L13 inflammatory bowel disease f

Inflammatory Bowel Disease

Lecture 13

IBD Definition

• Comprised of two major disorders:

Ulcerative Colitis (UC)

Crohn’s Disease (CD)

Introduction

• Crohn’s Disease is an idiopathic, chronic, transmural inflammatory process of the bowel that can affect any part of the gastro intestinal tract from the mouth to the anus.

• Most cases involve the small bowel, particularly the

terminal ileum.

Crohn’s Disease

• Crohn's disease seems to run in some families. It can occur in people of all age groups but is most often

diagnosed in young adults.

Burrill Bernard CrohnBBC

(June 13, 1884 – July 29, 1983) was an

American gastroenterologist and one of the first to describe the disease for which he is known, Crohn's diseas .

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Prevalence• Higher number of cases of Crohn’s disease found in

western industrialized nations. • Males and females are equally affected. • Smokers are three times more likely to develop

Crohn's disease.• Crohn's disease tends to present initially in the teens

and twenties.

Classification of CD On the area of the gastrointestinal tract which it

affects:

• Ileocolic Crohn's disease: Affects both the ileum and the large intestine (50%)

• Crohn's ileitis: Affects the ileum only (30%)

• Crohn's colitis: Affects the large intestine, accounts for the remaining twenty percent of cases.

Classification of CDOn the behavior of disease as it progresses:

• Stricturing disease causes narrowing of the bowel which may lead to bowel obstruction or changes in the caliber of the feces.

Stricturing

Classification of CD• Penetrating disease creates abnormal passage ways between

the bowel and other structures such as the skin.

• Inflammatory disease causes inflammation without causing strictures or fistulae.

Inflammatory Penetrating

Morphology

Crohn disease may occur in any area of the GI tract, but the most common sites involved at presentation are the terminal ileum, ileocecal valve, and cecum.

Disease is limited to the small intestine alone in about 40% of cases; the small intestine and colon are both involved in 30% of patients; and the remainder have only colonic involvement.

• The presence of multiple, separate, sharply delineated areas of disease, resulting in skip lesions, is characteristic of Crohn disease and may help in the differentiation from ulcerative colitis. Strictures are common.

• The earliest Crohn disease lesion, the aphthous ulcer, may progress, and multiple lesions often coalesce into elongated, serpentine ulcers oriented along the axis of the bowel. Edema and loss of the normal mucosal texture are common.

• Sparing of interspersed mucosa, a result of the patchy distribution of Crohn disease, results in a coarsely textured, cobblestone appearance in which diseased tissue is depressed below the level of normal mucosa

Fissures frequently develop between mucosal folds and may extend deeply to become fistula tracts or sites of perforation.

The intestinal wall is thickened and rubbery as a consequence of transmural edema, inflammation, submucosal fibrosis, and hypertrophy of the muscularis propria, all of which contribute to stricture formation.

• In cases with extensive transmural disease, mesenteric fat frequently extends around the serosal surface (creeping fat) .

• The microscopic features of active Crohn disease include abundant neutrophils that infiltrate and damage crypt epithelium. Clusters of neutrophils within a crypt are

referred to as crypt abscesses and are often associated with crypt destruction.

• Ulceration is common in Crohn disease, and there may be an abrupt transition between ulcerated and adjacent normal mucosa. Even in areas where gross examination suggests diffuse disease, microscopic pathology can appear patchy.

• Repeated cycles of crypt destruction and regeneration lead to distortion of mucosal architecture; the normally straight and parallel crypts take on bizarre branching shapes and unusual orientations to one another.

• Epithelial metaplasia, another consequence of chronic relapsing injury, often takes the form of gastric antral-appearing glands, and is called pseudopyloric metaplasia. Paneth cell metaplasia may also occur in the left colon, where Paneth cells are normally absent. These architectural and metaplastic changes may persist even when active inflammation has resolved. Mucosal atrophy, with loss of crypts, may occur after years of disease.

