IBD Flashcards

1
Q

Describe the pattern of gut inflammation in UC

A

Continuous inflammation from the rectum and extends proximally. If it involves splenic flexture, its called “pancolitis”
Always involves rectum
Limited to colon

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2
Q

Describe the pattern of gut inflammation in Crohn’s

A

Skip lesions separated by normal bowel
Rectal sparing
Can affect any part of the GIT but particularly distal ileum and proximal colon

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3
Q

Describe 6 histological features of UC

A
  • Superficial (confined to mucosal/submucosal)
  • Ulcerations
  • Architectural distortion - cryptitis, crypt formation, crypt abscesses
  • Lymphocytic infiltrate
  • Globlet cell depletion
  • No granulomas
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4
Q

Describe 5 histological features of Crohn’s

A
  • Transmural
  • Cobble stoning
  • Granulomas (30-50% of cases; HALLMARK)
  • Infiltrates of lymphocytes and macrophages
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5
Q

What are 4 gut complications of Crohn’s?

A

Fistulas
Strictures –> bowel obstruction
Abscess
Perforation –> peritonitis

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6
Q

How does smoking affect UC and Crohn’s?

A

Smoking increases risk of Crohn’s and protects against UC

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7
Q

What are 2 things that protect against UC?

A

Smoking

Appendicectomy

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8
Q

What are some environmental factors that affect IBD?

A
Smoking - increases risk of Crohn's, protects against UC
Appendicectomy protects against UC
Infection - M. paratuberculosis
Diet
Medications - aspirin, NSAIDs, OCP
Psychological stress
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9
Q

What are important investigations in IBD?

A

Raised ESR + CRP (more useful in colitis and better than ESR)
Raised Platelet count
Faecal MCS
Faecal calprotectin - can help us decide if C scope is needed when presentation is vague; better test than faecal leukocytes; picks up inflammatory cells in stool; if you are going to do a C scope, this test isn’t going to change anything; not specific to IBD, just shows inflammation of the bowel
Endoscopy and histology (gold standard)
Serology

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10
Q

Serology is generally not helpful in real life but comes up on MCQ
Which serology test suggests UC and Crohn’s?

A

Positive ASCA and negative ANCA = Crohn’s

Negative ASCA and positive ANCA = UC

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11
Q

What are the 2 ways to visualise the small bowel?

A

Capsule endoscopy
- $$$, unable to get tissue, false positive
Double balloon enteroscopy
- $$$, time consuming, limited availability
- Allows diagnostic and therapeutic intervention

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12
Q

How do people present with IBD?

A

Diarrhoea, abdominal pain, urgency, tenesmus, incontinence, PR bleed, fever, weight loss, extraintestinal features (eyes, joints, skin)

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13
Q

List 3 major groups of extraintestinal manifestations associated with IBD disease

A

3 major systems are affected
- Joints - polyarthralgias (parallels disease activity), HLA-B27 ankylosing spondylitis (does not parallel disease activity)

  • Skin - erythema nodosum (tender nodules on shins; parallels disease activity; more common in CD), pyoderma gangrenosum (ulcerated skin, almost necrotic; does not parallel disease activity; more common in UC)
  • Eyes - episcleritis (parallels disease activity), uveitis (doesn’t parallel disease activity)
  • Others: UC associated with primary sclerosing cholangitis (doesn’t parallel disease activity)
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14
Q

What are 2 gut complications of UC?

A

Colorectal cancer
Acute severe colitis (10% presents with fulminant or intractable disease)

Rx: colectomy

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15
Q

What are the 9 main therapies used in IBD?

A
  • 5-aminosalicylates (UC mainly)
  • Abx
  • Steroids
  • Biologics - best evidence is infliximab; response in 2-3 days
  • MTX (CD mainly)
  • Thiopurines
  • Cyclosporine (UC only)
  • Exclusive enteral nutrition (CD only)
  • Tofacitinib (UC only)
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16
Q

List side effects of 5-SA e.g. sulfasalazine

A
Diarrhoea
Headache
Nausea 
Rash
Generally well tolerated
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17
Q

When do you use 5-SA in IBD?

