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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. 2009 Feb;104(2):465-83. Talley NJ, et al. An Evidence Based Systematic Review on Medical Therapies for IBD. Am J Gastroenterol. 2011; 106:S2-S25.
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Page 1: Inflammatory Bowel Disease - 330 PM - Sonnenberg - IBD.pdf · Gastroenteritis 40% increase – US military database Irritable bowel syndrome after gastroenteritis – 5 fold increase

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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.

Page 2: Inflammatory Bowel Disease - 330 PM - Sonnenberg - IBD.pdf · Gastroenteritis 40% increase – US military database Irritable bowel syndrome after gastroenteritis – 5 fold increase

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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

Page 3: Inflammatory Bowel Disease - 330 PM - Sonnenberg - IBD.pdf · Gastroenteritis 40% increase – US military database Irritable bowel syndrome after gastroenteritis – 5 fold increase

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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

Page 4: Inflammatory Bowel Disease - 330 PM - Sonnenberg - IBD.pdf · Gastroenteritis 40% increase – US military database Irritable bowel syndrome after gastroenteritis – 5 fold increase

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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

Page 5: Inflammatory Bowel Disease - 330 PM - Sonnenberg - IBD.pdf · Gastroenteritis 40% increase – US military database Irritable bowel syndrome after gastroenteritis – 5 fold increase

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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

Page 6: Inflammatory Bowel Disease - 330 PM - Sonnenberg - IBD.pdf · Gastroenteritis 40% increase – US military database Irritable bowel syndrome after gastroenteritis – 5 fold increase

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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

Page 7: Inflammatory Bowel Disease - 330 PM - Sonnenberg - IBD.pdf · Gastroenteritis 40% increase – US military database Irritable bowel syndrome after gastroenteritis – 5 fold increase

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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

Page 8: Inflammatory Bowel Disease - 330 PM - Sonnenberg - IBD.pdf · Gastroenteritis 40% increase – US military database Irritable bowel syndrome after gastroenteritis – 5 fold increase

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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

Page 9: Inflammatory Bowel Disease - 330 PM - Sonnenberg - IBD.pdf · Gastroenteritis 40% increase – US military database Irritable bowel syndrome after gastroenteritis – 5 fold increase

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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

Page 10: Inflammatory Bowel Disease - 330 PM - Sonnenberg - IBD.pdf · Gastroenteritis 40% increase – US military database Irritable bowel syndrome after gastroenteritis – 5 fold increase

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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.

Page 11: Inflammatory Bowel Disease - 330 PM - Sonnenberg - IBD.pdf · Gastroenteritis 40% increase – US military database Irritable bowel syndrome after gastroenteritis – 5 fold increase

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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

Page 12: Inflammatory Bowel Disease - 330 PM - Sonnenberg - IBD.pdf · Gastroenteritis 40% increase – US military database Irritable bowel syndrome after gastroenteritis – 5 fold increase

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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

Page 13: Inflammatory Bowel Disease - 330 PM - Sonnenberg - IBD.pdf · Gastroenteritis 40% increase – US military database Irritable bowel syndrome after gastroenteritis – 5 fold increase

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Cobblestoning – Crohn’s

Ulcerations – Crohn’s

Noncaseating granuloma

Page 14: Inflammatory Bowel Disease - 330 PM - Sonnenberg - IBD.pdf · Gastroenteritis 40% increase – US military database Irritable bowel syndrome after gastroenteritis – 5 fold increase

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Ileocolonic Crohn’s Disease

CT Scan – Crohn’s

Ulcerative Colitis

Page 15: Inflammatory Bowel Disease - 330 PM - Sonnenberg - IBD.pdf · Gastroenteritis 40% increase – US military database Irritable bowel syndrome after gastroenteritis – 5 fold increase

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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

Page 16: Inflammatory Bowel Disease - 330 PM - Sonnenberg - IBD.pdf · Gastroenteritis 40% increase – US military database Irritable bowel syndrome after gastroenteritis – 5 fold increase

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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

Page 17: Inflammatory Bowel Disease - 330 PM - Sonnenberg - IBD.pdf · Gastroenteritis 40% increase – US military database Irritable bowel syndrome after gastroenteritis – 5 fold increase

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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

Page 18: Inflammatory Bowel Disease - 330 PM - Sonnenberg - IBD.pdf · Gastroenteritis 40% increase – US military database Irritable bowel syndrome after gastroenteritis – 5 fold increase

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Endoscopy

Friable Mucosa, Pseudopolyps

Treatment Crohn’s Disease

Page 19: Inflammatory Bowel Disease - 330 PM - Sonnenberg - IBD.pdf · Gastroenteritis 40% increase – US military database Irritable bowel syndrome after gastroenteritis – 5 fold increase

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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

Page 20: Inflammatory Bowel Disease - 330 PM - Sonnenberg - IBD.pdf · Gastroenteritis 40% increase – US military database Irritable bowel syndrome after gastroenteritis – 5 fold increase

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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

Page 21: Inflammatory Bowel Disease - 330 PM - Sonnenberg - IBD.pdf · Gastroenteritis 40% increase – US military database Irritable bowel syndrome after gastroenteritis – 5 fold increase

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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

Page 22: Inflammatory Bowel Disease - 330 PM - Sonnenberg - IBD.pdf · Gastroenteritis 40% increase – US military database Irritable bowel syndrome after gastroenteritis – 5 fold increase

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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

Page 23: Inflammatory Bowel Disease - 330 PM - Sonnenberg - IBD.pdf · Gastroenteritis 40% increase – US military database Irritable bowel syndrome after gastroenteritis – 5 fold increase

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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

Page 24: Inflammatory Bowel Disease - 330 PM - Sonnenberg - IBD.pdf · Gastroenteritis 40% increase – US military database Irritable bowel syndrome after gastroenteritis – 5 fold increase

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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

Page 25: Inflammatory Bowel Disease - 330 PM - Sonnenberg - IBD.pdf · Gastroenteritis 40% increase – US military database Irritable bowel syndrome after gastroenteritis – 5 fold increase

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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.

Page 26: Inflammatory Bowel Disease - 330 PM - Sonnenberg - IBD.pdf · Gastroenteritis 40% increase – US military database Irritable bowel syndrome after gastroenteritis – 5 fold increase

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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


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