Inflammatory bowel disease (IBD) is a general term that refers to both ulcerative colitis and Crohn's

disease. Both conditions are chronic relapsing disorders and show great variability in their symptoms,
severity and associated complications. Their aetiology is not well understood and it has been suggested
that there are both genetic and environmental components1.

Crohn's disease

The condition now known as Crohn's disease was first documented in 1791. It was not until 1932
that Bernard Crohn and his colleagues described this as a distinct clinical entity that affected
mainly the distal ileum. Reports published in the 1950's showed that Crohn's disease was not
only confined to the ileum, but could also occur in the colon. Today, Crohn's disease is
considered a chronic inflammatory condition, which can affect any region of the gastro-intestinal
tract, from the mouth to the anus.

The prevalence of Crohn's disease is 145 per 100,000 people in the UK (about half that of UC)3.
There are currently at least 115,000 people in the UK with Crohns disease1. Crohn's disease
presents most commonly in adolescence and early adulthood - the median age at diagnosis is
about 30 years3.

The most significant effect with IBD in children is growth retardation; this can occur even in mild forms
of the disease and can lead to permanent short stature.

Ulcerative colitis (UC)

UC on the other hand, posed other difficulties in its recognition. Its symptoms and pathology
were first described in 1859 but heated debate continued regarding its aetiology. Many
considered it to be a form of dysentry, others thought that it was psychosomatic in nature and
some thought that it resulted from the use of preservatives in recently introduced tinned food.
The first complete description of the condition was attributed to Hurst in 1909 and unlike
Crohn's disease, UC affects only the rectum and colon.

UC has a prevalence rate of 243 per 100,000 population per year and affects approximately
146,000 in the UK2. In a small percentage of patients it is not possible to determine if they have
UC or Crohns disease. Such patients are said to suffer from indeterminate colitis.

The peak incidence of UC is between 15 and 25 years of age, with a second smaller peak
between 55 and 65 years of age4.

It is important to have an awareness of the anatomy of the gastro-intestinal tract, in particular the
small and large intestine, when considering IBD. Drag and drop the boxes below to label the
large and small intestines anatomy.

Aetiology

Evidence suggests that the aetiology of UC and Crohn's disease may have a genetic, infectious,
psychological and/or immunological basis, although the causes are not fully known4. Probably
the most widely accepted hypothesis of inflammatory bowel disease is that it is the result of
genetically determined defective immunosuppression resulting in an overly aggressive response
to gut luminal contents.

Sensitising antigens activate cytotoxic T-lymphocytes to produce antibodies and induce the
inflammatory cascade evident in the gastro-intestinal tract5. This argument is given added weight
by the clinical response of patients to corticosteroids and other immunosuppressive agents. The
source of antigens remains the subject of much speculation. It has been suggested that the disease
may be auto-immune in nature or that dairy products containing albumin may be responsible.
While the evidence for these hypotheses is incomplete, an immunological basis for the disease
may also explain some of the extra-intestinal manifestations.

Smoking status affects the two conditions differently. The risk of Crohn's disease is increased in
smokers. This contrasts with UC, for which the risk of the disease is decreased in smokers
compared to non-smokers4.

The incidence of IBD is increased in women using oral contraceptives. However, the absolute
risk increase is so low that it should not influence contraceptive choice3, 6.

A family history is present in around 25 to 40% of children with Crohns disease3; siblings of an
individual with Crohn's disease are 17 to 35 times more likely to develop the condition than the
general population3, 7. First-degree relatives of people with UC have a 10 to 15% increased risk
of developing the disease4, 8. However, the genetics are complex and not fully understood.
Diarrhoea

In UC more than 90% of patients report bloody diarrhoea often accompanied with urgency,
tenesmus, passage of mucus and crampy abdominal pain. However, patients with proctitis may
have little diarrhoea and occasionally severe constipation.

In Crohns disease, diarrhoea is the most common presenting symptom accompanied by

abdominal pain and weight loss.

Ulcerative colitis is a disease affecting the colon and rectum only and involves continuous
inflammation of the mucosal lining. The colonic mucosa becomes fragile which leads to rectal
bleeding, although life-threatening haemorrhage is uncommon.

Ulcerative colitis is a disease affecting the colon and rectum only and involves continuous
inflammation of the mucosal lining. The colonic mucosa becomes fragile which leads to rectal
bleeding, although life-threatening haemorrhage is uncommon.
 Normal colonic mucosa

Mucosa in UC showing inflammatory changes

In contrast to this first picture, Crohn's disease may occur anywhere in the gastro-intestinal tract,
from the mouth to the anus, with 40 to 50% of patients showing ileocolonic involvement, 30%
small bowel disease only and in 30% the disease is limited to the colon10. Typically, areas of
normal gut are interspersed with areas of diseased intestine. This is known as segmental
inflammation or skip lesions. Inflammation seen in Crohn's disease is not confined to the
mucosa but affects the entire bowel wall (transmural). Segments of the gastro-intestinal tract
affected in this way tend to be fibrotic and rigid. The degree of inflammation may ultimately
cause thickening of the muscle leading to narrowing of the gut lumen (stricture) and possible
obstruction, accompanied by a feeling of an abdominal mass with associated pain11.
Gastro intestinal

Toxic megacolon

Toxic megacolon is more commonly associated with severe ulcerative colitis when the colon is
dilated (more than 6 cm in the left colon or more than 12 cm in the caecum). Distension of the
colon is caused by loss of motility through inflammation, diarrhoea-induced hypokalaemia and,
occasionally, by the use of opiates.

It constitutes a surgical emergency because of the risk of perforation and carries a mortality rate
of 50% (although perforation can occur in the absence of megacolon).
Abscess

Abscesses may occur because of the increased permeability of the affected gut to micro-
organisms. Treatment involves surgical drainage of the abscess coupled with aggressive
antibiotic therapy.
Fistula

Fistulae are channels that can form between the bowel and the skin or between the bowel and
another organ, such as the bladder. They occur more commonly in Crohn's disease. Treatment
may not be necessary for simple, asymptomatic perianal fistulae. Metronidazole or ciprofloxacin
may improve symptoms of fistulating Crohns disease while some fistulae may require
exploration and local drainage. Fistulae may close spontaneously in some patients as a result of
bowel rest when nutrition is provided by the parenteral route.
Haemorrhage

While bleeding is frequently seen in ulcerative colitis, major life-threatening haemorrhage is

uncommon in either form of inflammatory bowel disease.
Stricture

Ten percent of patients will develop strictures and these are caused by either the inflammatory
processes or carcinoma. If left untreated, a stricture may proceed to bowel obstruction11.
Carcinoma

The incidence of bowel carcinoma in patients with Crohn's disease is slightly higher (less than
5%) than that of the population, whereas patients suffering from UC have a much higher risk of
colonic carcinoma. The incidence increases with the extent and duration of disease, being most
frequently observed in patients whose colitis is chronic continuous in nature12. Patients should
undergo surveillance for colonic carcinoma at appropriate intervals.
EXTRA INTESTINAL

Joint disease

Often presenting as arthritis, this is the most common extra-intestinal condition in IBD. It is
usual for only one large joint to be affected and this may precede the onset of gastro-intestinal
symptoms. Ankylosing spondylitis occurs in 1 to 5% of patients.
Skin problems

Cutaneous lesions, such as erythema nodosum appear as red, tender nodules on the skin, and can
occur in up to 15% of patients with IBD.

