How to manage your IBD patient: Tips for diagnosis and care

Transcription

1 How to manage your patient: Tips for diagnosis and care Oriana M. Damas, M.D. Assistant Prof Clinical Medicine Division of Gastroenterology No relevant disclosures Case Presentation: A.R. 32 yo woman with ileal crohn s disease for 5 years. She is followed by a gastroenterologist who has started her on adalimumab for the last year. Her symptoms are controlled and laboratory markers indicate no active inflammation. She wants to discuss vaccinations. You can tell her: A. She can get all the age appropriate vaccinations for her age and comorbidities. B. She can get all the age appropriate vaccinations for her age and comorbidities except live vaccines. C. She should should not get any vaccines as they are contraindicated because of adalimumab. Objectives Understand inflammatory bowel disease () is a growing problem and its pathogenesis Discuss phenotype and clinical presentation Discuss management of patients with active symptoms including tests to order and dietary management Health maintenance in the patient and in pregnancy Inflammatory Bowel Diseases Ulcerative Colitis Crohn s Disease Confined to the colon Any portion of the GI tract The Spectrum of UC CD Frequency of Involvement Most Least Indeterminate colitis (-U) is NOT IBS!!! 1

2 Overview of Pathogenesis Inflammatory Bowel Disease Etiologic Contributions Bacterial Products Chronic Inflammation = Genetic Predisposition Mucosal Adaptive/Innate Immune System Normal Gut Mildly Inflamed Moderately Acutely Inflamed Normal Gut Environmental Triggers (luminal bacteria, infection) Evidence for a Genetic Cause of NOD2 Variant associated with fibrostenotic disease Racial and ethnic risks of Ashkenazi Jews Multiple family members with 10-15% of patients will have a family member with runs in generations of some families Fibrostenosing dz No fibrostenosing dz Abreu MT et al. Gastroenterology 2002 Probability of Remaining Surgery Free According to NOD2/CARD15 Gene Status 1 >200 risk loci and counting Cumulative Survival No variants NOD2/CARD15 gene variants p value = Months NOD2 PTPN22 CD genes 30 CD specifi c loci 110 loci Common pathways: Leprosy Mycobacterial susceptibility Other immunemediated disease UC genes 23 UC specifi c loci MHC Genes in common Jostins, L. et al. Nature 491, (01 November 2012) Alvarez-Lobos, M., et. Al. Ann Surg 2005; 242: CD10009-CD July 9,

3 A summation of events culminating in intestinal inflammation Environmental Triggers Infections Antibiotics Colonization Mechanisms Environmental Genetic with intestinal of polymorphisms genetic Factors flora modification (mother/diet) Diet = Antibiotics Mucosal disruption (NSAIDs) Pathogens Stressors (stress, smoking) NSAIDs Diet (?) Intestinal inflammation DNA methylation microrna Stress (?) Smoking Smoking in : A Tale of Two Diseases Inflammatory Bowel Disease Geographic Distribution Crohn s disease Two-fold risk in current smokers Smokers are less responsive to treatment Smokers are more likely to develop recurrence of disease after surgery Ulcerative Colitis Smoking can protect against UC Ex-smokers are more likely to develop UC High Incidence Moderate Incidence Unknown Ulcerative Colitis and Crohn s Disease same distribution Bimodal distribution of age of onset Why is it important to know about? Young age of onset Chronic inflammation of the bowel Remission and relapses Bowel surgery may be necessary Increased risk of depression or anxiety Age (yrs) Scope of the disorder (United States) 700,000 physician visits per year 100,000 hospitalizations per year Long-term outlook Chronic, lifelong disease without medical cures Surgery for 50% to 80% of Crohn s disease patients Surgery for 20% of ulcerative colitis patients Most patients live normal, productive lives! 3

4 Initial Workup Blood Surrogate markers of inflammation Serologic markers Stool Cdiff and fecal calprotectin Endoscopy WCE (be careful in crohn s) Radiology Ulcerative Colitis Ulcerative Colitis Proctitis Left-sided Colitis Pancolitis The small intestine is not involved Symptoms of Ulcerative Colitis Depend on Extent and Severity of Inflammation Rectal bleeding Tenesmus Diarrhea Abdominal cramping Extraintestinal symptoms Joint pain/swelling Eye inflammation Skin lesions Normal Colon Ulcerative Colitis Endoscopic Appearance Mild-moderate UC Severe UC 4

