Inflammatory bowel disease

Contributed by Dr Andrew Robinson consultant physician and gastroenterologist, Salford Royal NHS Foundation Trust.

Section 1: Epidemiology and aetiology
Nearly a quarter of a million people in the UK live with inflammatory bowel disease (IBD), of whom two-thirds have a diagnosis of ulcerative colitis (UC) and one-third have Crohn's disease.

The term IBD also encompasses smaller numbers of patients with indeterminate colitis, and some with macroscopically normal colon in whom histology shows lymphocytic or collagenous colitis.

The incidence of UC is fairly stable, but there has been a steady increase in the number of patients with Crohn's disease over the past couple of decades.

Endocscopic view: ulceration in Crohn’s disease (DAVID M. MARTIN, MD / SCIENCE PHOTO LIBRARY )

IBD is much more common in developed countries and in the northern hemisphere, and Ashkenazi Jews have the highest prevalence of Crohn's disease.

Aetiology
Smokers are three times more likely to develop Crohn's disease than non-smokers but are half as likely to develop UC; the reasons for the differential effects of smoking remain poorly understood.1

IBD runs in families. There is a 10-fold increased risk if there is any family history and a 30-fold increased risk if a sibling has IBD. Half of identical twins are concordant for Crohn's disease indicating a high, but not exclusively genetic aetiology.

The role of gut bacteria in IBD is controversial, although most researchers now believe that IBD results from the interaction of gut organisms and the immune system of genetically-susceptible patients.

Studies using interleukin-10 deficient mice - which develop a form of colitis similar to UC - show that the disease can be prevented by raising the mice in a sterile environment, which prevents naturally-occurring gut colonisation.

No single infectious organism has been reliably identified as the trigger for IBD, but Mycobacterium paratuberculosis, Helicobacter hepaticus and the measles vaccine have all been cited as possible candidates.

Genetics
Recent breakthroughs in IBD genetics may hold the key to understanding these diseases.

Several gene loci are linked to Crohn's disease susceptibility and the best characterised of these is the NOD2/CARD 15 gene on chromosome 16, which accounts for about 15 per cent of Crohn's disease in Western countries.2

This gene codes for an intracellular protein that recognises a bacterial cell wall antigen muramyl dipeptide. Therefore, mutations result in impairment of bacterial handling in the gut.

The protein is found in epithelial cells, macrophages and Paneth cells: Paneth cells are particularly plentiful in the distal small bowel, the most common site for Crohn's disease.

Section 2: Diagnosis
The symptoms of IBD are dependent on the site of inflammation and can therefore present with an array of gastrointestinal problems.

In some patients the diagnosis can be delayed for years as there is a significant symptomatic overlap with irritable bowel syndrome (IBS), which is much more common.

Early diagnosis is a particular problem for patients with small bowel Crohn's disease and those with colitis but without rectal bleeding. IBD should always be considered in patients with unresponsive symptoms.

Presentation
UC usually presents with diarrhoea, rectal bleeding, urgency and tenesmus. Many of the symptoms arise from inflammation in the rectum, and patients with localised rectal disease (proctitis) may be just as symptomatic as those with more extensive disease.

Crohn's colitis may mimic UC but if there is no rectal involvement there will be less urgency and tenesmus, and pain and weight loss may be the presenting symptoms.

Some 70 per cent of patients with Crohn's will have disease in the terminal ileum. This may be picked up asymptomatically (e.g. in a patient with iron deficiency anaemia) or present with pain after eating, weight loss or a painful mass in the right iliac fossa.

Stricturing disease can lead to vomiting and obstruction and fistulising disease can produce a variety of symptoms including recurrent UTIs, faeculent urine, pneumaturia (air in the urine) or vaginal discharge.

Around 30 per cent of Crohn's patients will have perianal disease including fissures, fistulae, abscesses or skin tags.

Any patient presenting with possible IBD should have a full history taken including symptoms, family history, extra-intestinal manifestations3 (see box below) and weight change.

Extraintestinal manifestations of IBD
Musculoskeletal
  • Ankylosing spondylitis
  • Large joint arthritis
  • Osteoporosis
Skin
  • Erythema nodosum
  • Pyoderma gangrenosum
Eyes
  • Uveitis
  • Episcleritis
Hepatobiliary
  • Sclerosing cholangitis
  • Autoimmune hepatitis
  • Gallstones (Crohn's)

Initial investigations
Examination is usually normal, although there may be signs of iron or vitamin deficiency (stomatitis or glossitis), mouth ulcers, pallor, arthritis, uveitis, abdominal mass or perianal disease.

