INFLAMMATORYBOWEL DISEASE

Dr. Ansuman Dash

IBD

Inflammatory bowel disease is an idiopathicinflammatory intestinal disease resulting from aninappropriate immune activation to host intestinalmicroflora.

Types of IBD are

Ulcerative colitis

Crohn’s disease

Indeterminate colitis

■ Ulcerative colitis - nonspecific inflammatory bowel disease of unknown etiology that effects the mucosa and submucosa of the colon and rectum

■ Crohn’s disease - nonspecific inflammatory bowel disease that may affect any segment of the gastrointestinal tract

■ Indeterminate colitis

– 15% patients with IBD impossible to differentiate

History

Morgagni provided a description of intestinal inflammation characteristic of Crohn's disease in 1761.

In 1932, the landmark publication of Crohn, Ginzburg, andOppenheimer called attention to “terminal ileitis” as a distinct entity and chronic disease.

The name “Crohn's disease” has been adopted to encompass the many clinical presentations of this pathologic entity. But for the alphabetic priority these authors chose Crohn's disease.

EPIDEMIOLOGY

■ Incidence and prevalence highest in westernized nations.

■ Prevalence rates are

■ 4.9-505 /1 lakh in Europe

■ 37.5 – 248 /1 lakh in north America

■ 4.9 – 168.3 in Asia

■ Peak incidence in 2nd to 4th decade with a 2nd peak in 7th – 9th

decade.

EPIDEMIOLOGY

■ A house to house survey of 4796 houses including 21921 persons (> 14 years age) in Haryana state revealed 10 cases (5 each in both sexes) which gave a prevalence of 45.5/105 population (42.8/105 for males and 48.6/105 for females).

■ In a later study from the neighbouring state of Punjab where cluster sampling method was employed the crude incidence and prevalence of UC was found to be 6.02/105 and 44.8/105 population which was the highest in Asia but still less than that of North America and Europe.

Etiopathogenisis

Genetic susceptibility

Environmental factors

Host immunity

etiology

• DIET:

• Fat intake

• Fast food ingestion

• Milk and fibre consumption

• Total protein and energy intake

• DRUGS:

• NSAIDS: DICLOFENAC

• Antibiotics: may precipitate the relapse

• Oral contraceptives increase the risk of developing CD

• Smoking is protective against UC but increases the risk of CD

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GENETICS:• If a patient has IBD, the lifetime risk that a first-degree

relative will be affected is ~15%.

• If two parents have IBD, each child has a 36% chance of being affected.

• In twin studies , 58% of monozygotic twins are concordant for CD and 6% are concordant for UC, whereas 4% of dizygotic twins are concordant for CD and none are concordant for UC.

• Mutations of gene CARD15/NOD2 on chromosome 16 is associated with SI CD 2 other genes – OCTN1, DLG5

■ ETHNIC: Jews are more prone to IBD than non jews.

■ STRESS: Increase the relapse of IBD

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CONTD..

■ INFECTION:– Mycobacterium paratuberculosis : CD

– Diarrhoea :Ulcerative colitis

IBD is currently considered an inappropriate immune response to endogenous commensal microbiota within the intestines, with or without some component of autoimmunity.

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PATHOPHYSIOLOGY

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Genetics

Crohn’s disease Ulcerative colitis

1. NOD2/CARD15

2. Autophagy-related genes

3. Interleukin (IL)-23

1. MDR 1

2. HLA-DR1

3. HLA-DR3,DQ2

Anatomical classification of ulcerative colitis and CROHN’s disease

ULCERATIVE

COLITIS CROHNS DISEASE

– Proctitis

– Proctosigmoiditis

– Left sided colitis

– Pancolitis

– Backwash ileitis

– Gastro duodenal Crohn’s disease( gastroduodenitis)

– Jejunoileitis

– Ileitis

– Ileocolitis

– Crohn’s (granulomatous) colitis

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Ulcerative Colitis

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UC Pathology

Macroscopic Appearance

■ Involves rectum and extends proximally to involve entire colon.

