IBD Epidemiology and Diagnosis Roberto E. Mera Lastra MD Gastroenterology University of Puerto Rico Medical Sciences Campus

Inflammatory Bowel Disease Definition: Conditions characterized by a tendency for chronic or relapsing immune activation and inflammation within the gastrointestinal tract. Crohn’s disease and ulcerative colitis

Definition: Conditions characterized by a tendency for chronic or relapsing immune activation and inflammation within the gastrointestinal tract.

Crohn’s disease and ulcerative colitis

Crohn’s disease chronic inflammation involving any location of the alimentary tract from mouth to anus propensity for the distal small bowel and proximal large bowel

chronic inflammation

involving any location of the alimentary tract from mouth to anus

propensity for the distal small bowel and proximal large bowel

Ulcerative Colitis Inflammatory disorder that affects the rectum and extends proximally to affect a variable extent of the colon

Inflammatory disorder that affects the rectum and extends proximally to affect a variable extent of the colon

Inflammatory Bowel Disease Epidemiology Pathogenesis Clinical Presentation of Crohn’s disease and Ulcerative Colitis Diagnosis Extraintestinal Manifestations

Epidemiology

Pathogenesis

Clinical Presentation of Crohn’s disease and Ulcerative Colitis

Diagnosis

Extraintestinal Manifestations

Epidemiology of IBD 1-2 million IBD patients in the U.S. Equal incidence of ulcerative colitis and Crohn’s disease Approximately 10,000 new cases diagnosed annually* Reassignment 10% in the first 2 years after diagnosis *Hanauer S. Inflammatory Bowel Disease. N Engl J Med. 1996;334(13):841-8

1-2 million IBD patients in the U.S.

Equal incidence of ulcerative colitis and Crohn’s disease

Approximately 10,000 new cases diagnosed annually*

Reassignment 10% in the first 2 years after diagnosis

Epidemiology of IBD: Overview Variable Finding Time trends in incidence Increased 1960s – 80s with recent plateau Incidence (per 100,000) 5-7 Peak age at onset (y) 15-30 Female-to-male ratio 1.1 to 1.8:1 Racial/ethnic incidence High in whites, Jews Andres PG et al. Gastroenterol Clin N Am . 1999;28:255.

Pathogenesis

Immune dysregulation IBD – Interaction of Genetic Susceptibility, Immune Dysregulation, and Environmental Triggers IBD Genetic susceptibility Environmental triggers

Immune dysregulation

Normal Intestine Vs. Intestine With IBD Environmental triggers (infection, bacterial products) Moderately inflamed Failure to down- regulate Chronic uncontrolled inflammation = IBD Down-regulate Normal gut controlled inflammation Normal gut controlled inflammation

IBD: Evidence of Genetic Influence Racial differences in incidence: White > Black > Asian Ethnic influences: Jewish > non-Jewish; Ashkanazi > Sephardic Twin studies: Monozygotic > dizygotic Association with specific HLA antigens, ? susceptibility loci on chromosomes 6, 16 NOD2 gene explains 20% of Crohn’s disease Sartor RB. Inflammatory Bowel Dis . 1995;24:475.

Racial differences in incidence: White > Black > Asian

Ethnic influences: Jewish > non-Jewish; Ashkanazi > Sephardic

Twin studies: Monozygotic > dizygotic

Association with specific HLA antigens, ? susceptibility loci on chromosomes 6, 16

NOD2 gene explains 20% of Crohn’s disease

Familial Patterns of Inheritance Approximately 10% of patients have positive family history 2%–10% risk if first-degree relatives affected 20–50-fold increase in prevalence among siblings 50–100-fold increase in prevalence for children of patients with IBD Yang H, Rotter JI. In: Inflammatory Bowel Disease. From Bench to Bedside. 1993:32.

Approximately 10% of patients have positive family history

2%–10% risk if first-degree relatives affected

20–50-fold increase in prevalence among siblings

50–100-fold increase in prevalence for children of patients with IBD

Immune dysregulation Sustained exaggerated inflammatory reaction may result from an ineffective immune response over-responsiveness to a persistent stimulus

Sustained exaggerated inflammatory reaction may result from an ineffective immune response

over-responsiveness to a persistent stimulus

Enviroment Breast Feeding Smoking Nsaids OCP’S

Breast Feeding

Smoking

Nsaids

OCP’S

Clinical Findings

Presentation of UC Diarrhea Bleeding NO abdominal pain (cramps) Extraintestinal manifestations

Diarrhea

Bleeding

NO abdominal pain (cramps)

Extraintestinal manifestations

Presentation of CD Diarrhea Chronic abdominal pain and tenderness Loss of appetite and weight loss Fever Perianal disease Complications such as fistulas Extraintestinal manifestations

Diarrhea

Chronic abdominal pain and tenderness

Loss of appetite and weight loss

Fever

Perianal disease

Complications such as fistulas

Extraintestinal manifestations

Complications of CD Fistulas Abscess Strictures Growth failure (pediatrics) Malnutrition Extraintestinal disorders

