Gastroenterology - Inflammatory bowel disease Flashcards
What is inflammatory bowel disease?
IBD are a group of chronic systemic diseases involving inflammation of the intestines and include, ulcerative colitis (UC) which only affects the colon; Crohn’s disease (CD) which can affect the entire GIT; and intermediate colitis which shows features of both UC and CD.
What is the aetiology of IBD?
IBD represents the outcome of three essential interacting co-factors: genetic susceptibility, the environment, and host immune response.
Genetic susceptibility:
- genetic association is stronger for CD than UC
- familial aggregation of disease
- concordance rates higher in MZ than DZ twins
- disease susceptibility genes - e.g. mutations in the CARD15 gene on chromosome 16, confer susceptibility to stricturing small bowel CD
- increased incidence of HLA-B27 in IBD with ankylosing spondylitis
Environment:
- smoking is associated with a two fold increased risk for CD. Smoking reduces risk in UC
- stress and depression may cause relapse
- enteric microflora is altered and the intestinal wall is contaminated by adherent and invading bacteria
What is the role of the host immune response in IBD?
IBD results from defective mucosal immune system producing an abnormal response to luminal antigens such as bacteria which enter the intestine via a leaky epithelium. In the genetically predisposed individual, there is an exaggerated immune response with effector T cells (Th1, Th2, Th17) predominating over regulatory T cells. Pro inflammatory cytokines (IL-12, IFN gamma, IL-5, IL-17) released by the activated T cells stimulate macrophages to produce tumour necrosis factor alpha, IL-1 and IL-6. There is also activation of other cells that together lead to increased production of a wide variety of inflammatory mediators, all of which lead to cell damage.
What are the macroscopic features of CD and UC?
Crohn’s:
- affects ANY part of the GIT
- oral and perianal disease
- discontinuous involvement (“skip lesions”)
- deep ulcers and fissures in mucosa, “cobblestone appearance”
UC:
- affects ONLY the colon
- begins in rectum and extends proximally in varying degrees
- continuous involvement
- red mucosa, bleeds easily
- ulcers and pseudopolyps
What are the microscopic features of CD and UC?
Crohn’s:
- transmural inflammation
- granulomas present in 50%
UC:
- mucosal inflammation
- no granuloma
- goblet cell depletion
- crypt abscesses
What are the clinical features of Crohn’s disease?
Symptoms depend on the region(s) of bowel involved.
Commonest site is ileocaecal (40%)
Small bowel disease causes abdominal pain, usually with weight loss
Less commonly, terminal ileal disease presents as an acute abdomen with right ileac fossa pain mimicking appendicitis
Colonic disease presents with diarrhoea, bleeding and pain related to defacation
In perianal disease there are anal tags, fissures, fistulae and abscess formation
What are the clinical features of ulcerative colitis?
Diarrhoea, often containing blood and mucus
Clinical course can be persistent diarrhoea, relapses and remissions or severe fulminant colitis
Patients may have one or more extraintestinal manifestations
What features suggest severe ulcerative colitis?
Bloody diarrhoea >6/ day Fever > 37.5 Tachycardia >90 ESR >30 mm/h Anaemia Hb<10g/dL Serum albumin <30 g/L
What extraintestinal manifestations are common in IBD?
Eyes - episcleritis, uveitis
Joints - arthralgia, small joint arthritis, anylosing spondylitis
Skin - erythema nodosum, pyoderma gangrenosum
Hepatobiliary - fatty liver, sclerosing cholangitis chronic hepatitis
Renal calculi - oxalate stones
VTE
All uncommon, occur in less than 10% of patients other than those with *
What investigations should be performed in suspected cases of IBD?
Blood tests Radiology - Rigid or flexible sigmoidoscopy - colonoscopy - small bowel imaging - perianal CD - ultrasonography - plain abdominal X ray - radiolabelled white cell scanning
What do blood tests typically show in IBD?
Anaemia is common and may be normochromic, normocytic, anaemia of chronic disease or due to deficiency of iron, B12 or folate. The platelet count, ESR and CRP are often raised in acute CD and the serum albumin is low in severe disease.
Liver biochemistry may be abnormal related to associated liver disease.
What imaging is most likely to show the difference between UC and CD?
Rigid or flexible sigmoidoscopy will establish the diagnosis of UC and CD (if the rectum and/or sigmoid colon is involved). A rectal biopsy is taken for histological examination to determine the nature of the inflammation.
Colonoscopy allows the exact extent and severity of colonic and terminal ileal inflammation to be determined, and biopsies to be taken.
Small bowel imaging is performed to determine the extent of small bowel disease involvement with CD. Affected bowel shows an asymmetrical alteration in the mucosal pattern, with deep ulceration and areas of narrowing (“string sign”) commonly continued into the ileum. Skip lesions may be seen. Video capsule endoscopy is increasingly used to detect small bowel disease and is more sensitive than a barium follow-through.
What differential diagnoses should be considered in cases of IBD?
CD must be differentiated from other causes of chronic diarrhoea, malabsorption and malnutrition. In children it is a cause of short stature. Other causes of terminal ileitis are tuberculosis and Yersinia enterolitica infection (causing an acute illness). IBD affecting the colon must be differentiated from other causes of colitis: infection, ischaemia, radiation and microscopic colitis.
What medical therapy is used to treat CD?
Patients with CD who smoke should be advised to stop with help offered.
Treatment of CD depends on the site and severity of the disease, and also if the disease is stricturing or fistulating:
1) Oral 5-ASA - less efficacious than in UC and is used only in mild disease. Rare potential side effects include bloody diarrhoea, Stevens-Johnson syndrome, acute pancreatitis and renal impairment
2) Steroids - oral prednisolone (40mg/day) is used for moderate/ severe disease. It is reduced gradually according to severity and patient response, usually over 8 weeks. A few patients with severe disease require inpatient admission and IV hydrocortisone. Budesonide is a poorly absorbed oral steroid with limited bioavailability and extensive first pass metabolism that has a therapeutic benefit with reduced systemic toxicity in ileocaeacal CD
3) Liquid enteral nutrition with an elemental (liquid preparation of amino acids, glucose and fatty acids) or polymeric diet induces a remission in active CD. The exact mode of action is unknown. Given by nasogastric tube
4) Thiopurine drugs - azothioprine (2.5mg/kg/day) or its metabolite 6-mercaptopurine (1.5mg/kg/day) are used to maintain a remission and are given to patients who require two or more corticosteroid courses per year
5) Metronidazole is useful in severe perianal CD as a result of both its antibacterial and immunosuppressive effects
6) Methotrexate (IM) is used in a minority of patients with active CD that is resistant to conventional treatment with steroids. It is also used to maintain remission in those intolerant or refractory to azothioprine
7) Anti-TNF antibodies (e.g. infliximab, adalimumab, certolizimab) are used to induce remission in patients resistant to corticosteroids/ immunosuppressives
What side effects are associated with the thiopurine drugs? What should be checked before treatment with these agents is started?
Major side effects are bone marrow suppression (neutropaenia, thrombocytopaenia, and anaemia), acute pancreatitis, and allergic reactions.
The enzyme, thiopurine methyltransferase (TPMT) is essential in the metabolism of thiopurines and activity should be measured on a blood sample before any treatment is given. Approx. 1 in 300 patients ave absent TPMT activity and will not metabolise the drug. These patients are at a high risk for pancytopaenia and treatment is contraindicated.