A stool specimen for microscopy and culture is essential for all patients with diarrhoea. FBC (anaemia and elevated platelet count support diagnosis), ESR, CRP, LFTs and albumin should be checked for all those with suspected IBD. Coeliac antibodies are useful for patients with diarrhoea and weight loss.

Further investigation
Patients with raised inflammatory markers, weight loss, rectal bleeding or persistent, unresponsive symptoms should be referred for further investigation.

Colonoscopy is undertaken in patients with suspected large bowel disease.

Small bowel Crohn's is usually diagnosed by barium meal and follow-through. Newer techniques, including MR scanning and capsule enteroscopy (a tablet-sized camera that is swallowed and transmits thousands of images to a receiver on the patient's belt), are making diagnosis easier.4

Perianal disease is best assessed by MR scanning or examination under anaesthetic.

Section 3: Management
Acute mild-to-moderate colitis is usually treated with a combination of oral and topical mesalazine resulting in remission for about 60 per cent.5

Those with more severe disease require urgent specialist management often with tapering oral prednisolone (40mg to zero over eight weeks) or IV hydrocortisone.

Drug treatment
All patients receiving steroids should be given concomitant calcium and vitamin D3. Those with more than six bloody motions per day, fever or systemic involvement also require an urgent abdominal X-ray to exclude toxic colonic dilation, a potentially life-threatening complication of acute colitis.

Hospitalised patients failing to respond to IV steroids will be considered for colectomy after three days.

Trials are underway comparing infliximab with ciclosporin as salvage therapy for unresponsive patients.

Patients with frequently relapsing disease, those who relapse when steroids are reduced and those with steroid intolerance are given immunosuppressant therapy.

Azathioprine or its metabolite 6-mercaptopurine are most frequently used, although metho-trexate has a role in unresponsive or intolerant patients.

Crohn's disease is also treated with steroids. There is less evidence that 5-ASAs are effective compared with in UC.

Antibiotics are also helpful in some patients with colonic and perianal disease but relapses are common and this is an area of continuing research.

Children with Crohn's disease are often treated with elemental diets to avoid excessive steroid dosing and as a bridge to azathioprine therapy.

Immunological therapies such as infliximab and adalimumab have had a huge impact on disease control for many patients with previously unresponsive severe disease.

Mesalazine can reduce the risk of relapse in UC by over 50 per cent. Furthermore, there is increasing evidence that regular mesalazine therapy reduces the increased risk of bowel cancer associated with colitis.6

This has focused attention on the 60 per cent non-adherence rate with long-term mesalazine therapy. Some preparations are now licensed for once-daily administration in an attempt to improve adherence rates.

Branded 5-ASAs should not be switched for generic preparations. These products are highly specialised drugs and switching can result in disease relapse due to altered pharmacodynamics.

Surgery
Some patients do not achieve sustained remission with medical therapy. For patients with UC, this means a colectomy, irrespective of the extent of disease.

Historically, this resulted in a permanent ileostomy but most patients now elect to undergo ileo-anal pouch surgery, where an artificial rectum is constructed from loops of neo-terminal ileum and anastomosed to the lower anal canal.

This technically demanding surgery should only be carried out in centres undertaking many procedures a year.

There are many surgical procedures undertaken for patients with Crohn's disease and laparoscopically-assisted operations are making recovery quicker and safer in patients with straightforward disease.7

A right hemi-colectomy to remove the terminal ileum and caecum is the most common procedure but ileal or colonic resections may be necessary for patches of stricturing or fistulising disease.

Patients with complex, inflammatory or fistulising disease often require a temporary ileostomy whilst their anastomosis heals. Where possible, fibrotic strictures are treated conservatively using stricturoplasty or balloon-dilated if within reach of an endoscope.

Section: 4 Prognosis
There are many exciting developments in the treatment of IBD, but it is important to get the basics right. A national audit of IBD management identified widespread differences between hospitals in a number of quality indicators.8

As a result, the National Association for Colitis and Crohn's disease (NACC), in collaboration with six professional bodies, has launched 'standards for healthcare services for people with colitis and Crohn's disease' to raise awareness and promote best practice.9

Advances in management
IBD specialist nurses now play an important role in IBD management. Over 50 per cent of hospitals have one or more nurses providing telephone advice, emergency consultations, immunological infusions, database management, education sessions for patients and clinicians, patient panels and counselling services.

