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.  CC: abdominal pain and blood (!) in stools
 HPI:
o 20 year old male patient was asymptomatic 4 days prior to hospital
admission
o 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
o Pain was often relieved by passing out stools
o The patient negates weight loss
 PMH: previously healthy
 NKDA
 SH: smoker, non-alcoholic
2

3. Amoebiasis
?
Hemo-
rrhoids?
Fissure?
Acute exa-
cerbation of
crohn w/
dehydration
Infective
colitis
Pseudo-
membran-
ous colitis
3

4.  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 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. FBG: 95
Scr: 2 (inc)
K: 3.8
Na: 133 (dec)
CL: 111
WBC: 8800
N: 65%
L: 29%
E: 3%
M: 2%
B: 0
ESR: 18 (inc)
RBC: 4
PLT: 245
Hg: 8 (dec)
Missed:
LFTs
Albumin
6

7.  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)
o The prevalence of C difficile infection among patients with new or
relapsing inflammatory bowel disease is between 5% and 47%
7

8. Colonoscopy
• Erythema and erosions in rectum and loss
of vascular pattern
• Multiple polypoid lesions in sigmoid
colon
Recto-sigmoid biopsy:
• Ulceration
• Crypt distention & abscess
• Infiltration in the lamina propia
To differentiate between infective &
inflammatory colitis
PS: done when hemodynamically
stable & mi blood loss
8

9. 9

10.  Crohn’s disease
o Skip lesions in the gut
o Deep lesions
o Causes cobblestoning & stricturing
10

11.  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. Based on subjective & objective
evidence: Amoebiasis on top of
severe procto-sigmoiditis
ulcerative colitis
12

13. Drug Indication Dose Route Frequency Date of start
Paracetamol Fever 650 mg PO TID Day 1
Metronidazol
e
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. Low fiber, low lactose diet
Vitamin D and ca
Fe and B9
• Should be in combination with topical 5ASA!Mesacol: mesalazine 800 mg tid
•Should be 40-60 mg/day for 3-4 weeks followed by a taper
•Should be on less than 10mg in 3 months
•If fail switch to IV HC 100 mg TID for 7-10 days
Prednisolone 25mg qd (morning)
Paracetamol prn for pain
Metronidazole to finish the 5-10 days
course
• Starting 8 years from now
Yearly colonoscopy (to R/O colon
cancer)
Up-to-date with vaccination
• Decreased quality of life with ulcerative colitis
Assessment of osteoporesis, anxiety
and depression
14

15. Disease
Overview
15

16. Affects sigmoid
& descending
colon
May affect the
rectum
• Casue mucopurulent,
erythematous and
granular superficial
ulceration
16

17. Unknown
Immune mediated mucosal damage
Less tolerance to normal bacterial flora which stimulate T-lymphocytes
Proposed mechanisms
• Viruses
• Mycobacteria
• Chlamydia
Diet ( low fiber, high sugar)
NSAIDS LEAD TO FLARE-UP (cox2 selective NSAIDs use is still controversial)
STRESS lead to flare-up
17

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

19. Distal
colitis
(proctitis &
procto-
sigmoiditis)
Extensive
colitis or
pancolitis
19

20. 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.  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. Symptomatic
treatment
Mucosal
healing
22

23. Nutrition support
• Increased TNF and Il6
increase protein turnover
• Decreased absorption
• Enteral feeding is
preferred over parenteral
• Probiotics ( ecoli, bifido,
lactobacilli, strep
theromphillus)
23

24.  Importance of separation between disease activity and disease
severity
 Disease 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:
o Severity
o Acute tx/ maintenance
o Complications
24

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

26. 26

27.  Induction:
o 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
o 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.  Maintenance
o FOR ALL PATIENTS
o 5 ASA preferred
o 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
o 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. 29

30.  Mod- Severe (>6 bloody motions/day + systemic sx : HGF,
tachycardia, anemia)
 Induction
o NPO
o IV fluids & parenteral nutrition
o 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.  D/C anti-cholinergic/ antidiarreal, NSAID, opiod drugs
o Inc risk of TOCIX MEGACOLON
 IV metronidazole or ciprofloxacin
o When High Grade Fever, WBC are increased with neutrophil shift
 Oral CS + high dose 5ASA + topical CS or 5ASA
o 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.  Maintenance
o Continue oral 5 ASA
o Switch To AZA or 6MP or anti TNF If patient have:
• >2 relapse year requiring CS
• Steroid dependent
• Can’t tolerate 5ASA
32

