Inflammatory Bowel Disease Digestive Specialists, Inc. 999 Brubaker Drive • Kettering, OH 45429 Anjali Morey, M.D., Ph.D.

Which would be considered a high risk Crohns Disease patient? Highly Symptomatic Advanced age of disease onset Prior Surgical resection Disease limited to one section of the colon 10

Which vaccine should not be given to an IBD patient on immunosuppressive therapy? Influenza Pneumonia Hep B Vaccine Gardasil Shingles

Objectives Review primary care workup for chronic diarrhea when IBD is suspected Report on current treatment recommendations for Ulcerative Colitis and Crohn’s Disease Discuss clinical follow-up of patients on immunosuppressive therapy Discuss lifestyle changes that can help maintain remission

http://ibd. cochrane. org/sites/ibd. cochrane. org/files/uploads/IBD2 http://ibd.cochrane.org/sites/ibd.cochrane.org/files/uploads/IBD2.jpg IBD Overview

Overview of Crohn’s Disease (CD) Any segment of GI tract (mouth-anus) Rectal Sparing Discontinuous “skip lesions” Perianal Disease skin tags fissures fistulae Transmural inflammation stricture fistula perforation abscess http://www.nature.com/nature/journal/v448/n7152/images/nature06005-f1.2.jpg Normal Crohn’s Disease

Overview of Crohn’s Disease (CD) Pathologic Changes Epithelioid non-caseating granulomas Chronic inflammatory infiltrate Crypt architectural distortion http://www.nature.com/nature/journal/v448/n7152/images/nature06005-f1.2.jpg

Overview of Ulcerative Colitis (UC) Confined to colon Begins in rectum and extends proximally in a continuous fashion Confined to mucosa and submucosa http://www.nature.com/nature/journal/v448/n7152/images/nature06005-f1.2.jpg Normal Ulcerative Colitis

Overview of Ulcerative Colitis (UC) Pathologic changes Cryptitis / crypt abscesses Crypt architectural distortion Lamina propria expansion with acute and chronic inflammatory cells http://www.nature.com/nature/journal/v448/n7152/images/nature06005-f1.2.jpg

Patients often present with diarrhea > 2 weeks Primary Care Patients often present with diarrhea > 2 weeks

CD: Signs & Symptoms Abdominal Pain GI Bleeding Diarrhea Weight Loss Fatigue Fever Joint Pain Skin Rashes

CD: Staging Workup If abdominal symptoms present Initial Steps Labs Colonoscopy TI exam & biopsy If iron deficiency anemia exists and colonoscopy negative EGD If EGD negative in the setting of iron deficiency anemia Small Bowel Capsule Endoscopy Consider imaging prior if any suspicion of narrowing / stricture If abdominal symptoms present CTE / MRE to assess small bowel

CD: Initial Labs CBC CRP / ESR CMP TSH Strongyloides Antibody Consider Prometheus Testing Consider Absorption Labs

CD: Absorption Labs Iron Studies / Ferritin B-12 / Folic Acid Vitamin D Vitamin D Target Range (for IBD Patients):  40-60 ng/mL Vitamin A Zinc

CD: Stool Studies to Rule Out Infection / Inflammation Stool Ova and Parasites Stool for C. difficile toxin Stool giardia antigen Stool for Cryptosporidium Stool culture and sensitivity Fecal Calprotectin

CD: Imaging CT Enterography / MR Enterography Cross-sectional imaging technology Assess for small intestine disease activity Assess for complications Abscess Fistula obstruction < 30 y/o, MRE preferred to avoid radiation exposure http://www.radiology.vcu.edu/images/photos/patients/photo1.jpg http://www.radiology.vcu.edu/patients/procedures/enterography.html

CD: High Risk Patients Surgical Resection Fistula / Stricture Abscess Early onset of disease Deep ulceration Perianal involvement and / or severe rectal disease Extensive anatomic involvement

UC: Signs & Symptoms Bloody Diarrhea Tenesmus Urgency Abdominal Pain Fever  Weight Loss Joint Pain Skin Rash Fatigue

UC: Labs CBC CMP CRP / ESR Fecal Calprotectin Stool studies to rule out infection

UC: Imaging Case-by-case based on clinical presentation and evaluation Can be used to assess disease extent and severity in severe flare CT of toxic megacolon or significant colitis http://img.medscapestatic.com/pi/meds/ckb/05/18205tn.jpg http://img.medscapestatic.com/pi/meds/ckb/02/18202tn.jpg

Mayo Scoring System for Assessment of UC Activity Used for initial evaluation and monitoring treatment response Scores range from 0 to 12 Higher scores indicate more severe disease ≤ 2 = Clinical remission 3-4 = Mild activity 6-10 = Moderate activity 11-12 = Severe activity

