Update on inflammatory bowel disease
Crohn’s disease and ulcerative colitis are both debilitating
bowel conditions. Although they are similar in some ways, there are differences
between them. Crohn’s disease is a chronic inflammatory disease affecting
any part of the gut from the mouth to the peritoneum, said Dr MARK McALINDON,
consultant gastroenterologist, Royal Hallamshire Hospital, Sheffield.
Crohn’s disease may be discountinuous, ie, an affected part of the gut
is followed by a non-affected part and so on, while ulcerative colitis
is a continuous disease. The distribution of disease determines the patient’s
presenting symptoms. Features of Crohn’s disease are typically associated
with disorders of the small intestine, such as weight loss and non-bloody
diarrhoea, and symptoms of obstruction. Ulcerative colitis, which invariable
affects the rectum, gives symptoms such as bloody diarrhoea. Systemic
complications are less common in ulcerative colitis than in Crohn’s disease.
The distribution of disease also influences the
proportion of patients who will eventually require surgery. In Crohn’s
disease, 60 per cent of those with ileocolitis will require surgery after
10 years compared with 20 per cent of those with colitis and 40 per cent
of those with ileitis. Between 10 and 40 per cent of ulcerative colitis
patients will need surgery; the outcome being determined by the extent
and severity of the disease.
Drug treatment
Treatment for inflammatory bowel disease is divided
into drugs to treat acute flare-ups and those used to maintain remission.
Dr McALINDON and Dr VAL HEATLEY, consultant gastroenterologist, St James’s
University Hospital, Leeds, described the advances in therapy since Bonnie
Prince Charlie was recorded as having one of the first described cases
of ulcerative colitis.
Corticosteroids are used to treat acute flare-ups
of inflammatory bowel disease and give a 70 per cent remission rate, said
Dr McAlindon. However, there is little evidence for their use in long-term
maintenance and the risk:benefit ratio in terms of adverse effects does
not favour their long-term use. Side effects occur in 30 per cent of Crohn’s
patients on low-dose oral corticosteroids and 50 per cent on high doses.
The side effect profile is improved with slow release budesonide capsules
which release in the ileosecal area. Dr Heatley added that only 10 per
cent of the contents of budesonide slow release capsules get into the
systemic circulation.
Salicylates are of little benefit in maintaining
remission in Crohn’s disease. However, they are the most commonly used
drug in ulcerative colitis, mainly for maintaining remission, said Dr
McAlindon. After one year, 70 per cent of patients on placebo relapse
compared with 20 per cent on salicylate treatment.
Immunosuppressant drugs are useful in Crohn’s disease
but evidence is less supportive for their use in ulcerative colitis, Dr
McAlindon said. The main immunosuppressant used is azathioprine. “The
efficacy of azathioprine is opposite of that of steroids,” said Dr Heatley.
“It is of little use in active disease and takes four weeks to work.”
The problem with azathioprine is its side effects including bone marrow
suppression, nausea, vomiting, pancreatis and hypersensitivity reactions,
she added.
Ciclosporin is effective in a limited number of
patients with active Crohn’s disease and is also of limited benefit in
maintaining remission, Dr Heatley said. She added that enemas of ciclosporin,
which are not commercially available, are useful. However, significant
adverse effects of oral ciclosporin meant that it was not used a great
deal.
Methotrexate has been shown to be beneficial in
maintaining remission when patients are weaned off steroids. Dr McAlindon
said that, in his experience, methotrexate was useful in about two-thirds
of patients. Other immunosuppressant drugs that are starting to be used
for inflammatory bowel disease are tacrolimus and mycophenolate, Dr Heatley
said.
It would be useful to know the causes of inflammatory
bowel disease because at the moment no-one has the faintest idea, said
Dr Heatley. There are lots of suggested causes: bacterial and viral infections,
immunological, familial and psychosomatic factors, and lymphatic obstructions.
“We think that Crohn’s disease is caused by an infection and that ulcerative
colitis has an immunological cause but we do not actually know that,”
she said.
“All the drugs described so far have a blunderbuss
mechanism of action and, because of this, have a high adverse reaction
profile,” Dr McAlindon said. Targeting inflammatory cells without affecting
other systems in the body was one way to overcome the side effects. Anti-tumour
necrosis factor (TNF) drugs are the first agents that aim to do this,
he said.
The inflammatory process is dependent on inflammatory
mediators, such as interleukin (IL) 1, 2 and 6, Dr Heatley explained.
On the other hand, IL 10 calms the inflammatory process. In inflammatory
bowel disease, IL 1 and 6 are upregulated. In terms of treatment advances
in inflammation, two mediators are being examined: TNFa (which is released
from macrophages) and IL 10, she said.
Infliximab is an anti-TNF drug and it represents
the first scientific approach to treating inflammatory bowel disease.
It is used in severe, active Crohn’s disease. Trials indicated that about
two-thirds of patients improve on infliximab. “Infliximab is only given
to no-hopers and [yet] they are getting better. It is one of the most
exciting developments I have seen,” she said. Infliximab also appeared
to work in ulcerative colitis. Trials are underway to examine the use
of infliximab for maintaining remission. The problem with it is potential
long-term side effects and the unknown possibility of it causing cancer,
she added. A humanised anti-TNFa drug is in clinical trials.
