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
Treatment of crohn’s disease
• No 5ASA
• Induce with steroids and maintain with
○ Azathioprine
○ Methotrexate oral or subcutaneous
Failing above:
- Infliximab or adalimumab - if you want quick response, excluding HBV/TB and nil history of cancers especially melanoma
- Vedolizumab - if you want to be safe, does not work for extra-intestinal
- Ustekinumab - has psoriasis
If complex perianal fistula/fistulising crohn’s
- Infliximab or adalimumab is drug of choice
- Can start biologic at same time as azathioprine
Management of perianal crohn’s disease
Medical Therapy
- Abx
- Anti TNFs
Surgical
- EUA
- Abscess drainage
- Seton placement
Exclusive enteral nutrition
- Involves administering a complete liquid diet comprised of formula for 4-12 weeks
- Most evidence to support use in paeds - remission rate of up to 80% in CD
Surgical management in IBD
UC: Proctocolectomy +/- ileoanal pouch or permanent ileostomy
- Fulminant colitis: perforation, haemorrhage, toxic megacolon
- Refractory disease
- High grade dysplasia not amendable to endoscopic removal/cancer
CD:
- Stricturing disease with obstruction
- Penetrating disease with perforation/abscess/phlegmon
- Internal fistula
- Perianal disease
- Severe colitis refractory to medical therapy
Extraintestinal manifestations of IBD (CUTANEOUS)
Erythema Nodosum
- Tender erythematous nodules on extensor surfaces
- Most common cutaneous
- Corresponds to disease activity
Pyoderma Gangrenosum
- Papule, pustule or nodule that breaks down into an ulcer with violaceous undermined border
- Pathergy - think trauma
- Location: lower extremity or peristomal
- Treatment: avoid trauma, if in remission infliximab is the drug of choice.
Sweet Syndrome
- Raised tender nodules on face, arms and trunks - normally upper parts of body
- Constitutional symptoms: fever
- Histology: intense neutrophilic infiltrate without vasculitis
- Treatment: luminal disease is moderate - severe, induce with steroid
Psoriasis
- If not on anti-TNF: treat luminal disease, biologic agent of choice ustekinumab
- If on one anti-TNF: is a side effect, up to 15% of cases, treat topical. If fails, switch to another TNF
Extraintestinal manifestations of IBD (ORAL + EYE)
ORAL
- Aphthous stomatitis (mouth ulcer)
- Angular stomatitis/glossitis
EYE
- Conjunctivitis
- Episcleritis: red eye, no impairment of vision, some burning
- Scleritis: red eye + impairment of vision
- Anterior uveitis: red painful eye with pain and photophobia
Extraintestinal manifestations of IBD (RHEUM)
Joints are most commonly affected
Peripheral Arthropathies
- Type 1: pauciarticular, large joints, often asymmetric - parallels disease activity
- Type 2: small joints, symmetrical, polyarticular - unrelated to disease activity
Axial Arthropathies
- Ankylosing spondylitis
- Sacroiliitis
Osteoporosis
Osteomalacia
Extraintestinal manifestations of IBD (HEPATOBILIARY)
- Fatty liver
- Gallstones
Primary sclerosing cholangitis Cancer risk: - Colorectal - Cholangiocarcinoma - HCC - Gall bladder
- Elevated ALP
- Best test: MRCP, if negative liver biopsy
- Doesn’t correlate with disease activity
- Treatment: no effective treatment, address complications like itching, cholangitis
- Management: annual colonoscopies - higher risk of colorectal cancer
Cancer surveillance in IBD
(1) HIGH RISK: annual colonoscopies, extensive colitis UC or >50% CD colitis +
- PSC
- FH CRC < 50
- Dysplastic polyp in colitic area in the last 5 years
- Colonic stricture
(2) INTERMEDIATE RISK: every 2-3 years, extensive colitis UC or >50% CD colitis +
- Inflammatory polyps
- FH CRC > 50
(3) LOW RISK: every 5 years
None of the above but more than one segment colitis
54yo male with a long standing history (>8 years) of Crohns’ colitis involving 2/3 of his bowel. His last colonsocopy was just before the covid 19 pandemic in February 2020. He is asking whether he really needs a colonoscopy this year. Which of the following risk factors would NOT warrant a repeat colonoscopy this year (annual colonoscopy)
A. PSC
B. Family history of colon cancer in a 1st degree relative at the age of 43
C. Personal history of a polyp with low grade dysplasia in a colitic area
D. Inflammatory pseudopolyps
E. Colonic stricture on previous scopes
D. Inflammatory pseudopolyps
Most EIMs get better with Crohn’s except:
- Pyoderma gangrenosum
- Primary sclerosing cholangitis
- Small joint and axial arthritis
Extraintestinal manifestations of IBD (URINARY AND OTHER)
Urinary
- urinary calculi
- oxalate stones associated with CD (think OCD)
- ureteral obstruction
Other
- Venothromboembolism
- Anaemia: iron deficiency, b12, folate
CRC guidelines for IBD
(A) Extent
- UC: beyond sigmoid colon
- CD: >1/3 colon involved
(B) When
- From 8 years after diagnosis
- Diagnosis of PSC
- Strong fam hx start earlier
(C) Frequency
- HIGH RISK = YEARLY
PSC, active inflammation, prior dysplasia, stricture, pseudopolyps, tubular/shortened colon, fam member CRC < 50years)
- INTERMEDIATE RISK = 3 YEARLY
- LOW RISK = 5 YEARLY
consecutive colonoscopies without active disease
What medication in IBD has the risk of lymphoma?
