Inflammatory bowel disease

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13 Inflammatory bowel disease

S.E. Cripps

Key points

• Ulcerative colitis and Crohn’s disease are the two most common inflammatory bowel diseases (IBD) of the gut. Both are chronic relapsing conditions with a high morbidity and remain largely incurable.
• Ulcerative colitis and Crohn’s disease are similar but there are contrasting features which relate to the site of involvement and extent of inflammation across the bowel wall. Ulcerative colitis is limited to the large bowel and the mucosa, whereas Crohn’s disease frequently involves the small intestine with inflammation extending through the bowel wall to the serosal surface.
• The aims of treatment are to control acute attacks promptly and effectively, induce remission, maintain remission and identify patients who will benefit from surgery.
• Choice and route of therapy will depend on site, extent and severity of the disease together with knowledge of current or previous treatment.
• A reduction in inflammation with corticosteroids and aminosalicylates is the mainstay of treatment, with immunosuppressants (e.g. azathioprine, methotrexate, ciclosporin) and biologic agents (e.g. infliximab and adalimumab), reserved for more severe and refractory cases.
• The management of IBD poses a challenge to the multidisciplinary team both clinically and economically.
• National standards for IBD aim to ensure patients receive consistent, high-quality care and IBD services throughout the UK are evidence based, engaged in local and national networking, based on modern IT and meet specific minimum standards.

Introduction

Inflammatory bowel disease (IBD) can be divided into two chronic inflammatory disorders of the gastro-intestinal tract, namely Crohn’s disease (CD) and ulcerative colitis (UC). Crohn’s disease affects any part of the gastro-intestinal tract whereas ulcerative colitis affects the colon and rectum only. Current available treatment for IBD is not curative. IBD follows a relapsing and remitting course that is unpredictable and causes disruption to a patient’s lifestyle and places a burden on the workplace and healthcare setting. The management of IBD patients poses a challenge to the multidisciplinary team both clinically and economically.

Epidemiology

The incidence of IBD is greater in North America, Europe, Australia and New Zealand, although the incidence in Africa, Asia and South America is rising steadily. This increase in developing countries may be due to improved sanitation and vaccination programmes along with a decreased exposure to enteric infections. Jewish and Asian people living in USA and UK are more commonly affected by IBD than those living in Israel and Asia. There appears to be no association between IBD and social class. The peak incidence of IBD occurs between 10 and 40 years, although it can occur at any age, with 15% of cases diagnosed in individuals over the age of 60 years. The incidence appears equal between males and females, although some studies in Crohn’s disease show a slight female predominance. Up to 240,000 people are affected by IBD in the UK.

The incidence of new cases of ulcerative colitis in Europe and USA is 2–8 per 100,000 per year with a prevalence of 40–80 per 100,000 per year. The incidence has remained fairly static over the last 40 years. In the UK, Crohn’s disease occurs with a similar frequency to ulcerative colitis with around 4 per 100,000 per year and a prevalence of 50 per 100,000. The rates in central and southern Europe are lower. In South America, Asia and Africa, Crohn’s disease is uncommon but appears to be on the rise (Mpofu and Ireland, 2006).

Aetiology

The causative agents of IBD are largely unknown, although a number of factors are thought to play a role.

Environmental

Diet

Evidence that dietary intake is involved in the aetiology of IBD is inconclusive, although several dietary factors have been associated with IBD, including fat intake, fast food ingestion, milk and fibre consumption, and total protein and energy intake. A large number of case-control studies have reported a causal link between the intake of refined carbohydrates and Crohn’s disease (Gibson and Shepherd, 2005). The mechanism for diet as a trigger is very poorly understood.

During the course of the disease, patients are able to identify foods which aggravate or exacerbate their symptoms, for example, milk or spicy foods. Up to 5% of patients with ulcerative colitis improve by avoiding cow’s milk, whilst patients with Crohn’s disease improve if they start to take elemental (amino acid based), oligomeric (peptides) and polymeric (whole protein) feeds, although symptoms may return when their normal diet is reintroduced.

