IBD - Inflammatory Bowel Disease

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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.

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

Crohn’s is very rare in the developing world, whilst UC, although still rare is becoming more common.
Both disease are most common in young adults. There is also a second incidence peak in the 7^th decade.
Crohn’s mean age of onset is 26
UC mean age of onset is 34.
Incidence of UC – 10-20 per 100 000
Incidence of Crohn’s – 5-10 per 100 000
The main distinction is that ulcerative colitis only involves the colon, whilst Crohn’s disease can involve any part of the GIt from the mouth to the anus. Crohn’s most commonly affects the distal ileum, however, differentiating between the two diseases can be difficult when Crohn’s also involves the large bowel.
Crohn’s tends to affect the terminal ileum more than anywhere else. ‘Satellite ‘ lesions may occur in the skin, distal from the main affected region, but these are rare. It is also quite rare for any region outside of the small and large intestine to be affected.
Both diseases are more present in the west than the rest of the world. Non-whites are less likely to suffer, whilst there is a specifically high incidence amongst the Jewish community.
Crohn’s disease is slightly more common in females than males
Crohn’s is very slightly more common in females – M:F – 1-12, but the exact opposite ratio is true for UC.
Test for pANCA is different in each disease – test is positive in UC and negative in Crohn’s.
Surgery is required in about 20%of UC, but 50-80% of crohns.
Crohn’s has ‘skip lesions’ whilst UC occurs in one continuous band of inflammation.
Crohn’s disease affects deeper layers of the mucosa than UC
Crohn’s can cause complications such as fistulation and structuring that are rarely seen in UC.
The extra-intestinal symptoms of Crohn’s and UC are the same.
Mortality of slightly higher for Crohn’s than UC, although both are relatively low.

Aetiology

High concordance in identical twins(50% chance if you have twin with disease – 10% chance if sibling, 1/1000 in general population)
10% of patients have a relative who also suffers from IBD
Associated with other auto-immune diseases
UC is more common in non-smokers and ex-smokers
Crohn’s is more likely in smokers than non-smokers (3-4x).
Associated with low-residue, high refined sugar diet
Appendicectomy protects against UC.
Bacteria! Certain bacteria trigger the disease.

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

Ulcerative Colitis

Epidemiology

Most often affects Caucasians in temperate climates.
It is very rare in Africa and Asia
It is roughly 2-3x more common than Crohn’s. Although the incidence of Crohn’s is increasing.
Incidence varies somewhat across developed contires, however some of this difference can be attributed to the fact that some countries class proctitis as a separate disease, whilst some say it is just UC confined to the rectum.
Similar incidence between males and females.

Pathology

There is continuous inflammation, that tends to be worse distally and the rectum is almost always involved.
The inflammation is generally confined to the mucosa and submucosa. It is this inflammation that leads to excess production of mucous and triggers the diarrhoea.

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.

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.
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.
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.
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

These vary widely depending on the severity of the disease.
The most common presentation is bloody diarrhoea in an otherwise fit patient. There may also be mucous and pus in the stool, and some slight abdominal discomfort.
Tenesmus may occur if the rectum is involved.
Patients with protosigmoiditis may also have tenesmus.
There may be generally symptoms of malaise and anorexia.
Abdominal pain often results from stricture – it comes on after eating – as a result the patient eats less – and may lose weight.
Urgency and tenesmus – these are related to inflammation of the rectum.
clubbing

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

Mucous membranes – Ulcers in mouth and vagina
Joints – Arthralgia / arthritis in large joints. 10% with IBD get arthritis in the large joints – knees, shoulders, elbows and spine.
Eyes – Iritis – a deeper inflammation than conjunctivitis. It is inflammation of the iris. 5-10% of IBD sufferers will get this.
kin
- Erythema nodosum – painful itchy raised round lumps in the skin 1-5cm. 5% of IBD sufferers will have these. Most commonly on the legs.
- Pyoderma gangrenosum – pussy dead tissue – a black necrotis ulcerating mass. Most commonly on the legs or around the stoma. 2% of IBD sufferes will have this.
Bile ducts / Liver – Cholangitis. This is one of the biggest killers in IBD – death results from liver failure. It occurs in less than 1% of cases of IBD.

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:

Fever (>37.5’)
Tachycardia (>90bpm)
ESR >30mm/hour
Anaemia – <10g/dl haemoglobin
Albumin – <30g/L

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

There are no obvious signs to look for in UC. The bowel may be slightly distended and tendr to palpation. The anus is usually normal.
Rectal examination will usually show the presence of blood.

