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    IBD IBD Presentation Transcript

    • Inflammatory Bowel Disease Crystal M. Byerly, PA-C Seton Hill University PA Program Grant from Centocor, Inc.
    • Learning Objectives
      • Describe the disease process of Crohn’s versus Ulcerative Colitis
      • Identify the clinical presentation of a patient with Crohn’s Disease and Ulcerative Colitis
      • Discuss the various diagnostic workups and how they may differentiate Crohn’s from other GI ailments
      • Select appropriate treatments for a patient with Crohn’s Disease and Ulcerative Colitis
    • Inflammatory Bowel Disease
        • Artwork is reproduced, with permission, from the Johns Hopkins Gastroenterology and Hepatology Resource Center,
        • www.hopkins-gi.org,copyright 2006, Johns Hopkins University, all rights reserved.
    • IBD = Crohn’s Disease and Ulcerative Colitis
      • Both are chronic inflammatory disorders of the GI tract that currently have no real cure.
      • disorders of unknown cause involving genetic and immunological influence on the gastrointestinal tract's ability to distinguish foreign from self-antigens.
        • Artwork is reproduced, with permission, from the Johns Hopkins Gastroenterology and Hepatology Resource Center,
        • www.hopkins-gi.org,copyright 2006, Johns Hopkins University, all rights reserved.
    • Ulcerative Colitis
    • Disease Process of Ulcerative Colitis
      • Disorder in which inflammation affects the mucosa and submucosa of the colon and terminal ileum.
      • Peak incidence in ages 15-30 years old.
      Artwork is reproduced, with permission, from www.medicinenet.inc all rights reserved. 2007
    • Ulcerative Colitis
      • Ulcerative Proctitis refers to inflammation that is limited to the rectum.
      • In many patients with ulcerative proctitis, mild intermittent rectal bleeding may be the only symptom.
        • If no bloody stools (ever), its not UC
      • Other symptoms:
        • rectal pain
        • urgency
          • sudden feeling of having to defecate and a need to rush to the bathroom for fear of soiling
        • tenesmus
          • ineffective, painful urge to move one's bowels
    • Ulcerative Colitis
      • Universal Colitis or Pancolitis refers to inflammation affecting the entire colon
        • right colon, left colon, transverse colon and the rectum.
      • Symptoms of Pancolitis include:
        • bloody diarrhea
        • abdominal pain and cramps
        • weight loss
        • fatigue
        • fever
        • night sweats
        • Extraintestinal disease
    • Ulcerative Colitis
      • Clinical presentation: A 26 year old woman gives a history of increasing abdominal pain with blood and mucus in the stool.
      • The plain film shows visible gas-filled colon with variable mucosal thickening, giving typical thumb-printing appearance.
      • The colon appears shorter than normal and has lost its usual haustral pattern giving the lead pipe appearance term.
    • Classifications of UC Severity
      • MILD
        • < 4 loose BM/day with small amounts of blood
        • No sign of toxicity: No fever or tachycardia
        • Mild anemia
        • Normal ESR<30 mm/hr
      • MODERATE
        • > 4 stools/d
        • Minimal signs of toxicity
      • SEVERE
        • >6 bloody stools/d
        • Fever, tachycardia
        • Anemia
        • Elevated ESR
      • FULMINANT
        • >10 stools/d with continuous bleeding
        • Toxicity
        • Abdominal tenderness/distention
        • Transfusion requirement due to anemia
        • Colonic dilatation on xray
    • Complications of Severe UC
      • Toxic Megacolon
        • The inflammatory complications extend beyond the submucosa into the muscularis, the colon dilates and produces a toxic patient
          • HR>120bpm, fever, hypotension, electrolyte disturbances, MS changes, abdominal distention
      • Perforation of colon
        • As a result of toxic megacolon or severe UC
      • Strictures
        • 12% patients will develop between 5-25 yrs. after dx
    • Crohn’s Disease
    • Crohn’s Three Main Patterns of Distribution
      • 40% Ileum and Cecum
      • 30% confined to small intestine
      • 25% of colon only
        • 2/3 pancolonic
        • 1/3 segmental
              • About 80% of patients have small bowel involvement
    • Crohn’s Disease
      • Can involve any part of the GI tract.
      • The esophagus, mouth, and liver can also become inflamed.
