What is crohn's disease ?
Crohn's disease is an inflammatory disease of the intestinal tract. This disease manifests itself frequently at the transition from the small to the large intestine, but can occur at any point in the intestinal tract. Along with ulcerative colitis is the the main chronic inflammatory disease of the bowel.
General
Crohn's disease is a chronic inflammatory bowel disease. It is a chronic inflammation of the mucous membranes of the gastro-intestinal tract. Usually the small and/or large intestine affected, but also the mouth or anus can be done. The inflammation of the gut in Crohn's disease has an extremely erratic. It can range from a rapid expansion to other intestine parts (acute phase) to a relatively quiet image that gives few complaints over the years and hardly need treatment (chronic phase).
Epidemiology
Tens of thousands of Dutch and Belgians have IBD. The disease often manifests itself between the 15th and 30th year of life. For unknown reasons, the age around the millennium started to fall (in 2006 there was even a few newborns established Crohn's disease). Crohn's disease is seen slightly more women and ulcerative colitis just slightly more common in men. International prevalence varies (prevention of disease) a lot depending on where you are in the world and ethnicity. In general, the disease most prevalent in North America and Northern Europe and least in areas where living conditions are not so good. In North America, Crohn's disease is most common in whites (43.6 per 100,000) and African Americans (29.8 per 100,000) and least common among Asians (5.6 per 100,000), and Hispanics.
Crohn's disease symptoms
- Loose stools or diarrhea: The inflamed intestine can not absorb enough moisture.
- Weight loss, anemia and growth retardation: The inflammatory bowel sufficiently to take certain nutrients causing shortages in the body may occur, for example, vitamin B12. As a result, fatigue also occurs.
- Blood loss: Because of the infection originated lesions in the gut causing bleeding in the stool may occur.
- Narrowing (stenosis): When the ignition at a particular place is very intense (acute phase), there may be a constriction in the intestine. It can also be caused by a developing scar tissue. Also at a relatively quiet running of the inflammation in the intestine may be on the long term scar tissue forms. This often rigid connective tissue can, just as in the acute phase give rise to the narrowing and even closure of the intestine.
- Fistulas: Once the inflammation spread to other intestinal parts or surrounding organs may form unnatural connections (fistulas). These fistulae may penetrate into other organs and in particular the skin.
- Joint pain: In case of a limited number of patients, the infection is not only to the gastro-intestinal tract. Swelling of example. Knees, elbows, ankles and wrists can occur, as well as in the back (ankylosing spondylitis).
- Eye and tissue disorders: Here, too, the inflammation is not only limited to the gastrointestinal tract.
Crohn's disease causes
The cause of Crohn's disease has been strongly associated in a genetic mutation of the NOD2 protein in cells of the innate immune system. There are clear indications that both genetic and environmental factors play a role in causing these diseases. The human body has defenses against invaders such as bacteria and viruses. There are indications that in Crohn's disease this defense mechanism attacks its own body, with an inflammatory response of the gastro-intestinal tract as a result. This is called an autoimmune disease.
Heredity
Several genes involved in the etiology of Crohn's disease: IBD1-9 and CARD15. Mutations in the CARD15 gene occur in 10-15% of patients. The exact mechanism by which these genes give rise to the onset of the disease is not yet known. However, it is known that the CARD15 mutations may give rise to an increased production of pro-inflammatory cytokines by monocytes and macrophages. Smoking (an environmental factor) approximately doubles the risk of having a child with Crohn's disease. A patient with Crohn's disease, which has two CARD15 mutations smokes and has 35% chance of progeny with the disease. The risk that a child of a parent with the non-smoking Crohn's disease, without CARD15 mutations develop the disease amounts to 2 percent. In general (without Crohn's disease in the family) is the risk of having a child with this condition 0.1 percent.
Environmental factors. Crohn's disease is most common in North America and Northern Europe, and the least in South America, Southeast Asia and Africa (excluding South Africa). Here genetic causes could contribute, but also environmental factors, as evidenced by the fact that the industrialization of Hong Kong and Japan the disease is becoming more common. In North America and Europe are more common in urban areas than in the countryside. Traditionally, the rare in underdeveloped areas. Poor living conditions decrease the risk of the development of Crohn's disease. Excessive hygiene, as it appears in the western world could interfere with the immune response, and contribute to the onset of the disease. Breast-feeding reduces the probability that the progeny develop the disease.
Stress
Setbacks, chronic stress and depression can worsen the disease, but are not the primary cause. If the disease is in a quiet phase wrong, it can thereby move in an acute inflammatory phase. Excessive activity of the hypothalamic-pituitary-adrenal stress can exacerbate gastrointestinal inflammation. The substance involved in stress, CRF, and the impact of stress on mast cells causes bacteria cause more damage to the intestinal wall.
