Crohn’s DiseasePrinciples of Pathology BIOM630Professor: Mark BlaisStudent: Olga MelnichukCrohn’s Disease: Historical BackgroundPast: the era of descriptionCrohn’s disease was first described in 1761 by Morgagni as intestinal inflammation.Recognition of the nosologic distinctions of Crohn’s disease and ulcerative colitis—the two major forms of idiopathic inflammatory bowel disease (IBD) allowed for attempts to treat them surgically and medically.First treatments: potassium permanganate, Dakin’s solution, antidysentery serum, E. coli vaccine, antiamoebic drugs, and sulfonamides.Crohn’s Disease: Historical BackgroundPresent: the era of explanationImmune tolerance is the normal state of the intestinal immune system.
Variety of cell types are involved in maintaining immunologic tolerance.Luminal flora is a key ingredient in the abnormal immune response of IBD.Genetic factors predispose individuals to an abnormal immune response to the flora.
Both innate and adaptive immune responses play integrated roles in the homeostasis of the intestinal mucosal immune response.Crohn’s Disease: Historical BackgroundFuture: the era of predictionPathogenesis of IBD is still not completely understood.Development of new approaches that could provide the targeted delivery of new safe drugs to the gut could increase clinical efficacy and limit potential adverse events.Stem-cell therapies.Crohn’s Disease: EpidemiologyIncidence of 3 to 20 cases per 100,000.
More common in the industrialized world, particularly in North America and Western Europe.Slightly higher predominance of CD in women and it is more common in individuals of Ashkenazi Jewish.Number of genetic and environmental factors that have been shown to increase the risk of the disease.
Crohn’s Disease: Signs and Symptoms It is a granulomatous inflammation of various parts of the digestive tract, characterized by a chronic recurrent and progressive course.For research and treatment purposes divided into phenotypic subtypes: inflammatory, stricturing, and fistulizing. Crohn’s Disease: Signs and Symptoms Inflammatory subtypeCharacterized by inflammation of the gastrointestinal tract with no evidence of stricturing or fistulizing disease.Crohn’s Disease: Signs and Symptoms Stricturing subtypeInflammation eventually leads to fibrosis and luminal narrowing – stricturing disease.Crohn’s Disease: Signs and Symptoms Fistulizing subtypeOngoing transmural inflammation results in the development of a sinus or fistulous tract – fistulizing CD Crohn’s Disease: Signs and Symptoms In addition to these 3 subtypes, patients can develop perianal complications. This complication develops regardless of the underlying luminal disease phenotype.Crohn’s Disease: Signs and Symptoms Accompanied by abdominal pain, diarrhea, intestinal bleeding. Systemic manifestations include fever, weight loss, musculoskeletal (arthropathy, sakroileitis), eye (episcleritis, uveitis), skin (erythema nodosum, pyoderma gangrenosum).
Common complication are intestinal obstruction and, fistulas, particularly anorectal fistulas.Crohn’s Disease: Diagnostic testing Currently there are no tests unique to IBD.Diagnosis is carried out with the help of colonoscopy, intestinal X-ray, CT.
findings on serum and stool testing, inflammatory markers including erythrocyte sedimentation rate and/or c-reactive protein, fecal calprotectin or fecal lactoferrin.Crohn’s Disease: TreatmentDepends on disease severity, location, and subtype.Treatment includes dietotherapy, anti-inflammatory, immunosuppressive, symptomatic therapy; with complications, surgical intervention. Immunosuppressants are used in combination with anti-TNF drugs to decrease their immunogenicity and increase anti-TNF drug concentrations. The mainstay of therapy for CD has been anti-TNF agents.Crohn’s Disease: TreatmentMedical therapy is aimed at inducing and maintaining a steroid-free clinical remission, preventing complications and surgery, and improving the patient’s quality of life.Recently approved drugs are monoclonal antibodies directed against certain integrins (?4 or ?4b7) or interleukins (IL-12/IL-23).