1. Diagnosis & Management of Ulcerative Colitis

2. Ulcerative colitis is a World-Wide disease Incidence (new cases): –5 cases per 100,000 –High incidence in White Population (Northern Europe, North America) –The incidence is increasing in the black population Prevalence (patients): –50 cases per 100,000 Equal male/female incidence Peak presentation –1 st peak between 15-25 years of age –2 nd peak between 55-65 years of age Epidemiology Cecil textbook of Medicine p. 722, 21st Edition, 2000

3. Factors associated with increased incidence First degree relatives Identical twins Associated with autoimmune thyroiditis & SLE Patients with HLA B27 develop ankylosing spondylitis More common in non smokers & ex smokers Associated with low fiber & high refined sugar diet

4. InflammationGenetics Infection Immuno- pathology ULCERATIVE COLITIS Ulcerative Colitis Etiology Cecil textbook of Medicine p. 722, 21st Edition, 2000

5. Ulcerative Colitis Ulcerative colitis is a chronic inflammatory disease of colon of unknown cause Pursue a protracted relapsing & remitting course Always affects the rectum Extends proximally to involve a variable extent of the colon Oxford Textbook of Medicine p. 1943, Vol. 2, 3rd Edition 1996

6. U.C Disease Distribution at Presentation n=1116 37% ENTIRE COLON 17% COLON UPTO LEFT FLEXURE 46% RECTO SEGMOID Farmer RG. Dig Dis Sci;38:1137-1146 Pancolitis Ulcerative proctitis or Proctosigmoiditis Left Sided Colitis

7. Pathology –Inflammatory reaction primarily involving the colonic mucosa –Grossly the colon appears ulcerated, hyperemic, and usually hemorrhagic –Inflammation is uniform and continuous with no intervening areas of normal mucosa –Rectum is usually involved (95% of the cases) –Inflammation extend proximally in a continuous fashion but for a variable distance Ulcerative Colitis Harrison’s Principles of Internal Medicine, p.1404, Vol 2, 13th Edition 1995

8. Symptoms: depend on site & activity of disease Proctitis : Rectal bleeding, mucus discharge & tenesmus Proctosigmoiditis: Bloody diarrhea, mucus & those with active disease have fever, lethargy & abdominal discomfort Extensive Colitis: Severe bloody diarrhea, mucus, fever, weight loss, malaise, abdominal pain, tachycardia Ulcerative Colitis Davidson’s Principles& practice of Medicine, 19 th edition

9. Clinical Course 60-75% of patients will have intermittent flares interrupted by periods of complete clinical remission 5-45% of patients unable to attain clinical remission; they have chronic unremitting symptoms 10% will have one attack and enter permanent clinical remission (probably misdiagnosed infectious colitis) Ulcerative Colitis

10. Six major factors thought to be responsible –Failure to comply with a maintenance regimen –Mesalamine sensitivity –Activation of eosinophils by environmental stimuli, including seasonal changes –Systemic and enteric infection –Use of NSAIDs / antibiotics –Changes in smoking status –Emotional stress Relapses Ulcerative Colitis

11. Transfusion<75% of normal value NormalHemoglobin >30 NormalErythrocyte sedimentation rate (mm/hr) >90 <90Pulse (beats/min) >37.5 NormalTemperature ContinuousFrequentIntermittentBlood in stool >10>6<4Stools (no./ day) FULMINANTSEVEREMILDVARIABLE Assessment of disease severity

12. Clinical Grading Mild –Less than four stool daily, with or without blood, –No systemic disturbance and normal ESR Moderate Between mild and severe Severe –At-least six stools daily, with bleeding Fever, Tachycardia, Falling Hemoglobin, Hypoalbuminaenia, Raised ESR and C-reactive protein Oxford Textbook of Medicine p. 1946, Vol. 2, 3rd Edition 1996 Ulcerative Colitis

13. Extra-intestinal manifestations Related to activity of colitis –Aphthous ulceration of the mouth –Fatty liver –Erythema nodosum –Peripheral arthropathy –Liver abscess / portal pyemia –Mesentric / Portal vein thrombosis –Conjunctivitis / Iritis / episcleritis / venous thrombosis Oxford Textbook of Medicine p. 1948, Vol. 2, 3rd Edition 1996 Ulcerative Colitis

14. Extra-intestinal manifestations of ulcerative colitis Usually related to activity of colitis –Pyoderma gangrenosum –Anterior uveitis Unrelated to colitis –Ankylosing spondylitis –Primary sclerosing cholangitis / Autoimmune hepattis –Cholangiocarcinoma –Gall stones –Amyloidosis Oxford Textbook of Medicine p. 1948, Vol. 2, 3rd Edition 1996 Ulcerative Colitis

15. Complications –Anemia –Hemorrhage –Toxic megacolon, perforation & peritonitis –Electrolyte disturbances –Dehydration –Strictures, benign and malignant –Cancer: patients ewith disease of > 8 years duration are at risk Ulcerative Colitis Harrison’s Principles of Internal Medicine, p.1408, Vol 2, 13th Edition 1995

