IBD Flashcards
what is IBD?
- Chronic disease
- Causes inflammation of the digestive tract
what are the two main forms of IBD?
– Ulcerative Colitis
– Crohn’s Disease
what is the key difference between UC and CD?
Key differences between the two are the LOCATION and
EXTENT of the inflammation
what complications occurs in UC?
pancolitis- all
distal colitis-
proctitis-
how/where does CD affect the intestines?
terminal ileum
ilecolon- patchy inflam and stricture
colon
what is CD?
Typically involves the distal ileum or colon but can affect the ENTIRE digestive tract.
* Starts as an inflammatory lesion which develops into ulceration of the mucosa and then progresses to deeper
layers
what is CD characterised by?
– Areas of healthy tissue .v. diseased tissue giving characteristic
‘skip lesions’
– Cobblestone appearance
what is the most common type of IBD?
UC
what is UC characterised by?
– Characterised by diffuse inflammation and crypt abscesses
how often does IBD occur?
Both diseases following a relapsing/remitting
course
* Patients can be well going long periods without (or with very few) symptoms, however, this is often followed by periods of active disease when symptoms flare up
where does CD affect?
– Typically involves distal ileum,
proximal colon
* Can affect the entire digestive tract
– Inflammation can go through entire
thickness of the bowel wall
where does UC affect?
– Only affects the colon
– Diffuse inflammation
– Affects the colonic mucosa
how do signs and symptoms vary for IBD?
depending on the site and severity of inflammation
what are the overlapping symptoms in UC and CD?
– Abdominal pain/cramping
– Diarrhoea
– Fever
– Tiredness/Fatigue
– Weight loss/Reduced appetite
– Mouth sores
where does abdominal cramping affect?
- In U.C this is usually in the lower abdomen and
tends to be a colicky type pain. Pain is usually
severe in severe colitis. - In C.D pain is often in the RLQ and more
prevalent than in U.C
what causes abdominal pain in IBD?
Inflammation/ulceration can affect the normal
movement of the intestines/colon and its
contents resulting in pain/cramping
is diarrhoea common in IBD?
– Common problem
– Intestinal cramping can contribute to it
– Blood can be present
– U.C: tend to get bloody, mucoid diarrhoea due to the
inflammation of the mucosa
– Can occur during the night as well
why would someone get a fever with IBD?
– Usually low grade and due to underlying inflammation
(and or infection)
why would someone be tired with IBD?
– Can be in part due to the development of
anaemia
why would weightloss/ reduced appetite be a probelm in IBD?
– Due to reduced ability to digest/absorb food
– Often get malabsorption
– Many IBD patients have a reduced BMI
what are some extra-intestional manifestations of IBD?
Inflammation of the skin, eyes, joints and liver
failure to thrive in children
what are the potential complications of IBD?
– Increased risk of colon cancer
– Surveillance monitoring is in place as per NICE
recommendations with colonoscopies for this patient
group
– Malnutrition
– Due to excess diarrhoea and malabsorption
– Anaemia
– Iron deficiency; bleeding from the GI tract due to
inflammation
risks ass with medication
blood clots
primary sclerosing cholangitis
what are potential complications of CD?
Narrowing of the bowel wall
* Obstruction
– Due to strictures caused by spasms, scarring, oedema
and luminal narrowing, this can lead to fistulas
* Fistulas
– Abnormal connection between two areas of the intestine
– Ulcers
– Anal fissures and perianal lesions such as
skin tags and abscesses
what are the potential complications of UC?
– Toxic megacolon
– Dilation of the colon causing severe abdominal
pain, tenderness and distention
– At a significant risk of bowel perforation
– Associated with a 50% mortality rate
– Perforated colon
what are the risk factors of IBD?
– Age
– Family History
(10 – 20%)
– Infection (50%)
– Smoking
– Medication
* NSAIDS
what are the causes for IBD?
– Not well understood
– Genetics
– Environmental
triggers
– Autoimmune
what type of IBD has an autoimmune component?
CD
what are environemtal risk factors for IBD?
- Smoking
– Associated with increased risk of developing C.D whereas with U.C at a greater risk of developing if you don’t smoke - Diet
– Certain foods might affect the already damaged mucosal lining and trigger a flare e.g. caffeine, spicy, fatty foods
how is diagnosis made?