33.  NPO
 Hospitalized
 Parenteral nutrition
 Antibiotics to ALL
 IV methylprednisolone (16-30mg TID) for 7-10D
o 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
o 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. Aminosalicylates
34

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

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

37. 37

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

39. Azathioprine
(
mercaptopurine:
metabolite)
Cyclosporin
Tacrolimus
39
Bridged with CS/ 5ASA/
infliximab for
6 months to kick in
For
remission
only

40.  N/V
 Nephrotoxicity/ hepatotoxicity/ pancreatitis
 BMS
 Infections
40

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

42. Monoclonal Ab
42
Infliximab
adalimumab
Golimumab
vidolizumab
Ustekinumab

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

44.  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. Adverse events
diarrhea, elevated cholesterol levels,
headache, herpes zoster (shingles),
increased blood creatine phosphokinase,
nasopharyngitis (common cold), rash and
URTI
Use of Xeljanz in combination with
biological therapies for ulcerative colitis
or with potent immunosuppressants, such
as azathioprine and cyclosporine, is not
recommended
45

46. IV infusion: 300mg 0,2,6 weeks then q 8weeks
The efficacy and safety of Entyvio SC were assessed in moderately-to-severely active UC as maintenance
therapy in 216 patients, in VISIBLE 1, a pivotal randomized placebo-controlled Phase III trial
• The primary endpoint evaluated the percentage of subjects achieving clinical remission (defined as a Mayo score of less than or
equal to 2 points) at Week 52
• 46.2% and 42.6% of patients administered 108mg and 300mg of Entyvio SC, respectively, achieved clinical remission compared to
14.3% of patients who received placebo at Week 52
• Entyvio SC safety data were consistent with the known safety profile of Entyvio IV
The drug is most likely going to be a first-line option for patients suffering from moderate to severe UC
The SC formulation will allow patients to take Entyvio from the comfort of their own home
VARSITY trial revealed that Entyvio IV is more efficacious than Humira
SC formulation of the drug will most likely decrease the use of Humira and Simponi in UC
46
PML

47. The approval of
ustekinumab (Stelara,
Janssen) – a human IL-
12 and IL-23 antagonist
– is based on data from
the phase 3 UNIFI trial
The first dose of
ustekinumab will be
administered IV in a
health care facility
• Ustekinumab induced and
maintained clinical
remission in a significantly
greater proportion of adults
with moderately to
severely active UC
compared with placebo
• The remaining doses will
be given SQ 8 weeks after
the first dose and then
every 8 weeks thereafter
47

48. Peritonitis with sepsis
Malignancy
• Screening colonoscopy for
cancer should be initiated 8
years after the diagnosis of
UC, and then continued every
1 to 3 years thereafter
Thromboembolism
Ocular ( uveitis,
scleritis, photophobia &
eye pain)
Arthritis Anemia
Dermatologic
(auto- immune dx)
48

49. Clinical presentation
• Dilated colon(> 6cm ), psesopolyps
• High temprature
• Tachycardia
• Increased WBC
• Dehydration
• Anemia
Broad spectrum antibiotics
Colectomy if unresponsive to drugs
The immediate involvement of a colorectal surgeon is imperative
Medical therapy for 24–48 h with intravenous hydration, broad- spectrum antibiotics & bowel rest
Cyclosporine and infliximab have been shown to successfully treat toxic megacolon in only 25–40% of the
population
49

50. Inflammation of
artificial ileal pouch
(in pts undergone
colectomy)
Metronidazole
250 mg TID
Ciprofloxacin
500mg BID
Probiotics
Prevent
recurrence
50

51. Unresponsive
to IV steroids
and immuno-
suppressants
Toxic
megacolon
Perforation
Massive
hemorrhage
Severe
systemic
symptoms
51

52.  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. Fecal transplant
• Places healthy bacteria
from a donor’s stool
into the colon of
someone with UC
• Good bacteria helps
heal damage from UC
and restore a healthy
balance of germs in the
gut
Stem cell therapy
• Have the potential to
heal all kinds of
damage
• In UC, stem cells may
alter the immune
system in a way that
helps bring down
inflammation and heal
damage
53

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