Pyoderma gangrenosum presents as small pustules in the skin that can develop into large ulcers.
It is rare but difficult to treat and is associated with extensive long-standing colitis or ileo-colitis
disease.
Oral manifestations

Aphthous ulcers occur in up to 9% of patients with Crohn's disease. Their presence usually
parallels the severity of the underlying disease.
Eye disease

Iritis is the most common eye complaint and is characterised by blurred vision, pain and
photophobia.
Hepatobiliary problems

Gallstones are found in 13 to 34% of patients with Crohn's disease of the ileum and are
particularly common in patients who have had part or all of the ileum removed. Primary
sclerosing cholangitis occurs more commonly in ulcerative colitis than Crohns disease.
Vascular disease

Inflammation of the veins, particularly in the legs and portal system, can occur in colitis.
Osteoporosis and osteomalacia

Osteoporosis and vitamin D deficiency are common in IBD. IBD is a cause of secondary
osteoporosis.
Anaemia

Iron deficiency and anaemia of chronic disease are the commonest causes of anaemia in
inflammatory bowel disease, though folate and vitamin B12 deficiency occur.
Initial investigations include:

full blood count (FBC)

urea and electrolytes (U&Es)
liver function tests (LFTs)
c reactive protein (CRP) - high CRP levels are indicative of active disease or a bacterial
complication
stool culture and microbiological testing for infectious diarrhoea including Clostridium
difficile toxin.

NICE recommends faecal calprotectin testing as an option to support clinicians with the
differential diagnosis of IBD or IBS in adults with recent onset lower gastrointestinal
symptoms37. Faecal calprotectin is a substance that is released into the intestines in excess when
there is any inflammation there. Its presence can indicate an IBD such as Crohns disease or UC.

Endoscopy is the most useful investigative tool for IBD, enabling visualisation of the intestinal
mucosa and allowing mucosal biopsy. The characteristic continuous mucosal inflammation seen
at colonoscopy enables a reasonably confident diagnosis of UC to be made before biopsy results
become available. Colonoscopy is valuable in the investigation of Crohns disease, enabling
visualisation and biopsy of patchily distributed colonic disease; it often reveals characteristic
terminal ileal involvement5, 10.

Sigmoidoscopy is easier for the patient and can be used for initial diagnosis or in severe disease
but it is not able to fully define the extent of the disease in UC. Endoscopies should not be
painful but may be uncomfortable. Biopsies (small samples of tissue) are often taken during an
endoscopy. These can then be examined under a microscope to confirm the diagnosis.

In UC, the disease is classified (see table below) according to the extent of colonic inflammation2
and this
information is essential in choosing the correct treatment.

In addition, the severity of disease for UC may be classified as follows:

Extent of inflammation and main

Involvement in the colon Classification
symptoms
Proctitis: bleeding, pain and tenesmus Limited to rectum E1
Left-sided: bloody diarrhoea, cramps, Limited to the portion of the colon
E2
pain and weight loss distal to the splenic flexure
Extends proximal to the splenic
Extensive (including pancolitis):
flexure, with the transverse colon in
bloody diarrhoea, cramps, pain, fatigue, E3
extensive colitis and the entire colon in
weight loss, night sweats
pancolitis
Classification Severity Symptoms
S0 Clinical remission Asymptomatic
S1 Mild Usually less than 4 bowel movements per day with or
 without rectal bleeding, no systemic illness and normal
ESR
Greater than 4 bowel movements per day and minimal
S2 Moderate
signs of systemic toxicity
More than 6 bowel movements per day with systemic
S3 Severe signs such as fever, tachycardia, anaemia and signs of
malnutrition such as hypoalbuminaemia.

Trevor Jones is a 47-year-old man who has had ulcerative colitis for 8 years. He takes
mesalazine 2.4g daily as maintenance. His symptoms have been worsening over the last 3 weeks
and, following a visit to his GP, he is prescribed a course of prednisolone 40mg/day. After 7 days
treatment his condition has not improved and he continues to experience diarrhoea, with 8-10
bowel movements per day. He is hospitalised at the request of his GP, and the following
objective signs and tests are recorded.

What aspects of Trevor Jones' history indicate that he may be suffering from an acute episode of
severe UC? What specific test abnormalities should be corrected?

Numerous scoring systems are available for quantifying disease activity in Crohns disease. The
Crohn's Disease Activity Index (CDAI) and the Harvey-Bradshaw Index (HBI)5 are often used to
classify Crohns disease. In both scoring systems patients are assessed on a number of
parameters, such as number of soft stools per day, abdominal pain, general well-being and extra-
intestinal features. Each system allocates the patient a score which can then be used to classify
the current disease activity. For example, a score of >300 in the CDAI represents a disease
activity that is currently severe.

The Montreal Classification for Crohns disease is based on the age of onset (A), location of
disease (L) and disease behaviour (B)2 as described in the table below:

Montreal classification
A1: less than 16 years
Age at diagnosis A2: between 17 and 40 years
A3: over 40 years
L1: ileal
L2: colonic
Location
L3: ileocolonic
L4: isolated upper digestive
B1: non-stricturing, non-penetrating
B2: structuring
Behaviour
B3: penetrating
P: perianal disease
Crohns disease can also be classified as localised (affecting <30cm of intestine) or extensive
(affecting >100cm), the length being the total amount of bowel affected in the discontinuous
segments.