Crohn’s disease in the colon (Photograph: spl)

NACC and gastroenterologists are keen to see at least one IBD nurse in every hospital.

Advances in diagnostics provide no-radiation imaging with MRI scanning for peri-anal and small bowel Crohn's, capsule enteroscopy to image the small bowel and double balloon endoscopy for small bowel imaging, biopsy and stricture dilation.

Many new anti-TNF therapies are becoming available and other monoclonal antibody treatments with novel target molecules present hope for patients with severe unresponsive disease.

These include anti-adhesion drugs, which prevent white cell adhesion to the bowel, and other anti-cytokine therapies.

The majority of patients with IBD have mild-to-moderate relapsing disease and do not require immunological therapies. The key to successful management is to maintain remission, respond promptly to relapses and provide timely advice where necessary.

Studies have shown that patients trained in self-management have quicker treatment, fewer hospital visits, reduced GP consultations and greater satisfaction with care than those with traditional management.10

Self-management
All patients should be offered a personalised self-management programme, a telephone helpline for advice and clinic requests, and rapid access to specialist care when required.

Patients with colitis have an increased risk of bowel cancer, although there is evidence that this risk is reduced in patients receiving 5-ASA therapy.

Surveillance colonoscopy is recommended after eight to 10 years to re-assess disease extent and take biopsies to look for dysplasia. The frequency thereafter depends on disease extent and patient agreement but is usually annually for patients with longstanding, extensive disease.

I would recommend NACC to all IBD patients and relatives for information, support and advice (www.nacc.org.uk)

 

References

1. Carter M J, Lobo A J, Travis S P L, on behalf of the IBD Section of the British Society of Gastroenterology Guidelines for the management of inflammatory bowel disease in adults. Gut 2004; 53 (Suppl 5): V1-16.

2. Subramanian S, Campbell B J, Rhodes J M. Bacteria in the pathogenesis of inflammatory bowel disease. Curr Opin Infect Dis 2006; 19(5): 475-84.

3. Bernstein C N, Blanchard J F, Rawsthorne P, Yu N. The prevalence of extraintestinal diseases in inflammatory bowel disease: a population-based study. Am J Gastroenterol 2001; 96: 1,116-22.

4. Bruining D H, Loftus E V. Current and future diagnostic approaches: from serologies to imaging. Curr Gastroenterol Rep 2007; 9(6): 489-96.

5. Travis S P. Review article: induction therapy for patients with active ulcerative colitis. Aliment Pharmacol Ther 2006; 24 (Suppl 1): 10-6.

6. Eaden J. Review article: the data supporting a role for aminosalicylates in the chemoprevention of colorectal cancer in patients with inflammatory bowel disease. Aliment Pharmacol Ther 2003; 18 (Suppl 2): 15-21.

7. Soop M, Larson D W, Malireddy K, et al. Safety, feasibility, and short-term outcomes of laparoscopically assisted primary ileocolic resection for Crohn's disease. Surg Endosc 2009 Jan 28. Epub ahead of print.

8. UK IBD Audit 2006. National Results for the Organisation & Process of IBD Care in the UK. Prepared by The UK IBD Audit Steering Group www.rcplondon.ac.uk/college/ceeu/ceeu_uk_ibd_audit_2006.pdf

9. The IBD Standards Group. IBD Standards: Quality Care Service standards for the healthcare of people who have Inflammatory Bowel Disease (IBD). NACC. www.ibdstandards.org.uk

10. Robinson A, Thompson D G, Wilkin D, Roberts C; Northwest Gastrointestinal Research Group. Guided self-management and patient-directed follow-up of ulcerative colitis: a randomised trial. Lancet 2001; 358(9286): 976-81.

Further reading

  • Stange E, Travis S, Vermeire S et al. European evidence-based consensus on the diagnosis and management of ulcerative colitis: Definitions and diagnosis. Journal of Crohn's and Colitis 2008; 2: 1-23.
  • Travis S, Stange E, Lemann M et al. European evidence-based consensus on the management of ulcerative colitis: Current management. Journal of Crohn's and Colitis 2008; 2: 24-62.
  • Biancone L, Michetti P, Travis S et al. European evidence-based consensus on the management of ulcerative colitis: Special situations. Journal of Crohn's and Colitis 2008; 2: 63-92.

For an archive of all GP clinical reviews visit www.healthcarerepublic.com/clinical/GP

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