Title: Inflammatory Bowel Disease

Key words: Ulcerative colitis, Crohn’s disease

Date: May 1999

Category: 13. Specific Conditions

Type: Article

Author: DJE Candlish

 

Introduction

Inflammatory bowel disease is a major problem, affecting 1 in 2000 individuals in the developed world. In its milder forms it causes diarrhoea and abdominal discomfort, but more severe forms can cause life-threatening blood loss, intra-abdominal infections and an increased risk of bowel cancer. This explains the effects of IBD upon the gastro-intestinal (GI) tract, along with the possible causes of the condition and the treatments available. Particular emphasis is placed on the two main conditions in IBD – ulcerative colitis and Crohn’s disease.

 

Inflammatory bowel disease (IBD)

The most important forms of IBD are ulcerative colitis (UC) and Crohn’s disease (CD). The tables below show the variation in incidence and prevalence of these conditions in different parts of the world and different locations (urban vs rural). In many places, the incidence appears to be rising due to increasing Westernisation of the population. The trends in incidence for Crohn’s disease reported in southern Wales are typical of those in other parts of the UK, Scandinavia and the USA.

The highest prevalence levels for Crohn’s disease occur in Scandinavia, where up to 150 per 10,000 people may be affected. In contrast, the disease is rare among the Chinese in Hong Kong and on the Indian subcontinent.

Incidence - the rate of occurrence of new cases of a disease in a defined population

Prevalence - the number of cases of a disease in a defined population at a given time

 

For ulcerative colitis, the prevalence is also greater in Scandinavia than Israel or Spain, for example. Incidence has risen sharply in Scandinavia but remained static in other countries. In parts of southern Europe ulcerative colitis is diagnosed more frequently than Crohn’s disease.

These figures for incidence and prevalence are taken from developed countries, as the populations here are more likely to seek medical attention and have access to reliable diagnosis and effective treatment. Although this makes the figures more reliable, there are significant variations from place to place. The incidence of Crohn’s disease is also higher in urban than rural areas.

 

 

Prevalence of Ulcerative Colitis

Location

Time period

No of cases per 100,000

Orebro, Sweden

1987

234

Rochester, MN, USA

1980

225

Copenhagen, Denmark

1987

161

Gallilee, Israel

1986

45

Adapted from Allison et al. 1998

Annual Incidence of Ulcerative Colitis

Location

Time period

No of cases per 100,000

Uppsala, Sweden

1965-1970

1971-1985

6.9

11.5

Iceland

1950-1959

1960-1969

1970-1979

2.8

4.7

7.4

Cardiff, UK

1968-1977

1978-1987

6.4

6.3

Orebro, Sweden

1973-1977

1978-1987

3.3

14.9

Malmo, Sweden

1956-1972

1973-1987

4.2

9.4

Copenhagen, Denmark

1962-1978

8.1

Northern Norway

1983-1986

12.8

Northern France

1988-1990

3.2

Northwest Greece

1982-1991

4.0

Central Spain

1981-1988

3.2

Southern Spain

1979-1988

2.0

Rochester, MN, USA

1971-1980

3.5

Beer Sheva, Israel

1981-1985

5.8

Gallilee, Israel

1967-1986

2.2

Adapted from Allison et al. 1998

Comparison of annual incidences of UC and CD in different areas

Location

Time period

Incidence of CD (per 100,000 population)

Incidence of UC (per 100,000 population)

Northern France

1988-1990

4.9

3.2

Northwest Greece

1982-1991

0.3

4.0

Central Spain (urban)

(rural)

1981-1988

1.6

0.9

3.2

3.2

Southern Spain

1979-1988

0.9

2.0

Uppsala, Sweden

1965-1983

5.8

10.4

Rochester, MN, USA

1971-1980

5.0

3.5

 

 

 

Risk Factors for IBD

From other available data, it appears that certain groups are at higher risk of developing IBD than the general population. There is clear evidence of a genetic link, as it is more likely that both twins will be affected with identical twins than non-identical twins. Patients with Turner’s syndrome are also more likely to develop IBD than the general population.

There is an increased incidence of IBD among the families of affected patients. However, among families where two or more members are affected by either CD or UC, affected first-degree relatives are not always concordant for the same disease. This has led to suggestions that UC and CD are different manifestations of the same disease. The particular form that develops may be determined by environmental factors, such as smoking, in genetically predisposed individuals.

More specific risk factors for IBD include:

In American and European studies, UC is slightly more common in men, while CD is slightly more common in women. Peak incidence occurs in young adulthood (15-25yrs) with a possible second peak again in later years (55-60yrs)

IBDs are more common among white people than black Americans, Latin Americans, Maoris or Asians. The highest incidences and prevalences are among the Ashkenazic Jews of western Europe and the USA. The incidence among this group remain high even when they migrate to areas of low incidence, such as Israel. Some studies suggest that people at managerial levels are more at risk than less affluent groups.

Incidences of both UC and CD are higher in urban than in rural locations

Possible Causes of IBD

The aetiology of both UC and CD are still unclear. The possible causes include:

Despite the defence systems described earlier, a vast number of micro-organisms are always present in a healthy individual’s alimentary canal. These are referred to as the intestinal microflora. In healthy individuals they cause no harm and may even contribute to the digestive process. However, if any of these organisms penetrate the wall of the alimentary canal and reach other parts of the body, they can cause serious infections. This can happen as a result of injury or disease, including UC and CD.

Certain observations suggest that the aetiology of IBD may involve bacterial infection. The tissue changes seen in IBD resemble those seen in infections, the intestinal microflora is abnormal in many patients with IBD and several infectious diseases of the colon cause inflammatory changes similar to those caused by IBD.

However, no organism has been directly implicated and the geographical spread of IBD does not resemble that of an infection, so at present, an infectious aetiology for IBD remains unproven.

Diet has often been proposed as a causative factor in IBD. Patients with IBD appear to eat more refined sugar and less dietary fibre than healthy individuals, for example. IBD is also less common in people who were breast fed than bottle fed as infants. As the number of people who were formula fed is much larger than the number of people with IBD, however, bottle feeding can only be a contributory factor.

Tobacco smoking has a complicated and unclear relationship with IBD. UC is more common in non-smokers and ex-smokers than current smokers, while the opposite is true for CD.

CD is more common in oral contraceptive users than non-users and some studies have shown that stopping oral contraceptives can lead to a remission of CD symptoms. This does indicate a possible role for female hormones in the aetiology of CD. Nonsteroidal anti-inflammatory drugs (NSAIDs) can reactivate UC and may even trigger the first attack. The relevance of these findings remains unclear, however.

No consistent psychological differences have been shown between IBD patients and the rest of the population. However, many clinicians believe that the pattern of relapse and remission in IBD is strongly influenced by the stressful life events an individual experiences.

Migrant studies have shown that environmental factors may be important in some way. Crohn’s disease, for example, is rare among Chinese people in Hong Kong but more common among Chinese migrants to Canada. Also, the incidence of ulcerative colitis in Sikhs and Hindus from Asia living in the UK is higher than in those in Asia. The factors responsible remain unknown.

