Crohn's disease

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Classification according to ICD-10
K50.- Crohn's disease [regional enteritis] [Crohn's disease]
K50.0 Crohn's Disease of the Small Intestine I5642
K50.1 Crohn's Disease of the Colon I5646
K50.8 Other Crohn's disease
K50.9 Crohn's disease, unspecified
ICD-10 online (WHO version 2019)

The Crohn's disease or Crohn's disease belongs to the group of chronic inflammatory bowel disease . It is a chronic granulomatous inflammation of unknown cause (possibly an autoimmune disease ) that can occur throughout the digestive tract from the oral cavity to the anus. Preference is attacked by the characteristic swelling and inflammation of the terminal ileitis , the lower are the small intestine ( terminal ileum ) and the large intestine (colon) , more rarely the esophagus ( esophagus ) and the mouth. The discontinuous, segmental infestation (so-called skip lesions ) of the intestinal mucosa is typical of Crohn's disease : At the same time, several areas are affected, which are separated from each other by healthy intestinal sections.

Other names for the disease are regional enteritis , regional enteritis Crohn , regional enterocolitis and sclerosing chronic enteritis ; Common abbreviations are MC (Crohn's disease) and CD (Crohn's disease) .

history

The clinical picture was first described in 1932 by the American gastrointestinal specialist Burrill Bernard Crohn (1884-1983) and his colleagues Leon Ginzburg and Gordon Oppenheimer, who brought together the clinical and pathological details in fourteen patients, all at the Mount Sinai Hospital in New York had been operated on. This first publication was entitled Regional ileitis: a pathological and clinical entity .

The clinical symptoms had already been described several times, first in 1904 by the Polish surgeon Antoni Leśniowski (1867–1940, English ) and in 1907 by the British surgeon and gastroenterologist Berkeley GA Moynihan. However, a description of the disease by the Italian doctor Giovanni Battista Morgagni from 1761 can also be interpreted as a representation of M. Crohn.

B. Crohn originally named the disease as Ileitis terminalis after its location in the terminal ileum, but renounced the term in order to “avoid associations with agony and death” and subsequently named it as Ileitis regionalis . The term Crohn's disease was then enforced by British doctors at a conference in Prague in order to be able to better familiarize the students with the disease, despite the protest of B. Crohn.

frequency

In the western industrialized countries, the incidence (the annual number of new cases) of Crohn's disease is around 7–8 per 100,000 inhabitants, the prevalence (the number of infected people) is around 150 per 100,000. The prevalence in Germany is currently around 300 per 100,000. The number of diseases has increased over the past twenty years. Until the end of the 20th century it was mainly found in the western world (North America, Europe, Oceania), since the end of the 20th century the incidence has been falling or stagnating there, but is increasing in Asia, South America and Africa, possibly in connection with lifestyle changes.

In North America and Europe alone, more than 3.5 million people suffer from chronic inflammatory bowel disease (Crohn's disease, ulcerative colitis).

Both sexes are equally affected, mostly young adults between the ages of 15 and 35 and older people from the age of 60 years. A familial accumulation can be observed. Germany has one of the highest prevalence rates in the world.

Development of Crohn's disease

The cause , development and development of Crohn's disease are not clear; however, a number of circumstances are known which are of importance in the development of the disease. Burrill B. Crohn considered Crohn's disease to be a disease caused by intracellular bacteria or viruses. Today, Crohn's disease is considered an autoimmune disease in the broader sense of the word, as the intestinal mucosa is damaged by an immune reaction against the commensal intestinal flora .

The good response of the disease to immune system-inhibiting drugs such as cortisone and azathioprine as well as the lack of evidence of a specific pathogen speak in favor of this classification . Perinuclear anti-neutrophil cytoplasmic antibodies (p- ANCA ) were serologically identified as autoantibodies in Crohn's disease (around 20% of patients) . As with many other autoimmune diseases, the development of Crohn's disease is poorly understood, which is why it cannot be treated causally, but only symptomatically ( immunosuppressive or immunomodulating ).