Those that are breastfed as infants have a reduced risk of developing IBD (Mpofu and Ireland, 2006).

Smoking

There is a higher rate of smoking amongst patients with Crohn’s disease than in the general population, with up to 40% of patients with the disease being smokers. Smoking worsens the clinical course of the disease and increases the risk of relapse and the need for surgery. Fewer patients with ulcerative colitis smoke (approximately 10%). Former smokers are at the highest risk of developing ulcerative colitis, while current smokers have the least risk. Stopping smoking can provoke the emergence of ulcerative colitis. This indicates that smoking may help to prevent the onset of the disease. The explanation for this is unclear. However, it is thought that in addition to its effect on the inflammatory response, the chemicals absorbed from cigarette smoke affect the smooth muscle inside the colon, potentially altering gut motility and transit time. In some studies, nicotine has been shown to be an effective treatment for ulcerative colitis (Guslandi, 1999).

Infection

Exposure to Mycobacterium paratuberculosis has been considered a causative agent of Crohn’s disease, although current evidence indicates it is not an aetiological factor.

Ulcerative colitis may present after an episode of infective diarrhoea, but overall there is little evidence to support the role of a single infective agent.

Enteric microflora

Enteric microflora plays an important role in the pathogenesis of IBD because the gut acts as a sensitising organ that contributes to the systemic immune response. Patients with IBD show a loss of immunological tolerance to intestinal microflora and consequently antibiotics often play a role in the treatment of IBD. More recently, manipulating the intestinal flora using probiotics, prebiotics and symbiotic has proven to be an effective therapeutic strategy. Probiotics such as Bifidobacteria and Lactobacilli alter the intestinal microflora balance favourably. Prebiotics stimulate the growth of specific, beneficial microorganisms in the colon whilst synbiotics, a combination of both prebiotics and probiotics, have been successfully used.

Drugs

Non-steroidal anti-inflammatory drugs (NSAIDs) such as diclofenac have been reported to exacerbate IBD (Felder et al., 2000). It is thought this may result from direct inhibition of the synthesis of cytoprotective prostaglandins. Antibiotics may also precipitate a relapse in disease due to a change in the enteric microflora. The risk of developing Crohn’s disease is thought to be increased in women taking the oral contraceptive pill, possibly caused by vascular changes.

MMR vaccine

There has been much debate about the link between bowel disease and measles, measles vaccine or combined measles, mumps and rubella (MMR) immunisation. However, current evidence has indicated no proven correlation.

Appendicectomy

Appendicectomy has a protective effect in both Crohn’s disease and ulcerative colitis (Radford-Smith et al., 2002). It is unclear whether this protective effect is immunologically based or whether individuals who develop appendicitis and consequently have an appendicectomy are physiologically, genetically or immunologically distinct from the population that is predisposed to IBD.

Stress

Some patients find that stress triggers a relapse in their IBD and this has been reproduced in animal models. It is thought that stress activates inflammatory mediators at enteric nerve endings in the gut wall. In addition to stress as a trigger factor, living with IBD can also be stressful. Its chronic nature, lack of curative treatment, distressing symptoms and impact on lifestyle make it difficult for patients to cope.

Genetic

Fifteen percent of first degree relatives have IBD. There is mounting evidence that Crohn’s disease and ulcerative colitis result from an inappropriate response of the immune system in the mucosa of the gastro-intestinal tract to normal enteric flora (Ahmad et al., 2004). Since the mid-1990s there has been considerable progress in understanding the contribution of genetics to IBD susceptibility and phenotype.

Mutations of the gene CARD15/NOD2 located on chromosome 16 have been associated with small intestinal Crohn’s disease in white but not oriental populations. Two other genes have been recently linked with Crohn’s disease (OCTN1 on chromosome 5 and DLG5 on chromosome 10).

Genetic studies in ulcerative colitis have shown human lymphocyte antibody (HLA) is more strongly linked. Genotype related to pattern of disease (HLA-DRI’103) is 5–11 times more common in patients who have undergone colectomy.

