Inflammatory bowel disease Medical Assignment Help

Two major forms of non-specific inflammatory bowel disease are recognized: Crohn’s disease, which can affect any part of the gastrointestinal tract, and ulcerative colitis, which affects only the large bowel. There is overlap between these two conditions in their clinical features, and histological and radiological abnormalities;
in 10% of cases of colitis a definitive diagnosis of either ulcerative colitis or Crohn’s disease is not possible. Currently, it is necessary to distinguish between these two conditions because of certain differences in their management. However, it is possible that these conditions represent two aspects of the same disease. The incidence of Crohn’s disease varies from country to country but is aproximately 5-6 per 100000 with a prevalence of  5O 60 per 100000. The incidence of ulcerative colitis is 5-10 per 100000 per year with a prevalence of 80-120 per 100 000.

EPIDEMIOlOGY AND AETIOLOGY

The aetiology is unknown, but the racial differences and geographical clustering suggest both genetic and environmental causes. A cluster of patients with Crohn’s disease has been found in a Cotswold village in England. both  conditions have a worldwide distribution but are more common in the Western World. The incidence is lower in the non-White races. Jews are more prone o inflammatory bowel disease than non-Iews: the Ashkenazi jew have a higher risk than the Sephardic Jews. 1 Familia}. Both conditions are more common amongst relatives of patients than in the general population. There is a high rate of disease concordance in mono-zygotic twins.
2 Genetic, There are no HLA markers but HLA-B27 is increased in patients with inflammatory bowel disease and ankylosing spondylitis.
3 Smoking. Patients with Crohn’s disease are more likely to be tobacco smokers, and there is an increased risk ofulcerative colitis amongst non-smokers or ex-smokers.
4 infecive agent. In Crohn’s disease the most attractive hypothesis is that of a transmissible agent. No bac-terium, virus or parasite has been definitely identified; recently the measles virus has been implicated.
(a) Mycobacterium. In cattle and sheep, Iohne’s disease, which is a chronic inflammatory disorder of the distal ileum, is caused by M. paratuberculosis.
A mycobacterium has been isolated from Crohn’s disease tissue, but current evidence is against this being an aetiological agent. Granulomas are characteristic of Crohn’s disease, but are also seen in TB and sarcoidosis suggesting a common pathogenetic link, although none has been found.

(b) Cell wall deficient organisms, L-forms, plasmids may be the transmissible agent but this theory  lacks any evidence.
(c) Viruses have been reported in tissue from ulcerative colitis and Crohn’s disease patients, but there are no compelling data.
5 Multifocal gastrointestinal infarction due to granulomatous angiitis has been suggested as a primary event in Crohn’s disease.
6 Serum antineutrophil cytoplasmic antibody (ANCA) is increased in ulcerative colitis, but not Crohn’s disease; it is distinct from the ANCA seen in Wegener’s granulomatosis. 7 Many immunological abnormalities have been described in inflammatory bowel disease. It is unclear whether they are the primary or secondary event in the pathogenesis. A suggested mechanism is that a specific or generalized luminal antigen can cause stimulation of immune (antigen specific) or inflammatory (antigen non-specific) responses. It is possible that these responses are abnormal or exaggerated in inflammatory bowel disease. Activation of T lymphocytes, tissue macrophages, eosinophils, mast cells, neutrophils and fibroblasts produce a wide variety of cytokines (e.g. interleukin IL-1, IL-6, TNF), eicosanoids (e.g. prostaglandins, thromboxane, LTB4), cell adhesion markers (e.g. E-selectins and endothelial cell leucocyte adhesion molecule (ELAM)) and free oxygen radicals, all of which can lead to tissue damage.

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. 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 be extensive, involving the whole of the colon
and/or small bowel. 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’). In a few of these patients there is also inflammation of the distal terminal ileum (‘backwash ileitis’).

Macroscopic changes

In Crohn’s disease the involved bowel is usually thickened and narrowed. There are deep ulcers and fissures in the mucosa, producing a cobblestone appearance. Fistulas and abscesses may be seen. An early sign is aphthoid ulceration that can be seen endoscopically. 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 disease most of the mucosa is lost, leaving a few islands of oedematousmucosa (mucosal islands) and toxic dilatation occurs. On healing, the mucosa can return to normal, although there is usually some residual glandular distortion.

Microscopic changes

In Crohn’s disease the inflammation extends through all layers 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  bscesses and goblet cell depletion are also seen. The differentiation between these two diseases is 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.

CLINICAL FEATURES

Crohn’s disease

This can present at any age; it is uncommon before the age of 10 years and has a peak incidence between 20 and 40 years. A late peak affecting mainly the colon has been reported in women aged over 60 years. Both sexes are equally affected.
The major symptoms are of diarrhoea, abdominal pain and weight loss. Constitutional symptoms of malaise, lethargy, anorexia, nausea, vomiting and low-grade fever may be present. Despite the recurrent nature of this condition, many patients remain well and have an almost normal life-style. However, patients with extensive disease may 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 may 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 usually contains blood, making it difficult to differentiate from ulcerative colitis. Steatorrhoea can be present in small bowel disease. Some patients (15%) present with only anorexia, weight loss and general ill-health, with an absence of any other gastrointestinal symptoms.

Histological differences between Crohn's disease and ulcerative colitis.

Histological differences between Crohn’s disease
and ulcerative colitis.

bowel disease. Some patients (15%) present with only anorexia, weight loss and general ill-health, with an absence of any other gastrointestinal symptoms. Crohn’s disease may present as an emergency with acute right iliac fossa pain mimicking appendicitis. If laparotomy is undertaken, an oedema to us, reddened terminal ileum is found. There are many other causes of an acute ileitis, e.g. infections such as Yersinia. Crohn’s diseaseis the cause of approximately 10% of acute ileitis.

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. This mass is due either to inflamed loops of bowel that are matted together or to an abscess. A careful examination of the anus should always be made to look for oedematous anal tags, fissures or perianal abscesses. These abnormalities are particularly common (80%) in colonic involvement. Other extra-gastrointestinal features of inflammatory bowel disease should be looked for, e.g. erythema nodosum, arthritis, iritis . Sigmoidoscopy should always be performed in a patient with Crohn’s disease. With small bowel involvement the rectum may appear normal, but a biopsy must be taken as non-specific histological changes may 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.

Ulcerative colitis

This also occurs at any age, but most frequently between 20 and 40 years with women affected more than men. 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 is seen. The disease can be mild, moderate or severe, and runs a course of remissions and exacerbations. Ten per cent of patients have persistent chronic symptoms, although some patients may have only a single attack. When the disease is confined to the rectum, blood mixed with the stool, urgency and tenesmus are common. In this group, there are normally very few constitutional symptoms but patients are nevertheless greatly inconvenienced by the frequency of defecation. In an acute attack patients have bloody diarrhoea, passing 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.

The definition of a severe attack is given. The patient may be very ill and needs careful monitoring in hospital with prompt treatment to avoid the development of complications, such as septicaemia, toxic dilatation and perforation.
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. Sigmoidoscopy is always abnormal and shows an inflamed, bleeding, friable mucosa. A biopsy should be taken for histological diagnosis.

Markers of a severe attack of ulcerative colitis.

Markers of a severe attack of ulcerative colitis.

Extra-gastrointestinal manifestations These occur with both diseases and some are related to the intestinal disease activity Patients with Crohn’s colitis have more extra-gastrointestinal complications than those with small bowel lesions alone.

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Gastroenterology

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