Ulcerative Colitis: Case Presentation & Disease Overview

patient presenting with bloody stools and systemic signs with no previous medical complaints was diagnosed with amoebiasis on top ulcerative colitis (sigmoid-proctitis)

1. Case Presentation & Disease Overview of Farah Al Souheil , PharmD , RPh 1

2. Patient Presentation CC: abdominal pain and blood (!) in stools HPI: 20 year old male patient was asymptomatic 4 days prior to hospital admission He presented to the ER with a history of bloody loose stools, accompanied by abdominal pain which was localized to central abdomen and vomiting and low grade fever since 4 days Pain was often relieved by passing out stools The patient negates weight loss PMH: previously healthy NKDA SH: smoker, non-alcoholic 2

3. Differentials 3

4. ROS General: conscious and cooperative (negative for dehydration/anemia), negative for jaundice and pruritus P/A: positive for abdominal pain, vomiting CVS: S1 and S2 present no murmurs CNS: no motor or sensory Extremeties : no hx of joint pain (extra-intestinal complications of crohn ) 4

5. Vitals Vitals Day 1 Day 2 Day 3 Pulse 90 88 80 BP 110/70 100/70 110/70 RR 22 27 27 Temp (c) 37.7 37.7 37.7 5

6. Lab Work-up 6

7. Microbiological Examination of S tool Stool was positive for blood and mucus Tetranucleate cysts of entamoeba histolytica were detected containing RBC All patients with suspected UC should be tested for  C difficile  infection ( NOT DONE) The prevalence of  C difficile  infection among patients with new or relapsing inflammatory bowel disease is between 5% and 47% 7

8. Further examination To differentiate between infective & inflammatory colitis PS: done when hemodynamically stable & mi blood loss 8

9. Endoscopy 9

10. Ulcerative colitis VS crohns ’ Crohn’s disease Skip lesions in the gut Deep lesions Causes cobblestoning & stricturing 10

11. Serological testing Not done Strongly discouraged lately Differentiate between CD and UC pANCA identified in some pts with UC ASCA yeast has been found in some pts with CD If seronegative -> better prognosis Fecal calprotectin can be used to measure disease activity and response to therapy 11

12. Assessment 12

13. Medication Chart Drug Indication Dose Route Frequency Date of start Paracetamol Fever 650 mg PO TID Day 1 Metronidazole Amoebiasis 100 ml (500mg) for 5-10 days IV TID Day 1 pantoprazole 40 mg IV BID Day 1 Ondansetron Vomiting 100 mg IV TID Day 1 Lactobacillus spores GUT flora PO BID Day 1 Hyoscine butyle bromide Abdominal pain 2 cc IV BID Day 1 Fe and B9 Low Hgb PO BID Day 1 Missing IV CS 13

14. Plan of discharge 14

15. 15

16. Disease overview 16

17. Etiolog y 17

18. Ulcerative colitis VS crohns ’ Systemic complications less more ( Renal & gallstone) Colonic carcinoma More Less bleeding more less Nutrition deficiency less More Smoking Protective Risk factor 18

19. Types of Ulcerative C olitis 19

20. Disease severity Fulminant >10 (bloody) >100 <30 >10 >100 >30 Abd pain Mild Mod Tender Severe Transfusion required No No Maybe Yes Dilated colon No No Bowel wall edema 5.5-6 cm This patient 20

21. Clinical presentation Fever Abdominal pain Diarrhea (bloody/water/mucopurulent) Wt loss UC Crohn’s Fever + + Tachycardia + - Lower abdominal cramps + - Increased WBC & ESR + + Decreased hgb + - Hemorroids , anal abscess + - fistula - + 21

22. Goals of tx 22

23. Non pharmaco treatment 23

24. Pharmacologic tx Importance of separation between disease activity and disease severity D isease activity refers to how sick the patient is at evaluation, whereas severity reflects the patient's prognosis and complicated outcomes, such as the need for surgery Depends on: Severity Acute tx / maintenance Complications 24

25. Treatment overview Ulcerative colitis Induce remission Active left sided disease PO aminosalicylate + PO CTCS +/- PR aminosalicylate or PR CTCS (if rectal sx ) Active distal disease Topical aminosalycylate ( suppo / enema) Topical steroid+ PO aminosalycilate / PO CTCS Severe IV and PR steroids Fluids Electrolytes Heparin Nutrition Antibiotics Followed by: ciclosporin or infliximab Maintenance: (in order of preference) 25

26. Mild - Moderate UC 26

27. Mild – moderate (<6 motions/day) Induction: Only rectum or sigmoid ( if not tolerate switch/ if fail then add another agent) 6-8 weeks then taper down 1 aminosalicylate enema (1 g/day for both induction and remission) 2 Steroid foam/ suppo 3 oral 5ASA If failed  add oral prednisolone 40-60 mg/day or infliximab More than the sigmoid (6-8 weeks) Combination: oral ASA + hydrocortione or 5ASA enema If fail (2-4weeks)-> add oral budesonide 9 mg for 8 weeks If fail -> switch budesonide to oral prednisone 40-60mg for 2 weeks followed by taper If fail (7-10D) -> steroid refractory -> switch to IV steroids If fail (3-7D) -> Cyclosporin as a bridge therapy with AZA or 6MP If cant tolerate any of the preceding agents -> infliximab 27

28. Mild – moderate (<6 motions/day) Maintenance FOR ALL PATIENTS 5 ASA preferred Combination: Oral (3g) + topical ( qd or QOD) The evidence shows that 5-ASA [ aminosalicylate ] in enemas, suppositories, and oral doses [is] more effective than oral treatment alone If CS can’t be tapered to less than 10mg in 3 months of steroids initiation or patient relpased in 3 months of discontinuation Add AZA or 6 MP (3-6 months to kick in while the patient is on steroids) Or Add anti TNF for induction and remission 28