Ethnic and familial

Jews are more prone to IBD than non-Jews, with Ashkenazi Jews having a higher risk than Sephardic Jews. In North America, IBD is more common in whites than blacks. First-degree relatives of those with IBD have a 10-fold increase in risk of developing the disease. A familial link is supported from research showing a 15-fold greater concordance for IBD in monozygotic (identical) than dizygotic (non-identical) twins (Jess et al., 2005).

Pathophysiology

In individuals with IBD, trigger factors typically cause a severe, prolonged and inappropriate inflammatory response in the gastro-intestinal tract and the ongoing inflammatory reaction leads to an alteration in the normal architecture of the digestive tract. Genetically susceptible individuals seem unable to downregulate immune or antigen non-specific inflammatory responses. It is thought that chronic inflammation is characterised by increased activity of effector lymphocytes and pro-inflammatory cytokines that override normal control mechanisms. Others, however, have suggested that IBD may result from a primary failure of regulatory lymphocytes and cytokines, such as interleukin-10 and transforming growth factor-β, to control inflammation and effector pathways. In Crohn’s disease, it is also thought that T-cells are resistant to apoptosis after inactivation. Non-pathogenic bowel flora appears to be an essential factor.

Disease location

The character and distribution, both macroscopic and microscopic, of chronic inflammation define and distinguish ulcerative colitis and Crohn’s disease. Table 13.1 shows the differences in location and distribution of ulcerative colitis and Crohn’s disease. Figure 13.1 details the histological differences.

Table 13.1 Location and distribution of ulcerative colitis and Crohn’s disease

  Ulcerative colitis Crohn’s disease
Location Colon and rectum
40% proctitis
20% pancolitis
10–15% backwash ileitis		 Entire gut (mouth to anus, rectal sparing)
45% ileocaecal disease
25% colitis only
20% terminal ileal disease
5% small bowel disease
5% anorectal, gastroduodenal, oral disease
Distribution Continuous, diffuse Often discontinuous and segmental ‘skip lesions’
  Full thickness (transmural)
No granulomas Granulomatous inflammation
Inflammation of mucosa  
Ulceration if fine and superficial Deep ulceration with mucosal extension
Fissures, fistulae and stricture Absent Common
Perianal disease Absent Present
image

Fig. 13.1 Histological features in the rectal biopsy that help to distinguish between ulcerative colitis and Crohn’s disease

(from Misiewicz et al., 1994, with kind permission from Blackwell Scientific Publications, Oxford).

Crohn’s disease

Crohn’s disease can affect any part of the gut from the mouth to the anus. Approximately 45% of patients have ileocaecal disease, 25% colitis only, 20% terminal ileal disease, 5% small bowel disease and 5% anorectal, gastroduodenal or oral disease. Crohn’s disease can involve one area of the gut or multiple areas, with unaffected areas in between being known as ‘skip lesions’. The areas of the small bowel affected are typically thickened and narrow. A ‘red ring’ is often the first visible abnormality seen on colonoscopy. This is a lymphoid follicular enlargement with a surrounding ring of erythema, which develops into aphthoid ulceration and may progress to deep fissuring ulcers with a cobblestone appearance, fibrosis and strictures. Intestinal strictures arise from chronic and extensive inflammation and fibrosis and bowel obstruction may arise. Local gut perforation may cause abscesses which may also lead to fistulae.

Microscopically, inflammation extends through all layers of the bowel. Inflammatory cells are seen throughout, resulting in ulceration and microabscess formation. Non-caseating epithelioid cells, sometimes with Langhans’ giant cells, are seen in about 25% of colonic biopsies and in 60% of surgically resected bowel. Chronic inflammation in the small intestine, colon, rectum and anus leads to an increased risk of carcinoma.

