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37 Cards in this Set

  • Front
  • Back
Both UC and Crohn’s are:
and how are they differentiated (process)
 Chronic
 Relapsing-remitting
 Characterised by non-infectious gut inflammation
UC and Crohn’s are differentiated on the basis
of clinical presentation and pathological
findings
IBD aetiology, and agrevating factors - genetics
Cause not fully understood, but though to be
due to environmental triggers in genetically
susceptible individuals
Environmental factors:
 Diet - linked as both a cause and aggravating factor
 Gut flora – may trigger immune response
 Smoking – worsens Crohn’s, effect on UC complex
 Drugs – NSAIDs and antibiotics may be triggers
 Infection - ? issues related to Mycobacteria
 Stress – may trigger relapse
Genetics
 Risk 10x in 1st degree relatives of patients
 Incidence higher in certain ethnic groups e.g. Jews

There has been an increasing prevalence of
inflammatory bowel disease in Western
Society over the last 30 years
Can first present at any age, although lateteens
/ early adulthood most common
Areas of bowel affected
 Ulcerative colitis
colon and rectum only
 Crohn’s
any part of the gut, from mouth to anus
although ileum and colon most commonly
areas of normal mucosa exist between
affected areas, known as “skip lesions”
Not just a disease of the GI tract, extraintestinal
manifestations may occur with both
UC and Crohn’s
what are the incidences of diffferent features of IBD
crohns - fistulas, fissures
UC polyps
what are the common extra intestinal features
Diagnosis is based on
Diagnosis is based on presenting signs and
symptoms, supported by tests which may
include:
 Pathology for inflammatory markers
e.g. C reactive protein
 Sigmoidoscopy or colonoscopy
To visualise macroscopic appearance, site, extent
 Histology
Biopsy to enable microscopic assessment
 Radiology
Ulcerative Colitis (UC) - what is affected, course of disease, theory on cells affected
Ulcerative colitis affect the superficial
epithelium, usually in the rectum and distal
colon, but may extend to involve the entire
colon in some cases
Remissions and exacerbations are common
during the course of the disease
Two factors support the hypothesis that there
is dysfunction of mucosal immune cells:
 the nature of the inflammation seen in UC
 a number of the drugs useful in the condition
interact with the immune system

disfuse involvement of mucosa, rectum to ascending colon, cecum not as heavily involved, terminal ileum not involved

pseudo polyes from severe inflammationn and mucosal errosion - the pseudopophys are whats left.

increased inflammatory cells, crypt abscesses
UC: Clinical Manifestations
UC typically presents with diarrhoea with
blood or mucus and abdominal pain
Stools may be firm if rectal disease only
These symptoms may persist for months to
years before systemic manifestations of the
disease
The severity of the disease is related to the
presence of prominent generalised symptoms
(esp. fatigue, weight loss… see table)
Patients usually present with an initial acute
attack and their prognosis depends on the
severity of the presenting symptoms
classifying severity of UC
Crohn’s Disease - invovlvement of what
In classical Crohn’s there is primarily a
granulomatous involvement of the terminal
ileum, however all parts of the
gastrointestinal tract may be affected
This results in chronic inflammation of all
layers of the GI mucosa
Again, there are extra-gastrointestinal
manifestations of the disease which follow
the pattern and frequency of those seen in
patients with UC

