Inflammatory Bowel Disease

Transcription

1 Inflammatory Bowel Disease William Sonnenberg, MD Titusville, PA Disclosure Dr. William Sonnenberg has no conflict of interest, financial agreement, or working affiliation with any group or organization. Inflammatory Bowel Disease Crohn s Incidence: 5/100,000 Prevalence: 50/100,00 Ulcerative Colitis Incidence: 10/100,000 Prevalence: 201/100,000 Work and medical expenses Lichtenstein, GR, et al. Management of Crohn s Disease in Adults. Am J Gastroenterol Feb;104(2): Talley NJ, et al. An Evidence Based Systematic Review on Medical Therapies for IBD. Am J Gastroenterol. 2011; 106:S2-S25. 1

2 Epidemiology of IBD Stabilized in North America and Northern Europe Increasing in southern Europe, Asia, and developing world Higher in whites, but differences narrowing Oral contraceptives Diets high in sugar, and mono and polyunsaturated fats Lack of breast feeding Smoking and IBD Ulcerative Colitis Smoking protective Ex-smokers more likely to develop UC Crohn s Disease Doubled risk in current smokers Smokers respond less to treatment More recurrence after surgery 2

3 Hormones and Inflammatory Bowel Disease Oral contraceptives 46% increase in CD 28% increase in UC No change in relapse rates Hormone replacement Incidence increased 71% in UC No change in CD Khalili H et al: Hormone therapy increases risk of ulcerative colitis but not Crohn s disease. Gastroenterology, 2012 Nov;143(5): ; Khalili H et al: Oral contraceptives, reproductive factors and risk of inflammatory bowel disease. Gut, 2013 Aug;62(8):1153-9; NSAIDs and IBD 1 NSAID tablet for 15 days/month 1.6x increase in CD 2x increase in UC No association with aspirin Gastroenteritis 40% increase US military database Irritable bowel syndrome after gastroenteritis 5 fold increase 2-3 fold increase UK study 3

4 Other Infections and IBD H. pylori Odds ratio more in CD Helminthes Childhood exposure reduces risk 80% in South African study Sonnenberg A, Genta RM: Low prevalence of Helicobacter pylori infection among patients with inflammatory bowel disease. Aliment Pharmacol Ther, 2012 Feb;35(4): Antibiotic Use Antibiotics in first year of life tripled risk Less significant in adults Diet Long-chain omega-3 polyunsaturated FAs 28% reduction in UC Fiber 40% reduction for CD Fruit fiber most effective Vitamin D > 30 ng/ml reduced risk 62% in women 4

5 Breast Feeding Meta analysis of 4 studies Odd ratios Crohn s Disease: 0.67 Ulcerative Colitis: 0.77 Am J Clin Nutr Nov;80(5): Stress and IBD Depression doubles risk of CD No association with UC Nurses Health Study Farm Livestock and IBD Born after 1952, living on a livestock farm for first five years of life halved risk of IBD Signe Timm, et al. Place of upbringing in early childhood as related to inflammatory bowel diseases in adulthood: a population-based cohort study in Northern Europe. European Journal of Epidemiology, 2014; 29 (6): 429 5

6 Bacterial Flora Adult flora tend to be stable over time Quadrillion cells 1,000 species IBD patients have depletion and reduced diversity Firmicutes Bacteriodetes Location Thickness Crohn s Disease Any part of GI tract Transmural Ulcerative Colitis Continuous starting in rectum, generally only in colon Mucosa and submucosa Colonoscopy Skip lesions Cobblestoning Ulcerations Strictures Pseudopolyps Continuous inflammation Anemia + ++ Abdominal pain ++ + Rectal bleeding + ++ Colon Cancer Risk Location Comparisons 6

7 Spectrum of IBS 4% Diagnosis of IBD Serology accurate screening tool Clinical suspicion and endoscopy CT superior to US or MRI Video capsule endoscopy for small bowel involvement in Crohn s Imaging for IBD Test Sensitivity Specificity Positive Likelihood Ratio Negative Likelihood Ratio CT MRI Scintigraphy Ultrasound Horsthuis K, Bipat S, Bennink RJ, Stoker J. Inflammatory bowel disease diagnosed with US, MR, scintigraphy, and CT: meta-analysis of prospective studies. Radiology. 2008;247(1):

8 Labs General Testing CBC BMP Liver enzymes C-reactive protein Stool Studies Culture O+P C. difficle toxin Nutritional Status Iron, ferritin, TIBC B12, folate Albumin, preablumin 25-OH vitamin D, calcium 8

