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Inflammatory bowel disease
Executive Editor, InnovAiT
Email: chantal.simon{at}oxfordjournals.org
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Abstract |
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Abstract
Inflammatory bowel disease and...Ulcerative colitis (UC) and Crohn's disease are collectively termed inflammatory bowel disease (IBD). Both UC and Crohn's disease are chronic, relapsing-remitting diseases characterized by acute, non-infectious inflammation of the gut. Diarrhoeal diseases likely to be IBD have been described for centuries. King Alfred (849–899 AD) suffered from an illness which caused pain on eating, discomfort, and much embarrassment. This affliction plagued the King from the age of 20, without remission. At the time the illness was thought to be due to witchcraft or a punishment for the King's infidelities. In retrospect, however, the illness was probably IBD. Despite this, UC was not formally described until 1859, and Burrill B. Crohn did not describe the disease later named after him until 1932.
GP curriculum statement 15.2: Digestive problems, requires GPs to be able to manage primary contact with patients who have a digestive problem. It lists inflammatory bowel disease (IBD) as an important condition that GPs should be familiar with and requires GPs to have an understanding of the secondary care management of both Crohn's disease and UC.
Person-centred care
Specific problem-solving skills
Scientific aspects
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Epidemiology and classification |
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Incidence and prevalence of UC and Crohn's disease are summarized in Table 1. Both affect men and women equally.
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In the case of UC, inflammation is limited to the colorectal mucosa. Extent varies from disease limited to the rectum (proctitis) to disease affecting the whole colon (pancolitis).
With Crohn's disease, any part of the gut from mouth to anus can be affected with normal bowel between affected areas (skip lesions). It is usually classified by the areas of the gut affected. Roughly half of all patients with Crohn's disease have ‘ileocolic’ disease or disease affecting both the ileum and large bowel; 30% have ‘ileal’ disease only; and 20% have isolated ‘Crohn's colitis’. Crohn's disease may also be classified by the behaviour of the disease into inflammatory, stricturing or penetrating disease (resulting in fistulae).
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Causes of IBD |
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The cause of IBD is not known. Relatives of sufferers have a higher chance of developing IBD than the normal population which suggests a genetic link. Twin studies confirm this (Table 2). Several genes have been identified that are associated with IBD. In particular, the NOD2 gene that is present in 30–40% of those with Crohn's disease and the NFKB1 gene that is a risk factor for the development of ulcerative colitis (UC).
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However, it is thought that for both diseases, an additional environmental factor must trigger the disease in genetically susceptible individuals. Several factors have been implicated, such as alterations in gut flora, food constituents and gut infections, but as yet none have been proven and multiple different factors may be involved.
There is a particularly interesting relationship between smoking and IBD. Smoking is strongly protective against UC and 95% of patients with UC are either non-smokers or ex-smokers. Conversely, smoking seems to be a contributory factor in the cause of Crohn's disease as two out of every three patients are smokers. Smoking cessation halves the relapse rate.
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Presentation of IBD |
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The differential diagnosis of IBD is listed in Box 1. In 10–15% of cases, Crohn's disease and UC may be difficult to distinguish. Tiredness and/or malaise are common non-specific features, as is weight loss. Severity of symptoms fluctuates unpredictably over time. Patients are likely to experience flare-ups in between intervals of remission or reduced symptoms.
Box 1. Differential diagnosis of IBD
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UC usually presents with diarrhoea with passage of blood and/or mucus with the stool. There may be associated faecal urgency or incontinence. However, the stool may be solid if disease is confined to the rectum only. Other common symptoms include lower abdominal pain and a feeling of incomplete emptying of the bowel (tenesmus).
