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IBD for 5th 2011.

IBD for 5th 2011.

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    IBD for 5th 2011. IBD for 5th 2011. Presentation Transcript

    • Inflammatory Bowel Disease Dr. Mohammad Shaikhani CABM,FRCP. Updated:2/2011
    • Introduction
      • IBD: an idiopathic chronic inflammatory disease of the GIT consistsing of 2 distinct clinical entities: ulcerative colitis & Crohn disease (regional enteritis),both cause macroscopic inflammation.
      • Microscopic colitis is less common& does not cause significant macroscopic abnormalities.
      • The pathogenesis not fully understood but likely involves a genetic predisposition& a dysregulated immunologic response to the local microenvironment of luminal bacteria.
      • Both are usually differentiated on the basis of differences in the distribution of pathology in the bowel & histopathologic appearance of the lesion.
      • 10% of patients cannot be shown to have either Crohn disease or ulcerative colitis ( indeterminate colitis).
    • Risk factors:
      • The peak incidence :second, third& fourth decades of life
      • A second peak in the seventh&eighth decades.
      • There are no sex differences.
      • Ashkenazi Jewish descent have a higher risk.
      • A 5-10% risk for first-degree relatives of affected patients.
      • Many candidate genes:
      • 1.Established link between Crohn disease &variants of the CARD15 (also known as NOD2 ) gene, in only some patients & does not affect the risk for colitis.
      • 2. IL-23 receptor affects the risk for both Crohn disease & colitis., as monoclonal antibody against the p40 subunit have demonstrated benefit in the treatment of Crohn disease.
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    • Less common colitis forms are:
      • Microscopic colitis (collagenous& lynphocytic)
      • Others
        • Diversion colitis after clostomies.
        • Radiation colitis
        • Drug induced colitis
        • Infectious colitis
        • Ischemic colitis
    • Clinical features: UC
      • Generally present with bloody diarrhea with rectal urgency, discomfort& cramps.
      • They have profound tenesmus (feelings of urgency& incomplete evacuation), secondary to proctitis, this can cause constipation to be a more common manifestation than diarrhea; in such patients, determining the activity of the disease& treating it can be challenging.
      • UC extends proximally from the anal verge&can progress to pancolitis involving the cecum.
      • Fever is infrequent, but weight loss secondary to the inflammatory disease itself or to the chronic diarrhea is common.
      • Physical examination findings can range from mild lower abdominal tenderness to abdominal distention with rebound tenderness& hypoactive bowel sounds, suggestive of toxic megacolon.
    • Clinical features: Crohn disease
      • More protean in its manifestations than ulcerative colitis, as the disease can affect any portion of the GIT& frequently has so-called “skip lesions” with areas of normal mucosa juxtaposed with severe inflammation.
      • The transmural nature of the disease results in three distinct manifestations: inflammatory, fistulizing& fibrostenotic.
      • Large-volume diarrhea can occur; diarrhea is associated with both small& large-bowel Crohn disease, whereas hematochezia is almost always a sign of colonic disease.
      • The inflamed tissue causes a secretory diarrhea& a protein-losing enteropathy, steatorrhea from fat malabsorption (with patients who have ileal or ilealocolic disease frequently being vitamin B12- & vitamin D-deficient)& other types of malabsorption.
      • Patients who have had their terminal ileum resected are also at risk for a choleretic diarrhea secondary to bile salt wasting.
    • Clinical features: Crohn disease
      • Fistulae are abnormal connections between the bowel& adjacent organs.
      • Abscesses may form& the fistula acts as a natural drainage mechanism, causing pus to emerge from the fistulae.
      • The fistulae become symptomatic with drainage of fecal material around the anus (perianal fistulae), seepage of bowel contents through the skin (enterocutaneous fistulae), passage of feces through the vagina (rectovaginal fistulae)& pneumaturia or recurrent urinary tract infections (enterovesical fistulae).