      • Peak incidence 15-25 y.o, but often <10 yrs. old
    • Crohn’s Disease Symptoms
      • Diarrhea
      • Abdominal pain
        • From serosal inflammation
        • Intermittent partial obstructions
      • Weight loss
        • Can be up to 20% of body weight
        • Malabsorption and decreased oral intake
      • Relapsing and remitting symptoms that can spontaneously improve in 30% cases
    • Crohn’s Disease
      • Thickened bowel wall with secondary narrowing of the bowel lumen occurs.
      • Discontinuous (skip) lesions are a characteristic feature.
      • “ Cobblestone” appearance comes from the confluent ulcers.
      • Transmural thickening and ultimate fibrosis produces the “string sign” on CT = strictures .
    • Crohn’s Complications
      • Extension of a mucosal breach through the intestinal wall into extraintestinal tissue results in:
      • Abcesses
        • Occur in 15-20% of patients
        • Most commonly terminal ileum but not exclusively
      • Fistulas
        • During a Crohn’s pt.’s lifetime ~1/2 will develop a fistula
        • 83% of fistulas require surgical intervention
        • can be multiple sites:
          • Enteroenteric
          • Enterocutaneous
          • Enterovesical
          • Enterovaginal
    • Extraintestinal manifestations of IBD
      • Colitic arthritis
      • Sacroiliitis
      • Ankylosing spondylitis
      • Hepatobiliary complications
      • Osteopenia, osteoarthritis
      • Avascular necrosis
      • Renal stones
      • UTI due to fistulae
      • Pyoderma gangrenosum
      • Erythema nodosum
      • Sweet syndrome
      • Uveitis
      • Episcleritis
      • DVT/PE, intracranial, intraocular thromboembolic events
        • Artwork is reproduced, with permission, from the Johns Hopkins Gastroenterology and Hepatology Resource Center,
        • www.hopkins-gi.org,copyright 2006, Johns Hopkins University, all rights reserved.
    • Genetics of IBD
      • IBD is a polygenic disorder. Not all of the genes have been identified.
      • Phenotypes change throughout the course of disease
      • 10-15% of IBD is familial
        • Smokers get Crohn’s
        • Nonsmokers get UC
    • ColoRectal Cancer and IBD
      • Both CD and UC are known risk factors for colorectal cancer.
      • The risk of development of colorectal cancer is related to the severity and duration of the disease.
      • IBD patients should undergo colonoscopic surveillance for epithelial dysplasia, a precursor to cancer, at routine intervals.
        • Surveillance should be performed every 1–2 years in patients with 8-10 years duration of disease
        • annually in those with disease history of over 15 years
    • Diagnosing IBD
    • Differential Diagnosis of IBD
      • Chronic infectious colitis
      • Ischemic colitis
      • Diverticulitis
      • Irritable Bowel Syndrome
      • Small Bowel Bacterial Overgrowth
      • Crohn’s Disease
      • Ulcerative Colitis
      • Colon Cancer
    • Current Diagnostic Tools for Initial IBD Diagnosis
      • History and Physical Exam=clinical suspicion
      • Stool studies
      • Colonoscopy
      • Serology studies
      • Small Bowel Series/SBFT
      • Barium Enema
      • WCE=Wireless Capsule Endoscopy
      • EUS=Endoscopic Ultrasound
      • Pelvic MRI
      • MRI Enterography
      • CT Enterography
      • PET Scan
      • WBC Scanning
    • There is no ONE single test to dx IBD.
