inflammatory bowel disease ward ppt

8/13/2019 Inflammatory Bowel Disease Ward Ppt

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PREPARED BY;DR. SYED FAHAD HAMID

INFLAMMATORY BOWELDISEASE


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Major forms

Two major forms;

1) Crohns disease

2) Ulcerative colitis


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CROHNS DISEASE

Definition;Crohns disease is a chronic recurrent disease

characterized by patchy transmural

inflammation involving any segment of the

gastrointestinal tract from mouth to the anus.


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ULCERATIVE COLITIS

Definition;Ulcerative colitis is a chronic, recurrent disease

characterized by diffuse mucosal inflammationinvolving only the colon. It invariably involvesthe rectum and may extend proximally in a

continuous fashion to involve part or all of thecolon.


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Crohns Disease

Incidence

4 10 per 100 000 per yearPrevalence

27 106 per 100 000

September 2004


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Ulcerative Colitis

Incidence6 15 per 100 000 per year

Prevalence

80 150 per 100 000

September 2004


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Jews are more prone than other ethnicgroups.

Crohns is slightly more commoner infemales.

Highest incidence and prevalence rates arefrom Northern Europe, UK and NorthAmerica.


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Aetiopathogenesis

Three major interactive co-factors.

1) Genetic susceptibility

2) The environment (both local

microenvironment and nutritional

environment

3) Host immune response


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Familial

Family history is the largest independent

risk factor.

1 in 5 with crohns and 1 in 6 with UC will

have a first degree relative with the

disease.


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Genetic

Increase concordance for the disease inmonozygotic twins than dizygotic twins.

Susceptibilty loci have been found onchromosome 16(IBD1), 12, 6, 14, 5, 19, 1,16(IBD8) and 3,These have been renamed IBD1-9respectively.


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Genetic; contd.

Significant loci also found on chromosome13q and in jewish families on 1p and 3q.

Linkage mutations on Card 15(NOD2), theunderlying gene on chromosome 16 (IBD1),and genes underlying IBD5 and IBD3 loci.The Card 15 (NOD2) gene is associated;Crohns disease in whites and stricturingsmall bowel crohns disease.


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Genetic; contd.

Recent SNP (single nucleotide polymorphism)scans have identified a locus for UC andCrohns disease at ECM1 (extracellular matrix

protein 1).Other risk loci; on IL23R, IL12B, NKX2-3 andMST1.

The autophagy genes ATG16L1 and IRGM,(along with CARD 15) are specific for Crohns disease.


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Genetic; contd.

HLA genes involved:HLA genes on chromosome 6 also appear tohave a role in modifying the disease.DRB 0103 allele- linked to aggressive courseof Ulcerative colitis and the need for surgery,and with colonic crohns disease.

DRB*0103 and MICA*010- perianal diseaseDRB*0701- ilealCrohns disease


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Environmental Factors

Good domestic hygiene has been shown to

be a risk factor for Crohns disease.


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Life style

Nutritional factors: Higher sugar and fat intake.

Smoking exacerbates Crohns disease.

Smoking improves Ulcerative colitis. Nicotine is

effective treatment of Ulcerative colitis.

Adverse life events and psychological factors

increase relapses in patients with quiescent

disease


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Appendicectomy

Is protective for Ulcerative colitis before 20

years of age.

Increases the risk of Crohns disease.


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Intestinal microflora

IBD is characterized by an overaggressive

immune response to luminal bacterial

antigens and other products in the

genetically susceptible.


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Intestinal microflora;contd.

Alteration in the bacterial flora :Increase in anaerobic bacteria in Crohns disease and aerobic in UC.

Bacterial antigens :Exert their pro-inflammatory influence byproducing toll like receptor ligands, whichinteract with the normal intestine withsurface toll like receptors (TLRs).The disruption of the surface TLR signallingprevents the mucosa to withstand bacterialinsults.


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September 2004

Medzhitov, R. et al. N Engl J Med 2000;343:338- 344

Toll-like Receptors


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Intestinal mucosal invasion;The intestinal wall in IBD patientsis contaminated by adherent and invading

bacteria.e.g. there is increased E.coli adherence tothe ileal-epithelial cells in Crohns disease.This occurs via E.colis type 1 pilli to a proteincalled carcinoembryonic antigen related celladhesion molecule 6 (CEACAM 6). The lattermay become a marker for inflammation.


