Inflammatory Bowel Disease:
Frequently Asked Questions

Version 3.0
This document was last modified on 3/15/1997

Part 3 of 3

2.2 Q: Are any other drugs used to treat IBD?

There are several different drugs in various stages of development for IBD.

2.2.1 Q Are nicotine patches ever used to treat UC?

Many UC patients have reported that their symptoms began after quitting smoking. In fact in the vast majority of studies where it has been checked a significantly lower proportion of UC patients smoke in comparison to controls. This data is clearly consistent with smoking having a preventive effect in UC. The mechanism of this is not understood.

In marked contrast a higher proportion of CD patients smoke compared to controls and continued smoking is a predictor of post surgical recurrence of CD. This data suggests that smoking may be a co-factor predisposing to the development of CD. The mechanism of this predisposition is not understood.

Due to the health risks of smoking, doctors have been skeptical of this data. Recently more attention has been devoted to understanding the relationship between smoking and IBD. One question that has stimulated considerable work has been whether nicotine is responsible for the apparently protective effect of smoking in UC?

Two relevant articles were recently published in The New England Journal of Medicine looking at the potential therapeutic benefit of nicotine patches, normally used to help people stop smoking, to induce remission of active UC and to maintain remission. The patches were helpful in some patients in the induction of remission but were not helpful in the maintenance of remission. Most non smoking patients in the studies suffered some side effects from the nicotine, including nausea, vomiting, lightheadedness, headache and sleeplessness. More work needs to be done to clarify the role of nicotine in therapy of UC.

2.2.2 Q: What about antibodies against TNF (Tumor Necrosis Factor)?

It is important to note that IBD has features in common with inflammatory diseases that involve other parts of the body such as rheumatoid arthritis and psoriasis for example. So therapies that are being developed for these diseases may also be useful for treating IBD.  There has been considerable publicity recently given to the new data about the treatment of CD with antibodies against Tumor Necrosis Factor (TNF).  These antibodies are also being evaluated in the treatment of rheumatoid arthritis.

2.2.2.1 Q: What is Tumor Necrosis Factor or TNF?

When the immune system is activated resulting in inflammation many chemical messengers are released. These chemical messengers are produced by the cells of the immune system and are called cytokines. These cytokines interact with other cells encouraging them to become activated and thus make the inflammation worse. TNF is one of the most important cytokines involved in this process. The term Tumor Necrosis Factor refers to one of its actions which led to its discovery.

2.2.2.2 Q: Does TNF serve any useful function?

In the setting of an infection TNF frequently plays an important role in helping the immune system respond promptly and effectively. However, it is believed that excessive and inappropriate production of TNF may be an important contributory factor in the development of several diseases characterized by inflammation and activation of the immune system such as multiple sclerosis, rheumatoid arthritis and others.

2.2.2.3 Q: Is TNF important in IBD? just CD? what about UC?

Various strategies have been used to evaluate the importance of TNF in both CD and ulcerative colitis (UC). Though some data does support a role it has been difficult to convincingly demonstrate that there is excessive production of TNF in either disease. The available data does seem to suggest that TNF may be of more importance in CD than UC. The fact that the new anti-TNF treatments seem effective in some patients is the best evidence that TNF is important in the disease process of CD.

There has been one small study of an anti-TNF antibody in UC and a preliminary report did not show impressive results.

2.2.2.4 Q: What is this new anti-TNF treatment?

The treatment consists of an antibody which is a protein that neutralizes the action of TNF. Originally, the antibody was made by a mouse when it was injected with human TNF. The immune system of the mouse recognized the foreign nature of the human TNF and made antibodies against it. One of these mouse antibodies was modified or humanized so that it would be less likely to provoke an adverse reaction when injected into a human. There are two antibodies that have been used to treat CD. The first, named cA2, was developed by the biotechnology company Centecor. The cA2 antibody was initially used in the treatment of severe infection. More recently it has been evaluated for the treatment of rheumatoid arthritis. Because of promising results in the arthritis studies a group of Dutch physicians gave the antibody to a child with severe CD and there was a dramatic response.  This encouraged more comprehensive studies of the effectiveness of the cA2 antibody to treat CD in Europe and the United States. The second anti-TNF antibody has been developed by the biotechnology company British Biotechnology and is called CDP571.

