Week 4/5 - F - I.B.D (Treatment - lifestyle, drugs (5-ASA, steroids, immunosuppressants, biological), surgery) - Crohn's and U.C

Question 1

What are the aims of therapy when treating inflammatory bowel disease?

Answer 1

Control inflammation and heal mucosa Try to induce remission and restore normal bowel habit Improve quality of life Balance the effects of the disease with side effects of treatment Avoid long term complications

Question 2

Treatment strategies for IBD * Lifestyle advice * Drugs * Surgery What lifestyle advice is given for the treatment of IBD?

Answer 2

Avoid smoking in Crohn’s disease (Although smoking technically may reduce incidence of UC, you cannot exactly promote it for this lol) Avoid NSAIDs

Question 3

What are the drug therapy options for UC and Crohns?

Answer 3

Ulcerative colitis * 5-ASA - mesalazine * Steroids * Immunosuppressants * Anti-TNF therapy Crohn’s * Steroids * Immunosuppresants * Anti-TNF therapy

Question 4

ULCERATIVE COLITIS What is the mainstay remission-induction / maintenance treatment for ulcerative colitis in mild disease? What are they chemically related to and how do they work? Give examples?

Answer 4

5-ASA are also known as Aminosalicylic acids- they are used to induce remission / maintenance treatment of ulcerative colitis usually in mild disease They are chemically related to aspirin, and work by damping down the inflammatory process, so allowing damaged tissue to heal. Examples include - sulfasalazine or mesalazine

Question 5

What are the different ways in which 5-ASA are given? What if 5-ASA treatment does not work to induce remission?

Answer 5

5-ASA is usually given topically either as a suppository or enema IF this does not work, oral formulations of 5-ASA can be given If remission is not achieved within 4 weeks, switch to a topical or an oral corticosteroid to achieve remission

Question 6

What is used to induce remission of UC in moderate disease? What is then given as maintenance treatment?

Answer 6

If moderate UC, give oral corticosteroids eg prednisolone, taper down dose Maintenance is then achieved with 5-ASA (eg sulphasalazine or mesalazine)

Question 7

What are the side effects associated with 5-ASA treatment?

Answer 7

5-ASA - can cause rash, haemolysis, hepatitis and pancreatitis Can also cause paradoxical worsening of UC

Question 8

What classified as a severe case of Ulcerative colitis? What is used to induce remission in these cases? (1st line and second line)

Answer 8

Severe cases of UC (truelove and witt criteria) >/= 6 bloody diarrhoea episodes per day with systemic signs of illness These patients should be treated in hospital * IV steroids are usually given first line here eg hydrocortisone or methylprednisolone * If these fail are are contraindicated, IV ciclosporin is usually given or surgery

Question 9

Following a severe relapse or >/= 2 course of steroids per year, what is then indicated for maintenance therapy of ulcerative colitis?

Answer 9

Following a severe relapse or >=2 exacerbations in the past year , an immunosuppresant is usually recommended to maintain remission Oral azathioprine or oral mercaptopurine is usually the drug of choice

Question 10

For patients intolerant of immunomodulation (eg due to side effects) or developing symptoms despite immunomodulation what can be given as maintenance therapy for ulcerative colitis?

Answer 10

Biiological agents are then recommended Anti-TNF alpha (monoclonal antibodies) therapy eg infliximab This reduced hospitalisation and the need for surgery in severe refractory cases of UC

Question 11

CROHNS DISEASE What is used to induce remission in Crohn’s disease? How long is it given for?

Answer 11

Oral corticosteroids can be given for mild/moderate disease eg prednisolone If severe give IV steroids eg hydrocortisone or methylprednisolone * Give these as a short course * High dose intitially * reduce dosage over 6-8 weeks

Question 12

What are different side affects associated with steroid use?

Answer 12

* Musculoskeletal - Avascular necrosis, Osteoporosis * Cutaneous - Acne, Thinning of skin * Metabolic -Weight gain, Diabetes, Hypertension * Neuropsychiatric - eg psychosis, anxiety , delirium * Cataracts * Growth failure

Question 13

What is an alternative approach to the use of steroids used to induce remission? an option that is carried out in children but not effective in adults How long is it carried out for?

Answer 13

In children with mild-moderate disease, a dietary approach to inducing remission remains an option in children * The preferred method of treatment is known as the Enteral diet where the patient is asked to trial a liquid only diet to induce remission. * This diet is normally carried out from a minimum of two weeks to a maximum of eight. * Once remission has been induced, normal foods can start to slowly be reintroduced to the patient’s diet to understand which foods cause symptoms to occur

Question 14

Corticosteroids should not be used to maintain clinical remission due to the extensive side effect profile * In UC, 5-ASA (Aminosalicyates) are used to maintain remission however have no role in Crohn’s disease * Azathioprine is given to maintain remission in UC if patient has a severe relapse or required >/=2 steroid course / year When is azathioprine given in Crohn’s disease?

