Faecal calprotectin diagnostic tests for inflammatory diseases of the bowel

IBS is a functional bowel disorder characterised by frequent bouts of bowel disturbance, abdominal pain and discomfort, and bloating. There is no clear cause, no distinctive pathology and treatment is symptomatic. Exacerbations may be triggered by diet or stress. Physiological studies often show an increase in bowel sensitivity, and the condition may be associated with abnormal muscle activity in the wall of the bowel. It is troublesome and can interfere with activities of daily life, although it does not usually cause serious morbidity.

The NICE guideline on irritable bowel syndrome in adults suggests a prevalence of between 10% and 20% in the general population. Prevalence figures can vary depending on the diagnostic criteria used, which may account for the range of reported values. The true prevalence of IBS may be higher than estimated because many people with IBS symptoms do not seek medical advice; the NICE guideline cites NHS Direct online data that suggest 75% of people using this service rely on self-care. IBS most commonly affects people between the ages of 20 and 30 years and is twice as common in women as in men. Recent evidence shows that there is also a significant prevalence of IBS in older people. In terms of non‑IBD conditions, the percentage of people with IBS is greater in adults than children.

IBD is the term normally given to a group of conditions that involves inflammation of the gastrointestinal tract, such as Crohn's disease and ulcerative colitis. These conditions can sometimes have serious complications, including a high risk of surgery and an increased risk of colorectal cancer. In both ulcerative colitis and Crohn's disease, some people have active disease but no symptoms.

Ulcerative colitis and Crohn's disease are the 2 most common forms of IBD. The incidence of ulcerative colitis is approximately 10–20 per 100,000 per year, with a reported prevalence of 100–200 per 100,000 people. The incidence of Crohn's disease is around 5–10 per 100,000 per year (and thought to be increasing), with a prevalence of 50–100 per 100,000 people. There is little gender difference in the prevalence of IBD, but it is more common in white people than in African‑Caribbean people or those of Asian origin. The condition is most prevalent in Jewish people of European origin. The ratio of Crohn's disease to ulcerative colitis varies between adults and children. In adults, the ratio of Crohn's disease to ulcerative colitis is 2:3, while the ratio in children is much higher (2.3:1).

Ulcerative colitis: is a relapsing and remitting disease characterised by inflammation of the colon, sometimes intense, with bloody diarrhoea, but more often milder. The cause is not known, but some people seem to be more genetically susceptible than others; around 10% of people with ulcerative colitis have a first‑degree relative with the condition. There may be an abnormal immune response to the natural bacteria that live in the gut. Sometimes, ulcerative colitis occurs after an episode of gastroenteritis caused by organisms such as Salmonella, Shigella and Campylobacter. However, in this case, the condition is more commonly triggered by resulting changes in the natural gut flora than by the direct effects of these organisms.

Crohn's disease: can present in different ways, depending on which part of the intestinal tract is affected. Like ulcerative colitis, it is a relapsing and remitting inflammatory disease. However, it can be a much more extensive disease and can affect any part of the gastrointestinal tract. The cause is unknown, but there is a genetic susceptibility. Like ulcerative colitis, it can occur after infectious gastroenteritis and is associated with disturbances in the natural gut flora. The highest incidence of Crohn's disease is in the 15–30 year age range, but 20–30% of people with the condition are younger than 20 years and onset occurs in people younger than 17 years about 25% of the time. The incidence of Crohn's disease in the general population has been increasing both within the UK and internationally.

The pattern of symptoms in children is different from that in adults. The largest prospective survey in the UK and Ireland was carried out by the British Paediatric Surveillance Unit, the British Society of Gastroenterology Research Unit and the Paediatric Register of IBD. The commonest presenting symptoms of Crohn's disease are abdominal pain, weight loss and diarrhoea, but 44% of children in the survey did not report diarrhoea, and only 25% reported all 3 together. Other symptoms at presentation included lethargy and anorexia. Paediatric IBD is often more extensive at diagnosis than in adults.

IBS is not associated with the development of serious comorbidities, and there is no indication that it is linked with a worse prognosis compared with the general population.

However, IBS can be painful, disrupt normal activities and reduce quality of life. For example, Spiegel et al. (2009) reported that quality of life in people with IBS is reduced by 26% on average and by 30% if the condition is severe when compared with a person at full health. Quality of life is reduced because of disturbed work and sleep, and anxiety. People with IBS can have symptoms for many years.

IBD can be painful, disrupt normal activities and reduce quality of life, particularly during periods of active disease. For example, Stark et al. (2010) reported that quality of life is reduced by an average of 16% (by 9% for those in remission and by 29% for those with active disease) in people with ulcerative colitis, and reduced by an average of 23% (by 11% for those in remission and by 39% for those with active disease) in people with Crohn's disease when compared with a person at full health.

Ulcerative colitis: at first presentation, most patients have mild disease and only 10% have severe disease. About 50% will continue to have mild disease or be in remission but, in about 20% of patients, ulcerative colitis will be chronic and continuous, and be more likely to become extensive throughout the colon. Ordas et al. (2012) noted that, 10 years after onset, 20% to 30% of patients will have needed removal of the colon (colectomy). Ford and Talley (2013) estimated a lower colectomy rate of around 10%. The risk of mortality does not seem to be raised in people with ulcerative colitis compared with the general population.

Crohn's disease: the outlook in Crohn's disease is worse than in ulcerative colitis. Only 10% of people with this condition have prolonged remission. Ford and Talley (2013) estimated that approximately 20% need hospital admission each year, and 50% will need surgery within 10 years of diagnosis. Life expectancy is slightly decreased in people with Crohn's disease compared with the general population (Baumgart and Sandborn 2012).