For almost 40 years the mainstay of drug treatment for inflammatory bowel disease was
sulphasalazine and corticosteroids. These together with improvements in fluid and electrolyte
therapy, reduced the mortality of inflammatory bowel disease significantly6,11. Currently, there
are four main groups of anti-inflammatory drugs, which work in different ways to reduce or
control inflammation:

aminosalicylates
corticosteroids
immunosuppressants: azathioprine, ciclosporin, mercaptopurine, methotrexate
biologics: infliximab, adalimumab, golizumab and vedolizumab.

Antibiotics and supportive therapies are frequently used in addition to anti-inflammatory drugs in
the treatment of inflammatory bowel disease.

The following pages will describe drug treatment under the five categories below:

anti-inflammatory drugs (Aminosalicylates, Corticosteroids)

drugs affecting the immune response (azathioprine, ciclosporin, mercaptopurine,
methotrexate, tacrolimus and TNF inhibitors)
antibiotics (metronidazole, ciprofloxacin)
 supportive therapies
other therapies.
During the 1930s, Dr Nanna Svartz suggested an infectious aetiology to rheumatoid
arthritis and proposed linking an antibacterial (sulphonamide) with an anti-inflammatory
agent (salicylic acid). This led to the development of sulphasalazine, which, in clinical
use, brought about an improvement in ulcerative colitis in patients who were primarily
being treated for rheumatoid arthritis.
Following these serendipitous observations, sulphasalazine was used in mild to moderate
inflammatory bowel disease at doses of 4-8g daily, and as maintenance therapy at lower
(2g daily) doses. The precise mode of action of sulphasalazine remains unclear although a
local effect on epithelial cells is proposed with the modulation of inflammation mediators
such as products of lipo-oxygenase and cyclo-oxygenase metabolism, platelet-activating
factors and cytokines14.

Dose-related Non-dose-related
Nausea Hypersensitivity
Vomiting Haemolytic anaemia
Dyspepsia Male infertility
Malaise Bone marrow suppression
Headache Hepatitis
Fibrosing alveolitis

The side-effects of sulphasalazine may be classified as either dose-related or non-dose-

related (see table above). The dose-related effects, principally nausea and vomiting,
frequently limit sulphasalazine's use in patients.
Answer

Upper GI side-effects are common with doses over 4g daily (BNF 64) but it is possible to
desensitise patients to these unpleasant effects by increasing the dose, in 0.5g increments, over 6
- 8 days to the maximum tolerated dose (4-8g/day).

Despite this type of regimen, non-dose-related effects can still be a problem and the BNF
recommends that any patient with unexplained bleeding, bruising, fever, or sore throat during
treatment, should report these, and that blood counts should be performed and treatment stopped
immediately if there is a suspicion of blood dyscrasia. Patients should also be advised that
mesalazine can increase the sensitivity of the skin to sunlight21.

Studies of the metabolism of sulphasalazine conducted in the 1970's demonstrated that

sulphasalazine is a prodrug comprising of 5-aminosalicylic acid (5-ASA) linked by an azo bond
to sulphapyridine. Little absorption of sulphasalazine takes place in the upper gastro-intestinal
tract; however, on reaching the colon, microbial activity splits the azo bond, liberating
sulphapyridine and 5-aminosalicylic acid (5-ASA). Sulphapyridine is rapidly and completely
absorbed into the systemic circulation and is an inert carrier. It is responsible for the dose-related
effects and many of the non-dose-related effects and is devoid of anti-inflammatory activity. The
active principal of sulphasalazine, necessary to treat inflammatory bowel disease, is therefore 5-
aminosalicylic acid (5-ASA), the generic name of which is mesalazine. In addition, balsalazide
(Colazide), a prodrug of 5-ASA and olsalazine (Dipentum), a dimer of 5-ASA are available.

Mesalazine is tolerated by 80% of patients who are intolerant to sulfasalazine.

Mesalazine has been associated with renal toxicity in some patients. Therefore, its use is contra-
indicated in patients with renal impairment.

Care should also be exercised when using ASAs in patients with severe ulcerative colitis as they
can cause diarrhoea, which may affect the monitoring of therapeutic response and the decision to
proceed to colectomy.

Mesalazine is formulated in a number of modified release forms that allow delivery to the lower
GIT and prevent rapid absorption from the small bowel. The tables below summarise the
properties of some formulations of mesalazine14, and olsalazine and balsalazide respectively.
Mesalazine based preparations according to release system

Modified release System Site of release

Coated with Eudragit S

Asacol MR resin, delayed release Terminal ileum and colon
above pH7

Coated with Eudragit L

Salofalk 100 resin, delayed release Terminal ileum and colon
above pH6
 Modified release System Site of release

Microgranules coated with

Pentasa Duodenum, jejunum, ileum and colon
ethylcellulose membrane

Coated with Eudragit S

Ipocol resin, delayed release Terminal ileum and colon
above pH7

Multi-matrix system,
Mezavant XL delayed release above Terminal ileum and colon
pH7

Coated with Eudragit L

Mesren MR 100 resin, delayed release Terminal ileum and colon
above pH7

Prodrugs

Drugs System Site of release

Two molecules of 5-ASA

(olsalazine) joined by an
Dipentum Colon
azo bond and cleaved by
enteric bacteria

5-ASA joined to a peptide

carrier (balsalazide) by an
Colazide Colon
azo bond which is cleaved
by enteric bacteria

The main role of ASAs is for inducing remission in mild to moderate ulcerative colitis and for
maintaining remission in ulcerative colitis. 5-ASAs are widely used in the management of
Crohns disease despite limited evidence. It may produce a mildly positive benefit in some
patients over placebo, particularly in mild colonic Crohns disease, but more effective treatments
should be used for patients with anything more than mild disease2.

There is insufficient evidence to support the use of mesalazine for maintenance treatment of
Crohns disease21.

Doses of >4g/day orally may be needed to treat active disease, combined with topical therapy,
and >2g/day in maintaining remission.
Recent studies have demonstrated that once daily dosing of mesalazine is more effective than
multiple daily dosing with lower relapse rates, greater rates of remission at up to 12 months,
greater mucosal healing and greater patient acceptability (MOTUS38, CODA39 and PODIUM40
studies).

Corticosteroids have been used in the medical management of inflammatory bowel disease since
the early 1950s. Initially hydrocortisone, then corticotrophin and later prednisolone were shown
to improve symptoms in these patients.

Corticosteroids have multiple actions in reducing the inflammatory cascade through inhibition of
the immune system and the blockade of prostaglandin and leucotriene production. They are
rapidly effective in the treatment of both ulcerative colitis and Crohn's disease, with a response
rate of 70-75%.

