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October 2008: GPs have central role in managing IBD

How can ulcerative colitis and Crohn's disease be distinguished?

Which patients require urgent referral?

How should patients with IBD be managed in the long term?

How can ulcerative colitis and Crohn's disease be distinguished?

Which patients require urgent referral?

How should patients with IBD be managed in the long term?

Ulcerative colitis (UC) and Crohn's disease together constitute inflammatory bowel disease (IBD). The prevalence of UC is about 30-100 per 100,000 and 30-50 per 100,000 for Crohn's disease. They characteristically present in young adults, but may present at any time of life, including childhood and old age, and a second peak of incidence is now recognised in the sixth decade of life.

UC always affects the rectum and then progresses to a variable extent around the colon, but never extends into the small bowel.

By contrast, Crohn's disease may occur anywhere in the GI tract, from the mouth to the anus, with skip lesions – inflamed areas affected by Crohn's disease – separated by areas of apparently normal mucosa. The ileocaecal region is the most common site. Crohn's also frequently affects the colon, and can diffusely affect the small bowel. It rarely occurs in the oesophagus, stomach and duodenum.

The area of gut affected largely determines how these diseases present.

Presentation

Patients with distal colonic disease tend to present with rectal bleeding. This may be associated with the passage of mucus and/or diarrhoea, although if the disease is very distal the number of bowel motions may be normal or the patient may even be constipated, with bleeding being the predominant feature.

Patients with more extensive colonic disease (either UC or Crohn's disease) can present with bloody diarrhoea and the passage of mucus. It is important to note that the appearance of the blood may be altered, and patients may not see it. Associated systemic symptoms including weight loss and lethargy may also be present.

Small bowel Crohn's disease may present more insidiously, with generalised symptoms of weight loss, anorexia, tiredness and incidental iron deficiency anaemia. Patients with this condition will often have diarrhoea, which may or may not be bloody, although this is not universal. Patients may also have an inflammatory mass on the right iliac fossa that is palpable on examination. Thus all patients in whom IBD is suspected should have a basic abdominal examination, and ideally a per rectum examination to look for blood and exclude mass lesions in the rectum.

Patients with perianal Crohn's disease present with pain, bright bleeding and discharge. If the condition presents late, patients may also have pyrexia and occasionally sepsis caused by perianal abscesses.

Sometimes patients may present with symptoms unrelated to the gut, such as large joint arthritis, iritis, mouth ulcers or erythema nodosum. These features are more common in Crohn's disease, particularly affecting the colon, but may also occur in UC.

IBD should always be considered as a possible underlying diagnosis in patients who present with these conditions, particularly in the presence of constitutional symptoms.

Diagnosis

Initially, blood tests including FBC, U&Es, LFTs, CRP, ESR and tissue transglutaminase should be performed. Patients with IBD will often have iron deficiency anaemia and may have a raised platelet count and inflammatory markers, particularly CRP. It is important to note that patients with distal disease may have normal inflammatory markers, and up to 10% of patients with more significant disease may have a normal CRP, so IBD cannot be excluded solely on the basis of normal inflammatory markers.1

Infective diarrhoea is a major differential diagnosis, although gut infection may also precipitate IBD in patients susceptible to the condition. All patients with suspected IBD should therefore have three stool samples sent for microscopy, culture and sensitivity.

Patients should be referred to a gastroenterologist for endoscopy if they have any of the following symptoms:

• Persistent diarrhoea for longer than one month, particularly with the passage of blood
• Significant weight loss and abdominal pain
• Markedly abnormal inflammatory markers with negative stool cultures.

Patients should be referred urgently if they present with any of the following:

• Significant abdominal distension or systemic upset with fever
• Tachycardia
• Anaemia
• Passing bloody diarrhoea more than six times a day.

These are signs of acute severe colitis, which may need urgent treatment and possibly surgery. See table 1, attached.

Treatment

The treatment of IBD depends on both its severity and its site.

Ulcerative colitis

Distal colonic disease

Topical treatment should be considered for patients with distal disease who do not have systemic symptoms. Mesalazine, either as a suppository or an enema, is the most effective topical treatment for UC, but if the patient is intolerant then steroid suppositories or enemas may be used.2

In more difficult cases, topical mesalazine and steroids may be combined. Foam enemas are generally easier for patients to use than liquid enemas and may treat disease up to the proximal descending colon.

However, systemic therapy may be required if the patient has frequent diarrhoea, as the drug may not stay in contact with the mucosa long enough to be effective. Suppositories are better tolerated and likely to stay in situ longer, but will only treat disease in the rectum and distal sigmoid colon.

Extensive disease

Generally, extensive disease requires systemic treatment. Mesalazine may be used if there are no features of severe disease (see figure 1, attached). There is some evidence that higher doses may be effective in moderate UC (up to 4.8g daily). These doses are safe to initiate in primary care in patients without significant systemic symptoms.3 In addition, combining oral therapy with topical treatment has an additive effect even in extensive UC.4

If a patient commences treatment with mesalazine, it is normal to wait for two weeks to see whether there is a clinical improvement. If there is a clinical response the higher dose should be continued for a further two weeks and then reduced to the normal maintenance dose. Patients who do not respond or continue to deteriorate should change to oral prednisolone (normally 40mg daily). There is no good evidence to guide steroid dose reduction. Most clinicians reduce the dose over the course of 8-10 weeks to stop the treatment.