      • The intestinal inflammation may extend to adjacent musculature &result in neuromuscular sequelae; for example, a patient with Crohn disease&a new limp likely has a psoas muscle abscess.
    • Clinical features: Crohn disease
      • Patients with intestinal strictures present with signs of obstruction: fever, abdominal distention, pain, nausea, vomiting.
      • Strictures may be secondary to severe inflammation or to fibrosis of the bowel& can be relieved only by surgical resection.
      • The most common site of strictures is in the terminal ileum where they result in partial or complete small-bowel obstruction.
      • Patients with duodenal Crohn disease may develop gastric outlet obstruction.
      • In patients with ileal disease, the abdominal examination commonly shows right lower quadrant tenderness; a phlegmonous mass may be present.
      • A detailed anorectal examination is important in patients with suspected Crohn disease: the presence of skin tags suggests the diagnosis& the examination may also show fistulae.
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    • Environmental Precipitants
      • Factors:
        • Early appendectomy (increase UC incidence)
        • Smoking (protects against UC but increases the risk of CD).
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    • UC
    • Distinguishing characteristics of CD and UC UC CD Feature Only colon (rarely “ backwash ileitis ” SB or colon Location Continuous, begins distally Skip lesions Anatomic distribution Involved in >90% Rectal spare Rectal involvement Universal Only 25% Gross bleeding Rare 75% Peri-anal disease No Yes Fistulization No 50-75% Granulomas
    • Endoscopic features of CD and UC UC CD Feature Continuous Discontinuous Mucosal involvement Rare Common Aphthous ulcers Abnormal Relatively normal Surrounding mucosa Rare Common Longitudinal ulcer No In severe cases Cobble stoning Common Uncommon Mucosal friability distorted Normal Vascular pattern
    • Pathologic features of CD and UC UC CD Feature Uncommon Yes Transmural inflammation No 50-75% Granulomas Rare Common Fissures No Common Fibrosis Uncommon Common Submucosal inflammation
    • Radiologic features of CD and UC UC CD Feature Collar button ulcers Nodularity granularity cobble stoning string sign of SB
    • Comparison of Features in Ulcerative Colitis and Crohn's Disease Crohn's Disease Ulcerative Colitis Feature Transmural Mucosal Depth of inflammation Skip areas Contiguous Pattern of disease Mouth to anus Colorectum Location Less common Usual Rectal involvement Common Backwash ileitis (15%–20% of patients ) Ileal disease Common Rare Fistulas Common Rare Perianal disease 10%–30% of patients Unlikely Granulomas Less common Usual Overt bleeding More common Unlikely Malnutrition Colorectal cancer, small bowel cancer (depending on disease location ) Colorectal cancer, cholangiocarcinoma (if primary sclerosing cholangitis is present ) Cancer risk Harmful Protective Tobacco use
    • UC
    • CD
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    • DDX of UC
      • Infectious
      • Drug induced
      • Microscopic colitis
    • CD
      • Anatomic distribution
      • CD activity index
      • DDx (lymphoma, Yersinea Enterocolitis, TB)
    • CD ilitis: DDx
      • Lymphoma
      • Yersinea Enterocolitis
      • TB
    • Extra-intestinal manifestations of IBD
      • Arthritis:
        • Peripheral arthritis, usu paralels the disease activity
        • Ankylosing Spondylitis, 1-6%, sacroiliitis
      • Ocular lesions:
        • Iritis (uvietis) (0.5-3%), episcleritis, keratitis,
      • Skin and oral cavity:
        • Erythema nodosum 1-3%
        • Pyoderma Gangrenosum 0.6%
        • Aphthus stomatitis, metastatic CD.
    • Extra-intestinal manifestations of IBD
      • Occur in 10-20% at some time in the course of their disease.
      • Arthritis, the most common, can either be related to the intestinal inflammation itself or be part of an overlap syndrome with rheumatoid arthritis.
