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A 17-year-old male presented with a 5-month history of abdominal pain and bloody mucus in his stool. Stool examination showed red blood cells, mucus, and pus cells but no pathogens. The patient experiences spontaneous remissions. The differential diagnosis includes inflammatory bowel disease. Further workup found the patient has inflammatory bowel disease, which is a chronic immune-mediated inflammation of the intestines that can manifest as ulcerative colitis or Crohn's disease. The document then discusses the epidemiology, pathogenesis, clinical features, pathology, and differences between ulcerative colitis and Crohn's disease in more detail.
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Git 6-csbrp
- 1. Inflammatory Bowel DiseaseInflammatory Bowel Disease Dr.CSBR.Prasad, M.D., May-2015-CSBRP
- 2. CaseCase • 17yo complains of pain abdomen and h/o passage of blood and mucus in his stool since 5months • He gives a h/o spontaneous remissions What are your differentials? May-2015-CSBRP
- 3. Case – continued….Case – continued…. • Stool examination: – Shows Mucus, RBCs & Pus cells – Negative for ova and parasites – Cultures: Repeatedly negative for pathogens What are your differentials? May-2015-CSBRP
- 4. Possible diagnosis: • Inflammatory bowel disease May-2015-CSBRP
- 5. Inflammatory Bowel DiseaseInflammatory Bowel Disease IBDIBD May-2015-CSBRP
- 7. IBDIBD • Def: IBD is a immune mediated chronic inflammatory condition of intestines • Major types: – Ulcerative colitis (UC) – Crohn’s disease (CD) Indeterminate colitis (IC): • In 15% of IBD patients it’s impossible to differentiate UC from CD. They are designated as IC May-2015-CSBRP
- 10. May-2015-CSBRP
- 11. Pathogenesis Current concept: • Inappropriate immune response to the endogenous commensal microbiota with in the intestine with / without some component of autoimmunity May-2015-CSBRP
- 12. Pathogenesis – genetic factors • IBD is a polygenic disorder • More than 100 disease associated loci on different chromosomes • 1/3rd of them overlap (UC & CD) • Genetic risk factors for IBD are also seen in other immune mediated diseases – RA (TNF A IP3) – SLE (TNF A IP3) – Psoriasis (IL 23R, IL 12B) – Ankylosing spondilitis (IL 23R) – Type-I DM (IL 10, PTPN2) May-2015-CSBRP
- 13. Pathogenesis – genetic factors May-2015-CSBRP
- 14. Pathogenesis – genetic factors May-2015-CSBRP Primary genetic disorder associated with IBD Psoriasis Ankylosing spondylitis Primary sclerosing cholangitis
- 15. Pathogenesis Oral tolerance: • Mucosal immune system is normally unreactive to luminal contents due to “Oral tolerance” • Mechanisms: – Deletion / anergy of Ag reactive T-cells – Induction of CD4+ T-cells that suppresses gut inflammation – By secreting IL10 & TGF-beta • In IBD oral tolerance is altered resulting in uncontrolled inflammation May-2015-CSBRP
- 17. Pathogenesis – Exogenous factors 1. Multiple pathogens have been implicated • Salmonella • Shigella • Campylobacter • Clostridium difficile May trigger an inflammatory response that then goes unregulated 1. Psychosocial factors May-2015-CSBRP
- 18. Ulcerative colitis (UC)Ulcerative colitis (UC) May-2015-CSBRP
- 19. Pathology – UC • Always involve rectum • Extends proximally to involve all / part of colon – 40-50% rectum / sigmoid – 30-40% beyond sigmoid – 20% total colitis – “Backwash ileitis” May-2015-CSBRP
- 20. Pathology – UC • Mild inflammation: the mucosa is erythematous with fine granular surface – sandpaper • More severe disease: the mucosa is hemorrhagic, edematous, and ulcerated • In long-standing disease: inflammatory polyps (pseudopolyps) • in Remission: The mucosa may appear normal • Patients with fulminant disease: – Toxic colitis or megacolon – Ulceration – Perforation May-2015-CSBRP
