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IBD – Inflammatory Bowel Disease

Dr Tom Leach

Summary

Symptoms of inflammatory bowel disease. Image from ibdreleif.com

 

Summary table of Crohn’s disease vs Ulcerative Colitis.
Crohn’s
UC
Incidence
5-10 per 100 000
10 to 20 per 100 000
Mean age of onset
26
Can also present in children – failure to thrive
and also in those in their 60’s
34
Male: Female
1.2 : 1
1 : 1.2
Affects
Any part of GI-tract, most commonly the terminal ileum. Also commonly affects the rectum, but not the colon
Only colon, usually more distal regions are worse affected
Mortality
Low
Lower
Surgery required in
50-80%
20%
Skip lesions
Yes
No
Mucosal Layers
Deeper
More superficial
Complications
Fistula, abscess, stricture. Most commonly the fistulae come from the anus to the peri-anal region and the produce pus
Rare. Toxic megacolon
pANCA
Negative
Positive
Race
Most common in Caucasians
Most common in Caucasians
Protective factors
High residue, low sugar diet, relatives with Crohn’s means you have an INCREASED RISK
Smoking, appendicectomy, high reside low sugar diet
Pathology
Thought to be very similar in both diseases. In genetically susceptible individuals there is an adverse reaction to bacterial lipopolysaccharide. Normally the reaction against this is self limiting, but in IBD patients once the inflammation starts it may not stop. Thus ultimately it is a kind of autoimmune disease – and the inflammation ends up damaging the gut wall. The diseases follow a relapsing and remising course.
Symptoms
Right iliac fossa mass/pain – this is present even when there is no abscess, abdominal discomfort, blood in the stools, vitamin B12 and iron deficiencies – Crohn’s commonly affects the small intestine and thus can cause malabsorption.
Diarrhoea due to excess mucus production. often also contains blood. Abdominal discomfort, bloating . symptoms usually less severe than Crohn’s
Extra-intestinal symptoms
These are generally the same for both conditions. They include; large joint arthritis, irisitis (like conjunctivitis, but worse), erythema nodosum (red rashes on the shins, more common in UC), ulcers on mucous membranes (mouth and vagina – more common in Crohn’s), cholangitis, pyoderma gangrenosum – this is nasty dead black necrotic tissue. Most commonly found on the legs and around the stoma, renal stones, gallstones, fatty liver, fat wrapping – only occurs in Crohn’s – this is where the messenetric fat spreads around the intestine
Crohn’s disease is associated with an increased risk of bowel cancer –this is typically adenocarcinoma of the distal ileum
Signs
The acute presentation may be mistaken for appendicitis. However, a good history may reveal some facts pointing to a background acute disease.
May be few in mild disease.may include weight loss and malaise. In an acute attack there can be fever, malaise, iron def anaemia, raised WBC, platelets and ESR, hypoalbuminaemia
Barium swallow
This is the most useful test. It can show areas of stricture, shortening of small bowel, fistulas and abscesses
PR
Blood
CT
Will shows areas of wall thickening, strictures and abscesses
CT
Thickened bowel wall
Colonoscopy
Not that useful but can biopsy. Also may help you differentiate pseudopolyps from true polyps
Barium enema
Reduced haustral folds due to fibrosis
CLUBBING!
Treatment
Cessation of smoking may induce remission in some patients. 
5-ASA compounds are not typically used
Immunosuppresants used in severe disease.
80% of Crohn’s patients will eventually require surgery. Many require B12 and iron supplements.
Low residue diets and low fat diets can help reduce symptoms. Patients may need to be given supplements of the fat soluble vitamins (A D E K). patients are often given antibiotics to reduce the intestinal flora and diarrhoea – metronidazole
Infliximab is used in patients that don’t respond to other types of treatment. 70% of Crohn’s patients will respond to it. It is particularly useful in perianal disease
Mild disease: 5-ASA
Moderate disease: steroid to initiate remission, then 5-ASA for maintenance
Severe disease: trial steroid for 5-7 days. If no remission, then operate immediately. Try to maintain remission with 5-ASA, if not then immunosuppressants may be used.
Steroids are often given as a rectal foam

In 10% of cases it is not possible to differentiate from Crohn’s disease or UC, and thus these patients are said to have indeterminate colitis.