Ulcerative colitis

At first presentation, ulcerative colitis is confined to the rectum (proctitis) in 40% of cases, the sigmoid and descending colon (left-sided colitis) in 40% and the whole colon (total ulcerative colitis or pancolitis) in 20% of cases. Proctitis extends to involve more of the colon in a minority, with 15–30% of patients developing more extensive disease over 10 years. The reason why some patients have extensive disease and some have limited disease is unknown. In severe total ulcerative colitis, there may also be inflammation of the terminal ileum. This is known as ‘backwash ileitis’ but is not clinically significant. The colon appears mucopurulent, erythematous and granular with superficial ulceration that in severe cases leads to ulceration. As the colon heals by granulation, post-inflammatory polyps may form.

Microscopically, superficial inflammation is seen with inflammatory cells infiltrating the lamina propria and crypts. Crypt abscesses occur, the crypt structure is lost and goblet cell depletion arises as mucin is lost. Dysplasia, which can potentially progress to carcinoma, may be seen in biopsies taken from patients with long-standing total colitis.

Other types of colitis

Crohn’s disease yet to be classified (sometimes referred to indeterminate colitis) is when chronic colitis persists, yet the pathology of the disease has not been identified as either Crohn’s disease or ulcerative colitis. In microscopic colitis, the main feature is watery diarrhoea in the presence of a normal colonoscopy and chronic inflammation in the absence of crypt architectural distortion on mucosal biopsies. Drugs such as NSAIDs and proton pump inhibitors (PPIs) are implicated as the cause in up to 50% of cases of microscopic colitis. Diversion colitis is when inflammation occurs in the defunctioned loop of a colostomy causing a mucous discharge. Pseudomembraneous colitis is caused by Clostridium difficile, usually after prolonged or multiple antibiotics. The use of PPIs predisposes patients to infection. It is diagnosed by sigmoidoscopy and detection of C. difficile toxin in the stool.

Clinical manifestation

The clinical differences between Crohn’s disease and ulcerative colitis are described in Table 13.2.

Table 13.2 Clinical differences between ulcerative colitis and Crohn’s disease

Symptom Ulcerative colitis Crohn’s disease
Prominent symptom Bloody diarrhoea Diarrhoea, abdominal pain, weight loss 30%, no gross bleeding
Fever ++ ++
Abdominal pain Variable ++
Diarrhoea +++ +++
Rectal bleeding +++ ++
Weight loss + ++
Sign of malnutrition + ++
Abdominal mass − ++
Dehydration +++ ++
Iron-deficiency anaemia, raised CPR/ESR, hypoalbuminaemia ++ ++

CPR, C-reactive protein; ESR, erythrocyte sedimentation rate; +, the likelihood this symptom will be present; −, symptom absent in patient.

Crohn’s disease

The clinical features of Crohn’s disease depend largely on the site of the bowel affected, the extent, severity and the pathological process in each patient. Crohn’s disease tends to be more disabling than ulcerative colitis with 25% of patients unable to work 1 year after diagnosis. The predominant symptoms in Crohn’s disease are diarrhoea, abdominal pain and weight loss. Weight loss occurs in most patients, irrespective of disease location. Ten to twenty percent of patients will have weight loss greater than 20%. The main cause is decreased oral intake, although malnutrition is also common. There is a slight increase in mortality in patients with extensive Crohn’s disease.

Small bowel, ileocaecal and terminal ileal disease

Patients present with pain and/or a tender palpable mass in the right iliac fossa with weight loss and diarrhoea, which usually contains no blood. Diarrhoea is caused by mucosal inflammation, bile salt malabsorption that causes steatorrhoea or bacterial growth proximal to a stricture. Small bowel obstruction may also occur as a consequence of inflammation, fibrosis and stricture formation. Patients often describe a more generalised intermittent pain which is colicky with loud gurgling bowel sounds (borborygmi), abdominal distension, vomiting and constipation. When inflammation or abscesses are the predominant pathology, many patients present with constant pain and fever. Enteric fistulae occur and may involve the skin, bladder or vagina. Although rare, perforation of the gut may present with an acute abdomen and peritonitis. Vitamin B12 and folic acid deficiencies predispose patients with disease of the terminal ileum to macrocytic anaemia, while bile acid malabsorption also occurs in such patients and predisposes them to cholesterol gallstones and oxalate renal stones.

