficile

10. Chronic Bloody Diarrhea: Work – up • Colonoscopy/biopsy - mainstays of diagnosis • Helpful to distinguish IBD vs. infection

11. Colonic Biopsy can Diagnose Specific Infections • Pseudomembranes C. difficile STEC • Viral Inclusions CMV HSV • Parasites Ameba Shistosomiasis • Tuberculosis

12. Diagnostic Approach to Chronic Diarrhea • Bloody – gross or occult • Fatty • Watery

13. Steatorrhea – Clinical Clues Dietary history – Intake compared to others Weight loss Stools – Not always diarrhea, may be bulky Hard to flush Oily droplets floating on toilet water (unhydrolyzed TG)

14. Steatorrhea – Vitamin Malabsorption Fat soluble vitamins D A K E Osteomalacia D Night blindness A Easy bruisability K Vitamin E

15. Fecal Fat Analysis Qualitative – Can be subjective Variable lab personnel Nl is less than 20 drops/ hpf Quantitative – 24 hr on 100 gm fat diet Weight < 200 – 300 gm Fat < 7 gm / 24 hr

16. Stool Fat Tests – Caveats 1. High carbohydrate diet – increases stool weight to 300 – 400 gms 2. Voluminous stools will raise fat excretion (up to 14 g/24 hour) 3. Correct for fat intake - low fat diets 4. False positives; Olestra, Brazil nuts

17. Steatorrhea MucosalLuminal Celiac sprue • Pancreatic Insufficiency Crohn’s• Bile salt deficiency Ileitis/ • Bacterial overgrowth Ilealresection • SIBO Short bowel syndrome

18. Celiac Disease – Not Just Diarrhea  Weight Loss  Infertility  Abdominal distension  Recurrent fetal loss  Abnormal LFTs – enzymes  Microscopic colitis  Iron deficiency

19. Celiac Diagnosis • Antibody tests - On gluten * IgA tTGand Serum IgA (2-3 % of sprue patients are IgA deficient) - EmA antibody – second line - Not antigliadinab (unless deaminated) • Small bowel biopsy + response to therapy • High suspicion – biopsy even if serology negative • Genotype-HLADQ2, DQ8 - Rules out if negative Rubio-Tapia et al. Guidelines, AM J Gastroentrol, Feb 2013

20. You have a patient on a gluten free diet who is convinced she has celiac disease. She does not want a gluten challenge. Which of the following applies to her?

21. A. Order HLA DQ2,8 – if positive it will confirm she has celiac disease • B. Order HLA DQ2,8- if negative it will rule out celiac disease • C. Order serology as it will help even on a gluten free diet • D. Screen her siblings for celiac disease

22. Answer B • HLA DQ2,8- if negative it does rule out celiac but does not everyone who is positive has celiac disease • The serology will be negative if on a true gluten free diet, and screening siblings is only helpful if you have a true case

23. Gluten and IBS • 34 patients with IBS Nonceliac • Double blind RCT – 6 weeks Gluten free muffins & bread vs. Placebo • Results Symptoms better Gluten free group 68% Placebo 40% Biesierkierski et al, Am J Gastroenterol 2011; 106:508-14

24. Symptoms Worse within 1 Week • Overall • Bloating • Pain • Fatigue • Satisfaction with stool consistency

25. GFD in IBS-D Non celiac patients RCT of GFD Reduced stool frequency (Vazquez-Roque et al, Gastroenterol. 2013)

26. Bottom Line • Non-celiac gluten Sensitivity probably exists • We need to know more

27. Malabsorption - think about… • Post gastric surgery or anti-reflux surgery - history • Chronic mesenteric ischemia - history • Drugs, including HAART - history • Radiation - history

28. Malabsorption - think about… • Parasites – stool tests • Giardia • Cryptosporidia • Cyclospora

29. Next Steps in Evaluation • Radiologic imaging- cross sectional CT Abdomen and pelvis and CT Enterography • Capsule study • Enteroscopyor DBE for biopsy

