INFLAMMATORY BOWEL DISEASE
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INFLAMMATORY BOWEL DISEASE. Norman H. Gilinsky, M.D., FACP, FACG Associate Professor of Medicine Medical Director, Digestive Diseases Center University of Cincinnati. Objectives At completion of this lecture, the student will be able to:.

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INFLAMMATORY BOWEL DISEASE

Norman H. Gilinsky, M.D., FACP, FACG

Associate Professor of Medicine

Medical Director, Digestive Diseases Center

University of Cincinnati


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ObjectivesAt completion of this lecture, the student will be able to:

  • Describe the main manifestations of each of the inflammatory bowel disorders

  • State the main clinical features that differentiate Crohn’s disease from ulcerative colitis

  • Formulate a management plan for diagnosis of disease extent and severity of each disorder

  • Develop a strategy to treat each disease

  • Differentiate treatment modalities that are more applicable to the management of Crohn’s disease than ulcerative colitis


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Inflammatory Bowel DiseaseUlcerative Colitis and Crohn’s Disease

Similarities

  • Chronic inflammation, usually limited to GIT

  • Majority young, therefore life-long disorder

  • Natural history: tends to relapse

  • Medications utilized generally similar

    Differences

  • Anatomic location and pathology (and therefore, presentation)

  • Nutritional consequences

  • Response to medical therapies

  • Surgical strategy, if required


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IBD: Location and Extent

5% Gastroduodenitis

40% Distal/ Left-sided colitis

30% Proctitis

25% Colitis

40% Ileocolitis

30% Ileitis

30% Extensive/ Pancolitis

Ulcerative Colitis Crohn’s Disease


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IBD: PATHOGENESIS

Chromosome 16 (IBD1)

Chromosome 12 (IBD2)

Chromosome 6 (IBD3-HLA)

Chromosome 14

NOD2

Genetic susceptibility

IBD

Infection

Diet

Smoking

NSAIDs

Immune dysregulation

Environmental trigger

TH 1

TH 2

Ahmad et al, Aliment Pharmacol Ther 2001; Hugot et al, Science 2001


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Inflammatory Bowel DiseaseExtra-Intestinal Manifestations

Joints

  • Peripheral arthritis

  • Ankylosing spondylitis, sacroileitis

    Skin

  • Pyoderma gangrenosum, Erythema nodosum

    Eyes

  • Episcleritis, uveitis, keratoconjunctivitis

    Biliary

  • Sclerosing cholangitis,cholangiocarcinoma

    Other

  • Hypercoagulability


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Ulcerative Colitis – Clinical Features

Presents with bloody diarrhea

  • Majority have limited left-sided disease

  • Majority consitutionally well

  • Majority safely managed in office setting

  • Profuse bloody diarrhea; >6 stools/day

  • Weight loss, anemia, hypoalbuminemia

  • Fever, abdominal pain, distension

Red Flags


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Ulcerative Colitis: Differential Diagnosis

Infection

  • Salmonella, shigella, campylobacter, amebiasis, etc.

    Ischemia

    Radiation

    Vasculitis

    Medications

    Toxins

Practice Point: Consider clinical setting, stool studies


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Ulcerative Colitis: Consequences of Disease

Acute

  • Fluid, electrolyte disturbance

  • Anemia

  • Fulminant colitis, toxic megacolon, perforation

    Chronic

  • Related to chronic disease, treatment

  • Related to extra-intestinal manifestations

  • Cancer


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Colorectal Cancer in IBD

  • Increased risk associated with:

    • Duration of disease

    • Anatomic extent of disease

  • Cancers develop in a dysplasia-to-cancer sequence

  • Cancers often flat, multiple, at advanced stage.

Practice Point: Colonoscopy with biopsy necessary for periodic cancer surveillance in patients with IBD.


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Ulcerative Colitis - Diagnostic Work-Up

  • Clinical suspicion

  • Stool studies

  • Endoscopy (with biopsy)

  • (Radiology)

  • Hematology and biochemistry (especially if clinically severe – i.e. CBC, albumin, electrolytes)

  • Serologies (if uncertainties remain, e.g. amebiasis; specific IBD serologies experimental)


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IBD: Treatment Modalities

5-Aminosalicylic Acid

[sulfasalazine, mesalamine]

Administered topically PO and/or PR

Corticosteroids

Administered PO, PR or IV

Immunomodulation

[6-MP, Azothioprine, Cyclosporine, etc]

Surgery


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Inflammatory Bowel DiseaseSulfasalazine / 5-Aminosalicylates

  • Ulcerative colitis

    • Induction therapy in mild to moderate disease (anticipate about 80% response)

    • Maintenance therapy, to reduce chances of relapse, once remission obtained

  • Crohn’s disease

    • Data not convincing

    • Best effects with high doses and for ileal disease

  • Balsalazide


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Inflammatory Bowel DiseaseSulfasalazine / 5-Aminosalicylates

5-ASA-diazo bond-sulfapyradine

  • Action

    • Topical / mucosal anti-inflammatory

  • Side-effects

    • Intolerance [gastric distress, headache]

    • Allergy

    • Cytopenias, hemolysis, folate deficiency

    • Nephritis, hepatitis

    • Pneumonitis, pancreatitis

    • Hypospermia

  • Balsalazide


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Inflammatory Bowel DiseaseMesalamine (5-ASA preparations)