40 – 50 % - disease limited to rectum and rectosigmoid

30 – 40 % - extends beyond sigmoid but not involving whole colon

20 % - Pancolitis

No skip lesions.

Backwash ileitis – Inflammation extends 2 – 3 cm into terminal ileum in 10 -20 %

■ Mild Inflammation – Mucosa is erythematous and has granular surface. (Sandpaper appearance)

■ Severe inflammation – Mucosa hemorrhagic, edematous and ulcerated.

■ Long standing disease – Pseudopolyps

■ Toxic megacolon – Transverse or right colon with diameter > 6cm with loss of haustrations in severe UC.

Microscopic Appearance

■ Limited to mucosa and submucosa.

■ Deeper layers may be affected in fulminant disease.

■ Distortion of crypt architecture

■ Basal plasma cells and lymphoid aggregates.

■ Mucosal vascular congestion with edema and focal hemorrhage.

■ Cryptitis and Crypt abscess – Neutrophils invade the epithelium in the crypts

■ Mucosal infiltration by Neutrophils, Lymphocytes, Plasma cells and Macrophages.

Crypt

distortion

Diffuse inflammation

CLINICAL FEATURES of UC■ Diarrhoea

■ Rectal bleeding

■ Tenesmus

■ Passage of mucus

■ Crampy abdominal pain

Proctitis –

■ Fresh blood and blood stained mucus, either with stool or streaked onto the surface of normal or hard stool. Sense of incomplete evacuation and urgency

■ Proctosigmoiditis – May have constipation

Severe Colitis

■ Grossly bloody diarrhea

■ Liquid stool containing blood, pus and fecal matter

■ Anorexia

■ Nausea

■ Vomiting

SIGNS –

■ Tender anal canal

■ Blood on DRE

■ Tenderness on palpation over colon in severe disease

Ulcerative Colitis: Disease Presentation

Mild Moderate Severe

Bowel movements <4/day 4-6/day >6/day

Blood in stools Small Moderate Severe

Tachycardia None <90/min >90/min

Fever None <99.5F >99.5F

Anemia Mild Moderate Severe

ESR <30 >30

Endoscopy Erythema, decreased vascular pattern, fine granularity

Marked erythema, coarse granularity, absent vascular markings, contact bleeding, no ulcerations

Spontaneous bleeding, ulcerations

INVESTIGATIONS

■ Elevated acute phase reactants like CRP and elevated ESR

■ Low Hemoglobin

■ Leukocytosis may be seen

■ Fecal lactoferrin and fecal Calprotectin levels – Correlate with histologic inflammation and predict relapses

■ Stool examination for bacteria, C. difficile toxin and ova and parasites

■ P-ANCA is positive in 60 -70 %. ASCA positive in 10 – 15 %.

■ SIGMOIDOSCOPY and COLONOSCOPY with biopsy – to assess disease activity and confirm diagnosis

■ Mild disease – Mild erythema and friability

■ Severe disease – spontaneous bleeding and ulcerations

RADIOLOGY

■ Earliest radiologic change with single-contrast barium enema is fine mucosal granularity.

■ Deep ulcers appear as collar – button ulcer

■ Loss of haustrations in long standing disease.

■ Colon becomes shortened and narrowed

CT and MRI

■ Mild mural thickening

■ Absence of small bowel thickening

■ Target appearance of rectum

■ Adenopathy

Etiology

■ Three prevalent theories include:– response to a specific infectious agent

– a defective mucosal barrier allowing an increased exposure to antigens– an abnormal host response to dietary antigens

■ One infectious agent that has generated some interest is Mycobacterium paratuberculosis, isolated in up to 65% of tissue samples from Crohn's patients

■ A statistically significant association between the onset of Crohn's disease and prior use of antibiotics has also been observed

■ Smoking appears to be a risk factor for Crohn's disease, and after intestinal resection, the risk of recurrence is greatly increased in smokers

COMPLICATIONS

■Massive hemorrhage

■Toxic Megacolon

■Perforation and Peritonitis

■Stricture in 5 – 10 % of patients. A stricture that is impassable to colonoscope should be presumed malignant unless proven otherwise.