Smoking: Smoking is a risk factor in the development of Crohn's disease and slows healing. Smokers tend to have Crohn's disease compared with non-smokers. The odds ratio was 1.76. Stopping smoking reduces the number of revivals of Crohn's disease by 40%. It appears that people with Crohn's disease who smoke are more often operated on their guts and feel less well. Possible explanations are that smoking promotes the formation of clots in the blood vessels (thrombosis) of the intestine, which makes an ignition may occur, inflammation of the wall of blood vessels in the intestines which is accompanied by granuloma formation, and other yet unidentified immunological effects.
Appendectomy (surgical removal of the appendix) can worsen the course of the disease. It is a risk factor for the formation of strictures (constrictions) into the intestine.
Crohn's disease diagnosis
The diagnosis often takes several months. Sometimes it is in the beginning not clear whether there really is a chronic inflammatory bowel disease. On the other hand, it happens that the diagnosis is made during an (emergency) operation for instance because a appendicitis is suspected.
- Case history: First the doctor will ask supplementary try to get a better picture of the complaints. These are questions about the nature and duration of abdominal pain and diarrhea, possibly weight loss, disorders of the anus and symptoms of skin, joints and eyes. It is also usually asked to avoid these problems in the area or with relatives.
- Physical examination: Although often no abnormalities are found, the physical examination remains important. The weight, the overall impression and the examination of the eyes, joints, skin and in particular of the stomach and the anus are important for diagnosis and treatment. In addition, in view of fistulas or other abnormalities around the anus.
- Laboratory tests: First, the blood is examined. Blood tests usually consists look out if there is anemia (hemoglobin or Hb) of inflammation (erythrocyte sedimentation rate or BSE or CRP) or protein loss through the intestine (albumin). An additional tool in the diagnosis is the measurement of antibodies against baker and brewer's yeast (called anti-Saccharomyces cerevisiae antibodies, either ASCA). These antibodies are found in about 70% of the Crohn's patients. Positive ASCA antibodies i.c.m. negative p-ANCA (perinuclear antineutrophil cytoplasmatic antibodies) antibodies, is suggestive of Crohn's disease. If the other (ASCA negative and positive p-ANCA), this could fit in ulcerative colitis. The blood test shows no other abnormalities, then IBD less likely, but not impossible. An increasingly important investigation is a stool research that looks at the calprotectin values. These values indicate how active the inflammation and are more valuable than a blood test. The stool is usually examined in order to rule out other causes of the symptoms. This may for example be an infection by bacteria, parasites, or worms. Sometimes it will be asked to save on the stools for a few days in order to investigate whether the fat content is increased herein. That may be a sign of impaired fat absorption.
- Colonoscopy: Endoscopy plays an increasingly important role in the study of people with symptoms suggestive of IBD. With the aid of a flexible endoscope, a thin and flexible hose, the interior of the large intestine and a part of the small intestine can be visualized. In this way, or can be made visible, and where there is an inflammation. It can be removed for examination under the microscope with tweezers small pieces of tissue (biopsies). Before a endoscopy can take place the gut must first be emptied as much as possible. For example, an optimal search can take place of the inside of the intestinal wall. This emptying usually starts the day before the examination. The patient drinks a laxeervloeistof and that day may continue to use only liquid food. The day of the examination, the patient gets a preparation. Then he / she to drink up to 4 liters of water with a saline solution to remove the residual waste. If the intestines of the patient have not yet been cleaned, it will just before the research is still an enema can be administered. Through the anus is hereby introduced a fluid to remove the remaining feces.
- Gastroscopy: a similar investigation as an endoscopy, but then through the mouth to expose the stomach and duodenum for research.
- X-ray or MRI scan: This is mainly performed for the examination of the small intestine. Usually, by a thin probe, which is brought through one nostril into the stomach, contrast agent (barium) is brought into the small intestine. Then pictures or scan made. In this way can be investigated whether there is an inflammation or a narrowing (stenosis) is present in the small intestine and whether there are any connections between the intestines and other organs (fistulas). Also applies here again that the gut must be drained as well as possible. Also a picture of the colon can be made. This is called a barium enema. Here is a paste with barium is introduced via a small tube through the anus into the colon. Then, X-rays are made. For a complete picture of the colon and small intestine is the barium drink.
- Ultrasound and CT scan may have a role in determining certain complications of the disease, but are rarely needed.
Crohn's disease treatment
Medications
It will often be started with a treatment medicine after the diagnosis. These drugs have on the one hand to inhibit the inflammation. On the other hand they suppress the formation of new infections. In addition, drugs are often prescribed in order to prevent diarrhea and anemia. A Crohn's patient so should generally long-term treatment with drugs and prolonged supervised by a specialist. The treatment of Crohn's disease is called symptomatic, aimed at inhibition of the ignition. This means that the treatment suppresses the signs and symptoms, but the disease itself does not heal. Approximately 80% of Crohn's patients used long-term medications. In addition to beneficial effects, in some cases, side effects can also occur. This is one of the reasons why, for long-term use of drugs often the blood is monitored.
