IBD Flashcards
Epidemiology of IBD
Rates are increasing especially for Crohns Developed world more than developing 20-30yrs and 60-70yrs peaks of onset M = F Familial = 10-15%
Immunopathology of IBD
Pro inflammatory state
TNF Alpha
IL-1, 8 and 12
IFN Gamma
Allelic variations of what gene are associated with Crohns disease
NOD 2/CARD 15
2 mutations = 3% absolute risk of CD More likely to require surgery - fast stricture formation High rate of recurrence Younger patients More likely small bowel disease
Environmental factors and IBD
Cigarette smoking = 90% increased risk of Crohns. Appears protective for UC
? Infections
? Drugs - NSAIDs - mucosal disruption
? Stress
? Diet
Natural history of Crohns Disease
Inflammation –> Stricturing –> penetration and surgery
Rapidly severe disease
75% of patients require surgery
Nearly 50% of these patients will have a clinical relapse
Natural history of Ulcerative colitis
1/3rd proctitis, 1/3rd left sided and 1/3rd extensive disease
Limited disease may extend over time - 50%
At any time only 50% of patients are in remission
20% of patients require colectomy - usually patients with pancolitis
Colorectal cancer risk in UC (and crohns colitis)
Gradually reducing with better treatments
Increased risk with:
- Increased duration of disease
- Increased extent of disease
- Severity of disease
- PSC and risk occurs earlier in disease
- Family history of CRC
- Dysplasia
- HISTOLOGICAL INFLAMMATION
How to preform IBD surveillance?
Chromoendoscopy for visualization
Can only perform endoscopic surveillance if dysplastic lesions are completely removed endoscopically otherwise –> colectomy
Start at 8yrs of disease duration for all UC extending above the rectum and Chron;s disease with more than 1/3rd of colon involved
After commencing surveillance how regularly to preform colonoscopy?
Annually if:
- Active disease
- PSC
- Family history of CRC <50yrs
- Colonic stricture or pseudopolyps
- Previous dysplasia
3 yearly if:
- Inactive Crohns
- Crohns colitis
- Family history of CRC >50yrs
5yrly if 2 previous normal colonoscopies
Predicting severe Crohns Disease
Age <40 Peri-anal disease Initial need for steroids Loss of weight >5kgs Fibro-stenosing disease Upper GI disease Depp ulcers in colon ASCA positive Anti OmpC, I2, CBir1 positive
Serologies to differentiate IBD types
ASCA + = Crohns
pANCA + = UC
Predicting severe Ulcerative colitis
Age <40yrs Extensive disease PSC Deep ulcers High titre pANCA
Simple approach to UC treatment
UC activity is generally reflected by symptoms
Treat by disease extent and severity
Drugs:
- 5ASAs - combination rectal and oral best
- Steroids - must taper
- Azathiopurine and mycophenolate mofetil - if need for steriods >1x/yr
- Anti-TNFs
Approach to Crhon’s treatment
Stop smoking
Assessment of disease activity difficult
CRP and Fecal calprotectin non invasive assessment tools. Endoscopy to assess for mucosal healing
Drugs:
- Antibiotics - fistulising disease and post resection. Metronidazole and ciprofloxicin
- Steroids
- Azathiopurine and MMF
- Methotrexate
- Anti-TNFs - infliximab and adalimumab
Complications of 5-ASAa
Infrequent Interstitial nephritis Pancreatitis Blood dyscrasias Diarrhoea
Sulfasalazine only:
- Sulfur intolerance
- SJS
- Azospermia
Side effects of antibiotics used in Crohns
Metronidazole –> Peripheral neuropahty
Ciprofloxicin –> Archilles tendon rupture
Side effects of Steroids
Effective induction agents only - must taper
Cushingoid weight gain Bruising Mood changes Insomnia Increased appetite Osteopenia DM HTN Glaucoma Increased infections Increased mortality
Thiopurine MoA
AZA –> 6-MP –> 6-TIMP –> either 6-MMP OR 6-TGN
6-MMP –> side effects
6-TGN –> Rac-1 blockade –> T-cell apoptosis
1 in 300 don’t have TPMT –> side effects
MUST MEASURE TPMT prior to using Thiopurines
Thiopurine metabolite monitoring
For non-responders or developing adverse effects
Absent 6TGN and absent 6MMP = non-compliance
Low 6TGN and low 6MMP = under-dosing
Low 6TGN and high 6MMP = thiopurine resistance
High 6TGN and high 6MMP = Thiopurine refractory
How do you improve 6-TGN and 6-MMP in shunters?
Allopurinol
100mg allopurinol and dose reduction of AZA/6-MP to 25-50% of original dose
–> increased 6-TGN and reduced 6-MMP
Side effects of Thiopurines
25% of patients stop due to side effects
Main side effects:
- Hepatotoxicity
- Myelo-suppression
- Pancreatitis
- N+V/flu like illness/hypersensitivity syndrome
- Infection
- Lymphoma and skin cancers
Must perform regular FBC and LFTs
Start low dose and increase
When to use anti-TNFs
Inflammatory Crohns disease refractory to steroids and AZA/MMF and MTX
Fistulizing Crohns disease refractory to other medical therapies
Acute severe UC
UC refractory to other therapies
Side effects of Anti-TNF alpha
Infection
- TB reactivation
- HBV reactivation
- Invasive fungal infections
Lymphoma Demylinating disorders Drug induced lupus Congestive heart failure Abnormal LFTs Dermatological rashes
Monotherapy Vs Combination therapy
Combination therapy results in higher rates of mucosal healing and steroid free remission
May result in higher rates of side effects though
Treatment of acute severe ulcerative colitis
Initial therapy =
IV hydrocortisone 100mg QID, clexane, IV fluids and Transfusion if necessary
Day 3-5 if no clinical response =
- Cyclosporine or infliximab OR
- Colectomy and J-pouch formation
Side effects of pouch surgery
Pouchitis:
- 50% of pouch recipients
- Recurrent in 10-15%
- Therapy = antibiotics
1% mortality SBO Fistulae Reduced fertility Cancer
Perianal fistulising Crohns disease
20-40% of patients during disease course
Aim of treatment is to drain sepsis and evaluate fistula –> treat Crohns with antibiotics and Anti-TNFs
Relapse in 30-50% of patients
Increased in smoking and proctitis
20-25% –> colectomy
Vaccination for IBD
HBV HPV Influenza VZV Pnuemococcus
Extra-intestinal IBD manifestations dependent on disease activity?
Apthous ulcers
Erythema nodosum
Appendicular arthopathy
Episcleritis
Extra-intestinal IBD manifestations independent of disease activity?
PSC
Uveitis
Pyroderma gangrenosum
Axial arthropathy
Mechanism of action of vedolizumab?
α4β7 integrin inhibitor
–> stops interaction of α4β7 integrin with MAdCAM-1 –> stops lymphocyte binding to endothelial surface and its extravasation into the GIT
Takes 8 weeks to work
Similar to natilizumab - no PML risk
Pregnancy and IBD?
Active disease = worse outcomes
Must maintain remission
Can’t use MMF or MTX
Complications with TNF inhibitors and live vaccines in infants
