Inflammatory Bowel Disease Flashcards
What is IBD?
Common feature chronic inflammatory diseases of the lower intestine.
Results from a breakdown of the homeostatic balance between mucosal immunity and the gut microflora.
Dysregulated immune response is directed against the normal non pathogenic microflora of the GI tract.
IBD = UC and CD
What are some contributing factors to IBD?
Environmental factors
Genetic predisposition
Gut microflora
Host immune response
What is ulcerative colitis?
Always involves the rectum and inflammation can extends continuously throughout the colon.
Only affects the colon and only affects the mucosa of the gut wall (shown in blue in the diagram).
Common in young adults15-25 and second peak in 6th decade.
What are the symptoms of ulcerative colitis?
Bloody diarrhoea
Fever
Passage of mucus
Episodic cramps
Anorexia
Nausea
Abdominal pain
What is the pathophysiology of UC?
Activation of CD4+ Th2 cells leads to inflammation and the influx of neutrophils, plasma cells and eosinophils in the colon.
Chronic inflammation results in ulceration with loss of goblet cells and the formation of abscesses.
What is Crohn’s disease?
Chronic transmural inflammation – i.e. involves all layers of the gut wall.
Not region specific i.e. can affect any region of the GI tract.
Small intestine involvement.
Distribution is asymmetric and discontinuous with segmental; “skip lesions”.
Common in young adults 15-30, second peak in the 6th decade.
What are the symptoms of Crohn’s disease?
Recurrent mild diarrhoea.
Cramps and fevers lasting for days or weeks.
Fatigue.
Non specific symptoms which may not involve diarrhoea.
Can result in malabsorption.
Explain the pathology of Crohn’s disease:
Loss of tolerance to intestinal microflora.
Th1 involvement – release of IL-12, TNF-alpha, INF-gamma.
Leads to expression of matrix metalloproteinases which cause the damage to the tissue.
Results in damage to the gut wall.
Can result in abscesses, strictures, fissures and fistula which can require surgery.
In some cases can require the creation of a stoma.
How do you distinguish IBD from IBS?
IBD is associated with greater inflammatory activity than functional digestive disorders such as irritable bowel syndrome.
Calprotectin is a neutrophil derived protein - acts as a GI specific inflammatory biomarker.
Presence of calprotectin in faecal matter can help distinguish between IBD, other causes of GI inflammation and IBS.
Detected via an ELISA.
How would a diagnosis of IBD be carried out?
Identify symptoms
Look for clinical signs.
Objective measures:
Blood tests. C-reactive protein [CRP]. Erythrocyte sedimentation rate [ESR]. Haemoglobin concentration. Serum albumin.
Faecal calprotectin analysis.
Sigmoidoscopy or colonoscopy for mucosal assessment.
How would you treat IBD?
Therapeutic goal is to induce and maintain remission by the use of drugs that will suppress the immune response.
Agents aimed at reduction of symptoms:
Analgesic (not NSAIDs).
Anti-cholinergic.
Anti-diarrhoeal.
Immunosuppressants:
Corticosteroids.
Aminosalicylates.
Ciclosporin.
Antimetabolites:
Azathioprine.
6-mercaptopurine.
Methotrexate.
Biologics:
TNF-α - Infliximab, Adalimumab, Golimumab.
Intergrin α4Beta7 cell adhesion molecule - Vedolizumab.
IL-12 / IL-23 - Ustekinumab.
JAK inhibitors:
JAK1 / JAK 3 -Tofacitinib.
How would you treat ulcerative colitis?
Therapy depends on disease location and severity.
Aminosalicylates are used first line.
Proctitis and Proctosigmoiditis / left sided colitis -Topical agents (suppository or enema) would be used initially.
Oral therapy in combination with a topical agent used for Extensive.
What is the step up treatment for ulcerative colitis?
Aminosalicylates - / + corticosteroid
Ciclosporin (acute serious)
TNF-α (moderate / severe)
Vedolizumab (moderate / severe)
Tofacitinib (moderate / severe)
What is the step up treatment for Crohn’s disease?
Corticosteroid or aminosalicylate 1st presentation
+ azathioprine or mercaptopurine
TNF-α (moderate / severe)
Ustekinumab or Vedolizumab (moderate / severe)
How would you maintain remission in ulcerative colitis?
Mild to moderate disease:
Oral aminosalicylate.
Azathioprine or 6-mercaptopurine if remission is not maintained by aminosalicylate.
Acute severe disease:
Azathioprine or 6-mercaptopurine.
biologics if non-biologics are contraindicated or ineffective.
Important to maintain therapy to reduce the risk of relapse