Inflammatory Bowel Disease 4th year MS 2009-2010 Khaled Jadallah, MD Assistant Professor of Medicine Gastroenterology, Hepatology & Nutrition Educational Objectives Definitions and spectrum of inflammatory bowel disease (IBD) Epidemiology of IBD Etiopathogenesis of IBD Clinical manifestations of ulcerative colitis (UC) Clinical manifestations of Crohn’s disease (CD) Distinguishing features between UC and CD Diagnostic approach to IBD Complications of IBD IBD management Inflammatory Bowel Disease IBD include a group of chronic relapsing disorders that cause inflammation or ulceration in the small and/or large intestines. IBD is classified as: Ulcerative colitis (UC)- causes ulceration and inflammation of the mucosa of the colon and rectum Crohn's disease (CD) - an inflammation that extends into the deeper layers of the intestinal wall, and also may affect other parts or layers of the digestive tract, including the mouth, esophagus, stomach, and small intestine Educational Objectives Definitions and spectrum of inflammatory bowel disease (IBD) Epidemiology of IBD Etiopathogenesis of IBD Clinical manifestations of ulcerative colitis (UC) Clinical manifestations of Crohn’s disease (CD) Distinguishing features between UC and CD Diagnostic approach to IBD Complications of IBD IBD management Epidemiology of IBD Incidence (US) Age of onset Male:female ratio Smoking Oral contraceptive Ulcerative colitis Crohn’s disease 11/100 000 7/100 000 15-30 & 60-80 15-30 & 60-80 1:1 1,1-1,8:1 May prevent disease May cause disease No increased risk Relative risk 1,9 Appendectomy Not protective Protective Monozygotic twins 8% concordance 67% concordance High Medium Low Educational Objectives Definitions and spectrum of inflammatory bowel disease (IBD) Epidemiology of IBD Etiopathogenesis of IBD Clinical manifestations of ulcerative colitis (UC) Clinical manifestations of Crohn’s disease (CD) Distinguishing features between UC and CD Diagnostic approach to IBD Complications of IBD IBD management Nature Nurture IBD Genes Environment Educational Objectives Definitions and spectrum of inflammatory bowel disease (IBD) Epidemiology of IBD Etiopathogenesis of IBD Clinical manifestations of ulcerative colitis (UC) Clinical manifestations of Crohn’s disease (CD) Distinguishing features between UC and CD Diagnostic approach to IBD Complications of IBD IBD management Ulcerative Colitis – clinical presentation Patients with proctitis usually pass fresh blood or bloodstained mucus either mixed with stool or streaked onto the surface of normal or hard stool; tenesmus is a feature When the disease extends beyond the rectum, blood is usually mixed with stool or grossly bloody diarrhea may be noted When the disease is severe, patients pass a liquid stool containing blood, pus, fecal matter Other symptoms in moderate to severe disease include: anorexia, nausea, vomitting, fever, abdominal pain, weight loss Ulcerative colitis – macroscopic features Mucosa is : - erythematous, has a granular surface that looks like a sand paper In more severe diseases: - hemorrhagic, edematous and ulcerated In fulminant disease a toxic colitis or a toxic megacolon may develop ( wall becomes very thin and mucosa is severely ulcerated) UC Disease Distribution at Presentation 37% 17% 46% UC – disease severity MILD MODERATE SEVERE BOWEL MOVEMENTS < 4 per day 4-6 per day >6 per day BLOOD IN STOOL small moderate Severe FEVER none <37,5°C > 37,5°C TACHYCARDIA none <90 mean pulse >90 mean pulse UC – disease severity MILD ANEMIA mild ESR <30mm ENDOSCOPIC APPEARANCE Erythema, decreased vascular pattern, fine granularity MODERATE >75% SEVERE <75% >30mm Marked erythema, coarse granularity, contact bleeding, no ulceration Spontaneous bleeding, ulceration Educational Objectives Definitions and spectrum of inflammatory bowel disease (IBD) Epidemiology of IBD Etiopathogenesis of IBD Clinical manifestations of ulcerative colitis (UC) Clinical manifestations of Crohn’s disease (CD) Distinguishing features between UC and CD Diagnostic approach to IBD Complications of IBD IBD management CD: Clinical Features Abdominal pain, often postprandial Diarrhea, usually watery Rectal bleeding Weight loss Right lower quadrant pain/palpable mass Fever Growth retardation in children Perirectal fistula Crohn’s disease – macroscopic features Can affect any part of GI tract from the mouth to the anus 30-40% of patients have small bowel disease alone 40-55% of patients have both small and large intestines disease 15-25% of patients have colitis alone In 75% of patients