- 25. Inflamed colonic mucosa demonstrating pseudopolyps in a patient with ulcerative colitis May-2015-CSBRP
- 26. Thinned out wall, ulcers, pseudopolyps May-2015-CSBRP
- 27. Serpigenous ulcers, mucosal bridges and pseudopolyps May-2015-CSBRP
- 29. Ulcers confined to mucosa May-2015-CSBRP
- 30. Marked lymphocytic infiltration of the intestinal mucosa and architectural distortion of the crypts May-2015-CSBRP
- 31. Chronic architectural changes in ulcerative colitis. Note the crypt branching and irregularity of size and shape, with an increase in chronic inflammatory cells in the lamina propria May-2015-CSBRP
- 33. UC – Clinical features • Diarrhea • Rectal bleeding • Tenesmus • Passage of mucus • Crampy abdominal pain • Anorexia, nausea, vomiting • Weight loss • o/e tender anal canal, blood on PR • Complications: – Toxic megacolon – Perforation – Peritonitis – Strictures (mimic carcinoma) – Carcinoma May-2015-CSBRP
- 35. Patients with ulcerative colitis can occasionally have aphthous ulcers involving the tongue, lips, palate and pharynx May-2015-CSBRP
- 36. Crohn’s disease (CD)Crohn’s disease (CD) 1884-1983 May-2015-CSBRP
- 37. Pathology - CD • Can affect any part of the gastrointestinal tract – 30–40% small-bowel disease (75% terminal ileum) – 40–55% both the small and large intestines, and – 15–25% have colitis alone – Rectum is often spared • “Skip areas” in the midst of diseased intestine • Perirectal fistulas, fissures, abscesses, and • Anal stenosis are present in 1/3rd of patients • Rarely, may involve the liver and the pancreas May-2015-CSBRP
- 38. Morphology • Involved segment is rubbery and thick (due to edema, inflammation, fibrosis and hypertrophied muscularis propria) • String sign in X-ray • Skip lesions • Cobble stone mucosa • Deep penetrating ulcers • Fistulae May-2015-CSBRP
- 42. May-2015-CSBRP
- 43. Stenosis of terminal ileum May-2015-CSBRP
- 44. ‘String sign’ – very thin luminal constrast in the terminal ileum May-2015-CSBRP
- 45. Double-contrast barium enema study demonstrates marked ulceration, inflammatory changes, and narrowing of the right colon in a patient with Crohn colitis May-2015-CSBRP
- 46. May-2015-CSBRP
- 47. May-2015-CSBRP
- 48. May-2015-CSBRP
- 49. Enterocolic fistula of Crohn's disease The barium study outlines the fistula connecting the small bowel to the colon May-2015-CSBRP
- 50. Morphology • Neutrophils in isolated crypts • Architectural distortion – Villous blunting – Atophy – Metaplasia • Transmural inflammation • Non-caseating granulomas • Submucosal fibrosis • Thickening of muscularis propria • Strictures May-2015-CSBRP
- 52. Deep knifelike, fissuring, transmural ulcer in Crohn disease May-2015-CSBRP
- 55. CD – Clinical features • Site of the disease influences the clinical manifestations • Patterns: 1. Fibrostenotic obstructive pattern 2. Penetrating fistulous pattern May-2015-CSBRP
- 56. The three most common sites of intestinal involvement in Crohn's disease: ileojejunal ileocolic and colonic May-2015-CSBRP
- 57. CD – Clinical features Ileocolitis: • Right lower quadrant pain • Pain releived by defecation • Weight loss • String sign in X-ray • Fistulae • Microperforations Colitis / perianal disease: • Strictures • Fistulae Jejunoileitis: • Malabsorption – Anemia – Hypoalbuminemia – Hypocalcemia – Coagulopathy • Nutritional deficiency – Pellagra – Osteoporosis – Megaloblastic anemia – Neurological symptoms May-2015-CSBRP
- 58. CD – Clinical features Fistulae: • Duodenocolic (fecal vomitus) • To mid small bowel (short circuiting - malabsorption) • Rectovaginal (feculent vaginal discharge esp. after hystrectomy) • Enterovesicle (fecaluria, pneumaturia) • Enterocutaneous • Perianal disease (fistulae, fissures) May-2015-CSBRP