A

Mild-moderate UC

  • Can be used to induce and maintain remission
  • Rectal more effective than oral for distal UC
  • combo of oral and rectal rx most effective

Little data in Crohn’s

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18
Q

When do you use abx in IBD?

A

No established role in uncomplicated IBD

Special circumstances include
Crohn’s - abscess (fever, focal tenderness), perianal disease (abscess, fistula), post-ileocolic resection

UC - acute severe colitis, toxic megacolon, pouchitis

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19
Q

When do you use corticosteroids in IBD?

A

Acute flares of UC and CD

Should not be used long-term (do not maintain remission)

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20
Q

What’s budesonide and when is it used in IBD?

A

Corticosteroid but it gets delivered specifically to ileum and proximal colon = very effective in ileocaecal CD

Another form gets delivered to colon = very effective in UC

$$ and not PBS covered
Few side effects due to limited absorption

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21
Q

When do you use thioprines in IBD?

e.g. azathioprine, 6-MP

A

To maintain steroid free remission

Takes 2-3/12 to work so not useful in inducing remission (used initially together with steroids)

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22
Q

Why is it important to do therapeutic drug monitoring when taking thioprines?
e.g. azathioprine, 6-MP

A

AZA –> 6-MP (–via TMPT—> 6MMP (inactive)) –> 6-TG (active)

We measure 6-TGN (active metabolite) and 6-MMP (inactive metabolite)

Both absent = not taking the drug
Both subtherapeutic = under dosing
Both supratherapeutic = if ongoing active disease, then there isn’t much room to increase the dose, and they are thioprine refractory. Switch drug.
Low 6-TGN and high 6-MMP = occurs in 10-20%; preferentially shunts production to 6-MMP = associated with hepatotoxicity and other AEs
- Add allopurinol (xanthine oxidase inhibitor) can overcome this shunt and drive production back to 6-TGN
- Reduce thioprine dose
- Meticulous monitoring of blood counts (to pick up myelotoxicity)
- Repeat metabolite level in 4/52

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23
Q

List side effects of thiopurines

A
Allergic reaction
Nausea
Leucopenia (2-5%)
Hepatitis (2%)
Pancreatitis
Serious infection (5%)
NHL
Non-melanoma skin cancer 

11% have to stop therapy due to adverse events

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24
Q

Why measure TMPT before starting azathioprine?

A

0.3% have abnormal TPMT enzyme activity –> shunt towards production 6-TGN (active metabolite) –> more susceptible to neutropenia

In those with homozygous/low activity TMPT require much lower dose of the drug

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25
Q

When do you use MTX in IBD?

A

2nd line agent
Induces and maintains remission in CD
Less data in UC

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26
Q

List some toxicities of MTX

A
Nausea, headache
Pneumonitis
Hepatotoxicity (monitor bloods)
Myelotoxicity (monitor bloods)
Teratogenic - avoid during pregnancy
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27
Q

When do you use cyclosporin?

A

Rescue therapy for UC that is failing steroids
To avoid surgery
Short-term bridge to therapy with AZA/6-MP
Not effective or safe for long-term use
Not used in CD

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28
Q

List some toxicities of cyclosporin

A
Nephrotoxicity
Hypertension
Neurotoxicity
Infections 
Drug interactions!!
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29
Q

What class is cyclosporin?

A

Calcineurin inhibitor (inhibits cell-mediated immunity)

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30
Q

When do you use anti-TNF-alpha antibodies?

A

Infliximab has the best evidence; response in 2-3 days

CD refractory to steroids and AZA/6-MP/MTX
Refractory fistulizing CD
Acute severe UC failing IV steroids
Moderate-severe chronic UC failing 5-ASA/thiopurine

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31
Q

List some examples of anti-TNF-alpha antibodies used in IBD?