Inflammation – the Key to IBD

The single most important feature of IBD is inflammation. In healthy people, the inflammatory response is an essential component of the immune system’s defence against infection and is also a key feature of the healing process. However, when inflammation occurs with no obvious cause, in response to normally harmless stimuli or is too prolonged or intense, it can cause tissue damage and painful, distressing symptoms. This is what happens in IBD.

Normally, the inflammatory response is triggered by tissue damage or infection. It has two components; cellular and non-cellular. The cellular component involves mast cells and neutrophils. Mast cells are activated by tissue damage in areas where infection is present or injury has occurred. They release inflammatory mediators and substances that draw neutrophils and other phagocytic cells into the affected tissues via blood vessels. These cells then attempt to engulf and destroy any micro-organisms or cell debris in the area. Lymphocytes are also stimulated to produce antibodies against antigens from the micro-organisms or damaged cells.

The inflammatory mediators released by mast cells have a range of effects, including:

The normal inflammatory response usually resolves in a matter of days as the infection is defeated or the tissue damage heals. In UC and CD, inflammation of the mucosa becomes chronic, and is itself a cause of tissue damage and structural changes to the alimentary canal. This is due to the presence of a range of immune cells in the affected areas. These cells continue to release inflammatory mediators and antibodies, which leads eventually to permanent damage and disability. Chronic inflammation of the mucosa is a hallmark of both UC and CD.

 

The Role of the Immune System

The immune system is clearly involved in the development and persistence of IBD. The inflamed intestinal mucosa is typically infiltrated by a range of immune cells, including:

In UC, inflammation is mainly confined to the mucosa and these cells are confined to the mucosa and the submucosal layer directly below it. In CD, where the inflammatory changes can affect the entire thickness of the wall of the alimentary canal, these cells are present, not just in the mucosa and submucosa, but also in deeper tissues.

Other indications of the role of the immune system are the raised numbers of neutrophils and macrophages circulating in the bloodstream. Many patients have raised levels of IgG producing cells in the mucosa, where IgA producing plasma cells normally predominate. In UC, there is a higher proportion of IgG1 and IgG3 subclasses, while in CD, the IgG2 subclass predominates.

In UC, the number of circulating lymphocytes is normal but in CD, it is depressed. This may be due to the number of these cells entering the tissues of affected areas, or to loss of lymphocytes into the intestinal lumen. In severe CD, malnutrition may reduce the production of lymphocytes.

There are two possible explanations for the role of the immune system in IBD. The immunological hypothesis suggests that the immune system is overreacting or reacting abnormally to an antigen to which most people are routinely exposed. The antigen may be a dietary component, such as a food additive or a protein. The raised IgE levels in UC support this theory, as IgE is linked with allergy, but further evidence is lacking. Deans 1998 p68 A variant on this theory is that IBD is an autoimmune disease. This would mean that body tissues were being attacked by the immune system as if they were foreign to the body.

To confirm this theory, a number of auto-antibodies, which attack body tissues, have been found in the serum of IBD patients, including colitis colon-bound antibody (CCA-IgG) in UC patients but not CD patients.

The second explanation is the infective hypothesis. This assumes that the immune system is reacting appropriately to an invading micro-organism (pathogen) which has not yet been identified. It is still not possible to be sure which of these hypotheses is correct and, indeed, both may be partially correct.

Ulcerative colitis

UC is a disease of the large intestine, mainly affecting the mucosa of the colon. The rectosigmoid area is usually affected (proctitis) and in around 50% of patients, the disease later spreads from the distal colon to more proximal areas, causing distal colitis or even total colitis. (dia)

Most patients suffer from chronic intermittent UC, with repeated attacks and periods of remission (freedom from symptoms) in between. A smaller number of patients only ever have a single acute episode. Less than 10% have chronic continuous UC, where symptoms occur continuously with no periods of remission.

In the majority of UC patients, the disease remains stable for many years. In a few, the frequency and severity of symptoms decrease over time, while in others it worsens (disease progression). The most common form of progression is the spread from distal to more proximal areas of the colon. Complications, such as infections, may develop as a result of the damage to the mucosa and these can cause serious illness.

In the early stages of UC, the surface of the mucosa is typically inflamed, red and swollen, due to hyperaemia (increased local blood flow) and the capillaries and mucosal tissue are fragile (friable) and bleed easily. The surface of the mucosa becomes covered by blood, mucus and cell debris. As the disease progresses to a more severe form, ulcers develop where the surface of the mucosa has been lost. These may join up (confluent ulceration) to leave large areas of the submucosa exposed. The swollen, hyperaemic patches of mucosa that remain are referred to as mucosal islands. Even in the early stages, microscopic examination of tissue samples shows epithelial erosion and other cellular changes in areas that still look normal on endoscopy.

The hallmarks of UC are infiltration of the mucosa by inflammatory cells and the formation of crypt abscesses, where the deep clefts or crypts in the wall of the colon become filled with pus (inflammatory cells, bacteria and cell debris).

With effective treatment, many of these changes to the mucosa and intestinal wall can be reversed. Ulcerated areas can heal, becoming covered with normal mucosal tissue, with a corresponding reduction in inflammatory cell numbers.

 

Symptoms and Signs of Ulcerative Colitis

Symptoms are subjective sensations caused by a disease, experienced by the patient and reported to clinicians. Signs are objective evidence obtained or observed by the clinician independently of the patient, such as heart rate or tissue changes detected in biopsy samples.

The symptoms of UC do vary, but the classical clinical presentation is diarrhoea, increased stool frequency (defecation) and passage of blood and mucus from the rectum. The symptom pattern is determined by the severity and extent of the disease. Patients with colitis affecting only the rectum and distal sigmoid colon usually complain of gradual onset rectal bleeding and tenesmus (painful, difficult defecation). Increased stool frequency, with pellet-like stools with blood and mucus are often reported.

Patients with severe UC on presentation tend to have diarrhoea, fever and tachycardia. The diarrhoea is due to irritation of the colonic mucosa causing faster than normal passage of faeces through the bowel. A few patients, however, suffer constipation or prolonged retention of faeces, due to muscular spasm of the rectum. Many patients will complain of abdominal tenderness or pain.

As the disease progresses, other symptoms develop, such as:

The signs of UC revealed by medical examination of patients include:

The severity of UC is assessed according to the presence and severity of these symptoms and signs.

 

Clinical Severity Index for UC

(Oxford Index)

Severe attack*

Mild attack*

* A moderate attack is simply defined as between mild and severe

The Oxford Index is useful in clinical practice but for objective evaluation in clinical trials, an endoscopic severity index may be more precise.

