IBD Flashcards
What are inflammatory bowel diseases (IBD)?
chronic
relapsing
immunologically mediated disorders
What 4 main processes are thought to contribute to IBD pathogenesis?
- luminal microbial antigens and adjuvants
- genetic susceptibility
- immune response
- environmental triggers
Of the 110 IBS loci that are common between UC and Crohn’s, what are the main pathways implicated?
leprosy
myobacterial susceptibility
other immune-mediated disease
Name 2 loci implicated in Crohn’s susceptibility
NOD2
PTPN22
Name a loci implicated in UC susceptibility
MHC
What are common triggers for IBD?
NSAIDs
antibiotics
infections (viral, bacterial, parasitic)
What causes the mucosal damage in IBD?
hyper activation of T cell adaptive immune responses to commensal enteric bacteria
in combo with genetic susceptibility and environmental factors
What does the mucosal damage in IBD result in?
translocation of luminal contents
abnormal immune responses
chronic inflammation
What is ulcerative colitis?
chronic inflammatory disease unknown aetiology affects colon only diarrhoea with blood and mucus systemic features if extensive/severe flare ups and remission 15-20% attacks are severe
What proportion of the colon is affected in UC?
Proctitis and distal colitis (36%)
Left-sided colitis (37%)
Pancolitis (37%)
What treatments can be used for UC?
proctitis: 5-ASA suppository
distal colitis: 5-ASA foam enema
L-sided colitis: 5-ASA liquid enema
pancolitis: topical and oral treatment
What is Crohn’s disease?
chronic granulomatous inflammatory disease affects any part of GI tract most common: ileo-colonic Crohn's colitis behaved similarly to UC small number of colitis cases are indeterminate
Which areas of GI tract are commonly affected in Crohn’s disease?
gastroduodenual (5%) small intestine alone (5%) distal ileum (35%) right colon (35%) colon alone (20%)
What are the main features of UC?
11:100,000 M=F incidence risk: 15-30, 60-80 yr smoking reduces risk of UC pANCA +ve in 75% of cases 8% concordance in twins
What are the main features of Crohn’s?
7:100,000 M>F risk: 15-30 60-80 yr smoking increased risk pANCA -ve ASCA +ve in 86% of cases 67% concordance in twins
What are the Sx of UC?
bloody diarrhoea mucus mucosal and submucosal inflammation continuous/confluent disease association with PSC
What are the Sx of Crohn’s?
systemic Sx (weight loss) abdo mass fistulae/strictures perianal disease rectal sparing skip lesions
What is the histology of UC?
granular, friable pseudopolyps acute + chronic inflammation muscularis and serosa are normal crypt abscesses diminished goblet cells
What is the histology of Crohn’s?
transmural submucosal oedema lymphoid aggregates fibrosis aphthous ulcers granulomas (e.g. sarcoid/TB)
What are the microscopic features of UC?
Architectural:
crypt distortion, decreased crypt density, villous surface
Inflammatory:
increased transmucosal laminal propria cells, diffuse basal plasmacytosis, mucin depletion, paneth cell metaplasia
What are the microscopic features of Crohn’s?
architecture: normal/irregular/villous, crypt atrophy, distorted/dilated crypts
inflammatory:
basal plasmacytosis, increased basal lamina propria cells (neutrophils, round cells)
specific: epithelioid granuloma, basal giant cells, histiocytes infiltration in lamina propria
What are basal giant cells?
basal cells are the lowest layer of the epidermis (outer layer of skin)
presence of basal giant cells can be indicative of a malignancy/neoplasm, named on their appearance not that have to be a primary basal cell tumour
What are some extra-intestinal symptoms of IBD?
many - can lead to deficiencies affect multiple systems
e. g. eye: episcleritis
skin: pyoderma gangrenosum
circulation: phlebitis
What musculoskeletal complications can develop with IBD?
arthritis - seronegative spondylo-arthropathies
type 1: pauciarticular (< 5 joints), associated with disease activity
type 2: polyarticular
Rx: NSAIDs/sulphasalazine
How often do IBD patients have musculoskeletal complications?
9-53% of patients
In which forms of IBD are musculoskeletal complications more common?
more common in:
- Crohn’s colitis than UC
- pancolitis UC than left-sided UC
- colonic than small bowel disease
Why is there osteoporosis risk for patients with IBD?
corticosteroid use - to reduce IBD inflammation reduced physical activity inflammatory-mediated bone resorption Ca/Vitamin D malabsorption poor intake (lactose intolerance)
Fracture risk is 40% higher than general population
What dermatological manifestations can present in IBD?
affects 2-34% of IBD patients
1-10.5% UC patients
0.5-20% of Crohn’s patients
erythma nodusom (EN) and pyodema gangrenosum (PG) are most common
others: psoriasis, angular stomatitis, aphthous stomatitis, Sweet syndrome
What is ertythema nodosum?
painful palpable nodes
F>M
Crohn’s > UC
mirror disease activity
What is pyoderma gangrenosum?
affects shins usually
adjacent to stoma
pathergy (exaggerated skin injury)
What is Sweet syndrome?
very rare inflammatory skin condition
causes sudden onset of fever and painful rash on skin of limbs
also called acute febrile dermatosis
What hepatopancreatobiliary complications are associated with IBD?