■Malignant transformation

Risk for carcinoma in UC

■ Disease duration– 25% at 25 yrs, 35% at 30 yrs, 45% at 35 yrs, and 65% at 40 yrs

■ Pancolonic disease– Left-sided only pts less likely to develop cancer than pancolitis pts

■ Continuously active disease

■ Severity of Inflammation– Colonic stricture must be considered to be cancer until proven

otherwise

CROHN’S DISEASE

Pathology

MACROSCOPIC FEATURES

■ Can affect any part of the GI tract from mouth to anus.

■ 30 – 40 % - small bowel ds alone

■ 40 – 55 % - both small and large intestine affected

■ 15 – 25 % - colitis alone

■ Terminal ileum is involved in 90 % of small intestinal ds

■ Skip Lesions

■ Perirectal fistulas, fissures, abscesses and anal stenosis seen in one third of CD patients.

■ Mild disease – small aphthous ulcers

■Linear serpiginous ulcers seen

■Cobblestone appearance

■Pseudopolyps may be seen

■ Fistula tracts may be seen

■ Fibrosis and stricture of bowel

■Creeping fat

■ Histologic– transmural inflammation, submucosal edema,

loose macrophage aggregation, and ultimately fibrosis

– Pathognomonic: the noncaseating granuloma, a localized, well-formed aggregate of epithelioid histocytes surrounded by lymphocytes and giant cells; found in 50% of resected specimens.

– Focal crypt abscess may be seen

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Clinical Presentation

ILEOCOLITIS –

Recurrent right lower quadrant pain and diarrhea

Palpable mass in right lower quadrant

Mimics acute appendicitis

May present as bowel obstruction.

JEJUNOILEITIS –

Malabsorption and steatorrhoea

Anemia, hypoalbuminemia, hypocalcemia, hyperoxaluria

COLITIS

■ Malaise

■ Diarrhoea

■ Crampy abdominal pain

■ Hematochezia

■ Incontinence, hemorrhoidal tags, anorectal tags, perirectal abscess in perianal disease

Unusual Presentations of CD

■ Gastroduodenal - H-pylori-negative peptic ulcer disease, dyspepsia or epigastric pain as the primary symptoms

■ Esophageal - < 2% of patients.

– Dysphagia, odynophagia, substernal chest pain, and heartburn

– Mouth ulcers

– Esophageal stricture and esophagobronchial fistula

■ acute granulommatous appendicitis -

Perianal disease of CD

1. Skin lesions- include maceration, superficial ulcers, abscesses, and skin tags

type 1 (elephant ears) are typically soft and painless and large

type 2 are typically edematous, hard, and tender.

2. Anal canal lesions - fissures, ulcers, and stenosis

3. Perianal fistulas.

Aggressive fistulizing disease

Fistulas are manifestations of the transmural nature of CD

Perianal fistulas are common and occur in 15% to 35% of patients.

Enterovaginal fistulas occur in women

Enterovesicular - recurrent polymicrobial UTI or as frank pneumaturia and fecaluria.

Enterocutaneous fistula after appendectomy

Other types- enteroenteric, enterocolonic, and colocolonicfistulas

Stricture

Stricture is another characteristic complication of long-standing inflammation

Symptoms can include colicky, postprandial abdominal pain and bloating, punctuated by more-severe episodes, and often culminating in complete obstruction.

String sign - markedly narrowed bowel segment amid widely spaced bowel loops

EXTRAINTESTINAL MANIFESTATIONS

Musculoskeletal

Clubbing

Arthritic manifestations

Peripheral arthropathy - 16% to 20% Pauciarticular arthropathy (type I, affecting four or fewer joints)

Polyarticular arthropathy (type II, with five or more joints affected)

Axial arthropathies - 3% to 10%

Metabolic bone disease

Granulomatous vasculitis, periostitis and amyloidosis.