 

 

 

UC Colitis Endoscopic Severity Index

Grade 0 Normal mucosa

Grade 1 Hyperaemic mucosa with loss of vascular pattern

Grade 2 Granular mucosa with bleeding at light contact

Grade 3 Friable mucosa with spontaneous mucosal haemorrhage

Grade 4 Discrete ulceration with excess mucus/pus

Grade 5 Confluent ulceration

Radiology can also be used in diagnosis of UC. Typically, the colon looks shorter and narrower in X-rays, due to muscular contraction caused by inflammation. The intestinal wall is often thinner than normal, in contrast to Crohn’s disease, where the wall becomes thick and fibrous.

 

Complications of Ulcerative Colitis

Damage to the colon causes most of the complications of UC, which are responsible for most of the morbidity and mortality associated with the disease.

Malnutrition

Deficiency of nutrients often develops in patients with UC. Several factors may be involved. Patients may eat less, hoping to avoid or reduce their diarrhoea. They may lose plasma proteins through their damaged mucosa or chronic diarrhoea may expel food from the alimentary canal before it has been fully digested. These factors all weaken the patient and reduce their resistance to the disease.

In children, UC can cause growth failure, mainly as a result of this malnutrition, but sometimes because UC treatment causes hormonal disturbances. Growth failure can lead to permanent short stature if parents and healthcare professionals are too focused on the course of the disease. Treatment must include dietary supplementation in addition to treatment of the underlying disease.

Colonic complications

Acute toxic megacolon is a serious complication which can develop in some patients. Part or all of the colon becomes distended and paralysed, losing its ability to absorb water and electrolytes. This can lead to dehydration and electrolyte imbalances which are potentially fatal.

Colonic perforation is the main cause of death in acute colitis. The symptoms and signs of perforation can be masked by systemic steroids (see Treatment Strategies section). The risk of perforation is increased by the tissue changes due to acute UC and to the thinning of the colon wall in toxic megacolon.

Patients with UC have an increased risk of cancer of the colon. The form of cancer is different, developing within flat mucosal areas rather than from polyps, as occurs with sporadic colonic cancer in the general population. Risk factors for colorectal cancers in UC patients include:

Diagnosis of colorectal cancer can be delayed because the symptoms are thought to be those of the underlying UC. The earliest mucosal change in cancer is low grade dysplasia, which can progress to villous dysplasia and intramucosal carcinoma, eventually leading to invasive adenocarcinoma. Early detection of mucosal dysplasia by endoscopy, followed by colectomy, can prevent this sequence of events. Current screening programmes involve annual or two yearly endoscopy, with tissue biopsies of any raised or pale-coloured mucosa seen on endoscopic examination.

Extra-intestinal complications

A significant proportion of UC patients develop extraintestinal manifestations or complications, due to inflammation developing outside the alimentary canal. The severity of these manifestations does not appear to be related to the severity of the inflammation in the colon.

The tissues most often affected include:

In the skin, the inflammatory changes result in the formation of large open sores. In the skeleton, arthritis affecting the large joints is common. Bone disorders such as clubbing, enlargement of the tips of the fingers and toes or inflammation of the joints or spine are common, more so in CD than UC, however. Some patients develop episcleritis, painful inflammation of the external tissues of the eye. Steroid treatment for UC can lead to cataracts and glaucoma.

The most common extraintestinal manifestations of UC are infiltration of the liver with fat and inflammation of both liver and bile duct, which can lead to liver failure. There is also an increased risk for cancer of the gall bladder and bile ducts among UC patients. Gallstones and kidney stones may develop, though these are more common in CD. Liver function tests are often abnormal and in severe cases, cirrhosis may develop.

The most common blood disorder in UC patients is anaemia. In most cases, this is due to chronic loss of small amounts of blood from the fragile capillaries of the mucosa. Malnutrition also plays a role in anaemia, as it can reduce the body’s ability to produce new red blood cells. A much rarer complication in UC is an auto-immune blood disorder that causes anaemia by attacking red blood cells.

In a small percentage of patients with UC, deep venous thrombosis (DVT) can occur. This is the formation of blood clots in the deeper veins, often in the lower legs.

UC and pregnancy

UC does not appear to adversely affect fertility overall, but stillbirths and foetal complications do tend to be more common in women with UC. If UC is in an inactive phase around the time of conception, it tends to remain that way throughout pregnancy. However, if it is active at conception, it may worsen during pregnancy.

Prognosis in UC

Prognosis is the medical term for the predicted course of a disease in one particular patient or more generally for the majority of patients with the disease. Modern diagnostic methods such as endoscopy, combined with improvements in treatment mean that the prognosis for UC patients has greatly improved in recent years. Patients are at greatest risk of severe illness or death in the first years they have the disease.

With current treatment, more than 80% of patients achieve remission after their first attack of UC. Around 8% will continue to have symptoms but can be stabilised with medical (drug) treatment. A further 8% will require surgical treatment. Only about 3% will die from their initial attack, either as a result of complications or during emergency surgery.

The severity of the initial attack determines the prognosis. Almost all the fatalities occur in cases initially classified as severe. The long term prognosis for many UC patients is a gradual spread of inflammation from distal to more proximal regions of the colon. Within 10 years of the initial diagnosis, ulcerative proctitis will have spread to the sigmoid colon in some 30% of patients and to the entire colon in 5-10%.

A number of factors influence the prognosis of UC. These prognostic factors predict relapse rates and complications of UC more reliably than extraintestinal complications.

 

Prognostic factorAge at initial attack

Mortality is highest in oldest and youngest patients. Risk of relapse lower in older patients. Growth impairment in younger patients

Severity of initial attack

The higher the severity, the higher the risk of mortality and the more likely surgery will be needed at some time in the future

Extent of disease at initial diagnosis

The greater the extent, the higher the risk of mortality in first attack, the greater the need for surgery later, the greater the severity of symptoms and risk of complications

Duration of disease

UC > 10 years increases the risk of colonic cancer

 

Proportions of UC patients developing complications

Complications % patients affected

Massive haemorrhage 3

of colon

Toxic megacolon 2-10

Strictures 11-15

Cancer of the colon 2 after 10 years, 10-30 after 30 years

Extraintestinal manifestations

Skin disorders 4-10

Bone and joint disorders 25

Disorders of the liver and

associated structures 2-4

Where disease severity, complications or risk or presence of cancer cause the patient to require surgical treatment, the standard procedure is a colectomy. Five years after diagnosis, around 5% of patients undergo colectomy, rising to 11% after 10 years.

 

 

 

Diagnostic Investigations

Because the symptoms of UC can resemble those of other conditions, such as intestinal infections, further investigation is needed to establish the diagnosis. The most important of these investigations are:

Colonoscopy

The investigation of choice for assessing UC is endoscopy or colonoscopy, which involves inserting a flexible fibre-optic endoscope into the colon to view the mucosal surface directly. Tissue samples or biopsies can also be taken for analysis, if required. In skilled hands, the colonoscope can reach the caecum in 95% of patients. The characteristic features observed in severe UC include:

Colonoscopy is an invasive procedure, requiring sedation and analgesia for the patient. Overall, however, it is considered to be the most accurate and reproducible method of diagnosis for severe cases of UC.