Drugs

Drug
Mechanism
Side-effects
Info
Sulfasalazine*
(ASA)
 Not fully understood. Thought to trap free radicals released in the inflammatory process Headache, nausea, vomiting, oligpspermia (low semen volume, but not reduced sperm count), rashes, nephrotoxicity Can both initiate and maintain remission. Other 5-ASAs include mesalazine and olsalazine. Both are thought to be less effective than sulfasalazine.
Corticosteroids Effective at quickly getting symptoms under control. Minimal in short-term use. Common in long-term or multiple use patients. Used in acute flares of moderate to severe disease that has not responded to other treatments.
Azathioprine
Immunomodulator. Inhibits purine synthesis. reduces the turnover rate of quickly dividing cells
Nausea, vomiting skin rashes, and other similar to other immunosupressants.
Side effects tend to reduce after 6 weeks. Immunomodulators are useful for maintaining remission, but slow to induce remission. Azathioprine is usually the first line immunomodulator. Widely used for maintenance of remission, particularly in CD
Methotrexate
Immunomodulator. Inhibits the metabolism of folic acid. Reduces the turnover rate of quickly dividing cells
Similar to above
Not licensed for Crohn’s. Evidence for its efficacy is not as good as azathioprine, particularly for UC.
Infliximab and other monoclonal antibodies
 Monoclonal antibody – this is an antibody to TNFα. Prevents TNF alpha binding to its  binding site, and thus reduces inflammation.
Not licensed for UC. Other examples of monoclonal antibodies include adalimumab, vedolizumab.
Cyclosporin Immunosuppressant. Inhibits T cell division. A calcineurin inhibitor – as is Tacrolimus. Nephrotoxicity, hypertension, hepatic dysfunction, tremor, headache, anorexia, nausea, vomiting, gum hypertrophy, excessive hair growth Generally a last resort in patients whom are not responding to high dose IV steroids.
*this is actually a combination of an ASA compound and a sulphapyridine. The sulphapyridine makes the drug pH sensitive, thus it is activated at the right place in the bowel (i.e. the colon).

Surgery

Crohn’s
Bowel resection – patients will often have to have several resections during their lifetime. Thus when you operate, you should be as conservative as possible. you should remove the affected area, and 2cm either side. Big wide resections do not decrease the recurrence rate. you should try to avoid small bowel syndrome by resecting too large an area
Stricturoplasty
In the case of a severe stricture, you can cut the bowel lengthways along the stricture, and then sew it back together to widen the strictured part.
 
Surgery is generally reserved for stricutres, fistulas, disease that does not respond to drug treatments. Abscesses are generally treated by percutaneous drainage and not by surgery
Fistulas can exist between parts of the bowel, e.g. between the small and large intestines. These can affect absorption
After surgery many patients will have a massive initial improvement in symptoms.
UC
The whole colon has to be removed, otherwise the disease will return in the part of the colon you have not taken out. You can either have a permanent ileostomy (rare) or a temporary one (restorative protocolectomy). In the restorative surgery, the colon is removed (1% chance of sexual dysfunction in males) and the end of the ileum is then folded over one itself to create a ‘pouch’. This pouch becomes the rectum. It requires two separate operations. One to create the pouch, the other to connect the pouch to the anus. It can be done in one, but this increases the risk of sepsis. After the operation, patients will have to empty the bowel about 5-6 times a day, but there will not usually be urgency. There are often n other symptoms, and thus for many patients, this is better than the symptoms they experiences during exacerbations of UC. Most patients will take anti-diarrhoeal agents at some point.
 
Toxic megacolon – this is where the colon becomes massively distended. It can induce tachycardia and shock, and may also present with fever. It is a medical emergency, and if it does not respolve, will require surgery to prevent perforation

 

More Information

There are two major types of non-specific inflammatory disease: Crohn’s disease and Ulcerative colitis. There is a great degree of overlap between the two diseases – in 10% of cases in cannot be determined which disease is present.
In such cases, the condition is known as indeterminate colitis and tends to look more like UC than Crohn’s, but it may involve skip lesions, or a rare variant of UC.
In cases where indeterminate colitis has to be surgically managed, then a colectomy and pouch formation is usually best advised, although the pouch failure rate is higher than in UC.
Both diseases follow a relapsing and remitting course.
In patients with a negative faecal occult blood test (FOBT) and negative faecal calprotectin, a diagnosis of IBD is very unlikely.

