Ulcerative colitis by Dr. Ali Hasan

Dr. S M Ali Hasan
MD Phase-B resident
Dept. of Gastroenterology

 Definition
 Epidemiology
 Etiology and Pathogenesis
 Pathology
 Diagnosis
 Assessment
 Management
 Complication and extra-intestinal manifestation

Ulcerative Colitis
 Chronic
 Inflammatory condition
 Mucosal inflammation without granuloma
 Involvement of the rectum with variable proximal extension
 Continuous fashion
 Relapsing and remitting course

Prevalence
 Europe (Norway- 505/100000)
 North America (USA- 286/100000)
 Southern Asia (India- 44/100000)
Incidence
 Europe (Faroe Islands- 58/100000/yr)
 North America (Canada- 23/100000/yr)
 Southern Asia (India- 6/100000/yr)
Ng, Shi et al. 2018

Genetic Susceptibility
- Family History
- Genetic Mutations
Environmental Factors
- Enteric infection
- Microbial dysbiosis
- Non/Ex-smoker
- Dietary Factors
- Drugs- NSAIDs,
OCP
Host Immunity
- Humoral Immunity
- Cell mediated
Immunity

 Increased risks
 Family history of UC
 NSAID (short term
COX2 inhibitor may be
safe)
 Decreased risks
 Appendicitis/ mesenteric
lymphadenitis in
childhood/ adolescence
 Smoking
 Protect PSC and
pouchitis

 Always involves the rectum
 Variable proximal extension
 Most severe distally
 Progressively less severe proximally
 Continuous and symmetrical
 Sharp transition between diseased and healthy segment of the
colon
 Limited to mucosa and superficial submucosa

 Rectal sparing:
 Topical therapy
 Untreated children
 Cecal patch
 Peri-appendiceal skip lesions (75%)
 More responsive course
 Risk of pouchitis after IPAA

 Backwash ileitis:
 More refractory course
 Risk of colonic neoplasia
 Needs small bowel evaluation to exclude CD

 According to disease extent (Montreal
classification), Silverberg et al.,
 E1 – Proctitis: Distal to rectosigmoid junction
 E2 – Left-sided: Limited distal to splenic flexure
 E3 – Pancolitis/Extensive: involvement proximal to splenic
flexure.

 Proximal extension of proctitis – 20-30%
 Importance:
 Choice of treatment and drug delivery system
 Selection for surveillance

According to disease severity
 Remission
 Active
 Mild
 Moderate
 Severe active disease

 Diagnosis depends on
 Clinical features
 Laboratory parameter
 Imaging
 Colonoscopy
 Histopathology
 Exclusion of infective cause

 Clinical features:
Depends on extent and severity
 Rectal bleeding (> 90%)
 Loose stool (> 6 weeks)
 Rectal urgency
 Tenesmus
 Mucopurulent exudate
 Nocturnal defecation
 Crampy abdominal pain

 Proctitis:
 Rectal bleeding
 Rectal urgency
 Mucus discharge
 Tenesmus
 Severe constipation
 Systemic symptoms:
 Weight loss
 Fever
 Tachycardia
 Nausea
 Vomiting
 Extra-intestinal manifestation
 Arthropathy
 Ocular
 Dermatological
 Hepato-biliary

 History
 Symptoms
 Family history
 Travel history
 Drug history
 Examination
 Anemia
 Pulse
 Blood pressure
 Height, weight
 Abdomen: Distension,
tenderness, Bowel sound
 Perianal: inspection,
DRE.

Differential diagnosis
 Crohn’s colitis
 Infectious colitis
 Ischemic colitis
 Radiation colitis
 SRUS
 Amoebic colitis
 Schistosomiasis
 Colon cancer
 NSAID enteropathy
 HSP, Behcet’s disease

Initial
 CBC – Hb- , PC-
 Electrolytes
 Liver function test
 Renal function test
 Iron profile
 Vitamin-D level
 CRP
 F. Calprotectin

 Exclusion of infective diarrhoea including C. difficile
 Stool RME
 Stool culture
 Toxin A & B
 Colonoscopy/Sigmoidoscopy
 Histopathology