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Defective chemical barrier or intestinaldefensins

Evidence suggests a decrease in human alphadefensin-1 (HD-1) in both Crohns disease andUC and lack of induction of HD-2 and HD-3,HD-5 in Crohns disease


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Impaired mucosal barrier function;

It explains the presence of unusual and

potentially pathogenic bacteria, e.g.

Mycobacterium paratuberculosis (MAP),

Listeria and mucosal adherent E.coli.


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Butyrate :

Sulphate producing bacteria increase luminal

levels of hydrogen sulphide resulting in

reduction of butyrate oxidation in colonic

mucosa, producing energy deficient state andleading to mucosal inflammation


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Pathogenesis

Defective mucosal immune system producingan inappropriate response to luminalantigens such as bacteria .Bacterial ligands interact with toll likereceptors TLRs expressed on epithelialmembranes via co-stimulatory moleculeswhich enable the epithelial cells to act asantigen presenting cells to the myeloiddendritic cells.


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Pathogenesis; contd..

Then follows the cascade of stimulation of thenaive Th 0 cells to the effector Th 1, Th2, andTh17 which predominate over the regulatory Tcells.Cytokines released from the above cellsstimulate the macrophages to secrete TNF-alpha, IL-1 & IL-6 in large quantitiesMacrophages are also stimulated by

plasmacytoid dendritic cells via natural killer cellswhich themselves can cause direct cytotoxiceffects on cells and secrete inflammatorycytokines.


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All the above result in leucocytes leaving thecirculation and releasing cytokines(lymphokines, arachidonic acid metabolites,neuropeptides, and free o2 radicals leading totissue damage and also attract moreinflammatory cells like a viscious circle.


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September 2004

Medzhitov, R. et al. N Engl J Med 2000;343:338- 344

Toll-like Receptors


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Pathology; Chrons disease

Any part can be affected.

Increase tendency to involve the terminal

ileum and ascending colon.

Can involve single(e.g. terminal ileum) or

multiple areas(skip lesions)

Can involve whole of the colon (total colitis)


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Pathology Ulcerative Colitis

Proctitis ( the rectum alone)

left sided colitis (Sigmoid and descending

colon)

Total colitis

backwash ilietis (inflammation of the

terminal ileum )


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Macroscopic changes; Crohns Disease

Small bowel is thickened and narrowedDeep fissures and ulcers in the mucosa

Cobble stone appearanceColon : fistulae and abscessesInitially the ulcers are aphthoid but laterlarger and deep ulcers appear in patchydistribution.


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September 2004

Copyright Science Press Internet Services

Aphthae


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September 2004

Ileitis


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Macroscopic changes;Ulcerative Colitis

Mucosa looks redenned, inflammed andbleeds easily

Severe disease -extensive ulceration and themucosa adjacent to it looks like inflammatorypolypsFulminant disease of either type- loss of mostof the mucosa leaving a few islands ofoedematous mucosa and toxic dilatationoccurs.


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September 2004

Ulcerative Colitis



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Microscopy; Crohns disease

Inflammation extends through all three layers

(transmural).

Increase in chronic inflammatory cells and

lymphoid hyperplasia

Non caseating granulomas in 50-60 %

G l


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September 2004Copyright Science Press Internet Services

Granuloma


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Microscopy; Ulcerative

colitisSuperficial inflammation.

Chronic inflammatory cell infiltrate in the

lamina propria

Crypt abscesses and goblet cell depletion


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September 2004

Ulcerative Colitis



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Differentiation

Sometimes it becomes difficult to diffrentiatebetween the two so in those cases,serological testing might help.


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Extragastrointestinalmanifestations

Occur in both the diseasesJoint complications are the commonest

The peripheral arthropathies are classified asType 1 (pauci articular) acute self limiting(


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EXTRAGASTROINTESTINALMANIFESTATIONS

ULCERATIVE COLITS(Percent cases)

CROHNS DISEASE(Percent cases)

EYESUveitisEpiscleritis,Conjunctivitis

25-8

53-10

JOINTSType 1(pauci-articular)ArthropathyType 2(polyarticular)arthropathyArthralgiaAnkylosing SponylitisInflammatory backpain

4

2.5

513.5

6

4

141.29

SKINErythema nodosum

Pyodermaan renosum

1

1

4

2


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Association of HLAs

HLA DRB1*0103 with pauci articular large

joint arthritis in Ulcerative Colitis and Chrons

disease

HLA-B44 Small joint symmetrical arthritis

HLA-B27 with sacroilietis


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Differential Diagnosis

All causes of diarrhoea should be excluded

Ileo colonic tuberculosis

Lymphomas


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CROHNS DISEASE


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Clinical presentation:

15% have no GI symptomsPatients with extensive disease have morefrequent recurrences30 % present with ilietis25 % present as anal and perianal disease

In 20-40 % enteric fistulae form, i.e. bladderor vagina.