The usual dose of oral prednisolone used to induce remission in the acute phase of ulcerative
colitis and Crohns disease is 40mg once daily, a dose that is a reasonable compromise between
efficacy and toxic effects. This dose should be reduced gradually by 5mg every 7 days over a
period of 8 weeks to prevent early relapse.

Patients hospitalised with severe disease are usually given intravenous hydrocortisone, 100mg
four times daily, until oral delivery can be used13.

Treatment - Anti-inflammatories - Corticosteroids - Part 2

Most patients with IBD are treated at some point with systemic steroids. Two large multicentre
trials15, 16 in Crohn's disease showed that up to 83% of patients were in remission after four
months' treatment with corticosteroids, compared to 30% on placebo. The use of corticosteroids
in non-active Crohns disease does not appear to be effective in reducing the risk of relapse.
Once an acute attack has been controlled, the dose of steroid should be tapered and withdrawn.
Rectal corticosteroids undergo systemic absorption and should not be administered indefinitely.
However, some patients will relapse shortly after steroid withdrawal and 10-20% with chronic
symptoms may become corticosteroid-dependant and will require long-term treatment. Please
note that although the trials are all over 30 years old, the results are still valid and consistent42.

Budesonide (9mg/day) is not as effective as prednisolone. It is poorly absorbed and rapidly

cleared by first-pass metabolism, thereby reducing the risk of adverse drug reactions. While it is
more expensive than conventional corticosteroids and produces more adrenal suppression than
placebo, budesonide is useful for patients in whom the minimisation of steroid side-effects is
particularly important12,17. It has an affinity for glucocorticoid receptors 50-100 times that of
prednisolone and so long-term treatment is not advocated and treatment should not be stopped
abruptly. Budesonide is licensed for Crohns disease affecting the ileum and the ascending
colon1.
Beclometasone dipropionate (5mg om for max. of 4 weeks) is licensed as an adjunct to
mesalazine for mild to moderate ulcerative colitis. Hydrocortisone, prednisolone and budesonide
are available for use as topical agents in UC and colitis in Crohns disease.

Steroid use is one of the risk factors in the development of osteoporosis. Click on the x-ray to
learn more.

Other steroids with promise are tixocortol pivalate (available in France and Canada) and
fluticasone propionate12,17,18 but tixocortol has a relatively low affinity for the corticosteroid
receptor and fluticasone has poor clinical efficacy.

Steroid use is one of the risk factors in the development of osteoporosis and osteomalacia,
alongside patient age and disease activity. Therefore, patients taking systemic steroids should
receive supplementation with calcium and vitamin D.

Co-administration of bisphosphonates while the patient is taking steroids is recommended for

patients over 65 years old or with known osteoporosis / osteopenia19.

Inflammatory bowel disease is a cause of secondary osteoporosis and is a risk factor for fragility
fracture. NICE have produced guidance on assessing the risk of fragility fracture in osteoporosis
(CG146)20.

In patients whose disease requires chronic steroids, the use of some immunosuppressants allows the
dose of steroid to be reduced or stopped, a property known as steroid-sparing. As these drugs suppress
the bone marrow, regular monitoring of blood counts is essential to avoid profound suppression. Click
on the headings to learn more.

Thiopurines

Azathioprine is well absorbed from the GI tract and is metabolised to 6-mercaptopurine, which is
thought to be the active agent. About 28% of patients who are unable to tolerate azathiopurine
because of GI side-effects are able to take mercaptopurine. Neither drug is licensed in IBD21.
Both drugs act by interfering with ribonucleic acid synthesis and thereby modulate T-cell
activity.

Azathiopurine at a dose of 2-2.5mg/kg/day or mercaptopurine at a dose of 1-1.5mg/kg/day can

induce and maintain remission in ulcerative colitis and Crohns disease, although the evidence is
stronger for its use in Crohns2. The slow onset of action (2-3 months for an effect to be seen)
limits its use in acute flare-ups. Influenza-like hypersensitivity reactions can occur within 2-3
weeks and will resolve on treatment cessation. Other adverse effects include nausea, vomiting,
hepatotoxicity and pancreatitis.

Before initiating treatment, a patients thiopurine methyltransferase (TPMT) enzyme activity

should be measured21. One in 300 patients have no functional TPMT activity and would be at
risk of severe immunosuppression with standard doses2. Stopping thiopurine treatment should be
considered after 4 years of full remission. Studies are currently being conducted in which an
interaction between allopurinol and thiopurines may be exploited, reducing the thiopurine dose
to around one quarter36.
Ciclosporin

Ciclosporin blocks T-lymphocytes and inhibits interleukins and cytokines affecting the
inflammatory cascade. Its use is limited to refractory ulcerative colitis, as a rescue and bridge to
starting treatment with immunomodulators or biologic medicines, and should rarely be continued
for more than 3-6 months2. Improvement may be expected in 7-10 days. If patients respond to
intravenous ciclosporin (2mg/kg/day), they should be switched to oral therapy (5.5mg/kg/day).

Side-effects occur relatively frequently and, as the margin between benefit and toxicity is very
narrow, serum concentrations should routinely be monitored. Side-effects include malaise,
tremor, headaches, hirsutism, abnormal liver function tests, neurotoxicity (seizures) and gingival
hyperplasia.
Methotrexate

Methotrexate has been used in Crohn's disease refractory to thiopurines to induce and maintain
remission. At doses of 25mg given once per week via the intramuscular route, methotrexate can
induce remission and is steroid-sparing in patients with corticosteroid-resistant Crohn's disease.
To maintain remission, 15mg intramuscularly or 10-25mg orally once weekly may be used.
Studies have shown that such patients can be maintained in remission on methotrexate for up to 8
years, but there is a loss of efficacy over time and no recommendation with regards to duration of
treatment can be made2.
The gastro-intestinal side-effects of methotrexate may be avoided or reduced by supplementation
with folic acid. Folic acid is given at a dose of 5 mg once weekly on a different day to the
methotrexate. Long-term concerns with methotrexate use are hepatotoxicity, pneumonitis and
opportunistic infections.

Tumour necrosis factor alpha (TNF-) is a pro-inflammatory cytokine produced by macrophages and
lymphocytes and found in large quantities in inflammatory diseases. Concentrations of TNF- are
elevated in inflammatory bowel disease and early investigations showed that binding of TNF- by a
genetically engineered antibody resulted in reduction in disease activity. Infliximab, adalimumab,
golimumab and vedolizumab are monoclonal anti-bodies that inhibit TNF-. Click on the headings to
learn more.

