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
How would you maintain remission in Crohn’s disease?
Some choose not to have maintenance therapy.
For those who do choose maintenance therapy the choice of therapy is dictated by that used to induce remission.
E,g, Azathioprine / 6-mercaptoethanol if corticosteroids induced remission.
Methotrexate.
Biologic.
N.B. not a corticosteroid.
After surgery - azathioprine + metronidazole for 3 months.
What are severe symptoms of UC?
Bowel movements (no. per day) - 6 or more plus at least one of the features of systemic upset.
Visible blood in stools.
Pyrexia (temperature greater than37.8°C).
Pulse rate greater than90 bpm.
Anaemia.
Erythrocyte sedimentation rate above 30 mm/hour.
What is the IBD treatment pathway?
Diagnosis.
Multidisciplinary provision of information and support.
Inducing remission.
Maintaining remission.
Monitoring treatment and bone health.
Surveillance.
What are the overall aims of drug treatment of IBD?
Induce remission.
Maintain remission.
Control symptoms.
Limit drug toxicity.
Modify disease progression.
Limit/avoid complications.
What are the main treatment options for UC and CD: inducing remission
UC:
Aminosalicylates. Corticosteroids. Ciclosporin. Infliximab, adalimumab, golimumab. Vedolizumab. Ustekinumab. Tofacitinib.
CD: Aminosalicylates. Corticosteroids. Infliximab, adalimumab, golimumab. Vedolizumab. Ustekinumab.
Why are aminosalicylates used for treatment?
5-ASA (mesalazine) is the active component.
5-ASA is unstable in acidic conditions - oral preparations are formulated to withstand the acidic conditions of the stomach.
Active 5-ASA is released in the colon or ileum to exert its anti inflammatory effect topically.
Formulation choice is important and is influenced by the site of disease.
What counselling points should be given with aminosalicylates?
Common side effects include: diarrhoea, headache, leucopenia, nausea, rash.
Rare side effects: agranulocytosis, neutropenia, pancreatitis.
Report any unexplained bleeding, bruising, purpura, sore throat, fever or malaise that happens during treatment.
Renal function will need checking before starting treatment, at 3 months and then annually.
What are the types of topical (rectal) aminosalicylates?
Often used in conjunction with oral treatment.
Suppositories - reach rectum.
Foam enemas - reach rectum and sigmoid colon.
Liquid enemas - reach rectum and rectosigmoid colon.
Why are corticosteroids used for treatment?
Aim to rapidly achieve remission but limit exposure.
IV, oral and rectal formulations.
IV should be used in severe disease.
Budesonide associated with less systemic absorption.
Using rectal steroids also minimises systemic absorption.
Not used to maintain remission.
