Inflammatory Bowel Disease (IBD)

Inflammatory Bowel Disease

Dr. Widjaja Luman
Consultant Gastroenterologist and General Physician
B Sc (St. Andrews), MB ChB (Man), MRCP (UK), M.D. (Edin),
CCST (UK), FRCP (Edin)

(Ahli penyakit pencernaan dan hepar)

 

WHAT IS IDIOPATHIC INFLAMMATORY BOWEL DISEASE or IBD ?

 

Inflammatory bowel disease (IBD) is a term used to describe chronic inflammatory disorder in the gastrointestinal tract. The two most common disorders are Crohn’s disease (CD) and Ulcerative colitis (UC). Both disorders are characterised by inflammation in the lining (mucosa) of the intestines. The mucosa becomes inflamed and breaks (ulcers) may occur on the surface.  In ulcerative colitis, the inflammation is restricted to the large intestines only. In Crohn’s disease, any part of the gastrointestinal tract may be affected i.e. from the mouth to the anus. Another difference between UC and Crohn’s disease is that UC only affects the inner most lining of the large bowel whereas Crohn’s disease involves the whole thickness of the bowel.

Less common form of IBD is microscopic colitis.

 

What are the symptoms?

When the lining of the intestine is inflamed, excessive amounts of mucus containing pus may be produced. The intestinal lining may also bleed. Hence common symptoms of inflammatory bowel disease are:

• diarrhoea
• bloody stools
• passage of mucous

Other symptoms include

• fever
• weight loss
• abdominal pain

 

What is the cause of IBD?

While there are many theories, and tremendous progress is being made in research, the actual reason why a patient gets IBD is still not known. Hence these 2 diseases are commonly called Idiopathic (cause unknown) inflammatory bowel disease.

One possible cause is dysregulation of the immune system. Our immune system is activated in the event of invading micro-organism and subsequently ward off the micro-organism. In normal situation, immune system is able to differentiate self from non self.   In patients with IBD, their immune system can go into uncontrolled “overdrive” mode and attacks the person’s own gastrointestinal tract. This is called “auto immune” disorder or “self attack own self”. This dysregulation of the immune system happens in genetically susceptible individuals as IBD is known to happen in persons with family member with IBD as well.   The incidence is higher among identical twins than non identical twins.

IBD is more common in industrialised countries. Environmental factors, including food high in fat and sugar content, may be contributory factors. Research has now focused on types of microorganism in our gut (gut microbiota). It is postulated certain composition of bacteria in the gut may make the person more susceptible to develop IBD.

 

How is it treated? Can it be cured?

IBD is a chronic (life-long) disease and as no cause has been found, there is also no definite cure. There are, however, effective drugs to control the disease and if properly managed, the patient lives a perfectly normal life. Medication however needs to be taken on a lifelong basis. The disease is known to undergo periodic flare ups (relapses) and inactive periods (remission). Lifelong medication aims to decrease the number of relapses a patient will suffer.

The amount and type of medication needed depends on the severity and location of disease in the gastro-intestinal tract. These medications may be taken by mouth, injected directly into the veins, injected into subcutaneous tissue (similar to insulin injection), or applied directly into the intestines through the anus. The most effective method of giving the medication is dependent on which part of the intestines is affected.

  

WHAT DRUGS ARE USED IN IBD?

The purpose of treatment is two folds:

1. to reduce the activity of the disease – medically this is called “inducing remission”
2. to maintain remission and minimize / prevent flare-ups (relapses)– medically this is called “maintenance therapy”

For induction of remission, higher dose of drugs will be used. Side effects, if they are to occur, are therefore more commonly experienced during this early phase of treatment. All side effects are however expected to reverse as doses are reduced.

During maintenance therapy, the number of drugs and the doses used will generally be lower and side effects are therefore also less common.

There are 3 major categories of drugs used in the treatment of idiopathic inflammatory bowel disease.

 

1. Drugs which have an effect on reducing the activity of the disease / inflammation

• Steroids e.g., prednisolone, hydrocortisone.
• 5-Aminosalicylates e.g. Salofalk^â, Pentasa^â, Salazopyrin^â
• Immunosuppressants e.g., azathioprine (Imuran^â), methotrexate, cyclosporine
• Biologics and biosimilar drugs.

2. Drugs which are used to relief some symptoms but which do not directly affect disease activity

• Antidiarrhoeal medications
• Pain relief medications

3. Miscellaneous drugs

• Vitamins, minerals
• Special nutritional solutions

 

Steroids
Steroids are the mainstay in the treatment of active disease. With recent advances in biologic drugs, steroid may be used less frequently in future due to its side effects. Steroids may be:

• taken by mouth (oral administration) in the form of tablets or capsules
• inserted directly into the rectum (topical administration) in the form of suppositories, liquid enemas, foam enemas.
• injected directly into the veins (intravenous administration) for severely ill patients.