Infliximab

Infliximab (also known as Remicade, Inflectra or Remsima) is a chimeric (murine/human)

monoclonal antibody, that was launched in the UK in September 1999.

The ACT (Active ulcerative Colitis Trials) I and II trials showed favourable results in efficacy of
infliximab in ulcerative colitis patients, who demonstrated better clinical response, mucosal
healing and remission, and improved quality of life at 54 weeks when compared with placebo34.

The ACCENT (a Crohns disease trial evaluating infliximab in a new long-term treatment
regimen) I and II studies provided evidence for its use in Crohns disease. After 1 year, patients
with moderate-severe active Crohns disease and fistulising Crohns disease had reduced
disease-related hospitalizations and surgeries, reduced corticosteroid use and an improvement in
their quality of life measures34.
Adalimumab

Adalimumab (Humira) was first launched in the UK in September 200322. Adalimumab is a

fully human monoclonal antibody that is less frequently associated with antibody formation and
hypersensitivity reactions than chimeric monoclonal antibodies (e.g. infliximab). Controlled
trials have shown that adalimumab is safe and effective for treating numerous inflammatory
diseases, such as rheumatoid arthritis, psoriatic arthritis, psoriasis, ankylosing spondylitis and
Crohns disease13.

The CLASSIC I (Clinical Assessment of Adalimumab Safety and Efficacy Studied as Induction
Therapy in Crohns Disease)24 study showed the efficacy of adalimumab in inducing remission
in patients with moderately to severely active Crohns disease who had not previously received
anti-TNF therapy.

The CLASSIC II25 study investigated the potential of this agent to maintain remission in this
same patient group. Results showed that patients receiving adalimumab were 1.6 2.0 times
more likely to have maintained remission at 56 weeks in comparison to those patients receiving
placebo.
Golizumab

Golizumab (Simponi) is a Human IgG1 monoclonal antibody. It was launched in the UK in

October 2009 and is licensed for certain patients with rheumatoid arthritis, psoriatic arthritis and
ankylosing spondylitis. Golizumab is indicated for moderately to severely active UC in adults
who have had an inadequate response to conventional therapy (corticosteroids, 6-
mercaptopurine, azathioprine), or who are intolerant or have contraindications26.

The efficacy of Golizumab was evaluated in two randomised, double-blind, placebo-controlled

clinical studies in adult patients. The induction study (PURSUIT-Induction) evaluated patients
with moderately to severely active UC. More Golizumab-treated patients demonstrated sustained
mucosal healing (42%) compared with patients in the placebo group (27%)26.

The results of the maintenance study (PURSUIT-Maintenance) were based on evaluation of 456
patients who achieved clinical response from previous induction with Golizumab. Among the
54% of patients who were receiving concomitant corticosteroids at the start of PURSUIT-
Maintenance, the proportion of patients who maintained clinical response through week 54 and
were not receiving concomitant corticosteroids at week 54 was greater in the 50 mg group (38%)
and 100 mg group (30%) compared with the placebo group (21%)26.
Vedolizumab

Vedolizumab (Entyvio) is a humanised IgG1 monoclonal antibody that binds to human 47

integrin. It was launched in the UK in May 2014 and is licensed for the treatment of adult
patients with moderately to severely active UC or Chrons disease who have had an inadequate
response with, lost response to, or were intolerant to either conventional therapy or a tumour
necrosis factor-alpha (TNF) antagonist27.

The GEMINI 1 study found Vedolizumab to be more effective than placebo as induction and
maintenance therapy for UC27.

The GEMINI 2 study reported that Vedolizumab-treated patients with active Crohn's disease
were more likely than patients receiving placebo to have a remission, but not a CDAI-100
response, at week 6; patients with a response to induction therapy who continued to receive
vedolizumab (rather than switching to placebo) were more likely to be in remission at week 52.
However, adverse events were more common with vedolizumab than placebo27.

Monoclonal antibody doses include:

infliximab is administered as a 5mg/kg infusion over 2 hours at 0, 2 and 6 weeks and then
every 8 weeks thereafter34
adalimumab is administered subcutaneously at an induction dose of 80mg followed by a
40mg dose two-weekly thereafter27
golizumab is administered subcutaneously initially at 200 mg, followed by 100 mg at
week 2, then 50 mg (if body weight < 80 kg) or 100mg (if body weight > 80 kg) every 4
weeks thereafter26
 vedolizumab is administered as a 300mg infusion at 0, 2 and 6 weeks and then every 8
weeks thereafter27.

Funding should be secured for each patient due to the expense of the medication and treatment
should be given for 12 months or until treatment failure. Treatment may be continued beyond 12
months only if there is evidence of active disease.

Biosimilar infliximab (Remsima) became available in the UK in February 2015, as the patent
for original infliximab (Remicade) ended. Potentially this is a time of uncertainty as, although
biosimilar infliximab is approved for the same indications as the original product, there is a lack
of high-quality data supporting its use in IBD. The attraction of biosimilars is that they will result
in a significant reduction in the price; it is hoped that this will improve patient access to anti-
TNF- therapy47.
NICE have published guidelines on the use of infliximab, adalimumab, golimumab and
vedolizumab in IBD. Click below to learn more.
NICE TA 163

States that infliximab is recommended as a possible treatment for people with acute, severely
active UC only if:

ciclosporin is considered inappropriate for them, or

they are taking part in a research study (clinical trial)43.
NICE TA 187

States that infliximab and adalimumab, are recommended as treatment options for adults with
severe active or active fistulising Crohn's disease whose disease has not responded to
conventional therapy (including immunosuppressive and/or corticosteroid treatments), or who
are intolerant of or have contraindications to conventional therapy.

Infliximab or adalimumab should be given as a planned course of treatment until treatment

failure (including the need for surgery), or until 12 months after the start of treatment, whichever
is shorter. People should then have their disease reassessed to determine whether ongoing
treatment is still clinically appropriate44.
NICE TA 329

States that infliximab, adalimumab and golimumab are recommended as possible treatments for
adults with moderate to severe UC if conventional therapy hasnt worked or isnt suitable.
Infliximab is also a possible treatment for children or young people aged 617 years with severe
UC, unresponsive to other conventional therapies.

People should be able to have the treatment for at least 12 months, unless it stops working well
enough. Their condition should be assessed at least every 12 months. Their doctor should discuss
with them the benefits and risks of continuing or stopping treatment. If treatment is stopped and
the UC gets worse, people should be able to start treatment again45.
NICE TA 342

States that vedolizumab is recommended as a possible treatment for adults with moderate to
severe UC.