In relapse or treatment refractory UC
 Test for C. difficile and CMV
 C. difficile infection
 Stool for c. difficile toxin
 Pseudo membrane are usually absent (0-13%)
 CMV
 Biopsy
 Histopathology:
multiple inclusion body
 IHC (> 2 CMV +ve cells)
 PCR in blood

 Biomarker
 pANCA limited sensitivity, routine use for Dx
 ASCA therapeutic decision is not justified
 F. calprotectin – most sensitive in activity, Dx & treatment
response
 Elastase
 Lactoferrin

 Acute severe colitis at admission
 CBC
 ESR, CRP
 Electrolytes
 LFT
 Stool RME, C/S, C. difficile toxin
 Plain X–ray abdomen
 Exclude dilation >5.5 cm
 Disease extent
 Predictors of poor treatment response (mucosal islands, > 2 gas
filled loops of small bowel)
Toxic megacolon

Acute severe colitis at admission
 Flexible sigmoidoscopy
 Confirm diagnosis
 Exclude infection – CMV
 Preparation: unprepared bowel. Phosphate enema can be
used
 Full colonoscopy is not recommended
 After active disease has been controlled in newly diagnosed
patient full colonoscopy should carried out to see extent and
to exclude CD

 Clinical assessment
 Endoscopic assessment
 Histological assessment
 Radiological assessment
 Biomarkers
 Quality of life (QoL)

Clinical assessment
 About 17 indices
 For assessment of mild to moderate disease
 Simple colitis clinical activity index (SCCAI)
 Partial Mayo clinic index (PMI)
 For severe disease
 Truelove and Witts criteria

Partial Mayo clinic
Index (PMI)

Mild Moderate Severe
Bloody stool < 4 ≥ 4 if ≥ 6 and
Pulse < 90 ≤ 90 > 90
Temperature < 37.5 ≤ 37.5 > 37.5
Hemoglobin > 11.5 ≥ 10.5 < 10.5
ESR < 20 ≤ 30 > 30
CRP Normal ≤ 30 > 30
Truelove & Witts

Endoscopic assessment of severity
 Ulcerative colitis endoscopic index of severity
(UCEIS)
 Mayo clinic endoscopic subscore

 UCEIS_ UC endoscopic index of severity
UCEIS_ UC endoscopic index of
severity
Vascular pattern Normal = 0
Patchy obliteration = 1
Complete obliteration = 2
Bleeding None = 0
Mucosal = 1
Luminal mild = 2
Luminal moderate or severe = 3
Erosions and ulcers None = 0
Erosions = 1
Superficial ulcers = 2
Deep ulcers = 3

 Mayo score (3 days)
Mayo index 0 1 2 3
Stool
frequency
Norma
l
1-2/day
> Normal
3-4/day
> Normal
≥ 5/day
> Normal
Rectal
bleeding
None Streaks Obvious Mostly blood
Mucosa Norma
l
Mild friability
Erythema
Decreased
vascular
pattern
Moderate
friability
Marked erythema
Erosion
Absent vascular
pattern
Spontaneous
bleeding
Ulceration
Physician’s
global
assessment
Norma
l
Mild Moderate Severe

Histological marker
 Remission
 Persistent architectural distortion to normalization
 Active
 Transmucosal inflammatory infiltrate
 Basal plasmacytosis
 Cryptitis
 Crypt abscess
 Histological inflammation can present in
endoscopically inactive disease
 Is a risk factor for CRC in long standing case

Histological assessment of severity
 26 indices, 2 are validated
 Nancy index mostly recommended
 Robarts histology index (RHI)

Ulceration
Yes
Grade- 4: Severe
Active disease
Acute inflammatory
cell infiltrate
No
No
Yes
Moderate
or Severe
Mild
Grade- 3:
Moderately Active
disease
Grade- 2: Mildly
Active diseaseChronic inflammatory
cell infiltrate
Moderate or
marked
increased
No or
mild
increase
Grade- 1: No active
inflammatory
infiltrate
Grade- 0: No
histologic
significance disease
NANCY INDEX

Radiological assessment
 Plain X-ray
 Used in Acute severe UC
 Toxic dilation (> 5.5 cm)
 Also to diagnose proximal constipation in refractory distal
UC