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

Raised white cell count
Raised platelets
Iron deficiency anaemia
Raised ESR
Raised CRP
Hypoalbuminaemia (in more severe disease)
pANCA may be positive – in Crohn’s disease this is usually negative.

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

Perforation
Bleeding
Toxic megacolon
Venous thrombosis – you should consider prophylaxis in hospital once diagnosis is confirmed
Colon cancer – there is a 15% risk in patients who have had a pancolitis for 20 years or more.

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

Carbohydrates – Glucocorticoids cause a decrease in the utilization of circulation glucose, and an increase in gluconeogenesis. This leads to a tendency for hyperglycaemia. There is also an increase in glucose storage, which is probably a result of increased secreted insulin as a response to the hyperglycaemia.
Proteins – causes increased catabolism and decreased anabolism – i.e. they cause an overall increase in ‘metabolism’ – breakdown of products to release energy, but a decrease in ‘growth’. Overall there is an increase in protein breakdown, and a decrease in protein synthesis – which can lead to muscle ‘wasting’.
Fats – has an effect on lypolitic hormones, and causes a redistribution of fat, like that seen in Cushing’s syndrome (e.g. Moon face and buffalo hump)
Electrolytes – glucocorticoids tend to reduce the amount of calcium in the body by reducing its uptake from the GIt, and increasing its excretion by the kidneys. This can induce osteoperosis. Glucocorticoids are also likely to cause sodium retention and potassium loss.

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 –

Acute inflammation – decreased influx and activity of leukocytes
Chronic inflammation – decreased activity of mononuclear cells, decreased angiogenesis (development of new blood vessels)
Lymphoid tissues – decreased action of B and T cells, and decreased release of inflammatory mediators by T cells.
Decreased production of cytokines
Decreased expression of COX-2 and thus decreased prostaglandin synthesis
Decreased generation of nitric oxide
Decreased histamine release from basophils
Decreased production of IgG
Decreased complement components in the blood
Increased anti-inflammatory factors such as IL-10 and annexin-1
Overall, this results in decreased immune response – both to acquired auto-immune problems, but also to the protective role of the immune system.

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.

Poor wound healing
Peptic ulceration
Cushing’s syndrome – which is basically a manifestation of all the metabolic and systemic effects described above.
Diabetes – as a result of the hyperglycaemia
Weakness and muscle wasting
Stunted growth in children – particularly if the treatment is continued for more than 6 months – even if the dose is low.
CNS effects – often the patient may experience euphoris, but it can also manifest as depression. In depressed patients, the depression may be due to a disruption of the circadian rhythm secretion of the steroids.
Oral thrush (candidasis) often occurs when the drugs are taken orally, as a result of suppression of local inflammatory processes.

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:

First line treatment (induction of remission) of mild to moderate UC
Mainting remission in UC
They are less effective in Crohn’s disease

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.

Note that sulfasalazine is metabolised to mesalazine in the gut

5-ASA are absorbed in the gut, and may be nephrotoxic.

About 20% of sulfasalazine is absorbed by the small intestine.
The rest remains in the gut lumen and travels to the large intestine, where the bond between the two components (sulphapryridine and mesalazine) is broken by floral bacteria. In some drugs the breaking of this bond is pH dependent – i.e. it breaks at a certain pH, and thus is targeted to a certain part of the GIt. It is not until this bond is broken that the compound has a therapeutic effect. Very little of 5-ASA is absorbed, and it exerts its effect from the lumen itself.
Sulphapyridine is absorbed, and it metabolised by the liver.
In some patients, the pH of the colon may be affected by the disease, and as a result, some preparations of 5-ASA in certain patients may pass into the faeces intact.
The drug can also be given without the sulfapyridine component, and in such cases it is known as mesalazine. However, this is nearly all absorbed in the gut when given orally, and as such it is clinically less effective than sulfasalazine.

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

Headache
Nausea
Vomiting
Rashes
Oligospermia – low semen volume – NOT a low sperm count
Agranulocytosis – reduced granulocytes (WBC’s) in the blood

5-ASA

Nausea, diarrhoea, abdominal pain
Headache and flushing
Nephrotoxicity – chronic interstitial nephritis and renal impairment
Skin rashes

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:

Nephrotoxicity. Almost always occurs. The damage caused is usually temporary but can be permanent.
Hypertension – occurs in about 50% of people as a result of fluid retention
Hepatic dysfunction
Tremor
Headache
Excessive hair growth and gum hypertrophy
Anorexia, nausea, vomiting

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).