Can colitis be cured

Internal Medicine Clinic

The term microscopic colitis encompasses two different diseases of the large intestine, which are referred to as collagenous and lymphocytic colitis.

Both diseases are characterized by watery diarrhea and are therefore also known as the "watery diarrhea syndrome"

Definition of microscopic colitis

The term microscopic colitis describes an inflammatory disease of the large intestine ("colitis"), which the doctor cannot detect with the naked eye during endoscopy, as the intestinal mucosa is normal. The doctor takes small tissue samples and examines them under a microscope.

Microscopic colitis can only be diagnosed under the microscope. In the case of collagenous colitis, special staining methods of the tissue samples reveal a thickened band of collagen, whereas in the case of lymphocytic colitis, an increased number of certain white blood cells, the lymphocytes, is noticeable.

Since microscopic colitis was first described in the 1980s, there has been a significant increase in the level of knowledge about this disease. Today it can be assumed that the incidence of microscopic colitis is as high as that of the inflammatory bowel diseases Crohn's disease and ulcerative colitis.

Various therapy options have since been investigated in studies. Budesonide (in the form of capsules for oral intake) has been officially approved for the treatment of collagenous colitis worldwide. In 2008 the first publications on the drug treatment of lymphocytic colitis with budesonide appeared.

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Clinical picture

Watery diarrhea is the leading symptom of microscopic colitis. This can occur suddenly and simulate an infection. In a larger study from Sweden, the following symptoms were also reported:

  • In almost 30% of the cases: nocturnal diarrhea
  • In over 40% of the cases: weight loss
  • In over 40% of cases: abdominal pain
  • In over 20% of cases: nausea
  • In over 10% of cases: flatulence

The causes of the weight loss are ultimately not fully understood, but it seems likely that the patients eat less food and lose weight as a result of well-meaning dietary restrictions.

Despite the frequent diarrhea, however, the problem of dehydration rarely occurs. Fecal incontinence and fatigue are other symptoms that accompany microscopic colitis and can significantly reduce the quality of life.

In the case of collagenous colitis, symptoms or diseases can also occur in other organs outside the intestine, such as B. rheumatic complaints in the joints, psoriasis on the skin or disorders of the thyroid function (Fig. 2). These diseases then need additional treatment.

Fig. 2: Diseases that can occur at the same time as collagenous colitis

The course of collagenous and lymphocytic colitis can be described as benign overall, even though approx. 40% of patients have chronic, i.e. H. permanent or recurring watery diarrhea complain. There is no increased risk of developing colon cancer.

When making the diagnosis, other diseases with similar symptoms must be taken into account and excluded: Typical intestinal disorders with diarrhea but without weight loss are irritable bowel syndrome (of the diarrheal type) and various forms of food intolerance, such as: B. the widespread lactose intolerance (intolerance to milk sugar).

The chronic inflammatory bowel diseases (Crohn's disease and ulcerative colitis) are usually clearly delineated, since typical changes in the intestinal mucosa with the appearance of ulcers are noticeable in the colonoscopy. If the large intestine is (also) affected in these two diseases, as is often the case, the diarrhea is usually accompanied by blood.

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Causes and development of microscopic colitis

The exact causes of both diseases are not yet known, but various theories are being discussed. Some studies see the cause of collagenous colitis in an increased use of certain drugs, which are mostly used to treat pain in joint complaints. These are so-called "non-steroidal anti-inflammatory drugs", but also preparations for treating high cholesterol levels or for preventing blood clotting.

It is also conceivable that by increasing the permeability of the intestinal mucous membrane (the cause for this is also unknown), ingredients from the food pulp may get into the intestinal wall and cause intestinal disorders there.

In about half of the patients with lymphocytic colitis, antibodies can be detected that are directed against their own body, in this case against the intestine, which is why this disease can possibly be counted among the so-called "autoimmune diseases".

In collagenous colitis, on the other hand, antibodies against certain bacteria are often found, but the bacteria themselves are not. This indicates an expired bacterial intestinal infection, which in turn could possibly have triggered the collagenous colitis due to increased permeability of the intestinal mucosa.

It is not yet clear how these phenomena lead to a thickening of the collagen ligament in collagenous colitis or to an increased occurrence of immune cells (lymphocytes) in the intestinal mucosa in lymphocytic colitis.

