Drs Sandeep Shivananda Siddhi (left) and Craig Mowat discuss the British Society of Gastroenterology recommendations on the management of ulcerative colitis and Crohn's disease

Since the publication of the British Society of Gastroenterology guideline on the management of inflammatory bowel disease (IBD) in 2004, there have been significant advances in the therapeutic options available for this condition.1 These advances are outlined in the consensus statements published by the European Crohn's and Colitis Organisation (ECCO).2–7

However, provision of quality care requires more than evidence-based therapeutics. A UK audit in 2006 measured the structure, organisation, processes, and outcomes of IBD services across the country, and identified wide variation in all aspects.8 Several key elements of the audit data have been adopted to validate clinical quality as part of the screening process in the annual health check of hospital trusts.9 Following publication of the audit data, a working party of healthcare professionals subsequently developed a statement of six service standards for IBD that can be applied across the UK.9

These events led to a compelling need for an updated guideline on the management of IBD specific for UK practice to:

  • address the variation in clinical practice and service provision
  • uphold service standards for healthcare of people with IBD
  • acknowledge that UK practice is influenced by guidance from NICE.

The salient points of the BSG guideline have been covered in this article, but readers should refer to the full guideline for more detail (see: www.bsg.org.uk/clinical-guidelines/ibd/guidelines-for-the-management-of-inflammatory.html).

IBD service standards

Throughout the guideline, statements are made as to how patient care can be improved to meet the IBD service standards. These service standards (www.ibdstandards.org.uk) address all aspects of care and lay emphasis on team-working, shared care, patient support and empowerment, education, IT support, and commitment to research and service improvement.9 Selected points from the BSG guideline relating to the IBD service standards are shown in Box 1. The standards will be assessed at future rounds of the national IBD audit.

Box 1: Key messages for GPs from the British Society of Gastroenterology guideline relating to the IBD service standards*1,9
  • Patients should be cared for by a defined IBD team with: gastroenterologists; colorectal surgeons; nurse specialists; dietitians; and a named pharmacist, gastrointestinal histopathologist, and radiologist (Standard A1)
  • Patients should have access to essential supporting services including general practice, with named personnel (Standard A2)
  • Care should be carried out by a multidisciplinary team and involve regular meetings and access to either joint or parallel medical and surgical clinics (Standard A3)
  • Local protocols should be in place to facilitate referral of symptomatic patients in whom IBD is suspected (Standard A4)
  • All patients with IBD who are not under immediate or ongoing care should have basic case information recorded and receive an annual review. This follow up can be performed in the hospital or community or via telephone (Standard A11)
  • Patients who have experienced a possible relapse should have access to specialist review within a maximum of 5 working days (Standard A11)
  • Arrangements for shared care should be defined between hospital staff and with the GP (Standard B1)
  • The IBD service standards state that there must be local protocols for prescribing and monitoring of immunomodulator (thiopurines) and biologic therapies, and local practices must be audited (Standard A6)
  • Patients should have access to dietitian and nutritional support. Nutritional assessment should be performed at diagnosis and regularly monitored. Adolescents must have their height and their weight centile charts monitored and a 6-monthly assessment of pubertal status (Standard A5)
  • Treatment with anti-TNF therapies should only be commenced by clinicians with expertise in their use for IBD (Standard B1).

*These key messages are deliberately concise; please refer to the service standards document for complete information and full details on each standard

IBD=inflammatory bowel disease; TNF=tumour necrosis factor

Definitions

Ulcerative colitis is characterised by diffuse mucosal inflammation limited to the colon. It is classified according to the extent of disease as this is related to the risk of complications. Crohn's disease is characterised by patchy, transmural inflammation, which can affect any part of the gastrointestinal tract. It can be classified by age of onset, location, or behaviour.1,5 Approximately 5% of patients with IBD are not classified because they have features of both ulcerative colitis and Crohn's disease. This is now termed as IBD, type unclassified (IBDU).1

Clinical features and disease course

The main symptom of ulcerative colitis is bloody diarrhoea, which can sometimes be associated with cramps, urgency, and tenesmus. Modern management now means that the disease has a slight excess of mortality in the first 2 years after diagnosis, but little subsequent difference from the general population. Approximately 90% of patients are fully capable of work after the first year.1

Crohn's disease is usually more heterogenous and can cause abdominal pain, diarrhoea, and weight loss. It can also present with malaise, anorexia, and fever. Intestinal obstruction, abscesses, and fistula (perianal) are common.1,5 Approximately 70%–80% of affected patients will require surgery in their lifetime.1,8 Crohn's disease generally causes more disability than ulcerative colitis. Only 75% of affected individuals are fully capable of work in the first year after diagnosis.1

Both ulcerative colitis and Crohn's disease are associated with an increased risk of colonic adenocarcinoma. Smoking increases the risk of Crohn's disease, but decreases the risk of ulcerative colitis.1