Colitis

The main symptoms are abdominal pain, profuse and frequent diarrhoea (more than six loose stools per day) with or without blood, and weight loss. Patients also complain of lassitude, anorexia and nausea and appear thin, tachycardic, anaemic, malnourished and febrile. Colitis may present insidiously with minimal discomfort. Patients with severe involvement of the colon or the terminal ileum often have electrolyte abnormalities, hypoalbuminaemia and iron-deficiency anaemia. Extra-intestinal complications are more common in those patients with large bowel disease.

Perianal disease

Patients may present with an anal fissure, fistula or a perirectal abscess. These symptoms can have a significant impact on the patient’s lifestyle.

Gastroduodenal and oral disease

These are both rare conditions. Gastroduodenal Crohn’s disease presents as dyspepsia, pain, weight loss, anorexia, nausea and vomiting. Oral disease is very painful and may cause chronic ulceration resulting in anorexia.

Stricturing Crohn’s disease

Patients presenting with pain, vomiting and constipation and a diagnosis of stricturing disease can lead to perforation if not surgically treated, although this is rare (see Fig. 13.2)

image

Fig. 13.2 Stricture formation in Crohn’s disease.

Ulcerative colitis

Typical symptoms of ulcerative colitis include bloody diarrhoea (the most predominant symptom) with mucus, abdominal pain with fever, and weight loss in severe cases. The typical appearance of a patient diagnosed with Crohn’s disease is low BMI, malabasorption, weight loss and growth retardation. Frank blood loss is more common in ulcerative colitis than Crohn’s disease. The symptoms of ulcerative colitis are similar to Crohn’s colitis with patients being tachycardic, anaemic, febrile, fatigued, dehydrated and thin. Approximately 50% of patients with ulcerative colitis have some form of relapse each year, and severe attacks can be life-threatening. Up until the 1960s, one-third of ulcerative colitis patients died from the condition; with advances in medical and surgical treatment death is now extremely rare.

Acute severe disease

In addition to the typical symptoms of ulcerative colitis, patients with acute severe disease may present with more than six bloody stools per day (10–20 liquid stools per day is not unusual), with a fever (>37.8 °C), tachycardia (>90 bpm), anaemia (Hb < 10.5 g/dL) or elevated inflammatory markers (ESR > 30 mm/h; CRP > 8). Severity is commonly assessed using the Truelove and Witts criteria (see investigations).

Moderately active disease

Stool frequency is less than six motions each day with diarrhoea, mucus and rectal bleeding. Moderatively active disease is more common in ‘left-sided’ disease. Toxic megacolon is rare in patients with rectosigmoidal involvement, and the incidence of colon cancer is much lower in these patients than those with total colitis.

Proctitis

The manifestations of active proctitis are less severe. These are tenesmus, pruritus ani, rectal bleeding and mucous discharge. Patients are often constipated.

Toxic dilatation

This can occur in untreated severe ulcerative colitis. There is a high risk of perforation with a mortality of 50%.

Extra-intestinal complications of IBD

Around 20–30% of patients with IBD will present with extra-intestinal manifestations. They are more commonly seen in patients where IBD affects the colon. Complications affect the joints, skin, bone, eyes, liver and biliary tree and are more common in active disease. Figure 13.3 highlights some of the extra-intestinal features of IBD.

image

Fig. 13.3 Some of the extra-intestinal illnesses and features of malnutrition found in patients with inflammatory bowel disease

(from Misiewicz et al., 1994, with kind permission from Blackwell Scientific Publications, Oxford).

