What s new in IBD? Dr AB Hawthorne Consultant Gastroenterologist University Hospital of Wales Cardiff

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1 What s new in IBD? Dr AB Hawthorne Consultant Gastroenterologist University Hospital of Wales Cardiff

2 Case: Kelly age 19 Admitted via medical intake to local hospital with D&V for 10 days. Ate take-away pizza just before symptoms started. Friend also unwell. BO x5/day bloody diarrhoea. Griping abdominal pain. No travel. No FH IBD. Non-smoker Examination: P 130 reg. BP 138/85. T Tender lower abdo. AXR:- Stool culture x2 sent Stool chart Hb 114 g/l Platelets 585 x10 9 /l WBC 16.4 x 10 9 /l CRP 67 mg/l, Albumin 31 g/l

3 Q.1 What is the most likely diagnosis? 1. Ulcerative Colitis 2. Salmonella gastroenteritis 3. Campylobacter gastroenteritis 4. Irritable bowel syndrome

4 Q.2 What treatment would you start initially? 1. Antibiotics 2. iv hydrocortisone 3. oral prednisolone 4. Antibiotics and steroids 5. Neither

5 Case: Kelly age 19 Admitted via medical intake to local hospital with D&V for 10 days. Ate take-away pizza just before symptoms started. Friend also unwell. BO x5/day bloody diarrhoea. Griping abdominal pain. No travel. No FH IBD. Non-smoker Examination: P 130 reg. BP 138/85. T Tender lower abdo. AXR:- Stool culture x2 sent Stool chart Hb 114 g/l Platelets 585 x10 9 /l WBC 16.4 x 10 9 /l CRP 67 mg/l, Albumin 31 g/l

6 Acute severe UC: management In suspected acute UC start iv hydrocortisone 100mg qds Stool cultures and AXR Clexane Avoid opiates/anticholinergics Correct K + Failure to settle after 3-5 days iv steroids colorectal consultation and consider salvage therapy (infliximab or ciclosporin) After 3 days iv steroids:- Stool frequency x3-8, and CRP>45 or Stool frequency >8 gives 85% chance of colectomy (Travis criteria)

7 Kelly: Acute severe UC Day 5 (after weekend) No growth on stool cultures Still being sick Diarrhoea cont, still bloody x7 Albumin 14, CRP 161 Flexible sigmoidoscopy:- Would you consider medical salvage therapy?

8 Time to Colectomy Kaplan-Meier plot of time (days) from randomisation to colectomy, censored at 28/02/2014 Williams et al. UEGW 2014 OP084 Slide courtesy of Prof JG Williams

9 Acute severe UC: salvage therapy No difference between infliximab and ciclosporin in short and long-term outcomes: 70-80% discharged without colectomy: Ciclosporin switch to oral 5-6mg/kg/day for 3 months with azathioprine (check TPMT) Infliximab induction doses at 0,2,6 weeks. Combo therapy with azathioprine (SUCCESS trial). Maintenance? 50% colectomy at 2 years CysIF trial Laharie, D. et al. Lancet 2012;380:1909 CONSTRUCT Williams JG et al. Lancet Gastroenterol Hepatol 2016Online June 22,

10 Q.3 Acute UC in a 49 yr old man. Settling with iv ciclosporin, still on steroids. Sudden onset of central chest pain, worse on swallowing. Likely cause? 1. Reflux oesophagitis 2. Angina triggered by low Mg 3. Candida oesophagitis 4. Herpes simplex/cmv oesophagitis

11 Complications of therapy 39 yr old man recent in-pt with acute UC: On azathioprine 150mg od (3 weeks) + reducing prednisolone (5mg) + awaiting 3 rd dose infliximab Admitted with 24 hrs severe central abdominal pain with vomiting. Diagnosis? Pancreatitis Amylase 620 4% on azathioprine (within 4 weeks) Resolves on drug cessation More common on concomitant steroids More common with Crohn s HLA-DQA1-HLA-DRB1 variants Heterozygous 9% risk Homozygous 17% risk Heap et al Nature Genetics 2014

12 Complications of therapy? 32 yr old woman recovering from acute UC admission 8 weeks earlier On azathioprine 150mg od and mesalazine (Salofalk) Doctor: the azathioprine is making my hair fall out!