Although generally safe, colonoscopy does carry a 0.3% risk of perforating the bowel wall, compared with 0.04% for barium enema. It should, therefore, not be carried out in patients with marked abdominal tenderness. Perforation can cause severe, acute peritonitis, the shock of which can prove rapidly fatal.

Sigmoidoscopy

Sigmoidoscopy involves visual examination of the sigmoid colon and rectum only, using either a rigid or a flexible sigmoidoscope. It is used to investigate anorectal symptoms, such as bleeding from the rectum and abrupt changes in bowel habit. The rigid sigmoidoscope is a rigid tube containing a light source, which reaches about 20cm into the rectum. The flexible sigmoidoscope is a flexible fibre-optic tube which is more difficult to use but can access most of the descending colon and rectum. Flexible sigmoidoscopy is increasingly widely used in the diagnosis and assessment of UC.

Barium enema

Two types of barium enema are used in the diagnosis of UC and other bowel disorders. Many patients consider barium enemas to be less painful than colonoscopy.

Features detected by barium enemas include:

Double contrast enemas provide better detail on X-rays, especially for identifying polyps < 1cm and small areas of mucosal ulceration. Single contrast enemas, however, are better for emergency situations and for debilitated (weakened) patients who cannot hold the air during the double contrast procedure. If bowel perforation is a possible risk, then a water-soluble enema should be used.

Barium enemas are a safe, accurate means of diagnosis in the colon, but do carry a slight risk of perforation. Risk factors for this include thinness and weakness of the bowel wall in elderly patients and those on long-term steroid treatment and diseases such as colonic cancer and, of course, severe UC. However, barium enemas, like endoscopy, are reserved for patients with more severe symptoms, as they are expensive and inconvenient procedures. Patients with mild symptoms are at low risk of complications.

Radiology

Plain X-ray films are a valuable, non-invasive, diagnostic tool. The erect chest film is the most useful and informative in the diagnosis of UC. Plain films can reveal obstructions, gas pockets, polyps, carcinomas and diverticular disease. In patients with suspected IBD, insertion of air into the rectum before radiography can provide valuable additional information.

Plain films can also reveal the dimensions of the colon, which can indicate toxic megacolon if over 5.5cm in diameter in patients with colitis. In elderly patients, the diameter of the colon can reach over 15cm with no pathology present. If the large bowel is obstructed by a carcinoma or stricture, the proximal colon can be seen to be distended with gas and fluid, while the distal colon is collapsed, with no gas in the rectum. Any intestinal loop completely filled with gas should be regarded as abnormal.

Ultrasound and computerised tomography

Ultrasound is particularly useful in identifying free intraperitoneal fluid or abdominal abscesses. It can help to confirm the diagnosis in suspected IBD, as it reveals the thickened intestinal wall that characterises CD. Colonoscopic ultrasound is useful in assessing colonic cancer. Ultrasound can also be used to guide the removal of tissue samples for biopsy and the therapeutic draining of abscesses. Computerised tomography is useful in assessing the extent of colonic wall involvement in colorectal cancer.

 

 

Laboratory investigations

Blood samples provide valuable information in the diagnosis of UC. The features they can reveal include:

Stool samples should also be taken, for microbiological culture, from all patients with symptoms indicating UC, to exclude the possibility of an infection causing the symptoms.

Differential diagnosis

This is the process of excluding other possible diagnoses to reach one conclusive diagnosis in an individual patient. With UC, this can be difficult, as several other conditions can cause similar symptoms. These conditions include:

Diverticular disease is due to the formation of sacs or pouches where the mucosa bulges out through the wall of the colon due to local weaknesses in the wall. The sacs are called diverticuli. In the colon, their development is called diverticulosis. This is a common age-related condition, occurring in up to a third of the UK population aged over 60. The condition only causes symptoms if the diverticuli become inflamed or infected. The symptoms include abdominal pain, diarrhoea, vomiting, and rectal bleeding, mimicking those of UC. A barium enema can show the presence of diverticuli very clearly, enabling the differential diagnosis to be made.

Infectious colitis occurs when a pathogenic micro-organism infects the colon. This can be identified by culturing the organisms present in stool samples or tissue biopsies taken from the patient.

Radiation colitis is a result of exposure of the colon to radiation, usually in the treatment for bowel cancer. This causes inflammatory damage to the colonic mucosa similar to that of UC. Diagnosis can be confirmed by a history of radiation treatment.

Ischaemic colitis develops when the blood supply to part of the colon is disrupted, causing localised tissue damage and cell death. Tissue biopsies from the affected area show characteristics signs of ischaemia.

 

Crohn’s Disease (CD)

Crohn’s disease (CD) is named after Burrill Bernard Crohn, who first described the condition as terminal ileitis in 1932. Around two thirds of patients develop symptoms between 10 and 30 years of age and 10% after the age of 50. However, as symptoms are often mild at first, diagnosis can be delayed for up to 10 years in 10% of patients.

The distinguishing feature of Crohn’s disease is the discontinuous nature of the spread of inflammation. Sharply outlined areas of severe inflammation (skip lesions) may be separated by large areas of normal mucosa. This is one of the most characteristic signs of CD. Crohn’s disease can affect any part of the alimentary canal but tends to occur mainly in the distal (terminal) ileum and colon. Around 60% of patients have CD localised to the ileocolic region, 20% the small intestine and 20% the large intestine.

In contrast with UC, the inflammation in CD can extend through the full thickness of the intestinal wall, mainly affecting the submucosa. The bowel wall can become fibrotic, leading to stricture formation and thickening of the wall. The strictures can be single or multiple, short or long and cause the characteristic ‘hosepipe’ appearance of the affected segment.

In the early stages of CD the affected areas of the mucosa look red with many tiny pinpoint haemorrhagic lesions and aphthous ulcers over the surface. Abscesses and narrow, deep ulcers or fissures develop, some of which may penetrate the wall, forming fistulae or abnormal openings. In approx. 25% of patients, the fissuring and ulcer formation becomes extensive and the mucosal wall takes on a ‘cobblestone’ appearance. Biopsies from these affected regions reveal granulomas or clumps of inflammatory cells. In areas with gross stricturing, the muscularis mucosae layer below the submucosa is extremely thick. This is very characteristic of CD.

Symptoms and signs of Crohn’s disease

CD causes a wide range of symptoms, the most common being chronic intermittent diarrhoea, abdominal pain and weight loss. Other symptoms include anorectal inflammation, rectal bleeding, anorexia, nausea and vomiting. The pattern of symptoms depends on the areas affected. Abdominal pain is more common when the ileum is affected and diarrhoea more common when the colon is most involved. Nausea and vomiting occur when the upper alimentary canal is affected.

The serosa or outer layer of the alimentary canal is often inflamed (serositis) and together with peri-intestinal fat can form adhesions between adjacent loops of the intestine. White nodules may appear on the serosa, consisting of granulomata and lymphoid tissue.

