Inflammatory bowel disease Flashcards
Two major forms of IBD
- Ulcerative colitis
- Crohn’s disease
- distinction incomplete in ~10% of patients=intermediate colitis
- affects ~300,000 people in UK
Genetic risk factors of IBD
- Genetic predisposition=201 loci identified
- people of white European origin most susceptible
Environmental risk factors of IBD
- smoking
- diet
- gut microbiome
Autoimmune disease
- defective interaction between mucosal immune system and gut flora=infection
- 10x more gut bacteria than host cells
- complex interplay between host and microbes leads to disrupted innate immunity and impaired clearance
- this leads to pro-inflammatory compensatory responses=results in physical damage and chronic inflammation
Ulcerative colitis
- Th2 mediated eg: IL-5 and IL-13
- limited clonal expansion and normal T cell apoptosis
- affects mucosa and submucosa
- starts in rectum, spreading proximally
- inflamed areas are continuous
- surgery can be curative
- abcesses/fissures/fistulae=not common
Crohn’s disease
- Th1 mediated eg: IFNgamma, TNFalpha, IL-17 and IL-23
- florid T cell expansion and defective T cell apoptosis
- affects all layers of gut wall
- affects any part of GI tract
- inflamed areas are patchy
- surgery is not always curative and often reoccurs
- abcesses, fissures and fistulae=common
Clinical features of IBD
- right iliac fossa pain
- skin rash (proderma, erythema nodosum)
- diarrhoea, blood, mucus
- weight loss
- arthritis, arthralgia
- abdominal pain
- anaemia, uveitis, fevers, sweats, jaundice
- apthous ulcers
- primary sclerosing colongitis
Supportive therapies of IBD
- fluid/electrolyte replacement
- blood transfusion/oral iron
- nutritional support (malnutrition common)
Active disease and prevention of relapse treatments
- Aminosalicylates eg: Mesalazine
- Glucocorticioids eg: prednisolone
- Immunosuppressives eg: Azathioprine
Aminosalicylates
- Mesalazine or 5-aminosalicylic acid (5-ASA)
- Olsalazine (2 linked 5-ASA molecules)
- anti-inflammatory drugs
Aminosalicylates and UC
- effective at induction and maintenance of remission
- combined oral and rectal administration probably more effective than either alone for generalised disease
- rectal delivery better for localised disease
- probably better than glucocorticoids
Aminosalicylates and CD
- literature unclear
- ineffective in inducing remission
- less clear cut than utility in UC
- glucocorticoids probably better
- may be effective in subgroup of patients
- physician beliefs and patient preferences are the major driving factors in prescribing this
Glucocorticoids
- Prednisolone, Fluticasone and Budesonide
- powerful anti-inflammatory and immunosuppressive drugs
- derived from cortisol
- activate intracellular glucocorticoid receptors which can then act as positive or negative transcription factors
Manipulation of the microbiome
1) nutrition based therapies
- different organisms have different effects so difficult to generalise
- no evidence for probiotics in CD
- some evidence for probiotics for maintenance of remission but less for induction
2) Faecal microbiota replacement therapies (FMT)
- weak evidence for induction in UC, no evidence for maintenance
- 2 of 3 RCTs showed benefit in UC
3) Antibiotic treatment (Rifaximin)
- interferes with bacterial transcription by binding to RNA polymerase=reduces inflammatory mediator mRNA coding
- induces and sustains remission in moderate CD cases
- may be beneficial in UC
- may be microbiome modulator
Biological therapies for IBD
- anti-TNFalpha antibodies (eg: Infliximab given by I.V.)
- other antibodies effective but some have more side effects
- new humanised antibodies being developed (eg: Entanacept)
