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Crohn's disease: diagnosis and long-term management

Emma Greig
PhD MRCP
Locum Consultant in Gastroenterology
Endoscopy Unit
Royal London Hospital
Whitechapel
London
E:egreig@doctors.org.uk

Crohn's disease is a type of chronic inflammatory bowel disease (IBD), affecting anywhere from the mouth to the anus. It differs from ulcerative colitis (UC), the other IBD, which affects only the colon. Some manifestations of disease may occur outside the gastrointestinal (GI) tract causing inflammatory conditions of the joints, eyes or skin. In addition, complications such as osteoporosis or anaemia are common. The cause remains elusive; however, the current hypothesis is of an exaggerated inflammatory process arising from an unknown environmental factor in genetically predisposed patients. Environmental agents that have been considered include stress, diet, infective agents such as measles or Mycobacterium paratuberculosis, and vaccinations such as MMR.(1) There is no convincing evidence for any of these at present.
Crohn's disease is more common in the Western world, is slightly more common in women, and has a peak age at diagnosis of 20-30.(2) The number of new cases diagnosed in the UK each year has increased over the last 40 years to approximately 7 per 100,000 population,(3) while the overall number of patients affected within the population has also increased to 2 per 1,000.(3)
While Crohn's may affect anywhere in the GI tract, certain patterns are more likely. In adults, 45% of new cases have disease of the terminal ileum and caecum, 25% have disease confined to the colon, and 20% in the terminal ileum only.(4) The most common symptoms are abdominal pain and diarrhoea, which may contain blood. In children and adolescents, however, diffuse disease of the jejunum and ileum is more likely, leading to abdominal pain, weight loss and nutritional deficiencies.(5) Other characteristic patterns are perianal disease (fresh red bleeding and rectal pain) and disease of the mouth, oesophagus, stomach or duodenum (pain on eating and weight loss). Some patients may develop fistulae, resulting in either abscesses or the formation of abnormal channels between two segments of the bowel or between the bowel and organs such as the bladder or the skin.
About 75% of patients with Crohn's disease are able to work normally, and the vast majority can lead a normal life.(6) Overall mortality is not increased compared with the general population; however, smokers, those with extensive small bowel disease and those having had multiple operations or patients who were very young or elderly at diagnosis do have an increased mortality.(7) Death usually results from infection, pulmonary embolism (PE), surgery or the side-effects of drug therapy.(7)


Making the initial diagnosis
Delays in making the diagnosis are frequent, resulting in more complex disease at presentation, which may be more difficult to treat.(4,8) While the majority of patients with diarrhoea and abdominal pain will have irritable bowel syndrome, certain signs and symptoms make Crohn's disease more likely (see Table 1).(1)

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Investigations used to make a diagnosis

Blood tests
These may reveal raised inflammatory markers (high C-reactive protein, ESR [erythropoietin sedimentation rate] and platelets), with anaemia and evidence of malabsorption (low folate, iron and B12). Inflammatory markers are used to monitor treatment response as they mirror inflammatory activity in the GI tract.

Stool microbiology
In patients with diarrhoea, stool culture, microscopy and testing for Clostridium difficile toxin rule out infection as a cause of worsening symptoms.

Endoscopy
Colonoscopy is vital, particularly in patients with diarrhoea, right iliac fossa pain or rectal bleeding. It allows visualisation of the colon and biopsies to be taken for histology to distinguish Crohn's disease from normal bowel and other conditions such as UC. For patients with pain on eating or swallowing, an endoscopy of the oesophagus, stomach and duodenum may show inflammation or strictures (narrowing of the intestines).

Radiology
Barium examinations are useful as large sections of the small bowel are beyond the reach of endoscopes. However, while disease may be detected, biopsies are not possible. Computed tomography and ultrasound scans have no real role in the initial diagnosis but may help in managing complications such as fistulae or abscesses.

Follow-up
Those patients suspected of having Crohn's disease need to be seen in a gastroenterology outpatient clinic to confirm the diagnosis and allow prompt treatment. In an ideal world, this would be run by a consultant with a particular interest in IBD.(9) There should be easy access to diagnostic services (endoscopy and radiology), a specialist IBD nurse, dietitian, stoma therapist and a surgeon.(9) IBD specialist nurses often have more time than doctors to provide extra information and frequently give emotional support.
A few patients develop complex disease requiring multiple operations and complex drug regimens. Their follow-up should be predominantly in the hospital setting. However, many patients with stable, inactive or limited disease may be keen for general practice follow-up, particularly if they live some distance from the hospital, so shared care guidelines become ­increasingly important.

Drugs used in treatment
Some patients require symptomatic treatment only, using antidiarrhoeal preparations such as loperamide or codeine phosphate. Iron tablets, folic acid and B12 are used to treat those patients with anaemia and deficiencies of these important vitamins and minerals.
Drugs can be divided into steroids, aminosalicylates, antibiotics and immunosuppressive agents (azathioprine, 6-mercaptopurine and methotrexate). Clearly expert knowledge is required to decide the best preparation(s), both for short-term control of active disease and in the longer term to maintain remission. In general, steroids are used in the short term for those patients who are first diagnosed or undergo relapse in an attempt to gain remission rapidly. Other agents can be considered for those patients who quickly relapse on stopping steroids, or who are unresponsive to steroids. All agents have side-effects, which need to be weighed against their potential advantages for treatment.(1)

Need for surgery
Surgery, while never curative, will be needed by 90% of patients by 30 years after diagnosis,(4) with 5% requiring further surgery each year.(1) Surgery should be part of an overall management plan. Regular medication should be considered postoperatively to maintain remission for as long as possible. The most common reasons for needing surgery are: disease unresponsive to medical therapy; recurrent bleeding; or fistula or abscess formation. Common sites requiring surgery include the terminal ileum and caecum (resection of this area is a right hemicolectomy) or colon (colectomy). For children, well-timed surgery aims to reduce complications of disease to allow growth and normal progress through puberty.