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Clinical presentation:

Acute or insidiousClinical features are variable and depend on the region ofthe bowel affectedThe abdominal pain can be colicky suggesting obstruction.

80 percent present with diarrhoea and in colonicinvolvement, will contain blood.Can present with steatorrea in small bowel diseaseCan present as an emergency mimicking appendicitisCan be complicated by anal and perianal disease in 25%preceding colonic and small intestinal symptoms by manyyears.


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Examination

Weight loss and general ill healthAphthous ulcers

Tenderness in RIF, although mostlyabdominal examination is normalMass (abscess or matted inflammed bowelloops)Oedematous anal tags, fissures or perianalabscess


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Extragastrointestinal featuresSigmoidoscopy : Rectum may appear normal,

but a biopsy must be taken to findnonspecific inflammatory changes. Inextensive colonic disease the rectum may bespared but there still can be patchyinvolvement with an oedematoushemorrhagic mucosa.


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Investigations

Blood tests Normochromic normocytic anemia of chronic

disease.

Iron or folate deficiency. Megaloblastic anemia due to B-12 deficiency is

unusual despite terminal ileum involvement. Hypoalbuminemia(in severe disease) Blood cultures (if septicemic) Raised ESR, CRP and TLC.


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Liver biochemistry may be abnormal Serological tests (saccharomyces cerevisiae

antibody) is usually present pANCA is negative

Stools cultures

Should always be performed if diarrhoea ispresent.


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Radiology and imaging Ba follow through or CT scan with oral

contrast, in every patient with crohns

disease.

Findings -asymmetrical alteration inmucosal pattern with deep ulceration andareas of narrowing and thickening.Terminal ileum is the most common site.


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Magnetic resonance enteroclysis ( forimaging of the small bowel)

Colonoscopy, if colonic involvement issuspected, except in severe acute disease.

Plain abdominal X-rays, U/S or CT in patientspresenting acutely with colonic symptoms,

High resolution U/S and CT scan are helpful indefining the thickness of the bowel wall andmesnetry as well as intraabdominal and paraintestinal abscesses.


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Endoanal US and MRI for perianal disease

Radionuclide scans with gallium labelled

polymorphs or indium or technetium

labelled leucocytes, to identify small

intestinal and colonic disease and to localiseextraintestinal abscesses


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Disease activity

Assessed by using simple parameters such asHb, white cell count .Inflammatory markers (ESR, CRP, and platletcount) and serum albumin.Calprotectin is a calcium binding protein andaccounts for 60 % of cytosolic protein ofneutrophils.

Faecal calprotectin is cheap noninvasive markerof disease activity in IBD and may be of help inpredicting response to and failure of treatment.


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Medical management

AimInducing remission

Maintaining remission

M f ild


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Management of mild symptoms

Mild symptoms- symptomatic treatment

Stop smokingDiarrhoea : anti diarrhoeals ( loperamide, codeinphosphate or co-phenotropeCholestyramine if diarrhoea is due to bile acid

malabsorptionAnemia depending on the cause should be treatedAnemia of chronic disease will improve as thedisease improves (erythropoetin can be used)Active (moderate to severe) disease may requirehospital admissionModerate to severe chrons colitis are treated as forUC


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Remission induction

Glucocorticoids oral or IV (30-60 mg/day)Slow realease formulations such asbudesonide in ileocaecal diseaseIt has a high topical activity and is rapidlyeliminated by the liver so less suppression ofthe cortisol and least adverse effectsRemission response rates vary(60-90 %)depending upon the site and extent of thedisease.


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Unresponsive patients - raise the dose ofazathioprine to levels that make patientsleucopenic.


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Remission maintenance

Flareups occur on tapering steroids orstopping enteral diets. They can be treated bytemporarily increasing steroid doses for

inducing remission.Aminosalicylates for treating remission incrohns colitis.Immunosuppressives (azathioprine,6mercaptopurine, methotrexate andmycophenolate mofetil) are used in all otherpatients for maintaining remission.