2.2.2.5 Q: How does the anti-TNF treatment work?

The antibodies blocks the action of TNF. The fact that it is so effective in some patients has raised the question whether it is having some additional effects on the immune system; however this remains to be clarified. The most important aspect of its use is that it implies that TNF does indeed seem to have an important role in the development of inflammation of CD in a significant percentage of patients.

2.2.2.6 Q: Are there problems with the treatment?

Like most treatments for IBD it does not seem to work in all patients. In the recently reported studies most patients who received the treatment had a beneficial response about half of whom actually went into remission.

In those patients who have a response the effect is temporary, lasting several months at best. The antibody is given by intravenous infusion and cannot be given by mouth. It is not clear whether it can be given safely to the same patient more than once. If indeed it can be given repeatedly it remains to be seen whether it will continue to have a beneficial effect or whether resistance will emerge.

The treatment will only be available as part of formal clinical studies for the next few years. If it continues to have positive results and becomes available as a standard therapy in the next few years it is likely to be expensive.

2.2.2.7 Q: What sort of patients are suitable candidates for treatment with anti-TNF antibody?

CD patients with active disease despite therapy with steroids; this is a prerequisite for enrollment in the studies. Those patients who may particularly be suitable for the anti-TNF therapy are those who cannot tolerate 6-mercaptopurine or in whom 6-mercaptopurine has not worked or have just been started on 6-mercaptopurine and a therapeutic effect is not expected for several months. IMPORTANT: the anti-TNF antibodies are only available as part of formal studies at present.

2.2.2.8 Q: What are the alternatives available at present?

The best tested and most effective medications at present are 6-MP and methotrexate. Other medications are also being developed which block the action of TNF which may be useful in the treatment of IBD in the future.

2.2.3 Q: What about Interleukin-10 (IL-10) therapy for CD?

IL-10 is another cytokine like TNF. Cytokines are chemical messengers produced by the cells of the immune system that regulate its activity.  Unlike TNF, IL-10 suppresses the immune system and is presently being studied in the treatment of CD. The results of this study are eagerly awaited.

2.2.4 Q: What about fish oil for therapy?

There is some evidence that fish oil (attributed to the eicosapentaenoic acid) has anti-inflammatory properties which may be useful in the treatment of IBD and rheumatoid arthritis. In addition it may also be helpful in preventing atherosclerotic cardiovascular disease. Patient acceptance of fish oil therapy has been poor because of the indigestion and bad breath associated with therapy. An Italian study last year using coated capsules containing fish oil showed evidence of benefit in preventing recurrences of CD with miminal side-effects. However, these capsules are not widely available at present. In the interim various fish oil preparations containing eicosapentaenoic acid are available from pharmacies and health food stores which may be of therapeutic benefit despite the possible side-effect of increased susceptibility to bleeding. Alternatively it may be helpful to simply eat more fish in one's diet!

2.3 Q: Can different drugs be used together to treat IBD?

Many patients require treatment with more than one medication to adequately control their symptoms. Frequently, several different combinations are tried before the best one is found. Once symptoms are brought under control then attempts are made to reduce the medications to a minimum.

2.4  Q:  Will I need to keep taking medications permanently?

At this point in time because there is no cure for IBD (except removal of the colon for patients with UC) it is advisable for many patients to continue taking medications to keep them in remission. The reason for this, which is supported by some studies, is that it is much easier to keep a patient in remission rather than treat a flare of the disease. Similarly, it is much easier to use sun screen to prevent sunburn rather than try to treat sunburn after it has happened.

3.1 Q: Drugs aren't working, what can surgery do for my UC?

Drug treatments are ineffective in about 20% of UC patients. These patients must have their colons removed due to debilitating symptoms. The colon may also removed because of the threat of cancer. Removal of the colon permanently cures the UC and usually all related symptoms. Patients having these surgeries are generally hospitalized for about a week and return to work in three to six weeks.