However, it is known that the collagen deposition of collagenous colitis is not an overproduction of collagen, but a reduced collagen breakdown.
Interestingly, the creation of an artificial anus leads to the complete normalization of the collagen ligament in the intestinal sections below the anus and thus to the disappearance of the disease. Fortunately, because of the good medical treatment options, such an operation only needs to be used very rarely.

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Diagnosis

To confirm the diagnosis of microscopic colitis, it has proven useful to clarify patients with watery diarrhea that persists for longer than 4 weeks by means of a colonoscopy and, especially if the endoscopic findings are normal - if the doctor sees no changes in the mucous membrane with the naked eye - samples from inconspicuous areas of the intestinal mucosa refer to. Assessment under the microscope then leads to diagnosis. The diagnosis of microscopic colitis is made in around 10% of patients with watery diarrhea lasting more than 4 weeks and normal endoscopic findings.

In any case, it is important to take samples from the entire large intestine, since about a quarter of all cases of collagenous colitis are found exclusively in the ascending part of the large intestine.

The microscopic examination of tissue samples from the intestine yields very characteristic results for both diseases: With the help of certain staining methods, a thickened collagen band in the intestinal mucosa can be seen in patients with collagenous colitis (Fig. 3).

Fig. 3: Scheme drawing (left) and microscopic image (right) of the intestinal mucosa in collagenous colitis. The pink colored, thickened collagen band is easy to see.

Collagen fibers represent a certain protein structure with a supporting function in the body. While this collagen band measures less than 5 micrometers (millionths of a meter) in healthy people, the collagen band in these patients is at least 10 micrometers thick and can be seen very well after staining.

In patients with lymphocytic colitis, the doctor will find an increased accumulation of cells of the immune system (lymphocytes, a subgroup of white blood cells) in the tissue samples. The number of lymphocytes is about 4–5 times higher than in healthy individuals (Fig. 4).

Fig. 4: Microscopic picture of the intestinal mucosa in lymphocytic colitis with increased lymphocytes

However, it is still unclear what influence the thickened collagen band or the increased occurrence of inflammatory cells have on the development and course of the disease. So far there has been no way of diagnosing the disease on the basis of a blood test.

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therapy

The drug treatment of collagenous colitis has been studied best so far. Here, bismuth, budesonide, prednisolone and frankincense extract were used as part of therapy studies. The first publication on acute drug therapy for lymphocytic colitis appeared in 2008. To date, only one drug has been officially approved worldwide for the treatment of microscopic colitis, namely budesonide for collagenous colitis.

Budesonide

Budesonide is a modern cortisone preparation that has very good local anti-inflammatory effects on the intestinal mucosa. The substance was first used as a spray in asthma therapy. In the 1990s, it was used in inflammatory bowel diseases. The budesonide - given as granules in a capsule - is only released in the transition from the small intestine to the ascending large intestine due to a special manufacturing process. There the substance has a strong anti-inflammatory effect on the mucous membrane, more intense than classic cortisones.

The particular advantage of budesonide is that after its action in the intestine, over 90% of it is broken down directly in the liver. This means that only a small proportion of the active substance enters the body's circulation, which is associated with significantly fewer undesirable effects of cortisone compared to classic cortisone preparations.

Budesonide is therefore very well suited to achieve a high level of local effectiveness on the intestinal mucosa with only a low rate of undesirable effects of cortisone. There are now three studies with budesonide for the treatment of collagenous colitis. The effectiveness was compared with a dummy drug (placebo). The daily dose of budesonide was 9 mg in each case and the duration of treatment was 6–8 weeks.

In over 80% of the patients there was a clinical improvement with the diarrhea disappearing, compared to only 17% in the patients who were treated with the dummy drug. If you look at the analysis of tissue samples from the intestine under the microscope, the effect of the dummy drug is also significantly weaker here (demonstrated by the decrease in the thickness of the collagen band).

The recommendation for the further therapeutic procedure in the event of recurrence of diarrhea after initial improvement under budesonide therapy is not yet clear. In another therapeutic study, continued treatment with budesonide (at 6 mg per day) for 6 months led to a significantly better result in the budesonide group compared to a dummy drug. However, the disease often relapses 2 months after discontinuing therapy. So far, budesonide has only been approved for the treatment of acute illness.