Answer 14

Azathioprine, a type of immunosuppressant from the thiopurine family is given if the patient is * refractory to steroid treatment * relapsing when tapering down on steroids * requiring >/= 2 steroid course per year The thiopurines are effective in maintaining remission of Crohn’s

Question 15

How does azathioprine work?

Answer 15

Azathioprine inhibits purine synthesis. Purines are needed to produce DNA and RNA. By inhibiting purine synthesis, less DNA and RNA are produced for the synthesis of white blood cells, thus causing immunosuppression.

Question 16

What drug should be avoided during azathioprine use?

Answer 16

Purine analogues such as allopurinol inhibit xanthine oxidase, the enzyme that breaks down azathioprine, thus increasing the toxicity of azathioprine and should be avoided during azathioprine use

Question 17

What are the side effects of azathioprine? Which cancers is it associated with a small incease in the risk of and therefore must be discussed with the patient?

Answer 17

Side effects of azathioprine include * Pancreatitis * Hepatitis * Bone marrow suppression - Leucopenia Monitoring is required when taking this drug (FBC, LFTs, U&Es) There is a small increase in the risk of lymphoma and non-melanoma skin cancer which must be discussed

Question 18

Which drugs can be given second line for maintenance therapy in Crohn’s should azathioprine fail?

Answer 18

Immunomodulators Azathioprine or mercaptopurine (both thiopurines) is used first-line to maintain remission Methotrexate is used second-line

Question 19

When are biological agents recommended in the treatment of both UC and Crohn’s disease? Give two examples

Answer 19

They are recommended in patients where conventional therapy has not been responded to or not tolerated and are effective in maintain remission Two examples include infliximab and adalimumab

Question 20

How do anti-TNF alpha biological agents work in treating inflammatory bowel disease?

Answer 20

Anti-TNFa agents work by causing cytotoxicity to CD4+ T cells. * As mentioned in the previous set of cards, CD4+ cells play an important role in modulating the immune response of the adaptive immune system * (CD4+Tcells will differentiate to become Th1 and Th2 implicated in Crohns and UC respectively) The toxicity of anti-TNFa drugs to these cells therefore decreases the patient’s immune response hence decreasing disease activity

Question 21

What is the difference in onset of action between azathioprine and anti-TNF alpha drugs?

Answer 21

Azathioprine has a slow onset of action - approx 16 weeks Anti-TNF alpha has a rapid onset of action

Question 22

What are different side effects of anti-TNFalpha drugs and when are they absolutely contraindicated?

Answer 22

Anti-TNFa agents increase the risk of infections, bone marrow suppression and are absolutely contraindicated in patients with active/latent TB, sepsis and underlying malignancy

Question 23

SURGERY When is surgery indicated in the treatment of inflammatory bowel disease? (emergency or elective surgery)

Answer 23

Emergency surgery is recommended in IBD for * Failure to respond to medical therapy * Small bowel obstruction * Abscess formation * Fistulae * Toxic megacolon Elective surgery is recommended in IBD for * Failure to respond to medical therapy * Dysplasia of colon mucosa * Growth retardation in children

Question 24

Can IBD be cured through surgery?

Answer 24

Surgery is needed at some stage in about 20% of patients with UC and * UC can be cured by surgery Surgery is needed by more than half of patients at least once with Crohn’s * Crohn’s is managed through surgery but never cured

Question 25

It is important to minimise the amount of bowel resected when carrying out surgery in Crohn’s What can repeated surgery of the small intestine result in? How long will the bowel be? What length usually indicates a need for home parenteral nutition?

Answer 25

Repeated surgery of the small intestine can result in Short bowel syndrome, small intestine <200cm When the small intestine is <50cm, this usually indicates the need for home parenteral nutiriton as the patient cannot absorb enough nutrients to match physiological demands

Question 26

What are the different surgical options for Ulcerative colitis?

Answer 26

The option of a Proctocolectomy and terminal ileostomy or Restorative proctocolectomy and ileo-anal pouch or Coloectomy with ileorectal anastamosis (not curative as rectum still present)

Question 27

Curative options * Proctocolectomy with ileostomy * Proctocolectomy with ileo-anal pouch The ileo-anal pouch, provides conitnence however it is not a rectum What may patients complcain of? If there is pouch failure, what can be carried out?

Answer 27

Restorative proctocoloectomy with ileo-anal pouch - may provide the possibility of long term continence however pouch opening frequency may still be often and can become infected If there is pouch failure, it can be reverse to ileostomy