INFLAMMATORY BOWEL DISEASE

Prepared by Dr. Yanushka Herath

Two major forms of non-specific inflammatory bowel disease

Crohns disease (CD), which can affect any part of the GI tract
Ulcerative colitis (UC), which affects only the large bowel.
There is overlap between these two conditions in their clinical features,
histological and radiological abnormalities.
In 10% of cases of colitis a definitive diagnosis of either UC or CD is not possible.
Currently it is necessary to distinguish between these two conditions because of
certain differences in their management.
Three additional forms of inflammatory bowel disease are also recognized, namely
microscopic ulcerative, microscopic lymphocytic and microscopic collagenous
colitis.
Epidemiology
Crohns disease is slightly commoner in females (M : F = 1 : 1.2) and occurs at
a younger age (mean 26 years) than UC (M : F = 1.2 : 1; mean 34 years).
Aetiopathogenesis
Although the aetiology of IBD is unknown, it
is becoming clear that IBD represents the
outcome of three essential interactive cofactors:
Genetic susceptibility
Environment - both the local
microenvironment (enteric microflora) and
also the nutritional environment
Host immune response

Familial. A positive family history is the largest independent risk factor for the
disease. Thus up to 1 in 5 patients with CD and 1 in 6 patients with UC will have a
first-degree relative with the disease.
Genetic. There is increased concordance for the disease (CD more than UC) in
monozygotic twins in comparison with dizygotic twins who demonstrated familial
aggregation. UC and CD are polygenic diseases. HLA genes on chromosome 6
also appear to have a role in modifying the disease.
Environmental factors. Good domestic hygiene has been shown to be a risk factor
for CD but not for UC.
Thus poor and large families living in crowded conditions with no tap or hot water
and consuming contaminated food have a lower risk of developing CD. A clean
environment may not expose the intestinal immune system to pathogenic or nonpathogenic microorganisms, particularly helminthic parasites, and therefore be
untrained to confront minor infections.
Lifestyle. Breast feeding may provide protection against inflammatory bowel
disease developing in offspring.
Smoking. Patients with CD are more likely to be smokers, and smoking has been
shown to exacerbate CD. By contrast, there is an increased risk of UC in non- or
ex-smokers and nicotine has been shown to be an effective treatment of UC.
Adverse life events and psychological factors such as chronic stress and
depression seem to increase relapses in patients with quiescent disease.
Appendicectomy is protective for the development of UC, particularly if
performed for appendicitis or for mesenteric lymphadenitis before the age of 20.
Evidence supports a hypothesis that IBD is characterized by an overaggressive
immune response to luminal bacterial antigens and other products, occurring
against a background of genetic susceptibility.

Extragastrointestinal manifestations

These occur with both diseases. Joint

complications are commonest, and the
peripheral arthropathies are classified
as type 1 (pauci-articular) and type 2
(polyarticular).as bacteria which enter
the intestine via a leaky epithelium.

Pathology
Crohns disease is a chronic
inflammatory condition that may
affect any part of the gastrointestinal
tract from the mouth to the anus but has a particular tendency to affect the
terminal ileum and ascending colon.
The disease can involve one small area of the gut such as the terminal ileum, or
multiple areas with relatively normal bowel in between (skip lesions).
It may also involve the whole of the colon (total colitis) sometimes without small
bowel involvement.
Ulcerative colitis can affect the rectum alone (proctitis), can extend proximally
to involve the sigmoid and descending colon (left-sided colitis), or may involve the
whole colon (total colitis).

Macroscopic changes
In Crohns disease the small bowel is thickened and narrowed. There are deep
ulcers and fissures in the mucosa, producing a cobblestone appearance.
Fistulae and abscesses may be seen in the colon.
An early feature is aphthoid ulceration, usually seen at colonoscopy.
Later larger and deeper ulcers appear in a patchy distribution, again producing a
cobblestone appearance.

In ulcerative colitis the mucosa looks reddened, inflamed and bleeds easily. In
severe disease there is extensive ulceration with the adjacent mucosa appearing as
Inflammatory polyps.

Microscopic changes

In Crohns disease the inflammation extends through all layers (transmural) of the
bowel, whereas in UC a superficial inflammation is seen.
In CD there is an increase in chronic inflammatory cells and lymphoid hyperplasia,
and in 5060% of patients granulomas are present. These granulomas are noncaseating epithelioid cell aggregates with Langhans giant cells.
In ulcerative colitis the mucosa shows a chronic inflammatory cell infiltrate in the
lamina propria. Crypt abscesses and goblet cell depletion are also seen.

