Management of Severe

Ulcerative Colitis

Dr.Siddharth Singh
 Classification into severe UC

● Truelove and Witts classification:Purely clinical it is based on only

clinical findings and laboratory parameters
● Stools more than six times per day
● Temperature more than 37.5 C
● Tachycardia (heart rate [HR] ≥90 beats/minute)
●
anemia (hemoglobin <10.5 g/dL or <75% of normal)
● ESR more than 30 mm /Hour
● Mayo Score:Sum of scores of 4 components:Stool frequency,rectal
bleeding,sigmoidoscopic findings and physicians global assessment.
Remission if score below 2,above 10 is severe disease.Clinical
response if score decreases by 3.
● Others:UCDAI/Sutherland index(similar 4 to Mayo)
● Fulminant colitis:Patients with severe colitis
who appear toxic with high fever (>38.3C)
,tachycardia,abdominal distension and signs of
localised or generalised peritonitis and
leucocytosis.
● Toxic Megacolon:Radiological evidence of
transverse colon dilatation more than 6 cm
 Treatment Protocols
● Induction therapy: IV glucocorticoids ,
Cyclosporine and Biological agents

● Maintenance therapy:
5-aminosalicylates:topical,oral and combination
Azathioprine and 6-MP
Infliximab or adalimumab
 5-AMINOSALICYLATES
● Sulphasalazine- 5-ASA is the principal therapeutic moeity and
sulfapyridine is carrier(so it gets absorbed in colon)
● Has not been proved in any tests to provide remission in severe UC but
can be used for maintenance once remission achieved.
● 5-ASA has dose dependent effect in maintenance therapy(2g/day)
● Other preparations:Olsalazine,Balsalazide and Mesalamine
preparations(these other drugs have similar efficacy as 5 – ASA but their
role in maintenance therapy is still under evaluation)
● Side effects:fever ,rash ,nausea , vomiting and headache.Less common
are hypersenstivity,folate deficiency and AKI.
● Topical formulations:Enemas(Upto splenic flexure),Suppositiries(!5-20cm
from anal verge) and foam preparations.
 Glucocorticoids
● Use upto 60mg/day,above this S/E>benefit
● Oral vs parenteral:no study but latter preferred for severe UC
● No maintenance benefits; if unable to taper prefer steroid sparing agents
● Regimens for intravenous steroids include prednisolone (30 mg IV every 12
hours), methylprednisolone (16 to 20 mg IV every eight hours), or
hydrocortisone (100 mg IV every eight hours) In patients who respond,
intravenous glucocorticoids should be converted to equivalent dose of oral
glucocorticoids in three to five days.
● Oral glucocorticoids should be tapered after the patient has been stable for
two to four weeks. Oral glucocorticoids should be tapered over eight weeks
by decreasing the dose by 5 to 10 mg every week until a daily dose of 20
mg is reached, and then by 2.5 mg every week
● Budesonide can be used less toxicity due to
high first pass metabolism by Liver and RBCs
into active metabolites
● TOPICAL: liquid and foam formulations;foams
very well tolerated by patients
Prolonged treatment with topical also related to
steroid related side effects
 IMMUNOMODULATORS
● Azathioprine and 6-MP:
Purine analogs,Steroid sparing,Prodrugs
● Azathioprine undergoes nonenzymatic
degradation to 6-MP which is metabolized into
a)6-TG which is the active metabolite
b)6-MP/6-MMP:by enzyme TPMT which are
responsible for the myelotoxicity and
hepatotoxicity
● Population polymorphism in TPMT gene
● Take 3-6 months for response so cannot be used as
monotherapy in severe UC
● If contnue mantain remisson whereas on stopping
risk of relapse is high , so maintenance indefinitely
● Side effects:Increase dose gradually and monitor
A)Aminotransferases:>50% increase then stop till
normalise and then reintroduce at low dose;but if
Bilirubin high dont
B)TC<3000 or Platelets<80000 then stop and
reintroduce on normalisation
● LYMPHOMA:especially if persistent leucopenia,
most common-Non hodgkins; Hepatosplenic T cell
lymphoma
● DEFINITIONS — The following definitions of ulcerative colitis have
been proposed :

●Steroid-responsive disease – Clinical response to high-dose

glucocorticoids (prednisone 40 to 60 mg/day or equivalent) within 30
days for oral therapy or 7 to 10 days for intravenous therapy.