Based on a combination of factors, not just
one element:
– Examination and history taking
* Abdomen may be tender and slightly distended;
PR may show presence of blood
– Colonoscopy/sigmoidoscopy
* Biopsies
* 2 biopsies from 5 different sites
– Stool cultures
* Relapses can be associated with pathogens,
therefore, always check in a flare
what blood test will be done for diagnosis and why?
Anaemia
* FBC: looking for presence of iron or B12 deficiency due to chronic
inflammation, blood loss and/or malabsorption
– Inflammation
* Increase in WCC, platelets, ESR an CRP (all useful markers of
active inflammation)
– LFT’s may be abnormal
* Reduced albumin due to malabsorption
* Raised ALP, AST, ALT and bilirubin due to primary sclerosing
cholangitis
– U&E’s
* Dehydration and electrolyte imbalances
– Faecal calprotectin
* Calprotectin: protein released into faeces when neutrophils gather
at the site of inflammation
* Help guide management and diagnosis
* Determine if urgent imaging is needed and has prevented
unnecessary referrals for colonoscopy
how will x-rays and endoscopy help in diagnosis?
Abdominal x-ray
– Rule out toxic megacolon
* Endoscopy
– If you suspect inflammation is higher up in the GI
Tract
what is it important to ruele out in the differential diagnosis?
– Colorectal cancer
– Other forms of IBD/colitis e.g. ischaemic
– Infection
– Diverticular disease
– Irritable bowel syndrome
– Appendicitis
– Ectopic pregnancy
– Pelvic inflammatory disease
what general support should you give to someone with IBD?
– Fertility and contraception
– Monitoring
– Advice
– Interactions
– Side-effects
what are general supportive issues that are important to inform patient of?
- Possible delay of growth and puberty in children
and young people - Diet and nutrition
– Avoid fatty, sugary foods – encourage a healthy high fibre diet - Fertility
– Can be reduced in active disease (women) - Prognosis
- Side effects of their treatment
- Cancer risk
- Smoking cessation
when are aminosalicylates mostly used?
UC
dont use a lot in CD
when are antibiotics used in therapy?
- Used if underlying infection
- In fistulating C.D
what is the treatment aim in IBD?
- Heal the inflammation and in turn reduce
symptoms during a flare up i.e. induce
remission - OR
- Prevent flare ups from happening
what should you treat a patient when inducing remission in CD?
Corticosteroids
– Offer monotherapy with a conventional glucocorticosteroid (prednisolone, methylprednisolone or intravenous hydrocortisone) to induce remission in people with a first presentation or a single inflammatory exacerbation of Crohn’s disease in a 12-month period.
what should you offer In people with one or more of distal ileal, ileocaecal or right-sided colonic disease who decline, cannot tolerate or in whom a conventional glucocorticosteroid is
contraindicated?
budesonide
less effective but fewer side effetcs
what should you consider when prescribing corticosteroids as treatment?
When long term corticosteroid therapy is used in some chronic diseases, the adverse effects of treatment may become greater than the disabilities of the disease.
* To minimise side-effects the dose should be kept as low as possible and used for the shortest possible time
what are some early and delayed side effects of corticosteroids?
- Early effects
– Acne
– Oedema
– Sleep & mood disturbance
– Dyspepsia
– Impaired Glucose tolerance - Delayed Effects
– Cataracts
– Osteoporosis & osteonecrosis
– Myopathy
– Susceptibility to infection
– Moon face
what are glucocorticoids side effects?
– Diabetes
– Osteoporosis
– Muscle wasting
(myopathy)
– Peptic ulceration
and perforation
– Psychiatric reactions
what are mineralocorticoid side effects?
– Hypertension
– Sodium retention
– Water retention
– Potassium loss
(more of an issue
with longer term
use)
– Calcium loss
when do you use oral corticosteroids?
Moderate to severe– Budesonide potent corticosteroid with reduced systemic toxicity -only effective in ileal disease due to site of release– Tapering – the more severe the exacerbation the slower the schedule should be. Average 5 mg / week– May need to adjust / slow down to cover introduction of aza/6mp (3 months to effect)
when do you use topical steroids?
Depend on the site of inflammation – used more in U.C– Suppositories - proctitis
when do you use IV steroids?
– Severe; patients are vomiting – Hydrocortisone
why may adrenal suppression occur? what are the signs and symptoms?
Acute withdrawal after a prolonged period can
lead to acute adrenal insufficiency, hypotension or death.
when should gradual withdrawl be used in steroid treatment?
