2.Inflammatory bowel disease type,diagnosis and treatment

Types,diagnosis and treatment of inflammatory bowel disease

1. Inflammatory Bowel Disease Professor mohammed Ahmed Bamashmos

2. Inflammatory bowel disease is an idiopathic and chronic intestinal inflammation Types : Ulcerative colitis : limited to the colon and rectum Crohn’s disease : affects any portion of the GI tract from oesophagus to anus Both exhibit extra intestinal inflammatory manifestations

3. Epidemiology Ulcerative colitis – most common IBD Peak age of onset of UC & CD is 15- 30 years – and 60 & 80 M:F = 1:1 for UC and F>M for CD Crohn’s diseases is more common in smokers, oral contraceptive users.

4. Etiology and pathogenesis : Etiology and pathogenesis have not been defined Current etiologic theories concerning IBD focus on environmental triggers, genetic factors, and immunoregulatory defects and microbial exposure Two key points : Strong immune responses against normal flora Defects in epithelial barrier functions Though idiopathic, it is postulated that IBD results from unregulated and exaggerated local immune response to commensals in gut, in genetically susceptible individuals

5. Genitical susceptibility : Familial predisposition with no clear mendelian inheritance Associated with HLA- DR1 , HLA- DR2, HLA-DR27 Role of intestinal flora: Exacerbate immune response by providing Ag and inducing constimulator and cytokines 🡪 t-cell activation 🡪 defects in barrier function Infection: Chlamydia, atypical bacteria, measeals virus, helicobacter Psychosocial factors: sensitive, reserved persons, death in family, divorce, conflict – STRESS. etc Environmental factors : diets and smoking (Crohns’s)

6. PATHOPHYSIOLOGY: The common end pathway is inflammation of the mucosal lining of the intestinal tract, causing ulceration, edema, bleeding, and fluid and electrolyte loss . Both UC and CD , activated CD4+ T-cells in the lamina propria and pheripheral blood secrete inflammatory cytokines

7.  various antigenic stimuli🡪Cytokines, released by macrophages 🡪bind to different receptors and produce autocrine, paracrine, and endocrine effects🡪 leads to intestinal damage and increased permiability T cells, type 1 (Th-1)= Crohn disease, whereas, Th-2 cells = Ulcerative colitis

8. IBD: Both UC and CD have waxing and waning in intensity and severity In most cases, symptoms correspond with degree of inflammation When patient is actively symptomatic, significant inflammation = flare-up of IBD When asymptomatic, inflammation absent (or less) = in remission

9. Ulcerative colitis (UC): Pathophysiology – Affects only the large intestine (very rarely terminal ileum may be inflamed superficially) Always starts in rectum and is continuous until some proximal part of the colon ; and no "skip areas" Involves the mucosa and submucosa with deeper layer unaffected ( except in fulminant disease).

10. Mucosa is : - Erythematous, has a granular surface that looks like a sand paper In more severe diseases : - Hemorrhagic, edematous and ulcerated; formation of crypt abscesses In fulminant disease : A toxic colitis or a toxic megacolon may develop ( wall become very thin and mucosa is severly ulcerated) As UC becomes chronic, colon becomes rigid and loses its haustral (pouch-like) markings Confined to rectum in 25% of cases; pancolitis in 10% of cases when whole colon involved – 1-2 cm ileum involved = Backwash ielitis

11. Ulcerative colitis – clinical presentation The major symptoms of UC are: - Diarrhea - Rectal bleeding - Tenesmus - Passage of mucus - Crampy abdominal pain - Loss of weight - Psychological disturbances

12. Patients with proctitis usually pass fresh blood or blood-stained mucus either mixed with stool or streaked onto the surface of normal or hard stool 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, weight loss

13. Investigation : Active phase: rise in CRP, platelet counts, ESR , decrease in Hb. Severe form : serum albumin will fall Dig.:- history, clinical symptoms , negative stool examination for micro organisms; sigmoidoscopic appearance ;histology

14. Radiologic change of UC The plain abd radiograph can show a dilated colon& small-bowel obstruction Contrast barium enema: Fine mucosal granularity Mucosa become thickenned and superficial ulcers are seen (collar-button ulcers)– mucosa penetration Loss of haustration Shortened and narrowed colon . Ileitis in UC (without the skip pattern)

15. CT & U/S best for demonstrating mesenteric inflammation, intra-abdominal abscesses and fistulas Colonoscopy recommended for making diagnosis and determining severity of disease

16. Ulcerative colitis - complication Hemorrhage Perforation Stricture Toxic megacolon (transverse colon with a diameter of more than 5 cm to 6 cm with loss of haustration) Malabsorbtion Obstruction Possibility of malignant transformation?

17. Colonic pseudopolyps

18. Ulcerative colitis :the left side of the colon is affected The image shows confluent superficial ulceration and loss of mucosal architecture.