The entire wall of the bowel is oedematous and thickened, and

there are deep ulcers which often appear as linear fissures; thus
the mucosa between them is described as cobblestone. These
may penetrate through the bowel wall to initiate abscesses or
fistulae involving the bowel, bladder, uterus, vagina and skin of
the perineum.

DDx
All

causes of diarrhoea should be excluded stool cultures.

Crohns disease should be considered in all
patients with evidence of

malabsorption, e.g. megaloblastic anaemia

malnourishment,
as well as in children with small stature.
Ileocolonic tuberculosis. Microscopy and culture for TB & a therapeutic trial of
antituberculosis therapy
Lymphomas can occasionally involve the ileum and caecum.

CROHNS DISEASE
Clinical features
The major symptoms are diarrhoea, abdominal pain and weight loss.
Constitutional symptoms of malaise, lethargy, anorexia, nausea, vomiting and lowgrade fever may be present.
15% of these patients there are no gastrointestinal symptoms.
The clinical features are very variable and depend partly on the region of the bowel
that is affected.
The disease may present insidiously or acutely.
The abdominal pain can be colicky.
Diarrhoea is present in 80% of all cases and in colonic disease it usually contains
blood,
making it difficult to differentiate from UC.
Steatorrhoea can be present in small bowel disease.
Crohns disease can present as an emergency with acute right iliac fossa pain
mimicking appendicitis.
If laparotomy is undertaken, an oedematous reddened terminal ileum is found.
Enteric fistulae, e.g. to bladder or vagina, equally divided between internal and
external Fistulae
.
Examination
Loss of weight
Aphthous ulceration of the mouth is often seen.
Abdominal examination is often normal although tenderness and/or a right iliac
fossa mass are occasionally found.
The mass is due either to inflamed loops of bowel that are matted together or to an
abscess.
The anus should always be examined to look for oedematous anal tags, fissures
or perianal abscesses.

Investigations
Blood tests
FBC - Anaemia is due to anaemia of chronic disease, deficiencyof iron and/or
folate
Raised ESR and CRP and a raised white cell count.
Hypoalbuminaemia is present in severe disease.
Liver biochemistry may be abnormal.
Blood cultures are required if septicaemia is suspected.
Serological tests. Saccharomyces cerevisiae antibody is usually present while
pANCA antibody is negative.
Radiology and imaging
A barium follow-through, CT scan -contrast
The findings include an asymmetrical alteration in the mucosal pattern with deep
ulceration, and areas of narrowing or stricturing. Although commonly confined to
the terminal ileum
Imaging of the small bowel may also be performed by magnetic resonance
enteroclysis.
Colonoscopy
Disease activity
This can be assessed using simple parameters such as Hb, white cell count,
inflammatory markers (raised ESR, CRP and platelet count) and serum albumin.
Formal clinical activity indices (e.g. CD activity index) are used in research
studies.
Calprotectin is a calcium-binding protein and accounts for 60% of cytosolic protein
of neutrophils. Faecal calprotectin has the potential as a simple cheap non-invasive
marker of disease activity in IBD and may be of value in predicting response to
and failure of treatment.

Medical management of Crohns

The aim of management is to induce and then maintain a remission.

Patients with mild symptoms may require only symptomatic treatment. Cigarette
smoking should be stopped.
Diarrhoea can be controlled with loperamide, codeine phosphate or co-phenotrope.
Diarrhoea in longstanding inactive disease may be due to bile acid malabsorption
and should be treated with colestyramine.
Anaemia, if due to vitamin B12, folic acid or iron deficiency,
should be treated with the appropriate haematinics.
Patients with moderate to severe total Crohns colitis are treated as UC
Induction of remission
Oral or i.v. glucocorticosteroids
Enteral nutrition
Oral glucocorticosteroids + azathioprine or 6 mercaptopurine (6MP)
Maintenance of remission
Aminosalicylates (colonic disease)
Azathioprine, 6MP, mycophenolate mofetil
Treatment of glucocorticosteroid/immunosuppressive therapy-resistant
disease
Methotrexate
Intravenous ciclosporin
Infliximab (TNF- antibody)
Adalimumab
Certolizumab
Perianal disease
Ciprofloxacin and metronidazole

ULCERATIVE COLITIS
Clinical features
The major symptom in UC is diarrhoea with blood and mucus, sometimes
accompanied by lower abdominal discomfort.
General features include malaise, lethargy and anorexia with weight loss.
In most patients runs a course of remissions and exacerbations.