Patients who have systemic features or who are severely troubled by their symptoms can be treated with oral prednisolone as first-line therapy. If there is no improvement within a week (or an earlier deterioration), patients should be referred urgently to a gastroenterologist for possible inpatient treatment.

Acute severe disease

The best clinical definition of acute severe colitis remains the Truelove and Witts criteria (see table 1, attached). Patients who meet these criteria or have evidence of dilatation of the gut should be referred urgently for inpatient management with intravenous steroids, and possibly second-line drugs such as ciclosporin5 or infliximab.6 Patients who do not respond to these therapies will require a colectomy.

Crohn's disease

Colonic Crohn's disease

The treatment for colonic Crohn's disease is similar to UC. However, mesalazine is less effective in Crohn's than UC and oral prednisolone may therefore be required earlier.

Diffuse small bowel

Oral prednisolone is the first-line treatment for adults with diffuse small bowel Crohn's disease, although dietary therapies are sometimes successful. In children and adolescents, dietary therapy with a polymeric or elemental diet is often very effective. Antibiotics such as metronidazole are not widely used as first-line therapy except in the treatment of perianal disease.

Ileocaecal Crohn's disease

Ileocaecal Crohn's disease is often treated with mesalazine, although there is little evidence to support its efficacy.

A more efficacious treatment is budesonide 9mg daily.7 Budesonide is 90% degraded by first-pass metabolism through the liver, and is thus able to act locally in the ileocaecal region with minimised steroidal side-effects. Despite this, it may still cause steroid-related problems in some patients. Patients who fail to respond to budesonide may respond to oral prednisolone, although trials suggest they are of similar efficacy.

Perianal Crohn's disease

Perianal Crohn's disease can be a very distressing condition. Initial therapy is with broad spectrum antibiotics, such as metronidazole and amoxicillin, but immune suppressants or anti-TNF agents may be required in more complex cases.8

Patients with perianal Crohn's disease require an MRI and surgical review to ensure that any sepsis can be drained and that medical therapy is effective.

Maintenance therapy

Most patients with UC and many patients with Crohn's disease will require maintenance therapy. In UC, this should be with mesalazine 1.6g daily, which has been shown not only to reduce the risk of relapse by about 60% but also to reduce the risk of colorectal cancer in UC by up to 80%.9

A proportion of patients will relapse repeatedly on mesalazine treatment or will be unable to withdraw from steroid treatment. These patients will require treatment with an immune modulator such as azathioprine.

It is now standard practice to check thiopurine methyltransferase (TPMT) levels prior to starting treatment with an immune modulator, as this will predict those at greatest risk of the major side-effects of treatment, such as leucopenia and pancreatitis. However, this is not foolproof and regular blood testing is still required throughout treatment. Both the

TPMT test and the initiation of immune suppression therapy should be carried out in secondary care.

Patients on immunosuppressant therapy require regular blood monitoring every two to three months when stable to ensure that they do not develop LFT abnormalities or leucopenia.

Those who do not enter steady remission despite treatment with an immunosuppressant will be considered for surgery if they have UC or started on anti-TNF therapy if they have Crohn's disease.10,11 Anti-TNF therapy is also effective for a proportion of patients with UC,12 but its use has not been recommended by NICE.

Surgery

Although most patients can be managed with drug therapy, surgery is an extremely valuable and, in some cases, lifesaving option.

Ulcerative colitis

About 10-15% of patients with UC will require a colectomy. This is normally because of acute severe disease refractory to medical treatment, but surgery can also be indicated because of chronic refractory colitis or colonic dysplasia.

Surgical options include the formation of a permanent ileostomy, or a restorative ‘pouch' can be fashioned from the distal ileum and anastomosed to the anus. This latter procedure allows patients to use a toilet normally, although frequency is increased, with most patients using the toilet 5-8 times a day.

Crohn's disease

Up to 80% of patients with Crohn's disease will require surgery. This is normally for stricturing or penetrating disease that does not respond to medical treatment, or for perianal disease. Surgery for Crohn's disease is conservative, as the disease recurs in the majority of patients and 50% will require at least one further operation. Normally a primary anastomosis is fashioned to prevent the need for a stoma.

Summary

Ulcerative colitis and Crohn's disease are extremely variable in their presentation and course, and treatment can be difficult. It is important that GPs have a high index of suspicion of IBD and initiate appropriate treatment for patients undergoing relapse of the disease.

GPs also have a vital role in the monitoring of patients, often in collaboration with gastroenterologists, particularly for those patients on immunosuppressant therapy.

GPs have central role in managing IBD Key points Table 1: Truelove and Witts criteria for acute severe colitis Figure 1: Algorithm for the management of IBD in primary care Useful information

The National Association for Colitis and Crohn's Disease (NACC) provides information and support groups for patients with IBD
support line: 0845 130 3344
www.nacc.org.uk

Author

MA MD DM FRCP
consultant physician and gastroenterologist, Imperial College Healthcare NHS Trust, reader in gastroenterology, Imperial College, London

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