Prednisolone

In the past, the classic cortisone preparation prednisolone was often used in patients to treat microscopic colitis. However, in contrast to budesonide, prednisolone is initially absorbed via the bloodstream after ingestion and therefore, in addition to the desired therapeutic effect, usually leads to pronounced typical cortisone side effects, such as e.g. B. full moon face, trunk obesity, high blood pressure, disorders of the psyche or weakened immune system.

Frankincense extract

Frankincense extract also works against inflammation in the intestines. According to the first available studies, a clinical improvement in collagenous colitis can also be achieved with this. Frankincense extracts are not officially approved in Germany.

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Common questions about microscopic colitis

  1. How common is microscopic colitis?

    Overall, microscopic colitis is diagnosed more and more frequently according to current figures (including from the USA) (Fig. 5). This increase is explained not only with improved diagnostics, but also with a real increase in the number of cases of illness. The figures show an annual new disease rate (incidence) of around 10 patients per 100,000 population.

    Fig. 5: Overview of the frequency of lymphocytic and collagenous colitis (a survey from the USA)

    The annual incidence of collagenous colitis varies greatly from country to country and is, for example, 1–2 per 100,000 inhabitants in Spain, while in Sweden a new incidence rate of 5 per 100,000 is given. Little data are available for lymphocytic colitis. In Scandinavia, an annual incidence rate of 4 per 100,000 inhabitants is assumed.

  2. Are there factors that encourage microscopic colitis to occur?

    All studies carried out to date show that women are approximately five times more likely to develop microscopic colitis than men. The risk increases significantly, especially for women over 65 years of age. This applies to both collagenous and lymphocytic colitis. The reasons for this are unknown.

    In addition, patients who already suffer from certain diseases of the immune system (so-called autoimmune diseases) also seem to develop microscopic colitis more often than patients without previous autoimmune diseases. Patients with an underactive thyroid or celiac disease (sprue) are particularly affected. Overall, up to 40% of patients with microscopic colitis suffer from an autoimmune disease at the same time.

    About 10% of patients also report having a history of cancer. The majority of the cases were colon, breast, prostate or lung cancer. If the cancer incidence in these patients is compared with that in the normal population, the risk of developing microscopic colitis is increased, especially for women over the age of 65. There may also be an increased risk if you have diabetes (diabetes mellitus). Obviously, older men are more likely to be affected by this. In general, a possible connection and the underlying causes between microscopic colitis and the diseases mentioned here must be further investigated.

  3. What is known about the causes of microscopic colitis?

    Ultimately, the causes of microscopic colitis are not known. It is noticeable that an increased use of painkillers (e.g. ibuprofen and acetylsalicylic acid) was found to be a possible triggering factor in a relevant number of patients. These drugs may increase the permeability of the intestinal mucosa and could thus promote the uptake of other, as yet unknown, disease-causing substances. But also other drugs, such as B. simvastatin (a cholesterol-lowering drug), ticlopidine (to inhibit blood clotting) or acarbose (to treat diabetes mellitus) have been described as possible triggers of microscopic colitis.

    In the course of various studies, Yersinia antibodies were found in approx. 80% of the patients. Yersinia are bacteria that can lead to an infection of the intestinal lining. On the other hand, in numerous stool examinations, Yersinia could not be detected in the stool of patients with microscopic colitis. There is also evidence that microscopic colitis has a family history. To what extent this suggests inheritance is still unclear.

  4. How is the thickening of the collagen band in the intestinal mucosa explained?

    The increase in the collagen ligament in collagenous colitis is not an increase in collagen formation, but rather a reduced breakdown. However, the exact mechanisms that lead to this reduced breakdown of collagen in the intestinal mucosa have not been fully investigated. It is also not known whether and how a thickening of the collagen ligament can cause the symptoms typical of collagenous colitis.

  5. Are there any symptoms outside the intestine in microscopic colitis?

    Microscopic colitis can be accompanied by a number of different diseases that indicate a reaction by the immune system against the body's own tissue. These include Rheumatic joint problems, psoriasis, sprue (celiac disease), functional disorders of the thyroid gland, circulatory disorders and dry mucous membranes (see also Fig. 2).