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Biological agents

Failure to induce or maintain remission,biological agents can be used.Infliximab a chimeric anti TNF-alphamonoclonal antibody Is the most widely used biological agent.Most successful at inducing remission incortocosteroid/immunosuppressive resistantpatients and also maintaining it.Efficacy is reduced due to formation ofantibodies


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Two other TNF-alpha antibodies are nowwidely used.Adalimumab fully human anti-TNFmonoclonal antibodiesUsed in patients who fail to respond toinfliximab as well as those who have notreceived it.


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Certolizumab pegol is a pegylated Fab fragment of humanized anti-TNF-alphamonoclonal antibody.Short-term and longer-term efficacy hasbeen demonstrated.


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Other new anti-TNF antibody therapie sinclude CDP571, etanercept and onercept.


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Surgical management

Approximately 80% require an operation atsome time in their life during the course of theirdisease

Nevertheless surgery should be avoided ifpossible and only minimal resection should beundertaken as recurrence(15%) is almostinevitable.

Chances of recurrences can be reduced inpatients undergoing their second surgery bytreating them with Azathiprine and 6-Mercaptopurine.


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Indication for surgeryFailure of medical therapy, with acute orchronic symptoms producing ill health.Complications (e.g. toxic dilatation,obstruction, perforation, abscesses andenterocutaneous fistula)Failure to grow in children despite medicaltreatment


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Surgical approachStricturoplasty(some strictures)Resection and end to end anastamosis(others)Subtotal colectomy and ileorectal anastamosiswhen entire colon is involved and rectum isspared.

Panproctocolectomy with an ileostomy is thestandard procedure for whole colonic and rectalinvolvement.


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ULCERATIVE COLITIS


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Ulcerative colitis

Clinical featuresMajor symptoms (diarrhoea with blood andmucous)General features include malaise, lethargy,anorexia and weight lossAphthous ulceration in mouth


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Can be classified as mild moderate andsevereRuns a course of remissions andexacerbations10% have persistent chronic symptomsOthers have only a single attackIn proctitis urgency, tenesmus, are common


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Toxic megacolon is a serious complication.On plain abdominal a dilated thin walledcolon with a diameter of >6cm will be seen.Serious complication and may result inperforation and high mortality(15-25%).Urgent surgery is required in all patients inwhom toxic dilatation has not resolved within48 hours.


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Severe attack; contd

Management

Admitt to hospital

Assess IV fluids

Monitor daily:Stool frequecyAbdominal X rayFBC, CRPalbumin


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Examination

Generally no specific signsSlight distention and tenderness on palpation

Rectal examination: blood will be seenRigid sigmoidoscopic examination:inflammed bleeding and friable mucosa. canbe normal in cases of rectal sparing.


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Investigations

Blood testsIron deficiency anemia

White cells and platlet counts are raisedESR and CRP are raisedLiver biochemistry may be abnormal

Hypoalbuminemia occurs in severe diseasepANCA may be positive


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Stool cultures

Should always be performed to excludeinfective causes of colitis


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ImagingPlain abdominal xrays with an abdominalultrasound : key investigations in moderateto severe attacksThe extent of the disease can be assessed bythe degree of air distribution in the colon.Thickening of the colonic wall can bedetected on ultrasound as can the degree ofhyperemia in the colonic wall.


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Radionuclide scansUsed to assess colonic inflammation


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ColonoscopyShould not be performed in acute attacksbecause of the risk of perforation.Can be performed in long standing chronicdiseases in defining the extent and activity ofthe disease and excluding the onset ofdysplasia and carcinoma in patients withlongstanding disease of 10 years duration ormore


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Medical management

All patients should be treated with anaminosalicylate.The active moiety is 5-aminosalicylic acid(5-ASA).The 5-ASA is absorbed in the small intestine (andmay be nephrotoxic) so the design of variousaminosalicylate preparation is based on the bindingof 5-ASA by an azo bond tosulphapyridine(sulphasalizine), 4 amino benzyl betaalanine(balsalazide), or to 5-ASA itself(olsalazine),coating with a PH sensitive polymer(Asacol), orpackaging of 5-ASA in microspheres(pentasa)


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Proctitis : Oral amino salicylates +local rectal steroidpreparation are the first line treatement .Mesalazine enemas and budesonide enemascan be tried.Resistant cases: oral cortiocosteroids alone orcombination with azathioprine can be tried


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Left sided proctocolitis:Oral aminosalicylates + local rectal steroidpreparationModerate to severe attacks: oralprednisolone.Unresponsive patient: to be admitted to thehospital


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Monitor clinical status (fever, tachycardia,abdominal signs). Daily FBC, ESR, CRP, electrolytes, urea,

LFTS, X-ray erect abdomen and stool weight.Persistent fever, tachycardia, falling Hb, risingTLC, falling potassium, falling Albumin, andpersistently raised stool weight(>500gm/day)with loose blood stained stool shows nonresponsiveness and is an indication forsurgery.