with small intestinal disease the terminal ileum in involved in 90% Crohn’s Disease: Anatomic Distribution Small bowel alone (33%) Ileocolic (45%) Frequency of involvement Most Least Colon alone (20%) Crohn’s disease – macroscopic features CD is a transmural process CD is segmental with skip areas in the midst of diseased intestine In one third of patients with CD perirectal fistulas, fissures, abscesses, anal stenosis are present Crohn’s disease – macroscopic features Active CD is characterized by focal inflammation and formation of fistula tracts The bowel wall thickens and becomes narrowed and fibrotic, leading to chronic, recurrent bowel obstruction Crohn’s Disease Activity Index (CDAI) Incorporates 8 variables: 1. liquid or very soft stools /day 2. Abdominal pain & cramping 3. Extraintestinal manifestations 4. Complications 5. Abdominal mass 6. Use of anti diarrheal medications anti7. Hematocrit 8. Body weight Crohn’s Disease Red Flags Onset after stopping smoking Bleeding only Diverticulosis Atherosclerosis Prolapse Extraintestinal Manifestations of IBD Skin Erythema nodosum Pyoderma gangrenosum Joints Peripheral arthritis Sacroileitis Ankylosing spondylitis Eye Uveitis Episcleritis Iritis Hepatobiliary complications Gallstones PSC Renal complications Nephrolithiasis Recurrent UTIs Educational Objectives Definitions and spectrum of inflammatory bowel disease (IBD) Epidemiology of IBD Etiopathogenesis of IBD Clinical manifestations of ulcerative colitis (UC) Clinical manifestations of Crohn’s disease (CD) Distinguishing features between UC and CD Diagnostic approach to IBD Medical management of IBD Indications for and role of surgery Symptoms of IBD UC vs CD Feature UC CD Fever Uncommon Common Rectal bleeding Common < ½ of patients Abdominal tenderness Abdominal mass May be present Common Uncommon Common Abdominal pain Uncommon Very common Weight loss Uncommon Common Tenesmus Very common Uncommon UC vs CD Complications/Response to Treatment UC CD Fistulas No Yes Small intestine obstruction Colonic obstruction Response to antibiotic Recurrence after surgery No Frequently Rarely Frequently No Yes No Yes UC vs CD Different endoscopic features UC CD Rarely Frequently Continuous disease „Cobblestoning” Yes Occasionally No Yes Granuloma on biopsy No Occasionally Rectal sparing Criteria for Indeterminate Colitis No evidence of small bowel involvement, fistula, or perianal disease Absence of diagnostic criteria for CD or UC by microscopy Differential Diagnosis of Chronic Diarrhea and Weight Loss Colonic diseases IBD Neoplasia Ischemic bowel Pancreatic Chronic pancreatitis Cancer Cystic fibrosis Enteropathic Celiac disease Tropical sprue Lymphoma Mesenteric ischemia Whipple’s disease Hormonal/drugs Vipoma ZES Medullary CA of thyroid NSAIDS use Educational Objectives Definitions and spectrum of inflammatory bowel disease (IBD) Epidemiology of IBD Etiopathogenesis of IBD Clinical manifestations of ulcerative colitis (UC) Clinical manifestations of Crohn’s disease (CD) Distinguishing features between UC and CD Diagnostic approach to IBD Medical management of IBD Indications for and role of surgery Diagnostic Approach to Patients with Suspected IBD History……history……history Clinical exam Laboratory tests Radiological imaging Endoscopy Special serological testing Genetic testing Diagnosis-LAB Blood test CD: Mild anemia, mild leukocytosis, elevated ESR, elevated CRP, positive ASCA UC: Anemia, hypokalemia, hypoalbuminemia, elevated ESR, elevated LFTs, positive p-ANCA Stool analysis Many WBCs and /or RBCs No ova or parasites What are the Serological Markers in IBD? pANCA (perinuclear staining pattern) Loss of perinuclear pattern after DNAase Differentiate from the “other pANCAs” Antibody against myeloperoxidase Antibody against cathepsin G, elastase, lysozyme, and lactoferrin ASCA (anti-Saccharomyces cerevisiae) Both IgG and IgA Recognize mannose in the cell wall mannan of Saccharomyces cerevisiae Why Use Serological Markers in Clinical Practice? Differentiate IBD from functional bowel disorders Accurately diagnose Crohn’s or UC in a patient with: Severe colitis Indeterminate colitis Predict disease course or complications in IBD CD phenotype Severity of disease Risk of pouchitis Summary pANCA and ASCA are specific for UC and CD respectively Neither pANCA nor ASCA are sensitive enough to exclude IBD In patients with IC, available serological markers do not accurately predict the subsequent disease course Antibody profiles can predict disease behavior in IBD Diagnostic Approach