You may be asked to use the rectal preparation along with oral treatment for better control of the disease.

Steroids are given in gradually reducing doses (medically referred to as “tailing regimes”). Depending on the response, each reduction may take place at 2 weekly intervals or longer. It is vitally important that you understand how your physician wants you to take and tail the medication. If in doubt, always ask.

Unless instructed by your physician, YOU MUST NOT stop steroids abruptly as it is dangerous for you to do so. If you run out of medication for any reason before your next appointment, you MUST get an interim refill by a doctor who knows your case.

In the majority of cases, steroids will ultimately be terminated once the disease is in remission. However, in some patients, a low dose of steroid has to be maintained on long term basis to keep the disease under control.

 

The side effects of steroids are:

• increased appetite/ weight gain
• mood swings
• fluid retention / facial bloating
• pimples (acne)
• elevation of blood sugar level (hyperglycemia) / worsening of underlying diabetes

If you are known to have diabetes and have been started on steroid therapy, you should step up the monitoring of your sugar level and see the doctor who is taking care of your diabetes more frequently. They can then monitor your diabetic condition more closely and advise on the need for diabetic drug dosage adjustments. It is very important for you to keep to a recommended diabetic diet.

You should similarly see you own doctor to have your blood pressure closely monitored while on steroid therapy. As the dose of steroid is reduced, your blood pressure will return to its baseline level.

If you already are known to have a stomach or duodenal ulcer, steroids can exacerbate the symptoms. If this occurs, see you doctor as specific treatment may be required.

If you need steroid long term, there will be the side effects of thinning of bones (osteoporosis).   Long term use of steroid should be avoided in children as it slows down their growth rate.

Topical steroids are steroid preparations which are administered directly, through the anus, to the site of the disease. Some patients only suffer from inflammation in the rectum. They come in tablet forms (suppositories) or liquid / foam enemas. They are useful for treating patients where the site of inflammation is located near the rectum and last part of the colon. As they are not well absorbed into the body and mainly act locally in the intestines, they have less of the side effects mentioned above.

Rectal enemas / foams should be given just before bedtime in the lying position. This allows the contents to be retained for as long as possible so as to achieve better effects. You may experience bloating sensation or abdominal cramps. Adopting the correct technique of administration of enemas minimizes the discomfort.

 

5-AMINOSALICYLATES

These drugs are used for both inducing remission and maintenance therapy. Therefore, your doctor will advise you to continue taking these medicines for life even when your inflammation is no longer active. Relapse rates of ulcerative colitis and Crohn’s disease has been shown to be high when you stop this medication.

There are a number of different preparations available e.g., Sulphasalazine (Salazopyrin^â) and mesalazine (Salofalk^â and Pentasa^â). Although these medicines contain the same active component, the formulations are not similar. Your doctor will decide which preparation will be most suitable for you.

Just like for steroids, 5-Aminosalicylates are available in both oral (tablets) and rectal preparations (suppositories, liquid & foam enemas). You may be asked to use the rectal preparation along with oral treatment for better control of the disease.

Please ask your pharmacist if you need clarifications on administration techniques of the topical steroids.

 

Side effects of 5-aminosalicylates

Some patients may experience

• indigestion
• nausea
• frequency to defecate
• possible low sperm count (only for sulphasalazine)
• anal irritation (patients who are using rectal preparations)

IMMUNOSUPPRESSANTS

An overactivation of the body immune system is associated with IBD. Immunosuppressants (IMM) are thus used to correct this problem.

These drugs are useful in patients who do not respond well to maintenance 5-aminosalicylates and need long term steroid.   IMM helps to reduce the total amount of steroids needed to control the disease and therefore also help reduce the side effects of steroids. IMM is also termed as “steroid sparing agents”. Some common examples of immunosuppressants are azathioprine (Imuran^â) and methotrexate. Azathioprine acts slowly and will only show a beneficial effect after several months (usually three months) starting the medication.

The common side effects are:

• nausea
• fever
• pancreatitis (inflammation of pancreas)
• Hepatitis (inflammation of liver)
• Drop in white blood count

Long term use may predispose to certain types of skin cancer and lymphoma. This risk is fortunately not frequent.

Some patients may be offered methotrexate if they are intolerant of azathioprine. Methotrexate is available in oral or injectable form. Similar to azathioprine, it can cause drop in white blood count. Long term use of methotrexate may also lead to liver fibrosis (hardening of the liver).