The signs of Crohn’s disease revealed by medical examination include:

The most common reason for patients first seeking medical attention is chronic intermittent diarhoea with colicky abdominal pain and general weakness (malaise).

Crohn’s disease severity index

Clinical feature Scoring

General well-being 0 = very well

1 = well

2 = alright

3 = poor

4 = terrible

Abdominal pain 0 = rare or none

1 = mild

2 = moderate

3 = severe

Liquid stools number per day

Abdominal mass 0 = absent

1 = possible, non-tender

2 = probable, minimal tenderness

3 = definite and tender

Complications e.g. arthralgia, aphthous ulceration

score one point for each complication

(see table ‘Extra-intestinal complications’)

Complications of Crohn’s Disease

Most of the complications of CD are so common they are almost considered as integral features of the disease. They include abscess and fistula formation, intestinal obstruction, anorectal lesions and malnutrition. Severe, life-threatening haemorrhage is rare in CD, but if it occurs, it requires surgical removal of the diseased section of bowel. The abscesses associated with CD may also require surgical intervention, although radiologically assisted percutaneous drainage may be an alternative.

Nearly 50% of patients undergoing surgery for CD have fistulae. About 80% of fistulae arise in the ileum, 15% in the ileocaecal valve and 5% in the colon. Most fistulae develop when a fissure penetrates the bowel wall, allowing the intestinal contents to leak out, forming an abscess that then penetrates other nearby structures. They are usually located at the proximal end of, or within, strictures. Fistulae may be of several types:

Perianal complications occur in about 25% of those with small intestinal CD, 40% with combined small and large intestinal involvement and 50% of those with only large bowel CD.

Extra-intestinal complications of Crohn’s disease

About 30% of all patients with CD have extra-intestinal complications. These are thought to be due to excessive antibody production by B lymphocytes, resulting from leakage of dietary and bacterial antigens through the damaged intestinal wall. A wide of body systems may be affected, including.

In the liver, fatty infiltration, abscess formation, hepatitis and cirrhosis are common complications. There is an increased risk of cancer of the gall bladder and bile ducts.

In the eyes, sight-threatening uveitis is the most serious complication, although conjunctivitis and episcleritis are also common. /2

Damage to the joints can lead to asymmetrical arthropathy, sacro-ileitis and ankylosing spondylitis. In the skin, CD often causes ulceration and localised areas of inflammation. This may be described as metastatic Crohn’s disease.

In the mucous membranes of the mouth, aphthous ulceration is more common in Crohn’s disease than UC. The severity of the ulceration may reflect the severity of the underlying CD.

Kidney stones may form in 5-10% of patients and the pressure from swollen intestines may block urine flow down the ureters, causing the kidney to swell with urine.

AS with UC, patients may develop anaemia, deep venous thrombosis or other inflammation of the blood vessels.

CD may also reduce fertility in women and increases the risk of foetal complications. The severity of CD does not appear to be affected by pregnancy, however.

 

 

Prognosis in CD

Thanks to improvements in diagnosis and treatment, prognosis has improved for CD patients. As with UC, the severity of the initial attack has an impact on subsequent outcomes. However, the acute symptoms, complications and extra-intestinal manifestations generally improve rapidly with effective medical treatment and improved nutrition. Despite this, the mortality rate for CD patients is 1.5 times higher than for the general population, with 50% of the deaths being directly related to their disease, complications or post-surgical problems.

Most patients with Crohn’s disease develop recurrent disease and require surgery within 20 years of their initial operation. Surgery does not halt the course of the disease. It is generally for complications of CD rather than failure of medical management. The surgery rate, 10 years from diagnosis is 90% for patients with ileocolitis and 66% for Crohn’s colitis.

Factors known to accelerate recurrence are cigarette smoking and the aggressive perforating form of the disease. The most common indications for surgery are perianal disease, recurrent small intestinal obstruction, abscess or fistula, massive haemorrhage or carcinoma.

Recurrences usually occur at or proximal to the original site of surgery. Tissue changes develop within a year of the initial operation but it may be many years before the recurrence of symptoms. The initial location of the disease affects the likelihood of recurrence. When both ileum and colon are involved, the risk is 1.5 times greater than when only the ileum or colon are involved.

The most serious long-term consequence of Crohn’s disease is cancer. As with UC, the severity and extent of colonic involvement are important risk factors.

Diagnostic Investigations

The methods available for diagnosis of CD are similar to those for UC., namely:

Endoscopic examination is less useful in CD than UC because the disease can be so widely scattered along the alimentary canal. It can be useful for direct assessment of localised strictures, cobblestone mucosa and perianal complications. The patchy nature of the disease, with apparently normal mucosa in between ulcerated areas, is the most useful endoscopic observation in confirming a diagnosis of CD. Colonoscopy with multiple biopsies is more accurate than either colonoscopy alone or barium enema assessment.

Sigmoidoscopy is also limited in usefulness because it can only examine the rectum and distal colon and the disease may be present anywhere along the alimentary canal.

Double contrast barium enemas can visualise both the colon and distal ileum, providing useful diagnostic cues. If the characteristic cobblestone mucosa in the colon is seen, this correlates well with disease activity. Radiographic barium studies can also reveal fine mucosal detail, such as aphthous ulcers. If longitudinal submucosal tracts are visible, these are highly suggestive of CD (Marshak’s sign).

Barium studies are better than CT scans at revealing mucosal disease, and post-surgical anatomy. CT however, is superior in revealing mesenteric inflammation, abscesses and fistulae. A combination of the two is normally performed.

Laboratory investigations include full blood cell count, ESR, electrolyte levels and serum proteins. They help to assess the nutritional state of the patient and are a useful index of disease activity. Decreased serum albumin and iron are common and patients may also have vitamin B12 and folic acid deficiency. Patients with chronic CD will also be anaemic. Low levels of zinc and vitamin A may reflect either decreased absorption or reduced intake.

Comparing Ulcerative Colitis with Crohn’s Disease

UC is confined to the colon and rectum while CD can affect any part of the gut. Differences in their microscopic and macroscopic pathology and sites of involvement are usually reflected in their clinical manifestations and common complications. However, patients with CD confined to the colon (Crohn’s colitis), can present in a very similar manner to those with UC. Colonoscopy and assessment of a series of biopsies may be needed to differentiate between them. In up to 15% of cases, this differentiation may not be possible and such cases are labelled ‘indeterminate colitis’.

Similarities between CD and UC include:

In some patients, the diagnosis may be changed after several years, usually from UC to CD. A change of diagnosis to CD may result from several observations:

Differential diagnosis of CD and UC can be made, in the majority of cases, using a combination of the reported symptoms and the results of investigations such as endoscopy, barium enemas and biopsy findings. Making the distinction is important because of the tendency of CD to recur, especially at the site of earlier surgery. Aggressive initial surgery may leave the patient with too little viable intestine to maintain nutrition if there is a recurrence. This is called the short bowel syndrome (see separate article in 13.).

