Inflammatory Inflammatory Bowel DiseaseBowel DiseaseDr. Mohammad ShaikhaniDr. Mohammad Shaikhani

CABM,FRCPCABM,FRCP..

2/20102/2010

Introduction Introduction A group of related conditions characterized by idiopathic A group of related conditions characterized by idiopathic

inflammation of GIT.inflammation of GIT. The 2 most common types are Crohn's disease & ulcerative The 2 most common types are Crohn's disease & ulcerative

colitis, both of which cause macroscopic inflammation.colitis, both of which cause macroscopic inflammation. Microscopic colitis is less common& does not cause significant Microscopic colitis is less common& does not cause significant

macroscopic abnormalities.macroscopic abnormalities. The pathophysiology is not well understood but most likely The pathophysiology is not well understood but most likely

involves immune dysfunction, genetically mediated, that causes involves immune dysfunction, genetically mediated, that causes inappropriate immune activation in response to luminal inappropriate immune activation in response to luminal microorganisms. microorganisms.

Although several features may differentiate Crohn's disease from Although several features may differentiate Crohn's disease from ulcerative colitis, there is significant overlap. ulcerative colitis, there is significant overlap.

Even after diagnostic evaluation, 10% have disorders that cannot Even after diagnostic evaluation, 10% have disorders that cannot be classified(indeterminate colitis).be classified(indeterminate colitis).

Less common colitis forms Less common colitis forms are:are:

Microscopic colitis (collagenous& Microscopic colitis (collagenous& lynphocytic)lynphocytic)

OthersOthers Diversion colitis after clostomies.Diversion colitis after clostomies. Radiation colitisRadiation colitis Drug induced colitisDrug induced colitis Infectious colitisInfectious colitis Ischemic colitis Ischemic colitis

IntroductionIntroduction

CD is a condition of chronic CD is a condition of chronic inflammation potentially inflammation potentially involving any location of the GIT involving any location of the GIT from mouth to anus.from mouth to anus.

UC is an inflammatory disorder UC is an inflammatory disorder that affects the rectum & extends that affects the rectum & extends proximally to affect variable proximally to affect variable extent of the colon.extent of the colon.

Epidemiology Epidemiology

CD:CD: 11stst peak 15-30 years of age, 2 peak 15-30 years of age, 2ndnd peak peak

around 60 yaround 60 y UC:UC:

High incidence areas: US, UK, High incidence areas: US, UK, northern Europenorthern Europe

Young adults, commoner in femalesYoung adults, commoner in females

Genetics 1st degree relatives have a *4-20 risk

higher than that of general population.

The best replicated linkage region, IBD1, on chromosome 16q contains the CD susceptibility gene, NOD2/CARD15.

Having one copy of the risk alleles confers a 2–4-fold risk for developing CD, whereas double-dose carriage increases the risk 20–40-fold.

Pathogenesis

The mucosa of CD patients is dominated by Th1 (T helper), which produce interferon-γ and IL-2.

In contrast, UC dominated by Th2 phenotype, which produce transforming growth factor (TGF-) and IL-5.

Activation of Th1 cells produce the down-regulatory cytokines IL-10 and TGF-.

Environmental Environmental PrecipitantsPrecipitants

Factors: NSAIDs use (?altered intestinal

barrier). Early appendectomy (increase UC

incidence) Smoking (protects against UC but

increases the risk of CD).

Environmental Environmental PrecipitantsPrecipitants

Smoking increases the risk of Crohn's disease, but not the risk of ulcerative colitis.

Arthritis, ophthalmologic disorders& dermatologic diseases are common extraintestinal manifestations of IBD.

Patients with IBD have an increased risk of developing intestinal dysplasia& colorectal cancer.

CD: PATHOLOGY

Early Findings: Aphthous ulcer. The presence of granulomas

Late findings: Linear ulcers. The classic cobble stoned appearance

may arise. Transmural inflammation Sinus tracts, and strictures. Fibrosis.