5 Histologic Features of Ulcerative Colitis Ulcerative Colitis - Pathology Classic findings: acute on chronic inflammation OR Acute inflammation in the setting of architectural distortion Mucosal inflammation Microulcerations Crypt abscesses Branched glands Decreased # of mucosal glands Common Symptoms of Crohn s Disease Crohn s Disease Diarrhea Abdominal pain and tenderness Loss of appetite and weight Fever Fatigue Rectal bleeding and anal ulcers Stunted growth in children Crohn s Disease Endoscopic Appearance Discrete Ulcer Cobblestoning Stricture (Narrowing) 5

6 Perianal Lesions in Crohn s Histologic Features of Crohn s Disease Skin tag 37% Hemorrhoids 7% Fissure 19% Anal ulcer 12% Low fistula 20% High fistula 6% Rectovaginal fistula 3% Perianal abscess 16% Anorectal stricture 9% Cancer Cumulative Incidence of Perianal Fistula Transmural inflammation Granulomas (~30%) Fissuring Ulceration Submucosal fibrosis Schwartz et al. Gastroenterology 2002 Extra-intestinal Manifestations of Fissuring Transmural Skin Eye Bones and Joints Kidney Liver/Gall Bladder Phenotype in Primary Sclerosing Cholangitis (PSC) patients PSC 50-80% 2-7% PSC EIMs should prompt questioning for GI sxs All patients with PSC need to have a colonoscopy, irrespective of GI symptoms Picture obtained from Norwegian PSC Research Center. De Vries A et al. Distinctive phenotype in psc. World journal of gastro

7 Erythema Nodosum Pyoderma Gangrenosum Treatment Menu of Options for Therapy Therapeutic Pyramid for Supportive Agents Antibiotics Aminosalicylates (5-ASAs) Corticosteroids Immune-modulators Biologics Anti-TNFs (e.g. infliximab) Anti-integrins (e.g. vedolizumab) Interleukin inhibitors (UST) Many more to come (e.g. mongersen) Induction of Remission/ Active Disease Tofacitinib Vedolizumab Tacrolimus Cyclosporine Ustekinumab Anti-TNF Corticosteroids 5-ASA Maintenance of Remission Tofacitinib Vedolizumab Anti-TNF Ustekinumab Methotrexate 6-MP/AZA 5-ASA 7

8 Immune-Modulators Azathioprine & 6-MP Monoclonal Antibodies, Fusion Proteins and Fc-Free Fab Fragments Against TNF Long-term (maintenance) treatments for UC or CD can treat fistulas in CD over long-term Primarily for patients unable to get off steroids Requires continuous monitoring of blood counts Cell lines Liver chemistries Take several weeks to take effect Chimeric monoclonal antibody Fc IgG1 Human monoclonal antibody Human recombinant receptor/fc fusion protein Humanized Fc-Free Fab fragment Infliximab Adalimumab Etanercept Certolizumab pegol Natural History of CD Behavior Top-down vs Step-up therapy Cumulative probability, % Penetrating Inflammatory Stricturing Patients at risk: Months n= % 18% Early combined immunosuppression (topdown) vs conventional management (step-up) Patients had never received steroids, immunomodulators, or biologics 133 patients May Jan 2004 Outcome was remission without steroids or surgery D'Haen's et al. Lancet 2008; 371: Cosnes J, et al. Inflamm Bowel Dis. 2002;8: Cosnes et al. Inflam Bowel Dis CD10009-CD July 9, 2010 Step-up vs Top-down? Immunogenicity Remission Rates Week 26 60% combined 36% conventional Week 52 62% combined 42% conventional D'Haens et al, Lancet 2008; 371: Human anti-chimeric antibodies associated with: Shorter duration of response Higher rate of infusion reaction - Infliximab levels lower in those with infusion reactions - Duration of response lower in those with infusion reactions Use of concommitant immunomodulators Lower antibody titers Higher infliximab trough levels Baert et al. NEJM 2003; 348:

9 SONIC trial Inpatient complications Thromboembolic Risk in Hospitalized Patients Patients with, particularly colitis are at increased risk for Cdiff infections Single center study: Risk Factor 173 patients experienced 200 thromboembolic events over an 11-year period DVT 48%; PE 12%; thrombophlebitis 12%; mesenteric venous thrombosis 4%; coronary ischemia 6%; stroke/tia 5% Surgery ( related / unrelated) Proportion of patients 30% / 6% Malignancy (past or current) 17% Estrogen use 9% Identified Prothrombotic State Number of patients, total tested = 44 (%) Antiphospholipid Ab 3 (7) Factor VIII mutation 3 (7) Hyperhomocysteinem ia Personal / family history of 20% / 25% Lupus anticoagulant 9 (20) TE Protein S deficiency 2 (5) Smoking Prophylaxis was documented in 11% only 40% of inpatients prior to the diagnosis of Total 20 (45) Prothrombotic the thromboembolic state event 12% (20 of 44 patients tested) 3 (7) Ananthakrishnan 51 AN, et al. Presented at DDW; May 20, 2013, Abstract 835. Levy A, et al. Presented at DDW; May 20, Abstract Mo1242. The role of the PCP in patients with How can you help a patient with UC or Crohn s? Role of the Primary Care Physician Prompt referral to gastroenterologists Alarms : Chronic diarrhea Iron deficiency anemia In Peds: failure to thrive Unexplained elevated markers of inflammation in the setting non-specific GI symptoms Presence of extra-intestinal manifestations: primary sclerosing cholangitis, erythema nodosum 9

10 Role of the Primary Care Physician Contact treating gastroenterologist in the setting of established and flare Check stool for C. diff Stop NSAIDs if possible Avoid antibiotics Start patients on a low residue/low fiber diet Dietary management of in flares There is no magic potion. No dietary studies have shown efficacy resulting in remission of, either UC or Crohn s. In general, patients with active or having an active flare, are intolerant to diets high in fiber. In patients who are having a flare, a low fiber diet (e.g. FODMAP) reduces symptoms. Long term low fiber diet however may be harmful in CD. Curcumin may help clinical symptoms in UC patients on mesalamine Diet in Lang, et al. Curcumin in Combination With Mesalamine Induces Remission in Patients With Mild-to-Moderate Ulcerative Colitis in a Randomized Controlled Trial. CTG Health maintenance in patients Age-appropriate screenings (pap smears, mammograms, prostate screenings). Bone Density scan Yearly influenza Pneumonia vaccine No LIVE vaccines on patients on immunosuppressants Sunscreen protection and/or yearly dermatology evaluations Smoking prevention and cessation Pregnant patients Most important factor is needs to be in remission! Most medications should be continued in pregnancy Contraindicated: cyclosporine, methotrexate. Most biologics, last dose is not given. Certolizumab given throughout. Pregnancy should be co-managed between GI and Obs. 10

11 61 PIANO: Achievement of Developmental Milestones Among Offspring of Women with Mahadevan U, et al. Presented at DDW, May 3, 2014; Abstract 1. In utero exposure to immunomodulator and biologic therapy did not lead to developmental delay compared to unexposed infants Pregnant patient 32 yo woman with PMH Ulcerative colitis, is thinking about getting pregnant. She is on Infliximab. In addition to reassuring patient that she stay on her medications and to follow with a GI, what other recommendations should you mention? A. All patients should have a c-section. B. She will not be able to get pregnant because of. C. Her baby should not receive live vaccines x 6 months. What can you do when you see a patient with? New presentation or flare of known disease: Prompt referral Send stool study for C.diff Start a low residue diet (low fiber) Stable patients, routine follow up: Vaccinations up to date Screening procedures up to date Case Presentation: A.R. 32 yo woman with ileal crohn s disease for 5 years. She is followed by a gastroenterologist who has started her on humira for the last year. Her symptoms are controlled and laboratory markers indicate no active inflammation. She wants to discuss vaccinations. You can tell her: A. She can get all the age appropriate vaccinations for her age and comorbidities. B. She can get get all the age appropriate vaccinations and comorbidities except live vaccines. C. She should should not get any vaccines as they are contraindicated Take Home Points 1. Be attentive to symptoms: Chronic GI symptoms, IDA, EIMs should prompt referral to gastroenterologist. 2. In the setting of GI flares: check C. diff and place patients on a low fiber/fodmap diet. 3. Address health maintenance: Your job is crucial here! No live vaccines to patients on immunosuppression. 4. Pregnant and : Its possible. Remission is key to a healthy pregnancy Thank you! Patient contact information: My odamas@med.miami.edu 11