●Steroid-dependent disease – Ulcerative colitis is defined as steroid-

dependent if glucocorticoids cannot be tapered to less than 10 mg/day
within three months of starting steroids, without recurrent disease, or if
relapse occurs within three months of stopping glucocorticoids.

●Steroid-refractory disease – Lack of a meaningful clinical response to

glucocorticoids up to doses of prednisone 40 to 60 mg/day (or
equivalent) within 30 days for oral therapy or 7 to 10 days for
intravenous therapy.
 Steroid refractory UC
● Choose either cyclosporine or Infliximab
● Cyclosporine:Bridge therapy(till surgery or effect of AZA/6-MP)
● Start as infusion over 24 hours 2mg/kg over a day or 4 mg/kg per day
and once improvement can switch to oral at double the dose of IV
preparation in 2 divided doses.
● Blood levels(Trough levels) of cyclosporine should be checked every
one to two days after each dose change, and every two to three days
when on stable doses. Goal levels for a dose of 4 mg/kg are 300 to 400
ng/mL. Patients dosed at 2 mg/kg should have levels no less than 200
ng/mL. Dose adjustments are based upon efficacy, side effects, and
blood levels of cyclosporine
 Side effects
● Electrolyte abnormalities, Renal dysfucntion
● Hypertension, hepatotoxicity
● Seizures (Esp if low cholesterol levels)
● Tremors ,gingival hyperplasia
● Rarely anaphylaxis
● Continue oral till 3-6 months till AZA or 6-MP
take effect for maintenance.
● Prophylaxis for P.Carinii
● TNF-alpha inhibitors:TNF alpha has major
pathological basis in Crohns.
Found in colon,stool,urine and rectal dialysates
● These are monoclonal antibodies .
● Infliximab:To use when:If patient is allergic/not
tolerating/not responding to AZA or 6 MP ; Use at
0,2,6 weeks and then 8 weekly
● Infliximab vs Adalimumab :there are no head to
head trials but network meta-analysis says that
infliximab better for producing clinical response or
mucosal healing
● ACT 1 and ACT 2 are two trials with 364 patients
each.
 Side effects of anti-TNF therapy
● Infusion or injection site reactions , delayed
type hypersenstivity and drug induced lupus
like reactions
● Infusion reactions: incidence of 4-16%; chest
pain breathing difficulty, urticaria , hypotension;
1-2 hours after starting
● Rarely lymphoma and skin cancer
● Oppurtunistic infections, Screen for latent TB
and Hep B
 Steroid dependant UC
● Rule out any concomitant diseases: IBS,Stress,
Lacotse intolerance
● Prefer taper and maintenance with Purine
analogs with +- ASA
 Newer agents
● Probiotics: Initial studies based on experiments
in monkeys; Still no evidence in severe disease
● Fecal microbiota transplantation:FMT and step
up FMT
●
 Surgery in severe UC
● Oxford index:colectomy is likely to be
necessary in a patient with ulcerative colitis if
● the C-reactive protein level is above 45 mg/mL
and a stool frequency of three to eight stools
per day,
● OR stool frequency greater than eight stools
per day on day 3 after the initiation of treatment
with intravenous glucocorticoids or cyclosporine
● Surgery cures UC by removal of colon and
rectum
● Indications:medically refractory
disease,intractable disease with impaired
quality of life and extreme side effects of
medical therapy,toxic megacolon, perforation ,
dysplasia/carcinoma and uncontrolled bleeding