UC: PATHOLOGY The inflammation is predominantly confined to the mucosa. Non-specific (can be seen with any acute inflammation)

The lamina propria becomes edematous. Inflammatory infiltrate of neutrophils Neutrophils invade crypts, causing cryptitis & ultimately crypt

abscesses. Specific (suggest chronicity):

Distorted crypt architecture, crypt atrophy & a chronic inflammatory infiltrate.

UCUC

Distinguishing characteristics of Distinguishing characteristics of CD and UCCD and UC

Feature CDUC

Location SB or colonOnly colon (rarely

“backwash ileitis”

Anatomic distribution

Skip lesionsContinuous, begins distally

Rectal involvement

Rectal spareInvolved in >90%

Gross bleeding

Only 25%Universal

Peri-anal disease

75%Rare

Fistulization Yes No

Granulomas 50-75%No

Endoscopic features of CD Endoscopic features of CD and UCand UC

Feature CDUC

Mucosal involvement

Discontinuous

Continuous

Aphthous ulcers

Common Rare

Surrounding mucosa

Relatively normal

Abnormal

Longitudinal ulcer

Common Rare

Cobble stoningIn severe cases

No

Mucosal friability

Uncommon Common

Vascular pattern

Normal distorted

Pathologic features of CD Pathologic features of CD and UCand UC

Feature CDUC

Transmural inflammation

Yes Uncommon

Granulomas 50-75%No

Fissures Common Rare

Fibrosis Common No

Submucosal inflammation

Common Uncommon

Radiologic features of CD Radiologic features of CD and UCand UC

Feature CDUC

Nodularitygranularity

cobble stoningstring sign of SB

Collar button ulcers

Comparison of Features in Ulcerative Colitis and Crohn's Disease

FeatureUlcerative ColitisCrohn's Disease

Depth of inflammation

MucosalTransmural

Pattern of diseaseContiguousSkip areas

LocationColorectumMouth to anus

Rectal involvementUsualLess common

Ileal diseaseBackwash ileitis (15%–20% of patients)

Common

FistulasRareCommon

Perianal diseaseRareCommon

GranulomasUnlikely10%–30% of patients

Overt bleedingUsualLess common

MalnutritionUnlikelyMore common

Cancer riskColorectal cancer, cholangiocarcinoma (if primary sclerosing cholangitis is present)

Colorectal cancer, small bowel cancer (depending on disease location)

Tobacco useProtectiveHarmful

UCUC

CDCD

PresentationPresentation UC typically involves the rectum & extends proximally with UC typically involves the rectum & extends proximally with

contiguous inflammation that is generally limited to the mucosa of contiguous inflammation that is generally limited to the mucosa of the colon & rectum. the colon & rectum.

Patients usually present with bloody diarrhea associated with Patients usually present with bloody diarrhea associated with rectal discomfort, fecal urgency& cramps. rectal discomfort, fecal urgency& cramps.

Although most patients have bloody diarrhea, those with proctitis Although most patients have bloody diarrhea, those with proctitis can present with constipation.can present with constipation.

Patients with mild ulcerative colitis may have no abnormal Patients with mild ulcerative colitis may have no abnormal physical findings.physical findings.

Fever, weight loss, tachycardia, dehydration& significant abd Fever, weight loss, tachycardia, dehydration& significant abd tenderness or rebound indicate more severe disease. tenderness or rebound indicate more severe disease.

Hypoactive bowel sounds or abdominal distention suggests Hypoactive bowel sounds or abdominal distention suggests perforation or megacolon. perforation or megacolon.

PresentationPresentation CD may affect any segment of the GIT, is often discontinuous & CD may affect any segment of the GIT, is often discontinuous &

may cause CD commonly present with abdominal pain, may cause CD commonly present with abdominal pain, diarrhea& weight loss. diarrhea& weight loss.

Disease involving the small intestine often causes nonbloody Disease involving the small intestine often causes nonbloody diarrhea, whereas hematochezia is more likely when the colon is diarrhea, whereas hematochezia is more likely when the colon is involved. involved.