19. lead pipe appearance

20. A 22-year-old man presented with abdominal pain, passage of blood and mucus per rectum, abdominal distention, fever, and disorientation. Findings from sigmoidoscopy confirmed ulcerative colitis. Abdominal radiographs obtained 2 days apart show mucosal edema and worsening of the distention in the transverse colon.

21. Diagnosis of UC H&P CT Stool exam Sigmoidscopy Colonoscopy Barium enema Lab studies

22. Crohn’s disease (CD) Crohn's disease differs from ulcerative colitis in the areas of the bowel it involves - it most commonly affects the last part of the small intestine and parts of the large intestine. In 75% of patients with small intestinal disease the terminal ileum in involved in 90% Crohn's disease isn't limited to these areas and can attack any part of the digestive tract Crohn's disease generally tends to involve the entire bowel wall Can have non-continuous pattern-” skip lesions ”, with areas of severe inflammation with intervening normal mucosa May be complicated by strictures, fistulas and abscesses

23. Distribution of gastrointestinal Crohn's disease. Based on data from American Gastroenterological Association .

24. Pathophysiology : 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

25. mild disease is characterized by: apthous or small superficial ulcerations In more active disease : stellate ulcerations fuse longitudinally and transversely to demarcate island of mucosa that are histologically normal Cobblestone appearance is characteristic of CD (both endoscopically and by barium radiography)

26. 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. Aphtoid ulceration and focal crypt abscesses with loose aggregation of macrophages which form granulomas is formed in all the layers. Transmural inflammation that is accompanied by fissures that penetrate deeply into the bowel wall

27. serpiginous ulcer, a classic finding in Crohn's disease

28. Crohn ’ s disease – sign and symptoms Ileocolitis - right lower quadrant pain and diarhhea - palpable mass, fever and leucocytosis - pain is colickly and relieved by defecation - fistula formation leading to adjecent organs and bowel causing recurrent bladder infections , dyspareunia or foul smelling vaginal discharges. Jejunoileitis - inflammatory disease is associated with loss of digestive and absorptive surface 🡪 malabroption and steatorrhoea

29. Crohn ’ s disease – sign and symptoms Colitis and perianal disease - low grade fever, malaise, diarrhea, crampy abdominal pain, sometimes hematochezia - pain is caused by passage of fecal material through narrowed and inflamed segments of large bowel Gastroduodenal disease - nusea, vomiting, epigastric pain - second portion of duodenum is more commonly involved than the bulb

30. The normal colon shows regular haustra and a transparent intact mucosa. The colon from the patient with Crohn's disease shows numerous deep ulcerations and areas of more normal appearing mucosa.

31. Endoscopic image of Crohn's colitis showing deep ulceration.

32. Crohn disease involving the terminal ileum. Note the "string sign" in the right lower quadrant

33. Crohn ’ s disease Diagnostic tests are the same except: 1- With Crohn’s will find string sign (segments of stricture separated by normal bowel) 2- With colonoscopy will find patchy areas of inflammations 🡪Skip areas & rectal sparing in CD 3- Need biopsy for definitive diagnosis Complications: Fistula formation Peritonitis due to rupture of intraabdominal absecess Intestinal obstructions Massive hemorrhage Malabsorption Severe preianal diseases

34. The fistulae become symptomatic with drainage of fecal material around the anus (perianal fistulae ), seepage of bowel contents through the skin ( enterocutaneous fistulae ), passage of feces through the vagina ( rectovaginal fistulae )& pneumaturia or recurrent urinary tract infections ( enterovesical fistulae ).

35. Serologic Test pANCA and ASCA Perinuclear antineutrophil cytoplasmic antibodies (pANCA) with ulcerative colitis, and anti-Saccharomyces cerevisiaeantibodies (ASCA) have been found in patients with Crohn’s disease.

36. IBD is associated with variety of extraintestinal manifestation. Almost one-third of the patients have at least one.

37. Extraintestinal manifestation Dermatologic 1. Erythema nodosum occurs in up to 15% of CD patients and 10% of UC patients The lesions of EN are hot, red, tender nodules measuring to 5cm in diameter and are found on the anterior surface of the legs, ankles, calves, thighs and arms 2. Pyoderma gangrenosum (PG) is seen in 1 to 12% of UC patients and is less common in CD colitis. PG may occur years before the onset of bowel symptoms. Lesions are common on the dorsal surface of the feet and legs but may occur on the arms, chest and even face.

38. Pyoderma gangrenosum

39. Extraintestinal manifestation Rheumatologic Peripherial arthritis developes in 15 to 20% of IBD patients, is more common in CD. It is asymmetric, polyarticular and migratory. Most often affects large joints of the upper and lower extremities Ankylosing spondylosis (AS) occurs in 10% of IBD. Sacroilitis is symetrical, occurs equally in UC and CD, often asymptomatic

40. Extraintestinal manifestation Ocular The incidence of ocular complications in IBM patients is 1 to 10% The most common is conjunctivitis, anterior uveitis, episcleritis Symptoms include: ocular pain, photophobia, blurred vision, headache

41. Extraintestinal manifestation Urologic The most frequent genitourinary complications are: calculi, ureteral obstruction, fistulas The highest frequency of nephrolithiasis (10-20%) occurs in patients with CD.