Fistulas

Abscess

Strictures

Growth failure (pediatrics)

Malnutrition

Extraintestinal disorders

Crohn’s Disease Complications: Fistulas A tunnel between two sections of the intestines or between the intestines and other organs, including the skin Small Intestine Large Intestine (Colon) Fistula Fistula

A tunnel between two sections of the intestines or between the intestines and other organs, including the skin

Crohn’s Disease Complications: Abscesses A localized collection of pus within the tissue of the GI tract Stomach Small Intestine Large Intestine (Colon) Abscess from a fissure in the small intestine into the peritoneal cavity

A localized collection of pus within the tissue of the GI tract

Complications of CD: Fistulas Abdominal Fistula Perianal Fistula

Differential Diagnosis of IBD Lymphoma Infectious etiologies Appendicitis Diverticulitis Carcinoma Ischemic Colitis Celiac disease

Lymphoma

Infectious etiologies

Appendicitis

Diverticulitis

Carcinoma

Ischemic Colitis

Celiac disease

Severity of UC

Diagnostic algorithm for IBD Intestinal symptoms Rectal bleeding, diarrhea, vomiting, anorexia, abdominal pain Extraintestinal symptoms Fever, perianal lesions, growth failure, mouth ulcers, erythema nodosum, etc. Differential diagnosis Gastroenteritis, appendicitis, IBD, antibiotic-associated colitis, etc Laboratory findings Anaemia, leukocytosis, thrombocytosis, elevated CRP, hypalbuminaemia, low vitamin levels, p-ANCA, ASCA Radiologic studies Plain abdominal x-ray, upper GI barium series Echo Endoscopy and biopsy Crohn disease Ulcerative colitis

Differentiating Crohn’s Disease from Ulcerative Colitis Feature Crohn’s Disease Ulcerative Colitis Abdominal pain Frequent and prominent Primarily cramping associated complaint but may not be present with bowel movement Diarrhea Watery or voluminous stools Usually; occasionally constipation with complaint but may not be present proctitis Gross blood in stool Occasionally; primarily with colonic disease Frequently Mucus in stool Occasionally Frequently Abdominal mass Frequently, particularly with ileocecal disease Rarely Abdominal tenderness Frequently Rarely Intestinal obstruction Frequently Rarely Perianal disease Frequently Rarely Perianal fistulas Frequently No

Rectal involvement 25–50% 95–100% (before treatment) Continuous colitis Rarely Yes Symmetry of inflammation Eccentric inflammation Circumferential inflammation Bowel wall thickening Marked None to moderate Cobblestone appearance Frequent Rare Background mucosa Normal Abnormal Fistula Often Rarely (rectovaginal) Mesenteric inflammation Frequent Rare, except with toxic megacolon Segmental inflammation Yes, skip areas frequently seen No, except for cecal Inflammation adjacent to appendiceal orifice Stricture Often Rarely Ulceration Depth: aphthous to deep Superficial Shape: linear, serpiginous, stellate Mesenteric proliferation of fat Frequent No

Feature Crohn’s Disease Ulcerative Colitis Rectovaginal fistulas Occasionally Rarely Abscess Occasionally No Recurrence after surgery Yes No recurrence after total proctocolectomy, though pouchitis may occur in ileal pouch Toxic megacolon Rare Infrequent Current smoker Frequently Rarely Former smoker Rarely Frequently Previous appendectomy Occasionally Rarely Macrocytic anemia Occasionally Rarely Perinuclear antineutrophil 20% 70% cytoplasmic antibodies (pANCA) Anti- Saccharomyces 65% 15% cerevisiae antibodies (ASCA) Distribution of disease May involve any segment of GI Contiguous involvement of colon from rectum proximally Abn prox to terminal ileum Sometimes No Abnormal terminal ileum Frequently Occasionally, from backwash ileitis Ileocecal valve Often narrowed Normal or gaping

Significant factors UC CD Anatomic location Colon/rectum Any part of GI tract Distribution Diffuse Focal with “skip” areas Fistula or abscess Rare Common Strictures Uncommon Common Current smoker Rare Common Bloody diarrhea Common Rare Differential Diagnosis Adapted from Surawicz CM. Contemp Intern Med. 1991;3:17 .

Significant factors UC CD

Anatomic location Colon/rectum Any part of GI tract

Distribution Diffuse Focal with “skip” areas

Fistula or abscess Rare Common

Strictures Uncommon Common

Current smoker Rare Common

Bloody diarrhea Common Rare

Crohn’s Disease – Extra-luminal dx (1) Anemia (2) Hepatobiliary disorders: - Fatty liver - Hepatitis - Cirrhosis - Sclerosing cholangitis - diffuse inflammation, leading to patchy stricturing of bile duct. (3) Rheumatic: - Arthritis - peripheral occurs in 10% - Ankylosing spondylitis - occurs in 5% (4) Dermatologic: - Erythema Nodosum (rashes), most commonly over tibia - Pyoderma gangrenosum - necrotic ulcer over skin (5) Ocular: - Uveitis - inflammation of uveal tract (iris, ciliary body, choroid) - Episcleritis - inflammation of connective tissue between sclera and conjunctiva

(1) Anemia

(2) Hepatobiliary disorders: - Fatty liver - Hepatitis - Cirrhosis - Sclerosing cholangitis - diffuse inflammation, leading to patchy stricturing of bile duct.