Lymphoma Risk in IBD is Mainly Driven by Thiopurines, not Anti-TNF
A 27 Y.O. male is diagnosed with Crohn’s colitis with an
IBD arthropathy and requires steroids at diagnosis. Six
months later he develops his first perianal fistula. Which
clinical feature is associated with the most aggressive
phenotype of Crohn’s disease?
A) Colonic disease location
B) Young age of onset
C) IBD arthropathy
D) Need for corticosteroids at diagnosis
E) Perianal disease
E) Perianal disease
A 25 Y.O. male with ileocolonic Crohn’s disease becomes steroid-dependent. All the of the following are effective maintenance therapies except – A) Azathioprine B) Infliximab C) Mesalazine D) Ustekinumab E) Vedolizumab
C) Mesalazine
5ASAs don’t work in crohns
A 48 yo male patient with recently diagnosed ileal
Crohn’s disease has been prednisolone dependent for a
period of 6 months. He has a history of coeliac disease
(compliant with gluten free diet) and a history of a
melanoma excised 4 years prior. What therapy is best
avoided due to safety concerns in this patient?
A) Azathioprine
B) Infliximab
C) Mesalazine
D) Vedolizumab
B) Infliximab
A 25yo female presents with a 3 month history of loose bowel
motions. She is opening her bowels up to 3x daily with some urgency and bleeding. Her blood tests are all within normal limits. A flexible sigmoidoscopy is performed which revealed 10 cm of
continuous mild inflammation with erythema and loss of vascular pattern. Above this point the mucosa appeared normal. Biopsies are consistent with ulcerative proctitis. Which is the best therapy to use in this patient?
A) Azithromycin for 3 days
B) Mesalazine PO 4g daily
C) Weaning prednisolone
D) Mesalazine PR 1g BD
D) Mesalazine PR 1g BD
25 Y.O. male with steroid-dependent Crohn’s disease
requires a thiopurine immunomodulator
(azathioprine/mercaptopurine). In discussing the risks
and benefits of these agents in IBD all of the following
are correct EXCEPT
A) Thiopurines are associated with an increased risk of
non-melanoma skin cancer (NMSC)
B) Thiopurines are associated with an increased risk of
lymphoma
C) Thiopurines are effective as steroid-sparing and
maintenance agents in Crohn’s disease
D) Thiopurines are associated with an increased risk of
colorectal cancer
D) Thiopurines are associated with an increased risk of
colorectal cancer
• A 23 Y.O. female with cystic fibrosis and recurrent chest
infections is diagnosed with ulcerative colitis and
requires multiple induction courses of corticosteroids
despite mesalazine. Which is the most appropriate
maintenance agent for this patient?
A) Azathioprine
B) Methotrexate
C) Adalimumab
D) Vedolizumab
E) Prednisolone
D) Vedolizumab
A 44yo male with ulcerative colitis is currently treated
with 5-ASA and 8 weekly infliximab therapy. They
present to the hospital with worsening bloody diarrhoea
up to 8x daily with mild abdominal and associated low
grade fever. What is the most important diagnosis to
exclude on endoscopy with histopathological analysis?
A) Clostridium difficile colitis
B) CMV colitis
C) Crohn’s Disease
D) Ischaemic colitis
B) CMV colitis
A 30 year old female with Crohn’s colitis develops
her first perianal abscess which is 3 cm in size. The
best treatment strategy is –
A) Surgical drainage only
B) Surgical drainage then medical therapy with
azathioprine
C) Surgical drainage then medical therapy with
combination infliximab / azathioprine therapy and
antibiotics
D) Medical therapy only with combination infliximab /
azathioprine therapy and antibiotics
C) Surgical drainage then medical therapy with
combination infliximab / azathioprine therapy and
antibiotics
Perianal disease in CD
Perianal fissures, fistulas and abscesses occur in up to 40% of patients with Crohn disease
Fistulas often need surgical exploration and local drainage
Antibiotics (weeks to months): metronidazole 400 mg orally BD OR ciprofloxacin 500 mg orally BD
Side effects of tofacitinib
Serious infectioins Shingles Venous thromboembolism Gastrointestinal perforation Non-melanoma skin cancer
What monoclonal ab are used in UC vs CD
UC
- anti TNF (adalimumab, infliximab, glimumab)
- vedolizumab a4b7 integrin inhibitor
- tofacitinib JAK inhibitor
CD
- Anti TNF: Infliximab or adalimumab
- Vedolizumab
- Ustekinumab - p40 subunit of IL12/23
Treatment for stricturing crohn’s disease
- Trial of Medical therapy
- Endoscopic balloon dilatation
- Surgical Options: stricturoplasty, resection
What Extraintestinal manifestations are concordant vs discordant to disease activity.
Concordant
- Spondyloarthropathies type 1
- Episcleritis
- Oral CD
- Erythema nodosum
Discordant
- Spondyloarthropathies type 2
- Uveitis
- Primary sclerosing cholangitis