16. Diagnosis History Stool culture Sigmoidoscopy Colonoscopy Radiology Ulcerative Colitis Oxford Textbook of Medicine p. 1946, Vol. 2, 3rd Edition 1996

17. Stool Culture –Performed to exclude superimposed infection in those who presents with exacerbations –Special culture conditions are required for Campylobacter spp., Yersinia, Gonococci and Clostridium difficile –Possibility of an infection with E. coli must be considered, specially when bleeding and abdominal pain are predominant symptoms Ulcerative Colitis Oxford Textbook of Medicine p. 1946, Vol. 2, 3rd Edition 1996

18. Sigmoidoscopy To evaluate for pattern and character of mucosal inflammation To obtain biopsies for confirmation The early sign of colitis on sigmoidoscopy are blurring of the vascular pattern associated with hyperemia and edema, leading to blunting of the valves of houston Ulcerative Colitis Oxford Textbook of Medicine p. 1946, Vol. 2, 3rd Edition 1996

19. Sigmoidoscopy In severe cases the mucosa becomes granular and than friable With severe inflammation the mucosa shows spontaneous bleeding and ulceration, these changes begin in the rectum, they are diffuse, and extend proximally to affect a variable length of the colon Ulcerative Colitis Oxford Textbook of Medicine p. 1946, Vol. 2, 3rd Edition 1996

20. Colonoscopy Colonoscopy with multiple biopsies is useful for assessing the extent of disease and is mandatory for patients with a colonic stricture May show pseudopolyposis or a cancer Biopsies specimens must be taken at sigmoidoscopy or colonoscopy preferably with small, cupped forceps. Histological assessment contributes to grading severity as well as the differential diagnosis Ulcerative Colitis Oxford Textbook of Medicine p. 1946, Vol. 2, 3rd Edition 1996

21. Laboratory Data Iron deficiency is common as a result of chronic iron loss Neutrophilic leucocytosis, thrombocytosis, esinophilia or monocytosis may also be present,indicators of active inflammation Biochemical abnormalities are rare in mild or moderate attack Hypokalaemia, hypoalbuminaemia, and a rise in  2 -globulin frequently accompany a severe attack Serum immunoglobulins rarely exceed the upper limit of normal during a relapse but usually fall as remission occurs Ulcerative Colitis Oxford Textbook of Medicine p. 1946, Vol. 2, 3rd Edition 1996

22. Radiology Barium enema may reveal the extent of the disease Helps define associated features such as stricture, pseudopolyposis, or carcinoma The earliest feature is incomplete filling due to associated inflammation In the chronic stage, the characteristic features are shortening of the bowel, depression of the flexures, narrowing of the bowel lumen, and rigidity Harrison’s Principles of Internal Medicine, p.1409, Vol 2, 13th Edition 1995 Ulcerative Colitis

23. Medical Management The main principles of therapy for the treatment are: –Control active disease rapidly –Maintain remission –Detect cancer at an early stage –Select patients for whom surgery is appropriate –Ensure as good a quality of life as possible Oxford Textbook of Medicine p. 1943, Vol. 2, 3rd Edition 1996 Ulcerative Colitis

24. TREATMENT PROCTITIS  Mesalamine suppositories 500 mg / rectum BD or  Hydrocortisone suppositories 100 mg OD PROCTOSIGMOIDITIS  Mesalamine Enema 4 gm OD  Hydrocortisone Enema 100 mg OD

25. TREATMENT EXTENSIVE COLITIS (mild-mod.)  Mesalamine tab 2.4-4.8 g / d or  Sulfasalazine 1.5-3 g / bd  Add prednisolone: Initially enema & then oral 40-60 mg / d if no response after 2-4 w

26. TREATMENT SEVERE COLITIS Hospitalization Stop all oral intake Correct fluid & electrolytes Transfusion for anemia Plain X ray abdomen to look for dilatation Methylprednisolone IV 48-64 mg or hydrocortisone 300 mg Surgery: If no response after 7-10 days of steroids

27. TREATMENT FULMINANT COLITIS Severely ill with fever, dehydration Risk of perforation or toxic megacolon Antibiotics for anaerobes & Gm-ve bacteria N/G tube suction If fail to improve within 48-72 hr, surgery indicated

28. TREATMENT REMISSION MAINTAINANCE 75% relapse within one year without maintainance therapy Mesalamine 800 mg TDS or sulfasalazine 1-1.2 g bd Decrease relapse rate to < 33%

29. TREATMENT REFRACTORY DISEASE Patients who refuse surgery may be given immunosuppressive drugs Azathioprine OR Mercaptopurine benefit 60% patients Infliximab 5mg / kg benefits some patients with refractory disease

30. The Drug of Choice ASACOL ™

31. Colon Cancer

32. Ekbom, et al NEJM, 1990

33. –First choice is an aminosalicylate, depending on which one the patient can tolerate. Aminosalicylates generally are effective and have minimal side effects. Ulcerative Colitis Conclusion