Joints and bones

Arthropathies occur in 10% of patients with IBD, are more common in women and are a well-recognised complication of IBD. Patients with pauciarticular disease, characterised by arthritis limited to five or fewer joints, often experience a flare in the arthropathy when there is an exacerbation of the IBD symptoms. When the IBD relapse is treated, the arthropathy improves. In contrast, in polyarticular arthropathy, a chronic condition which affects more than five joints, a flare of the IBD appears not to be temporally related to the activity of the arthropathy. About 5% of patients with IBD also have ankylosing spondylitis. This is thought to be immunologically mediated and not associated with IBD activity. Osteopenia, potentially leading to osteoporosis, is often seen in patients with IBD because of chronic steroid use (particularly when the cumulative dose of prednisolone exceeds 10 g) and/or malabsorption.

Skin

Both erythema nodosum and pyoderma gangrenosum are associated with IBD. Erythema nodosum appears as tender, hot, red nodules that subside over a few days to leave a brown skin discolouration. Disease flares are normally directly related to IBD activity in the 8% of patients affected.

Pyoderma gangrenosum presents as a discrete pustule that develops into an ulcer. In the 2% of patients affected, IBD activity does not appear to be directly related to the pyoderma gangrenosum, which may begin or worsen when the IBD is quiescent.

Sweet’s syndrome (an acute febrile neutrophillic dermatosis) which has some similarity to erythema nodosum may also be associated with IBD.

Eye

Ocular complications are infrequent, occurring in less than 10% of cases. Episcleritis (intense burning and itching with localised area of blood vessels) is the most common complication of IBD. Scleritis, which involves more of the eye, may impair vision. Uveitis (headache, burning red eye, blurred vision) is often associated with joint and skin manifestations of IBD. Conjunctivitis is frequently seen in IBD patients but is not specific and no true association has been demonstrated.

Hepatobiliary

Biliary complications of IBD are gallstones and sclerosing cholangitis which occurs in 5% of patients with ulcerative colitis but less frequently in those with Crohn’s disease. Conversely the prevalence of IBD (mostly ulcerativ colitis) in patients with sclerosing cholangitis is 70–80%. Sclerosing cholangitis, found predominantly in males, is a chronic cholestatic condition characterised by inflammation and fibrosis of the intrahepatic and extrahepatic bile ducts. Patients present with obstructive jaundice, cholangitis and raised liver enzymes (alkaline phosphatase and γ-glutamyltranspeptidase). Endoscopic retrograde cholangiopancreatography (ERCP) is useful in diagnosing and aiding the stenting of strictures. There is an increased risk of cholangiocarcinoma, with a liver transplant the only cure. Hepatic complications of IBD include fatty liver, pericholangitis, chronic active hepatitis and cirrhosis.

Thromboembolic

Thromboembolic complications occur in around 1–2% of IBD patients. The most common cause of death in hospitalised IBD patients is pulmonary embolism (Solem et al., 2004).

Anaemia

Around one-third of patients have haemoglobin levels below 12 g/dL. The main causes are chronic intestinal bleeding with iron loss (bowel inflammation) which causes a microcytic anaemia whereas the chronic inflammatory disease can cause normocytic anaemia giving rise to mixed features anaemia. Folate, iron, vitamin B12 malabsorption are also common. The side effects of commonly used drugs in IBD, for example, methotrexate and azathioprine can give rise to symptoms of anaemia.

Investigations

Radiological, pathological and clinical investigations help to confirm diagnosis, disease recurrence and response to treatment. Differential diagnoses of IBD include carcinoma, infection, drug-induced colitis, ischaemia, radiation damage, irritable bowel syndrome and diverticulitis.

Endoscopy

The key diagnostic investigation in IBD is lower gastro-intestinal tract endoscopy (sigmoidoscopy and colonoscopy), which allows direct visualisation of the large bowel and histopathological assessment from biopsies. The risk of developing colorectal cancer is 7–10% after 20 years in patients with colonic disease. Therefore, routine surveillance colonoscopy is essential in the early detection of colorectal cancer. Treatment response to biologics, for example infliximab, can be assessed via mucosal healing seen at colonoscopy.

In patients with severe symptoms, it is sometimes necessary to delay a full colonoscopy because of the increased risk of perforation. Wireless capsule endoscopy is a relatively new procedure where the small bowel can be viewed and can be useful in patients with non-stricturing Crohn’s disease.