Diagnosis and investigations

Diagnosis of IBD is confirmed by clinical evaluation and a combination of haematological, endoscopic, histological, and radiological investigations.1,5 A full history focusing on all aspects of symptoms and risk factors, including travel, family, and smoking is very important. Examination should cover general wellbeing, measurement of weight, calculation of body mass index, pulse rate, blood pressure, temperature, check for anaemia, fluid depletion, and searching for extra-intestinal manifestations.1

Laboratory investigations should include full blood count, renal functions, liver function test, C-reactive protein/erythrocyte sedimentation rate, and haematinics. Testing for faecal calprotectin, if available, is accurate in detecting colonic inflammation and helps to differentiate functional diarrhoea. Microbiological testing of stool samples to exclude standard organisms and in particular Clostridium difficile is recommended as it has a higher prevalence in IBD.5 At least four samples are required to diagnose 90% of cases.1

Colonoscopy is the key investigation as it can confirm the diagnosis both macroscopically and microscopically. Magnetic resonance imaging is fast becoming the gold standard for assessment of small bowel and perineal/pelvic disease in Crohn's disease.1,5 Computed tomography is the gold standard for extraluminal complications.1

Therapeutic management of inflammatory bowel disease

Key developments in the pharmacological management of IBD are:

  • the move to once-daily prescribing of mesalazine for ulcerative colitis
  • acceptance that mesalazine is not an effective treatment for Crohn's disease
  • use of maintenance anti-tumour necrosis factor (TNF) therapy in Crohn's disease.

Management of ulcerative colitis
Therapeutic strategies depend on the severity and disease extent. Patients with mild-to-moderate disease can be managed in the community while those with severe disease need to be admitted to hospital.1

Active (left-sided or extensive) ulcerative colitis
Oral mesalazine 2.4–4.8 g daily or balsalazide 6.75 g daily are effective first-line therapies for mild-to-moderate disease. Topical mesalazine added to oral mesalazine >2 g/day is more effective than oral therapy alone for left-sided and extensive colitis. Once-daily dosing of oral mesalazine is as effective as twice- or thrice-daily regimens and is associated with improved compliance. If mesalazine is ineffective, prednisolone 20–40 mg daily should be considered. This dosage should be reduced gradually over 8 weeks as more rapid reduction is associated with early relapse.

Active proctitis
Topical mesalazine 1–2 g daily may be effective for proctitis. Topical corticosteroids are less effective and should be reserved as second-line treatment. Individuals who do not respond to topical mesalazine or corticosteroids should be treated with oral steroids.

Acute severe colitis
Acute severe colitis is a medical emergency. It is indicated by increased frequency of bloody diarrhoea of more than six times in 24 hours1 nocturnal symptoms with night rising, systemic upset with fever, tachycardia, anaemia, and raised inflammatory markers.10

Intensive inpatient intravenous steroid treatment and early surgical intervention has reduced mortality from acute severe colitis to 2.9%. However, the colectomy rate of 30% has not changed for 40 years. The IBD service should have arrangements in place to admit patients with the condition directly to specialist areas or wards. Patients admitted with known or suspected IBD should be transferred to the care of a gastroenterologist or colorectal surgeon within 24 hours. Infective etiology must be ruled out—at least four stool samples must be sent to microbiology; C. difficile has a higher prevalence in IBD and every attempt must be made to exclude it.

Maintenance of remission

  • Patients with ulcerative colitis should be on maintenance therapy with aminosalicylates (mesalazine) or thiopurines (azathioprine [AZA] or mercaptopurine [MP])
  • Oral mesalazine 1.2–2.4 g/day or balsalazide 4.5 g/day is the first-line maintenance treatment. Annual monitoring of renal function is recommended in patients receiving aminosalicylates
  • Topical mesalazine can be used alone for maintenance of distal disease
  • First-line agents in steroid-dependent ulcerative colitis are AZA 2.0–2.5 mg/kg or MP 0.75–1.5 mg/kg. These drugs should be considered in a number of circumstances (see Box 2).

Before starting thiopurines, all patients should have levels of thiopurine methyl transferase checked (see Box 1, for related service standards). Methotrexate may be considered if patients do not respond to thiopurines or if they are not tolerated.1


Management of Crohn's disease

The general principle is to ascertain the site, pattern, and activity of Crohn's disease before making a decision on treatment. Complications arising from the disease or from previous surgeries should be investigated actively by specialists using clinical judgment and relevant imaging. Patients with Crohn's disease must be strongly advised to quit smoking.1 As a general rule, non-steroidal anti-inflammatory drugs should be avoided.1

Active ileal, ileocolonic, or colonic disease
Treatment should be tailored to patients and their preferences should be taken into account:1

  • Moderately active disease can be treated with oral corticosteroids, such as prednisolone 20–40 mg, which are gradually tapered off over 8 weeks or budesonide 9 mg, which is gradually reduced by 3 mg every 4 weeks. Budesonide is appropriate for isolated ileocaecal disease
  • Patients with severe active Crohn's disease should be admitted for treatment with intravenous corticosteroids. If this is not successful, anti-TNF therapy should be used in induction and subsequent maintenance treatments
  • Primary nutritional therapy (elemental or polymeric) can be considered when corticosteroids are contraindicated or should be avoided, but it is not as effective.