wall thickened, mucosa inflamed ulcerated
Crohn’s: Clinical Manifestations
These can vary depending on the site of the
active disease
There is a tendency for penetration of the
bowel wall, resulting in fistulas and
obstruction which are not evident in UC
Patients often present with many years of
slowly progressing symptoms, as they are
relatively non-specific, for example:
 diarrhoea
 anorexia
 anaemia
 lower GI pain
UC & Crohn’s Management - treatment aims, determinants, emengency
Treatment is palliative, no drugs modify the
underlying pathological condition
Treatment is largely determined by the severity
of the disease and the number / severity of
complications that the patient has
The aims of treatment are to increase the
periods of remission, reduce the number of
relapses and reduce recurrence after surgery
Severe colitis is a medical emergency and if
treatment is not effective within 7 days,
surgery is indicated
5-Aminosalicylates (5-ASAs) - esp useful for, types, countraindication
5-ASAs are a key treatment, especially in UC
Exert local anti-inflammatory action in bowel wall
Options:
 Mesalazine = 5-ASA
 Sulphasalazine = 5-ASA linked to sulfapyridine
 Olsalazine = 2 molecules of 5-ASA linked together
 Balsalazide = 5-ASA linked to inert carrier molecule
Where 5-ASA is linked, the active 5-ASA is
released when the bond is split by the action of
colonic bacterial
Allergy to salicylates is a C/I to use of all 5-ASAs
5-Aminosalicylates (5-ASAs) - adverse effects and differculty, different drugs, which one not interchangable and why
Range of adverse effects, including epigastric
pain, nausea and diarrhoea
More serious adverse effects include:
 blood dyscrasias - monitoring indicated
 skin reactions e.g. Stevens-Johnson Syndrome
Some differences between the options:
 with sulphasalazine additional adverse effects occur as a
result of the sulphonamide group
 diarrhoea may be more frequent with olsalazine
Mesalazine preparations utilise a pH dependent
coating that delays release of the 5-ASA until
reaches distal small bowel or colon
 different mesalazine preparations not interchangeable
UC treatment rough guide - approach
approach is severity
UC: Treatment of Acute Episodes
Mild Disease
 Prednisolone enemas 20mg/100mL at night
or twice daily
 Hydrocortisone rectal foam 10% at night or
twice daily
 Prednisolone reaches the splenic flexure,
while hydrocortisone only reaches the
sigmoid colon
 For very distal disease, prednisolone
suppositories may be used
 Topical therapy should be continued for 1
week after symptoms have resolved and
then reduced gradually over 1-2 weeks
 If no response to topical steroids, oral
therapy or ASA enemas may be useful
UC: Treatment of Acute Episodes
Moderately Severe Disease - and what may patients need to be maintained on
 Prednisolone 20-50mg orally daily (reduce
after 8-12 weeks of response)
and/or
 An 5-aminosalicylate, such as:
Mesalazine 1.5-4g daily (in 2-4 divided doses)
or Olsalazine 1g bd
or Sulphasalazine 2-4g daily (in 2-4 divided doses)
or Balsalazide 2.25g tds
 Some patients may require maintenance
dosing with oral steroids (e.g. Prednisolone
5-15mg daily)
UC: Treatment of Acute Episodes
Severe Disease
 Hydrocortisone 100mg IV 6 hourly for 5-7
days
 Severe deterioration or the development of
toxic megacolon usually requires colectomy
 Avoid loperamide or other antimotility
agents as these may precipitate toxic
megacolon
UC: Maintenance Treatment - when needed, dosing comparable to acute, which drug prolongs remission
Mild disease, maintenance usually not required
Severe or Moderately severe disease usually
requires a 5-aminosalicylate, such as
Mesalazine 750mg–2g daily (in 2-3 divided doses)
or olsalazine 500mg bd
or sulphasalazine 2g daily (in 2-4 divided doses)
or balsalazide 1.5g-3g bd
 Maintenance dose for 5-ASAs is usually at the
lower end of these ranges, with instructions to
double the dose for mild exacerbations
 Azathioprine may induce prolonged remission in
patients experiencing frequent relapses,
otherwise colectomy is required
Crohn’s: Treatment
What’s different to UC ?
Although they have a role, the 5-ASAs are
less effective in Crohn’s than in UC
Although steroids are effective, the risks
from long term use mean that patients
with Crohn’s are often managed with
immunomodulators
 Methotrexate
 Azathioprine / mercaptopurine
 Cyclosporin
 Anti-TNFs
Crohn’s:
Treatment
Approach to
treatment
Approach to
treatment based
on severity of
Crohn’s
Note: Asacol® and
Pentasa® = Mesalazine brands
what does eTG say on corticosetroids for crohns
Azathioprine & Mercaptopurine- MOA, place in therapy, adverse affects and whose at risk
Mode of action involves induction of T-cell
apoptosis by modulating cell (Rac1) signalling
Main role is as a “steroid sparer” in UC & Crohn’s
For example:
 Where ≥ 2 courses of steroids required per year
 If relapse occurs when Prednisolone dose falls <15mg
 If relapse occurs within 6 weeks of stopping steroids
Genetic variation in ability to metabolise
 Measuring TPMT levels may have a role in helping to
identify those who are at greatest risk of toxicity
Monitor FBCs and LFTs
Ensure patients aware of the signs of  WCC
Suppressed White Cell Count for immuno modulartors - signs, sypmtoms, what must patient do
Many drugs, not just some of
those used in UC / Crohn’s can
suppress white cell count
Patients should be aware of
potential warning signs and seek
medical attention if:
 Persistent sore throat
 Persistent / high fever
 Cuts / grazes that do not heal
normally
Patients should also ensure they
attend for required monitoring
Methotrexate - MOA, main role, when used, practice points, which IBD condiction
Mode of action involves inhibition of cytokines
and eicosanoids involved in inflammation
Again main role is as a “steroid sparer”
More evidence in Crohn’s than in UC
Some centres use only in those refractory to
azathioprine or mercaptopurine
Weekly dose essential to minimise toxicity
Monitor FBCs and LFTs
Ensure patient awareness of signs of  WCC
eTG on methotrexate for IBD
Tumour Necrosis Factor Inhibitors when used in IBD
 Crohn’s when moderate to severe, fistulising and
refractory to standard therapy
 UC when moderately severe to severe, in patients
who have had an inadequate response to
conventional therapy
Tumour Necrosis Factor Inhibitors - % response, time for response, duration of therapetuic effect from treatment, duration of treatment generally
Clinical trials have shown response rates to infliximab of 60% to
70% in patients with refractory active Crohn's disease.
 Response to a single dose is limited to 6 to 8 weeks. The
benefits of one infusion generally last for 6 to 8 weeks.
Treatment may consist of a single dose, or repeated treatments
may be necessary, depending on the degree and duration of the
clinical response
Tumour Necrosis Factor Inhibitors- dose, names, new one
eTG states:
 Infliximab therapy has also been shown to be
effective for the maintenance of remission for both
luminal and fistulising Crohn's disease. A typical dose
used would be:
 infliximab 5 mg/kg (adult or child) by IV infusion
over 2h, every 8 weeks.
AMH states:
 adalimumab in Crohn’s disease, SC, initially 160 mg
on day 0 (or 80 mg on days 0 and 1); then 80 mg on
day 14. If improvement in the first 4 weeks, give
40 mg on day 28 then 40 mg every 2 weeks
Another anti-TNF, golimumab is in IBD trials