 Cross-sectional imaging
 To assess complication
 Exclude small bowel inflammation and Crohn’s disease
 Severe stenosis or comorbidity limits colonoscopy
 MRI/USG
 Disease activity
 Disease extent
 Simplified MR colonography index (MRC-S)
 Bowel ultrasound severity score

Simplified MR colonography index (MRC-S)

Bowel ultrasound severity score

Laboratory marker of severity
 CRP
 ESR
 Procalcitonin
 Low albumin
 F. Calprotectin
 Lactoferrin
 Elastase

 CRP
Oxford Criteria in acute severe colitis

Quality of Life (QoL)
 IBD-Control
 IBDQ
 SIBDQ
 CUCQ-8
 Short form SF 36v2
 Short form SF 12v2
 EuroQol (EQ-5D)

Based on
 Distribution
 Proctitis
 Left-sided colitis
 Extensive colitis
 Age of onset
 Disease duration
 Pattern of disease
 Infrequent (≤ 1 year)
 Frequent (≥ 2/year)
 Continuous (no
remission)
 Disease course
 Response to previous
medication
 Side effect of medication
 Extraintestinal
manifestation

 Proctitis (Mild to moderate)
 1st line:
 Mesalamine 1 g suppository once daily
 Alternative: Mesalamine foam or enema
 Topical mesalamine >> more effective than topical steroid
 Combined topical Mesalamine with oral Mesalamine or
topical steroid is more effective

Topical Mesalamine
Topical Mesalamine +
Topical steroid
(Budesonide 2g foam)
Oral 5-ASA + Topical
Mesalamine / topical
steroid
Refractory proctitis

 May require
 Systemic steroid
 Immunomodulators and /or
 Biologics

 1st line: Mesalamine enema ≥ 1g/day plus oral Mesalamine ≥
2.4 g/day
 Topical Mesalamine is more effective than topical steroid
 Once daily Mesalamine is equally effective as divided dose.
 Mild to moderate disease refractory or intolerant to 5-ASA
may be treated with Budesonide 9mg/day

 Moderate to severe disease or mild disease not
responding to 5-ASA
 Severe disease require Hospitalization
 Systemic steroid: Prednisolone 40mg/day or Beclomethasone
5mg/day

Think about…
 Poor adherence
 Delivery of inadequate conc. Of active drug
 Unrecognized complications (Proximal constipation, infection)
 Inappropriate diagnosis (CD, CRC etc.)

Stool C/S, endoscopy and biopsy, X-ray abdomen
Oral steroid + oral
and rectal 5-ASA
1. IV steroid
2. Salvage therapy
- Oral/rectal ciclosporin
- Oral/rectal tacrolimus
- Infliximab
Colectomy
Refractory proctitis or distal colitis
Review of symptoms, treatment history, medication
adherence
Proximal constipation
affect drug delivery
Laxative
Failed

Mild to moderate
 1st line: Mesalamine enema ≥ 1 g/day plus oral Mesalamine ≥
2.4 g/day (more benefit at 4.8g/day)
Moderate to severe disease
or mild disease refractory to 5-ASA (already on ≥ 2g /day
Mesalamine with relapse):
 Oral Prednisolone 40 mg/day then taper 5mg weekly total 8
weeks
 2nd generation steroid:
 Oral Beclomethasone 5 mg/day – 4 weeks then alternate weekly
4 weeks (Similar efficacy to prednisolone 40mg)

 Diagnosis:
 Bloody diarrhoea ≥ 6 times/day and
 Any sign of systemic toxicity
 Pulse > 90 bpm
 Temperature >37.5 °C
 Hb <10.5 g/dl
 ESR > 30 mm/hr or CRP > 30 mg/L

 Hospitalization
 IV corticosteroid
 Methyl prednisolone 60 mg/day or
 Hydrocortisone 100 mg 4 times daily for 7-10 days
 Alternative: IV cyclosporine monotherapy if steroid contra-
indicated
 IV fluid & electrolyte replacement:
 Potassium supplementation at least 60 mmol/day
 Hypokalemia and hypomagnesaemia promote toxic
megacolon

