GP Update on Inflammatory Bowel Disease Clare Donnellan Consultant Gastroenterologist Leeds Teaching Hospitals

Overview Key features of IBD History & examination Investigations Treatment including DMARDs Flares – what should GPs do? What’s new?

Key Features

How common? Incidence UC 10 per 100,000 Incidence CD 6-7 per 100,000 Prevalence 400 per 100,000 (250/150) Onset between 15 and 40 years of age Similar in males and females

UC vs. Crohn’s Ulcerative colitis Crohn’s Disease IBD-unclassified 5% Proctitis Left-sided disease Pan-colitis Crohn’s Disease Affects anywhere Small bowel (80%) Small & Large bowel (50%) Peri-anal disease (35%) More likely to get complications IBD-unclassified 5%

Why do they occur? Genetics 10-25% of patients have at least one other family member affected No particular gene identified in UC NOD2/CARD15 gene abnormalities in CD Terminal ileal disease Possibly more chance of requiring surgery

Why do they occur? Environmental factors Smoking Appendicectomy Diet? Protective for UC Worsens outcome for CD Appendicectomy Unlikely effect for CD Diet? Bacteria? Bacteria: innate immune system (NOD2) – pathogen recognition receptors (NOD = intracellular) (TOLL = extracellular/membrane bound) – cascade of perpetual immune response to commensal bacteria.

Extra GI manifestations Episcleritis/scleritis 2 to 5% of patients Activity linked to GI tract Anterior uveitis 0.5-3%, but much more serious Females:males 4:1 75% of patients have arthritis Activity not linked to GI tract

Extra GI manifestations Erythema nodosum Most common skin manifestation of IBD (up to 15%) Typically flares at same time as GI symptoms Pyoderma grangrenosum Up to 5% of patients More chronic course

Summary of Extra-GI complications Related to GI activity Peripheral arthritis Episcleritis/scleritis Erythema nodosum Not related to GI activity Spondylitis/sacroiliitis Anterior uveitis Pyoderma Gangrenosum

History & examination

History – Is it UC? Bloody diarrhoea or prolonged diarrhoea (-ve MC&S) Abdominal pain Urgency Tenesmus If 1st presentation Stool frequency/day & night Systemic features Weight loss Fever Extra-GI features Travel DH (Abx, NSAIDs FH SH

History – known UC with flare ‘The professional patient’ Is it like a ‘usual’ flare? What are the usual strategies? IBD Helpline 0113 206 8679 Is it severe? Truelove and Witts criteria ≥6 bloody stools per day Systemic toxicity (HR>90, T>37.8, ESR>30) or Hb<10.5 NEEDS ADMITTING for IV steroids

History – Is it Crohn’s? Much more challenging to ΔΔ IBD vs. IBS…. Abdominal pain Diarrhoea (ask re: nocturnal symptoms) Weight loss Systemic features Extra-GI manifestations

History – known Crohn’s with flare ‘The professional patient’ Is it like a ‘usual’ flare? What are the usual strategies? IBD Helpline 0113 206 8679

Examination Systemically unwell? Dehydration BMI/weight Fever Tachycardia Dehydration BMI/weight Abdominal tenderness/distension/bowel sounds Palpable mass Peri-anal examination

General principles Follow ‘usual’ strategy Call helpline (pt or GP) if concerned Advice Early access to IBD clinic Admit if systemically unwell

Investigations

GP investigations FBC, U&E, LFT, CRP Haematinics Stool MC&S Stool C diff (Stool OC&P) Urgent referral to gastroenterology if high index of suspicion

Hospital investigations - acute UC Bloods AXR Urgent stool cultures Urgent flexible sigmoidoscopy within 24 hours (CMV PCR and CMV on biopsies) CT if risk of perforation

Hospital investigations - acute Crohn’s Varies on symptoms/distribution Low threshold for CT abdo/pelvis Flexible sigmoidoscopy often unhelpful MR pelvic if abscess/fistulising disease

Hospital investigations – O/P Small bowel Small bowel meal if suspected CD/suspected SB CD MR enterography (enteroclysis) if known SB CD OGD Ultrasound Wireless capsule endoscopy Isotope (labelled white cell scans) Colon Colonoscopy CT colonography

Examples

Treatment

UC 5-ASAs Prescribe by drug name But lower cost equivalents (Asacol = Mesren = Octasa) Dose Asacol 2.4 g vs. 4.8 g Minimum 2 g for maintenance (1.2 g cancer prevention) OD as effective and better adherence for maintenance Tablets + Local therapy often avoids steroids 5-ASA enemas better than steroid enemas

UC DMARDs Azathioprine 2-2.5 mg/kg 6-mercaptopurine 1-1.5 mg/kg Weekly bloods for 4/52 Then monthly Then 3 monthly S/E (Raised MCV and lymphopaenia)

UC Other DMARDs Methotrexate Mycophenolate Evidence not great Some evidence

UC Flares Prednisolone 30 mg daily with Ca/Vit D cover Optimise 5-ASAs first if sole treatment Maximise dose Add in local therapy (5-ASAs, not steroids) Prednisolone 30 mg daily with Ca/Vit D cover More prolonged course If not settling (or severe UC) IV steroids

UC Flares Is it severe? Truelove and Witts criteria ≥6 bloody stools per day Systemic toxicity (HR>90, T>37.8, ESR>30) or Hb<10.5 NEEDS ADMITTING for IV steroids Colectomy rate approx. 30%

UC Flares Day 3 (Travis criteria) 3 options If stool frequency > 8 or CRP > 45 85% chance of colectomy 3 options Surgery Infliximab as a bridge to Aza/6-MP Cyclosporin

UC Outcome Ciclosporin/infliximab Infection risks 70 – 80% leave hospital with colon 30% long-term Infection risks

CD No role for 5-ASAs except if mild colitis ? Role after surgery in preventing relapse

CD Flares If luminal disease Oral steroids IV steroids if no response Still no response? No role for ciclosporin Give infliximab +/- azathioprine for 1 year Nutrition support key

CD Flares If peri-anal disease Drain any sepsis Antibiotics Seton sutures Escalate therapy as appropriate

CD DMARDS Biologicals Surgery Azathioprine Infliximab Methotrexate (s/c) Mycophenolate Tacrolimus Surgery For complications Biologicals Infliximab Adalimumab (Humiara) NICE assessment at 1 yr

Other treatments Liquid diet for Crohn’s Bone protection Endoscopic dilatation of strictures

What’s new?

What’s new? Calprotectin Azathioprine metabolite levels Diagnosis Activity assessment Azathioprine metabolite levels Optimise dose Minimise side-effects ? Reduce number of patients needing biologicals Leucocytapheresis Mucosal healing

What’s new? Guided self-management More nurse-led clinics Reduce follow-up waits… Less ‘black and white’ in/out of service

Summary Significant morbidity Early, focused management Use helpline 0113 206 8679 Admit if systemically unwell Stool cultures Appropriate steroid course