According to a research report by the German Crohn's Disease Association (DCCV eV) from September 15, 2011, “Failure of the innate defense against intestinal bacteria is the trigger for the diseases […]. The chronic inflammation is therefore to be understood as a reaction and response to this immune deficiency. "

genetics

There may be a hereditary predisposition to the disease, as several genetic factors increase the risk of it developing. For some genes it has been shown that certain polymorphisms are probably causally related to Crohn's disease, e.g. B. NOD2 ( NOD2 receptor), IL23R ( chromosome 1p31) and ATG16L1 , DLG5 and NELL1 (chromosome 11p15.1). A reduced number of gene segments that are responsible for the production of beta- defensins also seems to have an effect. Defensins are a type of natural antibiotics that fight off bacteria in the mucous membranes. People with Crohn's disease in the colon have only three defensin-producing gene segments on chromosome 8. Healthy people generally have four of them; accordingly, the defensin level in their mucous membrane is also higher. However, this relationship does not exist for the much more common Crohn's disease in the small intestine.

Barrier disorder

There are many indications that the barrier between the intestinal lumen and the organism is defective in at least some of Crohn's disease patients . Specific indications of this barrier defect can be found e.g. B. in the lack of anti-infectious peptides (defensins) in the mucus (mucus) that is deposited on the intestinal mucosa. In addition, the sealing connections between the epithelial cells of the intestinal mucosa are often "leaky", i.e. H. no longer functional and diminished in number. It is unclear whether the controlled cell death ( apoptosis ) of many epithelial cells is a primary or secondary phenomenon and is therefore the underlying cause of the clinical picture or only contributes to the chronicity of the inflammation. Due to the defect in the barrier function - in contrast to the situation in healthy people - bacteria of the normal intestinal flora reach the epithelium of the intestinal mucosa in large numbers and sometimes also penetrate the intestinal wall , where they trigger inflammation as part of the body's defense, which the Damage the barrier even further, so that further bacteria of the intestinal flora penetrate the intestinal wall in a vicious circle and further fuel the inflammation. The primary defect of the barrier disorder can be at least partially genetic. The production of certain alpha-defensins in Crohn's disease patients with mutations characteristic of Crohn's disease in a gene (NOD2 / CARD15), which codes an intracellular sensor for bacterial structures, is even more reduced than in Crohn's disease patients without this genetic defect , although defensin production is already drastically reduced compared to healthy people even in Crohn's disease patients without this genetic defect. This applies to the small intestine ; if it is located in the large intestine , the number of beta-defensin genes and, accordingly, beta-defensin synthesis are reduced. Thus, the various defensive defects explain the different localizations of the disease.

Iron uptake disorder and anemia

There is an overproduction of a factor hepcidin , which is a functional inhibitor of the intestinal iron uptake transport protein ferroportin , which prevents the intestine from being able to absorb iron from food. According to current clinical knowledge, it is possible to use this system with an anti-TNF-alpha treatment with infliximab - but not with a conventional basic therapy e.g. B. with azathioprine - to influence. A system-related therapy that starts at the BMP6 was developed in the mouse model.

Mycobacterium avium subsp. paratuberculosis

There is some evidence that Mycobacterium avium subsp. paratuberculosis (MAP) together with special variants of the CARD15 / NOD2 gene can cause chronic inflammatory bowel disease in humans such as paratuberculosis in animals. Cattle suffering from paratuberculosis and Crohn's disease patients have an identical peculiarity in the CARD15 / NOD2 gene, which has a negative influence on defensin production (production of natural antibiotics). MAP triggers chronic intestinal inflammation in cattle and other animals and causes inflammatory reactions and tissue damage in sterile human intestinal sections. Mycobacterium avium paratuberculosis induces specific antibodies in humans. These antibodies are found in the blood of up to two-thirds of all Crohn's disease patients.

