1. بسم الله الرحمن الرحيم

2. management protocol of IBD

3. Presented by Dr. Kamal A. EL-Atrebi (FRCP) Consultant physician Hepatologist & Gastroenterologist (NHTMRI)

4. Management 1 st : Diagnosis 2 nd : Define site of the lesion 3 rd : Assess disease activity 4 th : Treatment

5. Diagnosis(1 st ) Symptoms Examination Investigations

6. Symptoms Chronic diarrhea (CD) : common,calling to stool overweight Acute diarrhea (rare) Bleeding/rectum (UC) Abdominal pain Alarming symptoms: (loss of weight, change of appetite) Constitutional symptoms: (fever, fatigue, tachycardia) Associations: (other autoimmune diseases) Symptoms of complications : (Malabsorption,fistula,abscesses, intestinal obstruction)

7. Examination Contribute little to diagnosis (it is a disease of history taking) Aphthous ulcers (mouth) PR examination & sigmoidoscopy: (erythema,granularity,contact bleeding, fistula,abscesses) Extra intestinal manifestations may be or not related to the disease activity  Eye  Skin  Joints  Liver (e.g. PSC)

8. Investigations Routine blood tests: FBC,CRP,s.albumin,s.ca++,electrolytes,s.B12,s.folic acid, iron status Auto antibodies: p- ANCA > in UC ASCA > in CD Stool analysis &culture: (exclusion) cl. difficile toxins, E.histolytica Endoscopy: (the most useful)  Sigmoidoscopy:  Sigmoidoscopy: can diagnose UC  Colonoscopy:  Colonoscopy: more useful, define UC extent & CRC screening,CD (up to terminal ileum)  Enteroscopy:  Enteroscopy: (up till now not practical ) time consuming but enables small intestinal biopsy, needs well trained hands

9.  Capsule endoscopy :  Capsule endoscopy : (not practical) no biopsies, expensive, rapid transient time  Upper endoscopy :  Upper endoscopy : useful in CD Radiology  Plain abdominal x-ray: o supine & erect position o megacolon > 5.5 cm & follow up o proximal constipation

10.  Barium studies: difficult colonoscopy, help in confirming diagnosis a) enema : osigmoidoscopy dangerous ocharacteristics features (lead pipe) ofistula, deep ulcers b) small bowel barium follow through : for suspected small bowel CD (rose thorn)  Abdominal pelvic u/s: CD related abscesses thickened fluid filled bowel loops  MRI scanning (replace CT): investigation of choice in mapping fistulae & sinuses in CD &follow up response  Nuclear medicine (rarely used): difficult endoscopy, avoid excess exposure to x-ray e.g. pregnancy

11. Define site of the lesion(2 nd ) proctatitis Lt sided colitis pan-colitis ileo-colonic ++ peri-anal and fistulating

12. Assessing disease activity in IBD(3 rd ) Clinically laboratory endoscopically radio/histo N.B. : Both endoscopic & radio/histo are adjuvant

13. IBD disease activity A)UC disease activity (more in practice) Severe > 37.5, PR > 100, pale Laboratory: : CRP > 45 for follow up ESR > 30 Platelets : HB albumin SeverityMildModerateSevere No. of stool /day < 4 4-6 > 6 blood Systemic manifestations No Minimalsevere

14. B) CD disease activity ( sophisticated & a lot of subjunctives useful in research purposes) 8 items 1.No. of liquid stools 2.Abdominal pain 3.Abdominal mass 4.General well being 5.Taking lomitil, opiates for diarrhea 6.Haematocrite 7.100% (standard wt. – actual wt. / standard wt.) 8.No. of the following : fever, Arthralgia, arthritis, iritis, uveitis, skin lesion, Aphthous ulcer,stomatitis, anal fistula, other bowel related fistula On line calc at http : //www.ibdjohn.com

15. Treatment(4 th ) Almost similar for both Our goals  Control the disease activity & induce remission  Maintain the remission Don’t ignore  Patients symptoms  Involve the dietician  Multidisciplinary approach e.g. surgery Spontaneous remission in 30% Drugs available  5ASA  Steroids  Immunomodulators  Biological treatment