  6. Is a rectoscopy sufficient for diagnosis?

    Since microscopic colitis occurs more frequently in the ascending, right-sided large intestine, a rectoscopy is not sufficient for making a diagnosis. In either case, the colon should be completely mirrored, with tissue samples taken from the different sections of the colon at the same time. Otherwise, microscopic colitis can be missed in up to 40% of patients.

  7. Does microscopic colitis favor colon cancer?

    No. There is no evidence that polyps or colon cancer are more common in collagenous or lymphocytic colitis.

  8. Are there any concerns about pregnancy?

    No. As for the condition itself, there are no concerns about pregnancy. However, with the drugs used, it is important to pay attention to the extent to which there are restrictions on use during pregnancy and breastfeeding.However, the disease is more likely to occur in older patients beyond menopause.

  9. Are there nutritional factors that positively influence the course of microscopic colitis?

    There is no reliable knowledge about a possible influence of nutritional factors on the triggering of the diseases. Furthermore, it is also not known whether adding or leaving out certain foods has a positive or negative effect on the course of the disease.

    However, as part of the preliminary diagnosis - due to the main symptom of watery diarrhea - lactose intolerance and the clinical picture of celiac disease should be excluded. In the case of these diseases, there is a clear recommendation to adhere to a lactose-free or gluten-free diet. Studies have shown that fasting in collagenous colitis can lead to a significant improvement in the symptoms of diarrhea. However, prolonged fasting is not a permanent therapy for microscopic colitis.

  10. Does Surgery Help With Microscopic Colitis?

    Surgery for microscopic colitis has so far only been carried out in the rare, very severe cases. The findings from these cases show, however, that after the intestinal contents are led out via an artificial anus (anus praeter) in the remaining intestine, through which no stool is now flowing, both the inflammation and the thickened collagen band disappear. This fact points once again to the importance of factors in the intestinal contents as possible triggers of microscopic colitis.

  11. Are there any spontaneous improvements or have the illnesses healed?

    Two studies on the long-term course of collagenous colitis show that some of the patients remain symptom-free for a long time after successful initial therapy even without further medication. In one of the two studies, after 10 years, 23% of the patients still had no watery diarrhea. On the other hand, up to two thirds of patients experience symptoms again within 2 months after discontinuing therapy. In these cases, a new therapy cycle is recommended.

  12. Is it possible to favorably influence the diarrhea with swelling agents?

    In the case of mild diarrhea, it is often sufficient to use stuffing agents or bile acid binders to increase the firmness of the stool and thereby reduce the frequency of stool. In a small study, the diarrhea disappeared in over 20% of the patients while taking a swelling substance preparation.

  13. How long should budesonide be taken in the acute phase of the disease?

    In the three therapy studies carried out so far with budesonide, budesonide was administered in a daily dose of 9 mg (3 capsules of 3 mg) over a period of 6 or 8 weeks. With this therapeutic approach, the majority of patients became almost symptom-free within 14 days. The budesonide can be spread over the day (morning, noon, evening) or the entire amount can be taken in a single dose in the morning.

  14. Is there maintenance therapy for collagenous colitis?

    After stopping budesonide therapy, diarrhea often recurs within the first 2 months, so that further therapy is required. The effectiveness of the preparation is then as good as when it was first taken. So far, budesonide has not yet been approved for long-term use for more than 2 months.

  15. Is there a reliable drug therapy for lymphocytic colitis?

    This question is currently being investigated in studies. Initial research results suggest that budesonide is also effective in lymphocytic colitis. However, these results need to be confirmed by further research. So far, budesonide has not been approved for the treatment of lymphocytic colitis.

    Other patient brochures on inflammatory bowel disease include: available free of charge:

    • Ulcerative colitis and Crohn's disease An overview of the clinical pictures and their treatment (S80) 71 pages
    • Patient questions on inflammatory bowel disease (S81) 63 pages
    • Crohn's disease, ulcerative colitis and pregnancy (S82) 58 pages
    • Nutrition in Crohn's disease and ulcerative colitis 20 questions - 20 answers (S84) 66 pages

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Author: Prof. Dr. med. Andreas Tromm
Published by the Falk Foundation
Leinenweberstr. 5
79108 Freiburg
www.falkfoundation.de