There is NO role for resections of only part of the colon in UC even when the disease is limited in extent as it inevitably recurs in the colonic remnant.

Once the colon is removed there are several options which may avoid the need to wear a bag appliance to collect waste.

3.1.1 Q: What's an ileostomy?

The entire colon and rectum are removed and a small opening, about the size of a quarter, called an ileostomy is made in the lower right corner of the abdominal wall. The small intestine is then connected to this opening and a colostomy bag is worn over the opening to collect waste. The patient then empties the bag about four times a day.

3.1.2 Q: What's a Continent Ileostomy?

Another operation that gained popularity over an ileostomy avoids the use of a colostomy bag by forming a pouch from the last 15-40 cm of ileum inside the wall of the lower abdomen. A nipple valve in the abdominal wall allows the patient to empty the pouch by inserting a catheter through the ileostomy. Initially, the pouch must be emptied frequently, eight to ten times daily. The pouch stretches and, after several months it will only have to be emptied four to five times a day. This operation used to be performed in two separate steps and the patient would have to wear a colostomy bag for several months before the pouch could be attached. The operation is now generally performed in one step, though it may be performed as two steps if the patient is severely ill at the time of surgery.

This procedure is generally not performed because it has many of the possible complications and none of the benefits of the Ileoanal Anastomosis, described below.

3.1.3 Q: What's an Ileoanal Anastomosis, or Ileoanal Pull-Through?

Since UC inflames only the innermost layer of the colon, the rectum can be stripped of this layer and attached to the ileum after the colon is removed. Early attempts to perform this surgery were frustrating as patients predictably suffered from  incapacitating diarrhea. The operation was modified in 1980, adding an S or J shaped pouch just above the rectum and patients achieved continence. The patient can then pass stools normally, though bowel movements are more frequent and watery than in an otherwise healthy individual without IBD.  Like the Kock pouch, eight to ten bowel movements a day are typical immediately after the surgery. The pouch continues to stretch for several years and eventually it's only necessary to have four or five bowel movements a day.  In rare cases (around 5% when the surgery is performed by an appropriately trained surgeon) when other complications, such as infection occur, the pouch may need to be converted to an ileostomy.

3.1.4 Q: What can go wrong with these surgeries?

The most common complication of these operations is inflammation of the pouch, called pouchitis.  Symptoms include pain, bloating, and diarrhea.  Most patients can control this by irrigating the pouch with saline solution and taking antibiotics. In a few cases, a diagnosis of CD is confirmed in patients thought originally to be suffering from UC.

Problems with the nipple valve in a continent ileostomy can cause leakage of stool and an inability to insert the catheter.  About 10% of patients require a second operation to repair the nipple valve.

Remember that these have the same risks as any surgery, but that's outside the scope of this FAQ.

3.2 Q: Are there surgical treatments for Crohn's?

Unlike in UC, there is no surgical cure for CD.

Physicians use the phrases "minimalist surgery" and "surgery avoidance" when discussing surgical options for CD. This is because new Crohn's lesions can appear after previously diseased areas have been removed and even diseased tissue may be functionally useful. Many surgeons also feel that "surgery in Crohn's patients just leads to more surgery".

Surgery for CD is usually a resection of the small intestines.

3.2.1 Q: What's a resection?

Severely affected portions of the intestine are removed and the healthy ends are sewn together. This in no way prevents inflammation from recurring later and is generally performed only when the inflammation is unable to be controlled by medical therapy.

3.2.2 Q: After surgery for CD can anything be done to prevent it recurring again?

Smoking is associated with recurrent disease following surgery in CD patients. Clearly, CD patients must be strongly encouraged to stop smoking.

There is some evidence that 5-ASA drugs (especially Pentasa for small bowel disease) may be useful in preventing disease recurrence after surgery. Some experts use 6-MP following surgery in patients with a high risk of recurrence and there is a trial in progress to see if it works in this setting. There is also some limited evidence that metronidazole may be helpful in preventing disease recurrence following surgery. Fish oil may also be a relatively safe option though it is not of proven benefit.

