1. Shad Johnson MPAS, PA-C Southeast Idaho Gastroenterology

2. Review Epidemiology and Risk Factors Understand symptoms of inflammatory bowel disease (IBD) and be able to discuss the differential diagnosis of inflammatory diarrhea Be able to recognize endoscopic and histologic features of IBD Appreciate differences between ulcerative colitis and Crohn’s disease Become familiar with therapeutic options for IBD

3. Epidemiology Incidence: ~10: 100,000 Prevalence: ~200: 100,000 Greater in U.S. and Europe (especially in Northern latitudes) More common in Jewish and Caucasian populations Urbanization and industrialization Risk Factors Age (15-40 years)—bimodal distribution in UC Family History (10-25% have a FH in a 1 st degree relative) Smoking (Crohn’s disease) Diet, obesity, infection, medication???

4. Dysregulation of the immune system Presence of inflammatory cells histologically Presence of autoantibodies in the serum Abnormal permeability of the epithelium Mice with altered epithelium develop spontaneous colitis Role of microflora Interactions between the immune system and intestinal microbes Genetic susceptibility These are idiopathic diseases!

5. Diarrhea Pay attention to profuse diarrhea, nocturnal stooling, and fecal incontinence Fecal urgency Rectal bleeding Abdominal pain (intermittent) Weight loss Fatigue, malaise, fever

6. Tachycardia and hypotension (if dehydrated) Decreased weight Abdominal tenderness to palpation RLQ pain in Crohn’s disease Physical exam may be normal or very nonspecific Perianal disease (abscess or fistula in Crohn’s disease) Extraintestinal manifestations

8. Uveitis Inflammatory arthritis Skin disorders Erythema nodosum Pyoderma gangrenosum Primary Sclerosing Cholangitis (PSC)

9. Erythema NodosumPyoderma Gangrenosum PSC

10. Occult blood positive Iron deficiency anemia B12 deficiency (terminal ileal Crohn’s disease) Elevated SED rate or CRP Leukocytosis Fecal leukocytes Elevated stool lactoferrin or calprotectin Be sure to rule out bacterial infection in suspected or confirmed inflammatory diarrhea

11. Bacterial Infection Clostridium Dificile (C. diff.) E. coli Salmonella, Shigella, Campylobacter Ischemic colitis Acute in onset Pain is the presenting symptom Radiation colitis Solitary rectal ulcer syndrome Medication-associated colitis (NSAIDs!!!)

12. Ulcerative Colitis Erythema Congestion and edema Friability Loss of vascular pattern Confluent inflammation (usually starting distally in the rectum) Crohn’s Disease Ulceration Skip lesions (rectal sparing) Cobblestoning (nodularity) Typically terminal ileum and proximal colon (can be found anywhere from the mouth to anus) Inflammation from Crohn’s disease is transmural Indeterminate Colitis

15. Ulcerative Colitis Crypt Abscess Crypt distortion Glandular dropout (lack of goblet cells) “chronic colitis” Crohn’s Disease Non-caseating granuloma (rarely seen) “chronic colitis” or “chronic ileitis”

16. Colonoscopy Computer Tomography Thickening of bowel Small bowel follow through Capsule Endoscopy Does not allow for biopsy Risk of entrapment if Crohn’s disease related stenosis

18. Ulcerative Colitis Toxic Megacolon Avoid antidiarrheals in inflammatory diarrhea Adenocarcinoma Controversy about when and how often to perform surveillance colonoscopy Crohn’s Disease Abscess Fistula Bowel obstruction Spontaneous perforation

19. 5-aminosalicylates Corticosteroids prednisone Solu-Medrol Uceris or Entocort (budesonide) hydrocortisone Immunomodulators Azathioprine/6MP Methotrexate Biologics Remicade Humira Cimzia Simponi Entyvio/Tysabri

20. Asacol®, Pentasa®, Lialda®, Apriso®, (mesalamine) pH dependent release Very little systemic absorption (favorable side effect profile) Best used for mild to moderate ulcerative colitis $$$ balsalazide (Colazal®) Prodrug cleaved by colonic bacteria Rowasa® enemas/Canasa® suppositories For distal disease Sulfasalazine Can decrease the absorption of folate More adverse effects (nausea, rash, fatigue) Inexpensive May help with inflammatory arthritis

21. prednisone/IV Solu-Medrol® Numerous adverse effects Short term: irritability, insomnia, weight gain, moon face Long term: cataracts, osteoporosis, elevated blood glucose Inexpensive Best for short term control of moderate to severe disease Uceris®/ Entocort® (budesonide) Uceris® pH of 8—ulcerative colitis (Uceris ® foam is available for proctosigmoiditis) Entocort® pH of 7—terminal ileal Crohn’s disease Extensive first pass metabolism by the liver (fewer systemic side effects) hydrocortisone suppositories/enemas For short term treatment of distal disease

22. azathioprine/mercaptopurine* Adverse effects Bone marrow suppression (depending on hepatic metabolism) Secondary infection Pancreatitis Elevated liver chemistries Hepatosplenic T cell lymphoma Fetal defects in animal studies (none in limited human studies) Requires frequent monitoring of CBC and liver chemistries Slow to take effect methotrexate* Adverse effects: congenital abnormalities, hepatotoxicity, interstitial pneumonitis, stomatitis, secondary infection, etc. *not FDA approved

23. TNF inhibitors (monoclonal Abs) Remicade®, Humira®, Cimzia® (Crohn’s only), Simponi® (UC only) Administered IV or SQ Adverse effects: Allergic reaction Secondary infection (must rule out latent TB and Hep B) Hepatosplenic T-cell lymphoma Demyelinating disease Yearly skin exams and immunizations (yearly flu, pneumococcal conjugate) α4 integrin inhibitors Tysabri® (Crohn’s only) Binds to α4β1 and α4β7 Black box warning for progressive multifocal leukoencephalopathy Entyvio® Binds to α4β7 alone (gut specific) For moderate to severe IBD, $$$$

24. Complete colectomy for ulcerative colitis Curative, but a last resort Beware indeterminate colitis! Segmental resection for Crohn’s disease Surgical management of fistulae or abscess

25. Step up therapy vs. top down therapy Antibiotics (use is somewhat controversial) Probiotics Vitamin supplementation Diet Lots of controversy Elimination diets? Lactose avoidance? Decreased fiber during flare of disease Goals of treatment Reduce or eliminate symptoms (improve quality of life) Prevent surgery Mucosal healing (lower risk of malignancy)

26. www.uptodate.com Sleisenger & Fordtran’s Gastrointestinal and Liver Disease, 7 th Edition, Feldman, Friedman, Sleisenger Mayo Clinic Gastroenterology and Hepatology Board Review, Hause www.ccfa.org