Studies are currently underway to determine whether patients can be treated successfully with a combination of antibiotics. Multi-antibiotic therapy has led to initial treatment successes in the USA and Australia. MAP has been detected several times in various dairy products. A percentage survives the conditions of pasteurization , the process by which the vast majority of milk is treated for dairy products.

Other factors

Excessive hygiene

This article or the following section is not adequately provided with supporting documents ( e.g. individual evidence ). Information without sufficient evidence could be removed soon. Please help Wikipedia by researching the information and including good evidence.

It is unclear which environmental factors lead to the widespread development of Crohn's disease in societies with a high hygienic standard. An infestation with certain parasites - for example worms - may lead to a specific modulation of the immune response , which prevents the inflammatory reaction from recurring chronically. There are other hypotheses, such as damage to the intestinal barrier through increasing exposure to detergents such as soaps, plasticizers or emulsifiers , which could contribute to damaging the barrier function of the intestinal wall and thus promoting the penetration of bacteria from the normal intestinal flora. It is probably secondary that the intestinal flora is changed in Crohn's disease patients: Compared to healthy people, there is a significant reduction in the number of different bacterial species.

Smoke

The risk of developing Crohn's disease is twice as high for smokers as for non-smokers. Quitting smoking usually has a positive effect on the course of the disease or on the recurrence rate after an operation.

nutrition

Associations with a specific diet that were previously suspected, such as increased use of refined types of sugar in MC patients, are now regarded as secondary, as many Crohn's disease patients have a generally reduced absorption and thus poorer food utilization due to the inflammation in the small intestine.

Psychosomatics

According to the guidelines for Crohn's disease, it is not a psychosomatic illness. Stressful life events, stress and mental disorders are therefore not the cause of this chronic inflammatory bowel disease. However, psychosocial stress can lead to a considerable degree of triggering or intensification of symptoms. It is assumed that in the case of inflammatory bowel diseases, psychosocial stress also leads to a dysregulation of the immune response and - with the appropriate predisposition - to activation of the disease. This stress can lead to renewed inflammation in Crohn's disease patients.

Feiereis deals in detail with the importance of psychological factors for etiology and pathogenesis in the standard work Psychosomatic Medicine published by Uexküll and others with numerous further literature references . He suggests considering the psychological findings in their various components and differentiating them as belonging to the premorbid personality structure , to psychodynamics , to the factors triggering a relapse and / or to the disease-dependent characteristics.

Symptoms

Typical symptoms of Crohn's disease are abdominal pain and diarrhea, sometimes bloody, which indicates defects in the mucous membrane ( ulcer) . The pain occurs particularly often in the right lower abdomen and often after eating or before a bowel movement. Also, fever , weight loss, loss of appetite, nausea and vomiting may occur. Growth retardation can be the only symptom, especially in children. Fistulas or abscesses on the anus can also be caused by Crohn's disease. Many patients, however, have different types and perceptions of symptoms. Most laboratory tests show inflammation with an increase in white blood cells and anemia . The symptoms usually come on in flares. Such an episode usually lasts for several weeks. Symptoms that only last a few days are in very few cases relapses of Crohn's disease.

Extraintestinal manifestations also occur in up to 50 percent of Crohn's disease patients . The joints are most often affected; it can cause arthralgia and arthritis come. In the context of Crohn's disease, skin changes in the form of erythema nodosum or pyoderma gangrenosum are also possible. It can also lead to rosacea and inflammation of the eye (such as uveitis ). The manifestations outside the intestinal tract (extraintestinal symptoms) can rarely occur months to years before the intestinal symptoms. Usually, extraintestinal symptoms go away when Crohn's disease is treated as an underlying condition. In addition to the disease itself, side effects of the medication can also trigger extraintestinal manifestations.