Diarrhea may be due to bacterial overgrowth, bile acid Diarrhea may be due to bacterial overgrowth, bile acid malabsorption, or steatorrhea, depending on the extent of disease, malabsorption, or steatorrhea, depending on the extent of disease, the presence of complications (e.g., strictures)& whether or not the presence of complications (e.g., strictures)& whether or not intestinal resection was performed.intestinal resection was performed.

CD may also present with bowel obstruction due to inflammation CD may also present with bowel obstruction due to inflammation or fibrosis.or fibrosis.

Those with fistulizing disease may have pneumaturia, fecaluria, Those with fistulizing disease may have pneumaturia, fecaluria, & recurrent or &vaginal drainage of feces (due to enterovaginal & recurrent or &vaginal drainage of feces (due to enterovaginal fistulas), or seepage of bowel contents through the skin (caused by fistulas), or seepage of bowel contents through the skin (caused by enterocutaneous fistulas).enterocutaneous fistulas).

PresentationPresentation Patients with upper GI involvement may have nausea, vomiting, Patients with upper GI involvement may have nausea, vomiting,

dyspepsia, DU or gastric outlet obstruction. dyspepsia, DU or gastric outlet obstruction. Abdominal exam may demonstrate tenderness or a mass that Abdominal exam may demonstrate tenderness or a mass that

most often occurs in the right lower quadrant. most often occurs in the right lower quadrant. High fever suggests an abscess or peritonitis. High fever suggests an abscess or peritonitis. Malnutrition may be present&growth failure is common in Malnutrition may be present&growth failure is common in

children. children. Perianal examination may reveal skin tags, inflammation, Perianal examination may reveal skin tags, inflammation,

induration, or fistulas. induration, or fistulas.

UC: PresentationUC: Presentation Must exclude infectious cause before Must exclude infectious cause before

making Dx.making Dx. Rectal Bleeding Rectal Bleeding Diarrhea:Diarrhea:

frequent passage of loose or liquid stool, often frequent passage of loose or liquid stool, often associated with passing large quantities of associated with passing large quantities of mucus.mucus.

Abdominal Pain:Abdominal Pain: it is not a prominent symptom. it is not a prominent symptom.

Anorexia, nausea, feverAnorexia, nausea, fever……

DDX of UCDDX of UC

InfectiousInfectious Drug inducedDrug induced Microscopic colitisMicroscopic colitis

UC: PresentationUC: Presentation Mild attack:Mild attack:

Most common form, mainly left sided colitis, <4 Most common form, mainly left sided colitis, <4 BM/day with no bloodBM/day with no blood

Moderate attack:Moderate attack: 25% of all patients, 4-6 BM/day with blood.25% of all patients, 4-6 BM/day with blood.

Severe or fulminant colitis:Severe or fulminant colitis: ~ 15% of cases, >6BM/day, bloody, fever, weight loss, ~ 15% of cases, >6BM/day, bloody, fever, weight loss,

diffuse abd tenderness, elevated WBC, most refractory diffuse abd tenderness, elevated WBC, most refractory to medical therapyto medical therapy

CDCD

Anatomic Anatomic distributiondistribution

CD activity CD activity indexindex

DDx DDx (lymphoma, (lymphoma, Yersinea Yersinea Enterocolitis, Enterocolitis, TB)TB)

CD: clinical CD: clinical presentationspresentations

Disease of the ileum: May present initially with a small bowel obstruction. Patients with an active disease often present with anorexia,

loose stools, and weight loss. Perianal disease

In 24% of patients with CD. Skin lesions include superficial ulcers, and abscesses. Anal canal lesions include fissures, ulcers, and stenosis.