 Appropriate investigations to diagnose and exclude
infection
 Unprepared Sigmoidoscopy with biopsy ( Dx and exclusion
of CMV)
 Stool culture and C. difficile toxin
 If C. difficile found positive then
 Oral vancomycin
 Fecal transplantation (FT) can be considered
 If possible, immunosuppressive drug should be stopped

 Subcutaneous LMWH to minimize risk of
thromboembolism
 Nutritional support:
 Enteral nutrition is most appropriate
 Bowel rest through IV nutrition does not alter outcomes
 Withdrawal of anti cholinergic, anti-diarrheal,
NSAID, opioids (risk of toxic megacolon)

 Antibiotic:
 Only if infection is considered
 Immediately prior to surgery
 Blood transfusion to maintain Hb conc. 8-10 g/dl

 IV steroid refractory UC
 Response should be assessed by 3rd day
 Prediction of IV steroid failure:
 Clinical marker:
 Stool frequency > 12 at Day-2, > 8/day or 3-8/day + CRP
>45mg/L at Day-3
 Biochemical marker: ESR >75 mm/hr, temp > 38°C
 Radiological/Endoscopic:
 Abdominal X-ray: dilatation > 5.5 cm or mucosal island
 Endoscopy: deep ulcerations

 Salvage therapy:
 Ciclosporin – 2 mg /kg/day for 8 days followed by 4 mg/kg/day
oral
 Tacrolimus
 Infliximab – 5 mg/kg on 0,2,6 weeks
 All responders
 Start Azathioprine at day 7
 Taper steroid from day 8
 Non responders following 4-7 days of salvage therapy:
 Colectomy

Complications
 Toxic megacolon
 Total or segmental non obstructive dilatation ≥ 5.5 cm plus
systemic toxicity
 Risk factors –
 Hypokalemia
 Hypomagnesaemia
 Bowel preparation
 Use of anti diarrheal therapy
 Management –
 i.v steroid
 Vancomycin until stool negative for C. difficile
 Consultation with colorectal surgeon
 If not improved - colectomy

 Perforation
 Inappropriate total colonoscopy
 Toxic megacolon
 Thromboembolism

• Thiopurines (EL-2)
• Anti TNF (EL-1)
preferably with
thiopurines
• Vedolizumab (EL-2)
• Methotrexate (EL-2)
Steroid dependent active UC
• Different Anti TNF
• Colectomy

• IV steroid (EL-4)
• Anti TNF (EL-1)
preferably with
thiopurines
• Tacrolimus (EL-2)
Oral Steroid refractory active UC
• Colectomy

• Anti TNF (EL-1)
preferably with
thiopurines
Immunomodulator refractory UC
• Colectomy

 Goals –
 Steroid free remission
 Clinical and endoscopic remission
 Long term therapy
 Intermittent therapy may be acceptable for some
patients with proctitis

 Choice of maintenance therapy depends on
 Disease extent
 Disease course
 Previous medication failure and adverse event
 Severity of most recent flare
 Treatment used to induce remission
 Safety of therapy
 Cancer prevention

 Stepwise escalation of therapy
Add Anti-
TNF/
vedolizumab
Add thiopurines
Dose escalation of oral
/rectal 5-ASA

 5-ASA
 1st line maintenance therapy after induction with 5-ASA/
oral or rectal steroid
 Rectal 5-ASA: for proctitis or left-sided colitis
 Combination of oral and rectal 5-ASA – 2nd line maintenance
therapy
 Oral mesalamine 2 g/day once daily administration is
preferred
 Sulfasalazine is equally or slightly more effective but more
toxic.