People should be able to have the treatment until it stops working or surgery is needed. Their
condition should be assessed 12 months after they started taking vedolizumab. If they still have
symptoms but it is clear that the treatment is helping, they can continue to have it. If they no
longer have symptoms, treatment could be stopped, and later restarted if symptoms return.

People who continue to take vedolizumab should be assessed at least every 12 months to see
whether the treatment is working well enough for them to continue46.
Ciprofloxacin

Ciprofloxacin by mouth is given at a dose of 500 mg twice daily. It may cause tendon weakness,
which is aggravated by steroids
Metronidazole

Metronidazole is as useful as mesalazine in some patients with Crohn's disease but is less
effective than corticosteroids. For example, patients with severe perianal involvement responded
to 10-20 mg/kg/day of metronidazole in divided doses and showed improved wound healing with
diminished pain and swelling. Relapse, which may occur after discontinuation of metronidazole,
can be overcome by reinstating the drug. Side-effects tend to be dose-related and include
metallic taste and gastro-intestinal upset. The major long-term side-effect is peripheral
neuropathy so it is usually given for one month but no longer than three months5.
Anti-diarrhoeals

A distressing feature of inflammatory bowel disease is diarrhoea and this may be alleviated using
codeine phosphate, diphenoxylate, loperamide and cholestyramine12. Care should be taken with
the opiate and anticholinergic agents as they can diminish colonic motility and may lead to stasis
and toxic megacolon.

Cholestyramine is useful in diarrhoea associated with bile acid malabsorption. Bile salts have a
cathartic effect on the colon, stimulating water and electrolyte secretion. A dose of 4g daily of
cholestyramine is sufficient to bind bile salts, inhibiting this cathartic action. However, the dose
should be titrated up to the maximum (12-24 g/day) to alleviate symptoms.
Laxatives

Some patients with IBD may suffer from constipation, particularly those who suffer from
proctitis. Osmotic laxatives are not absorbed and will soften the stools by increasing the amount
of water in the bowel, making the stools easier to pass.
Analgesics

Pain relief usually follows reduction of inflammation but, when analgesics are needed they are
best given in the form of paracetamol.

Non-steroidal anti-inflammatory agents should be avoided, as these can precipitate flare-ups

because of an effect on the intestinal mucosal lining21.

Opioids should be used sparingly, especially in an acute flare-up since they may precipitate toxic
megacolon and increase the risk of gut perforation by reducing intestinal motility.
Nutrition

There is uncertainty as to whether excluding certain foods from the diet benefits inflammatory
bowel disease9. One problem has been the variability in foods that appear to make the condition
worse. A balanced, healthy diet is usually advised.
Malnutrition in inflammatory bowel disease is common and multi-factorial in origin. Special
attention should be paid to calcium, vitamin D and other fat soluble vitamins, zinc, iron and
vitamin B12. Protein and calorific support may be indicated in some circumstances2.

Therapeutic liquid feeds (polymeric or elemental diets) may be useful in active Crohns disease
as an alternative to corticosteroids, particularly in children, thus avoiding the adverse effects of
steroids and ensuring optimal growth.

Patients should be assessed for their tolerability to comply with 3-6 weeks of treatment
exclusively with enteral nutrition1.
Probiotics

Probiotics may have some benefit in maintenance and treatment of ulcerative colitis. Some
promising results have been demonstrated for E. coli Nissle in inactive ulcerative colitis and a
multi-species product in active ulcerative colitis and inactive pouch patients. So far, no evidence
is available to support the use of probiotics in Crohns disease35.
Vaccination

Patients with IBD are generally immunosuppressed due to the underlying disease, surgery,
malnutrition or immunosuppressive therapy. A vaccine and infection history should be
documented at the time of diagnosis including TB exposure, chickenpox history and risk of
hepatitis B. Influenza and pneumococcal and their boasters and HPV (human papilloma virus)
should be considered. Live vaccines such as yellow fever, live typhoid and BCG should be
avoided in patients on immunosuppressants or steroids2.
Thromboembolism prophylaxis

Inflammatory bowel disease patients in hospital should be offered appropriate venous

thromboembolism prophylaxis as they are at a higher risk of venous thromboembolism than
those not suffering from the condition21.

Many other agents have been assessed for their efficacy in treating inflammatory bowel disease.
Examples of agents investigated include acetarsol, bismuth chelates, chloroquine, cromoglycate,
fish oil and sucralfate. Trial data for these drugs have produced negative or contradictory results
and they have not provided the efficacy associated with the aminosalicylates and corticosteroids.
These approaches to disease management are outlined in the table below.

Drug Comment
Similar to topical 5-ASA; appears to be a safe alternative when 5-
4-ASA28
ASA-induced pancreatitis occurs
Acetarsol29 Used for proctitis but evidence limited
Small clinical benefit
Fish oil
Poor patient acceptability
(omega-3 fatty acids)30
Insufficient data to recommend use
 Drug Comment
Small clinical benefit for UC patients
Short-chain fatty acids31 Putrid smell
Poor patient adherence
Lignocaine32 Benefit in UC
May normalise intestinal motility and reduce inflammatory
Cannabidiol33
responses in IBD

Reports in the medical literature document self-treatment with complementary and alternative
medicines by people with IBD.

Reports include the use of:

traditional Chinese medicine

aloe vera gel taken orally
wheat grass juice
turmeric
frankincense
acupuncture
bovine colostrum

Patients choosing alternative treatment should be counselled about potential problems such as
direct toxicity of some herbal remedies, deliberate contamination of products and lack of
regulation of, and consistency between, products and possible drug interactions between herbal
and conventional drugs12.

During an acute attack of IBD, drug therapy is intended to induce remission and, in practice, is
often continued. Some patients never experience complete freedom from symptoms and are said
to have chronic active disease, and the majority of these patients eventually require surgical
intervention. Factors that determine treatment choice are the: site of disease, pattern or extent of
disease, and disease activity.

UC responds better to medical management than Crohn's disease5. In mild or moderate disease,
admission to hospital is not required unless the patient fails to improve after two weeks
treatment. Patients with severe UC should be admitted to hospital as this group has the highest
mortality. Click on the boxes to learn more.
Active proctitis (E1)

For patients suffering from active proctitis topical mesalazine 1-2g daily may be effective alone
or may be combined with oral mesalazine therapy (2-4g daily) in resistant cases2. Oral
aminosalicylates may be used alone, although this is less effective. Topical corticosteroids or
oral prednisolone may be used in patients who cannot tolerate aminosalicylates and oral
prednisolone should be considered in patients with subactute illness.
If symptoms do not improve within 4 weeks of treatment or if symptoms worsen, add oral
prednisolone to aminosalicylate therapy (stopping beclometasone if used). Oral tacrolimus could
be added following inadequate response to oral prednisolone after 2-4 weeks41.