Comparison

Aetiology

Therefore you get the disease as a result of bacterial antigens in genetically susceptible people.

Ulcerative Colitis

Epidemiology

Pathology

The disease will develop as a result of an environmental trigger in a genetically susceptible individual. There are many cellular stages involved in the course of the disease, and these stages will probably be the target for future clinical intervention. The mechanism is thought to be the same in both UC and Crohn’s.
  1. Initially, bacterial or dietary antigens are taken up by M cells and pass into the lamina proporia through a ‘leaky’ gap between cells or through a lesion.
  2. The antigens are picked up by antigen presenting cells in the lamina proporia, causing them to secrete pro-inflammatory cytokines, such as TNF-α and IL-12 and IL-18.
  3. This effect, coupled with the presentation of antigens to the CD4+ T cells, results in activation of TH1 cells. These secrete further cytokines, attracting many more T cells to the region. This build up of T cells will lead to a full blown inflammatory response, including increased vascular adhesion and all that stuff. This can lead to ulceration and stricture formation.
  4. There may also be accompanying fever, malaise and anorexia.
In normal patients, this process is self-limiting, but in genetically susceptible individuals, something goes wrong, whereby it does not stop, and massive inflammation, ulceration and structuring can occur. It is thought that the main culprit in initiating this response in a genetically susceptible individual is bacterial lippolysaccharide.
In Crohn’s disease, two specific mutations have been identified; the CARD 15 and NOD-2 genes on chromosome 16 are thought to be responsible in some patients.
Basically, there is just massive inflammation of parts of the bowel wall, with resulting strictures and ulcers.
Crohn’s affects much deeper layers of bowel than UC. Therefore Crohn’s disease can fistulate, but UC cannot. There are four main types of fistulae. Complex severe fistulating Crohn’s is a death threat. Strictures are also a common complication that you cannot get in UC.

Proctitis – this refers UC that occurs only in the last 6 inches of the rectum. It also refers to any form of inflammation in the rectum.
Proctocolitis – means inflammation in the colon and rectum – i.e. more generalised than proctitis
Pancolitis – inflammation affecting the whole of the colon.

Types of ulcerative colitis. Image from ibdreleif.com

Clinical Features

Symptoms of ulcerative colitis. Image from ibdreleif.com

There are many other vague symptoms affecting various areas of the body:

Some patients may only ever have one attack, and then be in remission for the rest of their life. 10% of patients will have chronic disease for the rest of their life – i.e. it never goes into remission.
Disease confined to the rectum is generally not pathologically problematic; however it causes ‘inconvenient’ symptoms, such as urgency, tenesmus and blood mixed with the stool. This type of the disease is known as proctitis.
Acute attack
 This will cause bloody diarrhoea and the patient may pass liquid stools up to 20x a day. Sometimes they pass only mucous / blood (i.e. no faeces). This trend may also continue during the night ans is very disabling for the patient.
Other signs of an acute attack include:

The disease often starts off in the rectum and then progresses up the colon. Very occasionally the distal ileum will be affected, but this is thought to be chronic inflammation as a result of incompetence of the ileocaecal valve, rather than direct pathology affecting this part of the small bowel.

 
Generally, there are very few signs, and often few symptoms. The symptoms will be related to the part of the bowel that is affected.
 
Smoking actually decreases your risk of UC! If you have been diagnosed with UC, and then stop smoking, you increase your risk of relapse.
 

Examination

Investigations

PR exam – this may show blood on the glove
Rigid sigmoidoscopy – this will often show abnormal inflamed bleeding mucosa. There may also be ulceration and friability. In very rare cases, the rectum is not involved in the disease and thus the sigmoidoscopy will be normal.
Blood tests – in acute attacks, the following may be observed

Stool samples – should always be taken to exclude infective causes of colitis.
Plain AXR– may show the presence of air in the colon and colonic dilatation.
Ultrasound – may show thickening of the wall and the presence of free fluid in the abdominal cavity
CT –often used in acute attacks
Most of the imaging techniques above are only used in acute attacks – but this is when the patient presents anyway!
Colonoscopy – is unusual as an investigation in Crohn’s as it should not be performed during an acute attack. In gives a better view of what’s going on than a barium enema. In long-standing chronic disease it is used to assess the extent of the disease. In patients with disease of more than 10 years, colonoscopy should be performed to obtain biopsies of the affected areas to rule out the possibility of malignancy. It is particularly difficult to pick up malignancy on scans due to the appearance of the disease on such tests – i.e. the pathology of normal UC seen on a scan could ‘hide’ the presence of malignancy.
Barium enema – this will show the macroscopic extent of the disease as well as any ulceration. It will show loss of haustral and possibly a shortened colon as a result of scarring and fibrosis.
Rectal biopsy – this may show inflammatory infiltrates, goblet cell depletion, mucous ulcers and crypt abscesses.