Complications

  • Mechanical intestinal obstruction (ileus): Initially often caused by narrowing of the affected intestinal segment during the inflammatory process, in the later stage by fibrous strictures . An ileus occurs in around 20 to 30 percent of patients during the course of the disease.
  • Fistula (connection of the intestine with other organs or the body surface): Fistulas occur quite frequently in the chronic course and can be quite different: connection of the intestine with the body surface (cutaneous), course between the intestine and genital organs (enteroenteritic / enterovaginal), course between Intestine and urinary bladder (enterovesical), exit of the fistula in the area of ​​the anus (peranal), rectal. On the other hand, fistulas into the free abdominal cavity are less common, as the area around the intestine is usually strongly overgrown.
  • Abscess (encapsulated collection of pus): intra- and retroperitoneal abscesses occur.
  • intestinal bleeding
  • Toxic megacolon : (= abnormal expansion of the large intestine caused by "poison") rather seldom in Crohn's disease, but more common in ulcerative colitis
  • Carcinoma : There is an increased risk for colon carcinoma in particular (but also here more with ulcerative colitis).
  • Osteoporosis or osteopenia : Changes in bone density often occur as a consequence of malabsorption and as a side effect of cortisone therapy .
  • Gallstones (due to impaired liver and intestinal circulation)
  • Urolithiasis (urinary stone disease): caused by an increased absorption of oxalate from the intestine. The cause of this is a bile acid loss syndrome due to the shortened and inflammatory altered terminal ileum , so that calcium , which normally binds oxalate in the intestine, is now bound to the bile acids .
  • Exudative gastroenteropathy

Problem load and supply options

Disease-specific symptoms (e.g. diarrhea) can have a major impact on the everyday life of those affected. In addition, anxiety and depression often develop. Accordingly, the quality of life of those affected is often reduced. Psychological stress can also negatively affect the course of the disease. With regard to these different problem areas, when coping with illness it is important to look at the entire life situation.

For this purpose, an online questionnaire was developed at the University of Lübeck that evaluates 22 disease-related problem areas and thus gives patients an overview of their current health situation and their personal problem profile, with computer-generated suggestions for possible support offers. The benefit of the questionnaire and its effectiveness on the quality of life of those affected were confirmed in a randomized controlled study.

Diagnosis

Ultrasound image of Crohn's disease with wall thickening and increased blood flow in a loop of the small intestine
Endoscopic image of Crohn's disease. Paving stone relief in the terminal ileum
MR enteroclysis in Crohn's disease in the terminal ileum: Significant wall thickening and contrast medium uptake in the affected section of the intestine. This is also atypically stretched by the changes.

Pathology / morphology

Fine tissue section, Crohn's disease

Macroscopically, the following changes are characteristic:

  • Garden hose phenomenon: segment stenosis caused by fibrosis
  • Cobblestone phenomenon: Inflammatory thickened areas of the mucous membrane alternate with deeply ulcerated areas of the mucous membrane, which creates a cobblestone-like appearance.
  • Inflammatory conglomerate tumor: Different sections of the intestine stick together.

Histologically (histologically) one can see above all an accumulation of lymphocytes , (eosinophilic) granulocytes and histiocytes in the biopsy of the inflamed intestinal tissue. Adjacent lymph nodes are usually enlarged. Granulomas often form (inconsistent and by no means pathognomonic), which can be divided into two types: epithelial cell granulomas and microgranulomas (small and without central necrosis).

Differential diagnostics

Crohn's disease is sometimes difficult to differentiate from ulcerative colitis , in some cases it is not possible at all (for the differences see also the table under inflammatory bowel diseases ).

