INFLAMMATORY BOWEL DISEASE IBD

1. INFLAMMATORY BOWEL DISEASE (IBD) Two major forms of inflammatory bowel disease are recognized: Crohn's disease (CD), which can affect any part of the GI tract, and ulcerative colitis (UC), which affects only the large bowel.

2. Epidemiology Both conditions have a world-wide distribution but are more common in the West. The incidence is lower in the non-white races. Jews are more prone to inflammatory bowel disease than non-Jews. Crohn's disease is slightly commoner in females (M : F = 1 : 1.2) and occurs at a younger age (mean 26 years) than ulcerative colitis (M : F = 1.2 : 1; mean 34 years). Although the aetiology of IBD is unknown, it is becoming clear that IBD represents the outcome of three essential interactive co-factors: genetic susceptibility, environment and host immune response

3. Pathology Crohn's disease is a chronic inflammatory condition that may affect any part of the gastrointestinal tract from the mouth to the anus but has a particular tendency to affect the terminal ileum and ascending colon (ileocolonic disease). The disease can involve one small area of the gut such as the terminal ileum, or multiple areas with relatively normal bowel in between (skip lesions). It may also involve the whole of the colon (total colitis) sometimes without small bowel involvement. Ulcerative colitis can affect the rectum alone (proctitis), can extend proximally to involve the sigmoid and descending colon (left-sided colitis), or may involve the whole colon (total colitis).

4. Macroscopic changes In Crohn's disease the involved small bowel is usually thickened and narrowed. There are deep ulcers and fissures in the mucosa, producing a cobblestone appearance. Fistulae and abscesses may be seen in the colon. An early feature is aphthoid ulceration, usually seen at colonoscopy ; later, larger and deeper ulcers appear in a patchy distribution, again producing a cobblestone appearance. In ulcerative colitis the mucosa looks reddened, inflamed and bleeds easily. In severe disease there is extensive ulceration with the adjacent mucosa appearing as inflammatory polyps. In fulminant colonic disease of either type, most of the mucosa is lost, leaving a few islands of oedematous mucosa (mucosal islands), and toxic dilatation occurs. On healing, the mucosa can return to normal, although there is usually some residual glandular distortion.

5. Microscopic changes In Crohn's disease the inflammation extends through all layers (transmural) of the bowel, whereas in ulcerative colitis a superficial inflammation is seen. In Crohn's disease there is an increase in chronic inflammatory cells and lymphoid hyperplasia, and in 50-60% of patients granulomas are present. These granulomas are non-caseating epithelioid cell aggregates with Langhans' giant cells. In ulcerative colitis the mucosa shows a chronic inflammatory cell infiltrate in the lamina propria. Crypt abscesses and goblet cell depletion are also seen. The differentiation between these two diseases can usually be made not only on the basis of clinical and radiological data but also on the histological differences seen in the rectal and colonic mucosa obtained by biopsy . It is occasionally not possible to distinguish between the two disorders, particularly if biopsies are obtained in the acute phase, and such patients are considered to have an indeterminate inflammatory colitis. Serological testing may be of value in differentiating the two conditions

6. Extragastrointestinal manifestations These occur with both diseases. Joint complications are commonest, and the peripheral arthropathies are now classified as type 1 (pauci-articular) and type 2 (polyarticular). Type 1 attacks are acute, self-limiting (< 10 weeks) and occur with IBD relapses; they are associated with other extraintestinal manifestations of IBD activity. Type 2 arthropathy lasts longer (months to years), is independent of IBD activity . other extragastrointestinal manifestations: sacroileitis,ankylosing spondylitis, skin lesions(pyoderma gangrenosum,and erythema nodusum),vasculitis ,conjunctivitis and episcleritis ,reflecting acute illness.

7. Crohn's disease Clinical features The major symptoms are diarrhoea, abdominal pain and weight loss. Constitutional symptoms of malaise, lethargy, anorexia, nausea, vomiting and low-grade fever may be present and in 15% of these patients there are no gastrointestinal symptoms. Despite the recurrent nature of this condition, many patients remain well and have an almost normal lifestyle. However, patients with extensive disease often have frequent recurrences, necessitating multiple hospital admissions. The clinical features are very variable and depend partly on the region of the bowel that is affected. The disease may present insidiously or acutely. The abdominal pain can be colicky, suggesting obstruction but it usually has no special characteristics and sometimes in colonic disease only minimal discomfort is present. Diarrhoea is present in 80% of all cases and in colonic disease it usually contains blood, making it difficult to differentiate from ulcerative colitis. Steatorrhoea can be present in small bowel disease.

8. Crohn's disease can present as an emergency with acute right iliac fossa pain mimicking appendicitis. If laparotomy is undertaken, an oedematous reddened terminal ileum is found. There are other causes of an acute ileitis (e.g. infections such as Yersinia). Up to 30% of patients presenting with acute ileitis turn out eventually to have Crohn's disease. Crohn's disease can be complicated by anal and perianal disease and this is the presenting feature in 25% of cases, often preceding colonic and small intestinal symptoms by many years . Enteric fistulae, e.g. to bladder or vagina, occur in 20-40% of cases.

9. Examination Physical signs are few, apart from loss of weight and general ill-health. Aphthous ulceration of the mouth is often seen. Abdominal examination is often normal although tenderness and a right iliac fossa mass are occasionally found. The mass is due either to inflamed loops of bowel that are matted together or to an abscess. The anus should always be examined to look for oedematous anal tags, fissures or perianal abscesses. Extragastrointestinal features of inflammatory bowel disease should be looked for.