As any part of the gut may be affected, Crohn's disease can present in a more varied fashion with gastrointestinal symptoms anywhere from the mouth to the anus. Symptoms include:
- diarrhoea, with or without blood and/or mucus
- malabsorption
- crampy abdominal pain
- bowel obstruction as a result of strictures
- fistulae (often perianal)
- mouth ulcers (20% patients)
- abscesses (perianal and intra-abdominal)
Examination findings
General examination may reveal clubbing of the nails. This occurs in 58% of patients with Crohn's disease. Its presence correlates with the severity, activity and duration of the bowel disease and treatment may result in resolution of the clubbing. Apthous ulcers in the mouth (Crohn's disease) and/or signs of weight loss, anaemia or hypoproteinaemia are also common. Fever (over 37.5°C) and/or tachycardia of greater than 90 beats per minute are indicators of severe disease.
| Case study 1 Andrew is a 22-year-old student. He has always been very fit and well in the past and is a non-smoker. He returned a month ago from a round-the-world trip after graduating from university. While he was away, he developed crampy abdominal pain and diarrhoea. Although he had been careful with the food that he ate while away and had ensured that he only drank bottled water, he assumed that he had developed traveller's diarrhoea and self-treated first with rehydration salts and later with over-the-counter loperamide. After arriving home, he started a new job. However, he continued to experience frequent diarrhoea, often needing to go to the toilet seven to eight times daily to pass stool. The cramping abdominal pain had also continued. People at work had noticed that he had to keep going to the toilet, and it had become a bit of a joke in the office. He says that he feels very tired and ‘washed out’. He has come to see you because he has taken time off work as a result of the problem and needs a sick note. On closer questioning, Andrew admits to passing fresh red blood with his stool. He says that the stool is often mixed with mucus. He also says that he has lost about half a stone in weight since his symptoms began. You examine Andrew but there is nothing very much to find. He is slim but not overly thin. He is apyrexial and well hydrated. He is not obviously anaemic. Blood pressure is 110/70 mmHg with a pulse rate of 65 beats per minute. Examination of the abdomen reveals some tenderness across the whole of the lower abdomen but no guarding or rebound. Neither the liver nor the spleen is enlarged and there are no masses palpable. Rectal examination is unremarkable. Andrew has a scar from where his appendix was removed when he was 11 years old.
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Examining the abdomen, patients may have abdominal tenderness. Anal and perianal lesions (pendulous skin tags, abscesses or fistulae) and/or a mass in the right iliac fossa are characteristic of Crohn's disease.
Investigations
A full blood count is useful both to exclude anaemia and to look for a high white cell count that may indicate severe disease. Inflammatory markers such as the ESR and CRP are elevated when the disease is active. Check urea, creatinine and electrolytes to look for dehydration and electrolyte imbalance as a result of diarrhoea and liver function tests to exclude liver disease and check for hypoproteinaemia. Stool cultures (including Clostridium difficile) may be helpful to exclude an infectious cause for the patient's symptoms but note that up to 50% of attacks of colitis may be precipitated by pathogens. Specialist investigations include imaging, endoscopy (Figure 1) and histological evaluation of biopsy samples of affected bowel.
| Case study 2 You give Andrew his sick note and talk through the possible causes of chronic diarrhoea with him. You arrange for him to check a stool sample to exclude infection and check a full blood count, ESR, CRP, thyroid function tests, urea and electrolytes and liver function tests. The following week Andrew returns for review. His symptoms have continued unchanged. The stool sample is negative. The blood tests show that Andrew is very mildly anaemic with haemoglobin just below the lower limit of normal for a man at 11.5 g/dl. His white cell count is slightly raised at 12.8 x 109 per litre and both his ESR and CRP are markedly raised at 62 mm/h and 23 mg/l, respectively.
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Severity of IBD
The criteria for assessment of severity of UC are listed in Table 3. For patients with Crohn's disease, indicators of severe disease include:
- Severe abdominal pain—especially if associated with tenderness
- Severe diarrhoea (more than eight times daily) with or without bleeding
- Dramatic weight loss
- Bowel obstruction
- Fever of greater than 37.5°C or other signs of systemic disease (increased pulse rate over 90 beats per minute, raised ESR, raised white cell count, decreased haemoglobin to below 10 g/dl)
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When should I refer?