When the disease is confined to the rectum (proctitis), blood mixed with the stool,
urgency and tenesmus.
In an acute attack of UC, patients have bloody diarrhoea, passing up to 1020
liquid stools per day.
Diarrhoea also occurs at night, with urgency and incontinence that is severely
disabling for the patient.
Occasionally blood and mucus alone are passed.
Toxic megacolon is a serious complication. The plain abdominal X-ray shows a
dilated thin-walled colon with a diameter of > 6 cm. It is a particularly dangerous
stage of advanced disease with impending perforation and a high mortality.
Urgent surgery is required in all patients in whom toxic dilatation has not resolved
within 48 hours.
Examination
The abdomen may be slightly distended or tender to palpation.
Rectal examination will show the presence of blood.
Investigations
Blood tests
In moderate to severe attacks an iron deficiency anaemia is commonly present
and the white cell and platelet counts are raised.
The ESR and CRP are often raised; liver biochemistry may be abnormal, with
hypoalbuminaemia occurring in severe disease.
pANCA may be positive. This is contrary to CD, where pANCA is usually
negative.
.
Imaging
A plain abdominal X-ray with an abdominal ultrasound are the key investigations
in moderate to severe attacks.
The extent of disease can be judged by the air distribution in the colon and the
presence of colonic dilatation can be noted.
Thickening of the colonic wall can be detected on ultrasound as can the degree of
hyperaemia in the colonic wall, present in severe disease.
Colonoscopy
A colonoscopy should not be performed in severe attacks of disease for fear of
perforation.
For excluding the onset of dysplasia and carcinoma in patients with longstanding

.
Radionuclide scans
These can be used to assess colonic inflammation.
Medical management of ulcerative colitis
All patients with UC should be treated with an aminosalicylate.
Remission IV ; steroids, cyclosporine, infliximab
Maintaincence Sulphasalazine , 6 MP, mesalamine, Azathioprine.

Surgery continues to have a central role because it may be lifesaving, is curative

and eliminates the long-term risk of cancer.
Surgical Indications in UC
Fulminant acute attack
Failure of medical treatment (3 days)
Toxic dilatation
Haemorrhage
Perforation
Chronic disease
Incomplete response to medical treatment
Excessive steroid requirement
Non-compliance with medication
Risk of cancer
In acute disease, subtotal colectomy with end ileostomy and preservation of the
rectum is the operation of choice.
At a later stage,
Proctectomy with a permanent ileostomy.
To avoid a permanent ileostomy, ileorectal nastomosis can be performed and
annual biopsies of the rectal mucosa must be carried out to detect dysplasia, a
histological change that precedes the development of a rectal stump carcinoma.

With an ileoanal anastomosis a pouch of ileum is formed that. The pouch is

anastomosed to the anus at the dentate line. Continence is usually achieved. A third
of patients, however, will experience pouchitis in which there is inflammation of
the pouch.
Definition and management of a severe attack of ulcerative colitis
(a) Definition
Stool frequency > 6 stools per day with blood +++
Fever > 37.5C
Tachycardia > 90 per minute
ESR > 30 mm per hour
Anaemia < 10 g/dL haemoglobin
Albumin < 30 g/L
(b) Management
Admit to hospital
Assess i.v. fluids
Monitor daily:
stool frequency
abdominal X-ray
FBC, CRP
albumin

Cancer in inflammatory bowel disease

Patients with UC and Crohns colitis have an increased incidence of developing
colon cancer and patients with CD of the small intestine a small increase in
incidence of small bowel carcinoma. The following screening strategies are
suggested.
A screening colonoscopy with multiple biopsies should be done every 2 years in
patients with total UC and Crohns colitis of 10 years standing and annually after
20 years.
.
Pregnancy and inflammatory bowel disease
Women with inactive IBD have normal fertility. Fertility however, may be reduced
in those with active disease, and patients with active disease are twice as likely to
suffer spontaneous abortion than those with inactive disease.