Year 2002 Paper two: Questions supplied by Jo 1

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1 Year 2002 Paper two: Questions supplied by Jo 1 29) A 54 year old man with colonic Crohn s disease is in remission following an 8 week course of prednisolone. Which one of the following medications is most likely to maintain his remission? A. Prednisolone B. Sulfasalazine C. Azathioprine D. Metronidazole E. Methotrexate Answer: Pathophysiology Macro Micro Clinical Features - Depends on location, severity, duration Ulcerative Colitis Mucosal disease - Involves rectum and spreads proximally - In continuity Mild: red and sandpapery Severe: oedema, haemorrhage Chronic: pseudopolyps +/- atrophic, featureless mucosa Distorted crypt architecture - Cryptitis - Crypt abscesses Congested basal lymphocytes Rectally based symptoms - PR bleeding - Diarrhoea +/- mucous +/- pus if severe - Tenesmus - Crampy abdominal pain Moderate/ severe - Fever - Anorexia - N+V - Weight loss If toxic megacolon hepatic tympany If perforation - peritonitis Crohn s Disease Transmural disease - Affect anywhere from mouth to anus - Rectum spared - Skip lesions Small bowel alone: 30-40% Small + large: 40-55% Colon alone: 15-25% Anal disease: > 30% Cobblestone appearance +/- pseudopolyps Thickened mesentery with creeping fat Focal crypt abscesses Non-caseating granulomas 50% 2 patterns 1) Fibrotic-stenotic obstructive 2) Penetrating fistulous Ileocolitis (most common) - Ddx appendicitis - RLQ pain, fever, diarrhoea +/- palpable mass - High spiking fevers suggest abscess - Weight loss - Fistulas: enterovesical/ enterocutaneous/ enterovaginal (rare) Jejunoileitis - digestive and absorptive surface - Malabsorption and steatorrhoea

2 Year 2002 Paper two: Questions supplied by Jo 2 - Nutritional deficiencies eg albumin/ vit D/ hyperoxalosis w renal calculi - If active: diarrhoea (bacterial o/growth + bile acids malabsorption + water reabosorption) Colitis and perianal disease - Gross bleeding uncommon (only 1-2%) - Otherwise similar to UC - Strictures -> obstruction - Fistulas: enterocolic, rectovaginal (10%) - Perinanal 30%: incontinence, anal tags, anorectal fistula, abscesses Gastroduodenal (rare <5%) - H Pylori negative gastritis - Mimics GORD/PUD - Gastric outlet obstruction from strictures Dx - Often difficult - Hx and Sx and site Impossible in 10% ie indeterminate colitis with implications on Rx Serology markers UC Crohns p-anca +ve 60-70% +ve 10-15% Associated colonic disease similar to UC ASCA +ve 10-15%` +ve 60-70% Anti OMPc Ab CRP Tends to be er in Crohn s (also relates well with disease activity and some say risk of relapse) Colonoscopy/ ileoscopy + histopathology Others: CT enteroclysis (emerging as best test) Small bowel MRI Pill cam Gastroscopy (if upper GIT Sx) Barium follow through (not recommended nowadays)

3 Year 2002 Paper two: Questions supplied by Jo 3 Extra intestinal Features - >30% have >1 - er risk with perinal Crohn s Erythema nodosum - More common in Crohn s (15%) than UC (10%0 - Occurs after onset bowel Sx - Simultaneous arthritis common - Responds to Rx of IBD Pyoderma gangrenosum - Up to 12% UC but rare in Crohn s - May occur years post bowel Sx - Course independent of bowels - Often signifies severe disease - Responds poorly even to colectomy and may recur Peripheral arthritis %, more common in Crohn s - Exacerbated by active bowel disease - Assymetrical, polyarticular and migratory - In severe UC, colectomy cures arthritis AS - 10% affected, more common in Crohn s - 2/3 of Crohn patients are HLA B27 +ve - Not related to activity of bowel disease - Does not remit with colectomy or steroids - Progressive Sacroilitis (symmetrical) - Similar in both - Not relationship to bowel activity Ocular - 10%: conjunctivitis, anterior uveitis, episcleritis - May occur even during remission Hepatobiliary - Steatosis in 50% (malnutrition, steroids) - Gallstones more common in Crohns (malabsorption of bile acids) - PSC: 1-5% patients with IBD have PSC, but 50-75% of PSC patients have IBD (usually no Sx at dx, ERCP, 10% develop cholangiocarcinoma) Urological - Renal calculi (Crohn s following ileal resection with ca oxalate stones) - Enterovesical fistulas and infections Others - risk thromboembolic disease - Osteomalacia and osteoporosis ( calcium/ Vit D, steroids) - Myocarditis, ILD (rare) - Amyloidosis

4 Year 2002 Paper two: Questions supplied by Jo 4 Malignancy (Need surveillance scopes) Rx to induce remission Rx to maintain remission Colonic dysplasia Colitis associated colon cancer - Ddx sporadic colon cancer - From flat dysplasia or dysplasia associated lesion/mass rather than adenomatous polyp - More likely synchronous - Found anywhere (sporadic cancer more common on L) Risk with duration and severity - 1% every year post 10 year of disease if pancolitis Mild to moderate: 5-ASA (including sulfasalazine) Moderate to severe: Glucocorticoids +/- 5-ASA (Prednisolone 40-60mg/d or topical steroid foams for rectum) If fail, can try: - Azathioprine/ 6MP - Infliximab - Cyclosporine NO ROLE for antibiotics (apart from pouchitis after colectomy) NO ROLE for steroids 5-ASA If fails 5-ASA + steroid dependant - Azathioprine/ 6MP - Cyclosporine Colonic cancer risk equivalent to UC but more likely if colonic/ ileocolonic disease Extra-intestinal cancers: - NHL - SCC skin - 12x risk of small bowel cancer (but absolute risk very small anyway) Mild to moderate: 5-ASA (including sulfasalazine) Moderate to severe: Glucocorticoids (60% response) eg CR ileocolic budesonide 1 st line in perianal + fisulous (2 nd line if failed 5-ASA in others) Metronidazole Ciprofloxacin If fail, can try: - Infliximab - Perinal and fistula: azathioprine/ cyclosporine NO ROLE for steroids Unclear if 5-ASA effective Azathioprine/6MP effective - Even for perianal + fistulas - Effective for post-op prophylaxis Methotrexate Infliximab Perinal and fistula 1 st line still antibiotics

5 Year 2002 Paper two: Questions supplied by Jo 5 Other therapies Bowel rest +/- TPN (as effective as glucocortocoids at inducing remission of active disease but no good as maintenance) Selected drugs and common side effects: 5 ASA Sulfasalazine broken down by azo bacteria in colon Newer agents sulphur dose, active ingredient Eg Asacol and Pentasa Side effects often intolerable at dose (sulphur): - Headache - N+V + anorexia Agranulocytosis Hypersensitivity pneumonia Pancreatitis Impaired folate absorption Azathioprine (Purine analogue) Rapidly absorbed and metabolised to active thioisinic acid Efficacy at 3-4 weeks Measure compliance by endproducts: 6 thioguanine and 6 methylmercaptopurine 3-4% pancreatitis (reversible with drug cessation) Fever/ rash BM suppression with leukopenia (often delayed and dose related) 1 in 300 lack enzyme for metabolism 11% are heterozygotes for intermediate enzyme activity risk toxicity Infliximab (Anti TNF Ab) - chimeric mouse protein Development of Ab against infliximab: - risk infusion reactions - response to therapeutic dose Small association with lymphoma CCF TB and intracellular pathogens Demyelination Therefore answer is C