CD ilitis: DDxCD ilitis: DDx

LymphomaLymphoma

Yersinea Enterocolitis Yersinea Enterocolitis TBTB

CD: clinical CD: clinical presentationspresentations

Colonic disease The typical presenting symptom is diarrhea,

occasionally with passage of obvious blood. Proctitis

May be the initial presentation in some cases of CD

Extra-intestinal manifestations Extra-intestinal manifestations of IBDof IBD

Arthritis:Arthritis: Peripheral arthritis, usu paralels the disease Peripheral arthritis, usu paralels the disease

activityactivity Ankylosing Spondylitis, 1-6%, sacroiliitisAnkylosing Spondylitis, 1-6%, sacroiliitis

Ocular lesions:Ocular lesions: Iritis (uvietis) (0.5-3%), episcleritis, keratitis,Iritis (uvietis) (0.5-3%), episcleritis, keratitis,

Skin and oral cavity:Skin and oral cavity: Erythema nodosum 1-3%Erythema nodosum 1-3% Pyoderma Gangrenosum 0.6%Pyoderma Gangrenosum 0.6% Aphthus stomatitis, metastatic CD.Aphthus stomatitis, metastatic CD.

Extra-intestinal manifestations Extra-intestinal manifestations of IBDof IBD

occur in 10% occur in 10% Arthritis is the most frequent & can be axial or peripheral. Arthritis is the most frequent & can be axial or peripheral. The most common types of axial arthritis are sacroiliitis& The most common types of axial arthritis are sacroiliitis&

ankylosing spondylitis. ankylosing spondylitis. Ophthalmologic / dermatologic manifestations are also fairly Ophthalmologic / dermatologic manifestations are also fairly

common. common. Episcleritis /uveitis occur in patients with either CD or UC. Episcleritis /uveitis occur in patients with either CD or UC. Erythema nodosum is more frequent CD& causes tender skin Erythema nodosum is more frequent CD& causes tender skin

nodules, especially on the legs. nodules, especially on the legs. Pyoderma gangrenosum occurs more often in UC& can range Pyoderma gangrenosum occurs more often in UC& can range

from small indurated lesions to large ulcers. from small indurated lesions to large ulcers.

Extra-intestinal manifestations Extra-intestinal manifestations of IBDof IBD

Primary sclerosing cholangitis occurs in 5% of patients with Primary sclerosing cholangitis occurs in 5% of patients with UC&to a lesser extent CD.UC&to a lesser extent CD.

Patients may present incidentally with jaundice, portal Patients may present incidentally with jaundice, portal hypertension, or lab findings indicative of cholestasis.hypertension, or lab findings indicative of cholestasis.

Patients with UC&primary sclerosing cholangitis are at an even Patients with UC&primary sclerosing cholangitis are at an even higher risk of developing colon cancer than are those with higher risk of developing colon cancer than are those with ulcerative colitis alone. ulcerative colitis alone.

Metabolic bone disease is common , especially those with CD,can Metabolic bone disease is common , especially those with CD,can occur independent of corticosteroid use& is associated with an occur independent of corticosteroid use& is associated with an increased risk of fractures. increased risk of fractures.

Patients with prolonged IBD, malabsorption, a history of using Patients with prolonged IBD, malabsorption, a history of using corticosteroids for >3 months, cigarette smoking, older age, corticosteroids for >3 months, cigarette smoking, older age, history of fractures, or a family history of osteoporosis should be history of fractures, or a family history of osteoporosis should be evaluated for the presence of metabolic bone disease. evaluated for the presence of metabolic bone disease.

Kidney stones / gallstones are other extraintestinal manifestations Kidney stones / gallstones are other extraintestinal manifestations of inflammatory bowel disease.of inflammatory bowel disease.

Extra-intestinal manifestations Extra-intestinal manifestations of IBDof IBD

Liver and Biliary tract disease:Liver and Biliary tract disease: Pericholangitis, fatty infiltration, PSC Pericholangitis, fatty infiltration, PSC

(1-4%, more with UC), (1-4%, more with UC), cholangiocarcinoma, gallstonescholangiocarcinoma, gallstones

Thromboembolic disease, vasculitis, Thromboembolic disease, vasculitis, Renal disease (urolithiasis, GN), Renal disease (urolithiasis, GN), clubbing, amyloidosis.clubbing, amyloidosis.