      • Historically the two main tests used:
        • Colonoscopy
        • SBFT
      • Lab studies have become an additional tool
    • Common Bloodwork in diagnosing IBD
      • C-Reactive Protein
        • Inflammation reflects inflammatory disease activity initially
        • Can be used as a marker to treatment response
      • pANCA = Anti-neutrophil cytoplasmic antibody with perinuclear staining
      • ASCA = anti-saccharomyces cerevisiae
    • Differentiating type of IBD Sandborn WJ et al, Inflamm Bowel Dis 2001;7:192-201 Peeters M et al, AM J Gastroenterology 2001; 96:730-4 LAB TEST SENSITIVITY SPECIFICITY TYPE IBD + pANCA 50-65% 85-92% UC +ASCA 55-61% 88-95% CROHN’S +pANCA & ASCA - 44-57% 81-97% UC -pANCA & ASCA+ 38-56% 94-97% CROHN’S
    • Immune Markers being studied for diagnosing IBD
      • Anti-12 = antibody to pseudomonas flourescens transcription factor
      • Omp C = antibody to Escherichia coli outer membrane porin C
      • PAB = Pancreatic antibodies
      • Fecal lactoferrin = fecal inflammation iron-binding glycoprotein
      • Anti-flagellin = CBir 1 antigen
    • IBD Management
      • Management can be divided into
        • Acute exacerbation
        • Maintenance of remission: conventional and biologic therapies
        • Surgical
        • Artwork is reproduced, with permission, from the Johns Hopkins Gastroenterology and Hepatology Resource Center,
        • www.hopkins-gi.org,copyright 2006, Johns Hopkins University, all rights reserved.
    • Acute Management of IBD
      • IV->PO Hydrocortisone or Methylprednisolone
        • Fast symptom relief
        • Not advised for prolonged use (120 day max)
        • No mucosal healing
        • Does not improve long term surgery rates
      • Cipro +/- Metronidazole
        • Effectiveness arguable but often seen used anyway
      • IV Cyclosporine 2-4 mg/kg
        • Effective for induction of remission but not long-term maintenance
      • Bowel Rest
      • Rectal +/- Oral 5-ASA; Sulfasalazines
    • Chronic Therapy of IBD
      • Goals:
        • remission of bowel inflammation
        • 1-4 BM/day with mucosal healing
        • Prevention of strictures, fistulas, other complications
        • Prevention of need for surgery
      • Hopefully feeling NORMAL, not just better
    • Corticosteroids
      • Severe IBD with hospitalization should be treated with IV steroids for rapid symptom relief.
      • Not a long-term solution
      • Convert IV to PO then taper off advised
      • Steroid dependence occurs in 28% pts.
      • Should be used in combination with AZA/ 6-MP +/- cyclosporine for severe IBD symptoms
    • Cyclosporine
      • IV dosing effective for induction of remission in severe UC
      • Little efficacy for maintenance of remission
      • No data on mucosal healing
      • Nephrotoxicity, seizures rare SE
    • Mesalamines: 5-ASA/Aminosalicylates
      • Aminosalicylates has been the mainstay of therapy because of its anti-inflammatory activities.
      • 50-70% response in high doses for UC.
      • Some mucosal healing found.
      • Excellent safety profile.
      • Not always beneficial. Be quick to move on if patient is not seeing benefit.
      • No fistula closure benefits to treatment found.
    • Mesalamines continued
      • Different formulations have been released and are thought to target specific regions of the bowel in oral and rectal formulations:
      • Sulfasalazine and Balsalazide
        • Are primarily released in the colon
        • Folic acid supplement advised with sulfasalazine
      • Dipentum and Asacol
        • Releases in the distal ileum and colon
      • Pentasa
        • Releases in the distal colon
      • Rowasa
        • Primarily effective in the distal colon and rectum
    • Thiopurines
      • Azathioprine/ 6-MP (mercaptopurine)
        • up to 6-12 weeks until effective
        • Has been shown beneficial in both induction and maintenance of remission
        • NOT as beneficial a 5-ASA for UC
        • Not as many trials for data with UC as with CD
        • Some chance of fistula closure with use
        • Must monitor CBC and LFTs with use
          • Bone marrow suppression
          • Liver toxicity possible
    • Methotrexate
      • Used with patients who are allergic or unresponsive to trial of Thiopurines (6-MP or AZA) at adequate dosing.
      • Has been shown to induce and maintain remission.
      • Little data to prove fistula closure on this drug
      • 1mg Folate supplementation advised
      • Monitor CBC and LFTs
        • Bone marrow suppression
        • Risk of hypersensitivity pneumonitis
        • Liver toxicity
    • Biologic Therapy –vs- Conventional Therapy in IBD
      • Conventional therapy
        • Aimed at symptom relief
        • Reduces hospitalizations
        • Doesn’t reduce long term surgery rates
        • Doesn’t maintain mucosal healing
      • Biologic therapy
        • 25-50% remission sx at 1 month
        • Reduces hospitalizations
        • Lowers surgery rates
        • Maintains long term mucosal healing
        • Fistula closures more often
    • Biologic Therapy with CD
      • If patients are not able to be in complete remission on Azathioprine with mucosal healing, and off steroids, the clinician should consider starting biologic therapy and discuss this with their patient as an effective treatment option.