dose repeated after 1st in two weeks, another repeat after 6 weeks.
Tumour Necrosis Factor Inhibitors - adverse effect common and uncommon
- infections including TB, lymphoma
most common- fatigue, fever, GI disturbances
- worsening congestive heart failure, countrainidicated in 3 and 4 stage
-delayed hypersensitivety
- SLE in less in 1% - but 30-50% for antibodies
Cyclosporin - use in IBD, monitoring, adverse effects
Mode of action involves inhibition of
calcineurin, preventing expansion of T-cells
Has a rapid onset of action
Evidence of benefit in UC, but not in Crohn’s
May be used as a “salvage” therapy when
alternative is surgery
Monitor renal function and BP (reversible renal impariment, and hypertension)
Risk of opportunist infections
Metronidazole
- role in chrohns
- adverse effects, nausea, diarrhea, metallic taste
-avoid alcohol
- issue with LT use and associated paraesthesiae and peripheral nethropathy
UC & Crohn’s: Surgery- when, percent
Surgery may be required for some patients
In UC, 20-30% of patients with pancolitis will
require colectomy
In Crohn’s 50% of
patients require
surgery within 10
years of onset,
many will require
further operations
UC & Crohn’s: Other issues
Nutrition:
 Patients are prone to malnutrition
 May require nutritional support
 Weight and BMI should be monitored
 Check Vitamin B12 levels if ileum resected
Osteoporosis:
 Malabsorption
pre-disposes to # risk
 Use of steroids adds
to this risk
Smoking
 Cessation beneficial in Crohn’s
UC & Crohn’s: Other treatments
Leukapheresis
 Blood drawn from patient
 Leukocytes removed
 Remaining blood returned to patient
 Mainly studied in UC, but some work in Crohn’s,
 Some benefits reported
 Quality of evidence not great
 Even where response good, appeared to have limited
duration of effect
UC & Crohn’s: Other treatments
Extracorporeal photophoresis
 Blood drawn from patient
 Platelets and red-cells separated and returned to
patient
 Buffy-coat cells (containing leukocytes) treated with
photosensitizer (“psoralen”) and exposed to UV light
 This arrests cell proliferation leading to cell death
 Dying cells returned to patient
 Patient then mounts immune response which
interferes with pathogenesis of Crohn’s
 Clinical data very limited, currently under further
research
Inflammatory Bowel Disease
Signs and symptoms
requiring hospital
admission:
 Severe abdominal pain
 Severe diarrhoea (>8x/day)
+/- bleeding
 Dramatic weight loss
 Bowel obstruction
 Fever / other signs of
systemic disease