In addition, it is necessary to exclude a number of other diseases, which is done with the help of imaging ( sonography , CT ) and additional examinations:

Activity index

The Crohn's Disease Activity Index (CDAI) can be used to quantify disease activity. The CDAI was developed by WR Best and colleagues in 1976. The index is made up of eight variables, each of which is multiplied by a factor and then added up. The components of the CDAI and their weighting factors are as follows:

Clinical or laboratory variable Weighting factor
Number of unformed bowel movements in the past seven days x 2
Abdominal pain (0 = none, 1 = slight, 2 = medium, 3 = severe) as the sum of the last seven days x 5
General condition (0 = good, 1 = impaired, 2 = bad, 3 = very bad, 4 = unbearable) as the sum of the last seven days x 7
Presence of complications * x 20
Symptomatic diarrhea treatment ( loperamide or similar) x 30
Abdominal resistance (0 = no, 2 = questionable, 5 = certain) x 10
The hematocrit deviates from 47% in men and 42% in women x 6
Percentage deviation from the standard weight x 1

* One point is added for each of the following complications:

Remission in Crohn's disease is defined as a CDAI less than 150. A relapse is defined from 220 points and a CDAI greater than 450 has a severe relapse. In daily practice, however, this index is used less because it is complicated and often too inflexible for individual treatment. It is mainly used in scientific research.

The Harvey-Bradshaw Index was developed in 1980 as a simplified version of the CDAI. It consists only of clinical parameters:

  • General condition (0 = good, 1 = impaired, 2 = bad, 3 = very bad, 4 = unbearable)
  • Abdominal pain (0 = none, 1 = slight, 2 = medium, 3 = severe)
  • Number of liquid bowel movements
  • Abdominal resistance (0 = no, 1 = questionable, 2 = certain, 3 = certain and painful)
  • Complications: arthralgia, uveitis, erythema nodosum, oral aphthae, pyoderma gangrenosum, anal fissure, new fistula, abscess (1 point each)

The first three points refer to the previous day.

After adding up, <5 points correspond to remission, 5–7 to a mild relapse, 8–16 to moderate activity and> 16 to a severe relapse.

therapy

In the treatment of Crohn's disease, a basic distinction is made between relapse therapy and maintenance of remission. The aim of relapse therapy is to alleviate the acute symptoms when the symptoms worsen, i.e. when there is a relapse . With remission-maintaining therapy, the number of relapses is to be reduced, that is, the time of remission is to be extended. The conservative (medication) and operative therapeutic approaches complement each other. Basically, one tries to avoid resections of the bowel, but in some situations surgery is superior to internal medicine. This is especially the case with fistulas, stenoses (scarred constrictions) and life-threatening complications.

There is currently a scientific debate going on as to whether the goal of therapy should be freedom from symptoms for the patient or the complete absence of inflammation (so-called mucosal healing). Proponents of Mucosal Healing argue that this could prevent both a loss of function of the bowel and frequent relapses and the development of cancer. Evidence for these hypotheses is still pending.

For diagnosis and therapy, there are evidence-based guidelines of the German Society for Digestive and Metabolic Diseases and also at European level the European evidence-based consensus on the diagnosis and management of Crohn's disease for diagnosis, general therapy and special cases.

Feiereis considers a multi-dimensional approach to be necessary, which, depending on the case structure, consists of “medicinal, dietary, relaxation and psychotherapeutic, surgical, rehabilitative and follow-up procedures” and requires the coordination of a “ group of doctors who work closely with one another in consultation ” .

Acute episode

In relapse therapy, a distinction is made between mild to moderate relapses and moderate to severe relapses. In addition, the localization of the disease, especially in Crohn's disease, which can affect the entire gastrointestinal tract, plays an important role in the treatment decision. In the case of perianal involvement with fistulas or abscesses, other therapies are used.