– Received more than 40mg of prednisolone (or equivalent) for
more than 1 week
– Been given repeated doses in the evening
– Received more than 3 weeks treatment
– Recently received repeated courses
– Taken a short course within 1 year of stopping long term therapy.
why is osteoporosis linked to IBD?
due to higher levels of corticosteroid use but also:
– Lower BMI
– Reduced physical activity
* Increased risk of poor posture, balance and muscle weakness
– Disease activity
how do you manage osteoporosis in IBD?
– Management of underlying disease, good nutrition, avoidance of steroids as far as possible.
– Lowest effective dose or steroids for shortest time possible
– Aza/6MP use at early stage
– Biological therapy or surgery should be considered if patient is unable to maintain a steroid free remission
when should bisphosphonates be given in patients with osteoporosis in IBD?
– When on steroids for all >65 years
– If <65 but need steroids for >3 months
– Stopped when steroids stopped unless indicated on other grounds
how should you induce remission in a patient with crohn’s disease?
In people who decline, cannot tolerate or in whom a conventional glucocorticosteroid is contraindicated,consider 5-aminosalicylate treatment for a first presentation or
a single inflammatory exacerbation in a 12-month period.
when would you consider as an add on treatment when inducing remission in CD?
Consider adding azathioprine or 6-mercaptopurine to a
conventional glucocorticosteroid or budesonide to induce
remission of Crohn’s disease if:
– there are two or more inflammatory exacerbations in a
12-month period, or
– the glucocorticosteroid dose cannot be tapered
what should you assess before add on treatment?
Assess TPMT activity before offering azathioprine or
mercaptopurine. Do not offer azathioprine or 6-mercaptopurine if TPMT activity is deficient (very low or absent). Consider azathioprine or mercaptopurine at a lower dose if TPMT activity is below normal but not deficient
when should you consider adding methotresate to steroid to induce remission in CD?
people who cannot tolerate azathioprine or
mercaptopurine, or in whom TPMT activity is deficient.
what should people be warned about on azathioprine?
– Patients should be warned about the possibility of bone marrow suppression i.e. infection or unexplained bleeding or bruising
– Should report to prescriber immediately
what monitoring should be done for azathioprine?
– TPMT before prescribing
– FBC every 2 weeks for 3 months, then 3 monthly
– ALT* Increases in response to drug toxicity
– CRP * If levels reduce – good marker that the treatment being used is being successful
– U&Es* Check renal function for excretion of the drugs
what are the main interactions to be aware of for azathioprine?
Allopurinol
– high risk of increased toxicity.
– Life-threatening reaction
* Warfarin
– Possible reduction in INR
– Monitor closely and remember may take 3 months for effect
* Trimethoprim / co-trimoxazole
– Increased risk of thrombocytopenia & neutropenia – avoid
* Clozapine
– Increased risk of agranulocytosis - avoid
what is 6MP?
Metabolite of azathioprine
* Better tolerated and may be more effective
than AZA
* Interactions, side effects and monitoring –
as for azathioprine
what is TPMT?
Thiopurine Methyl Transferase
* Enzyme responsible for metabolism of azathioprine / 6MP
what happens to people with no TPMT enzyme?
can become severely ill if treated with normal doses of thiopurine drugs
what should you use if methotrexate is not tolerated?
Use if Azathioprine / 6MP not effective or not tolerated
* Avoid in women of child bearing potential as it is teratogenic
what monitoring needs to be done with methotrexate?
– FBC & LFTS before and every month
what are the side effects of methotrexate?
bone marrow sup
liver tox
pulmonary tox
GI tox
what are the interactions with methotrexate?
Drugs which reduce the renal excretion of
methotrexate including NSAIDs
– Drugs with antifolate activity such as
trimethoprim
what is TNF-a ? what does it do?
umour necrosis factor alpha (TNF-α) is a pro-
inflammatory mediator:
– Over expressed in IBD
– Partly responsible for the chronic inflammatory processes in the
intestinal tissue
– Therefore indicated in certain patient groups who have failed
previous therapies/other therapies not appropriate
when is TNF-a used?
Now recommendations for use to induce remission as a
monotherapy or in combination with an
immunosuppressant
what are biologics?
Large, complex molecule
* Sometimes referred to as biotherapeutics or
biopharmaceuticals
* Chemically synthesized
– Made from protein and other substances which occur in nature
– Manufactured in a living system e.g. modified plant and animal cells
what are the main biologics used in IBD?