• Noncaseating granulomas, a hallmark of Crohn disease, are found in approximately 35% of cases and may occur in areas of active disease or uninvolved regions in any layer of the intestinal wall. Granulomas may also be present in mesenteric lymph nodes. Cutaneous granulomas form nodules that are referred to as metastatic Crohn disease. The absence of granulomas does not preclude a diagnosis of Crohn disease.

Gross pathology of Crohn disease. A, Small-intestinal stricture. B, Linear mucosal ulcers and thickened intestinal wall. C, Perforation and associated serositis. D, Creeping fat.

Microscopic pathology of Crohn disease. A, Haphazard crypt organization results from repeated injury and regeneration. B, Noncaseating granuloma. C, Transmural

Crohn disease with submucosal and serosal granulomas (arrows).

Symptoms• Onset of Crohn's disease is between 15-30

years of age.

• People with Crohn's disease will go through periods of flare-ups and remission.

Common symptoms of Crohn's disease:• abdominal pain• diarrhoea• weight lossLess common symptoms include:• poor appetite• fever, night sweats• rectal pain/rectal bleeding Some patients with Crohn's disease also develop symptoms outside of

the gastrointestinal tract; these symptoms include:• arthritis• skin rash• inflammation of the iris of the eye.

Symptoms

Clinical Features

• The clinical manifestations of Crohn disease are extremely variable. In most patients disease begins with intermittent attacks of relatively mild diarrhea, fever, and abdominal pain.

• Approximately 20% of patients present acutely with right lower quadrant pain, fever, and bloody diarrhea that may mimic acute appendicitis or bowel perforation. Periods of active disease are typically interrupted by asymptomatic periods that last for weeks to many months.

• Disease re-activation can be associated with a variety of external triggers, including physical or emotional stress,

• specific dietary items, and • cigarette smoking.

• Smocking is a strong exogenous risk factor for development of Crohn disease and, in some cases, disease onset is associated with initiation of smoking. Unfortunately, smoking cessation does not result in disease remission.

• Iron-deficiency anemia may develop in individuals with colonic disease, while extensive small bowel disease may result in serum protein loss and hypoalbuminemia, generalized nutrient malabsorption, or malabsorption of vitamin B12 and bile salts. Fibrosing strictures, particularly of the terminal ileum, are common and require surgical resection.

• Disease often recurs at the site of anastamosis, and as many as 40% of patients require additional resections within 10 years. Fistulae develop between loops of bowel and may also involve the urinary bladder, vagina, and abdominal or perianal skin. Perforations and peritoneal abscesses are common.

Extra-intestinal manifestations of Crohn disease

uveitis, migratory polyarthritis, sacroiliitis, ankylosing spondylitis, erythema nodosum, and clubbing of the fingertips, any of which may

develop before intestinal disease is recognized.

Pericholangitis and primary sclerosing cholangitis occur in Crohn disease but are more common in ulcerative colitis. Risk of colonic adenocarcinoma is increased in patients with long-standing colonic disease.

Comparisons of various factors in Crohn's disease and ulcerative colitis

Crohn's Disease Crohn's Disease Ulcerative Colitis Ulcerative Colitis

Involves terminal ileum Involves terminal ileum Commonly Commonly Seldom Seldom

Involves colon? Involves colon?

Involves rectum? Involves rectum?

Usually Usually

Seldom Seldom

Always Always

Usually Usually

Peri-anal involvement Peri-anal involvement Commonl Commonl Seldom Seldom

Bile duct involvement? Bile duct involvement? Not associated Not associated Higher rate of Primary Higher rate of Primary sclerosing cholangitis sclerosing cholangitis

Distribution of Disease Distribution of Disease Patchy areas of Patchy areas of inflammation inflammation

Continuous area of Continuous area of inflammation inflammation

Endoscopy Endoscopy Linear and serpiginous Linear and serpiginous (snake-like) ulcers (snake-like) ulcers

Continuous ulcer Continuous ulcer

Depth of inflammation Depth of inflammation May be transmural, deep May be transmural, deep into tissues into tissues

Shallow, mucosal Shallow, mucosal

Fistulae, abnormal Fistulae, abnormal passageways between passageways between

organs organs

Commonly Commonly Seldom Seldom

Biopsy Biopsy Can have granulomata Can have granulomata Crypt abscesses and Crypt abscesses and cryptitis cryptitis

Surgical cure ?Surgical cure ?