Roughly 50% of severe attacks of UC are first attacks in patients who do not have a prior diagnosis. If any patient presents with bloody diarrhoea with a fever of greater than 37.5°C or tachycardia of greater than 90 beats per minute, then admit the patient as an acute medical emergency. Infrequently, patients with UC (and very rarely Crohn's disease) develop toxic megacolon as a result of a severe, acute attack. The colon distends and may perforate. If suspected, admit as an acute surgical emergency.
If any patient presents with persistent, unexplained diarrhoea lasting for more than 6 weeks and/or persistent abdominal pain, refer urgently for further investigation to establish a diagnosis. NICE recommends urgent referral (to be seen by a specialist within 2 weeks) to exclude malignancy for any patient:
- Over the age of 40 years, reporting rectal bleeding with a change of bowel habit towards looser stools and/or increased stool frequency persisting for more than 6 weeks
- Over the age of 60 years, reporting rectal bleeding persisting for 6 weeks or more without a change in bowel habit and without anal symptoms or change in bowel habit to looser stools and/or more frequent stools persisting for 6 weeks or more without rectal bleeding
For patients already with a diagnosis of IBD, refer back to the gastroenterologist supervising care if the patient has continuing disabling symptoms despite treatment and/or the patient has worsening or new symptoms but does not require admission. Urgency of the referral will depend on the clinical state of the patient.
| Case study 3 You decide to refer Andrew for further investigation to the local gastroenterologist. He sees Andrew 3 weeks later and does a sigmoidoscopy in clinic. At sigmoidoscopy, there are some lesions visible that suggest UC. Biopsies are taken and Andrew is reviewed a week later with the results. The diagnosis is confirmed. He is then referred to have a colonoscopy to confirm the extent of the disease.
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Associated conditions |
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Extraintestinal manifestations occur in up to 50% of patients with IBD and are particularly common among those with colonic involvement. Skin, joints and eyes are the preferred sites.
Joint disease
Joint diseases in the form of seronegative spondylarthropathies affect 25–50% of patients with IBD. Peripheral arthritis is common affecting 12%. Patients present with acute painful swelling of one or two joints only. The condition tends to affect joints in the lower limbs and accompanies the activity of the underlying bowel disease. Treatment of the patient's bowel disease results in improvement of arthritis. This type of arthritis does not result in destruction of the joint.
Sacroileitis is the most common joint disease and is often found incidentally on X-ray. It may be symptomless. Patients with the HLA B27 antigen are likely to go on to develop ankylosing spondylitis (AS). AS affects 4% of patients with IBD and 12% of patients with Crohn's disease. It may precede the bowel disease and follow a slow, relentless course irrespective of IBD activity.
Eye disease
Eye disease affects 10% of patients with Crohn's disease and 4% of patients with UC. The incidence increases if the patient has other extraintestinal manifestations of IBD. For example, 30% of patients with Crohn's disease and arthritis have eye manifestations.
Episcleritis (Fig. 2) is the most common eye manifestation of IBD. It presents with diffuse non-tender inflammation of the eye with no discharge. Inflammation is usually unilateral (two-thirds). Episcleritis may precede gastrointestinal symptoms and responds to treatment of the underlying bowel disease. It is a good indicator of disease activity and if episcleritis recurs after treatment of Crohn's or UC, it may signal reactivation of the bowel disease.
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Uveitis usually presents as iritis (anterior uveitis). Patients develop acute onset of pain, photophobia and watering of the eye. There is blurred vision or reduced visual acuity. On examination, there may be redness around the cornea, a small or irregular pupil and possibly keratitic precipitates on the posterior surface of the cornea (Fig. 3) and/or a hypopyon (anterior chamber pus, causing a white ‘fluid-level’ line). Pain increases as the eyes converge and pupils constrict. Uveitis is associated with a high incidence of HLA B27 antigen, 90% of those patients with IBD who develop uveitis also have arthritis and 30% have erythema nodosum. It always needs specialist management.
