Game of Crohn’s: The good, the bad and the ugly sides of Inflammatory Bowel Disease (IBD) Disclosures None to report Introduction Learning Objective(s) • Describe and differentiate the epidemiology, pathophysiology, intestinal and extra-intestinal clinical presentation, laboratory, endoscopic, and radiological diagnostic assessment and findings, pharmaceutical and surgical treatment options, and potential complications of Crohn’s Disease vs. Ulcerative Colitis Inflammatory Bowel Disease (IBD) By Definition Inflammatory Bowel Disease n. Abbr. IBD A chronic disorder of the gastrointestinal tract, especially Crohn's disease or an ulcerative form of colitis (inflammation of the inner lining of the colon) Two Main Types Setting the Scene… IBD Overview There is NO cure IBD is a result of an immune response against the bodies own intestinal system Most commonly begins in early 20’s to 30’s, but also seen in 50- 80 year old’s (but this peak is mainly for CD) Not contagious Cause UNKNOWN Both are characterized by diarrhea and abdominal pain Risk Factors Age and gender: 15-40 years of age 2nd peak 50-80 years of age (CD) Slight female predominance in CD Slight male predominance in UC Race and ethnicity: Jews Lower in black and Hispanic populations Genetic susceptibility Etiology Unknown but several contributing factors include: Infectious Environmental Diet Obesity NSAID or aspirin use (Cyclooxygenase-mediated disruption of the intestinal epithelial barrier) Psychosocial factors – NO consistent psychopathology Smoking – negative correlation between smoking and UC (smoking may even decrease the risk of flares) but a positive correlation between smoking and CD recurrence Genetics Activation of the immune system is the cause of the inflammation in IBD It is believed that genetics plays a major role but no specific trigger has been identified. First degree relatives 3-20 times more likely to develop IBD Genetic factors more important in CD than in UC First confirmed IBD gene (IBD1) confers increased risk of CD Clinical features of CD demonstrate a heritable pattern with concordance in disease location Over 100 distinct susceptibility loci for IBD Several genetic syndromes have been associated with IBD including Turners syndrome, Hermansky-Pudlak syndrome, and glycogen storage disease type 1b Symptoms Abdominal cramps and pain - common Diarrhea (can be bloody) - common Urgency Fever Loss of appetite Weight loss Fatigue Vomiting Anemia Ulcerative Colitis Ulcerative Colitis Limited to mucosal layer of the colon Toxic megacolon (clinical term, aka toxic colitis) Bleeding from ulcers The appearance of the mucosa in UC varies depending on the extent of the disease. The inflammation always begins in the distal rectum and spreads proximally in continuous fashion. The characteristic histologic lesion - is the crypt abscess (typical but not diagnostic) Extent of Involvement of Colon in UC Ulcerative proctitis - limited to the rectum Ulcerative proctosigmoiditis - limited to the rectum and sigmoid colon and not involving the descending colon Left-sided or distal ulcerative colitis - is disease that extends beyond the rectum and as far proximally as the splenic flexure Extensive colitis - disease extending proximal to the splenic flexure but sparing the cecum Pancolitis is used when the inflammatory process extends beyond the splenic flexure to the cecum Toxic Megacolon Rare, life-threatening form of ulcerative colitis Signs include Fever >101oF/38.6oC Tachycardia Abdominal distention Signs of localized or generalized peritonitis Leukocytosis A dilated colon It may occur anytime during the course of UC but usually occurs early on Toxic Megacolon: Presentation Jalan et al described the diagnostic criteria, which are as follows: Radiographic evidence of colonic dilatation - The classic finding is more than 6 cm in the transverse colon Any 3 of the following - Fever (>101.5°F; 38.6°C), tachycardia (>120 beats/min), leukocytosis (>10.5 x 10 3/µL), or anemia Any 1 of the following - Dehydration, altered mental status, electrolyte abnormality, or hypotension Toxic Megacolon: Pathophysiology & Epidemiology Although the precise pathophysiology is unproven, several factors may contribute to its development and precipitation The microscopic hallmark of TM is inflammation extending beyond the mucosa into the smooth-muscle layers and serosa The lifetime risk of TM in ulcerative colitis has been estimated to be 1-2.5% No data exist regarding race or gender and the incidence of TM Toxic Megacolon: Treatment • Treatment of TM includes 3 main goals: 1. Reduce colonic distention to prevent perforation, 2. Aggresive correction of fluid and electrolyte disturbances, and 3. Treatment of toxemia