Complications

 

Treatment

Corticosteroids

Common examples include; hydrocortisone, prednisolone and dexamethasone
These can be given orally, IV, or by enema.
They are effective at inducing a remission, but not at maintaining it.
They have many side effects, and this is the main reason why they are not used long-term to maintain the remission. Steroids are very effective at what they do, but the side effects can be nasty.
They are produced naturally by the body in small amounts, and are synthesised as required by the pituitary gland in response to circulating ACTH levels. They are released in a definite circadian rhythm, with the highest levels of secretion in the morning, that gradually reduce throughout the day, until the very low levels at night.

Mechanism

These products enter cells passively via diffusion, and will then bind with cytoplasmic receptors, causing a conformational changes in the receptor, which exposes a DNA binding site. This new complex will then migrate to the nucleus, and bind to a receptor and will cause a change in gene transcription.
About 1% of genes can be regulated in this fashion.
As well as their DNA effects, glucocorticoids cause transduction effects one they have bound to their ligand, but are still floating around in the cytoplasm. The effects caused through this pathway are thought to be those involved in the anti-inflammatory property of steroids.
An activated glucocorticoid receptor will cuse release of the protein annexin-1 which has potent effects on the movement of leukocytes.
The effects on inflammation happen very quickly (within minutes) as opposed to the effects on DNA transcription which occur over a much longer time frame.
 

Metabolic actions

 

Regulatory actions

Hypothalamus and anterior pituitary – causes a feedback effect resulting in reduced release of endogenous glucocorticoids
Cardiovascular system – reduced vasodilation and decreased fluid exudation (oozing)
Musculoskeletal system – decreased osteoblast, and decreased osteoclast activity
Inflammation and immunity –

Glucocorticoids are the ‘Holy grail’ of treating inflammation. They act on both the late and early stage reactions – and thus are effective in chronic inflammation. They will reverse virtually any type of inflammation, whatever the cause.
They are also useful after graft surgery – because they can suppress the response against the ‘foreign’ tissue.
It is interesting to note that natural levels of glucocorticoids actually rise when our immune system is more active. It is thought this occurs to prevent our immune system from ‘getting out of control’ and threatening homeostasis. Cortisone is a glucocorticoid – its levels have been shown to be high when we are stressed – thus reducing the immune response in times of stress. Note that cortisone and prednisone are inactive until they are converted into hydrocortisone and prednisolone in vivo.
Corticosteroids are inactive in the liver and elsewhere in the body.
 

Unwanted effects

These are most likely to occur with large and/or prolonged doses.

Sudden withdrawal after treatment can result in adrenal insufficiency as a result of the patient’s inability to synthesis corticosteroids. Phased withdrawal patterns should always be followed.

Pharmacokinetics

Corticosteroids can be taken by pretty much any route imaginable! Usually, when they are not given orally, this is to avoid systemic effects.
When systemic therapy is necessary, taking the drug on alternate days has been shown to reduce the risk of side effects.
Endogenous corticosteroids are carried in the blood by corticosteroid-binding globulin (CBG) and albumin. About 77% is carried by CBG. However, when the drug is administered, much of it travels unbound. Bound steroids are inactive – so I guess this means the binding, in normal circumstances – acts as a storage and buffer system.
Hydrocortisone has a half life on 90 minutes, but its effects are present for 2-8 hours after administration.
 

5-ASA compounds

5-ASA compounds are recommended for:
Those with mild to moderate UC should be treated as a first line with an amino-salicylate. They are effective at both inducing and maintaining remission. They are less effective in Crohn’s than in UC, especially when there is no colonic involvement in the Crohn’s disease. The most commonly used form of these is sulfasalazine. Other examples include mesalazine and olsalazine. 
5-ASA are absorbed in the gut, and may be nephrotoxic.
The usually dose of sulfasalazine is 2-4g daily. This will benefit about 80% of patients with mild to moderate colitis. It is never used alone in severe colitis. It may be used to try to achieve remission (dose of 4g daily) and then to maintain the remission with a dose of 2g daily.
It can be safely continued during pregnancy.