Complications of IBDComplications of IBD

BleedingBleeding StrictureStricture FistulaFistula Toxic megacolonToxic megacolon Cancer: Cancer: Patients with either UC or CD have an increased risk Patients with either UC or CD have an increased risk

of intestinal dysplasia & CRC that is related to the duration, of intestinal dysplasia & CRC that is related to the duration, extent& severity of the inflammation,so those with extent& severity of the inflammation,so those with extensive/longstanding disease should undergo regular extensive/longstanding disease should undergo regular colonoscopic examinations with mucosal biopsies to detect these colonoscopic examinations with mucosal biopsies to detect these complications. complications.

Complications of IBDComplications of IBD

UC:UC: Risk of cancer begins after 8 years, risk of Risk of cancer begins after 8 years, risk of

pancolitis 7% at 20 years and 17% at 30 years.pancolitis 7% at 20 years and 17% at 30 years. Increased risk: early age of onset, pancolitis.Increased risk: early age of onset, pancolitis. Need for colonoscopic screening after 8 yearsNeed for colonoscopic screening after 8 years

CD:CD: True incidence of cancer is uncertain, but True incidence of cancer is uncertain, but

could be as high as UCcould be as high as UC Need the same screening policy.Need the same screening policy.

Complications of Complications of IBDIBD

Colonoscopy with intubation of the terminal ileum& biopsies of the involved mucosa

Stool analysis for ova / parasites & Clostridium difficile toxin plus stool culture

Barium radiographs of small bowel, CT enterography&/or capsule endoscopy if Crohn's disease is suspected

Plain abd radiographs if bowel obstruction, toxic megacolon, or perforation is suspected

Abdominopelvic CT scan if abscess or fistula is suspected

Standard Diagnostic Evaluation for Suspected IBD:

Dignosis/assessing severity & Dignosis/assessing severity & extent:extent:

Lab, endoscopic,histologic findings assist in diagnosing Lab, endoscopic,histologic findings assist in diagnosing /assessing severity./assessing severity.

Stool examination is needed for all patients to exclude an Stool examination is needed for all patients to exclude an infectious cause. infectious cause.

The presence of significant anemia, acidosis, leukocytosis, The presence of significant anemia, acidosis, leukocytosis, or hypoalbuminemia indicates severe disease.or hypoalbuminemia indicates severe disease.

Evidence of malnutrition / vitamin deficiencies occurs Evidence of malnutrition / vitamin deficiencies occurs more commonly in CD than in UC. more commonly in CD than in UC.

Dignosis/assessing severity of extent: Colonoscopic Dignosis/assessing severity of extent: Colonoscopic fingings in UCfingings in UC

At presentation, 40% of patients with ulcerative colitis At presentation, 40% of patients with ulcerative colitis have proctitis, 40% have left-sided colitis (up to the splenic have proctitis, 40% have left-sided colitis (up to the splenic flexure)& 20% have pancolitis. flexure)& 20% have pancolitis.

Endoscopic findings can be subtle in patients with mild Endoscopic findings can be subtle in patients with mild disease&may show only mucosal edema / erythema. disease&may show only mucosal edema / erythema. increased inflammation causes friability, ulceration& increased inflammation causes friability, ulceration& bleeding bleeding

Histologic studies show distorted crypt architecture with Histologic studies show distorted crypt architecture with acute / chronic inflammation & crypt abscesses. acute / chronic inflammation & crypt abscesses.

Dignosis/assessing severity of extent: Colonoscopic Dignosis/assessing severity of extent: Colonoscopic fingings in CDfingings in CD

30% with CD have isolated small bowel disease, 40% have 30% with CD have isolated small bowel disease, 40% have ileocolitis, 25% have colitis alone, 5% have primarily ileocolitis, 25% have colitis alone, 5% have primarily upperGI or perianal disease.upperGI or perianal disease.

Endoscopic examination may show aphthous ulcers or Endoscopic examination may show aphthous ulcers or large ulcers that can coalesce and cause a “cobblestone” large ulcers that can coalesce and cause a “cobblestone” appearance. appearance.