Smoking Smoking

Often returns following Often returns following removal of affected removal of affected

part part

Higher risk for smokers Higher risk for smokers

Usually cured by Usually cured by removal of colon, can removal of colon, can

be followed by be followed by

po uchitis po uchitis

Lower risk for smokers Lower risk for smokers

Autoimmune disease Autoimmune disease Generally regarded as Generally regarded as an autoimmune an autoimmune

disease disease

No consensus No consensus

Cancer risk? Cancer risk? Lower than ulcerative Lower than ulcerative colitis colitis

Higher than Crohn's Higher than Crohn's

Comparisons of various factors in Crohn's disease and UC (Cont.)

Features UC CD

Morphologic

Distribution Diffuse,mucosal &submucosal, left sided

Focal, trans-

mural, right sided

Mucosal atrophy Marked Minimal

Cytoplasmic mucin ↓ Preserved

Lymphoid aggregate Rare Common

Edema Minimal marked

Features UC CDMorphologic

Hyperemia Extreme Minimal

Granuloma Absent 60% present

Fissuring Absent Prsent

Crypt abscess Common Rare

Rectal involvement Always 50%

Ileal involvement Minimal 50%

Lymph nodes Reactive Granulomas

Ulcerative Colitis

• Ulcerative colitis is a disease that causes ulcers in the lining of the rectum and colon. Ulcers form where inflammation has killed the cells that usually line the colon.

• Ulcerative colitis can happen at any age, but it usually starts between the ages of 15 and 30. It tends to run in families.

SymptomsCommon symptoms of ulcerative colitis include:• rectal bleeding and diarrhoea• Variability of symptoms reflects differences in the extent of

disease (the amount of the colon and rectum that are inflamed) and the intensity of inflammation.

• Generally, patients with inflammation confined to the rectum and a short segment of the colon adjacent to the rectum have milder symptoms and a better prognosis than patients with more widespread inflammation of the colon.

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. Other patients with more severe rectal inflammation may, in addition, experience rectal pain, urgency (sudden feeling of having to defecate and a need to rush to the bathroom for fear of soiling), and tenesmus (ineffective, painful urge to move one's bowels).

• Proctosigmoiditis involves inflammation of the rectum and the sigmoid colon (a short segment of the colon contiguous to the rectum). Symptoms of proctosigmoiditis, like that of proctitis, include rectal bleeding, urgency, and tenesmus. Some patients with proctosigmoiditis also develop bloody diarrhea and cramps.

Ulcerative Colitis

• Left-sided colitis involves inflammation that starts at the rectum and extends up the left colon (sigmoid colon and the descending colon). Symptoms of left-sided colitis include bloody diarrhoea, abdominal cramps, weight loss, and left-sided abdominal pain.

• Pancolitis or universal colitis refers to inflammation affecting the entire colon (right colon, left colon, transverse colon and the rectum). Symptoms of pancolitis include bloody diarrhoea, abdominal pain and cramps, weight loss, fatigue, fever, and night sweats.

• Fulminant colitis is a rare but severe form of pancolitis. Patients with fulminant colitis are extremely ill with dehydration, severe abdominal pain, protracted diarrhea with bleeding, and even shock. They are at risk of developing toxic megacolon (marked dilatation of the colon due to severe inflammation) and colon rupture (perforation).

ULCERATIVE COLITIS

Associated with: liver disease

• Arthritis, uvietis

• Pyoderma gangreonosum, Wegener’s granulomatosis

Complications: perforation, peritonitis, abscess

• Toxic megacolon

• Venous thrombosis• Carcinoma