Mayo Scoring System for Assessment of UC Activity Variable 0 Points 1 Points 2 Points 3 Points Bowel movement (BM) frequency Normal 1-2 BM > normal 3-4 BM > normal >5 BM > normal Rectal bleeding None Streaks on stool < 50% BM’s Obvious fresh blood with most BM’s BM’s with fresh blood Endoscopy Mild Erythema,  vascularity, Mild friability Marked erythema, Lack vascular pattern, Friability, Erosions Severe spontaneous bleeding, Ulceration Physician Global Assessment (PGA) Mild Moderate Severe

UC: Colonoscopy Used to Assess Disease Severity Normal / Inactive Disease No friability or granularity Intact vascular pattern Mild Disease Erythema Decreased vascular pattern Mild Friability Moderate Disease Marked erythema Absent vascular pattern Friability Erosions Severe Disease Moderate signs plus: Spontaneous bleeding Ulceration Mayo Score = 0 Mayo Score = 1 Mayo Score = 2 Mayo Score = 3 Double check score/subscore Full Mayo score includes bowel movement frequency, rectal bleeding, endoscopy, and physician global assessment Mayo Endoscopic Subscore

IBD Therapies

Goals of IBD Therapy Achieve mucosal healing and induce remission Maintain steroid-free remission Prevent / treat complications of disease Avoid short and long term toxicity of therapy Enhance quality of life 5-ASA Products and Corticosteroids

IBD Therapies Aminosalicylates (5-ASA) Corticosteroids Immunomodulators (6 MP / AZA / MTX) Biologics Anti-TNF Anti-Integrin Anti IL-12 / IL-23

Azathioprine/6 MP Pharmacology 6 TG (active metabolite) 235-400 Therapeutic range > 400 Higher risk for bone marrow suppression 6 MMP > 5700 Higher risk for hepatotoxicity

Biologic therapy for IBD Certolizumab - Cimzia Adalimumab - Humira Golimumab -Simponi Infliximab - Remicade Anti-Integrin antibody: Natalizumab -Tysabri (PML –Progressive Multifocal Leucoencephalopathy) Anti-Integrin antibody: Vedolizumab - Entyvio Anti IL-12 / IL-23 antibody: Ustekinumab – Stelara - moderate to severe CD.

Crohn’s Disease Therapies Disease Severity at Presentation Biologics + Thiopurine + Corticosteroid Severe Moderate Mild Biologics Biologics or Thiopurine + Corticosteroid Biologics or Thiopurine Change How Biologics are Positioned for UC Pentasa Pentasa Induction Maintenance Therapy is modified according to severity at presentation or failure at prior step

Sequential Therapies for UC Disease Severity at Presentation Colectomy Biologics + Thiopurine + Corticosteroid Severe Moderate Mild Biologics Aminosalicylate or Thiopurine + Corticosteroid Aminosalicylate or Thiopurine Change How Biologics are Positioned for UC Aminosalicylate Aminosalicylate Induction Maintenance Therapy is stepped up according to severity at presentation or failure at prior step

Guidelines for Initiating and Follow-up of Immunosuppressive Therapy

Labs Prior to Start of Immunosuppressive Therapy QuantiFERON / Chest X-ray (TB Testing) Acute Hepatitis Panel https://www.researchgate.net/figure/233909633_fig1_Initial-chest-X-ray-showing-old-scar-of-pulmonary-tuberculosis-without-infiltrative http://www.biomerieux-diagnostics.com/vidas-hepatitis-panel – Hep B http://www.ssi.dk/~/media/Indhold/DK%20-%20dansk/Produkter%20og%20ydelser/Diagnostica/Pictures/Product%20photos/Immunoassays/Quantiferon/kit.ashx?mw=440

For Patients on Immunosuppressive Therapy Annual head to toe dermatology skin exam Sun precautions Annual Pap smear Annual TB Testing (Quantiferon / chest x-ray) Serial labs (CBC with Diff and Hepatic Function Panel) if on Imuran, 6MP or MTX

Lifestyle Modifications

Mediterranean Diet Primarily plant-based foods (fruits and vegetables, whole grains, legumes and nuts) Replace butter with healthier fats (olive oil) Herbs and spices instead of salt Limit red meat (beef and pork) to no more than a few times a month Fish, chicken, and turkey at least twice a week Red wine in moderation (optional)

Other Dietary Considerations Eat smaller, more frequent meals Drink plenty of fluids Consider multivitamin once daily Talk to a dietitian Probiotics – Kefir once daily Dairy, gluten, excessive caffeine / carbonation can exacerbate symptoms http://www.mayoclinic.org/diseases-conditions/inflammatory-bowel-disease/basics/lifestyle-home-remedies/con-20034908

Lifestyle Changes Stress Management Exercise (20 minutes / day) Relaxation and breathing exercises (yoga and meditation) Smoking Cessation / avoid second hand smoke exposure Avoid unnecessary antibiotic exposure Utilize Patient Education Resources (CCFA)

Final Thoughts Early diagnosis / avoid treatment delays Treating IBD patients is a collaborative approach between primary care and GI and other specialists Increase patient satisfaction Tell a story here?