13 Complications of therapy? Doctor: the azathioprine is making my hair fall out! Telogen Effluvium: wks after acute illness - Scalp normal - Full recovery - NOT due to drugs - Exclude iron/zinc deficiency

14 Medical Therapy for UC 1 st line therapy: mesalazine 2 nd line therapy: azathioprine Biologics: - Anti-TNF therapy: infliximab (biosimilars), adalimumab, golimumab Vedolizumab gut-specific lymphocyte traffic inhibitor. Iv. Slow onset effect. Good safety data. NICE approved Tofacitinib (Pfizer) oral JAK 1,2,3 inhibitor. FDA approval for RA. JAK only expressed on immune cells

15 Implications of new medical therapies in UC Colectomy rates are falling (preceded biologics era) Colorectal cancer incidence lower Long-term corticosteroid use less Need for infection screening and vaccinations Cost

16 International genotype phenotype study in >34,000 patients Genotype determines disease location (mainly fixed over time) Ulcerative Colitis, Colonic Crohn s and Ileal Crohn s genetically distinct Little genetic association with disease behaviour (changes over time++) Disease behaviour in Crohn s Inflammatory Obstructive Penetrating Cleynen et al Lancet 2015;387:156

17 Crohn s disease Diarrhoea, abdominal pain and weight loss, with mouth ulcers

18 Atypical presentations of Crohn s disease Anorexia in a 16 yr old girl: Clinical: poor appetite due to nausea/pain on eating, cheilitis Tests: albumin, platelet count, B12 and folate Diagnosis: faecal calprotectin, MR enterogram, Irritable bowel syndrome : Clinical: FH? Tests: Hb, albumin, CRP? Diagnosis: Faecal calprotectin Colonoscopy if >150 Inflammatory low back pain Altered bowel habit and pain not due to NSAIDs?

19 Oral Crohn s disease More common in children/young adults Aphthous ulcers Angular cheilitis Glossitis Candida True oral Crohn s = OFG Non-specific

20 8 yr old boy is it Crohn s? Diarrhoea, abdominal pain, and growth failure Colonoscopy whole colon oedematous with cobble-stone appearance and granulomatous inflammation suggestive of Crohn s disease Treated with steroids and azathioprine good response Admitted with pneumonia on 2 occasions. CT scan suggests bronchiectatic changes. Diagnosis?? Chronic granulomatous disease - Neutrophil oxidation defects bacterial and fungal infection - More in boys (often X-linked defects) but milder AR defects - Diagnosis: Neutrophil oxidative function tests

21 Monogenic very early onset IBD Uhlig et al Gastroenterol 2014

22 Medical treatment of Crohn s disease Corticosteroids (budesonide for mild/moderate ileocaecal disease) Little role for mesalazine in small bowel Crohn s Dietary (exclusive enteral nutrition) Antibiotics Early use of azathioprine or methotrexate Biologics Anti-TNF therapy: infliximab (biosimilars), adalimumab Vedolizumab Ustekinumab (coming soon)

23 Ustekinumab (Stelara) Already available for psoriasis Higher doses for Crohn s: iv loading then sc 8 weekly ABT-74(Briakinumab) Ustekinumab Th-1 Th-17 ABT-74(Briakinumab) Ustekinumab

24 Complications of therapy Infection: bacterial, viral, fungal Surgical complications Haematological Lymphoma Non-melanoma skin cancer (SCC, BCC) Malignant melanoma

25 Complications of therapy Lupus-like syndrome (anti-tnf therapy) Arthralgia, +/- mucocutaneous and pleuropericardial inflammation 9% mild 1% severe requiring cessation. Correlates with dsdna titre Psoriaform rashes (anti-tnf therapy) 5% (1/3 required cessation) Palmoplantar pustulosis

26 What causes IBD? Khor et al Nature 2011

27 Answers to questions Q.1 1. ulcerative colitis Q2 Q3 Q4 2. iv hydrocortisone 4. Herpes simplex/cmv oesophagitis 4. Melkersson-Rosenthal syndrome