4.1 Q: What role does diet play in IBD?

Most patients find that certain foods are tolerated less well than others when symptoms are active, but there is no evidence that these foods directly affect the inflammation. The most common offenders are milk products (see the section on lactose intolerance below), spicy foods, fats, and sugars. In general, a bland low fiber diet avoiding fruits, vegetables, nuts, and whole grains is preferable when the disease is active. A high fiber diet is to be recommended when symptoms aren't present.

Due to reduced appetite, malabsorption of nutrients, and increased nutritional needs, it's important to make sure you follow a proper diet.  Since the small intestine is where the body absorbs nutrients from food, CD patients may have problems absorbing these nutrients.  If more than two or three feet are either diseased or surgically removed, malabsorption, especially of fats, the minerals calcium and magnesium, and the fat soluble vitamins A,E, and D, can be a problem. Resection of at least two feet may also increase absorption of oxalate, which reacts with calcium to form kidney stones. A low oxalate and low fat diet will help prevent kidney stones. Spinach, cocoa beans, rhubarb, beets, instant coffee, diet sodas and tea are all high in oxalate. If only the terminal ileum, the last two to three feet of the small intestine, is diseased or resected, absorption will be normal except for vitamin B-12 which can be supplemented by monthly injections. Iron supplements are helpful in treating the anemia and patients should drink plenty of fluids to replace those lost from diarrhea.

4.1.1 Q: What is an elemental or astronaut diet?

Astronaut diets (for example Ensure, Sustacal and Peptamen) are liquids meeting all nutritional needs and are almost completely absorbed in the upper intestinal tract. Because they don't require much digestive effort by diseased bowel they often seem to be better tolerated than regular food by patients with active and/or severe disease. Elemental diets (for example Vivonex) consist mainly of pure amino acids (the building blocks that make up proteins) and are even easier to digest. There is some evidence that elemental diets may be helpful therapeutically in CD. However, these diets are expensive and patients find it difficult to comply with them on a long term basis so they have not evolved into a practical treatment.

In contrast there is no evidence that elemental diets are of benefit in UC.

4.1.2 Q: What is total parenteral nutrition?

Total parenteral nutrition (TPN), or hyperalimention, delivers a concentrated solution of nutrients intravenously. This is used in very active disease either giving it time to subside, or to nourish the patient before surgery.

People with Crohn's Disease generally benefit more than those with UC because CD usually affects the small intestine, which is where nutrients are absorbed. TPN may, however, occasionally be warranted in critically ill people with UC.

4.1.3 Q: What is lactose intolerance?

It's commonly estimated that about 30% of the world's adult population suffers from lactose intolerance, though this may be even higher in patients with IBD. A much higher than normal fraction of Asians suffer from lactose intolerance.

Lactose is a sugar found in milk, milk products, and foods made with milk.  The enzyme lactase, normally produced in our intestines, breaks down lactose during digestion. Lactose intolerant people don't produce enough lactase and therefore cannot digest lactose.

Symptoms of lactose intolerance include a bloated feeling, abdominal pain, flatulence, and diarrhea shortly after consuming milk or milk products.  Sound familiar?  It's not something that you want to subject yourself to in addition to the symptoms of Crohn's or UC. A simple laboratory test can determine whether one is lactose intolerant or not.  The severity of symptoms is highly individual and most people do not need to eliminate lactose from their diet entirely.

4.1.3.1 Q: So what can I do about lactose intolerance?

1.  Reduce or Remove milk and milk containing foods from your diet. These include milk chocolate, butter, cheeses, ice cream and lactose--it's an ingredient by itself in some foods.  Check the label!

2.  Eat foods containing lactose with meals containing protein and fat, not alone.

3.  Use a lactose reducing product available over the counter at most pharmacies (Dairy Ease or Lactaid). These contain lactase and are either consumed with lactose rich food or added to it before eating.

Some dairy products have reduced lactose content. These include yogurt and Lactaid Milk.

4.  Fermented milk products, such as aged cheeses, contain less lactose and are usually better tolerated.  Cottage and ricotta cheese are OK, cheddar has about the least. Buttermilk contains as much lactose as milk.