  • Route of administration

    • Oral

    • Enema

    • Suppository

  • Side-effect profile

    • Less intolerance

    • No hypospermia, folate deficiency

  • Efficacy

    • No better (than sulfasalazine) for colitis

  • Cost

    • More expensive

  • Balsalazide


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Inflammatory Bowel DiseaseRole of Corticosteroids

  • Good drug for controlling acute flare (available oral, rectal or IV – use depending on disease location, clinical severity)

  • Of no value in maintenance situation

  • High frequency side-effects

  • Symptoms may flare with tapering

  • Steroid dependency common


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Inflammatory Bowel DiseaseRole of Immunosuppressive Agents

6-Mercaptopurine, azathioprine, methotrexate, cyclosporine

  • Steroid-sparing

  • Induces remission in majority

  • Speed of onset variable

  • Maintains remission

  • Useful in chronic grumbling disease, wish to avoid surgery, compliant patient

  • Requires periodic monitoring

  • Generally acceptable side-effect profile


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Inflammatory Bowel DiseaseManagement of Severe Colitis

  • Hospitalize, IV therapy

  • IV steroids, antibiotic cover

  • May require nutritional support

  • Rule out infection, megacolon

  • Frequent monitoring

    • Clinical condition, vitals

    • CBC, albumin

    • Radiology

  • Surgery if deteriorates, doesn’t settle

  • Concern = perforation, high relapse rate


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Crohn’s Disease:

Main Characteristics (1)

  • Any or > 1 region of GIT involved (perianal, skip areas)

  • Colon spared in > 20%

  • Small bowel involved in > 60%; therefore predisposed to nutritional sequelae, malabsorption, metabolic disorders, trace element and vitamin deficiencies

  • Inflammation transmural, therefore efficiency of topical therapy limited


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Crohn’s Disease:

Main Characteristics (2)

  • Disease pathology diverse

    • Inflammatory

    • Stricturing

    • Perforating

  • Presentation and outcome therefore diverse

  • No ‘cure’, therefore surgery (if required) limited to localized complications

  • Recurrences post-surgery not unusual


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Crohn’s Disease - Presentation

Inflammatory

  • Pain, tenderness, diarrhea, RLQ mass

    Obstuction

  • Cramps, distension, vomiting, obstruction

    Fistulizing

  • Enererocutaneous, enteroenteric, rectovaginal, enterovesical, etc.


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Crohn’s Disease: Disease Consequences

Constitutional

  • Fevers, weight loss, debilitation, pain

    Nutritional sequelae

  • Malabsorption, depletion syndromes

  • Growth retardation

    Perianal involvement

  • Abscess, fissure, fistula

    Other

  • Short-bowel syndrome

  • Renal calculi, gallstones

  • QOL, Psychologic


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Crohn’s Disease: Differential Diagnosis

  • Infectious etiologies

  • CMV, TB, Yersinia, C difficile, toxigenic E coli, etc.

  • Appendicitis

  • Diverticulitis

  • Ischemia

  • Carcinoma, lymphoma

  • Ulcerative colitis

  • Celiac disease

Practice Point: Great mimicker


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Crohn’s Disease - Diagnostic Work-Up

  • Clinical suspicion

  • Stool studies

  • Endoscopy (with biopsy)

  • Radiology

    • Abdominal X-ray

    • Small bowel follow-through

    • CT scan, etc.

  • Hematology and biochemistry (especially if clinically severe – i.e. CBC, albumin, electrolytes)

  • Malabsorption

  • Serologies (specific IBD serologies experimental)


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Crohn’s Disease: Treatment Modalities

5-Aminosalicylic Acid

Biologic Agents

[Monoclonal antibodies – Infliximab]

Antimicrobials

Surgery

Corticosteroids

Nutritional Aspects

Immunosuppressive

Psychologic Support


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The future – Biologic Therapies?

  • Approved

    TNF- antibodies (infliximab, Remicade®)

  • Experimental

    • CDP-571

    • Interleukin 10

    • Gene therapies?


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Inflammatory Bowel DiseaseOther Issues for the Specialist and Primary Care Physician

  • Perineal / ano-rectal disease [CD]

  • Symptomatic fistula [CD]

  • Short bowel syndrome / nutritional support [CD]

  • The pediatric and adolescent patient

  • The pregnant patient

  • Bone disease

  • Work and Psychologic issues


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Panproctocolectomy

Failure of medical therapy

Dysplasia or carcinoma

Debility, poor QOL

Intolerant of medications

Massive hemorrhage, perforation

Intractable pyoderma, hemolysis

Directed to specific complication

Symptomatic obstruction

Symptomatic fistulae

Perforation

Hemorrhage

Dysplasia or carcinoma

Perianal disease

IBD: Indications for Surgery

Ulcerative Colitis Crohn’s Disease


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IBD: Other Key References

  • Your Internal Medicine Textbook – plus:

  • Hanauer et al. Management of Crohn’s disease in adults. Am J Gastroenterol 2001; 96:634-43

  • Kornbluth et al. Ulcerative colitis practice guidelines in adults. Am J Gastroenterol 1996; 92:204-211

  • Lichtenstein. Inflammatory bowel disease. Gastroenterol Clin N Am 1999; 28:2


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