Mechanism

This is very poorly understood. It is thought that it acts by trapping free radicals, and thus reducing the response of inflammatory cells, and reducing cytokine release.
These drugs are particularly useful at targeting the bowel.

Unwanted Effects

Sulphapyridine
 
5-ASA
 

Immunosuppressants

These may be used in severe cases of UC that do not respond to other treatments.
These drugs are often not as effective in Crohn’s, and as such they may often not be licensed for use in Crohn’s, although some practitioners try to give them anyway and get round the rules.
Examples include azathioprine and cyclosporin. They are more commonly used after organ transplant to suppress the host’s immune system.
When used to treat UC they may allow a lower dose of steroid to be used.
Cyclosporin inhibits T cell division, by inhibiting production of IL-2. Cyclosporin also inhibits other activated protein kinases that are activated by IL-1 and TNFα.
It is usually given orally. It has many unwanted effects including:
Azathioprine works by inhibiting the synthesis of purine, and thus inhibiting the proliferation of quickly dividing cells, particularly leukocytes. Side effects are similar to cyclosporin. It is also important to note that because these drugs suppress the immune system, you are at greater risk of succumbing to infection.
Often the side-effects of these drugs will lessen after 6 weeks of use (particularly the nausea, vomiting and skin rashes).
Azathioprine is actually the same drug as 6-mercaptopurine – azathioprine is the pro-drug of this.
Methotrexate is another drug given in UC be not licensed for Crohn’s. It inhibits the metabolism of folic acid, and thus slows the division of quickly dividing cells.
 

Monoclonal Antibody – aka TNFα antibody

Infliximab is the first of these to be approved for treatment of Crohn’s. it is not licensed for treatment of UC. Infliximab inhibits the binding of TNFα to its receptors, and thus prevents the release of IL-1 and IL-6. TNFα is crucial to the inflammatory cascade. Stopping it will help reduce leukocyte migration, infiltration and activation.
Even in Crohn’s it is only 33% effective. In UC it is much less effective. It costs £1000 a dose and you need a dose every 6-8 weeks. Although its side-effects are rare, they can be serious.
It is given IV roughly every 8 weeks.
Generally, infliximab is used to obtain remission, and remission is maintained with an immunosuppressant.
Some studies have also shown that Infliximab can actually close fistulae in Crohn’s.

Unwanted effects

Surgery

This is used as a last resort. For many patients with severe chronic UC, the idea of a stoma is much more appealing than having to live with the severe symptoms of UC. However, you cannot remove just the affected part, as the disease will return in part of the colon that you haven’t removed, so you must remove the whole colon.
Surgery is also used in cases of perforation, toxic megacolon, dysplasia and acute attack where there has been no improvement for 72 hours on other treatment.
Toxic megacolon – this is where deeper layer of the bowel become affected, and the colon can become massive and may perforate. It is diagnosed when the diameter of the colon has stretch to more than 6cm.
 An acute attack may involve tachycardia, pyrexia and heavy bleeding.
Dysplasia – if there are signs of dysplasia at two separate locations in the colon where the mucosa has turned flat, then this is an indication for surgery to avoid the possibility of malignancy.
Note that perforation is less likely in UC than in Crohn’s due to the fact that UC does not affect as many layers of bowel mucosa.
Also, surgery may be performed if after 5-7 days on steroids, the improvement is so mild that remission is unlikely to be obtainable. You should not keep a patient on steroids for a longer period than this if they show no or little improvement, because their condition is likely to deteriorate, and may deteriorate to such a stage that they become inoperable.
 
Good resuscitation and management during an acute attack, with subsequent early surgery gives a mortality rate of only 3%.
On the other hand, colonic dilation followed by perforation has a mortality of 33%.
About ½ of patients with severe acute colitis will recover with drug treatment alone, however, many of these will experience further similar attacks in the future and will ultimately require surgery.