- 59. Complications • Serosal adhesions • Perforations • Peritonitis • Intraabdominal / pelvic abscesses • Perianal disease • Obstruction May-2015-CSBRP
- 60. May-2015-CSBRP
- 61. Patients with Crohn’s disease can occasionally have aphthous ulcers involving the tongue, lips, palate and pharynx May-2015-CSBRP
- 62. Feture Crohn’s disease Ulcerative colitis MacroscopicMacroscopic Site Ileum +/- colon Colon only Distribution Skip lesions Diffuse Strictures Early Late Wall appearance Thickened Thin Dilatation No Yes MicroscopicMicroscopic Pseudopolyps No Marked Ulcers Deep linear Superficial Lymphoid reaction Marked Mild Granulomas Present Absent Fibrosis Marked Mild Fistulae/sinuses Present Absent ClinicalClinical Malabsorptions Yes No Malignant potential Yes Yes Response to surgery Poor Good May-2015-CSBRP
- 64. Introduction – “Oral toleranceOral tolerance” • Entry of pathogen is associated with production of: – Antibodies or – Activated lymphocytes • Sites where bacteria are present normally in the body as commensals: – Skin – Oropharynx – Large intestine • Reaction of our defences to normal commensals is inappropriate Inflammation No Inflammation May-2015-CSBRP
Editor's Notes
- Ref: Harrison, 17th ed
- Both exogenous and endogenous factors play a role in genetically predisposed individual.
- FIGURE 17-33 One model of IBD pathogenesis. Aspects of both Crohn disease and ulcerative colitis are shown. T helper 17 cell: (Th17) are a subset of T helper cells producing interleukin 17 (IL-17). They are developmentally distinct from Th1 and Th2 cells. They create inflammation and tissue injury in autoimmune disease such as multiple sclerosis (which was previously thought to be caused by Th1 cells), psoriasis, autoimmune uveitis, juvenile diabetes, rheumatoid arthritis, and Crohn's disease. Th17 has also been suspected to play a role in allergen-induced airway responses. Their normal role is to provide anti-microbial immunity at epithelial / mucosal barriers. They produce cytokines (such as interleukin 22) which stimulates epithelial cells to produce anti-microbial proteins to clear out certain types of microbe (such as Candida and Staphylococcus). Thus, a lack of Th17 cells leaves the host susceptible to opportunistic infections. Transforming growth factor beta (TGF-β), interleukin 6 (IL-6), interleukin 21 (IL-21) and interleukin 23 (IL-23) contribute to Th17 formation in mice and humans.
- Note: the normal intestines contain a large number of immune cells in a chronic state of so called physiologic inflammation, in which gut is restrained from full immunological response to the commensal microbiota and dietary antigens by very powerful regulatory pathways that function within the immune system (eg: Fox P3+ T-regulatory cell) During the course of infection in the normal host, full activation of the gut associated lymphoid tissue occurs but is rapidly superseded by dampening of the immune response and tissue repair. In IBD this process may not be regualted.
- Many genetic risk factors identified in IBD are also seen in other immune mediated diseases
- During the course of infection in the normal host, full activation of the gut associated lymphoid tissue occurs but is rapidly superseded by dampening of the immune response and tissue repair. In IBD this process may not be regualted.
- During the course of infection in the normal host, full activation of the gut associated lymphoid tissue occurs but is rapidly superseded by dampening of the immune response and tissue repair. In IBD this process may not be regualted.
- Psychosocial factors may worsen the symptoms such as pain, bowel dysfunction, bleeding et.c. These factors include: illness/death in family, divorce, interpersonal conflict.