16. I.Amino salicylates e.g.sulfasalazine,mesalalzine,olsalazine,balsalazide  Induction of remission (mild to moderate activity) Success in 60% in UC & less in CD (particularly if colonic)  Maintenance the remission Success in 75% in UC & less in CD  Dose: from 2.4 gm to 4.8 gm (if tolerated) 3 divided doses, 6m, tapering up to 1.5 gm  Decrease development of CRC in UC  Side effects: GI symptoms, allergy  Route : oral, rectal  Monitoring: renal function tests  All used in colonic lesions, except mesalazine also in ileum

17. II.Steroid  Induction of remission (moderate to severe activity)  Not for maintenance remission except if 5ASA & AZA are CI  Route : rectal, I.V., oral  Side effects: (well known)  Budesonide has less systemic side effects but expensive & less effective

18. III.Immunomodulators A)AZA/6mp  Induction of remission (CD&UC)  With 5ASA  In chronically active (failure of steroid)  Rapid relapsing  Maintenance of remission (CD & UC)  with 5ASA  Dose : 2.5 mg/kg,dec with Allopurinol  Side effects: leucopenia  Monitoring : CBC  Full response is delayed

19. B) MTX  Chronically active CD (failure of steroid)  Could be for CD maintained remission  Rapid onset of action > AZA  Serious side effects : hepatic toxicity, pneumonitis, bone marrow depression C) Cyclosporin  Severe acute UC avoid colectomy (failure of steroid)  Not for maintain remission  CD (little role)  Serious side effects : renal, hepatic, electrolyte imbalance, abnormal facial features

20. IV.Biological treatment  Infliximab (IFX) (chimeric MC anti TNF Ab ) In CD (no response to other treatment), also in UC With(better) or without other immunomodulators In perianal fistulae ( 0,2,6 w) Route : I.V. infusion 5mg/kg (0,8 w) precautions: inf.e.g old T.B.and CHF Anti-IFX Ab develops  Adalimumab & Certolizumab (human MC anti TNF Ab ), longer half-life FDA approved in 2008 for moderate to severe CD (If failed IFX)

21. V.Others - Antibiotics (in CD) colonic & peri-anal Cipro &Metronidazole - Anti tuberculous (not proven to be effective) - Probiotics (live non-pathogenic bacteria) effective in maintenance remission in non-active UC (still under evaluation), could be one of our research lines VI.Nutritional support Better in CD liquid entral diet (2-6w)----induce remission in 60%=steroids VII.Adjuvant therapy -Improving quality of life -Stop smoking in CD -Symptomatic treatment.e.g diarrhea, abdominal pain

22. Management algorithm of IBD Mild/moderate Proctatitis/distal colitis Topical 5ASA ± steroid enema ± oral 5ASA Failed add on oral steroid Failed withdraw steroid & add immuno - modulators e.g.AZA Failed add on IFX Pancolitis / iliocolonic Lt sided colitis Oral 5ASA Failed as previous Perianal & fistulating Discuss with GI surgeons AZA+ IFX or IFX alone Failed inc IFX dose or Adali (surgery) severe Admission,involve surgery early IV steroid (5-7 D) f/u Failed IV cyclo &/or IFX Failed surgery

23. Your follow-up Symptoms Labs for F/U(ESR,CRP,CBC± S.Ca, S.Alb) Endoscopically Labs for drug side effects Drug compliance &side effects CRC screening (diff to be applied) 1-3 years in 10 years pan-colitis 1-3 years in 15-20 years LT-sided colitis 2-4 biopsies / 10 cm If PSC --------annual colonoscopy

24. Sum up IBD is a disease of history taking Easily diagnosed (if you suspect it),but diff to treat IBD can be controlled and rarely to be cured (UC) Needs good clinicians and multidisciplinary teams Available medications is good but unsatisfactory (serious side effects and expensive)

25. Thank you