      • Sacroiliitis &ankylosing spondylitis, in association with HLA B27, occur in 5-10%.
      • Uveitis & episcleritis may also occur.
      • Erythema nodosum, which manifests as small exquisitely tender nodules on the anterior tibial surface, occurs more commonly in Crohn disease, whereas pyoderma gangrenosum is more common in ulcerative colitis& can range from small lesions to large ulcers. Even small amounts of trauma to the skin can activate this inflammatory process.
    • Extra-intestinal manifestations of IBD
      • Primary sclerosing cholangitis: occurs in 5% of patients with UC & may occur in Crohn disease as well.
      • Up to 80% of patients with PSC have underlying IBD.
      • May present with only an isolated elevation in SAP or with jaundice, biliary obstruction, & evidence of portal hypertension.
      • These patients may have recurrent episodes of cholangitis as well as a malignant transformation to cholangiocarcinoma& a much higher than normal incidence of colorectal cancer.
      • Therapy with ursodeoxycholic acid has been shown to be chemoprotective against colon cancer.
    • Extra-intestinal manifestations of IBD
      • Increased risk for CRC; the risk is associated with the age of onset; duration, extent, severity of disease& whether the patient has a family history of CRC.
      • Annual CRC rate in extensive colitis is at least 0.5% /year after the first decade of colitis.
      • Screening recommendations include colonoscopy every 1 to 2 years beginning 8 years after diagnosis.
      • Unlike sporadic colorectal cancer that develops primarily from colon polyps, inflammatory bowel disease-associated colon cancer can arise from flat dysplastic mucosa which is not readily detectable from underlying inflammatory tissue.
    • Extra-intestinal manifestations of IBD
      • 50% with IBD have osteopenia, with a substantially increased risk of osteoporosis & fracture.
      • The risk is present in patients with ulcerative colitis / Crohn disease, in both sexes&in patients who are taking corticosteroids & those who have never taken them.
      • Patients with prolonged IBD, malabsorption, a history of using corticosteroids for >3 months, cigarette smoking, older age, history of fractures, or a family history of osteoporosis should be evaluated for the presence of metabolic bone disease.
      • Kidney stones / gallstones are other extraintestinal manifestations of inflammatory bowel disease.
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    • Complications of IBD
      • Bleeding
      • Stricture
      • Fistula
      • Toxic megacolon
      • Cancer: Patients with either UC or CD have an increased risk of intestinal dysplasia & CRC that is related to the duration, extent& severity of the inflammation,so those with extensive/longstanding disease should undergo regular colonoscopic examinations with mucosal biopsies to detect these complications.
    • Complications of IBD
    • Dignosis/assessing severity & extent:
      • Should be considered in any young patient with chronic diarrhea or hematochezia.
      • Infection should be excluded by stool culture for ova/ parasites, Giardia& Clostridium difficile .
      • Laboratory findings suggestive of IBD include anemia, hypoalbuminemia, leukocytosis, vitamin deficiencies (more likely in small-intestinal Crohn disease than ulcerative colitis).
    • Dignosis/assessing severity & extent:
      • 2/3 with ulcerative colitis, but only 15- 20% with Crohn disease &< 5% of persons without IBD have p-ANCA , a serum antibody directed against a particular histone H1 antigen& detectable by immunofluorescence or specific enzyme immunoassay.
      • Approximately 50% with Crohn disease have anti- Saccharomyces cerevisiae antibodies (ASCA), as opposed to < 5% of patients with ulcerative colitis &control subjects.
      • So measuring both serum p-ANCA & ASCA is reasonably reliable for the diagnosis of Crohn disease or ulcerative colitis.
      • Newer antibody tests, directed against the outer membrane porin of Escherichia coli (Omp-C)& against the flagellum of pathogenic polyflagellated organisms (Cbir1), are also predictive of classic Crohn disease,but not differentiating atypical presentations or diagnosing indeterminate colitis.