Rectal sparing is common& areas of disease activity may Rectal sparing is common& areas of disease activity may be separated by areas of normal mucosa (“skip areas”). be separated by areas of normal mucosa (“skip areas”).

Histologic findings are similar to those in ulcerative colitis. Histologic findings are similar to those in ulcerative colitis. Granulomas are often absent but, when present, suggest Granulomas are often absent but, when present, suggest Crohn's disease. Crohn's disease.

Dignosis/assessing severity of extent: Dignosis/assessing severity of extent: ImagingImaging

Abd XRs are helpful in diagnosing bowel obstruction / Abd XRs are helpful in diagnosing bowel obstruction / dilatation in patients with CD & UC.dilatation in patients with CD & UC.

Radiographs of small bowel are more useful for Radiographs of small bowel are more useful for evaluating CD. evaluating CD.

Barium radiographs, enteroclysis, CT enterography, Barium radiographs, enteroclysis, CT enterography, capsule endoscopy are also helpful. capsule endoscopy are also helpful.

Although no single test is ideal, CT enterography is being Although no single test is ideal, CT enterography is being used more often because this study can assess various signs used more often because this study can assess various signs of inflammation & detect extraluminal findings such as of inflammation & detect extraluminal findings such as fistulas & abscesses. fistulas & abscesses.

Capsule endoscopy is a sensitive test for identifying small Capsule endoscopy is a sensitive test for identifying small bowel ulcers but should not be used in patients with bowel ulcers but should not be used in patients with obstructive symptoms because the capsule can be retained obstructive symptoms because the capsule can be retained in the intestine.in the intestine.

TreatmentTreatment :outline :outline

Goals of therapyGoals of therapy Induce / maintain remission.Induce / maintain remission. Ameliorate symptomsAmeliorate symptoms Improve pts quality of lifeImprove pts quality of life Adequate nutritionAdequate nutrition Prevent complication of both the disease & medicationsPrevent complication of both the disease & medications

Divided into active &maintenance strategies. Divided into active &maintenance strategies. Specific treatment choices depend on the type, extent& Specific treatment choices depend on the type, extent&

severity of the diseaseseverity of the disease

TreatmentTreatment :Active UC :Active UC Topical therapy is appropriate for distal disease. Options include cortisone foam & mesalamine or corticosteroid

suppositories for proctitis & hydrocortisone or mesalamine enemas for left-sided colitis.

Oral 5-aminosalicylates, including sulfasalazine, mesalamine, balsalazide& olsalazine, are appropriate for distal disease that does not respond to topical therapy or for mild to moderate pancolitis.

Oral prednisone is used when symptoms do not respond to 5-aminosalicylates.

Because prednisone & other corticosteroids have many acute / chronic toxic effects that are dose-/ duration-dependent, the lowest effective dose should be given for the shortest time.

Azathioprine (AZA) or 6-mercaptopurine (6-MP) may be used for patients who have incomplete disease remission while on corticosteroids,but both have delayed onset of action,so concomitant use of either AZA or 6-MP together with a 3- to 4-month course of prednisone is often necessary.

TreatmentTreatment :Active UC :Active UC

IV corticosteroids (equi to 40-60 mg of methylprednisolone) are indicated for treatment of severe ulcerative colitis unless the patient has fulminant disease or a complication that requires urgent surgery.

IV corticosteroids should only be used for 7 - 10 days. If the patient does not respond, surgery, infliximab, or

cyclosporine should be considered. Although cyclosporine is generally effective, its use is

limited because of its potential toxic effects. Narcotics / anticholinergic agents should be avoided in

order to reduce the risk of precipitating megacolon. Infliximab is effective for treating UC that is refractory to

other therapies & favored by some because of a perception of fewer side effects with infliximab than with cyclosporine.

TreatmentTreatment :Active UC :Active UC

Surgery is indicated for patients with refractory disease or corticosteroid dependence & for those with complications such as perforation, dysplasia, or malignancy.

