What do these people all have in common? Stewart Lee - comedian Sir Steve Redgrave – Olympic rower William Wilberforce – abolition of the slave trade

Ulcerative Colitis

Epidemiology Most common IBD Incidence = 10 in 100 000 Prevalence = 240 per 100 000 Age of onset Peak incidence: 15 -25 years Second smaller peak 55-65 years M=F

Aetiology UNKNOWN - ?autoimmune Risk factors: Smoking – protective Genetics – FHx of UC or CD Developed countries Ethnicity – Caucasian (Northern Europe and America) Smoking – protective

Pathogenesis Genetically susceptible host – MDR1 gene variants Increased immune response to enteric commensal bacteria Innate immune system – macrophages, neutrophils Acquired immune system – T cells, B cells Release of inflammatory cytokines Environmental factors – stress, infection, NSAIDs

Symptoms Bloody, mucoid diarrhoea/rectal bleeding Colicky abdominal pain Urgency Tenesmus Constipation Weight loss Malaise Extra-intestinal symptoms: Joints – sacroiliitis, ankylosing spondylitis Skin – pyoderma gangrenosum, erythema nodosum Eyes – anterior uveitis

Signs Guarding on abdominal palpation Thin, pale Tachycardia Pyrexia Signs of anaemia

Diagnosis Stool sample - raised faecal calprotectin = suggestive of colonic inflammation Bloods - raised ESR/CRP, anaemia AXR (rule out toxic megacolon) Colonoscopy with multiple biopsies Continuous inflammation of mucosa from rectum Only in the colon (vs CD) – may be backwash ileitis No skip lesions, granulomas, deep ulcers, strictures, fissures or fistulas

Treatment Aminosalicylates – mesalazine (topical and/or oral) Induction and maintenance of remission Corticosteroids – prednisolone (topical or oral) Induction of remission (relapse, severe) Thiopurines – azathioprine Corticosteroid intolerance/regular relapses Surgery – colectomy in 30% Unresponsive to treatment, complications (toxic megacolon, colorectal neoplasia)

Prognosis Relapsing-remitting course, variable Social stigma of colostomy bag, using disabled toilets 2x increased risk of colorectal cancer Surveillance colonoscopy after 10 years of disease, every 1-5 years dependent on risk Colectomy for high-grade dysplasia

Case study 15 year old male Reports frequently passing stool with abdominal discomfort What else should you ask?

Case study How many times a day? Any blood? Every time or just sometimes? Fresh/mixed in? Mucus? Associated nausea/vomiting? Recent travel? Food triggers? Weight loss? Mouth ulcers? Rectal fissures? Extra-intestinal symptoms?

Case study Investigations: Management: Bloods – FBC, CRP/ESR, U&E, LFT, coeliac screen (tTG) Stool sample – faecal calprotectin, culture (OCP) Imaging – AXR, ?CT/MRI Endoscopy – colonoscopy with biopsy Management: Induce remission – mesalazine +/- prednisolone Maintain remission – mesalazine Monitor regularly, recognition of relapse

MCQ What is the peak age of onset of ulcerative colitis? 5-15 15-25 25-35 35-45

MCQ Which of the following is NOT a risk factor for developing UC? Gastrointestinal infection MDR-1 gene variation Stress Smoking

MCQ Which of the following may be a sign of UC? Pale stools Vomiting Weight loss Bradycardia

MCQ Which of the following is first-line treatment for induction of remission in UC? Azathioprine Mesalazine Mercaptopurine Budesonide

MCQ What is the peak age of onset of ulcerative colitis? 5-15 15-25 25-35 35-45

MCQ Which of the following is NOT a risk factor for developing UC? Gastrointestinal infection MDR1 gene variation Stress Smoking

MCQ Which of the following may be a sign of UC? Pale stools Vomiting Weight loss Bradycardia

MCQ Which of the following is first-line treatment for induction of remission in UC? Azathioprine Mesalazine Mercaptopurine Budesonide

Summary Most common type of IBD Multifactorial aetiology Relapsing-remitting course Bloody diarrhoea/rectal bleeding = most common symptom Diagnosis = colonoscopy with biopsies Treatment: Remission with mesalazine +/- prednisolone Maintenance with mesalazine Increased risk of colon cancer and toxic megacolon -> colectomy

SUMMARY

SUMMARY: UC Vs. Crohn’s? CROHN’S DISEASE ULCERATIVE COLITIS ORIGIN Terminal ileum Rectum PROGRESSION PATTERN Skip lesions, irregular Proximally contiguous INFLAMMATION Transmural Submucosa or mucosa SYMPTOMS Crampy Abdominal pain BLOODY DIAHRRHEA COMPLICATIONS Fistulas, obstruction, abscess Toxic megacolon, Hemorrhage RADIOGRAPHS String Sign: Barium X-ray Lead pipe colon: Barium X-ray SURGERY Certain complications (Strictures) Can be CURATIVE SMOKING HIGHER RISK LOWER RISK COLON CANCER RISK? SLIGHT Increase MARKED Increase

IBS Vs. IBD

Thank you! Any questions?

References Ulcerative Colitis - http://patient.info/doctor/ulcerative-colitis-pro Mechanisms of Disease: Pathogenesis of Crohn's Disease and Ulcerative Colitis - http://www.medscape.com/viewarticle/540142_7 Pathology Outlines - http://www.pathologyoutlines.com/topic/colonuc.html NHS choices - http://www.nhs.uk/Conditions/Ulcerative-colitis/Pages/Treatment.aspx NICE guidelines for UC - https://pathways.nice.org.uk/pathways/ulcerative-colitis#content=view- node%3Anodes-step-1-therapy-left-sided-and-extensive-ulcerative- colitis&path=view%3A/pathways/ulcerative-colitis/inducing-remission-in-people-with-ulcerative- colitis.xml