Tacrolimus is an immunosuppressant drug that must be prescribed by brand. It inhibits the

production of interleukin-2, a molecule that promotes the development and proliferation of T
cells, which are vital to the body's immune response. Tacrolimus has been shown to be effective
in the suppression of outbreaks of UC and is an add-on option recommended by NICE when oral
prednisolone and aminosalicylate therapy have not induced UC remission.
Active left-sided or extensive ulcerative colitis (E2 and E3)

First-line therapy is with high dose oral aminosalicylate to which topical aminosalicylate or oral
beclometasone dipropionate could be added. Oral prednisolone is appropriate in patients who
cannot tolerate aminosalicylates or who have subacute disease. The dose should be reduced over
8 weeks41.

If symptoms do not improve within 4 weeks of treatment or if symptoms worsen, add oral
prednisolone to aminosalicylate therapy (stopping beclometasone if used). Oral tacrolimus could
be added following inadequate response to oral prednisolone after 2-4 weeks41.
Active severe ulcerative colitis

Active severe ulcerative colitis is a medical emergency with a mortality rate of 2.9% in the UK
and a colectomy rate of 30%6. Treatment may include the following2. Click to view.
Monotherapy

Offer monotherapy with prednisolone, methylprednisolone or intravenous hydrocortisone to

induce remission in people with a first presentation or a single inflammatory exacerbation of
Crohn's disease in a 12-month period. In people with one or more of distal ileal, ileocaecal or
right-sided colonic disease who decline, cannot tolerate or in whom a conventional
glucocorticosteroid is contra-indicated, consider budesonideA. Budesonide is less effective than a
conventional glucocorticosteroid but may have fewer side-effects.

In people who decline, cannot tolerate or in whom a conventional glucocorticosteroid is contra-

indicated, consider 5-ASA treatmentB for a first presentation or a single inflammatory
exacerbation in a 12-month period. Explain that 5-ASA is less effective than a conventional
glucocorticosteroid or budesonide but may have fewer side-effects than a conventional
glucocorticosteroid.

Do not offer budesonide or 5-ASA treatment for severe presentations and do not offer
azathioprine, mercaptopurine or methotrexate as monotherapy to induce remission.
Add on therapy

Consider adding azathioprine or mercaptopurineA to a conventional glucocorticosteroid or

budesonideB to induce remission of Crohn's disease if:

there are two or more inflammatory exacerbations in a 12-month period, or

the glucocorticosteroid dose cannot be tapered.

Assess TPMT activity before offering azathioprine or mercaptopurineA. Do not offer

azathioprine or mercaptopurine if TPMT activity is very low or absent. Consider azathioprine or
mercaptopurine at a lower dose if TPMT activity is below normal but not deficient (according to
local laboratory reference values).

Consider adding methotrexateC to a conventional glucocorticosteroid or budesonideB to induce

remission in people who cannot tolerate azathioprine or mercaptopurine, or in whom TPMT
activity is deficient, if:

there are two are more inflammatory exacerbations in a 12-month period, or

the glucocorticosteroid dose cannot be tapered.
Infliximab and Adalimumab

Infliximab and adalimumab are recommended as treatment options for adults with severe active
Crohn's disease whose disease has not responded to conventional therapy (immunosuppressive
and/or corticosteroid treatments) or who are intolerant of, or have contra-indications to,
conventional therapy.

In either case, treatment should be given as a planned course until treatment failure (including
the need for surgery) or until 12 months after the start of treatment, whichever is shorter.
Treatment should only be continued if there is clear evidence of ongoing active disease as
determined by clinical symptoms, biological markers and investigation, including endoscopy if
necessary. The need to continue treatment should be reviewed at least every 12 months. People
whose disease relapses after treatment is stopped should have the option to start treatment again.

Treatment with infliximab or adalimumab should only be started and reviewed by clinicians with
experience of TNF inhibitors and of managing Crohn's disease.

Long-term maintenance therapy is generally recommended. Aminosalicylates are efficacious in

the maintenance of remission of ulcerative colitis and a once-daily dosing regimen should be
considered. The patient's preferences should be taken into account and it should be explained that
once-daily dosing can be more effective, but may result in more side effects. Aminosalicylates
should be considered first line. For distal disease, topical aminosalicylate with or without oral
treatment may be used, oral aminosalicylate alone may not be as effective as combined
treatment. A low maintenance dose of an oral aminosalicylate is recommended in more extensive
disease.

NICE41 states that some oral aminosalicylates do not have a UK marketing authorisation for this
indication in children and young people and suggests that the prescriber should follow relevant
professional guidance, taking full responsibility for the decision. Informed consent should be
obtained and documented.

Corticosteroids are not suitable for maintenance therapy so, once remission has been achieved,
steroids should be reduced and stopped.

In resistant or frequently relapsing cases consideration should be given to the use of azathioprine
or mercaptopurine (unlicensed indications).

If remission cannot be achieved, surgery may be a necessity.

Chron disease

The most important contribution to prevention of relapse in Crohn's disease patients who smoke
is for them to stop. Smoking cessation is associated with a 65% reduction in the risk of relapse6.
As per recent NICE guidance1, the options for maintaining remission are as follows:

Offer azathioprine or mercaptopurineA as monotherapy to maintain remission when previously

used with a conventional glucocorticosteroid or budesonide to induce remission.

Consider azathioprine or mercaptopurineA to maintain remission in people who have not

previously received these drugs.

Consider methotrexateB to maintain remission only in people who:

needed methotrexate to induce remission, or

have tried but did not tolerate azathioprine or mercaptopurine for maintenance or
 have contra-indications to azathioprine or mercaptopurine (for example, deficient TPMT
activity or previous episodes of pancreatitis).

Prognosis

Most patients with Crohn's disease (75%) will undergo surgery after 10 years of disease6,
although this is by no means curative. The condition is characterised by periods of remission
followed by relapse with possible progression of the disease to other areas of the GI tract. This
frequently occurs even after extensive surgery. Thus, surgery tends to be palliative and is not a
definitive form of treatment. Patients who have had multiple and extensive surgical resections
may have insufficient GI tract remaining to absorb enough nutrients for their dietary
requirement. This is known as short bowel syndrome and these patients may require long-term
parenteral nutrition.