9 Serology for IBD Crohn s Disease anti-ompc (Escherichia coli outer membrane porin C) Antibody to Saccharomyces cerevisiae CBir1 complicated disease Ulcerative colitis panca (perinuclear cytoplasmic antibody) IBD v. IBS? Surrogate markers for bowel inflammation Fecal lactoferrin Fecal calprotectin Pain relief with defecation Few nocturnal symptoms Absence of occult fecal blood and leukocytes Crohn s Disease 9

10 Crohn s Disease Any part of GI tract Teens and 20 s Rising incidence Perianal findings Presentation Crohn s Mild to moderate pain Intermittent diarrhea Weight loss with more extensive cases Epidemiology Median age of diagnosis years Women > Men More in developed countries Northern hemisphere Sandler RS, Loftus EV. Epidemiology of inflammatory bowel disease. In: Sartor RB, Sandborn WJ, Kirsner JB, eds. Kirsner's Inflammatory Bowel Diseases. 6th ed. Edinburgh, United Kingdom: Saunders, 2004:

11 Cause Unknown Mutation on NOD2 gene 40x risk 3% absolute risk 50-60% concordance in identical twins Smoking 2X risk NSAIDS Appendectomy risk Common Symptoms Abdominal Pain Diarrhea Fatigue GI bleeding Weight loss Extra intestinal Symptoms Symptom Prevalence (%) Anemia 9%-74% Anterior uveitis 17% Aphthous stomatitis 4% - 20% Cholelithiasis 13% - 34% Episcleritis 29% Erythema nodosum 2% -20% Inflammatory arthropathies 10%- 20% Nephrolithiasis 8%- 19% Osteoporosis 2% - 30% Pyoderma gangrenosum 0.5% - 2% Scleritis 18% Venous thromboembolism 10% - 30% Larsen S, et al. Ann Med. 2010;42(2):

12 Endoscopy Crohn s Colonoscopy with ileoscopy at junction of colon and ileum with biopsy Skip lesions Cobblestoning Ulcerations Noncaseating granulomas Skip Lesion in Crohn s Cobblestoning in Crohn s 12

13 Cobblestoning Crohn s Ulcerations Crohn s Noncaseating granuloma 13

14 Ileocolonic Crohn s Disease CT Scan Crohn s Ulcerative Colitis 14

15 Ulcerative Colitis Mucosal inflammation confined to colon Bloody diarrhea Less systemic symptoms Less disability long term Demographics of Ulcerative Colitis Industrialized and western countries Higher latitudes Sexes similar Smokers less like likely Less with appendectomy Talley NJ, Abreu MT, Achkar JP, et al.; Am J Gastroenterol. 2011;106(suppl 1):S2 S25 Other Risk Factors Sibling with UC increases risk 4.6 fold Monozygotic twins increases risk 95 fold Refined sugar, fat and meat increases risk Vegetable diet decreases risk 15

16 Infections Salmonella or Campylobacter 8-10 fold increase risk in one year Risk diminishes but last 10 years Bacterial flora abnormal Jess T, Simonsen J, Nielsen NM, et al. Enteric Salmonella or Campylobacter infections and the risk of inflammatory bowel disease. Gut. 2011;60(3): Presentation Ulcerative Colitis Mild to moderate diarrhea with blood and/or mucous Less constitutional symptoms Fever, weight loss, dehydration with severe cases Acute abdomen with toxic megacolon Extraintestinal Symptoms Symptom Prevalence (%) Arthritis 21% Aphthous stomatitis 4% Primary Sclerosing Cholangitis 4% Uveitis 4% Erythema nodosum 3% Ankylosing Spondylitis 2% Pyoderma Gangrenosum 2% Psoriasis 1% Vavricka SR, Brun L, Ballabeni P, et al. Frequency and risk factors for extraintestinal manifestations in the Swiss inflammatory bowel disease cohort. Am J Gastroenterol. 2011; 106(1):113 16

17 Erythema Nodosum Pyoderma Gangrenosum Tests for Ulcerative Colitis C-reactive protein and ESR abnormal less than ½ time Can t be used to exclude UC Fecal calprotectin and lactoferrin sensitive tests panca 17