5.  A calcium supplement may be needed if dairy products are reduced or eliminated from your diet.

5.1 Q: What part does stress play in IBD?

Emotional stress plays a large part in the health of some patients and is often cited as the trigger of a relapse, though there is no clear cause and effect relationship proven. It may be more likely be that stress is one result of a flare-up rather than being a factor contributing to one.  Treatment of IBD sometimes may usefully include the teaching of stress
reduction techniques such as meditation.

This is a controversial subject with somewhat "political" overtones. Many patients resent the assumption of family and friends and even some doctors that stress is a cause of their illness, when in fact it is just an exacerbating factor (as is the case with other illnesses, as well). Many people need reassurance that all this is not their fault or "all in their head". It's been proven that stress does NOT cause IBD, although with IBD as with any illness stress can exacerbate symptoms.

Because of the nature of these illnesses and the unpleasant symptoms that result patients frequently feel very uncomfortable about discussing them even with close friends and family. Denial may be a factor that inhibits patients from getting appropriate evaluation and therapy.

Many patients find patient support groups to be extremely helpful in addressing these issues and enabling patients to constructively and positively learn how to live with these chronic illnesses. Many patients not comfortable with group discussions  have found it particularly helpful to consult with a psychologist experienced in the evaluation of patients
with IBD.

5.2 Q: Can anything else cause a flare up?

Significant anecdotal evidence suggests that flares of IBD often occur after increased use of non-steroidal anti-inflammatory drugs (NSAID's), such as aspirin and ibuprofen. Accordingly, patients should be very careful about taking these medications and be aware that they may cause a flare of their disease. In fact, some physicians who are very experienced in managing IBD feel these drugs should rarely if ever be used by IBD patients.

6.1 Q: How can I make the most of my consultations with my physician?

For your physician to treat you most effectively it is vital that you adequately describe your symptoms. Many patients are reticent about describing urgency and episodes of incontinence for example which may be readily treated with local topical therapy. If despite the best efforts of your physician you are not doing well either having continued symptoms or requiring continued high dose steroids then it may be appropriate to consider asking for a second opinion. This is best done in conjunction with your regular physician.

Recommended Books:
Listen To Your Gut : Natural Healing and Dealing with Inflammatory Bowel Disease by Jini Patel Thompson
The IBD Remission Diet by Jini Patel Thompson
Positive Options for Living with Your Ostomy: Self-Help and Treatment by Craig A. White
Coping with Crohn's Disease: Manage Your Physical Symptoms and Overcome the Emotional Challenges by Amy B. Trachter

Source:  Copyright 1997 by Kevin Horgan, M.D., Christopher Holmes and Michael Bloom.   All rights reserved.   This document, or any derivative works thereof, may not be sold or redistributed for profit in any way without express (not email) written permission of the authors.  This includes, but is not limited to, translations into foreign languages, mass archival as on a CD_ROM and inclusion in commercially published compilations (books).   You are free to copy this list for personal use, or to make it available for redistribution in its electronic format, provided that:  (1) it remains wholly unedited and unmodified, (2) no fee or compensation is charged for copies of or access to this list, and (3) this copyright notice and the following disclaimer remain attached.

DISCLAIMER:
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This FAQ is provided by the authors "as is", and any express or implied warranties, including, but not limited to, the implied warranties of merchantability and fitness for a particular purpose are disclaimed.  In absolutely no event shall the authors be liable for any direct, indirect, incidental, special, exemplary, or consequential damages (including, but not limited to, procurement of substitute goods or services; loss of use, data, or profits; or business interruption) however caused and on any theory of liability, whether in contract, strict liability, or tort (including negligence or otherwise) arising in any way out of the use of the information herein contained, even if advised of the possibility of such damage.  In other words, this document is in no way intended to be a substitute for medical care; the information contained herein is presented by the  authors purely for informational purposes only.  In no way are any of  the materials presented here meant to be a substitute for professional medical care or attention by a qualified practitioner, nor should they be inferred as such.  ALWAYS check with your doctor if you have any questions or concerns about your condition, or before starting a  new course of treatment or otherwise making any decisions about treatment.