(3) Rheumatic: - Arthritis - peripheral occurs in 10% - Ankylosing spondylitis - occurs in 5%

(4) Dermatologic: - Erythema Nodosum (rashes), most commonly over tibia - Pyoderma gangrenosum - necrotic ulcer over skin

(5) Ocular: - Uveitis - inflammation of uveal tract (iris, ciliary body, choroid) - Episcleritis - inflammation of connective tissue between sclera and conjunctiva

Ulcerative Colitis – Extra-luminal dx (1) Hematologic - Anemia, thromboembolic disease (2) Hepatobiliary disorders: - Fatty liver, hepatomegaly, Pericholangitis - Cirrhosis (1-5%), Primary Sclerosing cholangitis (1-4%) - Bile duct carcinoma (3) Rheumatic: - Arthritis - peripheral occurs in 15-20% - Ankylosing spondylitis - occurs in 3-6% (4) Dermatologic: - Aphthous ulcers in oral mucosa - Erythema Nodosum (rashes), most commonly over tibia - Pyoderma gangrenosum - necrotic ulcer over skin (5) Ocular (4-10%): - Uveitis, Episcleritis, Marginal ulcerations of cornea, Cataracts, Keratopathy, Central Serous Retinopathy

(1) Hematologic

- Anemia, thromboembolic disease

(2) Hepatobiliary disorders: - Fatty liver, hepatomegaly, Pericholangitis - Cirrhosis (1-5%), Primary Sclerosing cholangitis (1-4%) - Bile duct carcinoma

(3) Rheumatic: - Arthritis - peripheral occurs in 15-20% - Ankylosing spondylitis - occurs in 3-6%

(4) Dermatologic: - Aphthous ulcers in oral mucosa - Erythema Nodosum (rashes), most commonly over tibia - Pyoderma gangrenosum - necrotic ulcer over skin

(5) Ocular (4-10%): - Uveitis, Episcleritis, Marginal ulcerations of cornea, Cataracts, Keratopathy, Central Serous Retinopathy

Endoscopic, Radiographic, and Histologic Findings Diagnosis of Crohn’s Disease and Ulcerative Colitis

Ulcerative Colitis: Bleeding 101402.7 Lindenbaum - On-screen

Severe Crohn’s Colitis Reprinted by permission of Blackwell Science, Inc. Marion JF et al. In: Di Marino AJ, Benjamin SB (eds). Gastrointestinal Disease: An Endoscopic Approach. 1997:511.

Pseudopolyps in CD Reprinted by permission of Blackwell Science, Inc. Marion JF et al. In: Di Marino AJ, Benjamin SB (eds). Gastrointestinal Disease: An Endoscopic Approach . 1997:511.

Perianalis fistula

Normal endoscopic finding

Ulcerative colitis endoscopic finding

Crohn colitis

Crohn disease Enterography: String-sign (arrow) is demonstrated. Sac-formation may be observed on the antimesenteric side (double arrow).

Ulcerative colitis pseudopolyps

Crohn’s Dx – String Sign

Ulcerative Colitis - Ulcerations

Ulcerative Colitis – “Lead Pipe”

Fibrostenosis in CD Courtesy of J-F Colombel, MD.

Intestinal Complications of Ulcerative Colitis Toxicity 101402.7 Lindenbaum - On-screen

Extraintestinal Manifestations

Extraintestinal Manifestations of IBD Skin disorders Erythema nodosum Pyoderma gangrenosum Joint disorders Peripheral arthritis Sacroiliitis Ankylosing spondylitis Ocular disorders Iritis, uveitis, and episcleritis

Skin disorders

Erythema nodosum

Pyoderma gangrenosum

Joint disorders

Peripheral arthritis

Sacroiliitis

Ankylosing spondylitis

Ocular disorders

Iritis, uveitis, and episcleritis

Extraintestinal Manifestations of IBD Hepatobiliary Gallstones Sclerosing cholangitis Cholangiocarcinoma Renal Renal stones Amyloidosis Other manifestations Aphthous stomatitis Hypercoagulable state

Hepatobiliary

Gallstones

Sclerosing cholangitis

Cholangiocarcinoma

Renal

Renal stones

Amyloidosis

Other manifestations

Aphthous stomatitis

Hypercoagulable state

Erythema Nodosum in IBD Courtesy of J-F Colombel, MD.

Pyoderma Gangrenosum in CD

Sacroiliitis in IBD Courtesy of J-F Colombel, MD.

Ankylosing Spondylitis Reprinted from the Clinical Slide Collection on the Rheumatic Diseases, copyright 1991, 1995, 1997. Used by permission of the American College of Rheumatology.

Scleritis in IBD Courtesy of J-F Colombel, MD.

Aphthous Stomatitis in IBD Courtesy of J-F Colombel, MD.