    • Biologic Therapy
      • Infliximab is currently approved for use in Crohn’s Disease.
        • CD mucosal healing has been confirmed with endoscopy
        • Lower rates of hospitalization and surgery
        • Lessened fistulas
        • 800,000 patients treated with NO infusion reaction deaths
        • Some delayed hypersensitivity reactions
    • Adalimumab
      • Recombinant human IgG1 monoclonal antibody directed against tumor necrosis factor
      • Approved for tx of CD
      • Subcutaneous injection
    • Combination Therapy for Crohn’s
      • AZA + Biologic combinations
        • Slightly higher benefit
        • Higher blood concentrations with demonstrated lower C-Reactive Protein
        • Tolerated well
        • Lower rates of antibody formation to the drug
    • Biologic therapy with UC
      • Infliximab approved for moderate-severe Ulcerative Colitis who have had inadequate response to steroids and AZA.
        • Best results in overall sx reduction and healing with remission for UC.
      • Future therapies
        • Visilizumab
        • MLN-02
        • Natalizumab
    • IBD Surgery Treatment
    • Crohn’s Surgery
      • Probability of needing surgery increases with time
      • By 30 years post-diagnosis nearly 100% of patients will have had one surgery
      • Previous to biologic therapy the rate of surgery increased 10% per year with CD
      • Studies are looking at ways to predict future surgery needs based on new tx and serologies.
    • Surgical Therapies with Fistula
      • I & D for abcesses
      • Seton- keeps open with permanent suture material to prevent recurrent abcess.
      • Fistulectomy-currative with superficial fistula
      • Diverting surgical procedures
      • Rectal advancement flap or sleeve
      • Proctectomy or total proctocolectomy
    • Ileal Resection in Crohn’s Disease
      • Indications:
        • Failure of medical therapy
        • Recurrent obstruction
        • Perforation
        • Fistula
        • Abcess
        • Hemorrhage
        • Growth retardation (children)
        • carcinoma
        • Artwork is reproduced, with permission, from the Johns Hopkins Gastroenterology and Hepatology Resource Center,
        • www.hopkins-gi.org,copyright 2006, Johns Hopkins University, all rights reserved.
    • Post-Op Recurrence of CD
      • Commonly see recurrence near the ileocolonic anastomosis from previous surgery.
      • Endoscopic recurrence is found as high as 73% only 1 year later.
      • Prevention of recurrences using
        • Mesalamine/5-ASA, 6-MP, probiotics (lactobacillus), metronidazole
    • Ulcerative Colitis Surgery Indications
      • ABSOLUTE INDICATIONS:
        • Hemorrhage
        • Perforation
        • Cancer or dysplasia
        • Unresponsive acute sx
      • RELATIVE INDICATIONS:
        • Chronic intractability
        • Steroid dependency
        • Growth retardation
        • Systemic complications associated with UC
    • Surgery types with UC
      • IPAA = Ileal pouch-anal anastomosis
        • Gold standard as “cure” but not without its own complications
          • Incontinence, diarrhea, sexual dysfunction, decreased fertility, pouchitis, cuffitis
      • Conventional Ileostomy (Brooke)
      • Continent ileostomy (Koch pouch)
      • Ileorectal anastomosis
        • Artwork is reproduced, with permission, from the Johns Hopkins Gastroenterology and Hepatology Resource Center,
        • www.hopkins-gi.org,copyright 2006, Johns Hopkins University, all rights reserved.
        • Artwork is reproduced, with permission, from the Johns Hopkins Gastroenterology and Hepatology Resource Center,
        • www.hopkins-gi.org,copyright 2006, Johns Hopkins University, all rights reserved.
    • Conclusion Review of Learning Objectives
      • Describe the disease process of Crohn’s versus Ulcerative Colitis
      • Identify the clinical presentation of a patient with Crohn’s Disease and Ulcerative Colitis
      • Discuss the various diagnostic workups and how they may differentiate Crohn’s from other GI ailments
      • Select appropriate treatments for a patient with Crohn’s Disease and Ulcerative Colitis
    • Thank You