Endoscopy Endoscopy useful for Initial diagnosis Assessment of severity Tissue diagnosis F/U during treatment Assessment of disease exacerbation Surveillance for risk of cancer Treatment of certain complications (e.g. strictures) Crohn’s Disease Endoscopic Features Asymmetric patchy inflammation Skip lesions Rectal sparing Ulcerations-deep/serpiginous Cobblestoning-common Pseudopolyps-rare Biopsy Erosions and normal mucosa Granulomas in 15 to 35% of specimens Ulcerative Colitis Endoscopic Features Diffuse involvement Rectum always diseased Superficial ulcerations Friability/bleeding Flattening/disappearance of haustral folds Pseudopolyps No cobblestoning Bx: No granulomas Imaging for Crohn Disease Traditional Techniques Abdominal Radiographs Barium UGI Barium small bowel follow through Barium Enteroclysis Barium Enema Imaging for Crohn Disease Newer Techniques CT CT Enteroclysis CT Enterography Magnetic Resonance Ultrasound Nuclear Medicine Imaging for Crohns Disease Summary Useful Newer Techniques evolving CT Enterography Comprehensive evaluation of all bowel & solid organs Magnetic Resonance Useful for ano-rectal disease Real-time MR has potential for detection of strictures Traditional imaging techniques still of value in selected cases The Capsule (WCE) WCE • • • • • • Diameter 11mm: Length 26mm Optical dome: Intestinal illumination by white light emitting diodes (LED’s) Lens Complementary metal-oxide silicone imager (color camera chip) Transmitter Two batteries (silver oxide) GE Junction Jejunum Duodenum Ileocecal Valve Educational Objectives Definitions and spectrum of inflammatory bowel disease (IBD) Epidemiology of IBD Etiopathogenesis of IBD Clinical manifestations of ulcerative colitis (UC) Clinical manifestations of Crohn’s disease (CD) Distinguishing features between UC and CD Diagnostic approach to IBD Complications of IBD IBD management IBD-Complications GI Bleeding Toxic megacolon Perforation Thromboembolic phenomena Fistulas/fissures Abscess Strictures/obstruction Malabsorption/malnutrition Cancer Best Protection Surveillance colonoscopy Procto-colectomy (for UC) Descending Colon Stricture Colonic Strictures Consider nonsurgical management if: Endoscopically accessible Multiple prior resections Shorter strictures (less than 5 cm) Steroid injection if significant inflammation Fistula: Definition A communication between two epithelial-lined organs. Lifetime risk of fistula in CD:30% Perianal Fistula Pretreatment 2 Weeks 10 Weeks 18 weeks Educational Objectives Definitions and spectrum of inflammatory bowel disease (IBD) Epidemiology of IBD Etiopathogenesis of IBD Clinical manifestations of ulcerative colitis (UC) Clinical manifestations of Crohn’s disease (CD) Distinguishing features between UC and CD Diagnostic approach to IBD Complications of IBD IBD management Goals of Therapy for IBD Inducing remission Maintaining remission Restoring and maintaining nutrition Maintaining patient’s quality of life Prevention of complications Surgical intervention (selection of optimal time for surgery) Inductive Therapies For UC Aminosalicylates Corticosteroids Cyclosporin For CD Aminosalicylates Corticosteroids Antibiotics Anti-TNF Maintenance Therapies Immunosupressors Azathioprine 6-MP Methotrexate Aminosalicylates Anti-TNF NOT corticosteroids IBD Management Summary There is no “one size fits all” to IBD therapy Algorithms are based upon available evidence Therapy and decision making are tailored to the individual Evidence is in constant flux Success of algorithms depends upon optimization of each step of therapy and considerable judgment about each outcome Skillful application of medical therapy makes all the difference in outcomes Surgery for IBD General Concepts Majority will need surgery: 78% over twenty years Surgery generally indicated for complications of disease Surgery must be directed at area of bowel responsible for complication Indications for Surgery Intestinal obstruction (most common) Intractability/steroid dependence Non-healing fistula/Abscess Toxic megacolon/Free perforation Uncontrollable GI bleeding Severe perianal disease Cancer Growth retardation (children) Severe uncontrollable extraintestinal manifestations Management of IBD Summary The goals of therapy are Treatment depends on Relieve symptoms Prevent relapse Correct nutritional deficiencies Control inflammation Prevent complications, especially colon cancer Type of disease Site of disease Disease severity Treatment may include drugs , nutrition supplements , surgery or a combination of these options