42. Patients with IBD have an increased prevelance of osteoporosis secondary to vitamin D deficiency, calcium malabsorbtion, malnutrition, corticosteroid use More common cardiopulmonary manifestations include endocarditis, myocarditis, pleuropericarditis and interstitial lung disease.

43. Treatment Treatment of inflammatory bowel disease involves drug therapy and in certain cases surgery

44. 5-ASA agents – (5-aminosalicylic acid) Main stay of management for mild to moderate UC and CD Sulfasalazine and other 5ASA agents are used. Used effectively at inducing remission in both UC and CD and in maintaining remission in UC. Newer 5-ASA preparation lack sulfa moiety of sulfa salazine and are associated with few side effects. MESALAMINE Asacol 800- 1600 mg tid --🡪 UC as well as for CD Pentasa 0.5 – 1.0 mg BD 🡪 for diffuse CD also in UC Osalazine

45. Glucocorticoids : Inducing remission of active UC and chrons disease. Not recommended for mild diseases. Used concurrently with other anti- inflammatory drugs ocular lesions, skin disease, and peripheral artheritis also responds Prednisolone 40-60 mg once daily and tappering off in 3-6 wks. In severe 🡪 IV administrations of methylprednisolone 20 -40 mg daily BD Higher dose in refractory disease Not recommended for maintenance therapy Budesonide may have less systemic effects >>> mild to moderate ileocolonic CD.

46. Immunosuppressive agents : 6- mercaptopurine Cause supression of T-cell activation and antigen recognition 1.0 – 1.5 mg/kg daily More favourable then glucocorticoids Methotrexate 15 – 25 mg IM or PO weekly Cyclosporine IV 🡪 used in refractory cases of UC. Benefits is temporary Azathioprine

47. Antibiotics Metronidazole : 250 – 500 mg TID Alternate first line agent or adjunctive therapy in mild to moderate Crohns disease. Ciprofloxacin : 500mg XPO X BD The two agents can be used concurrently in perianal Crohns disease

48. Infliximab - Antibody against tumor necrosis factor –alfha that induces inflammatory cell lysis by binding to tumor necrosis factor receptors on the cell surface. IV infusions of 5 mg /kg used in fistulous Crohns disease, refractory inflammatory type CD unresponsive to conventional therapy and more recently to SEVERE ulcerative colitis .

49. Local therapy : Ulcerative colitis 🡪 rectum and distal left colon can be treated effectively with 5-ASA and /or glucocorticoids enemas or suppositories Antidiarrheal agents Contraindicated in severe exacerbations and toxic megacolons.

50. Low roughage diet Elemental diets Total parenteral nutrition and bowel rest in severe disease Supplements of – Vit B12, calcium, magnesium, folate, iron, vit A. ,Vit D and other micronutritions

51. Surgery : Impaired quality of life Failure to medical therapy Fulminant colitis Patients with fistulas , obstructions, abscess, perforations, or bleeding rarely for medically refractory disease and neoplastic transformations Multiple resections should be avoided For ulcerative colitis PANPROCTOCOLECTOMY with Ileostomy Proctocolectomy with ileal anal pouch anastomosis For Crohn disease is the segmental resection

52. Feature Ulcerative colitis Crohn’s disease Epidemology 15- 40 yrs Major of cases occurs between 11- 35 yrs -Lower incidence in smokers - Lower incidence in previous appendectomy <20years Smoking is risk factors M:F= 1:1 F>M slightly Extent Mucosal and submucosal Transmural Location - Mainly rectum ( begins in this location ) -Extend into left colon contineously - Does not involve other area -Terminal ileum alone (30%) ileum and colon (50%) -Colon alone (20%) - Mouth to anus involved - Avoids rectum Gross feature -Inflammatory pseudo polyps -Areas of friable, bloody residual mucosa - Ulceration and hemorrhage -Thick bowel wall and narrow lumen 🡪 obstructions -Apthous ulcers in bowel early - Skip lesions , strictures , fistulas -Deep linear ulcers with cobbel stone patterns -Fat creeping around serosa

53. Features Ulcerative colitis Crohn’s disease Microscopic - Ulceration and crypts abscess containing neutrophils -Dysplasia or cancer may be present Noncaseating granulomas ( 60%) Dysplasia and cancer less likely Clinical findings Recurrent left sided abdominal cramping with bloody diarrhea and mucus - Recurrent right lower quadrant colicky pain . - ( obstruction ) with diarrhea Bleeding occurs only with colon or anal involvement ( fistulas , abscess) Apthous ulcer in mouth Radiology Lead pipe appearance in chronic disease - Collar button ulcers String sign Complications -Toxic mega colon - Adenocarcinoma Fistulas , obstructions, colon cancer (UC>CD) Renal calculi Malabsorbtion Macrocytic anemia