 Thiopurines
 Mild to moderate disease
 Indications
 Early/ frequent relapse on Mesalamine optimum dose
 Mesalamine intolerant
 Steroid dependent
 Induction with Ciclosporin or Tacrolimus
 Reduce risk of colectomy after induction with ciclosporin

• Oral Ciclosporin for 6
months
• Continue Azathioprine
Start Oral ciclosporin 4
mg/kg/day and Azathioprine
Induction with i.v Ciclosporin
2mg/kg/day – 8 days

• Vedolizumab and
maintenance with
Vedolizumab (EL2)
Continue Anti TNF ±
thiopurines (EL1)
Induction with Anti TNF
Alternative:
thiopurines (EL3)
 Anti TNF & anti adhesion therapy

Anaemia (21%)
 Iron deficiency
 Anaemia of chronic disease
 Both
 Investigation
 CBC, PBF
 Ferritin, T. SAT
 CRP

Anaemia
Without active
inflammation
Active disease/inflammation
Ferritin <30 µg/L Ferritin upto 100
µg/L
Ferritin > 100 µg/L,
TSAT < 20%
ACD
IDA

 Atypical case:
 Vitamin B12
 Folate
 Haptoglobin
 LDH
 Coombs test
 Treatment
 Iron supplementation (oral >> parenteral)
 Blood transfusion (Hb <8, Ferritin <15)
 Erythropoetin (refractory case)

 Arthropathy (20%) – 2nd most common
Arthropathy
Axial Peripheral
Type – I Type – II
• Pauci-articular (< 5)
• Large joint
• Asymmetrical
• Acute self limiting
• Related to
intestinal disease
activity
• Poly-articular (>5)
• Small joint
• Symmetrical
• Chronic persistent
• Independent of
disease activity
• Inflammatory
LBP
• MRI/Radiological
evidence of
sacroilitis
Exclusion of
other form

 Treatment:
 Target:
 Reduce inflammation
 Pain relief
 Reduce disability
 Type-I:
 Effective treatment of UC flare
 Sulfasalazine
 Rest
 Physiotherapy

 Type – II
 NSAID/systemic steroid
 Axial/ AS
 Consultation with rheumatologist
 Sulfasalazine, MTX, Azathioprine are ineffective
 Choice
 NSAID
 Anti-TNF – Infliximab, Adalimumab, Golimumab

Metabolic bone disease
 Diagnosis: BMD
 Persistently active disease
 Repeated exposure to steroid
 Long duration disease
 Treatment:
 Calcium 500-1000 mg/day
 Vitamin-D 800-1000 IU/day
 Prophylactic Calcium/Vit-D with steroid
 Bisphosphonates: post menopausal women, spontaneous
fracture.

Cutaneous manifestations
 Erythema nodosum:
 Diagnosis: Clinical,
atypical case – skin biopsy
 Treatment:
 Treatment of underlying UC
 Systemic steroid (severe case)
 Immunomodulators/Anti-TNF (refractory case)

 Pyoderma gangrenosum:
 Dermatological consultation
 Infliximab/Adalimumab
 Topical CNI

Ocular manifestation
 Episcleritis:
 Topical steroid and NSAID
 Uveitis:
 Topical/ Systemic steroid
 Urgent referral to ophthalmologist
 Resistant case – Anti TNF

Hepatobiliary
 PSC – increased risk of CRC
 Diagnosis: MRCP
 Treatment: UDCA
 Pericholangitis
 Steatosis
 Cirrhosis
 Chronic hepatitis
 Gall stone

 UC doesn’t affect fertility
 If pregnancy occurs at remission >> risk of relapse
is equal as non pregnant
 If pregnancy occurs at active disease >> Risk of
persistent disease activity
 Should advised to conceive during remission

 Disease activity is associate with preterm labor,
LBW
 No specific risk for congenital malformation
 Medications are safe except MTX

 All patient should be tested for HBV and HCV
infection at diagnosis
 If HBV found negative >> vaccination
 If HBsAg Positive, before, during and 12 months
after IM therapy >> Antiviral drug irrespective of
HBV-DNA level.(EL2)
 Or monitoring HBV-DNA 2-3 months interval
without antiviral. (EL5)

 All patient should screen for latent or active TB at
diagnosis and before starting of Anti-TNF
 History
 Chest X ray
 MT/IGRA
 UC & Latent TB:
 Anti TB at least for 3 weeks before Anti-TNF
 UC & Active TB:
 Anti TB at least 2 months before Anti-TNF

Risk factors for CRC
 Disease duration
 Disease extent
 More severe / persistent inflammation
 PSC
 Family history of CRC
 Male gender
 Raised CRP level