Complications of the disease
Complications of disease can occur as a direct result of disease in the GI tract. These may be undernutrition or weight loss, short bowel syndrome following multiple operations, and carcinoma of the colon, which is discussed below. Other complications include gallstones, kidney stones and osteoporosis, both from malabsorption of calcium and steroids used for treatment. Finally, both growth retardation and delayed puberty may occur in up to 35% of children with Crohn's disease.(1)

Extraintestinal manifestations of disease
Significant manifestations of disease that occur outside the bowel may involve the joints (arthritis, particularly of the sacroiliac joints), eyes (uveitis), skin (erythema nodosum) and liver (sclerosing cholangitis). These conditions are beyond the scope of this article and often require specialist input from rheumatologists, ophthalmologists, dermatologists and hepatologists respectively.

Areas of concern for patients- frequently asked questions

Inheritance
Relatives of patients with Crohn's disease are at increased risk of IBD (both UC and Crohn's). The risk of a child developing Crohn's disease if one parent is affected with either type of IBD is 10%; if both parents have IBD it is 40%.(10)


Fertility, pregnancy and childbirth
Patients with Crohn's disease may have problems with body image or self-confidence, particularly if they have a stoma. For both men and women, active disease may impair fertility. Therefore if a patient is considering  starting a family, they should ensure that disease is in remission.(11) This advice is particularly important for women, as there is good evidence that remission at conception remains throughout pregnancy, while disease that is active at conception remains active and may even worsen.(12) Active Crohn's disease in pregnancy increases the risk of spontaneous ­abortion, stillbirth and congenital abnormality.(11) Female patients who smoke, have undergone previous bowel resection or have ileal involvement are at ­particular risk of problems during pregnancy.(12)
Most medication used to treat Crohn's may be used safely during pregnancy. Preparations such as amino-salicylates, steroids, azathioprine and metronidazole (for up to one week) seem safe, but azathioprine should not be started for the first time during pregnancy or if a patient is trying to conceive.(11) Several drugs are contraindicated as they may cause birth defects; methotrexate, ciprofloxacin, metronidazole (for more than one week) and infliximab. Sulfasalazine (one of the aminosalicylates) may cause abnormalities in sperm number and function in 60% of men, which are reversible on stopping the drug.(12)
Vaginal delivery is not contraindicated but may worsen the symptoms of those with perianal disease.(13) Even women with a stoma may have a vaginal delivery, although episiotomy should be avoided as it predisposes to perianal involvement in the future.(13) Steroids and aminosalicylates may be used safely in breastfeeding women, although there is less evidence for the safety of azathioprine and 6-mercaptopurine.(14,15)


Dietary advice
For many patients, their first question on being diagnosed with Crohn's disease is, "How do I alter my diet?" The best advice for most patients is to aim for a healthy, balanced diet containing adequate nutrients and including enough calcium to reduce the risk of osteoporosis. Some patients find that individual foods provoke symptoms, and it is reasonable to exclude these from their diets. A few will require occasional prescription of nutritional supplements such as high-energy drinks or soups, particularly if they have active inflammation or infection, as both increase calorie requirements.
There are a small number of patients where an ­exclusive, prescribed liquid formula diet is used as a medical therapy to heal intestinal inflammation. This therapy is used particularly in children, but it does have a role in adults, especially where steroids should be avoided. Efficacy approaches that of steroids, but patients may relapse rapidly when they reintroduce normal foods after 1-2 months.(16)
One special circumstance is patients with strictures (narrowing of the small bowel) when a low-residue diet is advised. This avoids high-residue foods such as sweetcorn, celery, nuts and pulses and aims to reduce the risks of precipitating bowel obstruction.


Smoking
Smoking is the most important environmental factor in Crohn's disease, and it is well established that the need for steroids, immunosuppressive drugs and surgery is increased in smokers, particularly women.(17) In a recent prospective study of patients with Crohn's disease who stopped smoking, the risk of relapse returned to that of nonsmokers over a two-year period.(17) All patients should thus receive smoking cessation counselling.(17)

Colon cancer risk
There is an increased risk of colon cancer to approximately 7% by 20 years after diagnosis, but only if the patient has inflammation of the colon (colitis) as part of their disease. There is a particular risk in older patients, those with a family history of colorectal cancer, and those with sclerosing cholangitis.(18,19) At present, a screening programme is used to pick up patients at risk of cancer by using the presence of abnormal (dysplastic) cells that are highly likely to develop into cancers if left untreated. The patient should have a full colonoscopy, and many biopsies taken about 8-10 years after their initial diagnosis of Crohn's disease of the colon. This is repeated every two years. They are advised that if abnormal cells are found they will probably need to have their colon removed (colectomy), which may involve stoma formation, which in turn could be permanent.

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References

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