- When whole colon is involved the inflammation may extend 2-3cms into the ileum, this is known as ‘backwash ileitis’.
- With mild inflammation, the mucosa is erythematous and has a fine granular surface that looks like sandpaper. In more severe disease, the mucosa is hemorrhagic, edematous, and ulcerated (Fig. 289-1). In long-standing disease, inflammatory polyps (pseudopolyps) may be present as a result of epithelial regeneration. The mucosa may appear normal in remission, but in patients with many years of disease it appears atrophic and featureless and the entire colon becomes narrowed and shortened. Patients with fulminant disease can develop a toxic colitis or megacolon where the bowel wall thins and the mucosa is severely ulcerated; this may lead to perforation.
- Small image is the endoscopic view of normal colon.
- Pan-ulcerative colitis. Mucosa has a lumpy, bumpy appearance because of areas of inflamed but intact mucosa separated by ulcerated areas. (Courtesy of Dr. KE Rosado and Dr. CA Parkos, Division of Gastrointestinal Pathology, Department of Pathology, Emory University, Atlanta, Georgia; with permission.) REF: Harrison’s medicine
- Microscopically, the inflammation of ulcerative colitis is confined primarily to the mucosa. Here, the mucosa is eroded by an ulcer that undermines surrounding mucosa.
- Biopsy sample (H&E stain) that demonstrates marked lymphocytic infiltration (blue/purple) of the intestinal mucosa and architectural distortion of the crypts.
- H&E stain of a colonic biopsy showing a crypt abscess, a classic finding in ulcerative colitis
- PR = per rectal examination Tenesmus=A painfully urgent but ineffectual attempt to urinate or defecate.
- Over time, there is a risk for adenocarcinoma with ulcerative colitis. Here, more normal glands are seen at the left, but the glands at the right demonstrate dysplasia, the first indication that there is a move towards neoplasia.
- CD can affect any part of the gastrointestinal tract from the mouth to the anus. Some 30–40% of patients have small-bowel disease alone, 40–55% have disease involving both the small and large intestines, and 15–25% have colitis alone. In the 75% of patients with small-intestinal disease, the terminal ileum is involved in 90%. Unlike UC, which almost always involves the rectum, the rectum is often spared in CD. CD is segmental with skip areas in the midst of diseased intestine (Fig. 289-3). Perirectal fistulas, fissures, abscesses, and anal stenosis are present in one-third of patients with CD, particularly those with colonic involvement. Rarely, CD may also involve the liver and the pancreas.
- ‘String sign’ – very thin luminal constrast in the terminal ileum from spasm and eventual fibrosis is most often seen in Crohn’s disease
- Double-contrast barium enema study demonstrates marked ulceration, inflammatory changes, and narrowing of the right colon in a patient with Crohn colitis.
- One complication of Crohn's disease is fistula formation. Seen here is a fissure extending through mucosa at the left into the submucosa toward the muscular wall, which eventually will form a fistula. Fistulae can form between loops of bowel, bladder, and skin. With colonic involvement, perirectal fistulae are common.
- Microscopically, Crohn's disease is characterized by transmural inflammation. Here, inflammatory cells (the bluish infiltrates) extend from mucosa through submucosa and muscularis and appear as nodular infiltrates on the serosal surface with pale granulomatous centers.
- At high magnification the granulomatous nature of the inflammation of Crohn's disease is demonstrated here with epithelioid cells, giant cells, and many lymphocytes. Special stains for organisms are negative.
- PR = per rectal examination Tenesmus=A painfully urgent but ineffectual attempt to urinate or defecate.
- PR = per rectal examination Tenesmus=A painfully urgent but ineffectual attempt to urinate or defecate.
- PR = per rectal examination Tenesmus=A painfully urgent but ineffectual attempt to urinate or defecate.
- FIGURE 17-32 Distribution of lesions in inflammatory bowel disease. The distinction between Crohn disease and ulcerative colitis is primarily based on morphology.