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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
When do you use MTX in IBD?
2nd line agent Induces and maintains remission in CD Less data in UC
26
List some toxicities of MTX
``` Nausea, headache Pneumonitis Hepatotoxicity (monitor bloods) Myelotoxicity (monitor bloods) Teratogenic - avoid during pregnancy ```
27
When do you use cyclosporin?
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
28
List some toxicities of cyclosporin
``` Nephrotoxicity Hypertension Neurotoxicity Infections Drug interactions!! ```
29
What class is cyclosporin?
Calcineurin inhibitor (inhibits cell-mediated immunity)
30
When do you use anti-TNF-alpha antibodies?
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
31
List some examples of anti-TNF-alpha antibodies used in IBD?
Infliximab Adalimumab Golimumab (only UC)
32
List adverse events with anti-TNF therapy
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
33
What can you do if there is a loss of response to anti-TNF therapy?
Measure trough drug level --> if sub-therapeutic --> measure anti-drug-antibodies --> if present, switch to another anti-TNF
34
How does vedolizumab work in IBD?
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
35
How does ustekinumab work in IBD?
IL12/IL23 inhibitor | Indications: CD, psoriasis/psoriatic arthropathy
36
Risk of lymphoma is higher with thiopurine or anti-TNF therapy?
Thiopurine
37
Combination therapy (e.g. azathioprine + infliximab) has higher steroid free remission when compared to monotherapy in IBD. What are the risks?
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
How do you treat moderate-severe CD?
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
How long to keep patients on maintenance for CD if there is steroid free remission?
CD has High relapse rate in general Choose your patients carefully - normal CRP and colonoscopy indicates low risk of relapse
40
When is surgery indicated in CD?
``` Failed medical therapy - ineffective or poorly tolerated Abscess Fistula Strictures Perforation ```
41
What is the rate of recurrence post-op in CD?
At 1 year after ileo-colonic resection - 80% endoscopic recurrence - 30% clinical recurrence - 10% surgical recurrence
42
What are the risk factors for recurrence post-op in CD?
Young person/Short duration of disease before surgery Smoking Previous resection Perforating disease
43
How to prevent post-op recurrence in CD?
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
Describe the step up management of UC
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
When is surgery indicated in UC?
Fulminant disease Failed medical therapy - lack of efficacy, intolerance Dysplasia or cancer
46
What's an ileoanal pouch?
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
What's a common complication post ileoanal pouch?
Pouchitis | Rx: abx
48
Partial small bowel obstruction is common in longstanding CD. How do you manage this?
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
How to manage strictures in CD?
Most strictures are made of both inflammation and fibrosis. Medical rx Fibrotic strictures may need - Endoscopic dilatation - Stricturoplasty - Surgical resection
50
How do you manage fistulas in CD?
Seton +/- abx +/- 6-MP/AZA +/- Anti-TNF Anti-TNF is probably the most effective If failing above, consider tacrolimus or surgery
51
How do you define acute severe UC/colitis?
``` Truelove and Witts' criteria Bloody stool >6/day plus 1 of: - Pulse >90bpm - Temp >37.8 - Hb <105 - ESR >30 ```
52
How to manage acute severe UC?
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
What's the Travis or oxford criteria?
In acute severe UC, by day 3 of IV hydrocortisone, use travis or oxford criteria to determine likelihood of needing colectomy
54
Why is regular colonoscopy surveillance important in IBD?
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
What are some non-pharmacological management in IBD?
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
Which drugs can be used in pregnancy in IBD?
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
How is UC linked to primary sclerosing cholangitis?
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
What are some poor prognostic markers in UC?
Young age of dx Previous hospitalisation Early need for steroids for flares UC complicated by C.diff
59
Why is budesonide a better steroid than others in IBD?
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
``` No bloody diarrhoea Crampy abdominal pain Weight loss Rash on shins Smoker Is it CD or UC? ```
``` 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
What is the treatment approach of CD?
Top down approach
62
What to check before giving biologics?
Hepatitis | TB
63
Which IBD patients are at risk of colorectal cancer?
>1/3 colon affected
64
How often to do monitoring colonoscopies in IBD?
every 1-2 years | Should take biopsies of bowel even if it looks macroscopically normal
65
How does IBD affect your bones?
People on chronic steroid use - Should be on vitamin D and calcium - Regular DEXA scans - Treat OP aggressively
66
Why do IBD patients have Fe deficiency?
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
Why do IBD patients have B12 deficiency?
1) Ileal resection | 2) Ileal involvement in IBD
68
Useful investigations in IBD
Blood - CRP, ESR - FBC - Iron studies - Albumin - Coeliac serology Stool - Faecal calprotectin - Rule out other infective causes with C.diff, MCS, parasites etc
69
What's faecal calprotectin?
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
What criterias can we used to determine severity of UC?
``` 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
Risk factors at diagnosis for colectomy in UC
Need for systemic steroids Extensive colitis (extends beyond splenic flexure) <40 years Elevated inflammatory markers
72
Disease distribution in CD
Terminal ileum only 59% Colon only 20% Ileocolonic 27% Upper GI tract 4%
73
What's the montreal classification?
Helps define phenotype in CD Extent of CD Strictures +/- fistulas Perianal disease involvement
74
Are symptoms indicative of CD control?
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
Benefit of budesonide over prednisolone?
High first pass metabolism so minimal systemic AE Used particularly in Rt sided CD
76
Topical 5-ASA - what are the different formulations and when are they used?
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
Onset of 5-ASA
Initial response within 14 days | Takes up to 8 weeks for full response
78
5-ASA side effects
Generally well tolerated Hypersensitivity - inflammation can get worse Small risk of interstitial nephritis/nephrotic syndrome - need to monitor renal function
79
What should we check before starting thiopurines?
TMPT activity Low metaboliser (1 in 300 caucasian) = severe myelosuppression High metaboliser (90% population) = standard dose given
80
What should we monitor while people are on thiopurines?
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
If high 6MMP and low 6TGN, what to do?
Due to high TMPT activity Give allopurinol - increases 6TGN and reduces 6MMP Need reduction of dose due to risk of myelotoxicity
82
Side effects of thiopurines
Dose related - leucopenia, hepatitis Malignancy risk - lymphoma, skin, AML Infections Avoid live vaccines Check LFTs and FBC every 3 months
83
MTX is used in IBD. True or false
Only in CD
84
Can we stop treatment after achieving remission in IBD?
Not really... Can take a drug holiday But ultimately will need to go back on treatment. High relapse rate.
85
Exclusive enteral nutrition | What is it used for?
UC only | Liquid diet for 4-12 weeks
86
How often to do CRC screening in IBD?
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
Pregnancy in IBD | Which drugs to avoid?
MTX and tofacitinib are CI Other ones are generally safe Sulfasalazine causes sperm abnormalities and subfertility

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