Most patients with UC live a normal life span. Acute attacks of the disease have a mortality of
less than 1% and death usually results from complications such as perforation, haemorrhage,
sepsis, or carcinoma. Surgery is a curative measure, although some of the systemic
manifestations may not resolve. Up to 30% of patients will ultimately require colectomy for
ulcerative colitis6. The cumulative risk of developing colorectal cancer in ulcerative colitis is
negligible within the first decade of onset, rising to 10-15% in the second decade and over 20%
in the third decade21.

Having ulcerative colitis used to carry a high mortality and major morbidity rate. However,
advances in treatment mean that patients overall have a normal life expectancy. There is a slight
excess of mortality in the first 2 years after diagnosis and severe colitis is still a potentially life-
threatening condition.

Overall mortality in Crohns disease is slightly higher than the general population and is greatest
2 years after diagnosis or in those with upper GI disease. Crohns disease tends to cause greater
disability than ulcerative colitis.

Both ulcerative colitis and Crohns colitis are associated with an increased risk of colonic
carcinoma2.

Indications for surgical intervention in patients with IBD:

failure to respond to intensive medical therapy

perforation of the colon
massive or recurrent haemorrhage
toxic megacolon
growth retardation in children
prevention of carcinoma in high-risk patients
development of dysplasia on surveillance biopsy.
IBD is a general term that refers to both UC and Crohns disease.
UC affects the colon and rectum only, while Crohn's disease may occur anywhere along
the GI tract.
 Patients may experience both extra-intestinal and intestinal symptoms.
Sulfasalazine and newer formulations of its active component, mesalazine, are used in
inducing and maintaining remission in UC and with less evidence in Crohns disease.
Corticosteroids are ineffective in maintaining remission and should not be used.
Immunomodulators, such as azathioprine and ciclosporin, may be used in IBD to reduce
the need for steroids and induce and maintain remission. Patients should be carefully
monitored and advised of side-effects.
Cytokine modulators, infliximab and adalimumab, should be used in accordance with
NICE guidelines. They increase the risk of infection and have associated adverse events.
Patients must be advised of a rare association with lymphoma and be carefully monitored.
Supportive therapies, e.g. anti-diarrhoeals, analgesia, may be required.
Suppositories, foam enemas and liquid enemas are often employed and are particularly
useful in UC patients with proctitis.
Treatment protocols exist for the induction and maintenance of remission in UC and
Crohns.
Patients with Crohns disease who smoke should be advised of the need to stop smoking
and offered assistance with this.
Surgery may be required in up to 40% of UC and 70% of Crohns disease patients.
Abscess: localised pus-filled area caused by pyogenic organisms, which can become
painful and swollen.
Anal fissure: a crack or split in the skin around the anus, which can become painful and
bleed.
Biosimilar: this compound is highly similar to the reference product notwithstanding
minor differences in clinically inactive compounds. There are no clinically meaningful
differences between the biological product and reference product in terms of safety,
purity and potency.
Colectomy: excision of part or the whole of the colon.
Colonoscopy: is the endoscopic examination of the large bowel and the distal part of the
small bowel with a camera on a flexible tube passed through the anus.
Colitis: inflammation of the colon.
Crohns colitis: Crohns disease, which affects the colon.
Dyscrasia: morbid general state resulting from the presence of toxic materials in the
blood.
Dysplasia: changes in the shape, size and pattern of cells in the gastro-intestinal tract,
this may lead to the development of cancer cells.
Endoscopy: in an endoscopy a doctor or specialist endoscopist uses an endoscope, i.e. a
long thin, flexible, tube with a camera on its tip to examine the digestive system. The
endoscope is inserted through the mouth and down the throat, or through the anus.
Fistula: an abnormal channel which in Crohns disease may link two loops of intestine or
intestine to the skin or another organ.
Hirsutism: excessive hair growth.
Lassitude: a state of physical or mental weariness with a lack of energy.
Abscess: localised pus-filled area caused by pyogenic organisms, which can become
painful and swollen.
Anal fissure: a crack or split in the skin around the anus, which can become painful and
bleed.
 Biosimilar: this compound is highly similar to the reference product notwithstanding
minor differences in clinically inactive compounds. There are no clinically meaningful
differences between the biological product and reference product in terms of safety,
purity and potency.
Colectomy: excision of part or the whole of the colon.
Colonoscopy: is the endoscopic examination of the large bowel and the distal part of the
small bowel with a camera on a flexible tube passed through the anus.
Colitis: inflammation of the colon.
Crohns colitis: Crohns disease, which affects the colon.
Dyscrasia: morbid general state resulting from the presence of toxic materials in the
blood.
Dysplasia: changes in the shape, size and pattern of cells in the gastro-intestinal tract,
this may lead to the development of cancer cells.
Endoscopy: in an endoscopy a doctor or specialist endoscopist uses an endoscope, i.e. a
long thin, flexible, tube with a camera on its tip to examine the digestive system. The
endoscope is inserted through the mouth and down the throat, or through the anus.
Fistula: an abnormal channel which in Crohns disease may link two loops of intestine or
intestine to the skin or another organ.
Hirsutism: excessive hair growth.
Lassitude: a state of physical or mental weariness with a lack of energy.
Pancolitis: inflammation of the entire colon.
Pancreatitis: inflammation of the pancreas.
Perforation: an abnormal opening of the bowel wall, which causes the contents of the
bowel to leak into the normally sterile bowel cavity.
Perianal: the area surrounding the anus.
Pneumonitis: inflammation of lung tissue.
Proctitis: inflammation of the rectum.
Proctosigmoiditis: inflammation of the rectum and lower sigmoid colon.
Sigmoidoscopy: examines the lining of the sigmoid colon and is inserted through the
anus.
Steatorrhoea: passage of pale, bulky, greasy, foul-smelling stools.
Striae: streaks or stripes.
Stricture: a narrowing of a section of the bowel due to thickening of the bowel wall,
inflammation or scarring.
Tenesmus: painful, ineffectual straining to empty the bowel.
Thiopurine methyltransferase (TPMT): enzyme which is detected in a blood test, that
is needed to metabolise thiopurines, and if deficient may lead to accumulation of
thiopurines and toxic effects.
Toxic megacolon: widening of the colon which may cause perforation, sometimes seen
in a very severe acute case of ulcerative colitis or Crohns disease, and is a medical
emergency.
Transmural: affects many layers through the bowel wall.
Tumour necrosis factor: pro-inflammatory cytokine, which is overproduced in IBD causing
ongoing inflammation.