Radiology

Radiological imaging is complementary to clinical and endoscopic assessment. It is used in the initial evaluation or diagnosis, preoperative review, to highlight the presence of complications during exacerbations and to evaluate extra-intestinal manifestations. Radiological examination still plays a key role in IBD affecting the small bowel, although endoscopy has generally replaced conventional X-ray examinations of the colon.

Computed tomography (CT scan) and magnetic resonance imagery (MRI) are the best radiological methods for locating and defining fistulae and abscesses in active Crohn’s disease.

Radiolabelled leucocyte scans that utilise autologous leucocytes labelled with 99technetium-hexamethylenamine oxime may provide further information of disease site and severity.

Laboratory findings

Although not diagnostic, active disease is suggested in patients with raised inflammatory markers that include erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) in addition to a low haemoglobin and raised platelet count. Vitamin B12 may be low in patients with chronic terminal ileal disease. Low red cell folate and serum albumin, magnesium, calcium, zinc and essential fatty acids also indicate chronic inflammation and malabsorption. Anti-Saccharomyces cerevisiae antibodies (ASCA) are more likely to be present in Crohn’s disease. Serology can be used to exclude infection as a cause of diarrhoea.

Malabsorption, indicated by low serum trace elements, for example, magnesium and zinc, is not seen in ulcerative colitis. Low albumin may indicate relapse in active disease. Patients with sclerosing cholangitis often present with altered liver function tests.

Stool tests

Red and white blood cells can be seen on microscopic examination of fresh stools. Microscopic identification of infective cells such as amoeba may also be visualised. C. difficile toxin can be assessed through culture and toxin assay. Stool tests do not diagnose IBD but contribute to excluding alternative diagnoses.

Clinical assessment tools

The Crohn’s Disease Activity Index (CDAI) or the Harvey–Bradshaw Index (HBI) is used in most clinical trials to define remission in Crohn’s disease. However, in clinical practice the CDAI is rarely used as it needs to be measured prospectively and is complex. The HBI is a simple measure of stool frequency, pain and other clinical features that is increasingly used to document selection for and response to biologic therapy. A CDAI of <150 or an HBI ≤3 suggests patient is in remission (NICE, 2010).

The Truelove and Witts criteria is a useful tool in defining the severity of ulcerative colitis (see Table 13.3). A severe attack is defined as more than six bloody stools a day plus one or more of the following: pulse > 90 beats/min, temperature >37.8 °C, haemoglobin <10.5 g/dL or ESR >30 mm/h. In this case, the patient should be admitted to hospital.

Table 13.3 Truelove and Witts criteria for assessing severity of ulcerative colitis (Travis et al., 2008)

image

Remission in ulcerative colitis is defined as complete resolution of symptoms with a normal bowel pattern (< 3 stools/day), no urgency and no visible bleeding. Mucosal healing is confirmed by endoscopy. Steroid-free remission is the goal of therapy.

Treatment of inflammatory bowel disease

At present there is no cure for IBD since the exact cause of the condition is unknown. A wide range of drugs and nutritional supplements are available to maintain the patient in long periods of remission in both Crohn’s disease and ulcerative colitis. However, surgical intervention will eventually become necessary when the patient relapses and fails to respond to drug therapy. Since the majority of people with IBD are diagnosed under the age of 30, effective treatment and avoidance of relapses is of paramount importance in this chronic long-term condition.

Nutritional therapy

Nutritional therapy can be considered as an adjunctive or primary treatment. Although a potential problem for all patients with IBD, patients with Crohn’s disease are at particular risk of becoming malnourished and developing a variety of nutritional deficiencies (Fig. 13.3). It is, therefore, important for patients to receive optimal nutrition and dietary manipulation as needed. Low-fibre diets help to reduce clinical symptoms of intestinal obstruction in Crohn’s disease (Fernandes-Banares et al., 1999). Functional and structural damage to the small bowel can cause malabsorption problems and occasionally patients may require a low-lactose diet. Patients with poor oral intake and loss of appetite often respond to supplemental enteral feeds. Enteral nutrition in the form of an elemental or polymeric diet can be used as primary therapy and is widely employed in paediatrics (Heuschkel and Walker-Smith, 1999).