Infliximab - Remicade®
* Adalimumab - Humira
how do you prescribe biologics?
Prescribed by BRAND
who are infliximab and adalimumab recommended for?
- as treatment options for adults with severe
active Crohn’s disease - whose disease has not responded to
conventional therapy or - who are intolerant of or have contraindications
to conventional therapy.
how should these main biologics be given?
as a planned course of treatment until
treatment failure (including the need for
surgery), initiated by a specialist or
– until 12 months after the start of treatment,
whichever is shorter.
who are biologics C/I in?
Crohn’s related abscess (infection)
– Moderate to severe heart failure
– Multiple sclerosis (exacerbates symptoms)
– TB
– Need to check for dormant TB as they significantly aggravate the dormant cells, therefore screening prior to treatment is essential
– Lymphoma
– Recurrent infections
– Hepatitis B infection (adalimumab only)
– Active infection
what are the signs and symptoms of an infusion reaction of infliximab?
itching, fever, chills, chest pain, changes in blood pressure and problems with breathing (monitor for signs of throughout).
– May be attenuated by reducing the rate of infusion or by stopping it for a while
– Rarely, reactions are severe and the infusion must be stopped.
how is adalimuab given?
s/c injection
– Patients can inject at home (no need to come
to hospital as with infliximab)
– Watch for injection site reactions and
infections
what are the side effects of these biologics?
– headaches
– sore throat
– swallowing problems
– aches and pains in the muscles and joints
– swelling in the legs or face
– nausea, diarrhoea and abdominal pain
May take up to six months to be completely removed from the body, therefore, still monitor for side-effects after stopping therapyi
immunosuppressive
what are the long term effects of these biologics?
– Possible increased risk of developing lymphoma
– Patients with COPD & heavy smokers may have an increased
risk of cancer with infliximab or adalimumab
– May exacerbate multiple sclerosis
what is an example of an anti-tnf agent and when is it used?
Golimumab - Simponi®
Is licensed in moderate to severe ulcerative
colitis where other treatment has failed or is
not tolerated
s/c thigh to stomach
what is Vedolizumab - Entyvio?
Gut selective integrin blocker – over production in WBC causes inflammation. Vedolizumab stops the WBC from entering the gut lining and selectively targets the gut = fewer
side-effects.
* Possible to use for adults with moderate to severe CD if anti-TNF therapy is not suitable, contra-indicated or has not worked well enough
what is Ustekinumab - Stelara®? how does it work?
Moderate to severe active Crohn’s disease
– Where anti-TNF therapy not tolerated/CI
– IV infusion initially followed by s/c injection
* Targets IL-12 and IL- 23
– Which are increased in IBD and contribute to ongoing gut inflammation
– They therefore bind to IL-12 and 23 reducing
inflammation
what are biosimilars?
Copy of an original biological agent (not
identical) already licensed for use
– Similar in terms of quality, safety and efficacy
– Not considered generic equivalents because the size and complexity of the medicine and the way they are produced results in natural variability in molecules
prescribed by brand
when can person switch from origional product to biosimilar?
– Only in patients who are in remission or are having a stable
clinical response to originator product
– Same dose and dosing interval
– Based on evidence from use in RA and ankylosing spondylitis as
well as IBD
– Trials showed no difference in safety or effectiveness
– Currently trials ongoing in IBD
– Patient choice
what is the maintenance therapy in CD?
patient specific
– Azathioprine or mercaptopurine
– Methotrexate
– Infliximab or adalimumab
how do you induce remission for mild to moderate proctitis?
– Topical aminosalicylate alone
– Consider adding oral aminosalicylate to topical agent (more
effective than either agent alone)
– Consider oral aminosalicylate alone (least effective)
* Comes down to patient choice
* Once daily oral dosing has also been shown to be as effective as
conventional dosing and is as safe
what if the patient cant tolerate/ decline remission therapy in proctitis?
– A time-limited course of topical CCS OR
– Consider oral prednisolone (if don’t respond to other treatments)
how do you induce remission for mild to moderate proctosigmoiditis and left-sided ?
– Topical aminosalicylate first line
– High-dose of oral aminosalicylate OR
– Switch to high-dose oral aminosalicylate and a time-
limited course of topical CCS
– If unable to tolerate aminosalicylates, consider time-
limited topical or oral steroid
how do you induce remission in mild to moderate extensive disease?