A

Infliximab
Adalimumab
Golimumab (only UC)

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32
Q

List adverse events with anti-TNF therapy

A

10% stop therapy due to adverse events

Serious Infections (3%)
TB
- Always screen for TB before starting therapy
Malignancy - NHL, melanoma
Skin reaction - infusion or injection site reactions (3-20%), psoriasiform reactions (4.8%)
Drug related lupus like reaction (1%)
MS, heart failure, severe liver injury (case reports only)

Hepatosplenic T cell lymphoma

  • Rare
  • Young males on thiopurine + anti-TNF
  • Limit duration on combo therapy
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33
Q

What can you do if there is a loss of response to anti-TNF therapy?

A

Measure trough drug level –> if sub-therapeutic –> measure anti-drug-antibodies –> if present, switch to another anti-TNF

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34
Q

How does vedolizumab work in IBD?

A

Binds to integrin on T cells and blocks adhesion of T cells to intestinal epithelium.
Used in UC and CD
Gut specific
Excellent safety profile

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35
Q

How does ustekinumab work in IBD?

A

IL12/IL23 inhibitor

Indications: CD, psoriasis/psoriatic arthropathy

36
Q

Risk of lymphoma is higher with thiopurine or anti-TNF therapy?

A

Thiopurine

37
Q

Combination therapy (e.g. azathioprine + infliximab) has higher steroid free remission when compared to monotherapy in IBD. What are the risks?

A

Opportunistic infections
Lymphoma (especially thiopurine)
Hepatosplenic T cell lymphoma - rare but aggressive. Mostly in young men taking azathioprine +/- combination therapy. Almost universally fatal disease.

Hence try and limit combination therapy to 12/12 then withdraw azathioprine if patients are doing well.

38
Q

How do you treat moderate-severe CD?

A

1) Steroids (prednisolone or budesonide) to induce remission
1) Start thiopurine (or MTX) at the same time due to slow onset

2) Wean steroids when there is clinical response. Goal is to be off steroids in 2-3/12.

3) If steroid free remission at 3-6/12, keep patient just on AZA/6-MP/MTX monotherapy
3) If no remission, add infliximab or adalimumab –> if no response, consider vedolizumab, ustekinumab

39
Q

How long to keep patients on maintenance for CD if there is steroid free remission?

A

CD has High relapse rate in general

Choose your patients carefully - normal CRP and colonoscopy indicates low risk of relapse

40
Q

When is surgery indicated in CD?

A
Failed medical therapy - ineffective or poorly tolerated
Abscess
Fistula
Strictures
Perforation
41
Q

What is the rate of recurrence post-op in CD?

A

At 1 year after ileo-colonic resection

  • 80% endoscopic recurrence
  • 30% clinical recurrence
  • 10% surgical recurrence
42
Q

What are the risk factors for recurrence post-op in CD?

A

Young person/Short duration of disease before surgery
Smoking
Previous resection
Perforating disease

43
Q

How to prevent post-op recurrence in CD?

A

Usually 3/12 metronidazole given post-op
5-ASA - slight benefit
Thiopurines - moderately effective
Anti-TNF therapy - highly effective

Initial therapy is based on clinical risk factors
Perform colonoscopy at 6 months post-op. If endoscopic findings of CD, escalate therapy

44
Q

Describe the step up management of UC

A

Mild
- 5-ASA for induction and maintenance of remission

Mod

  • Steroids for flares
  • If needing steroids, probably time to escalate to MTX/thiopurine

Severe

  • In refractory disease, may need anti-TNF or cyclosporine (in hospital with acute disease)
  • Long term therapy with anti-TNF therapy, thiopurine, vedolizumab (anti-integrin therapy)
  • Colectomy for those failing therapy, chronic active disease
45
Q

When is surgery indicated in UC?

A

Fulminant disease
Failed medical therapy - lack of efficacy, intolerance
Dysplasia or cancer

46
Q

What’s an ileoanal pouch?

A

Ileum is refashioned to form a pouch which is then joined with the anus
Preserves continence
Suitable for those who have had a total protocolectomy
6-8 bowel motions/day
Reduced fertility due to pelvic dissection that is involved in surgery

47
Q

What’s a common complication post ileoanal pouch?

A

Pouchitis

Rx: abx

48
Q

Partial small bowel obstruction is common in longstanding CD. How do you manage this?