 

 

Differences between UC and CD

 

Ulcerative colitis

Crohn’s disease

Symptoms

rectal bleeding

mucus in stools

abdominal pain

common

common

variable

rare

rare

common

Barium enema assessment

disease distribution

fistulae

continuous

rare

discontinuous

common

endoscopic assessment

vascular pattern

cobblestone mucosa

friable mucosa

distorted

not present

present

normal

common

rarely present

Biopsy findings

disease location

ulceration

aphthous ulcers

granulomas

location of immune cells

mucosal

only in affected area

very rare

not present

mainly in mucosa

transmural

in affected areas and apparently normal mucosa

very common

widespread

transmural (mucosa, submucosa and deeper tissues)

 

Treatment strategies in UC and CD

Once the diagnosis is established, appropriate treatment can be given. This may be nutritional, medical or surgical, or any combination of these. In UC, medical treatment is the mainstay and surgery is a last resort. In CD, medical treatment is just as important, but surgery is more likely to be needed, often more than once in a given patient.

A similar range of drugs is used in the medical treatment of both UC and CD. Detailed information on individual drugs is provided later, but the main classes involved are:

These may be given orally, as an enema or foam via the rectum or, more rarely, by injection.

 

 

 

 

Nutritional therapy

Nutritional support is essential for both UC and CD patients, especially children. Malnutrition is one of the most serious complications of UC and is a major cause of growth failure in affected children. CD affecting the upper alimentary canal can cause nausea and vomiting, leading to malnutrition in these patients too.

Nutritional support can be given in two ways; via the alimentary canal (enteral nutrition) or by other routes (parenteral nutrition).

Enteral nutrition is the simplest method, provided that the patient can both absorb and tolerate the nutrients supplied. A range of formulations is available, usually in liquid form for ease of administration and absorption. These provide all the essential dietary components – carbohydrate, protein, fat, electrolytes, minerals and vitamins.

Patients who are conscious and able to eat can take enteral nutrition by mouth. If oral feeding is not possible, then a nasogastric tube can be used to deliver nutrition direct to the stomach or duodenum. In patients who are vomiting, have severe bowel obstruction or diarrhoea in response to enteral feeds, parenteral nutrition becomes necessary.

Parenteral nutrition bypasses the alimentary canal and delivers nutrients directly through a cannula into the venous bloodstream. In total parenteral nutrition (TPN), all the patients nutrition is received in this way. TPN is indicated in patients with severe malnutrition, chronic intestinal obstruction, growth impairment or who have had so much small intestine removed surgically that they can no longer absorb sufficient nutrients (short bowel syndrome).

In these patients, TPN corrects the malnutrition and may allow catch-up growth and the onset of puberty in affected children. It also allows fistulae to heal in CD patients, partly due to ‘resting’ the bowel and partly through correcting nutritional deficiencies.

Parenteral nutrition does have its drawbacks, however, such as the risk of damage to the veins. Inappropriate formulations may also cause metabolic complications.

Medical therapy

Drug treatment is the basis of disease management for both UC and CD. Different drugs may be used for treatment of active disease and for maintenance therapy to prevent relapse.

5-ASA drugs (aminosalicylates)

In the majority of UC patients, the aminosalicylates are the mainstay of treatment. The first of these, sulphasalazine, was first discovered to be effective in the 1940s. It consists of 5-aminosalicylic acid (5-ASA or mesalazine), linked by a diazo bond to sulphapyridine. The bond is cleaved by colonic bacteria, releasing the two components into the bowel, where it has a local anti-inflammatory effect.

In UC, sulphasalazine is effective against active disease and also helps prevent relapse. Many patients take 1g twice daily as maintenance therapy for many years. Unfortunately, the sulphapyridine component causes side-effects in some patients. The most frequent of these include:

More serious side-effects, such as hepatitis and kidney damage, are less common. To avoid the risk of any of these adverse effects, different methods of delivering mesalazine to the large intestine have been developed. Oral administration is ineffective because the drug is absorbed in the small intestine and does not reach the colon in significant amounts.

The first new method of delivery for mesalazine was pH dependent resin coating. This did not release the active drug until it reached the large intestine. Unfortunately, rapid colonic transit, due to diarrhoea, can prevent an effective dose being delivered. pH dependent microspheres have also been developed, but have similar limitations.

Azo-bonding two molecules of mesalazine together produces a prodrug called olsalazine. This is cleaved into the two molecules in the colon in the same way as sulphasalazine. Replacing the sulphapyridine with an inert carrier molecule produced balsalazide, another prodrug. This prodrug is also cleaved in the colon to deliver the mesalazine where it is needed. These preparations are usually well tolerated by sulpha-sensitive patients and are effective in active disease and maintenance therapy in UC.

In CD patients, high doses of 5-ASA-type drugs can help control active disease, especially in combination with steroids. They are of less value in maintaining remission.

Corticosteroids

Corticosteroids, such as prednisolone, budesonide and hydrocortisone are important in controlling active UC and CD, but are of less value in maintenance therapy. Hydrocortisone is often given intravenously in acute colitis. The adverse effects of steroid treatment can be serious, so their use must be restricted. Short courses of high dosage followed by a period of ‘tapering down’ the dosage helps minimise adverse effects.

Corticosteroids may be given as suppositories or enemas to control left-sided colonic disease. Prednisolone liquid enema was the first available. Many patients find the more recent foam enemas are easier to retain than liquid enemas. Formulations of budesonide have lower systemic availability and so are less likely to cause systemic adverse effects, such adrenal suppression.

In CD, a combination of steroids and 5-ASA drugs may be more effective than either drug alone. A controlled-ileal-release form of budesonide is useful in treating Crohn’s disease of the small intestine and ileocaecal region. In some patients, a four week simple ‘elemental’ diet is as effective as steroids in controlling CD.

Corticosteroid side-effects

Systemic steroids, used long term are most likely to cause adverse effects than short courses of topical steroids, such as budesonide.

Alimentary canal Dyspepsia (indigestion)

Candidiasis (thrush)

Skin Hirsuitism (overgrowth of hair)

Striae (lines)

Bruising from skin atrophy and capillary fragility

Metabolic Obesity

Diabetes

Hypertension and oedema from sodium retention

Musculoskeletal Muscle wasting

Osteoporosis (bone weakening)

Aseptic necrosis of bone

Eyes Cataracts

Glaucoma (sight threatening increase in intra-ocular pressure

Others Psychiatric disturbance

Reduced resistance to infection

Immunosuppressants

Azathioprine and its metabolite 6-mercaptopurine have a steroid sparing effect. They also help to prevent relapse after steroid therapy in Crohn’s disease. The disease often starts to reactivate during or soon after tapering down the steroid dosage. These drugs have some intrinsic activity of their own against the disease but can take three to four months to work.