Total proctocolectomy with ileal pouch–anal anastomosis is favored for younger patients& end-ileostomy is recommended for older patients.

TreatmentTreatment :Maintain :Maintain remission in UCremission in UC

Patients with mild distal disease may not need maintenance therapy. Patients with more severe disease should most likely continue treatment to prevent

relapse. The same medication used to achieve remission can often be given successfully for

maintenanceas oral or topical 5-aminosalicylate. Because 5-aminosalicylates have dose-dependent efficacy, tapering the dose during

maintenance may increase the chance of relapse. Topical & systemic corticosteroids are neither effective nor safe for use as

maintenance therapy. Patients whose acute symptoms responded to oral corticosteroids may receive

maintenance 5-aminosalicylates for milder disease or AZA/6-MP for more severe ulcerative colitis.

AZA/6-MP may also be used for patients who did not respond to a 5-aminosalicylate alone.

If a 5-aminosalicylate is used for maintenance therapy, corticosteroids should be tapered over several weeks,but disease flares during corticosteroid taper indicate the need for AZA/6-MP followed by slow tapering of corticosteroids over a 3- to 4-month period.

When remission is achieved with IV corticosteroids, changing to oral prednisone & AZA/6-MP is appropriate.

TreatmentTreatment :Active CD :Active CD

Treatment for Crohn's disease is similar to that for ulcerative colitis with the following exceptions:

1) smokers should be encouraged to stop; 2) 5-aminosalicylates are less effective for treating CD 3) metronidazole is an option for induction therapy. Drugs targeting the colon, as sulfasalazine, balsalazide,

olsalazine, are ineffective for treating small-bowel CD. Instead, mesalamine may be used for mild disease of the small bowel (Asacol® for ileal delivery and Pentasa® for more proximal delivery

Patients who do not respond to this regimen are treated as for those with moderate disease.

TreatmentTreatment :Active CD :Active CD Patients with moderate disease (presence of fever, weight loss,

abdominal tenderness without rebound, nausea or vomiting without obstruction, significant anemia) require corticosteroids.

Budesonide is an option for disease limited to the distal ileum and right colon because this corticosteroid is designed to deliver drug to this area of the bowel& has limited toxicity as a result of extensive metabolism in the liver.

Prednisone is used for more diffuse disease. Patients who have an incomplete response or become corticosteroid-

dependent should be given AZA/6-MP or methotrexate, especially if surgery is contraindicated.

Patients with severe Crohn's disease (presence of high fever, persistent vomiting, obstruction, abdominal tenderness with rebound, cachexia) in whom infection has been excluded require hospitalization and the same treatment used for those with severe ulcerative colitis. Infliximab should be considered when there is no response to IV corticosteroids.

TreatmentTreatment :Active CD :Active CD

Surgical resection is an option for patients with medically refractory disease, especially if large segments of small intestine are not involved.

Other indications for surgery include obstruction, fistulas, abscess, hemorrhage, dysplasia, cancer.

TreatmentTreatment :Maintain :Maintain remission in CDremission in CD

Mesalamine & AZA/6-MP are used for maintenance after medically induced remissions.

5-aminosalicylates, which are used for maintenance treatment of UC, are less effective for maintaining remissions in patients with Crohn's disease.

Patients with more severe disease may benefit from infliximab.

Mesalamine /AZA/6-MP may be effective for maintaining postoperative remissions, but the benefit is either minimal.

TreatmentTreatment :Perineal CD :Perineal CD

Small, minimally symptomatic fistulas may not require treatment.

More troublesome fistulas are treated with antibiotics, most commonly metronidazole / ciprofloxacin, with drainage of any abscesses.

Recurrence is common when antibiotics are stopped, and prolonged therapy may be needed.

Although AZA and 6-MP are effective for healing fistulas, these agents have mostly been replaced by infliximab.

Drains may be needed while fistulas are being treated medically.