and precipitating factors with broad-spectrum antibiotics • Careful and frequent monitoring of the patient is required, especially in the first 12 hours • Patients should be put on bowel rest, and a nasogastric tube (NGT) or long intestinal tube should be placed to assist with gastrointestinal decompression Toxic Megacolon: Prognosis The survival prognosis of TM should be excellent in the absence of perforation In the case of ulcerative colitis, a proctocolectomy cures patients of the disease With the use of tumor necrosis factor (TNF)-alpha inhibitors, it is hoped that more cases can be managed medically in future Crypt Abscess “The tubular crypt of Leiberkuhn rounds the corner, in and out of the plane of section twice, giving it a double look. Contrast the healthy crypts at the left edge with the abscessed crypt, and the neutrophils in the crypt abscess with the lymphocytes and plasma cells between the crypts.” Crohn’s Disease Crohn’s Disease Transmural inflammation and skip lesions Mouth to anus Obstruction and strictures Perforation of bowel Abscesses (up to 20 percent; intra-abdominal or extra-abdominal) Fissures (40 percent; a small tear) and fistulas (an abnormal connection between organs) Clinical manifestations of CD more variable than UC Fatigue Prolonged diarrhea with abdominal pain with or without gross bleeding Weight loss Fever malabsorption Malignancy Risk and incidence increases 8-10 years after diagnosis The extent of colonic involvement and the duration of the disease are strongly correlated with cancer risk Extraintestinal Complications • Depression • Arthritis • Liver and kidney disorders including renal stones • Inflammation of the eye (Anterior Uveitis) • Skin conditions (Erythema Nodosum / Pyoderma Gangrenosum) • Bone loss and osteoporosis • Primary Sclerosing Cholangitis • Venous and arterial thromboembolism • Vitamin B12 deficiency • Spondyloarthropathy and ankylosing spondylitis Physical Examination For UC & CD physical examination is often normal at presentation Some of the findings that may be seen include: pallor evidence of weight loss abdominal tenderness red blood on rectal examination Crohn’s disease - More specific findings include perianal skin tags and sinus tracts Routine Laboratory Studies Tests that may be done but do not confirm IBD include: Fecal occult blood test Complete blood count (CBC) Blood chemistry including electrolytes, renal function tests, liver enzymes, and blood glucose Erythrocyte sedimentation rate (ESR) C-reactive protein (CRP) Serum iron and vitamin B12 level Stool Cultures – Ova and Parasites, C. Difficile, Giardia stool antigen test STI – for UC Antibody Tests – used to distinguish between CD and UC and to determine the probability of IBD vs. other types of colitis Antibody Tests Antineutrophil cytoplasmic antibodies (pANCA) and anti- Saccharomyces cerevisiae antibodies (ASCA) The sensitivity of the antibody tests alone or in combination was in the range of 40 to 60 percent, and the specificity was greater than 90 percent for distinguishing patients with IBD from controls. Anti-OmpC antibody – The anti-OmpC antibody has been identified as a potential serologic marker of IBD Diagnosis Characteristic history Typical endoscopic appearance of the mucosa Confirmatory histology seen on colonic biopsy Diagnostic Studies for IBD • Upper GI series with small bowel follow through (SBFT) – initial study • Barium enema • Contrasted CT scan – used more to determine complications of the disease such as abscesses or fistulas rather than for specific diagnosis • May show marked thickening of bowel wall in UC, but finding is nonspecific • Endoscopy – preferred study • Small bowel enteroscopy • Capsule endoscopy • EGD (ulcerations occur in the stomach and duodenum in 5-10% of patients with crohn’s disease) Endoscopy Findings in UC In mild disease: A fine granular appearing mucosa In more severe disease: Discrete ulcers are seen In long-standing disease: Loss of haustral markings Shortening of the colon Tubular appearance of the colon along with pseudopolyps Endoscopy Findings in CD Characteristic findings of small bowel disease include: Skip lesions Cobblestoning Luminal narrowing Characteristic findings on colonoscopy include: Aphthae ulcers (small shallow ulcers with a red halo) Skip lesions Rectal sparing Differential Diagnosis Broad - because of the segmental nature of CD, a variety of disorders can mimic its clinical presentation IBS Lactose intolerance Infectious colitis Appendicitis Diverticulitis Diverticular colitis Ischemic colitis Perforating or obstructing carcinoma Lymphoma Chronic ischemia Endometriosis and carcinoid - NB: Can both give a radiologic and clinical picture that is easily confused