29. Moderate- S evere 29

30. Moderate- Severe Mod- Severe (>6 bloody motions/day + systemic sx : HGF, tachycardia, anemia ) Induction NPO IV fluids & parenteral nutrition IV hydrocortisone 100 mg q6hr or IV methylpredinsolone 40-60mg qd If systemic symptoms continue beyond 1 week add IV cyclosporin 4mg/kg If patient improves  switch to PO steroids 30

31. Moderate- Severe D/C anti-cholinergic/ antidiarreal , NSAID, opiod drugs Inc risk of TOCIX MEGACOLON IV metronidazole or ciprofloxacin When High Grade Fever, WBC are increased with neutrophil shift Oral CS + high dose 5ASA + topical CS or 5ASA If fail -> IV CS + IV fluids If fail -> steroid refractory Cyclosporin as a bridge therapy with AZA or 6MP antiTNF Tofacitinib If responded -> swtich back to PO CS in 3-5D 31

32. Moderate-Severe Maintenance Continue oral 5 ASA Switch To AZA or 6MP or anti TNF If patient have: >2 relapse year requiring CS Steroid dependent Can’t tolerate 5ASA 32

33. Severe- fulminant NPO Hospitalized Parenteral nutrition Antibiotics to ALL IV methylprednisolone (16-30mg TID) for 7-10D If FAIL (3D) -> steroid refractory -> swtich to Cyclosporin followed by AZA or 6MP Infliximab Methotrexate and systemic corticosteroids should be avoided in the maintenance of remission of UC Thiopurines as maintenance therapy Patients with acute severe UC who fail to respond to medical therapy within 3 to 5 days should receive surgical consultation Patients with fulminant UC are commonly treated with steroids, and other rescue thera - pies.226 Clostridium difficle and cytomegalovirus must be excluded by laboratory studies and treated if positive.226 Monitoring should include CRP levels, stool frequency, frequent abdomi - nal exams, and abdominal imaging. Clinical instability and limited improvement in 4–7 days are indications for surgical intervention 33

34. 34

35. Sulfasalazine For induction (4-6g/day) & maintenance (2-4 g/day ) Inhibits The synthesis of leukotriene & prostaglandin Neutrophil chemotaxis The activattion of nuclear regulatory factor Activated in the colon by azo-reductase bacteria Composed of Sulfapyridine Excreted in the urine Causes side effects (GI, megaloblastic anemia, leukopenia, HA) Take with food with slow escalation Mesalamine Active moeity Excreted in the stool Stop in case of: BMS, pancreatitis, hepatitis, nephritis, pneumonitis 35 Sulfa Allergy Yellow- orange urine color Reversible decrease in sperm count

36. 5 Amino-salicylate 1 st line for Mild-mod UC Side effects: HA, malaise, cramps, gas, diarrhea ( Include : mesalamine ( Canasa ) Delayed release for Distal ileum & right colon Microgranuels for CD of small & large intestine Enema for proctitis olsalazine ( Dipentum ) More expensive Cause Diarrhea that resolves in 4-8 weeks balsalazide ( Colazal , Giazo ) Cause Diarrhea that resolves in 4-8 weeks 36 No Sulfa Moiety

37. PO 5 ASA dosing 37

38. Steroids It’s controversial whether local or systemic steroids are better IV hydrocortisone 100 mg TID PO prednisone 40-60mg/ day for 3-4 weeks Taper by 5mg/week to reach 20mg Taper by 2.5mg/week PO Budesonide Released in terminal ileum & ascending colon More potent than prednisone 9mg/day for 6-8 weeks Taper by 3mg q2weeks Rectal Enema/ foam -> procto -sigmoiditis & proctitis Cream/ suppo -> proctitis 38

39. Immunosuppresants 39 Bridged with CS/ 5ASA/ infliximab for 6 months to kick in For remission only

40. Azathioprine & 6MP N/V Nephrotoxicity/ hepatotoxicity/ pancreatitis BMS Infections 40

41. Cyclosporin PO/ IV Faster onset than azathioprine Side effects: Immunosuppression Neuro/ nephro / ototoxicity HTN Hypercholesterolemia 41

42. 42 Infliximab adalimumab Vedolizumab Golimumab vidolizu mab Ustekinumab

43. Infliximab Anti-TNF Moderate-severe colitis Induction & maintenance 5mg/kg IV infusion 3 dose regimen: 0,2,6 weeks then every 8 weeks Side effects: TB, pneumonia, septicemia, lymphoma, serum sickness Avoid all MAbs in heart failure or latent infections Pre-medicate with diphenhydramine and APAP 90 min prior to infusion 43 Very rapid onset of action

44. Adalimumab In pts who no longer respond to infliximab SQ and humanized 160mg SQ then 80mg after 2 weeks then 80mg q2weeks Increase lipid and cholesterol 44

45. Tofacitinib ( xeljanz ) 45

46. Vidolizumab 46 PML

47. Ustekinumab 47

48. Complications 48

49. Toxic megacolon 49

50. Pouchitis 50

51. Surgery indications 51

52. Vaccination Patients on immuno-modulators at increased risk of infections According to the age group Inactivated influenza vaccine, pneumococcal vaccination (PCV13 and PPSV23), hepatitis A, hepatitis B, Haemophilus influenza B, human papilloma virus (HPV), tetanus, and pertussis 52

53. Treatments Under investigation 53

54. References Up-to-date Medscape American society of gastroenterology guidelines 54