    • Dignosis/assessing severity & extent:
      • 50% with ulcerative colitis have proctosigmoiditis only
      • 15-20% have left-sided disease.
      • 1/3 present with pancolitis.
      • Patients with proctitis generally have a benign course, but 11% develop more extensive disease by 5 years&19% by 10 years.
      • Endoscopic findings range from a decreased vascular pattern& minimal friability in patients with mild disease to spontaneous bleeding&deep ulcerations in severe disease.
      • Histopathology typically consists of crypt abscesses with branching&architecture distortion& acute/ chronic inflammation.
    • Dignosis/assessing severity & extent:
      • Crohn disease has a different pattern of distribution than ulcerative colitis
      • 30% having isolated small-bowel disease
      • 25% colonic disease
      • 40% ileocolonic disease.
      • A few patients have upper GIT or isolated perianal disease in the absence of colonic inflammation.
      • The mildest endoscopic lesions are aphthous ulcers, which can, however, coalesce to form deep ulcerations&cobblestone appearance.
      • Affected areas are commonly separated by normal mucosa, the so-called “skip lesions” that are the hallmark of Crohn disease.
      • Granulomas are almost pathognomonic of Crohn disease but are rarely seen on endoscopic mucosal biopsies.
    • Dignosis/assessing severity & extent:
      • Radiographic studies establish the location, extent& severity of inflammatory bowel disease.
      • The plain abd radiograph can show a dilated colon& small-bowel obstruction.
      • A barium-contrast small-bowel series or enteroclysis provides information about location& amount of inflammatory or stricturing small-bowel disease.
      • Separation of loops of bowel, thumbprinting,spiculation (formation of needle-like projections) are all indicators of jejunoileitis.
      • CT enterography is the most comprehensive study, highlights the areas of bowel inflammation,stricture, abscesses, fistulae& mesenteritis.
    • Dignosis/assessing severity & extent:
      • Video capsule endoscopy provides the most direct evidence of small bowel ulcerations & approved in the diagnosis of Crohn disease.
      • It is highly sensitive& can lead to a false-positive diagnosis because 15% of normal volunteers may have ulcerations in the small bowel.
      • In a patient with possible obstruction, a patency capsule, which is a capsule system designed to determine small-bowel patency before video capsule endoscopy, should be ingested by the patient.
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    • Treatment :outline
      • Treatment of inflammatory bowel disease involves drug therapy and in certain cases surgery
    • Treatment : 5-ASA (sulfasalazine, olsalazine, balsalazide, mesalamine: oral, rectal UC: induction/maintenance CD (weak): induction/maintenance Inters nephritis (rare Diarrhea (olsalazine) Medication Indication Side Effects
    • Treatment : Antibiotics: Metronidazole, Ciprofloxacin CD: perianal/ colonic disease Metronidazole:PN , metallic taste, antabuse effect Ciprofloxacin: arthropathy, seizure) Medication Indication Side Effects
    • Treatment : CS (oral, IV, rectal) UC/CD: induction, not maintenance Acne, moon facies, truncal obesity, osteoporosis, osteonecrosis, DM, hypertension, cataracts, inf Budesonide CD (ileal/R colon): induction Minimal CS effects Medication Indication Side Effects
    • Treatment : Methotrexate CD: induction/maintenance Bone marrow suppression, hepatotoxicity, pulmonitis 6-MP, Azathioprine UC/CD: steroid withdrawal, maintenance Pancreatitis, fever, infection, leukopenia, hepatotoxicity, lymphoma Anti–TNF-α: Infliximab UC/CD: induction/maintenance Infusion reaction, tuberculosis reactivation, demyelination, infection,HF,Lymphoma. Adalimumab UC/CD: induction/maintenance Cyclosporine UC: steroid refractory Hypertension, nephro &neurotoxicity Medication Indication Side Effects
    • Treatment : Crohn Disease
      • 5-Aminosalicylates
      • MOA: anti-inflammatory effects secondary to inhibition of arachidonic acid in the bowel mucosa by cyclooxygenase.