30. Uncommon Small Intestinal Diseases • Collagenous sprue • Whipple’s disease • Eosinophilic enteritis • Lymphoma • Amyloid

31. Luminal - Pancreatic Insufficiency • Direct function test: secretin test, research tool • Indirect tests • Serum amylase/lipase • Serum trypsin • Fecal chymotrypsin • Fecal elastase All have poor sensitivity/specificity

32. Fecal Elastase 1 • 6% of pancreatic enzymes • Abnormal: < 200 μg/gram stool • But abnormal in many other conditions • Celiac disease • IBD • IBS • HIV • Diabetes (Leeds et al, Nature Rev Gastro Hep 2011)

33. Pancreatic Insufficiency • Empiric trial of enzymes – reasonable • High dose – monitor wt gain or fecal fat • If respond, image pancreas • Another option is to rule out mucosal disease first

34. Bile Acid Diarrhea • Bile acids cause colonic salt and water secretion and increased colon motility • Secondary bile acid malabsorption Ileal resection or disease (Crohn’s) < 100 cm – watery > 100 cm - malabsorption • Primary bile acid malabsorption? (misnomer)

35. Luminal - Small Intestinal Bacterial Overgrowth (SIBO) • Structural causes • SI diverticulosis • Stricture • Surgical diversions • Dysmotility • Scleroderma • Intestinal pseudo-obstruction • Others ? • Diabetes • IBS • Acid suppression

36. SIBO Diagnosis • Clue: high folate, low B12 Bacteria produce/consume • SB aspirate • Breath tests – not great • Therapeutic trial – probably best Antibiotics

37. Watery Diarrhea • If Not Bloody and • Not fatty • It’s Watery . . . All the rest

38. Watery Diarrhea –History • Surgery – gall bladder, stomach, intestine • Family history • Celiac • IBD • Sexual history • Infections • HIV • Travel History – Traveler’s diarrhea • High risk areas

39. Watery Diarrhea – History • Medications - 7% of all drug side effects especially “new” ones • Antimicrobials • PPIs (lansoprazole) • NSAIDS, 5-ASAs • SSRIs • Psycholeptics • Allopurinol • Metformin • Angiotensin ARBs

40. Watery Diarrhea - Diet • Alcohol • Dairy • Nutritional supplements, herbals, OTC drugs • Herbals • Fructose and sorbitol – osmotic diarrhea

41. Watery Diarrhea -Diabetes • Visceral autonomic neuropathy - Often nocturnal • Bacterial overgrowth • Celiac disease • Pancreatic insufficiency • Unabsorbed CHO (Sugarless sweets)

42. Watery Diarrhea - Post Cholecystectomy Diarrhea • Incidence 20% • Can be delayed • Rarely severe • Rx – bile acid binders

43. Watery Diarrhea – Initial Labs • CBC • Chemistries (total protein, albumin) • Thyroid tests • Celiac serology • ESR/CRP • Stool FOBT

44. Watery Diarrhea - Infections • Ameba • Giardia • Cryptosporidia • Cyclospora • Blastocystis hominis (?) • Candida (?) • Yersinia • Salmonella • Aeromonas • Plesiomonas • C. difficile (recurrent) Stool exam low yield

45. Watery Diarrhea - Mucosal Disease • Colonoscopy + biopsy • Crohn’s • Microscopic colitis • Colon cancer • Large rectal villous adenoma • Small bowel diseases - EGD + duodenal biopsy • Previously Mentioned

46. Chronic Diarrhea – Yield of Biopsy at Colonoscopy Series vary: 10—20% Most commonly: IBD Microscopic Colitis Pseudomelanosis coli Spirochetosis

47. Pseudomelanosis coli • Surreptitious laxatives • Factitious Diarrhea

48. Microscopic Colitis—Collagenous and Lymphocytic Typically: Chronic watery diarrhea Colon bx diagnostic Other w/ u – negative Histology: increased lamina propria lymphocytes, intraepithelial lymphocytes, increased collagen band in CC, not LC

49. Collagenous Colitis

50. Lymphocytic Colitis