Diagnosis & Management of Ulcerative Colitis Epidemiology • 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 – 1st peak between 15-25 years of age – 2nd peak between 55-65 years of age Cecil textbook of Medicine p. 722, 21st Edition, 2000 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 Ulcerative Colitis Etiology Inflammation Genetics ULCERATIVE COLITIS Immuno- Infection pathology Cecil textbook of Medicine p. 722, 21st Edition, 2000 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 U.C Disease Distribution at Presentation Pancolitis n=1116 Ulcerative proctitis 37% ENTIRE or Proctosigmoiditis COLON 46% RECTO SEGMOID 17% COLON UPTO LEFT FLEXURE Left Sided Colitis Farmer RG. Dig Dis Sci;38:1137-1146 Ulcerative Colitis 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 Harrison’s Principles of Internal Medicine, p.1404, Vol 2, 13th Edition 1995 Ulcerative Colitis 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 Davidson’s Principles& practice of Medicine, 19th edition Ulcerative Colitis 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 Relapses • 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 Assessment of disease severity VARIABLE MILD SEVERE FULMINANT Stools (no./ day) <4 >6 >10 Blood in stool Intermittent Frequent Continuous Temperature Normal >37.5 >37.5 Pulse <90 >90 >90 (beats/min) Hemoglobin Normal <75% of normal Transfusion value Erythrocyte Normal >30 >30 sedimentation rate (mm/hr) Ulcerative Colitis 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 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 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 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 Harrison’s Principles of Internal Medicine, p.1408, Vol 2, 13th Edition 1995 Ulcerative Colitis Diagnosis • History • Stool culture • Sigmoidoscopy • Colonoscopy • Radiology Oxford Textbook of Medicine p. 1946, Vol. 2, 3rd Edition 1996 Ulcerative Colitis 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 Oxford Textbook of Medicine p. 1946, Vol. 2, 3rd Edition 1996 Ulcerative Colitis 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 Oxford Textbook of Medicine p. 1946, Vol. 2, 3rd Edition 1996 Ulcerative Colitis 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 Oxford Textbook of Medicine p. 1946, Vol. 2, 3rd Edition 1996 Ulcerative Colitis 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 Oxford Textbook of Medicine p. 1946, Vol. 2, 3rd Edition 1996 Ulcerative Colitis 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 Oxford Textbook of Medicine p. 1946, Vol. 2, 3rd Edition 1996 Ulcerative Colitis 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 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 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 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 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 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 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% 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 ASACOL ™ The Drug of Choice Colon Cancer Cumulative Incidence for Colorectal Cancer Based on Extent of Disease at Time of Diagnosis 40 pancolitis 30 left-sided colitis Cumulative CRC (%) 20 10 0 0 10 20 30 40 Years follow-up Ekbom, et al NEJM, 1990 Ulcerative Colitis Conclusion – First choice is an aminosalicylate, depending on which one the patient can tolerate. Aminosalicylates generally are effective and have minimal side effects.