Pre-operative management

It is very important that the site of the proposed stoma is marked on the patient carefully and discuss with the patient. You don’t want to end up with a stoma that is in a natural skin crease, as this can be very leaky and difficult to manage by the patient.
Equally, you don’t want to end up with a stoma that is below the level of the waist of the trousers, particularly in men who like to wear their trousers high.

Surgical Options

Restorative proctocolectomy – this involves total removal of the colon and rectum, however, the anal canal and sphincter and associated nerves are left in place for anastomosis. It is possible to perform the whole procedure in one go, but this is associated with higher morbidity and mortality (probably due to the steroids the patient will be on to trea the UC), and so is usually carried out in two or three steps. You need to leave in at least 2cm of anus to rejoin the bits together later on.  This surgery carries a 1% risk of sexual dysfunction in males.
The best thing about this surgery is that it will only require a temporary stoma. It will usually involve two operations. In the first, the rectum and colon are removed, and a pouch created with the terminal ileum. This will then be left for about 6 months to ‘bed in’. During this period, the patient will have to have a stoma. This temporary form of stoma is known as a loop ileostomy.  After this time, the pouch (which now performs the job of a ‘rectum’) will be joined to the anal canal to create a continuous bowel. The stoma can be removed at this stage.
After this procedure, 80& of patients will make a full recovery, and 20% will experience some morbidity. Complications include; sepsis (which may involve breakdown of the anastomosis), small bowel obstructions, and ileostomy problems.
After surgery, most patients will have continued improvement of symptoms for the first 18months. They will defecate 5-6 times a day, and can usually hold off (i.e. there is not urgency).
There may be faecal spotting for 25% of patients during the day, and 40% at night, however full blown incontinence is rare.
50% of patients will use antidiarrheal agents at some stage.
In 2% of patients, the pouch will fail completely, and have to be taken out.
Some patients will experience ‘pouchitis’ where there is diarrhoea, abdominal cramps, tenesmus, fever and a general feeling of unwell. This is usually treated with metronidazole.

Complete protocolectomy and permanent ileostomy – luckily, this is now rarely performed. It is generally used in elderly patients with poor anal sphincter control, those with advanced stage rectal cancer and in those unwilling to undergo the more complex and lengthy treatment that involves anastomosis.

 
The ileo-anal pouch
This is where part of the ileum is folded back on itself to form a little pouch that will eventually go on to perform the job of a rectum.
The ileum is folded back on itself, then stapled together, and the internal walls removed, so that you have a ‘pouch’ that is twice the thickness of normal ileum, and it forms a reservoir. You can also fold the ileum over more times to form a bigger reservoir. The pouches are named according to how many times the ileum has been folded over to create them; 2 folds (j-pouch), 3 folds (s-pouch), 4 folds (w-pouch).
This is allowed to fully heal before being attached to the rectum as this greatly reduces the risk of infection from faeces passing through the pouch.
 

Emergency surgery options

The ideal option is subtotal colectomy with ileostomy as it allows the possibility of later anastomosis. A restorative protocolectomy is not advisable at this stage due to the higher mortality, and the fact that in an acute situation, you may not know if it is Crohn’s or UC that is present.
The splenic flexure is the most dangerous area in an emergency colectomy due to the risk of perforation.
 
 

Management of UC

How to use the above treatments
Before you manage the patient, you have to asses how serious the condition is. There are three classifications for the severity of the disease, mild, moderate and severe. The disease can be classed according to the Truelove and Witts criteria:
 
Mild
Moderate
Severe
Motions per day
<4
4-6
>6
Rectal bleeding
Small
Moderate
Large
Temp at 6am
Apyrexial
37.1-37.8
>37.8
Pulse
<70
70-90
>90
Haemoglobin
>11g/dL
10.5-11g/dL
<10.5g/dL
ESR
<30mm/h
–
>30mm/h
 

Inducing Remission

Mild UC

Moderate UC

Severe UC

Novel therapies

Maintaining Remission

Administering steroids topically

Suppository – Rectum only
Foam – 30cm
Liquid enema – will go as far as the splenic flexure.
 

Course and prognosis of the disease

10-15% of patients will have continuous chronic disease and will rarely achieve remission for any period of time.
5-10% will have an initial acute attack that requires surgery. Virtually nobody will have one attack then relapse permanently.
Extensive disease is more likely to relapse than distal disease, and is also therefore morelikely to be treated by colectomy.
90% of patients are able to cope without the disease affecting their daily living beyond acceptable levels (i.e. they still hold down a normal job etc.)
Mortality compared with that of the general population is almost identical
Risk of mortality in a severe acute attack is about 2%.
 