Surgical diversion or proctectomy is indicated for refractory perianal Crohn's diseas

Infliximab - mucosal healing

Baseline Week 10 Week 54

Rutgeerts et al. DDW 2002: [abstract] W1367.

Microscopic colitis Characterized by chronic diarrhea, often with abdominal pain & mild

weight loss. Elderly persons (70 years of age / older) are affected most often. A possible association with certain medications, including nonsteroidal

anti-inflammatory drugs, has been suggested. Colonoscopy with biopsies is required for diagnosis. The colonic mucosa appears normal on gross examination; histologic

studies show surface epithelial lymphocytosis and a mixed inflammatory infiltrate.

Microscopic colitis is further classified into subtypes based on whether a thickened subepithelial collagen band is present (collagenous colitis) or absent (lymphocytic colitis).

Unlike the histologic findings in UC/CD, crypt architectural distortion is not present in microscopic colitis.

Collagenous colitis is more common in women, whereas lymphocytic colitis affects men & women almost equally.

Coexisting celiac sprue should be considered in patients with microscopic colitis that is refractory to therapy.

Microscopic colitis: treatment Lopeamide, diphenoxylate, bismuth subsalicylate, either alone

or in combination, are effective,well-tolerated as initial therapy.

If this initial regimen is ineffective, cholestyramine or a 5-aminosalicylate should be tried, although the latter drug is useful in only a minority of patients.

Patients who do not benefit from a 5-aminosalicylate may respond to corticosteroids.

Corticosteroids should only be used to induce remission,& one of the drugs used for initial therapy should also be used for maintenance.

Budesonide is effective for most patients with collagenous colitis. If this drug is not beneficial, the diagnosis should be reconsidered.

If no other cause for symptoms is found, AZA/6-MP or surgery (diverting ileostomy or proctocolectomy) is an option.

5-Aminosalicylic Acids5-Aminosalicylic Acids

The mainstay treatment of mild to moderately active UC and CD (induction).

5-ASA may act by blocking the production of

prostaglandins and leukotrienes, inhibiting bacterial peptide–induced

neutrophil chemotaxis and adenosine-induced secretion,

scavenging reactive oxygen metabolites

5-Aminosalicylic Acids5-Aminosalicylic Acids

For patients with distal colonic disease, a suppository or enema form will be most appropriate.

Maintenance treatment with a 5-aminosalicylic acid can be effective for sustaining remission in ulcerative colitis but is of questionable value in Crohn's disease.

Corticosteroids

Topical corticosteroids can be used as an alternative to 5-ASA in ulcerative proctitis or distal UC.

Oral prednisone or prednisolone is used for moderately severe UC or CD, in doses ranging up to 60 mg per day.

IV is warranted for patients who are sufficiently ill to require hospitalization; the majority will have a response within 7 to 10 days.

CorticosteroidsCorticosteroids No proven maintenance benefit in No proven maintenance benefit in

the treatment of either UC or CD. the treatment of either UC or CD. Many and serious side effects. Many and serious side effects. Budesonide: Budesonide:

less side effects, less side effects, its use is limited to patients with distal its use is limited to patients with distal

ileal and right-sided colonic diseaseileal and right-sided colonic disease

Anti-TNF Therapy: Anti-TNF Therapy: Infliximab Infliximab

It is a chimeric monoclonal antibody, binds soluble TNF.

Prompt onset, effects takes 6weeks to max of 6m.

Indicated in fisulizing crohns, refractory CD and refractory UC

Complications (it is safe and usu tolerable) Acute infusion reactions, which may include

chest tightness, dyspnea, rash, and hypotension. Delayed hypersensitivity reactions, consisting of

severe polyarthralgia, myalgia, facial edema, urticaria, or rash, are an unusual complication occurring from 3 to 12 days after an infusion.

Infliximab: side effectsInfliximab: side effects

Increase risk of upper respiratory infections.

Reactivation/dissemination of TB causing death.

Any patient suspected of having a pyogenic complication of CD or any serious infection should undergo adequate drainage & treatment with antibiotics before starting infliximab.