Azathioprine is also effective in patients with refractory ulcerative colitis, especially in patients with chronic left-sided disease or a short history of extensive refractory disease, when surgery is not imminent. The drug may be also used in combination with aminosalicylates.

Antimicrobials

Metronidazole is a broad spectrum antibacterial drug. It has been shown to be as effective as sulphasalazine in the treatment of acute Crohn’s disease. It is particularly suitable for active colonic disease. Ciprofloxacin, another broad spectrum antibiotic is also being assessed. Both drugs have proven value in the treatment of perianal Crohn’s disease.

Use of metronidazole, however, is often limited by adverse effects, including anorexia, fatigue, vomiting and neurotoxicity (damage to peripheral nerves). These are usually reversible on stopping the drug. Metronidazole is a useful alternative in some patients who cannot tolerate sulphasalazine. Its mode of action is unclear. It may help by reducing bacterial numbers or by some effect on the immune system.

New developments

TNF-alpha blocking agents are a new type of drug, currently indicated for the treatment of moderate to severely active Crohn’s disease, when conventional therapy is inadequate and for CD patients with fistulae.

These drugs are believed to block intestinal inflammation in patients with CD by binding to and neutralising tumour necrosis factor alpha (TNF-alpha) on the cell membrane and in serum and by destroying the TNF-alpha producing cells.

This drug is an antibody, derived from both human and mouse lines. It is intended for use as adjunctive therapy in patients whoi will continue to receive corticosteroids, antibiotics, aminosalicylates or other immunomodulators. Around 50% of non-fistula patients have entered remission within 4 weeks in clinical trials. Dosage is a single infusion of 5mg/kg bodyweight. For fistulas, an initial dose of 5mg/kg is administered, repeated at two weeks and six weeks later.

 

Summary of drugs and their uses

Type of drug

Name of drug

Indications and remarks

 

 

Ulcerative colitis

Crohn’s disease

Corticosteroids

prednisolone

control of active disease

not maintenance therapy

Treatment of active disease

Can be given topically for left-sided colonic disease

 

budesonide

control of active disease

not maintenance therapy

High first-pass metabolism reduces risk of adverse effects

Can be given topically for left-sided colonic disease

Treatment of active disease

Controlled-release form for ileocaecal disease

High first-pass metabolism reduces risk of adverse effects

Can be given topically for left-sided colonic disease

 

hydrocortisone

used intravenously in acute colitis

 

Aminosalicylates

sulphasalazine

treatment of active UC and prevention of relapse

Treatment of active Crohn’s colitis

 

mesalazine

treatment of active UC and prevention of relapse

Treatment of active CD (high doses) and maintenance of remission or after bowel resection

 

olsalazine

treatment of active UC and prevention of relapse

Treatment of active CD (high doses) and maintenance of remission or after bowel resection

 

balsalazide

treatment of active UC and prevention of relapse

Treatment of active CD (high doses) and maintenance of remission or after bowel resection

Antibiotics

metronidazole

 

treatment of active colonic and perianal disease

 

ciprofloxacin

 

used with metronidazole if sepsis present

Immuno-modulators

azothioprine or 6-mercaptopurine

azothioprine is useful in patients with refractory UC

Slower onset than steroids – often given in combination with aminosalicylates

Treatment of chronic disease

Effect not seen for 3-4 months

Steroid-sparing and useful in maintaining remission

Toxicity limits role to second-line therapy

 

TNF-alpha blockers

future use as adjunctive therapy only

Treatment of refractory CD and/or fistulae

 

 

 

Surgical options

Surgery is always a last resort in the treatment of UC and CD. It is, however, curative in UC, although it carries a significant risk of complications or even death. For patients who are seriously ill, do not respond to medication or who develop serious complications, surgery may be the only answer.

The standard procedure for UC patients is colectomy – complete removal of the large intestine. There are many variations on this procedure. Two of the most widely used are panproctocolectomy with ileostomy and ileorectal anastomosis.

Panproctocolectomy involves removal of the rectum and anus as well as the colon. It has the advantage of removing all the diseased tissue, reducing the risk of subsequent cancer.Deans 1998 p83 Recovery is generally good, although there is a mortality rate of 3%, rising to 10% if this surgery is performed as an emergency. Patients can usually return to normal activities within 2 months.

The major drawback to the procedure is the need for a stoma. A stoma is constructed by the surgeon. The cut end of the ileum is brought up to the surface of the skin, to provide an artificial alternative to the anus. Faeces are collected in a bag over the stoma, which must be removed and replaced frequently, as control over defecation is lost. Many patients find this deeply distressing.Deans 1998 p83

In an ileorectal anastomosis, the cut end of the ileum is connected to the rectum, allowing faeces to be passed through the anus. Postoperative stool frequency tends to be more frequent than normal, but the result is more cosmetically acceptable to many patients than a stoma.

More recent surgical techniques, such as restorative proctocolectomy, are gradually replacing these procedures. In this procedure, a pouch is formed internally from the end of the ileum and attached to the rectum. Different shapes of pouch , S, J, W or Y may be formed, as a substitute for the rectum to store faeces prior to defecation. The mucosa is removed from the rectum and anus to reduce the risk of cancer. This procedure is contra-indicated in Crohn’s disease, but 5-10% of patients undergoing it turn out later to have CD. Complications, such as anal or vaginal fistulae, require removal of the pouch or the ileum (ileostomy) in up to half of these patients, compared to around 3% of those with UC. The functional results of this procedure improve for up to two years and are best in children. Patients undergoing this type of surgery require intensive post-operative care, often needing antibiotics, TPN and other treatment.

In Crohn’s disease, surgery is needed in a higher proportion of patients and may need to be repeated. The most common surgical procedures are local resection, strictureplasty and, as in UC, panproctocolectomy with ileostomy. Many fistulas can be treated conservatively with parenteral nutrition, unless sepsis develops. Local resection is simply the surgical removal of a section of badly affected intestine, the two ‘healthy’ remaining ends being reconnected surgically. The principles of surgery for CD are to remove as little bowel as possible. This is due to the likelihood of recurrence at the site of previous surgery and the risks of short bowel syndrome.

Strictureplasty is used to preserve the diseased bowel while overcoming the restriction on movement of bowel contents. It involves cutting the bowel longitudinally and suturing it transversely, to restore its diameter.

Ileorectal anastomosis and pouch formation are not used in CD because of the risk of local recurrence or cancer of the remaining rectum. This is due to the involvement of the full thickness of the bowel wall in CD, in contrast to UC, where the mucosa is usually the only tissue affected.

Summary

Inflammatory bowel disease is a major worldwide health problem. The symptoms and other problems it causes are due to inflammation within the alimentary canal.

The alimentary canal consists of the mouth, oesophagus, stomach, small intestine, large intestine, rectum and anus. The whole length of the canal is a continuous muscular tube. The structure of this tube is fairly constant throughout its length, consisting of four layers. The innermost layer, the mucosa, is most involved in IBD. The liver and gall bladder are also involved in the overall digestive process.