All UC patients
With PSC Without PSC
No further
surveillance
• Rectum without
• Past/current
• Endoscopic/Histolo
gic inflammation
proximal to rectum
• Others without only
rectum involvement
After Dx of PSC
annually irrespective
of activity, extent,
duration
All patients at 8 year of Dx
To reassess extent & exclude dysplasia
• High risk
• Intermediate risk
• No risk

Intermediate risk No riskHigh risk
• Stricture or dysplasia
detected within 5 year
• PSC
• Extensive colitis with
severe active
inflammation
• Extensive colitis with
mild to moderate active
inflammation
• Post inflammatory polyp
• F/H of CRC in 1°
relative ≥ 50 years
Annually 2-3 yearly 5 yearly

Surveillance colonoscopy
 Should be done at remission
 Chromoendoscopy with targeted biopsy
 High detection rate
 White light endoscopy
 Random biopsy every 10 cm &
 Targeted biopsy of any visible lesion

 Mesalamine – decrease incidence of CRC
 Other medication having no significant evidence of
chemoprevention

 LGD/HGD should be confirmed by independent GI
specialist pathologist

Endoscopically visible
dysplasia
Polypoid dysplasia Non-polypoid dysplasia
Polypectomy 1 Endoscopic resection possible
2. No evidence of non-polypoid or
invisible dysplasia elsewhere
Other cases
Colectomy
regardless of
Grade of dysplasiaEndoscopic resection and
continued surveillance

Endoscopically Non-
visible dysplasia
High grade dysplasia Low grade dysplasia
Colectomy Colectomy or
Annual surveillance
Referral to expert IBD
surveillance endoscopist
Repeat with high definition
chromo-endoscope
Controversial
Discuss with the
patients, GI specialist
and surgeon

Goals:
 To remove the disease
 With little alteration of normal physiology and life style

 Indications
Acute indications Chronic indications
• Fulminant colitis
• Toxic megacolon
• Perforation
• Massive hemorrhage
• Unresponsive to medical
Mx
• Poor quality of life and
fear of carcinoma
• Steroid dependency,
toxicity or refractory
• High grade dysplasia
• Carcinoma
• Severe EIM
• Growth retardation
• Chronic bleeding
requiring transfusion
• Large bowel obstruction

 The surgical choices are:
Restorative
proctocolectomy with IPAA
Total colectomy with IRA
Total proctocolectomy with
permanent end ileostomy

Restorative proctocolectomy with IPAA
 Resection of colon and rectum
 Formation of ileal pouch
 Pouch anal anastomosis
Indication:
 Procedure of choice

Contraindications:
 Poor sphincter control
 Crohn’s disease
 Low rectal cancer
Complications
 Pelvic sepsis
 Small bowel
obstruction
 Anastomotic stricture
 Pouchitis
 Pouch failure

Diagnosis:
Symptoms:
 Increased frequency
 Liquid stool
 Abdominal cramping
 Urgency
 Tenesmus
 Pelvic discomfort
 Rectal bleeding
 Fever
 EIM

Endoscopy:
 Defuse erythema
 Edema
 Granularity
 Friability
 Spontaneous or contact
bleeding
 Loss of vascular pattern
 Erosion
 Ulceration
Histological evidence of
pouchitis

 Differential diagnosis
 Ischemia
 Crohn’s disease
 CMV or C. difficile infection
 Collagenous pouchitis

 Risk factors
 Extensive UC
 PSC
 Being non-smoker
 pANCA positive serology
 NSAID use

 Management
Pouchitis
Acute pouchitis (< 4 weeks) Chronic Pouchitis (> 4 weeks)
Metronidazole or Ciprofloxacin
Antidiarrheal drug
Combination of 2 antibiotic
Oral steroid
Topical tacrolimus
Infliximab (refractory)
Adalimumab
Maintenance of remission: Probiotics (VSL#3)

 ECCO 2017: Third European evidence-based
consensus on diagnosis and management of
ulcerative colitis
 Sleisenger and Fordtran’s gastrointestinal and liver
disease: Pathophysiology/diagnosis/management
(10th edition)
 AIG IBD Manual: A clinician’s guide for day-to-day
practice

Ulcerative colitis by Dr. Ali Hasan

Ulcerative colitis by Dr. Ali Hasan

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