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Skin changes
Skin changes occur in up to 25% of patients with IBD. In UC, erythema nodosum (Fig. 4) correlates with disease activity. In Crohn's disease, erythema nodosum may precede gastrointestinal symptoms or occur when the Crohn's disease is quiescent. Its presence suggests colonic involvement. In both cases, the skin condition responds to treatment of the underlying bowel disease. Pyoderma gangrenosum (Fig. 5) almost exclusively affects patients with UC. It is not related to disease activity.
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Liver disease
Several types of liver disease have been described as associated with IBD. Patients with Crohn's disease affecting the terminal ileum tend to get gallstones. This is because they are unable to recycle enough bile acid through absorption in the terminal ileum and the cholesterol in the bile precipitates out forming stones as a result.
UC is associated with both autoimmune hepatitis (roughly, 16% of patients with severe autoimmune hepatitis UC) and primary sclerosing cholangitis (a condition resulting in multiple strictures in the biliary tree in the absence of gallstones, affecting 5% of patients with UC). Some patients may have both. Rarely, primary sclerosing cholangitis is also described in association with Crohn's disease with colonic involvement. All patients with IBD and jaundice or persistently raised transaminase levels should be investigated.
Gastrointestinal malignancy
Patients with IBD have increased risk of gastrointestinal cancer. Those with Crohn's disease have increased risk of both large and small bowel cancer with 5% developing a tumour within 10 years of diagnosis.
Of all colonic cancers, only 1% are attributable to UC. However, around 5% of all patients with UC develop colonic cancer. Cancer tends to develop at a relatively young age with a peak incidence at the age of 48 years. Patients with UC have an increased risk of colonic cancer if:
- They have had UC for more than 8 years
- Onset was in childhood or adolescence
- They are aged over 45 years
- There is a family history of colonic cancer
- The patient has extensive colitis
- The patient has sclerosing cholangitis
Patients with UC and Crohn's disease affecting the colon should be screened regularly with colonoscopy. The majority of IBD-associated tumours found are TNM stage I (18%) or stage II (37%), suggesting that surveillance identifies patients at an early stage of cancer. The frequency of screening depends on the severity of the disease and duration of symptoms.
Other associated conditions
Patients with IBD are at increased risk of venous thromboembolism (odds ratio 3.6). They also have an excess risk of osteoporosis (odds ratio 1.5). Patients with Crohn's disease have a particularly high risk of osteoporosis and it is thought that this is due to a direct effect on bone metabolism. Amyloidosis also affects a small proportion of patients with Crohn's disease.
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Management of UC |
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Follow-up of patients with UC in secondary care is routine. Most patients require lifelong therapy. Long-term treatment reduces the risk of colonic cancer in patients with UC by 75%.
The mainstay of treatment of UC is the 5-aminosalicylic acid (5-ASA) derivative mesalazine 1–2 g daily as maintenance therapy or an equivalent alternative such as balsalazide 2.5 mg daily. This is usually started by the specialist supervising care, and continued prescriptions are provided by the GP. Dose of mesalazine can be increased to 2–4 g daily in primary care to treat flare-ups of disease. Topical 5-ASA derivatives (such as rectal mesalazine 1 g daily) are a useful adjunct for patients with troublesome rectal symptoms or can be used alone as maintenance treatment for patients with disease confined to the rectum or descending colon. In addition, proximal constipation is treated with stool-bulking agents or laxatives. Non-steroidal anti-inflammatories can precipitate relapse, so avoid them.