      • 5 oral formulations developed from sulphaslazine.
      • 2 mesalamines are released in the small bowel in a pH- time-dependent manner used to treat both CD &ulcerative colitis.
      • Mesalamine is available in suppository & enema formulations, which are effective alone in patients who have inflammation limited to the rectosigmoid & may also be used in combination with an oral 5-ASA.
    • Treatment : Crohn Disease
      • Because Crohn disease is a transmural disease, the 5-ASA agents have not proved to be as efficacious as they are in ulcerative colitis but are often used in the treatment of mild disease.
      • Delayed-release mesalamine is commonly used for SB disease.
      • Other preparations of mesalamine are released in the distal ileum& therefore may have a role in treating ileal disease.
      • The azo-bonded 5-ASAs, such as balsalazide, olsalazine, and sulfasalazine have a potential effect only in Crohn colitis.
    • Treatment : Crohn Disease
      • CSs:
      • Ileal-release preparations of budesonide are indicated for the treatment of patients with mild ileal & right-sided colonic Crohn disease.
      • Budesonide is a topically active corticosteroid with a very high affinity for the glucocorticoid receptor (*15 that of prednisolone *195 that of hydrocortisone).
      • Only 10-15% of the drug reaches the systemic circulation; the rest is converted in the liver to inactive metabolites.
      • Conventional corticosteroids are effective in the short-term induction of remission in patients with Crohn disease but are generally used in patients with moderate disease at any location or in patients with ileal disease who have failed to respond to the 5-ASAs or budesonide.
      • Because of the toxic effects of long-term corticosteroid therapy (for example, osteoporosis, avascular necrosis, psychosis), it is important to devise a strategy for tapering the dosage& discontinuing corticosteroid therapy before the therapy is started.
    • Treatment : Crohn Disease
      • Immunomodulator:Azathioprine/ 6-mercaptopurine
      • Their onset of full activity is slow, may take up to 3 months.
      • These drugs are effective for the maintenance of remission in patients with Crohn disease regardless of disease distribution.
      • Adverse side effects include leukopenia, hepatotoxicity.
      • Before being treated with these agents, patients should be tested for thiopurine methyltransferase, the enzyme involved in the conversion of 6-mercaptopurine to inactive metabolites; patients who have low enzyme activity (or who are homozygous deficient in thiopurine methyltransferase) should not be treated with these agents.
      • Methotrexate is an immunomodulator induce / maintain remission in Crohn disease but not in ulcerative colitis.
      • There is a risk for hepatotoxicity& patients with persistently elevated liver tests may need to undergo liver biopsy.
      • Methotrexate is both a teratogen&abortifacient contraindicated in pregnant patients & breastfeeding.
    • Treatment : Crohn Disease
      • Biologicals:
      • (TNF-α) is a potent proinflammatory cytokine involved in the pathogenesis of both IBDs.
      • Infliximab / adalimumab are monoclonal antibodies against TNF-α: infliximab a chimeric antibody givenIV; adalimumab / certolizumab are humanized antibodies given subcutaneously.
      • These medications can reduce & close fistulae&induce remission in inflammatory Crohn disease within 4 to 8 weeks.
      • ? earlier use of potent biologic therapies to induce remission quickly while sparing the effects of systemic corticosteroid therapy.
      • All three anti-TNF-α agents are contraindicated in patients with active tuberculosis, tuberculin skin test / chest radiograph are required before the initiation of therapy.
      • Patients with latent tuberculosis require isoniazid prophylaxis because the disease can reactivate.
      • Treatment can lead to the reactivation of viral hepatitis , results in other infections& possibly lymphomam,specially concomitant use of infliximab /6-mercaptopurine.
    • Treatment : Crohn Disease
      • Biologicals:
      • In fibrostenotic stricturing disease leading to bowel obstruction, there is generally no viable medical therapy.
