inflammatory bowel disease - 330 pm - sonnenberg - ibd.pdf · gastroenteritis 40% increase – us...
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Inflammatory Bowel DiseaseWilliam 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. 2009Feb;104(2):465-83.Talley NJ, et al. An Evidence Based Systematic Review on Medical Therapies for IBD. Am JGastroenterol. 2011; 106:S2-S25.
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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 ColitisSmoking protective
Ex-smokers more likely to develop UC
Crohn’s DiseaseDoubled risk in current smokersSmokers respond less to treatmentMore recurrence after surgery
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Hormones and Inflammatory Bowel DiseaseOral contraceptives
46% increase in CD28% increase in UCNo change in relapse rates
Hormone replacementIncidence increased 71% in UCNo change in CD
Khalili H et al: Hormone therapy increases risk of ulcerative colitis but not Crohn’s disease. Gastroenterology, 2012 Nov;143(5):1199-206; 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/month1.6x increase in CD2x 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
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Other Infections and IBD
H. pyloriOdds ratio 0.64. more in CD
HelminthesChildhood 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):469-76
Antibiotic Use
Antibiotics in first year of life tripled risk
Less significant in adults
Diet
Long-chain omega-3 polyunsaturated FAs28% reduction in UC
Fiber 40% reduction for CDFruit fiber most effective
Vitamin D > 30 ng/mL reduced risk 62% in women
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Breast Feeding
Meta analysis of 4 studiesOdd ratiosCrohn’s Disease: 0.67Ulcerative Colitis: 0.77
Am J Clin Nutr. 2004 Nov;80(5):1342-52
Stress and IBD
Depression doubles risk of CDNo 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
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Bacterial Flora
Adult flora tend to be stable over timeQuadrillion cells1,000 species
IBD patients have depletion and reduced diversity FirmicutesBacteriodetes
Crohn’s Disease Ulcerative Colitis
Location Any part of GI tract
Continuous starting in rectum,
generally only in colon
Thickness TransmuralMucosa and submucosa
Colonoscopy
Skip lesionsCobblestoning
UlcerationsStrictures
PseudopolypsContinuous
inflammation
Anemia + ++Abdominal pain ++ +Rectal bleeding + ++
Colon Cancer Risk ++ ++++
Location Comparisons
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Spectrum of IBS
4%
Diagnosis of IBD
Serology accurate screening tool
Clinical suspicion and endoscopy
CT superior to US or MRIVideo capsule endoscopy
for small bowel involvement in Crohn’s
Imaging for IBD
Test Sensitivity SpecificityPositive
LikelihoodRatio
NegativeLikelihood
Ratio
CT 84.3 95.1 3.8 0.03
MRI 93.0 93.8 2.8 0.02
Scintigraphy 87.8 84.5 1.2 0.03
Ultrasound 89.7 95.6 4.4 0.02
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):64–79
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Labs – General Testing
CBCBMPLiver enzymesC-reactive protein
Stool Studies
CultureO+PC. difficle toxin
Nutritional Status
Iron, ferritin, TIBCB12, folateAlbumin, preablumin25-OH vitamin D, calcium
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Serology for IBD
Crohn’s Diseaseanti-OmpC (Escherichia coli
outer membrane porin C)Antibody to Saccharomyces
cerevisiaeCBir1 – complicated disease
Ulcerative colitispANCA (perinuclear
cytoplasmic antibody)
IBD v. IBS?
Surrogate markers for bowel inflammationFecal lactoferrinFecal calprotectin
Pain relief with defecationFew nocturnal symptomsAbsence of occult fecal
blood and leukocytes
Crohn’s Disease
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Crohn’s Disease
Any part of GI tractTeens and 20’sRising incidencePerianal findings
Presentation – Crohn’s
Mild to moderate pain Intermittent diarrheaWeight loss with more
extensive cases
Epidemiology
Median age of diagnosis 20-30 years
Women > MenMore in developed
countriesNorthern 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: 245–262.