There are 3 main serious intestinal complications in Crohn's disease. One is stricture (narrowing) of the bowel, which can lead to intestinal obstruction, so Crohn's disease can present as an 'acute abdomen' needing surgery, sometimes mimicking appendicitis. Another is fistulas, which are abnormal connections between sections of the bowel, or between the bowel and bladder. The third is colorectal cancer, and surveillance for this is needed.

The symptoms of lower gastrointestinal disorders (including IBD and IBS) can be sufficiently similar to sometimes make diagnosis difficult. Tests are often carried out to exclude conditions rather than to diagnose them, leading to repeat visits and investigations.

In most cases the diagnosis of IBS can be made on the basis of clinical history alone. The NICE guideline on irritable bowel syndrome in adults recommends that people presenting with abdominal pain or discomfort, bloating or a change in bowel habit for at least 6 months should be asked if they have any red flag indicators such as unexplained weight loss. They should also be clinically tested for red flag indicators, including anaemia, rectal masses, inflammatory biomarkers for IBD (faecal calprotectin is not specifically mentioned) and late onset (older than 60 years) change in bowel habits. Presence of any of these indicators should result in a referral to secondary care for further investigation. Therefore, patients presenting with symptoms or test results indicative of IBD are referred to secondary care for specialist investigation (most likely to a gastroenterology clinic).

If there are no red flag indicators to cause concern, the NICE guideline on irritable bowel syndrome in adults states that patients who meet the IBS diagnostic criteria should receive the following laboratory tests to exclude other diagnoses:

• full blood count

• erythrocyte sedimentation rate or plasma viscosity

• C-reactive protein

• antibody testing for coeliac disease (endomysial antibodies or tissue transglutaminase antibody).

Of these, the 2 main tests for inflammation are erythrocyte sedimentation rate and C‑reactive protein. However, these tests can be influenced by non‑intestinal diseases and can lack diagnostic accuracy. Therefore, while both tests can identify inflammation, they cannot localise it to the bowel. As a result, many patients are referred for further investigation involving endoscopy, which may not be needed. The NICE guideline on irritable bowel syndrome in adults states that an endoscopy (and a range of other tests) is not needed to confirm the diagnosis of IBS.

Most people diagnosed with IBS at this stage are managed in primary care.

People with lower bowel symptoms are likely to be referred to secondary care when there is uncertainty about the diagnosis, or a high clinical suspicion of IBD that needs further investigation.

British Society of Gastroenterology guidelines on IBS (2007) suggest that tests conducted in secondary care are largely based on the likely differential diagnosis. Initial laboratory tests in secondary care include full blood count, erythrocyte sedimentation rate, C‑reactive protein, endomysial antibodies and tissue transglutaminase antibody. These tests may already have been done at the request of primary care. The next level of investigation involves endoscopy and imaging.

British Society of Gastroenterology guidelines on IBD (2011) state that 'the diagnosis of IBD is confirmed by clinical evaluation and a combination of biochemical, endoscopic, radiological, histological, or nuclear medicine based investigations'. Initial laboratory investigations in common practice include full blood count, erythrocyte sedimentation rate, C‑reactive protein and other tests such as kidney function tests. The guidelines state: 'faecal calprotectin is accurate in detecting colonic inflammation and can help identify functional diarrhoea'. The next level of investigation involves endoscopy (with or without a biopsy), histology and imaging.

Endoscopy can be colonoscopy, involving inspection of the whole colon; sigmoidoscopy, inspecting only the distal part of the bowel (the sigmoid colon); or gastroscopy, visualising the oesophagus, stomach and upper part of the small bowel. There are some sections of the small bowel that cannot currently be reached by widely available forms of endoscopy. Options then include capsule camera endoscopy (the 'camera pill'), and imaging methods including ultrasound and MRI.

Therefore, the British Society of Gastroenterology guidelines suggest that patients with symptoms indicative of IBD or IBS presenting in secondary care follow a similar diagnostic pathway of initial investigations before receiving endoscopy (second level of testing). As in primary care, erythrocyte sedimentation rate and C‑reactive protein are the main markers used to measure intestinal inflammation.

A UK and Ireland survey found that delays in diagnosis of Crohn's disease in children were common; 18% had had a pre‑diagnosis symptom for 1 to 3 years, and 9% had had one for more than 3 years. Only 9% had isolated small bowel disease.

The aetiology of IBS has not yet been established and, as a result, management focuses on the relief of symptoms. The symptom profile can vary and can need a combination of different interventions to achieve effective relief. These include watchful waiting, diet and lifestyle interventions, patient education and self‑help, drugs, behavioural and psychological therapies, and complementary and alternative therapies. Drugs include antispasmodic agents, laxatives, antimotility agents and, as second‑line treatment, antidepressants. The treatment of IBS often requires trials of different therapies because some do not improve symptoms. The process of trying different therapies may take several months; the significance of this is that the patient may have IBD and there may be a delay before the correct diagnosis is suspected and the patient is referred for specialist investigation.

The treatments and the aims of management for IBD have changed in recent years. Schoepfer et al. (2012) comment that the aims have evolved from relieving symptoms towards mucosal healing. They consider that this shift has been driven by the arrival of new medications such as the anti‑tumour necrosis factor (anti‑TNF) drugs, which can induce and maintain mucosal healing.

The aim of treatment in active disease is to secure and maintain remission. Management involves diet and lifestyle interventions, drugs and surgery to induce and maintain remission. Drugs include aminosalicylates, corticosteroids, thiopurines, disease-modifying anti-rheumatic drugs (such as methotrexate), immunosuppressants (such as ciclosporin) and anti‑TNF drugs (such as infliximab). There is an increased risk of colorectal cancer, so surveillance is part of patient care.