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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 |
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IBD aetiology, and agrevating factors - genetics
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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 |
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Areas of bowel affected
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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 |
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what are the incidences of diffferent features of IBD
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crohns - fistulas, fissures
UC polyps |
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what are the common extra intestinal features
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Diagnosis is based on
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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 |
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Ulcerative Colitis (UC) - what is affected, course of disease, theory on cells affected
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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 |
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UC: Clinical Manifestations
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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 |
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classifying severity of UC
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Crohn’s Disease - invovlvement of what
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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 |
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Crohn’s: Clinical Manifestations
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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 |
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UC & Crohn’s Management - treatment aims, determinants, emengency
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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 |
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5-Aminosalicylates (5-ASAs) - esp useful for, types, countraindication
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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 |
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5-Aminosalicylates (5-ASAs) - adverse effects and differculty, different drugs, which one not interchangable and why
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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 |
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UC treatment rough guide - approach
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approach is severity
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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 |
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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) |
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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 |
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UC: Maintenance Treatment - when needed, dosing comparable to acute, which drug prolongs remission
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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 |
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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 |
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Crohn’s:
Treatment Approach to treatment |
Approach to
treatment based on severity of Crohn’s Note: Asacol® and Pentasa® = Mesalazine brands |
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what does eTG say on corticosetroids for crohns
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Azathioprine & Mercaptopurine- MOA, place in therapy, adverse affects and whose at risk
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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 |
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Suppressed White Cell Count for immuno modulartors - signs, sypmtoms, what must patient do
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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 |
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Methotrexate - MOA, main role, when used, practice points, which IBD condiction
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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 |
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eTG on methotrexate for IBD
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Tumour Necrosis Factor Inhibitors when used in IBD
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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 |
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Tumour Necrosis Factor Inhibitors - % response, time for response, duration of therapetuic effect from treatment, duration of treatment generally
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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 |
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Tumour Necrosis Factor Inhibitors- dose, names, new one
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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. |
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Tumour Necrosis Factor Inhibitors - adverse effect common and uncommon
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- 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 |
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Cyclosporin - use in IBD, monitoring, adverse effects
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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 |
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Metronidazole
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- role in chrohns
- adverse effects, nausea, diarrhea, metallic taste -avoid alcohol - issue with LT use and associated paraesthesiae and peripheral nethropathy |
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UC & Crohn’s: Surgery- when, percent
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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 |
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UC & Crohn’s: Other issues
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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 |
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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 |
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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 |
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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 |