IBD Flashcards
In which condition (UC or CD) is smoking protective?
Smoking is protective in UC
Environmental risk factors for UC and CD
UC
- Smoking is protective
- Appendectomy protective
- Breastfeeding protective
- Drugs: HRT, OCP, NSAID
CD
- Early tobacco exposure
- Abx
- OCP
- Low sunlight exposure
What is faecal calprotectin
Non invasive marker of intestinal inflammation
Contrast UC and CD
UC:
- Only involves colon
- Continuous disease
- Always involves rectum
- NO perianal fistula
- Usually has bloody diarrhoea
- No granuloma
- UC involves the terminal in 7-15% of the cases, has to be pancolitis
- Smoking and appendectomy is protective
- CRC markedly increased compared to CD
- Macroscopic blood
- EIM: Pyoderma gangrenosum, primary sclerosing cholangitis
CD
- Can affect any part of GI, 80% terminal ileum involved
- Skip lesions
- Variable rectal involve
- Can have perianal fistulas
- Variable bloody diarrhoea - microscopic blood
- Granulomas
- EIM: Ankylosing spondylitis, sacroilitis, erythema nodosum, uveitis
Disease extent for UC
- Proctitis
- Left sided colitis
- Extensive colitis
- Backwash ileitis
Clinical severity of UC
Assessed by the truelove and witt’s criteria
Mild
- <4x bloody diarrhoea, normal ESR, nil fever/tachycardia/anemia
Severe
- More than 6 bloody diarrhoea
- Fever 37.8 and higher
- HR > 90
- Hb < 10.5g/DL
- ESR> 30
Histological features of UC and CD
UC
- Epithelial (superficial)
- Neutrophilic infiltrate
- Crypt abscesses
- Atrophy of glands
- Absent granulomas
- Depleted goblet cells
CD
- Transmural, fissuring ulcers
- Goblet cells preserved
- NON CASEATING GRANULOMAS 30%
- Fewer crypt abscesses
- Distortion of crypt architecture
- Paneth cell metaplasia
Treatment for Ulcerative Colitis
(A) MILD TO MODERATE UC
INDUCTION
- Best initial treatment for mild to moderate UC are 5ASAs
- If nil response after 4 weeks, add PO corticosteroids
- Budesonide due to high first pass metabolism, has minimal systemic side effects - usually ileal/ileocolonic crohns, right sided crohns
- If nil response to 5ASAs + steroids for immunomodulatory agents (eg: azathioprine, mercaptopurine, methotrexate)
- If nil response after 3 months: infliximab
Routes for 5ASAs:
- Proctitis: Suppository
- Left Sided: Enema + oral
- Extensive: Oral 5ASA + rectal
Types of 5ASA:
- Mesalazine
- Sulfasalazine: Worse side effect profile (AIN, HA and rash). Drug of choice when co-existing arthritis
MAINTENANCE
- 5ASA: if successful induction or if remission with corticosteroid in mild flare
(B) SEVERE
INDUCTION: steroids, anti TNF (adalimumab, infliximab, glimumab), vedolizumab, tofacitinib
- Defined as 6 or more bloody diarrhoea plus one of the following: temp > 37.8, HR >90, Hb < 105, ESR >30
- IV steroid
- If nil response after 3 days with IV steroids, will require SALVAGE THERAPY via medical (infliximab, cyclosporin) or surgical (total or subtotal colectomy with end ileostomy)
MAINTENANCE
- Thiopurines (mercaptopurine)
- If ineffective: anti-TNFs, vedolizumab, tofacitinib
Acute Flare
- Oral steroids
- Acute severe ulcerative colitis (eg: fever, tachycardia, anaemia, ESR >30): IV steroids and DVT prophylaxis (high risk of DVT/PE)
- Abdominal X-ray to rule out toxic megacolon
Induction Therapy:
Mild to Moderate CD: Prednisone
- If ileocaecal disease, consider budenoside
Severe CD: IV hydrocortisone or methylpred
- If unable to tolerated or refractory to corticosteroid therapy:
Immunomodulatory Drug: Azathioprine/Mercaptopurine OR
Methotrexate
- If unresponsive after at least 3 months:
TNF inhibitor: infliximab, adalimumab OR
Anti-integrin antibody: vedolizumab
SE of aminosalicylates (5ASAs), eg: sulfasalazine, mesalazine
- 1-10%: Watery diarrhoea, rash, headache, nausea
- <1%: Pneumonitis, pericarditis, thrombocytopenia, hepatitis, pancreatitis
- Rare: renal dysfunction (interstitial nephritis/nephrotic syndrome)
SE unique to sulfasalazine
- Sulfur intolerance
- SJS
- Azospermia - reversible
SE of thiopurine - azathioprine, mercaptopurine (inhibit purine synthesis)
Main adverse effects:
- Myelosuppression
- Hepatitis
- Pancreatitis
- Nausea, vomiting, fever, rash
- Cholestatic jaundice
- Malignancy: lymphoma, non melanoma skin cancer, AML
- Nodular regenerative hyperplasia - rare
- No live vaccines
SE of methotrexate
- Leukopenia
- N+V
- Hepatitis
- Hepatic fibrosis
- Hypersensitivity pneumonitis
- No live vaccines
- CI in pregnancy + breast feeding
SE of TNFI
- Infection - reactivation of latent TB
- Lymphoma
- Melanoma risk increased (doubled)
- Demyelinating disorders
- Drug induced lupus like syndrome
Anti-TNFs used in UC
Adalimumab
- Fortnightly subcut injections
- Anti TNF, quick and broad spectrum
- Check TB and HBV before starting, can’t use if history of melanoma
- Latent TB - can start TNF inhibitor 1 month after TB treatment
Golimumab
- monthly subcut injections
- Anti TNF, quick and broad spectrum
- Check TB and HBV before starting, can’t use if history of melanoma
Infliximab
- quickest, ASUC (acute severe UC), steroid refractory
- Anti TNF, quick and broad spectrum
- Check TB and HBV before starting, can’t use if history of melanoma
Vedolizumab
- Safest as it is gut specific, traveller to TB endemic areas, elderly, has a history of cancer
- Humanised monoclonal IgG-1 antibody, α4β7 INTEGRIN RECEPTOR INHIBITOR, gut specific, safe but narrow
- Not useful if patients have extra-intestinal manifestations
- Inhibition of leucocyte trafficking from the blood into inflamed GIT .
Tofacitinib and ustekinumab
Tofacitinib
- not approved yet, last resort before surgery
- JAK 1,3 inhibitor
- Higher risk of DVT
Ustekinumab
- not approved yet
- Fully human IgG1k monoclonal ab that binds to the p40 subunit of IL-12/IL-23, helps psoriasis
RF at diagnosis for colectomy
- Systemic corticosteroids
- <40yo
- Extensive colitis
- Elevated inflammatory markers
Complications of UC
- Toxic megacolon
- Stricture
- Malnutrition, anaemia
- CRC
Crohn’s disease complications
- Fistulae: Bladder, Skin, Bowel, Vagina
- Perianal abscesses
- Intestinal obstruction due to stricture formation
- Toxic megacolon (less common than UC)
- Anaemia
- CRC
- Kidney stones due to poor digestion of fats, acidosis and increased absorption of oxalate