Steroids (prednisolone 40 mg od orally together with a rectal preparation) are added if a prompt response is needed or treatment with a 5-ASA derivative proves unsuccessful. This may be done by either the patient's GP or specialist supervising care. Review all patients on steroids frequently and taper off the dose of steroids once symptoms start to improve over a period of about 8 weeks. Rapid withdrawal increases the risk of relapse. Always consider concomitant osteoporosis prophylaxis with a bisphosphonate. Cyclosporin or infliximab (anti-TNF antibody) may be effective as acute therapy for severe, steroid refractory disease. This should be specialist initiated.
| Case study 4 Andrew returns to see you 3 months later. He is much better. His abdominal pain has gone and, although he still has to pass stools 2–3 times a day, he says that he can live with that. He has no blood or mucus in his stool now. You review his medication. He was prescribed a course of prednisolone by his consultant to settle his symptoms down. He has been tailing off the dose over the past few weeks and is now down to 5 mg daily. He has instructions from his consultant about how to stop the tablets completely. He has discussed the risks and benefits of steroid treatment with his consultant and does not need a bisphosphonate for osteoporosis prophylaxis unless he requires repeated courses of steroids. Andrew is also taking mesalazine 1 g daily. You ensure that this is added to his repeat medication on the computer. You warn him not to take non-steroidal anti-inflammatories, even those bought over the counter, as these may worsen his symptoms. Andrew has lots of questions about UC and in particular the risk of developing bowel cancer associated with it. You talk this through with him, stressing the importance of taking his medication and ongoing consultant follow-up, and give him the web address of the National Association for Colitis and Crohn's disease so that he can obtain more information at his leisure. Andrew is aware that UC is a lifelong condition and that he may have relapses of symptoms in the future. He knows to contact you if this occurs.
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Azathioprine is a third-line agent usually initiated by the specialist supervising care. It is used for the 10% of patients with UC who are intolerant to 5-ASA derivatives. It is also added to treatment with a 5-ASA derivative if:
- the patient is having recurring attacks despite mesalazine maintenance
- the patient is having two or more courses of steroids per year
- the disease relapses as the dose of steroid is tapered
- the disease relapses within 6 weeks of stopping steroids
Patients taking azathioprine require regular supervision with a full blood count and liver function tests at least every 3 months once the patient is stable. Local policies apply. A serious side effect of azathioprine is dose-related bone marrow suppression. Patients should be warned to report immediately any signs or symptoms of bone marrow suppression such as infection, unexplained bleeding or bruising. The risk of myelosuppression is increased in those with a low activity of the enzyme thiopurine methyltransferase (TPMT) that metabolizes azathioprine, and particularly, in the very few individuals who are homozygous for low-TPMT activity. It is possible to test for TMPT levels before starting the drug. Azathioprine is metabolized to mercaptopurine, and doses should be reduced when allopurinol is given concurrently.
Surgery is a last resort but should not be delayed if the patient has severe colitis and is failing to respond to medical therapy. In severe UC, a CRP of greater than 45 g/dl after 3 days of steroid treatment indicates an 85% risk that the patient will require a colectomy and 20–30% of patients with pancolitis require colectomy. Following colectomy, one in three patients develop pouchitis (a non-specific inflammation of the ileal reservoir) within 5 years.
Prognosis
At any time 50% of patients with UC are asymptomatic, 30% have mild symptoms and 20% have moderate or severe symptoms. Less than 5% are free from relapse after 10 years. Relapses usually affect the same part of the colon.
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Management of Crohn's disease |
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Follow-up in secondary care is routine. Treatment is aimed at minimizing the impact of the disease. The most effective measure that patients can take to alleviate the symptoms of Crohn's disease is to stop smoking. Treat diarrhoea symptomatically with codeine phosphate or loperamide unless it is due to active colonic disease. Cholestyramine (4g one to three times daily) reduces diarrhoea due to terminal ileal disease or resection. Non-steroidal anti-inflammatories can precipitate relapse, so avoid them.
The 5-ASA derivatives, such as mesalazine, are less effective in Crohn's disease than for UC. Mesalazine is ineffective for maintenance treatment at doses under 2 g daily and flare-ups should be treated with 4 g daily.