Crohn’s Disease

In contrast to UC, this will cuase skip lesions – where there are unaffected parts of bowel in between affected bits. In UC, there are just continuous affected bits.
Crohn’s is basically a condition of young adults, with most diagnosise occurs between the gaes of 20-29. There is a second incidence peak in the 7th decade. Crohn’s is also known to affect young children.
The main symptoms of Crohn’s are abdominal pain, diarrhoea (which may contain blood), vomiting and weight loss. The initial onset may mimic appendicitis in terms of its symptoms.
The disease is probably brought on by a combination of 3 factors – genetic susceptibility, environmental factors (in this case mainly dietary) and the patient’s own immune response.

Symptoms

Symptoms of Crohn’s disease. Image from bid relief.com

Signs

Systemic signs- these are pretty much identical to those seen in UC.

Crohn’s disease and cancer

Crohn’s disease is associated with an increased risk of GI malignancy. Typically the cancers will be adenocarcinomas that arise in the distal ileum and have a very poor prognosis. The value of a screening program for cancers secondary to Crohn’s is highly debatable due to the inaccessibility of the small bowel.

Types of Crohn’s

Generally, Crohn’s can be divided into 3 types:
The duodenum is affected in about 2% of cases, and the stomach even more rarely. Where the stomach and duodenum is affected, there may be symptoms of B12 and iron deficiencies.
In lots of cases of Crohn’s there is malabsorption of various things due to structuring and fibrosis (leading to shortening) of the small intestine.
Types of Crohn’s Disease. Image from bid relief.com

Symptoms

There will often be a long history, although some cases present acutely. Of in the acute presentation, the disease may be mistaken for appendicitis, and the true disease is only discovered on operation. However, a good history taking is likely to reveal some sort of lengthy history which will favour the diagnosis towards Crohn’s.

Investigations

Blood tests

Management

The severity of the disease is harder to asses than in UC. Generally, the higher the following results, the more severe the disease: ESR, temperature, pulse, CRP, WCC.
Stopping the patient smoking is technically the best method to maintain remission. It is associated with a more benign course of the disease, and also reduced re-lapse rate after surgery.

Nutritional Management

Managing the diet of the patient may help reduce the symptoms. A low residue diet should be advised in those with stricture, and a low-fat diet may help to reduce steatorrhea.
Many patients also have vitamin deficiencies, particularly of B12 and iron, and these should be treated accordingly.
In patients with extensive disease of the small bowel, then there may also be deficiencies of the fat soluble vitamins; A, D, E, K. In patients with particularly severe disease (usually those with a shortened bowel) then parenteral nutrition may be advised as a temporary solution until surgery can be undertaken.

Elemental diet

This is a diet made up of single amino acids and it is antigen free. It is not as effective at inducing remission as steroids, but does still have some effect.

Low residue diet

Will not induce remission on its own, but has been shown to be beneficial alongside other treatments.
Unlike UC, Crohn’s will not be treated if it is asymptomatic – i.e. you won’t give 5-ASA’s during periods of remission in an attempt to maintain the remission. This is because there is no evidence that they are more effective than a placebo as a treatment to maintain remission. In cases of chronic disease, then the drug of choice to maintain ‘remission’ is azathioprine.

Mild attacks

Severe Attacks

Severe Chronic disease

Surgery

About 80% of Crohn’s patient’s will require surgery at some point in their life. This is much more than for UC.
Surgery for Crohn’s is not as simple as it is for UC. The basic principles are as follows:

You should remove the most affected part(s) of the bowel and make an end to end anastomosis, you should try to leave 2cm at either side of non-diseased tissue, however in extensive disease this is not necessary (and may not be possible) and so you may end up having inflamed tissue being anastomosed.
Big wide resections do not decrease the recurrence rate.
Surgery should generally be conservative to avoid small bowel syndrome, particularly as many patients will require more than one resection during their lifetime. Therefore surgery is generally restricted to patients with:

For disease at the distal ileum, there is a 25% chance the patient will need further surgery within 5 years.
Recurrence of the disease is common after surgery, however, for those with a stricture causing obstruction, the patient will notice a massive and immediate improvement in symptoms after surgery.
Nearly all patients will develop an ulcer within 12 months on the ileal side of an ileocolic anastomosis.
As an alternative to resection, a strictureplasty may be performed in patients with structuring disease. This is where the strictured piece of bowel is cut longitudinally along its anti-messenteric side, and then sutured transversely.
The worse the inflammation before surgery, the higher the chance of recurrence.