      • Limited small-bowel or ileocolic resection or bowel-sparing small-bowel stricturoplasties are the only therapy in this setting.
      • Recurrence of disease at the sites of previous surgery is common, and therefore surgery is not a preferred strategy for inflammatory disease.
      • 3 months of metronidazole reduce severe recurrences 12 months after surgery.
      • 6-mercaptopurine& likely azathioprine is modestly effective for decreasing both endoscopic&clinical postoperative recurrences in patients with Crohn disease.
    • Treatment : UC
      • The choice depends on both severity& extent of disease.
      • The 5-ASAs, which are not widely effective in Crohn disease, have well-documented efficacy& remain the mainstay of both induction & maintenance therapy in mild to moderate ulcerative colitis.
      • The 5-ASAs are the only medications shown to be effective as chemoprophylaxis for colorectal cancer in patients with ulcerative colitis.
    • Treatment : UC
      • CSs:
      • In patients not responsive to the 5-ASAs or in those with more severe disease, corticosteroids may induce remission.
      • In hospitalized patients IV therapy is usually administered, whereas in the outpatient setting oral & rectal corticosteroids are used.
      • No dose effect above the equivalent of prednisone 60 mg/d has been found.
      • Corticosteroid therapy does not maintain remission & is appropriate only as short-term therapy.
      • Although some patients may be put back successfully to 5-ASA as maintenance therapy after corticosteroid induction therapy, often an immunomodulator such as 6-mercaptopurine or its prodrug azathioprine is warranted; these agents are corticosteroid-sparing & maintain remission.
    • Treatment : UC
      • Inflixi/cyclospoine:
      • If corticosteroid therapy does not induce remission, patients may be treated with either infliximab or cyclosporine; in hospitalized patients, these medications are considered after a 7- to 10-day trial of corticosteroids.
      • Cyclosporine requires close monitoring for hypertension, neurologic& renal toxicity, infliximab may be favored despite its increased risk for opportunistic infection & possibly malignancy.
    • Treatment : UC
      • Surgery:
      • Medically refractory UC is treated surgically with curative total proctocolectomy with either end-ileostomy or ileal pouch-anal anastomosis, in which a neorectum is constructed from a segment of ileum and connected to the anus to retain continence.
      • Total proctocolectomy may also be warranted in patients with neoplasia, toxic megacolon, perforation, and refractory bleeding.
    • Infliximab - mucosal healing Baseline Week 10 Week 54 Rutgeerts et al. DDW 2002: [abstract] W1367.
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    • Microscopic colitis
      • Microscopic colitis is another type of IBD and may be classified as lymphocytic colitis or collagenous colitis.
      • The incidence of microscopic colitis parallels that of ulcerative colitis, more common in northern industrialized countries.
      • The disorder occurs disproportionately in middle-aged women, with a peak incidence at age 65 years.
      • Symptoms include a chronic relapsing-remitting pattern of watery diarrhea that varies in severity and may be accompanied by weight loss, abdominal pain, fatigue, and nausea.
      • Comorbid autoimmune diseases are common, including thyroid disorders, celiac disease, diabetes mellitus, RA.
      • The cause is probably multifactorial& likely represents an abnormal mucosal response to various luminal exposures including infection and drugs such as NSAIDs.
      • The mucosa usually appears normal macroscopically
      • Diagnosis is made solely on characteristic histologic findings.
    • Microscopic colitis
      • Collagenous colitis is characterized by a thickened subepithelial collagen layer
      • Lymphocytic colitis by increased number of intraepithelial lymphocytes is found in.
      • Supportive treatment with antidiarrheal agents, as loperamide, bismuth subsalicylate, diphenoxylate, may be effective for mild cases.
      • Otherwise, budesonide has the best-documented efficacy; prednisolone, 5-ASA, antibiotics& probiotics have been studied but the data is less robust.
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