Inflammatory Bowel Disease

Learning Objectives
Describe the disease process of Crohns versus Ulcerative Colitis Identify the clinical presentation of a patient with Crohns Disease and Ulcerative Colitis Discuss the various diagnostic workups and how they may differentiate Crohns from other GI ailments Select appropriate treatments for a patient with Crohns Disease and Ulcerative Colitis

Introduction
CD is a condition of chronic inflammation potentially involving any location of the GIT from mouth to anus. UC is an inflammatory disorder that affects the rectum & extends proximally to affect variable extent of the colon.

Inflammatory Bowel Disease

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IBD= Crohns 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.

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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.

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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

SEVERE

> 4 stools/d Minimal signs of toxicity >6 bloody stools/d Fever, tachycardia Anemia Elevated ESR >10 stools/d with continuous bleeding Toxicity Abdominal tenderness/distention Transfusion requirement due to anemia Colonic dilatation on xray

FULMINANT

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

Crohns Disease

Crohns 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

Crohns 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

Crohns 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

Crohns 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.

Crohns 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 Crohns 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 Crohns 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 12 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 Crohns 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

LAB TEST SENSITIVITY SPECIFICITY TYPE IBD + pANCA 50-65% 85-92% UC

+ASCA
+pANCA & ASCA -pANCA & ASCA+

55-61%
44-57% 38-56%

88-95%
81-97% 94-97%

CROHNS
UC CROHNS

Sandborn WJ et al, Inflamm Bowel Dis 2001;7:192-201 Peeters M et al, AM J Gastroenterology 2001; 96:730-4

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 ironbinding glycoprotein Anti-flagellin = CBir 1 antigen

IBD Management

Management can be divided into

Acute exacerbation Maintenance of remission: conventional and biologic therapies Surgical
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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

Dipentum and Asacol Pentasa Rowasa

Are primarily released in the colon Folic acid supplement advised with sulfasalazine Releases in the distal ileum and colon Releases in the distal colon

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 Doesnt reduce long term surgery rates Doesnt 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 Crohns 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 Crohns

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

Crohns 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 Crohns Disease

Indications:
Failure of medical therapy Recurrent obstruction Perforation Fistula Abcess Hemorrhage Growth retardation (children) carcinoma

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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 Crohns versus Ulcerative Colitis Identify the clinical presentation of a patient with Crohns Disease and Ulcerative Colitis Discuss the various diagnostic workups and how they may differentiate Crohns from other GI ailments Select appropriate treatments for a patient with Crohns Disease and Ulcerative Colitis

Thank You