Steroids (prednisolone 40 mg od po or budesonide 9 mg daily) are added if active disease is unresponsive to mesalazine. Review frequently and taper the dose over 8 weeks. Rapid withdrawal increases risk of relapse. Steroids are associated with increased risk of severe sepsis and mortality in Crohn's disease, so alternatives to steroid therapy are increasingly sought and steroid maintenance for longer than 3 months should always be avoided. Elemental or polymeric diets for a period of 4–6 weeks can be a useful adjunct or alternative to steroid treatment—take consultant advice. Other medical treatments used with consultant supervision for treatment of active disease and/or maintenance treatment include metronidazole, azathioprine, methotrexate and antitumour necrosis factor (infliximab or adalumimab).
Surgery is an option if medical treatment has failed. About 50% need surgery within 10 years of onset of Crohn's disease. Surgery is not curative and 50% will require a further operation at a later stage. After ileal resection, check B12 levels annually.
Prognosis
About 75% of patients with Crohn's disease are back to work after the first year but 15% remain unable to work long term.
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Long-term support in primary care |
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A multidisciplinary approach coordinating care in general practice with specialist gastroenterology and surgery services is essential. IBD is a chronic, embarrassing, lifelong condition that has a major impact on the patient's work and domestic life. Many patients even find discussing their symptoms with health professionals acutely embarrassing. Ask directly about the patient's symptoms, and adopt a caring, non-judgemental attitude to minimize communication difficulties. Provide both verbal and written information and support as needed.
There is a great deal of useful information available from the National Association for Colitis and Crohn's disease [Website: www.nacc.org.uk, Tel: 0845 130 2233 (information); 0845 130 3344 (support)]. Patients who join the NACC are issued with a combined membership and ‘Can’t wait’ card. The card carries the message ‘Please help—our member has a medical condition which means that they need to use your toilet facilities urgently. Your kindness and cooperation would be much appreciated’. RADAR (www.radar.org.uk) operates a National Key Scheme to enable people access to disabled toilets. Keys and an accompanying information booklet are available from the RADAR shop by mail order.
Key points
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References |
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Carter MJ, Lobo AJ. Travis SPL Guidelines for the management of inflammatory bowel disease in adults (. (2004) Accessed via www.bsg.org.uk/pdf_word_docs/ibd.pdf.
Delaunoit T, Limburg PJ, Goldberg RM, Lymp JF, Loftus EV. Jr. Colorectal cancer prognosis among patients with inflammatory bowel disease. Clinical Gastroenterology and Hepatology (2006) 4:335–42.[CrossRef][Web of Science]
Miehsler W, Reinisch W, Valic E, et al. Is inflammatory bowel disease an independent and disease specific risk factor for thromboembolism? Gut (2004) 53:542–48.
NACC. Inflammatory bowel disease basics. Accessed via: www.nacc.org.uk/content/ibd.asp.
NICE. NICE Referral guidelines for suspected cancer (2005) Accessed via www.nice.org.uk/nicemedia/pdf/CG027fullguideline.pdf.
RCGP. RCGP Curriculum statement 15.2: Digestive problems. Accessed via www.rcgp-curriculum.org.uk/PDF/curr_15_2_Digestive_problems.pdf.
Rutter MD, Saunders BP, Kwilinson KH, et al. Thirty-year analysis of a colonoscopic surveillance program for neoplasia in ulcerative colitis. Gastroenterology (2006) 130:1030–38.[CrossRef]
Scott NR, Lewis BB. British Society of Gastroenterology guidelines for osteoporosis in inflammatory bowel disease and coeliac disease (2007) Accessed via www.bsg.org.uk/pdf_word_docs/ost_coe_ibd.pdf.
Simon C. Oxford GP Library: Gastroenterology (2008) Oxford: Oxford University Press.
Thompson NP, Driscoll R, Pounder RE, Wakefield AJ. Genetics versus environment in inflammatory bowel disease: results of a British twin study. British Medical Journal (1996) 312:95–96. Accessed via www.bmj.com/cgi/content/full/312/7023/95?ijkey=fe52354dee7fbaf04d010ed92133a36ccba6043d&;keytype2=tf_ipsecsha.
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