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Cause
UnknownMutation on NOD2 gene
40x ↑ risk
3% absolute risk
50-60% concordance in identical twins
Smoking 2X risk NSAIDS Appendectomy ↑ risk
Common Symptoms
Abdominal PainDiarrheaFatigueGI bleedingWeight loss
Extra intestinal SymptomsSymptom 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):97–114
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Endoscopy – Crohn’s
Colonoscopy with ileoscopyat junction of colon and ileum with biopsy Skip lesions
Cobblestoning
Ulcerations
Noncaseating granulomas
Skip Lesion in Crohn’s
Cobblestoning in Crohn’s
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Cobblestoning – Crohn’s
Ulcerations – Crohn’s
Noncaseating granuloma
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Ileocolonic Crohn’s Disease
CT Scan – Crohn’s
Ulcerative Colitis
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Ulcerative Colitis
Mucosal inflammation confined to colon
Bloody diarrheaLess systemic symptomsLess disability long term
Demographics of Ulcerative Colitis Industrialized and
western countriesHigher latitudesSexes similarSmokers less like
likelyLess 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
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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):318–324
Presentation – Ulcerative Colitis
Mild to moderate diarrhea with blood and/or mucous
Less constitutional symptomsFever, weight loss,
dehydration with severe casesAcute abdomen with toxic
megacolon
Extraintestinal SymptomsSymptom 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
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Erythema Nodosum
Pyoderma Gangrenosum
Tests for Ulcerative Colitis
C-reactive protein and ESR abnormal less than ½ timeCan’t be used to exclude UC
Fecal calprotectin and lactoferrin sensitive tests
pANCA
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Endoscopy
Friable Mucosa, Pseudopolyps
Treatment Crohn’s Disease
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Mesalamine Products
Azulfidine and 5-ASA for mild to moderate disease
Side effects azulfidineNausea, headache, fever, rash, male
infertilityRare agranulocytosis in first 2 months
5-ASA side effects – fewerHeadache, nausea, diarrhea,
abdominal pain
Antibiotics
Ciprofloxacin and metronidazoleAnti-inflammatory, anti-infectiousControlled trials inconsistent
Moderate Disease
CorticosteroidsAzathioprine and 6-mercaptopurineMethotrexateAnti-TNF Agents
InfliximabAdalimumabCertolizumab
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Severe Disease
Hospitalization and GI consultCT scanFluids, antibioticsNutritional supportAnti- TNF??Surgical intervention
Perianal and Fistula
GI and surgical consultAntibiotics Infliximab benefits
closure with ABX, steroid, or immunomodulation failure
Surgery
Maintenance Therapy
Azathioprine MethotrexateSteroids and 5-ASA
ineffective
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Surgery Indications - CD
Obstructing stricturesComplicating fistulaPeri-anal abscessToxic megacolonLocalized unresponsive disease Intractable hemorrhagePerforation
Common Procedures
Resection
Stricturoplasty
Abscess drainage
Surgical Outcomes
½ patients require surgery within 10 years
10% have a prolonged remissionMore postop infections with
steroidsNo increased infection with
azathioprine, 6-mercaptopurine, nor inflixamab
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Treatment Ulcerative Colitis
5-ASA
Strong evidence in UC – first lineActive flaresMaintain remission
Anti-inflammatory propertiesOral or enemas in distal diseaseRare side effects
Pancreatitis, interstitial nephritis, hepatitis
5-ASA Release Site
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Use of 5-ASA
Oral for mild to moderate active ulcerative colitis
Add topical if oral ineffectiveSteroids next step
Steroids
Acute flairs in UC and CD IV, PO, or rectalNot for maintenance therapyRisk of chronic use
InfectionsBone lossDiabetes
Talley NJ, et al. An Evidence Based Systematic Review on Medical Therapiesfor IBD. Am J Gastroenterol. 2011; 106:S2-S25.
Next Step
IV cyclosporine InfliximabPostpones 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):771–777
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Surgery in IBD
Ulcerative Colitis Surgery (colectomy)
is curative
Colectomy & ileostomy
Colectomy & ileo-anal anastomosis (J-pouch)
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 attackToxic megacolonAcute complicationsChronic Sx unresponsive to therapyMedication side effects without
disease controlDysplasia 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):536–544
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Maintenance of Ulcerative Colitis 5-ASA suppositories and enemasOral 5-ASA for extensive diseaseNo steroidsAzathioprine 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;53:1617-1623
Summary of TreatmentsMedications Active UC Maintenance
UC Active CD MaintenanceCD
5-ASA Yes Yes No No
Steroids Yes No Yes No
Antibiotics No ?? No No
Methotrexate No No Yes Ye
Thiopurines No Yes No Yes
IVCyclosporin Yes(severe) No No No
TNF antibiodies Yes ?? Yes yes
Talley NJ, et al. An Evidence Based Systematic Review on Medical Therapiesfor IBD. Am J Gastroenterol. 2011; 106:S2-S25.
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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 therapySmoking Active disease
Crohn’s > Ulcerative Colitis
Female
Adherence
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Adherence