Patients who have extensive small bowel resection may experience many nutritional deficiencies because of malabsorption. Iron depletion, hypoproteinaemia, deficiencies in water- and fat-soluble vitamins, trace elements and electrolytes may all occur and must be corrected using a suitable replacement regimen.

Where appropriate, and when enteral nutrition is not indicated or adequate, a total parenteral nutrition (TPN) regimen may be prescribed. Some patients receive concurrent enteral and parenteral feeding.

Drug treatment

The main goals of drug treatment are to treat acute attacks promptly and effectively, induce and maintain remission, limit drug toxicity, modify the pattern of disease, avoid and/or manage complications and select patients who will benefit from surgery. Morbidity and mortality can also be reduced by the prompt use of effective and appropriate drug therapy. The choice of drug and route of administration depends on the site, extent and severity of the disease together with the individual’s treatment history. Drug therapy is often required for many years and patient preference, acceptability and possible side effects not only affect choice but will impact on medication adherence. There is a need for therapeutic strategy and consistency in the management of patients with IBD.

Corticosteroids, aminosalicylates and immunosuppressive agents (immunomodulators) such as azathioprine are the mainstays of treatment. Immunomodulators are not licensed for use in IBD but are routinely used.

Modern advances in treatment, such as the use of humanised monoclonal antibody preparations and other biologic agents which modify the affected biochemical inflammatory pathways, now have a significant role in treatment of the disease. These are likely to be the main area of future development.

Other drugs such as antibiotics, for example, metronidazole, are helpful in some cases, while colestyramine, thalidomide, sodium cromoglicate, bismuth and arsenical salts, nicotine, lidocaine, sucralfate, new steroid entities, cytoprotective agents, aloe vera, probiotics and fish oils are rarely used. However, for some patients they provide alternative or supplemental therapy.

The choice of drug treatment is dependent on whether it is prescribed to induce remission or as maintenance therapy. The majority of patients are managed successfully as hospital outpatients or by their primary care doctor. Only severe extensive or fulminant disease requires hospitalisation and the use of parenteral therapy and/or surgical intervention. Oral medication can be given to most patients for maintenance of moderate disease.

The route of administration is a particularly important factor in IBD. In contrast to most other conditions, minimal systemic absorption and maximal intestinal wall drug levels are required with oral therapy. Several delivery strategies have been used to achieve this including the chemical modification of drug molecules, delayed and controlled-release formulations and the use of bioadhesive particles.

Disease confined to the anus, rectum or left side of the colon is more appropriately treated with rectally administered topical preparations where the drug is applied directly to the site of inflammation (Table 13.4).

Table 13.4 Comparison of commercially available preparations for rectal administration in inflammatory bowel disease

Generic name (proprietary name) Formulation Site of release
Sulfasalazine (Salazopyrin®) Suppositories
Retention enema		 Rectum
Transverse, descending colon and rectum
Mesalazine (Pentasa®, Salofalk®) Retention enema Transverse, descending colon and rectum
Mesalazine (Asacol®, Salofalk®) Foam enema Rectum and rectosigmoid colon
Mesalazine (Asacol©®, Pentasa®, Salofalk®) Suppositories Rectum
Prednisolone sodium phosphate (Predsol®) Retention enema
Suppositories		 Transverse, descending colon and rectum
Rectum
Prednisolone sodium metasulphobenzoate (Predenema®) Retention enema Transverse and descending colon
Prednisolone sodium metasulphobenzoate (Predfoam®) Foam enema Rectum and rectosigmoid colon
Prednisolone sodium phosphate (Predsol®) Retention enema Transverse and descending colon
Hydrocortisone acetate (Colifoam®) Foam enema Rectum and rectosigmoid colon
Budesonide (Entocort©®) Retention enema Rectum and rectosigmoid colon
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