Introduction of Inflammatory bowel disease-Crohn’s disease Dr Mamlook Elmagraby

Objectives of the lecture: Upon completion of this lecture, students should be able to: Know the two forms of idiopathic inflammatory bowel disease (IBD) Describe Crohn disease with respect to: clinical features and extra-intestinal manifestations, pathogenesis, pathology (gross and microscopic features), complications (especially adenocarcinoma preceded by dysplasia)

Idiopathic inflammatory bowel diseases Idiopathic inflammatory bowel diseases include chronic crypt destructive diseases (chronic ulcerative colitis, and Crohn’s disease) They are chronic relapsing inflammatory disorders of unknown origin which share many common features Ulcerative colitis and Crohn’s disease differ in: Natural history Clinical and pathologic associations Response to treatment Relapse (of someone suffering from a disease) suffer deterioration after a period of improvement

Idiopathic inflammatory bowel diseases Pathogenesis: IBD is characterized by an exaggerated and destructive mucosal immune response Inflammation is the final common pathway for the pathogenesis of IBD Both the clinical manifestations and the morphologic changes of IBD are the result of activation of inflammatory cells: Initially, neutrophils later in the course, mononuclear cells

Idiopathic inflammatory bowel diseases The products of these inflammatory cells cause nonspecific tissue injury Inflammation causes: Impaired integrity of the mucosal epithelial barrier Loss of surface epithelial cell absorptive function These events give rise to intermittent bloody diarrhea

Idiopathic inflammatory bowel diseases Etiology: Genetic susceptibility Failure of immune regulation Triggering by microbial flora Genetic Predisposition NOD2 has been identified as a susceptibility gene in Crohn disease Some polymorphisms of the IL-23 receptor gene are protective in both Crohn disease and ulcerative colitis

Idiopathic inflammatory bowel diseases Immunologic Factors It is not known whether the immune responses in IBD are directed against self-antigens or to bacterial antigens The primary damaging agents appear to be CD4+ cells The tissue inflammation may be the result of secretion of the cytokine IL-17 by the "TH17" subset The inflammatory cytokine TNF may play an important role in Crohn disease

Idiopathic inflammatory bowel diseases Microbial Factors The sites affected by IBD are flooded with bacteria It is likely that microbes provide the antigenic trigger to dysregulated immune system

One model of IBD pathogenesis One model of IBD pathogenesis. Aspects of both Crohn disease and ulcerative colitis are shown

EXTRAINTESTINAL MANIFESTATIONS OF INFLAMMATORY BOWEL DISEASE

Idiopathic inflammatory bowel diseases Prognosis The prognosis in a patient with IBD is determined by: The relapse rate The rate of surgery The incidence of colon cancer   About 20% to 30% of patients with pan-UC will require colectomy within their lifetime More than 60% of Crohn’s patients require surgery

Idiopathic inflammatory bowel diseases The risk for colon cancer is increased in patients with UC In colonic Crohn’s disease, the risk of colorectal cancer is equivalent to that in patients with UC of similar extent and duration The rates of small bowel carcinoma and lymphoma are increased in patients with Crohn’s disease

Crohn Disease

Crohn Disease This disease may affect any level of the alimentary tract It most commonly located at the terminal ileum Crohn disease must be viewed as a systemic inflammatory disease with predominant gastrointestinal involvement It occurs at any age but the peak age of detection is the second and third decades of life Crohn disease occurs three to five times more often among Jews than among non-Jews

Crohn Disease Morphology There is involvement of the small intestine alone in 30% of cases, of small intestine and colon in 40%, and of the colon alone in 30% The disease is characterized by: Sharply defined transmural involvement of the bowel by an inflammatory process with mucosal damage The presence of noncaseating granulomas Fissuring with formation of fistulae

Crohn Disease Gross: The sharp demarcation of diseased bowel segments from adjacent uninvolved bowel and skip lesions are characteristic The serosa becomes granular and dull gray The mesenteric fat wraps around the bowel surface The intestinal wall is rubbery and thick The lumen is narrowed

Crohn Disease Early disease shows focal mucosal ulcers, edema With progressive disease, ulcers join together into long, linear ulcers Narrow fissures develop between the folds of the mucosa Further extension of fissures leads to fistula formation

Small and large intestines, Crohn disease, mucosal surface The specimen is a section of normal ileum, thickened ileum, and right colon. The intestinal wall is thick, the result of edema, inflammation, fibrosis, and hypertrophy of the muscularis propria. Unlike ulcerative colitis, the diseased areas are sharply demarcated from adjacent uninvolved bowel. Note the area of normal colonic mucosa on the left and area of normal small bowel on the right. In diseased bowel segments, the serosa is thickened and fibrotic, and often the mesenteric fat wraps around the bowel surface

Crohn’s enterocolitis. Longitudinal ulcers (train track) with intervening normal-appearing mucosa

Crohn’s enterocolitis. Resection specimen with longitudinal ulcers (train track) and intervening normal mucosa

Crohn Disease Microscopical features: The mucosa shows: inflammation, ulceration, chronic mucosal damage Granulomas may be present Fibrosis affects all tissue layers Lymphoid aggregates can be seen The muscularis mucosae and muscularis propria are thickened

Bowel, Crohn disease focal areas of ulceration, submucosal edema, and transmural inflammation with lymphoid nodules Fissures are narrow microscopic clefts that penetrate from the ulcer surface into muscle and are lined by granulation tissue. When the entire bowel wall is traversed, a sinus tract is formed that may open to the skin or adhere to an adjacent viscus

Bowel, Crohn disease, noncaseating granulomas Noncaseating granulomas are present in the lamina propria of an uninvolved region of colonic mucosa. Noncaseating granulomas are present in about half of Crohn disease cases in all tissue layers, both within areas of active disease and in uninvolved regions of the bowel.

Crohn Disease Clinical Features After an initial attack, the manifestations remit either spontaneously or with therapy, but they are followed by relapses The clinical presentation of Crohn’s disease depends on the section of gastrointestinal tract involved Symptoms in Crohn’s disease often include: Right lower quadrant abdominal pain Fever Weight loss Diarrhea Sometimes a palpable inflammatory mass Remission diminution of the symptoms of a disease

Crohn Disease Hematochezia is less common than in UC The transmural inflammation in Crohn’s disease can result in the formation of fistulous tracts   Fistulas may form between different segments of bowel or between bowel and skin, bowel and bladder, or rectum and vagina 30% to 40% of patients develop disabling perianal involvement with fissures, fistulas, and abscesses Chronic inflammation can cause fibrosis and stricture formation, which may result in partial or complete intestinal obstruction

Crohn Disease Strictures can also lead to stasis with subsequent small intestinal bacterial overgrowth Extensive ileal mucosal disease may lead to malabsorption of vitamin B12 and bile salts Weight loss may result from generalized malabsorption caused by loss of absorptive surfaces