– Topical aminosalicylate + high dose oral
aminosalicylate
– Stop topical and give high dose oral
aminosalicylate with a time-limited course of
oral CCS
when is tacrolimus C/I?
CI if history of hypersensitivity to macrolides (as
tacrolimus is a macrolide antibiotic)
what monitoring needs to be done for tacrolimus?
Drug levels
– Blood pressure – can cause hypertension
– ECG
– U&E’s, renal, liver function; coagulation and
neurological parameters
what is the general advice for tacrolimus?
– Avoid excessive exposure to UV light including
sunlight
– May affect performance of skilled tasks e.g. driving
– Take 1 hour before or 2 – 3 hours after a meal
– Avoid grapefruit and grapefruit juice (increase levels)
– Report signs of bone marrow suppression
– Avoid in pregnancy; contraception is required during
treatment and for at least 3 months after stopping
treatment
– Passes through breast milk
– Potassium sparing medications may exacerbate
tacrolimus induced hyperkalaemia
how do you induce remission in severe UC?
Step 1
– IV CCS
– Consider ciclosporin
* Can not tolerate CCS/CI/decline
* Step 2
– Add IV ciclosporin to IV CCS
* No improvement with 72 hours
* Symptoms worsen
– Consider biologic or surgery
what is ciclosporin?
Used to induce or maintain remission
* Often notice improvement within a few days with IV
administration or within a few weeks with oral agent
* Prescribe by brand
what interactions does ciclosporin have?
– Amiodarone
– Atorvastatin
– Carbamazepine
– Clarithromycin
– Dabigatran
– Diclofenac
what monitoring does ciclpsporin require?
– Toxicity
– Drug associated mortality is 3%
– Check serum cholesterol must be checked prior to
starting (low levels can predispose to seizures)
– Monitor
* Blood pressure – causes hypertension
* Weekly for 4 weeks, then 2 weekly for 3 months
– Renal function
– Liver function
– Serum potassium, magnesium
– Drug levels
what is budesonide?
Second-generation CCS are starting to
emerge as a treatment option
* Multi-matrix system – Cortiment® MMX®
– Licensed for mild to moderate active U.C in
adults where 5-ASA treatment is not sufficient
how do you maintain remission in UC?
- Proctitis and proctosigmoiditis
– Topical and/or oral aminosalicylates (daily or
intermittent) - Left-sided and extensive
– Low dose oral aminosalicylate (superior to
placebo)
when do you consider oral aza or mercaptopurine to maintain remission in UC?
– After 2 or more exacerbations in 12 months requiring treatment with systemic CCS
* OR
– If remission is not maintained by aminosalicylates
what should you give after a single epsoide of acute severe UC?
– Azathioprine or mercaptopurine
– Oral aminosalicylates as second line
what medicne issues are there with UC?
Potassium levels & supplementation
– Supplements may be required if levels are low
– Key patient safety area
– Too much can cause life-threatening arrhythmias
– Avoid M/R formulations as they are associated
with GI ulceration
– Dose against clinical parameters
– Oral agents include Sando K and Kay Cee L
* Osteoporosis prevention & treatment
what interactions should you be aware of for UC? especially for excretion
Consider MTX is renally excreted, therefore any
medication that can reduce renal function can
increase MTX levels
* Main 3 drugs = NSAIDs, Diuretics and ACEi
what should you consider in UC with pregnancy or conception?
Consider teratogenic effects and also due to
malabsorption most effective types of contraception
– Many medications used in the management of IBD are teratogenic
* Azathioprine has emerging evidence for use in pregnancy
* If male, need to consider paternal risk
– Good pregnancy planning, speak with specialist
– During pregnancy also have additional dietary and nutritional needs
what vaccinations should patients with IBD get?
- Influenza (inactivated) vaccine annually
- Pneumococcal vaccine
- Hepatitis B vaccine (in all HBV seronegative
patients) - Human papillomavirus
- Varicella zoster vaccine (if no history of shingles
or chicken pox in VZV seronegative patients)
what considerations was made to patients medications during covid 19
Corticosteroids
* Avoid if possible but will still be needed for some –
they should observe shielding guidelines when on
prednisolone when dose is > 20mg daily
* Consider using budesonide 9mg/day for flares
– MMX
– Entocort
– Budenofalk
– Immunomodulators
* Azathioprine
* 6-Mercaptopurine
* Methotrexate
– Anti-TNF therapy
* Adalimumab
* Infliximab
