Crohn's Flashcards
define crohn’s
chronic inflammatory disease
characterised by transmural granulomatous inflammation affecting any part of the gut from mouth to anus (esp terminal ileum)
there is unaffected bowel inbetween areas of active disease
aetiology of crohn’s
inappropriate immune response against the gut flora in a genetically susceptible individual
Th1 and Th17 response
innate immune system
risk factors
- smoking 3-4x
- refined sugar
- link to infectious agents eg mycobacterium proposed
- NSAIDs may exacerbate
- familial aggregation
- genetic predisposition eg mutation of the NOD2 gene, HLA-B27 in people with ankylosing spondylitis
- associated with autoimmune disease eg SLE, autoimmune thyroid disease
pathology of crohn’s
inflamm can occur anywhere along the GI tract (40% involving the terminal ileum)
skip lesions with inflammed segments of bowel interspersed with normal segments
mucosal oedema and ulceration with ‘rose-thorn’ fissures (cobblestone mucosa), fistula, abscesses
transmural chronic inflammation with infiltration of macrophages, lymphocytes and plasma cells
granulomata with epithelioid grant cells may be seen in blood vessels or lymphatics
fistulas from 1 loop of bowel to the next – erode through and get connection
strictures - Scarring through thickness of wall – shrink with time
extensive small disease occurs but rare
epidemiology of crohn’s
prevalence 100-200/100000
incidence 10-20/100000/yr
typically presents 20-40yrs
female slightly more
sx of crohn’s
diarrhoea - may be bloody or steatorrhoea
crampy abdo pain - due to transmural and peritoneal inflammation, fibrosis or obstruction of bowel
weight loss/failure to thrive
systemic symptoms: fatigue, fever, malaise, anorexia
Perianal/vulval/oral ulcers;
erythema nodosum;
pyoderma gangrenosum.
signs of crohn’s
bowel ulceration
abdominal tenderness or mass
perianal abscess/fistulae/skin tags
anal strictures
clubbing
skin, joint and eye problems
signs of anaemia
aphthous ulceration of the mouth
Ix for Crohn’s
FBC - low Hb, high platelets, high WCC
high ESR, high or normal CRP, U&E, LFT (low albumin), INR, ferritin, TIBC, B12, folate.
stool: MC&S and CDT - exclude c difficile, campylobacter, E coli.
Faecal calprotectin
colonoscopy and biopsy - even if mucosa looks normal, may help differentiate between UC and crohn’s. monitor malignancy and disease progression
small bowel - detect isolated proximal disease eg by capsule endoscopy
MRI - assess pelvic disease and fistulae, small bowel disease activity and strictures
US - small bowel imaging
AXR - toxic colon
erect CXR if risk of perforation
small bowel follow through - fibrosis or strictures (string sign of kantor), deep ulceration (rose-thorn), cobblestone mucosa
radionuclide-labelled neutrophil scan - localisation of inflammation when other tests are CI
Mx of crohn’s
help them stop smoking
opyimise nutrition
assess severity - high temperature, pulse, RR, BP, ESR, WCC, CRP, and low albumin may need admission for IV steroids
monitor platelets, stool frequency, Hb, assess for complications
mild to moderate disease: symptomatic but systemically well
- prednisolone 40mg/d PO for 1wk, then taper by 5mg every wk for next 7wks
- diet - based on elemental or polymeric diets effective in children, less in adults
- maintenance
severe
- IV hydration/electrolyte replacement
- IV steroids eg hydrocortisone 100mg/6hr or methylprednisolone 40mg/12hr
- AB
- analgesia
- high dose 5ASA analogues eg mesalazine, sulphasalazine may induce remission
- thromboembolism prophylaxis
- multiple stool MC&S/CDT to exclude infection
- monitor temp, pulse, BP, stool freq/character on a stool chart
- physical examination daily - daily FBC, ESR, CRP, U&E and plain AXR
- consider blood transfusion if Hb <80g/L and nutritional support
- if improving switch to oral prednisolone (40mg/d) - if not use biologics
- consider abdo sepsis complicating disease - especially if abdominal pain (US, CT and MRI assess this) seek surgical advice
perineal disease
- in 50%
- MRI and examination under anaesthetic (EUA)
- oral AB, immunosuppressant therapy +- anti-TNFa and local surgery +- insertion
azathioprine for Crohn’s
2-2.5mg/kg/d PO - used if refractory to steroids, relapsing on steroid taper or requiring >=2 steroid courses a yr
takes 6-10wks to work
SE cause treatment cessation (30%): abdo pain, nausea, pancreatitis, leucopenia, abnormal LFTs
monitor FBC, U&E, LFT weekly for 4 weeks, then every 4wks for 3months then at least 3 monthly
alternative immunomodulators: 6-mercaptopurine and methotrexate
contraindication - women of reproductive age
anti-TNF-a for crohn’s
TNFa involved in pathogenesis
monoclonal Ab like infliximab and adalimumab can reduce the disease activity
counter neutrophil accumulation, granuloma formation and cause cytotoxicty to CD4+ T cells ie clear the cells that drive the immune reponse
involved in induction and maintenance therapy
CI: sepsis, active/latent TB, increased LFT >3fold above top end of normal
SE rash
avoid in people with known underlying malignancy
TB may reactivate when on infliximab, so screen patients before starting the treatment (CXR, PPD, interferon gamma release assay (IGRA)).
Combined AZA and infliximab can increase efficacy of Rx at 12 months, but there are long-term safety issues (eg increased lymphoma risk).
anti-integrin for crohn’s
monoclonal Ab targeting adhesion molecules in gut lymphocyte trafiking ge vedolizumab
reduce disease activity
have gut-specific mechanism of activity
anti-IL12/23 for crohn’s
represents a new cytokine target with an emerging role in treatment eg ustekinumab
diet for crohn’s
enteral nutrition is preferred - consider TPN as a last resort
elemental diets contain aa and give remission
low residue diets help symptoms in those with active disease or strictures
surgery for crohn’s
50-80% need >=1 op in life. It never cures
surgery indications: drug failure, failure to thrive in children, GI obstruction from stricture, perforation, fistulae, abscess
surgical aims: resection of affected areas (but beware of short bowel syndrome), to control perianal or fistulising disease, defunction (rest) distal disease eg with a temporary ileostomy
surgery doesnt prevent recurrence
pouch surgery is avoided - increased risk of recurrence
long term mx of crohn’s
steroids for acute exacerbations
regular 5ASA analogues to reduce number of relapses in Crohn’s colitis
or steroid sparing agents - e.g. azathioprine, 6-mercaptopurine, methotrexate, infliximab
