Inflammatory Bowel Disease (IBD)

• Inflammatory bowel disease includes all inflammatory diseases of the intestine including the colorectum.
• IIBD is restrictive for Crohn’s disease, ulcerative colitis and indeterminate IIBD- features of the first 2 conditions.
• Differentiation from other colitis can be difficult sometimes.
• They are chronic relapsing inflammatory disorders of obscure origin.
• Diagnosis depends on clinical and pathological criteria, and exclusion of other causes of inflammatory lesion.
• They also exhibit extraintestinal inflammatory manifestations.

Etiology and Pathogenesis of IBD

• Arises from a loss of dynamic balance between factors that activate the host immune system [luminal microbes, dietary antigens, endogenous inflammatory stimuli], and host defenses that maintain the integrity of the mucosa and down-regulate inflammation.

Role of Ethnicity in IBD

• Incidence and prevalence is significantly dependent on geographic location, racial, and ethnic backgrounds.
• IBD occurs worldwide; there is a low incidence in Asian and Middle Eastern countries, whereas a high incidence in Europe, US, Canada, Australia, and New Zealand.
• Incidence is higher in Caucasians than non-Caucasians in the US.
• Jews in the US have the greatest risk compared with non-Jewish Caucasians.

Role of Genetics in IBD

• Evidences of familial clustering – 5% to 10% of patients with IBD have an affected family member.
• Individuals with a first-degree relative have a 10-15 fold increased risk and concordance in monozygotic twins for CD is 42-58% while only 4% in dizygotic twins.
• Susceptibility genes: A number of potential genetic susceptibility loci for IBD have been identified.

Other Factors in IBD

• Immunological factors include both innate and acquired immunity.
• Autoantibodies are produced such a antineutrophil cytoplasmic antibodies (ANCAs).
• Apoptosis occurs when Mucosal T lymphocytes are resistant to apoptosis, especially in CD.
• Caused by exogenous agents such as diet (food antigen), infectious agents, tobacco use and exposure, use of NSAIDs.

Summary of interplay of various factors

• Genetic predisposition: differential associations with class II HLA (HLA-DR1/DQw5 allelic combination in some patients with CD, HLA-DR2 in patients with UC).
• Infectious causes: viruses (measles), chlamydia, mycobacteria, etc, have been implicated.
• Abnormal host immunoreactivity: Failure to down-regulate after stimulation by luminal antigens.
• Inflammation as the final common pathway: products of inflammatory cells cause the tissue injury.

Crohn's Disease Introduction

• Transmural, granulomatous, inflammatory disease that may affect any part of the GIT but occurs principally in the small intestine and sometimes the colon.
• First described in 1932

Crohn's Disease Epidemiology

• Occurs throughout the world
• Annual incidence of 0.5 – 5/100,000
• Appears in adolescents or young adults
• Most common among persons of European origin, higher frequency among Jews
• Slight female predominance, 1.6:1

Crohn's Disease Morphology

• Major features that differentiate CD from other IIBD
• Transmural inflammation – involves all the layers of the bowel
• The inflammation is discontinuous (skip lesions)

Crohn's Disease Morphology Contd

• 40% of patients show involvement of the ileocecal region
• 30% have small bowel disease
• 25% have colonic disease
• 15% have anorectal region involvement
• Rarely involves the esophagus, stomach, and duodenum.

Crohn's Disease Gross Pathology

• Bowel wall appears thickened and edematous and the serosa demonstrates fat wrapping.
• ‘Cobblestone’ appearance – nodular swelling, fibrosis, and ulceration of the mucosa.
• Ulcers – initially superficial, becoming deeper and appearing as fissures.
• Fistula formation – may penetrate into other organs, including bladder, uterus, vagina, and skin and perianal fistula is a common presenting feature.

Crohn's Disease Microscopic Pathology

• Transmural inflammation that extends through all layers of the bowel wall.
• May be confined to the mucosa and submucosa in early cases.
• Discrete noncaseating granulomas are often present, mostly in the submucosa.
• Absence of granulomas does not exclude the diagnosis.

Crohn's Disease Clinical Features

• Onset is insidious and manifestations are highly variable; findings are related to anatomical localization of the disease.
• 75% of patients present with abdominal pain and diarrhea.
• 50% have recurrent fever.
• Involvement of ileum and caecum may mimic appendicitis
• Ileum involvement includes right lower quadrant pain, intermittent diarrhea, and fever.
• Colon involvement includes diarrhea and sometimes colonic breeding
• Diffuse small intestine involvement includes malabsorption and malnutrition
• Anorectal region involvement includes recurrent anorectal fistulas

Crohn's Disease Extra Intestinal Manifestations

• Can include Uveitis, Ankylosing spondylitis, Erythema nodosum, Pericholangitis and sclerosing cholangitis, and Amyloidosis

Crohn's Disease Complications

• The most common are intestinal obstruction and fistulas.
• Can include occasional free perforation of the bowel and strictures.
• Risk of small intestinal cancer is increased (3-fold).
• Predisposes to colorectal cancer; the risk is small compared to ulcerative colitis.