 

BIOLOGICS drugs

This class of drugs are made of protein called immunoglobulin. It is similar to our own antibodies. The first generation of biologic drugs is called anti tumour necrosis factor (anti TNF). It works by neutralizing a protein produced by our immune system which leads to inflammation (TNF; tumour necrosis factor). Examples include infliximab (Remicade), adalimumab (Humira) and golimumab (Simponi). In recent years, there have been introduction of “biosimilar” drugs to anti TNF.   Biosimilars are similar to the branded / original biologics drugs in term of efficacy and side effects. They are generally cheaper than the branded drugs.

Other newer biologic therapies are targeted at other parts of the immune system. Vedolizumab (Entyvio) and ustekinumab (Stelara) are the two recently introduced agents. They work at different sites in the immune system from anti TNF but essentially aim to modulate the over drive immune system.

The therapeutic armamentarium for IBD will be more complex in the coming years with the introduction of newer biologics drugs. This means that there will be more effective therapy and fewer patients will need to undergo surgery. Hopefully the cost of these drugs will come down as well.

 

What are the complications of IBD?

Ulcerative colitis and Crohn’s disease can cause many complications if the disease is not controlled well.   These complications can be due directly to the disease or due to side effects of medication

• Bowel cancer.  Having IBD increases your risk of colon or small bowel cancer. The risk of malignancy becomes significant after disease duration of more than 10 years. Patients with Crohn’s disease affecting the small bowel are predisposed to small bowel cancer. Discuss with your doctor the timing to start screening for these cancers.
• Skin, eye and joint inflammation. Arthritis, eye inflammation (uveitis) and skin inflammation may happen during flare of IBD.
• Blood clot in the legs (deep vein thrombosis).
• Liver inflammation. Liver inflammation can be auto immune in nature (Primary sclerosing cholangitis) or due to side effects of medication.   Azathioprine can cause hepatitis and long-term use of methotrexate can lead to liver fibrosis.
• Bowel obstruction. Patients with Crohn’s disease affecting the small bowel may develop narrowing of small bowel (stricture) and this may lead to bowel obstruction.
• Fistula and abscess. As the inflammation in Crohn’s disease can affect the whole thickness of the bowel, it may lead to perforation of bowel with leakage of bowel content into peritoneal cavity leading to abdominal abscess.       Abscess is pus collection in the abdominal cavity. The whole thickness wall inflammation of bowel may lead to abnormal connection between two loops of bowel, or between bowel and bladder, or between bowel and vagina. This abnormal connection is called fistula.
• Perianal disease. This highly incapacitating disease happens in patients with Crohn’s disease. There are multiple fistulae and abscesses at area of buttock surrounding the anus.       It is a highly incapacitating complication.

 

 

How will IBD affect my life style?

Except for severe relapses of the disease, you will probably not require hospitalisation or medical leave from work. However, you may have to make adjustments in work, domestic and social routines and activities in order to cope with the occasional flare up of symptoms. In the majority of patients, IBD can be effectively controlled and the majority of patients lead normal life and can expect normal life span.

 

Some of the commonly asked questions?

Can I travel?

Answer: You should avoid travelling during periods of IBD relapse because of the inconvenience of frequent toilet visits, medications and abdominal pain.  When travelling abroad, you should always ensure that you have ADEQUATE supply of medicine. When traveling to a country on another time zone, you should take the medication according to their local time. Always carry at least some of your medication in the hand-carry case. This is a precautionary measure in case your check in luggage is lost / misplaced.

Is IBD influenced by diet?
Answer: There is no need for any specific dietary adjustments for most patients with IBD. Food types have NO relationship to disease flares. In particular, you are encouraged to maintain a well-balanced diet and food fads are strongly discouraged.

Is sexual function affected by IBD?

Answer: There should be no sexual dysfunction compared to general population if IBD is well controlled. Patients with frequent relapses will experience loss of interest in sex. Patients with perianal disease, especially in female patients, may experience pain during sexual intercourse. You should discuss with your physician if you have difficulties with your partner in this aspect.

Can I breast feed while on medication?

Answer: Most drugs used in IBD are safe during breastfeeding. The drugs are usually secreted in very tiny amount in the breast milk and therefore would not have any harmful effect on your baby. Breastfeeding is not discouraged but discuss this with your doctor before you proceed.

Will I require surgery?

Answer: Surgery may sometimes be indicated. The reasons for surgery for Ulcerative colitis and Crohn’s Disease are not entirely similar but they do overlap. As and when they occur, your doctor will discuss the details with you. Generally, surgery may be required for the following reasons:

• a severe episode of IBD that is not responding despite intensive medical treatment.
• patients who suffer from frequent repeated episodes of attacks and are not responding well to medical treatment
• pre-cancer changes are noted in the intestines
• blockage of the intestines (intestinal obstruction)
• leakage of the intestines and infection (perforation and abscess formation)
• uncontrolled bleeding (haemorrhage)
• Development of an abnormal connection between the intestines with other organs or the skin (fistula)