Surgery for fistulas and abscesses
These two complications often co-exist.
Often abscesses can be seen on CT, and then drained via CT guided percutaneous drainage.
Many fistulas are asymptomatic and only discovered upon surgery. You can have:
Usually these fistulas are just sewn up locally as the bowel is removed.
 

Crohn’s Colitis

i.e. Crohn’s in the colon.
Symptoms
Clinical features
Fibrosis and stricture often lead to large bowel obstruction. There may be fistulas – to the vagina and bladder.
Perianal disease up to 50% of Crohn’s patients will have this, particularly those with anal disease. There may be painful anal ulcers, and complex perianal fistulas, but usually the condition is not that painful. Abscesses can be very difficult to live with as they mean its painful to sit down and to walk, and the patient’s quality of life can suffer as a result. Some of the fistulas may open out onto the perineum, and their structure is often very complex. Stricture at the anal ring is also very common.
In cases of this, surgery should be pretty much avoided at all costs to try and maintain the anal sphincter. Dietary modification will be of benefit, and regular drainage will probably be necessary.
Antibiotics will often be given to prevent infection, and infliximab is becoming quite a common treatment when this type of disease is present.
A seton is sometimes used. This is where a thread of nylon is threaded up the fistula and out through the anus and tightened in a tight loop. The loop will be tightened every 10 days or so. This basically cuts through the fistula slowly, and then the tissue behind the seton heals over. Eventually it will cut all the way through to the anal canal, and the fistula will have gone. This is a painful treatment, and is also quite risky as it may destroy the anal sphincter, but it is a useful alternative to surgery.
As well as healing up the fistula, the seton acts as a drain. Basically, fistulas are problematic because they turn into abscesses which then may become infected and painful. This occurs because once a fistula has formed, one end of it will then heal over, and thus create a cavity. This cavity will be full of bacteria that can now thrive, and thus form an abscess. If you keep the fistula as an open loop, it prevents a cavity being formed.

Complications of Crohn’s

Prognosis for ​Crohn’s disease

Generally, the mortality is quite good, being only a 2x the risk of the general population.
However, as you have probably gathered, there is serious morbidity.
Mortality is not greatly increased during the first 15 years of the disease but then gets progressively worse.
After surgery, 30% of patients will have recurrence of the disease within 5 years, and 50% within 10 years. Half of these will require further surgery.
Actual mortality of Crohn’s disease is about 10-15%.
Smoking – why does it have opposite effects on these two diseases?
It is thought that the beneficial effect seen in UC is due to the nicotine present in the cigarettes, but that the negative effect seen in Crohn’s is a result of reduction of blood flow in the mesenteric arteries. This second method (i.e. the detrimental effect of smoking) is thought to be the mechanism by which smoking has a negative effect on many diseases.
Anti diarrhoeal agents
These should be avoided at all costs, due to the chance of precipitating toxic megacolon.
 
Loperamide – Immodium
This is a very common anti-diarrhoea drug and is available OTC in the UK.
It is an opiod receptor agonist, acting on µ-opiod receptors of the myenteric plexus of theGIt. It has the same effect on bowel movements as an opiod.
It basically prolongs the transit time of stuff in the colon by reducing propulsive movements of the small intestine and colon. This prolonged transit time provides the opportunity for enhanced absorption of fluids.
Most opioids have short half-lives, however, loperamide has an intermediate half-life giving it an advantage over similar treatments because it has a longer duration of action. It also has a quicker onset.
It has a very high first-pass metabolism, and thus is quite specific for the gut, and systemic effects are not seen.
Toxic megacolon is a complication of intestinal conditions. It is life-threatening. It is characterised by an extremely distended colon, with accompanying abdominal distension, fever, abdominal pain, tachycardia and sometimes shock.
Decompression should be attempted, and you should try to prevent the patient from swallowing air. If the situation has not improved after 24hours, then partial or total resection of the colon may be necessary to prevent perforation.
Codeine should also be avoided for the same reasons.

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