Crohn's Disease Differential Diagnoses

• Ulcerative colitis
• Amebic colitis
• Tuberculosis
• Schistosomiasis
• Campylobacter infection
• Acute appendicitis
• Meckel diverticulitis, etc

Ulcerative Colitis Introduction

• A chronic inflammatory disease of the large intestine characterized by chronic diarrhea and rectal bleeding, with exacerbation and remission and the possibility of serious local and systemic complications.
• Limited to the large intestine and affecting only the mucosa and submucosa.

Ulcerative Colitis Epidemiology

• Global in distribution
• No sex predominance
• Onset typically in early adult life, with peak incidence in the 3rd decade
• Childhood onset and old age are not rare
• Whites are affected more than blacks in US

Ulcerative Colitis Morphology

• 3 main features that differentiate UC from other inflammatory colitis
• A diffuse disease – from most distal part of the rectum; involvement of the rectum alone is termed ulcerative proctitis.
• Involves the entire large intestine – Universal colitis
• Inflammation is confined to the colon and rectum; rarely involves the adjacent ileum (backwash ileitis).
• It is limited to the submucosa.

Ulcerative Colitis - Early Colitis

• Mucosal surface appears raw, red, and granular, and bleeds easily.
• Later ulcer appears.
• Raised areas of mucosa corresponding to inflammatory polyps (pseudopolyps) can be seen.

Early Colitis Histology

• Mucosal congestion, edema, microscopic hemorrhages, diffuse chronic inflammation infiltrates in the lamina propria
• Damage and distortion of the crypts (crypt distortion), crypts are infiltrated by neutrophils (cryptitis)
• Suppurative necrosis of the crypts, resulting in dilated degenerated crypts filled with neutrophils (crypt abscess).

Ulcerative Colitis - Progressive Colitis

• Mucosal folds are lost with disease progression.
• Tissue destruction with formation of highly vascular granulation tissue in the denuded areas.

Progressive Colitis Histology

• The crypts appear tortuous, branched, shortened.
• Mucosa may be diffusely atrophic.

Ulcerative Colitis Advanced Colitis

• The large intestine is often shortened especially in the left side.
• Mucosal folds are indistinct and replaced by a granular or smooth mucosal pattern.

Advanced Colitis Histology

• Chronic inflammatory infiltrates, atrophy.

Ulcerative Colitis Clinical Features

• Highly variable –
• 70% have intermittent attacks with partial or complete remission between attacks.
• 10% have a very long remission after the first attack.
• 20% have continuous symptoms without remission.

Ulcerative Colitis Clinical Features Contd

• Can include rectal bleeding, tenesmus, recurrent episodes of loose bloody stool, crampy abdominal pain, low grade fever.
• 10% have fulminant ulcerative colitis (about 15% of patient with fulminant UC die of the disease).
• About 30% of patients with UC require colectomy within the first 3 years of onset due to uncontrollable disease.

Ulcerative Colitis Extra Intestinal Manifestations

• Arthritis – seen in 20% of UC
• Uveitis – seen in about 10%
• Skin lesions (e.g., erythema nodosum) – 10%
• Liver diseases (e.g., pericholangitis) – 3%

Ulcerative Colitis - Differential Diagnosis

• Crohn’s disease
• Shigella colitis
• Salmonella infection
• Amebic colitis
• etc

Ulcerative Colitis Complications

• Fulminant UC
• Toxic megacolon with radiologic diagnosis: diameter of the colon measured at the transverse colon exceeds 6cm.
• Toxic megacolon carries maximum risk of mortality, occurring in 2-4% of patient with UC, with Perforation is common with more than 50% mortality.
• Secondary infection – is possible, especially Clostridium difficile
• Backwash ileitis

Ulcerative Colitis Complications Contd

• Polyps – may be inflammatory or adenomatous
• Colorectal cancer - long standing extensive UC have a higher risk of CRC than the general population.
• The risk is related to the extent of involvement and the duration of the inflammatory disease.
• Strictures – occur in about 5% of UC

Indeterminate Colitis

• Indeterminate colitis involves the overlapping pathologic features of UC and Crohn’s disease.