10. Sigmoidoscopy should always be performed in a patients with Crohn's disease. With small bowel involvement the rectum may appear normal, but a biopsy must be taken as non-specific histological changes can sometimes be found in the mucosa. Even with extensive colonic Crohn's disease the rectum may be spared and be relatively normal, but patchy involvement with an oedematous haemorrhagic mucosa can be present.

11. Investigations Blood tests Anaemia is common and is usually the normocytic, normochromic anaemia of chronic disease. Deficiency of iron and/or folate also occurs. Despite terminal ileal involvement in Crohn's disease, megaloblastic anaemia due to B12 deficiency is unusual, although serum B12 levels can be below the normal range. Raised ESR and CRP and a raised white cell count Stool cultures : These should always be performed on presentation if diarrhoea is present. Radiology and imaging : A barium follow-through examination should always be performed in patients suspected of having Crohn's disease. The findings include an asymmetrical alteration in the mucosal pattern with deep ulceration, and areas of narrowing or stricturing. Although commonly confined to the terminal ileum , other areas of the small bowel can be involved and skip lesions with normal bowel are seen between affected sites.

12. Options for medical treatment of Crohn's disease Induction of remission Oral or i.v. glucocorticosteroids Enteral nutrition Oral glucocorticosteroids + azathioprine or 6 mercaptopurine (6MP) Maintenance of remission Aminosalicylates Azathioprine, 6MP, mycophenolate mofetil Treatment of glucocorticosteroid/immunosuppressive therapy-resistant disease Methotrexate Intravenous ciclosporin Infliximab (TNF-a antibody) New biological agents Perianal disease Ciprofloxacin and metronidazole

13. Approximately 80% of patients will require an operation at some time during the course of their disease. Nevertheless, surgery should be avoided if possible and only minimal resections undertaken, as recurrence (15% per year) is almost inevitable. The indications for surgery are: failure of medical therapy, with acute or chronic symptoms producing ill-health complications (e.g. toxic dilatation, obstruction, perforation, abscesses, enterocutaneous fistula) failure to grow in children.

14. Ulcerative colitis Clinical features The major symptom in ulcerative colitis is diarrhoea with blood and mucus, sometimes accompanied by lower abdominal discomfort. General features include malaise, lethargy and anorexia. Aphthous ulceration in the mouth is seen. The disease can be mild, moderate or severe, and in most patients runs a course of remissions and exacerbations. Ten per cent of patients have persistent chronic symptoms, while some patients may have only a single attack. When the disease is confined to the rectum (proctitis), blood mixed with the stool, urgency and tenesmus are common. There are normally few constitutional symptoms, but patients are nevertheless greatly inconvenienced by the frequency of defecation. In an acute attack of UC, patients have bloody diarrhoea, passing up to 10-20 liquid stools per day. Diarrhoea also occurs at night, with urgency and incontinence that is severely disabling for the patient. Occasionally blood and mucus alone are passed.

15. Examination In general there are no specific signs in ulcerative colitis. The abdomen may be slightly distended or tender to palpation. The anus is usually normal. Rectal examination will show the presence of blood. Rigid sigmoidoscopy is usually abnormal, showing an inflamed, bleeding, friable mucosa. Very occasionally rectal sparing occurs, in which case sigmoidoscopy will be normal. Investigations Blood tests In moderate to severe attacks an iron deficiency anaemia is commonly present and the white cell and platelet counts are raised. The ESR and CRP are often raised; liver biochemistry may be abnormal, with hypoalbuminaemia occurring in severe disease. pANCA may be positive. This is contrary to Crohn's disease, where pANCA is usually negative .

16. Stool cultures These should always be performed to exclude infective causes of colitis. Imaging A plain abdominal X-ray with an abdominal ultrasound are the key investigations in moderate to severe attacks. The extent of disease can be judged by the air distribution in the colon and the presence of colonic dilatation can be noted. Thickening of the colonic wall can be detected on ultrasound, as can the presence of free fluid within the abdominal cavity. CT is also valuable in acute attacks. An instant unprepared barium enema is sometimes performed. Colonoscopy : A colonoscopy should not be performed in severe attacks of disease for fear of perforation. In more long-standing and chronic disease it is useful in defining extent and activity of disease, and in patients with total ulcerative colitis of 10 years' duration or more, colonoscopy and multiple biopsies should be performed to exclude dysplasia and carcinoma.

17. Medical management of ulcerative colitis (UC) All patients with ulcerative colitis should be treated with an aminosalicylate. The active moiety of these drugs is 5-aminosalicylic acid (5-ASA). 5-ASA is absorbed in the small intestine (and may be nephrotoxic) so the design of the various aminosalicylate preparations is based on the binding of 5-ASA by an azo bond to sulfapyridine (sulfasalazine), coating with a pH-sensitive polymer (Asacol) or packaging of 5-ASA in microspheres (Pentasa).

18. Indications for surgery in ulcerative colitis Fulminant acute attack Failure of medical treatment Toxic dilatation Haemorrhage Perforation Chronic disease Incomplete response to medical treatment Excessive steroid requirement Non-compliance with medication Risk of cancer

19. Normal colon Ulcerative colitis.

20. Norml. Chrons disease.