Mucocutaneous

Pyoderma gangrenosum

Erythema nodosum

Granulomatous inflammation of the skin

Aphthous ulcers of the mouth

Angular cheilitis

Pyoderma Gangrenosum

ErythemaNodosum

Ocular

Occur in 6% of patients .

Episcleritis

Scleritis

Uveitis - the anterior segment

Keratopathy and night blindness

Hepatobiliary

Gallstones

Asymptomatic and mild elevations of liver biochemical tests

PSC more often is associated with UC

Autoimmune hepatitis.

Vascular

venous thromboembolism

arterial thrombosis.

Renal and Genitourinary

Inflammatory entrapment of the ureter

Uric acid and oxalate stones.

Membranous nephropathy &Glomerulonephritis

Renal amyloidosis.

. Penile and vulvar edema

Investigations

CBC

Nutritional evaluation: Vitamin B12 , iron studies, folate & other nutritional markers

ESR and CRP levels

Fecal calprotectin level

Serologic studies: pANCA, ASCA, anti-CBir1

Stool studies: Stool R/M, C/S, evaluation for Clostridium difficile toxin

DISTINGUISHING CHARACTERISTICS OF CROHN’s disease AND Ulcerative colitis

Characteristic Feature Ulcerative Colitis Crohn’s Disease

Abdominal tenderness May be present Common

Abdominal wall and internal fistulas Common Absent

Abdominal pain Uncommon Common

Fever , Malaise Uncommon Common

Bloody Diarrheoa Frequent Occasional

Location Only colon GIT

Anatomic distribution Continuous, begins distally Skip lesions

Weight loss Occasional Frequent

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Characteristic Feature Ulcerative colitis Crohn’s disease

Palpable mass Rare Common

Intra-abdominal abscess Rare Common

Bowel Obstruction Rare Common

Antibiotic response Rare Frequent

Skip lesions Rare Frequent

Effect of smoking Often improves Often worsens

Serologic markers

ASCA +

P-ANCA +

15%

70%

65%

20%

Iron deficiency anaemia, raised CPR/

ESR, hypoalbuminaemiaCommon Common

Recto vaginal fistula Rare Frequent

Perianal Fistula Rare Frequent

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PATHOLOGIC FEATURES OF CD AND UCCharacteristic feature Crohn’s disease Ulcerative colitis

Transmural Inflammation Common Uncommon

Granulomas Common Rare

Fissures Common Rare

Fibrosis Common No

Sub mucosal inflammation Common Uncommon

Rectal involvement Rare Common

Ileal involvement Very Common Rare

Strictures Common Rare

Crypt abcess Rare Very common

Linear clefts Common Rare

Cobblestone appearance Common Absent

ComprEhensive pharmacy review –LEON shargel, CLINICAL PHARMACY AND THERAPEUTICS- ROGER WALKER, pHARMACOTHERAPY a pathophysiologicappraoch josepht. dipiro

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Imaging studies

Upright chest and abdominal radiography

Barium double-contrast enema radiographic studies

Abdominal ultrasonography

Abdominal/pelvic computed tomography scanning/magnetic resonance imaging with enterography

Colonoscopy, with biopsies of tissue/lesions

Upper gastrointestinal endoscopy

Capsule enteroscopy/double balloon enteroscopy

Plain radiograph

In severe disease, the luminal margin of the colon becomes edematous and irregular.

Thickening of the colonic wall often is apparent on a plain film

Plain films also are useful for detecting the presence of fecal material.

The presence of marked colonic dilatation suggests fulminant colitis or toxic megacolon.

Barium studies

Aphthous ulcers, a coarse villus mucosal pattern, and thickened folds.