  • Dieting, perhaps with parenteral nutrition or fully absorbable, low-fiber liquid foods, can relieve symptoms during a severe flare-up. Especially in children, a relapse can be treated with enteral tube feeding alone . There are also studies in adults showing that enteral tube feeding can be used for treatment. The advantage of this form of treatment is that it avoids the side effects of glucocorticoids . However, with this form of therapy you have to insert a feeding tube through your nose every day , which most patients find very uncomfortable.
  • Glucocorticoids are the main drugs used in the treatment of Crohn's disease. Even in the most severe cases, they lead to remission in half of all patients. With a mild to moderate relapse, the symptoms improve in around 90 percent of all patients. If the right half of the large intestine and the terminal ileum are affected , budesonide , a cortisone preparation that works primarily there and causes few side effects in the rest of the body, can also be used. If the rectum is infested , cortisone can also be used as an enema, which also causes fewer side effects. Patients who take glucocorticoids for more than three months a year are usually treated with remission-maintaining therapy.
Pathological preparation of a surgically removed piece of intestine
  • In contrast to mesalazine (5-aminosalicylic acid), salazosulfapyridine can definitely lead to an improvement in the case of a mild to moderate attack in the left colon. Although around half of all Crohn's patients are prescribed one of these two drugs, it has now been shown that the effectiveness is poor. However, investigations into whether subgroups of patients might benefit from mesalazine are still pending.
  • Metronidazole and ciprofloxacin can mainly be used to treat fistulas.
  • In severe or refractory attacks, TNF blockers such as infliximab and adalimumab are used in particular .
  • Surgical therapy with resection of affected intestinal sections does not lead to definitive healing, but in more severe cases it may be essential to avoid or treat severe complications such as stenoses, fistulas, abscesses or perforations .

Remission maintenance

There is currently no drug that would be used in every patient with Crohn's disease to prevent relapses. While mesalazine is very effective in ulcerative colitis , in Crohn's disease it has a relapse-suppressing effect only in operated patients.

According to the current guidelines, patients who have severe relapses, in whom frequent relapses occur, but also patients in whom the disease flares up again and again when trying to stop cortisone, should receive remission-maintaining therapy. There are currently three drug groups that can be considered:

  • Immunosuppressants : The immunosuppressants that have been shown to be effective in Crohn's disease are azathioprine , 6-mercaptopurine and methotrexate . These drugs can cause severe side effects in individual cases, so that unwanted effects must be checked regularly at the start of therapy. If these checks are carried out, the immunosuppressants can be taken by those affected for several years or even decades. Treatment with azathioprine must be carried out under constant medical control and monitoring of the blood count, as it has an effect on the blood-forming system.
  • TNF-α blockers : Infliximab and adalimumab are approved for the treatment of Crohn's disease in the EU , and certolizumab in Switzerland . Tuberculosis can be reactivated during therapy with TNF-α blockers , so that an infection with tubercle bacteria must be excluded or treated before therapy with these drugs .
  • Integrin antagonists: Vedolizumab

Ustekinumab : IL12 / IL23 antagonist

Accompanying therapies

Due to the intestinal disease, some patients with Crohn's disease suffer from malnutrition and malnutrition . This can have different causes. On the one hand, in severe cases, the disease causes the intestine to insufficiently absorb nutrients ( malassimilation ). In addition, patients have an increased energy requirement due to the inflammation or they lose iron due to intestinal bleeding . The iron metabolism is also impaired by the inflammation. In addition, some people avoid certain foods that they think may make the condition worse. This, too, can lead to malnutrition and nutritional deficiencies. Thus, in addition to the actual illness, nutrient deficiencies ( iron , vitamin B 12 , zinc ) and malnutrition (e.g. with additional drinking food ) must be treated. The inflammation and ingestion of glucocorticoids can lead to osteoporosis in Crohn's disease . This complication is also often treated concomitantly.

It is currently not entirely clear whether psychotherapy and relaxation methods (e.g. behavior therapy , mind body therapy , progressive muscle relaxation , autogenic training , Feldenkrais method ) are helpful. They do not seem to help improve the condition, but can be used if anxiety disorders , depression, or excessive stress occur as a result of the condition.

Alternative and Complementary Therapies

Acupuncture may be helpful as an accompanying measure.