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Rescue therapy to avoid colectomy: (forpatients with poor prognostic signs and a CRPmore than 45mg/L after 3 days of IV

hydrocortisone)Hydrocortisone + IV cyclosporin 2mg/kg/dayor TNF- alpha antibody therapyOther agents: visilizumab andleucocytapheresis(selective removal of whitecells from blood and reinfusion of RBCs andleucocyte poor plasma)


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Patients responding to i.v. hydrocortisonetreatement, oral prednisolone therapy shouldbe substituted and doses should be tailedoff(5-10mg/weekly)Maintenace of remission is withaminosalicylates.

In patients in whom it is not possible toreduce the dose without a flareup,azathioprine is used.

S i l M


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Surgical ManagementTreatment of Ulcerative colitis is mainlymedical, but surgery has a very central role aswell.Indications for surgery in Ulcerative colitis

areFulminant acute attack:Failure of medical treatment (3 days)

Toxic dilatationHaemorrhageperforation


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Chronic diseaseIncomplete response to medical treatment

Excessive steroid requirementNon-compliance with medicationRisk of cancer


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Surgical approachSubtotal colectomy with end ileostomy andpreservation of the rectum is the operation ofchoice in acute diseaseLater a number of options can be tried. Theseinclude, proctectomy with a permanent

ileostomy orIleorectal anastomosis if a permanentileostomy is to be avoided


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Annual biopsies of the rectal mucosa must becarried out to detect dysplasia.With ileoanal anastomosis, a pouch of theileum is formed that acts as a reservoir.A third patients will experience pouchitiswhich is characterized by the pouch mucosa

with clinical symptoms of diarrhoea,bleeding, fever and at times exacerbationwith extracolonic manifestations


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Pouchitis is twice as high in primarysclerosing cholangitis.Two thirds will recur as acute relapsing orchronic unremitting forms.Treatment is not always satisfactory andincludes topical and oral 5-ASA,

corticosteroids, metronidazole andciprofloxacin.


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Probiotics (four strains of lactobacillus,three strains of bifidobacterium, and one ofstreptococcus) have been shown to prevent

the onset of pouchitis and to maintainremission. Short chain fatty acid enemas andalicaforsen( a selective inhibitor ofintercellular adhesion molecule 1, ICAM-1,expression) enemas have shown promise inpouchitis treatment.

C d P g i


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Course and Prognosis

Third of the patients with distal inflammatoryproctitis due to Ulcerative colitis will developemore proximal disease, with 5-10%developing total colitis.A third will have a single attackOthers will have relapsing course

A third will undergo colectomy within 20years of diagnosis

C d IBD


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Cancer and IBD

There is an increased riskScreening strategiesScreening colonoscopy with multiple biopsiesshould be done every 2 years in patients with

total UC andcrohns

colitis of 10 years and everyyear after 20 yearsLeft sided UC and those with less than totalcrohns colitis should have a screeningcolonoscopy at 15 years and therafter biannuallyPatients with Ulcerative colitis and primarysclerosing cholangitis are particularly at risk ofdeveloping colon cancer and should have yearlyscreening

Pregnancy and Inflammatory


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bowel disease

Women with inactive IBD have normalfertilityFertility however may be decreased in activediseaseSpotaneous abortions are twice as likely inthose with active disease than those with

inactive disease.Relapse rates in pregnancy are similar tothose of non pregnant patients.


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Flareups in the first trimester enhances therisk of flareups in puerperial period.There is no risk of flareup in pregnancy forboth Crohns disease and ulcerative colitisRelapse if it does occur is however more likelyin the first trimester.

Amino salicylates, steroids, and azathiprineare safe at the time of conception and duringpregnancy


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THANKYOU FOR YOUR PATIENCE

inflammatory bowel disease ward ppt

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