The lifetime cost per patient of treating inflammatory
bowel disease is comparable with coronary heart disease and cancer, Dr
Heatley said. There are fewer patients with inflammatory bowel disease
but it develops in young people so treatment lasts for a long time. “In
the United Kingdom, there are approximately 100,000 patients with inflammatory
bowel disease and they cost about £0.5bn a year [in terms of health and
social care] to look after,” she said. Of this money, 30 per cent is spent
on 2 per cent of patients with the most severe disease.
In terms of cost breakdown, the greatest proportion
was for surgery and admissions to hospital, making up 50 per cent of the
total. The second largest was sick leave which accounted for between 10
and 25 per cent.
“Out of the total equation, drug treatment is only
a tiny proportion. It is a complete waste of time for the Government to
be trying to save money on drugs,” she said. Although inflammatory bowel
disease was, overall, expensive to treat, she pointed out: “We should
bear in mind the costs of not treating the disease.”
Surgery is needed when medical treatment fails,
when a patient is intolerant to steroids and in adolescents who fail to
grow, said Mr ANDREW SHORTHOUSE, consultant surgeon, Royal Hallamshire
Hospital, Sheffield. It is also used when perforation, bleeding, malignancy,
fulminant colitis and toxic megacolon occur.
The minimum necessary amount of bowel is removed
in surgery. The ends of the section removed are made into a stoma if the
patient has compromised nutrition. In ulcerative colitis, surgery that
removes the whole colon is curative. Restorative surgery can be considered
if the rectum is retained by marking a pouch out of the ileum and joining
it onto the anal canal. However, complications can occur with a pouch
and sometimes an ileostomy is a preferred option. Following surgery, patients
with Crohn’s disease, who will have had the diseased part of the gut removed
and may or may not have a stoma, need to be maintained on medication because
the disease can occur in other parts of the gut. Ulcerative colitis patients
no longer need drug treatment following surgery.
Nutrition
NERISSA FLETCHER, senior dietician, Royal Hallamshire
Hospital, Sheffield, said that malnutrition is common in people with inflammatory
bowel disease, particularly in the acute inflammatory stages of the disease.
This is because of inadequate oral intake, malabsorption and increased
loss of nutrients. Consequences of malnutrition include decreased muscle
function, poor immune resistance, impaired wound healing, altered gut
function and increased morbidity.
If a patient is malnourished, there are a number
of dietary treatments that can be used, she said. A polymeric diet, based
on high protein and calorie intake, with supplements such as Fortisip
or Ensure to give additional calories, is usually tried first. Peptide-based
diets and elemental diets are also used in Crohn’s disease. An elemental
diet is based on special liquid supplements and water only for four to
six weeks after which time food is gradually re-introduced to identify
if any particular foods cause a problem. The problem with elemental diets
is the quantity of liquid supplement needed and the fact that the supplements
are only available in three flavours. Parenteral nutrition is not widely
used and is reserved for patients with bowel obstruction, short bowel
syndrome, or patients who had high-output fistulae.
A meta-analysis has compared enteral nutrition with
corticosteroids for treating inflammatory bowel disease. Although both
induced remission, corticosteroids were more effective and were less expensive
than enteral nutrition.
Nutritional treatments that are being researched
include fish oils and glutamine, she said. Omega 3 fatty acids are anti-inflammatory
and have been found to have a steroid-sparing effect in ulcerative colitis.
The amino acid, glutamine, is essential in the inflammatory response and
has been found to improve gut barrier function.
Stoma management
BART TAPPE, a stoma nurse at the Royal Hallamshire
Hospital, Sheffield, said that some patients with inflammatory bowel disease,
who had had their lives ruined by unrelenting bowel movements and malnutrition,
welcome the prospect of an ileostomy but others feel that it is a failure
of not being able to control the disease.
There are many types of appliance, he said. The
size used is a personal preference but he recommended that women started
with a medium size and men a large size. Drainable appliances are better
for liquid faecal output and closed bags should only be used where the
output is more formed, he said.
Many patients have lost a lot of weight before surgery
and then regain the weight afterwards. This can lead to the appearance
of a moat around the stoma. Patients with a moat need to have a convex
appliance to avoid leakages.
The skin often needs protection to avoid irritation
from leakages. This is particularly the case for patients who have been
on long-term corticosteroid treatment whose skin may be paper-thin, he
added. Useful skin protectors are Cavilon spray, Clinishield and Comfeel
protective film. Barrier creams are useful if patients have sore skin.
However, only a small amount should be used otherwise adherence problems
with the appliance are possible. Mr Tappe had found Comfeel barrier cream
and Cavilon cream useful. Pastes, such as Stomahesive paste, are needed
if the stoma is in a crease.
If the output from a stoma becomes too liquid, then
dietary modifications are used. If the output becomes particularly liquid
overnight, then having Weetabix, eaten as a biscuit with butter or jam,
before going to bed can help. Bananas, natural plain yogurt, white bread
and boiled white rice also thicken output. If dietary measures are not
sufficient, then loperamide can be used. Marshmallows, nuts and sweetcorn
are not advisable because they can cause a blockage.
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