Digestion begins in the mouth, but food is mainly processed in the stomach in preparation for absorption of nutrients, most of which takes place in the small intestine. The large intestine is where water and electrolytes are absorbed and undigested food and waste matter are formed into faeces and stored for excretion.

The alimentary canal has physical chemical and immune system defences against invading micro-organisms.The immune system is involved in the aetiology of IBD, but its precise role is unclear. Immunoglobulins and inflammatory cells are strongly associated with IBD.

Ulcerative Colitis is more common in men, Crohn’s disease more common among women, though the differences are small. UC is mainly confined to the rectum, colon and distal ileum. CD can affect any part of the alimentary canal, but is most common in the small and large intestines.

The hallmarks of UC are infiltration of the mucosa by inflammatory cells and formation of crypt abscesses. Toxic megacolon and perforation are the two of the most serious complications of UC

The hallmarks of CD are skip lesions (sharply outlined areas of ulceration separated by areas of normal tissue), aphthous ulceration, fistula formation, cobblestone mucosa and granulomas.

Investigations for IBD include sigmoidoscopy, endoscopy, colonoscopy, radiology, ultrasound scanning, barium enemas and laboratory investigations.

The medical treatment of IBD involves nutritional support, aminosalicylates (5-ASA drugs), steroids, antimicrobials and immunosuppressive drugs. Surgery is often necessary, often more than once in CD.

GLOSSARY OF TERMS

abscess – localised collection of pus within a tissue

ACTH response – a measure of adrenal impairment

acute toxic megacolon – distension of the colon with paralysis and loss of ability to absorb water and electrolytes – potentially fatal

aphthous ulcers – shallow, painful areas of damaged mucosa in CD patients

auto-antibodies – antibodies which attack their own body cells

autoimmune disease – a condition in which cells of the body are attacked by its own immune system

biopsy – small sample of tissue for microscopic analysis

cataracts – opaque tissue forming in the eye, affecting sight

chronic intermittent UC – long-term UC, with periods of remission between acute flare-ups

cirrhosis – chronic liver disorder in which fibrous scar tissue gradually replaces normal liver tissue

clubbing – thickening of the bones of the fingertips and toes

colonoscope – flexible fibre-optic (endoscope) speculum used to examine the colon internally

colonoscopy. This involves inserting an endoscope into the colon to view the mucosal surface directly and to take tissue samples for analysis if required

colorectal – the area of the colon adjoining the rectum

complication – a condition occurring during the course of or as a result of another disease and often aggravating it

confluent ulceration – ulcers that have joined up to cover large areas

crypt abscess – a deep cleft in the colon wall that fills with inflammatory cells, bacteria and cell debris (i.e. pus) as a result of UC

deep venous thrombosis – a blood clot that forms in and blocks one of the deep veins

disease progression – the gradual worsening of a disease

distal – far from the centre of the body e.g fingers are on the distal end of the arm

distal colitis – inflammation of the rectal end of the colon

distension – swelling or dilation of a hollow organ or body cavity due to internal pressure

diverticular disease - formation of sacs or pouches of mucosal tissue through the intestinal wall

dyscrasias – blood disorders that can be a rare adverse effect of treatment with mesalazine or balsalazine

dysplasia – abnormal development of tissues, organs or cells

endoscope – an instrument for viewing the interior of a bodily canal or hollow organ

endoscopy – the use of an endoscope in a body cavity such as the alimentary canal

enema – the injection or insertion of liquid into the rectum for cleansing, laxative or other therapeutic purposes

enteral nutrition – nutrients delivered via the alimentary canal

enteric pathogens – micro-organisms causing infections in the alimentary canal

episcleritis – painful inflammation of the external eye tissues

fibrotic – the stiff, fibrous structure of affected parts of the bowel wall in CD

fistulas – abnormal communication between a hollow organ and its surface

friable – fragile, easily damaged, crumbly

glaucoma – raised intraocular pressure that can cause blindness

granulomas – lumps formed from clumps or aggregates of inflammatory cells

haemorrhage – sudden flow of blood from damaged blood vessels

haemorrhagic lesions – bleeding defects in the mucosa of CD patients

infectious colitis – inflammation of the colon due to infection by a pathogenic organism

infiltration – gradual entry of cells or substances into a body tissue

insufflated – air or other gas or vapour blown into a body cavity

ischaemic colitis – inflammation of the colon due to localised loss of blood supply causing tissue damage

malignancy – an abnormal growth threatening health and/or life – often spreads or metastasizes to other parts of the body

metastatic Crohn’s disease ulcerated areas of skin appearing on patients with CD

microbiological culture – a process used to detect and identify micro-organisms

mucosal islands – raised, red, swollen patches of mucosa left on an otherwise ulcerated area of the intestinal wall

nasogastric tube – a thin tube inserted through the nasal passages, down the oesophagus and into the stomach or duodenum

necrosis – death of living tissue due to disease, injury or interruption of blood supply

nephrotoxicity – toxic effects occurring within the kidney

neurotoxicity – drug-induced damage to peripheral nerves

osteoblasts – cells involved in forming and replacing bone

osteocytes – cells involved in the removal or replacement of bone

osteoporosis – brittleness and weakening of bone due to old age or as a side effect of steroid treatment

parenteral nutrition – nutrients delivered by any route except the alimentary canal

percutaneous – through the skin

peritonitis – infection of the intra-abdominal space

hypothalamus – pituitary – adrenal (HPA) axis interaction between these glands controls

prophylaxis (prophylactic treatment) – preventive treatment, taken to stop symptoms developing – as opposed to standard treatment of symptoms as they occur

prostration – inability to stand up due to muscular weakness caused by illness

proximal – near to the centre of the body (opposite to distal)

pus – a fluid containing bacteria and inflammatory cells plus cell debris - associated with infection and inflammation

pyrogens – temperature-raising chemicals released by inflammatory cells

radiation colitis – inflammation of the colon due to exposure to radiation – usually as part of cancer treatment

radiology – the use of X-rays in medical diagnosis or ionising radiation in radiotherapy or diagnosis

short bowel syndrome – potentially fatal condition due to removal of too much small intestine, causing inability to digest food adequately

sonography – use of sound to form images e.g ultrasound scanning

splenic flexure – the junction of the transverse and descending colon near the spleen

stoma – a surgically constructed alternative external exit point for faeces

stricture – a narrowing or restriction in a tube such as the alimentary canal

suppositories – solid drug dosage forms, shaped for insertion into the rectum

suppurating – forming and/or discharging pus

tenesmus – painful, difficult defecation with pellet-like stools in UC

total parenteral nutrition – provides all the nutrients needed by severely ill patients, bypassing the alimentary canal

ulcer – an inflammatory, often suppurating lesion on the skin or internal mucus membrane, causing tissue necrosis and usually taking a long time to heal

ultrasound – sound frequencies above 20 kHz, the upper limit for human hearing – used in sonography to visualise internal tissues

uveitis – sight-threatening inflammation of the iris and associated structures