Pseudo sacculation of the antimesenteric border

Cobblestone appearance

Fistulas, sinus tracts, and fixed strictures

The earliest radiologic change of UC seen is fine mucosal granularity

String sign

lead-pipe or stove-pipe appearance

MR enterography

Intestinal wall thickening, submucosal edema, vasa recta engorgement, and lymphadenopathy are signs of active diseas

FIESTA images can add information regarding the functional status of fibrotic segment

MRI images yield a diagnostic accuracy of 91%.

Colonoscopy The hallmark of UC is continuous inflammation that begins in

the rectum.

The earliest endoscopic sign of UC is a mucosal erythema and edema

As disease progresses, the mucosa becomes granular and friable.

In severe inflammation, the mucosa may be covered by yellow-brown mucopurulent exudates associated with mucosal ulcerations.

Ulcerative Colitis

Uses of colonoscopy

Determine the extent and severity of colitis

Provide tissue to assist in the diagnosis.

Therapeutic use is stricture dilation

Capsule Enteroscopy

Swallows encapsulated video camera

Transmits an image to a receiver outside the pt.

It is most commonly used for finding obscure sources of GI blood loss,

The images can find ulcerations associated with CD if endoscopy and colonoscopy are unrevealing

The major risk is the potential to get lodged at the point of a stricture

Complications of CD

Perforation

Abscess formation

Stricture & small bowel obstruction

Nutritional deficiencies

Cancer: small bowel adenocarinoma

Cancer: colon???

Complications of UC

Toxic Megacolon:

Defined as a transverse or right colon with a diameter of >6 cm, with loss of haustration in patients with severe attacks of UC.

It occurs in about 5% of attacks and

It can be triggered by electrolyte abnormalities and narcotics.

About 50% of acute dilations will resolve with medical therapy alone

Urgent colectomy is required for those that do not improve

Complicatins of UC

Colon adenocarcinoma

After 8–10 years of colitis, annual or biannual surveillance colonoscopy with multiple biopsies at regular intervals should be performed

extensive mucosal involvement (pancolitis)

family history of carcinoma of the colon.

Perforation

Massive hemorrhage

DIFFERENTIAL DIAGNOSIS

SUMMERY

INVESTIGATIONSCrohn’s disease Ulcerative colitis

Blood Test

•CP with morphology: Normocytic normocromicanemia of CHRONIC disease•Serum B12 level may be low.•Raised ESR, CRP and raised WBC count.•Hypo albuminaemia.•Blood culture in septicaemia.

•Fe deficiency anemia•Raised white cell and platelet count•Raised ESR, CRP•Hypo albuminaemia

Serological Test

• Saccharomyces cerevisiae antibody is usually present•P-ANCA positive in 5 – 10 %

•P-ANCA positive in 60 – 70 %

•ASCA positive in 10 – 15 %

Stool culture

•Should always be performed in both to rule out infective cause

CONTD..Crohn’s Disease Ulcerative Colitis

Radiography

Plain ABD. X-ray:•Loss of haustral markings and shortening of bowel Is seen in sever lession.

•Narrowing of bowel lumen is seen

Ultrasound:•Thickened small bowel loops and mesentery or abscess

•Thickening of colonic wall and presence of free fluid in abdominal cavity

Barium Enema (contraindicated in toxic megacolon)•Skip lesions•Rose thorn appearance•String appearance•Cobble stone appearance•Omega sign are also seen

•Ulcerations•Pseudopolyps•Loss of haustration•Shortening of bowel is seen

CONTD..Crohns disease Ulcerative colitis

Instant Barium enema•Patchy sup. Ulceration to wide spread deep•Cobble stone appearance and narrowing

•Superficial ulcers •Shortened and narrowed colon in long standing disease

Colonoscopy•Fissures and fistulae •Pseudopolyps

•Mucosal granularity and hyperemia

High resolution USG. And spiral CT•Radionuclide scan with gallium labeled polymorphs or indium or technetium labeled leucocytes •Capsule imaging of the gut.

•Radionuclide scan used to assess colonic inflammation

Stricture evaluation and dilationcomplicated Lesser complicated