18 Endoscopy Friable Mucosa, Pseudopolyps Treatment Crohn s Disease 18

19 Mesalamine Products Azulfidine and 5-ASA for mild to moderate disease Side effects azulfidine Nausea, headache, fever, rash, male infertility Rare agranulocytosis in first 2 months 5-ASA side effects fewer Headache, nausea, diarrhea, abdominal pain Antibiotics Ciprofloxacin and metronidazole Anti-inflammatory, anti-infectious Controlled trials inconsistent Moderate Disease Corticosteroids Azathioprine and 6-mercaptopurine Methotrexate Anti-TNF Agents Infliximab Adalimumab Certolizumab 19

20 Severe Disease Hospitalization and GI consult CT scan Fluids, antibiotics Nutritional support Anti- TNF?? Surgical intervention Perianal and Fistula GI and surgical consult Antibiotics Infliximab benefits closure with ABX, steroid, or immunomodulation failure Surgery Maintenance Therapy Azathioprine Methotrexate Steroids and 5-ASA ineffective 20

21 Surgery Indications - CD Obstructing strictures Complicating fistula Peri-anal abscess Toxic megacolon Localized unresponsive disease Intractable hemorrhage Perforation Common Procedures Resection Stricturoplasty Abscess drainage Surgical Outcomes ½ patients require surgery within 10 years 10% have a prolonged remission More postop infections with steroids No increased infection with azathioprine, 6-mercaptopurine, nor inflixamab 21

22 Treatment Ulcerative Colitis 5-ASA Strong evidence in UC first line Active flares Maintain remission Anti-inflammatory properties Oral or enemas in distal disease Rare side effects Pancreatitis, interstitial nephritis, hepatitis 5-ASA Release Site 22

23 Use of 5-ASA Oral for mild to moderate active ulcerative colitis Add topical if oral ineffective Steroids next step Steroids Acute flairs in UC and CD IV, PO, or rectal Not for maintenance therapy Risk of chronic use Infections Bone loss Diabetes Talley NJ, et al. An Evidence Based Systematic Review on Medical Therapies for IBD. Am J Gastroenterol. 2011; 106:S2-S25. Next Step IV cyclosporine Infliximab Postpones colectomy Leblanc S, Allez M, Seksik P, et al.; GETAID. Successive treatment with cyclosporine and infliximab in steroid-refractory ulcerative colitis. Am J Gastroenterol. 2011;106(4):

24 Surgery in IBD Ulcerative Colitis Surgery (colectomy) is curative Colectomy & ileostomy Colectomy & ileoanal anastomosis (Jpouch) Crohn s Disease Surgery does not sure Disease recurs Less after ostomy Resect inflamed segments to treat complications or refractory disease Surgery Indications - UC Failed control of severe attack Toxic megacolon Acute complications Chronic Sx unresponsive to therapy Medication side effects without disease control Dysplasia or cancer Surgical Benefits 12 months postop, QOL equal to general population Colectomy 54% reoperation rate Pouchitis common Heikens JT, de Vries J, van Laarhoven CJ. Quality of life, health-related quality of life and health status in patients having restorative proctocolectomy with ileal pouch-anal anastomosis for ulcerative colitis: a systematic review. Colorectal Dis. 2012;14(5):

25 Maintenance of Ulcerative Colitis 5-ASA suppositories and enemas Oral 5-ASA for extensive disease No steroids Azathioprine Infliximab Probiotics in Ulcerative Colitis Escherichia coli strain Nissle 1917 No less effective than 5-ASA VSL#3 + 5-ASA can help induce remission in mild-to-moderate ulcerative colitis. Kruis W, Fric P, Pokrotnieks J, et al. Maintaining remission of ulcerative colitis with the probiotic Escherichia coli Nissle 1971 is as effective as with standard mesalazine. Gut 2004;53: Summary of Treatments Medications Active UC Maintenance UC Active CD Maintenance CD 5-ASA Yes Yes No No Steroids Yes No Yes No Antibiotics No?? No No Methotrexat e No No Yes Ye Thiopurines No Yes No Yes IV Cyclosporin TNF antibiodies Yes(severe) No No No Yes?? Yes yes Talley NJ, et al. An Evidence Based Systematic Review on Medical Therapies for IBD. Am J Gastroenterol. 2011; 106:S2-S25. 25

26 Preventing Colon Cancer in IBD Adherence to maintenance medications 5-ASA Follow-up and surveillance colonoscopies Every 1-2 years after 10 yeas Yearly after 20 years Colectomy if: Dysplasia Unwilling to do surveillance exams Osteoporosis in IBD Steroid therapy Smoking Active disease Crohn s > Ulcerative Colitis Female Adherence 26

27 Adherence 27