A

IVT
NGT
TPN

For those with proximal small bowel dilation and who have no evidence of long stricture (>10cm) = consider IV steroids

Surgery for those that don’t respond to medical therapy or have small bowel ischaemia

49
Q

How to manage strictures in CD?

A

Most strictures are made of both inflammation and fibrosis.

Medical rx

Fibrotic strictures may need

  • Endoscopic dilatation
  • Stricturoplasty
  • Surgical resection
50
Q

How do you manage fistulas in CD?

A

Seton +/- abx +/- 6-MP/AZA +/- Anti-TNF

Anti-TNF is probably the most effective

If failing above, consider tacrolimus or surgery

51
Q

How do you define acute severe UC/colitis?

A
Truelove and Witts' criteria
Bloody stool >6/day plus 1 of:
- Pulse >90bpm
- Temp >37.8
- Hb <105
- ESR >30
52
Q

How to manage acute severe UC?

A

IV hydrocortisone + IVT + replace electrolytes + IV abx + Tf to aim Hb >100 + clexane

D3 - is there clinical response?
(Use Travis or oxford criteria - CRP >45 or >8 bowel motions/day has a 85% probability of needing colectomy)
If no clinical response, consider salvage therapy with cyclosporin or infliximab or surgery (colectomy)

53
Q

What’s the Travis or oxford criteria?

A

In acute severe UC, by day 3 of IV hydrocortisone, use travis or oxford criteria to determine likelihood of needing colectomy

54
Q

Why is regular colonoscopy surveillance important in IBD?

A

Increased risk of colorectal cancer

Factors that increase risk

  • Disease duration
  • Disease extent
  • Severity of inflammation
  • Primary sclerosing cholangitis
  • FHx of CRC
  • Presence of dysplasia
55
Q

What are some non-pharmacological management in IBD?

A

Quit smoking (CD only)
Nutrition - monitor vitamin D, iron, B12
OP management (due to steroids use)
Psychological wellbeing
Vaccination - flu, pneumococcus, HBV, HPV, VZV (live vaccine; can’t have this if immunosuppressed)
Cancer prevention - skin checks, pap smears, colonoscopy

56
Q

Which drugs can be used in pregnancy in IBD?

A

Most medications are safe except MTX (cat X)
- 5-ASA, anti-TNF (avoid 3rd trimester), corticosteroids, thiopurines
Best outcomes if remission prior to conception and during pregnancy

57
Q

How is UC linked to primary sclerosing cholangitis?

A

90% of PSC have UC
10% UC has PSC

Hence if someone comes in with PSC, do a C scope to find out if they have UC

58
Q

What are some poor prognostic markers in UC?

A

Young age of dx
Previous hospitalisation
Early need for steroids for flares
UC complicated by C.diff

59
Q

Why is budesonide a better steroid than others in IBD?

A

High 1st pass metabolism steroid (gets metabolised by the liver before it reaches the systemic circulation)
Has oral and rectal form
Has systemic side effects
But its probably a little less effective than pred, so if budesonide fails, can try something like pred

60
Q
No bloody diarrhoea
Crampy abdominal pain
Weight loss
Rash on shins
Smoker
Is it CD or UC?
A
CD
Can affect anywhere in the GIT so often no bloody diarrhoea
CD often gets crampy abdominal pain 
Erythema nodosum
Smoking makes it worse 

DDx: IBD

61
Q

What is the treatment approach of CD?

A

Top down approach

62
Q

What to check before giving biologics?

A

Hepatitis

TB

63
Q

Which IBD patients are at risk of colorectal cancer?

A

> 1/3 colon affected

64
Q

How often to do monitoring colonoscopies in IBD?

A

every 1-2 years

Should take biopsies of bowel even if it looks macroscopically normal

65
Q

How does IBD affect your bones?

A

People on chronic steroid use

  • Should be on vitamin D and calcium
  • Regular DEXA scans
  • Treat OP aggressively
66
Q

Why do IBD patients have Fe deficiency?

A

1) Losing blood in rectal bleeding
2) Not eating enough
3) CD with duodenal involvement - may not absorb Fe as much
4) Pro-inflammatory state

A lot of these people may need Fe infusion. Oral Fe doesn’t get absorbed.