The choice of medication is dependent upon the severity of the inflammation and of the place. For example, there are drugs that act mainly in the small intestine. Other works precisely in the last part of the colon.
Medications may be administered in different ways: through the mouth, through a blood vessel or through the anus with a suppository, an enema or a subcutaneous injection. In addition, there are drugs that act at a particular site in the body and others who work in the whole body. The route of administration of a drug is dependent on the location of the inflammation is located.
The main drugs are:
- 5-ASA preparations, sulfasalazine (Salazopyrine) and mesalazine (Claversal, Pentasa and Salofalk). The active ingredient of these agents is 5-aminosalicylic acid (5-ASA), anti-inflammatory, in tablet form or enema.
- Azathioprine: An immunosuppressant. It takes an average of 2 to 3 months to give the therapy outcome. Tablet.
- Methotrexate: Affects the immune system, anti-inflammatory. Response after 6-8 weeks. Usually intravenously.
- Infliximab (TNF-alpha inhibitors): One of the newer agents from the group of biologicals that are registered for the treatment of severe active Crohn's disease in patients that do not respond fully to treatment with prednisone. Also known as Remicade. To be administered by infusion. Affects the immune system. Very expensive in the Netherlands fully reimbursed through the GVS in Belgium and 95% repaid through the "insurance fund".
- Adalimumab (Humira) and certolizumab pegol (TNF inhibitor) as an alternative to infliximab.
- Antibiotics such as ciprofloxacin, rifampicin and metronidazole in cases of fistula formation, and antibiotics such as Tazocin, TAVANIC and Tiberal in case of inflammation.
- Tioguanine, a cytostatic. After years of off-label use was recorded in May 2015 in the Netherlands under the trade Thiosix®.
- Study of patients with Crohn's disease, conscious pigs with lash the parasitic worm (Trichuris suis) were infected, showed improvement in the symptoms to at about three-quarters of patients.
Dietary Supplements
From a Cochrane meta-analysis from 2007 showed that fish oil supplements are safe but probably not effective therapy to maintain remission in Crohn's disease.
Operation
In some cases it is necessary to carry out an intestinal operation. This may for instance be the case of a severe narrowing of the intestine or when it does not respond to medication. The approach to the Crohn's disease and ulcerative colitis is hereby clearly different. In Crohn's disease, one operates as sparingly as possible. If there is an operation, one often takes the last part of the small intestine and the beginning of the large intestine road (ileocaecal resection). One can also remove a narrowing (stenosis), carry out a fistula surgery or an incision abscess. In some people with Crohn's disease or ulcerative colitis is sometimes necessary to apply a temporary or permanent artificial intestine exit: a stoma.
Course of the disease
Problem in Crohn's disease is the uncertainty about the future course. Sometimes the inflammation is restricted to a small part of the intestine. In other cases, the ignition covers a much larger portion of the intestine. There are major differences in severity and nature of the complaints and the outcome of treatment. Most patients after treatment can lead a normal life. They have relatively few complaints. The quality of their life is comparable to that of people without IBD. However, a number of patients with IBD has a very hard to control inflammation. This requires extensive drug therapy. Sometimes hospitalization is necessary and surgery. Also, most patients should be regularly checked by a specialist. This is a general internist, a gastroenterologist, a pediatrician and / or a surgeon. Especially when drug use is regulated blood tests. In patients who do not respond well to treatment is sometimes needed again an endoscopic examination.
- Pregnancy: In general, women with IBD as much chance of a normal pregnancy as women without IBD. Some women with Crohn's disease who have had surgery or fistulas in the pelvis, are less likely to become pregnant. The course of the disease during pregnancy is sometimes better, sometimes worse, but usually equals the course without pregnancy. There are many medications that are harmful to the unborn child (eg, prednisolone). Always consult your doctor! The accompaniment of the pregnancy, which will be especially given the growth of the child is usually done by a gynecologist.
- Complications: Most people with chronic bowel disease respond favorably to treatment. If not reduce the discomfort after treatment, or even worsen, or if the ignition spreads outside the intestinal tract which is considered as a complication of IBD. Complications are seen at around 10 to 20% of the patients. Extension of the disease outside the colon relates mainly to inflammations of the joints, skin, eyes, and the liver. Flare joint pain often runs parallel with a revival of intestinal inflammation.
- Malignant degeneration: It has been demonstrated in several studies (not too big) relationship between ulcerative colitis and colorectal cancer. Crohn's disease is this relationship proved less robust, there may be a relationship with small intestine. In general, it applies that the risk of colorectal cancer is increasing at an early age at diagnosis IBD, longer duration of the symptoms, and more severe course of the IBD. Possible treatment with 5-ASA has a protective effect against the development of colorectal cancer.