PSC cholelithiasis portal vein thrombosis drug-induced hepatotoxicity drug-induced pancreatitis
What is PSC?
primary sclerosing cholangitis (PSC)
inflammation, stricturing and fibrosis of intra- and extra-hepatic bile ducts
5% of UC patients have PSC
2% of Crohn’s patients have PSC
pancolitis > left-sided UC
30-59 years
M > F (2:1)
raised ALP raised ANA (33%) raised pANCA (80%)
12-15% of patients with PSC undergoing liver transplantation
increased risk of colorectal Ca
What malignancies is PSC a risk factor for?
cholangiocarcinoma
also increases risk of colorectal cancer
What is cholelithiasis in IBD?
gall stones
affects mostly Crohn’s patients with ileal disease
causes interruption of enterohepatic circulation of bile acids
-> bile acid malabsorption
Why does pancreatitis present in IBD patients?
common side effect of azathioprine and 6-mercaptopurine
immunosuppressive medications used in IBD
What ocular manifestations are common in IBD?
affects 0.3-5% of IBD patients
less common is isolated small bowel disease
episcleritis - can mimic intestinal inflammation, treat bowel disease to correct. Can also use topical steroids
Scleritis: can impair vision. More severe cases may require systemic steroids/immunosuppression
uvetis: associated with musculoskeletal and/or dermatological presentations
f > M (4:1)
What renal compilations present with IBD?
affects 6-23% of IBD patients
nephrolithiasis (kidney stones)
obstructive uropathy (hindrance to normal urine flow, normally structural or functional)
renal fistulae
treated with NSAIDs/sulphasalazine
What is the main pulmonary complication of IBD?
Pulmonary embolus (PE)
What is acute colitis?
bloody diarrhoea
Sx of colonic inflammation irrespective of cause
How is colitis assessed?
history
toxicity extent: pulse, temperature, abdo tenderness and distension, wellness of patient
bloods: ESR/CRP, Hb, WCC, Platelets, albumin
Abdo X-ray
What is the Ddx for (acute) colitis?
Infective: campylobacter, shigella, salmonella, E coli, C. diff, CMV colitis
IBD
Ischaemic colitis
Behcet’s
Drug-related (in UC): NSAIDs, cocaine, amphetamines
Drugs: nicorandil
What is nicroandil used for?
used to treat angina
causes vasodilation
What is Behcet’s disease?
inflammatory disorder affect multiple systems
most common; painful mouth sores, genital sores, eye inflammation, arthritis
sores last a few days
cause is unknown, likely partly genetic
What pharmacological treatment can be used for UC?
5-ASA: amino salicyclates azathioprine: immunosuppressive oral steroids IV hydrocortisone ciclosporin: immunosuppressive infliximab (monoclonal Ab targeting TNFa)
What are the Truelove and Witts criteria for severe colitis?
- 6+ bloody stools daily one or more of: - temp > 37.8 - pulse > 90 - Hb < 10.5 g/dL - ESR > 30mm/h
What is the mortality for acute ulcerative colitis?
untreated 24%
steroids 7%
timely surgery <1%
What are the reasons why mortality of acute ulcerative colitis is thought to be <24% in DGHs?
- delays in surgery
- delays in Dx
- undue persistence with unsuccessful medical treatment
What are the factors predicting colectomy in severe UC?
Day 1
stool frequency > 9/day
albumin <30
HR >90
Day 3
Stool frequency >8/day
CRP > 45
(colectomy 85%)
Any
colonic dilatation (>5.5cm)
mucosal islands on AXR (abdo x ray)
(colectomy 75%)
What are the Travis criteria (in UC)?
CRP > 45
Stool frequency >= 8
after 3 days of IV hydrocortisone
85% colectomy rate unless treatment is escalated
By day 3 of treatment (in severe UC), what management must be implemented?
- stool culture results
- corrected electrolytes (esp. Mg)
- colonic biopsy results
- decision on treatment escalation (gastroenterologists)
What is the role of Mg in the intestine?
intestinal inflammation can be caused by Mg deficiency
What is toxic megacolon?
acute form of colonic distension
with abdo distension, fever, abdo pain and shock
very dilated colon observed on AXR
bad sign - call surgeons
What investigations are done to screen for toxic megacolon?
daily abdo X-ray (AXR)
What does treatment escalation depend on
in (severe) colitis?
- age
- severity
- “colitis history”
- pre-flare up therapy
- patients wishes
Rx options
- cyclosporin
- infliximab
- surgery
How is the treatment option decided for colitis?
cyclosporin/infliximab vs surgery
- ongoing azathioprine/6-mercaptopurine therapy
- co-morbidies
- patient wishes
What are the types of staged surgery available for UC?
colectomy + ileostomy
ileoanal pouch
What is cyclosporin?
calcineurin inhibitor
blocks activation of pro-inflammatory mediators
rapid onset of action (IV route)
high oral bioavailability
How effective is cyclosporin?
response rate 80-90%
colectomy rate reduced to 30-47% in patients who respond to cyclosporin (6-9 months after Rx)
colectomy avoided at 5 years for 55-70%
What is infliximab?
monoclonal antibody
targeting TNFa
mainly used in Crohn’s
increasing evidence for use in UC
How can C. difficile infection complicate IBD?
C. diff + IBD = colectomy rate 20%
C. diff can mimic/precipitate IBD flares
C.diff enteritis is more problematic in IBD patients