67
Q

Why do IBD patients have B12 deficiency?

A

1) Ileal resection

2) Ileal involvement in IBD

68
Q

Useful investigations in IBD

A

Blood

  • CRP, ESR
  • FBC
  • Iron studies
  • Albumin
  • Coeliac serology

Stool

  • Faecal calprotectin
  • Rule out other infective causes with C.diff, MCS, parasites etc
69
Q

What’s faecal calprotectin?

A

Marker of intestinal inflammation
Calcium binding protein found in cytosol of neutrophils
Release with cell damage in GI tract

Correlates with endoscopic activity, histological activity, post-op recurrence

Can help distinguish from IBS

70
Q

What criterias can we used to determine severity of UC?

A
Truelove and Witt's criteria
Clinical severity 
Bloody diarrhoea
HR
Temp
Hb
ESR or CRP

Mayo severity classification
Endoscopic severity
0 = normal
3 = severe

71
Q

Risk factors at diagnosis for colectomy in UC

A

Need for systemic steroids
Extensive colitis (extends beyond splenic flexure)
<40 years
Elevated inflammatory markers

72
Q

Disease distribution in CD

A

Terminal ileum only 59%
Colon only 20%
Ileocolonic 27%
Upper GI tract 4%

73
Q

What’s the montreal classification?

A

Helps define phenotype in CD

Extent of CD
Strictures +/- fistulas
Perianal disease involvement

74
Q

Are symptoms indicative of CD control?

A

No
Mismatch between symptoms and inflammation

Note there is a significant overlap between IBS and IBD hence could have bad symptoms but actually minimal inflammation

75
Q

Benefit of budesonide over prednisolone?

A

High first pass metabolism so minimal systemic AE

Used particularly in Rt sided CD

76
Q

Topical 5-ASA - what are the different formulations and when are they used?

A

Suppository - first 10cm (proctitis)

Foams - up to 25cm

Liquid - up to 30cm i.e. splenic flexure (left sided and extensive; extensive may need oral too)

77
Q

Onset of 5-ASA

A

Initial response within 14 days

Takes up to 8 weeks for full response

78
Q

5-ASA side effects

A

Generally well tolerated

Hypersensitivity - inflammation can get worse
Small risk of interstitial nephritis/nephrotic syndrome - need to monitor renal function

79
Q

What should we check before starting thiopurines?

A

TMPT activity

Low metaboliser (1 in 300 caucasian) = severe myelosuppression

High metaboliser (90% population) = standard dose given

80
Q

What should we monitor while people are on thiopurines?

A

Due to risk of myelosuppression despite being normal TPMT

Weight based dosing

Monitor metabolites (at 6 weeks after commencing then at 3 months)

  • 6TGN (active metabolite)
  • 6MMP (inactive metabolite associated with hepatotoxicity)
81
Q

If high 6MMP and low 6TGN, what to do?

A

Due to high TMPT activity
Give allopurinol - increases 6TGN and reduces 6MMP
Need reduction of dose due to risk of myelotoxicity

82
Q

Side effects of thiopurines

A

Dose related - leucopenia, hepatitis

Malignancy risk - lymphoma, skin, AML

Infections

Avoid live vaccines

Check LFTs and FBC every 3 months

83
Q

MTX is used in IBD. True or false

A

Only in CD

84
Q

Can we stop treatment after achieving remission in IBD?

A

Not really…
Can take a drug holiday
But ultimately will need to go back on treatment. High relapse rate.

85
Q

Exclusive enteral nutrition

What is it used for?

A

UC only

Liquid diet for 4-12 weeks

86
Q

How often to do CRC screening in IBD?

A

High risk - yearly
> PSC, active inflammation, prior dysplasia, stricture, pseudopolyps, tubular/shortened colon, family member CRC ≤50 years

Intermediate risk - 3 yearly

Low risk - 5 yearly
> Consecutive colonoscopies without active disease

87
Q

Pregnancy in IBD

Which drugs to avoid?

A

MTX and tofacitinib are CI

Other ones are generally safe
Sulfasalazine causes sperm abnormalities and subfertility