IBD Flashcards
Describe the pattern of gut inflammation in UC
Continuous inflammation from the rectum and extends proximally. If it involves splenic flexture, its called “pancolitis”
Always involves rectum
Limited to colon
Describe the pattern of gut inflammation in Crohn’s
Skip lesions separated by normal bowel
Rectal sparing
Can affect any part of the GIT but particularly distal ileum and proximal colon
Describe 6 histological features of UC
- Superficial (confined to mucosal/submucosal)
- Ulcerations
- Architectural distortion - cryptitis, crypt formation, crypt abscesses
- Lymphocytic infiltrate
- Globlet cell depletion
- No granulomas
Describe 5 histological features of Crohn’s
- Transmural
- Cobble stoning
- Granulomas (30-50% of cases; HALLMARK)
- Infiltrates of lymphocytes and macrophages
What are 4 gut complications of Crohn’s?
Fistulas
Strictures –> bowel obstruction
Abscess
Perforation –> peritonitis
How does smoking affect UC and Crohn’s?
Smoking increases risk of Crohn’s and protects against UC
What are 2 things that protect against UC?
Smoking
Appendicectomy
What are some environmental factors that affect IBD?
Smoking - increases risk of Crohn's, protects against UC Appendicectomy protects against UC Infection - M. paratuberculosis Diet Medications - aspirin, NSAIDs, OCP Psychological stress
What are important investigations in IBD?
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
Serology is generally not helpful in real life but comes up on MCQ
Which serology test suggests UC and Crohn’s?
Positive ASCA and negative ANCA = Crohn’s
Negative ASCA and positive ANCA = UC
What are the 2 ways to visualise the small bowel?
Capsule endoscopy
- $$$, unable to get tissue, false positive
Double balloon enteroscopy
- $$$, time consuming, limited availability
- Allows diagnostic and therapeutic intervention
How do people present with IBD?
Diarrhoea, abdominal pain, urgency, tenesmus, incontinence, PR bleed, fever, weight loss, extraintestinal features (eyes, joints, skin)
List 3 major groups of extraintestinal manifestations associated with IBD disease
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)
What are 2 gut complications of UC?
Colorectal cancer
Acute severe colitis (10% presents with fulminant or intractable disease)
Rx: colectomy
What are the 9 main therapies used in IBD?
- 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)
List side effects of 5-SA e.g. sulfasalazine
Diarrhoea Headache Nausea Rash Generally well tolerated
When do you use 5-SA in IBD?
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
When do you use abx in IBD?
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
When do you use corticosteroids in IBD?
Acute flares of UC and CD
Should not be used long-term (do not maintain remission)
What’s budesonide and when is it used in IBD?
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
When do you use thioprines in IBD?
e.g. azathioprine, 6-MP
To maintain steroid free remission
Takes 2-3/12 to work so not useful in inducing remission (used initially together with steroids)
Why is it important to do therapeutic drug monitoring when taking thioprines?
e.g. azathioprine, 6-MP
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
List side effects of thiopurines
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
Why measure TMPT before starting azathioprine?
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
When do you use MTX in IBD?
2nd line agent
Induces and maintains remission in CD
Less data in UC
List some toxicities of MTX
Nausea, headache Pneumonitis Hepatotoxicity (monitor bloods) Myelotoxicity (monitor bloods) Teratogenic - avoid during pregnancy
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
List some toxicities of cyclosporin
Nephrotoxicity Hypertension Neurotoxicity Infections Drug interactions!!
What class is cyclosporin?
Calcineurin inhibitor (inhibits cell-mediated immunity)
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
List some examples of anti-TNF-alpha antibodies used in IBD?
Infliximab
Adalimumab
Golimumab (only UC)
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
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
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