Maintenance therapy
The thiopurines, AZA 2.0–2.5 mg/kg or MP 0.75–1.5 mg/kg, should be considered as first-line treatment for maintenance therapy in a number of circumstances (see Box 2).1

Methotrexate is effective in individuals who do not tolerate or fail to respond to thiopurines. In?iximab and adalimumab are effective for maintenance treatment of Crohn's disease, although long-term data are lacking. However, concurrent infection and sepsis should be looked for and treated before initiating this treatment. There is no role for aminosalicylates (mesalazine) in maintenance treatment.1

Service standards for IBD relating to the management of Crohn's disease are shown in Box 1.

Perianal Crohn's disease
Perianal Crohn's disease is associated with a poor prognosis; the first priority is specialist referral. Close collaboration between medical and surgical teams is very important for management of this common complication. Metronidazole 400 mg tds and/or ciprofloxacin 500 mg bd are appropriate treatment options for simple fistulas. Thiopurines are effective for simple perianal or enterocutaneous fistulae where distal obstruction and abscess have been excluded. Anti-TNF therapy should be considered in cases of refractory disease.1

Box 2: Circumstances under which thiopurines should be considered
  • People who:
    • have had a severe relapse or frequently relapsing disease
    • require more than two or more steroid courses in 12 months
    • have had a relapse within 6 weeks of stopping steroids
  • People whose disease relapses as the dose of steroid is reduced below 15 mg
  • Following ciclosporin or infliximab given as rescue treatment for severe ulcerative colitis.

Other considerations

The BSG recommendations on managing IBD also cover:1

  • calcium and vitamin D supplementation if steroids are used
  • co-administration of bisphosphonates with steroids in patients aged over 65 years or who have known osteopenia/osteoporosis
  • offering influenza, pneumococcal and human papillomavirus (females) vaccines to patients with IBD because they are at increased risk of infections. The hepatitis B vaccine should be considered in non-immune high-risk patients especially before the use of immunosuppressives or anti-TNF agents
  • management of extra-intestinal manifestations of IBD; these are common, particularly in Crohn's disease. Arthritis, ocular inflammation, and skin lesions, such as erythema nodosum and pyoderma gangrenosum can occur. These conditions usually respond to treatment of underlying bowel disease, but sometimes require specific management; liaison with rheumatologists, ophthalmologists, or dermatologists may be warranted.

Management in pregnancy

Approximately 25% of female patients conceive after a diagnosis of IBD. Many of the adverse outcomes in pregnancy are related to poor disease control rather than medications used in IBD. Optimum disease control should ideally be achieved prior to conception and relapses treated aggressively.1 Pregnant women with IBD should be managed jointly by a gastroenterologist and obstetrician. Acute severe colitis or life-threatening complications from IBD should be managed as for non-pregnant patients (including abdominal radiographs). Flexible sigmoidoscopy may be used safely where the information obtained would significantly affect management. Mode of delivery should be considered carefully—Caesarean section should be considered in those with perianal diseases or pouch formations.

The BSG guideline provides specific advice on using medication in pregnancy, which includes the following:

  • Maintaining adequate disease control is of paramount importance to foetal health
  • Corticosteroids and mesalazine can be used during pregnancy and lactation
  • AZA/MP should also be continued as the risk to the foetus from disease activity is greater than from continued therapy. Babies may weigh less than normal and this should be discussed with patients
  • Methotrexate is absolutely contraindicated
  • Caution is advised if initiating or continuing anti-TNF therapy during pregnancy as long-term data are lacking; treatment should be stopped after the second trimester.

Surveillance for colonic carcinoma

The risk of carcinoma is similar in both ulcerative colitis and Crohn's disease. Healthcare professionals should refer to the revised BSG guidelines on the surveillance of patients at high risk of colorectal cancer.11,12 Risk is determined by disease duration and extent, and the presence of inflammation. Surveillance intervals depend on the risk category of the patient.1 It is recommended that all patients have a screening (index) colonoscopy 10 years after symptom onset to identify risk status. Surveillance colonoscopy should be performed during disease remission, but this should not be delayed unduly if remission cannot be achieved.1

Role of primary care

Healthcare professionals in primary care have important roles to play in the diagnosis and management of IBD:

  • Awareness of the IBD standards and the BSG guideline
  • Recognition and appropriate referral of new or exacerbations of known disease to specialist services
  • Close liaison with the hospital teams to manage mild to moderate disease in the community
  • Monitoring stable disease and therapy
  • Patient education.

Summary

Quality care requires more than evidence-based therapeutics. The UK IBD service standards set a new benchmark for care in this clinical area. Primary care has a key role to play in achieving these aspirational standards.

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