The special carbohydrate diet has repeatedly anecdotally achieved great success in treatment and is said to have led to complete remission. The group of poly- and disaccharides is completely removed from the diet. Its effectiveness has now been proven in several studies. A further development of the special carbohydrate diet was recently developed at the University of Massachusetts Medical School and successfully tested in a study with patients suffering from Crohn's disease and ulcerative colitis .

There is insufficient scientific evidence to suggest that the following alternative or complementary therapy options are useful in the treatment of Crohn's disease:

  • Lutz diet , a low-carbohydrate and high-fat diet according to Wolfgang Lutz
  • According to an observational study, cannabis has a beneficial effect
  • A pilot study found that the administration of mastic , the resin of the mastic tree, has a positive effect
  • Treatment with eggs of the pig whipworm ( Trichuris suis ) has been considered. First there was a small scientific study. A large study ran between 2010 and 2013. It found insufficient effect.

forecast

It is a chronic disease with a high rate of recurrence, i.e. recurrence. In most cases, complications require surgical treatment, which, however, does not lead to a definitive cure. However, in almost half of patients, the severity of the disease decreases significantly over time. While one in three experiences relapses with no symptoms in between, around one fifth of all patients report constant activity without periods of symptom-free life. Compared to the normal population, patients with Crohn's disease have a mathematically slightly higher mortality .

literature

  • Hubert Feiereis: Crohn's disease . In: Thure von Uexküll u. a. (Ed.): Psychosomatic Medicine . 3. Edition. Urban & Fischer, Elsevier 1986, ISBN 3-541-08843-5 , pp. 798-814 .
  • F. Grange, F. Djialali-Bouzina, AM Weiss, A. Polette, JC Guillaume: Corticosteroid-resistant pyoderma gangrenosum associated with Crohn's disease: rapid cure with infliximab. In: Dermatology. 2002; 205, pp. 278-280, PMID 12399677 .
  • H. Herfarth, F. Obermeier, T. Andus, G. Rogler, S. Nikolaus, T. Kuehbacher, Stefan Schreiber : Improvement of arthritis and arthralgia after treatment with infliximab (Remicade) in a German prospective, open-label, multicenter trial in refractory Crohn's disease. In: Am J Gastroenterol . 2002; 97, pp. 2688-2690, PMID 12385472 .
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  • A. Menozzi, C. Pozzoli, E. Poli, M. Lazzaretti, A. Cantoni, D. Grandi, E. Giovannini, G. Coruzzi: Effect of the macrolide antibacterial drug, Tylosin, on TNBS-induced colitis in the rat. In: Pharmacology . 2005; 74, pp. 135-142, doi: 10.1159 / 000084324 .
  • EA Petrelli, M. McKinley, FJ Troncale: Ocular manifestations of inflammatory bowel disease. In: Ann Ophthalmol. 1982; 14, p. 356, PMID 6125121 .
  • DK Podolsky: Inflammatory Bowel Disease. In: N Engl J Med. 2002; 347, pp. 417-429, PMID 12167685 .
  • D. H Present, P. Rutgeerts, S. Targan, SB Hanauer, L. Mayer, RA van Hogezand, DK Podolsky, BE Sands, T. Braakman, KL DeWoody, TF Schaible, SJ van Deventer: Infliximab for the treatment of fistulas in patients with Crohn's disease. In: N Engl J Med. 1999; 340, pp. 1398-1405, PMID 10228190 .
  • BE Sands, FH Anderson, CN Bernstein, WY Chey, BG Feagan, RN Fedorak, MA Kamm, JR Korzenik, BA Lashner, JE Onken, D. Rachmilewitz, P. Rutgeerts, G. Wild, DC Wolf, PA Marsters, SB Travers , MA Blank, SJ van Deventer: Infliximab maintenance therapy for fistulizing Crohn's disease. In: N Engl J Med. 2004; 350, pp. 876-885, PMID 14985485 .
  • M. Stoll, S. Schreiber: Crohn's disease: second disease-associated gene discovered. In: Biology in Our Time . 34 (4), 2004, pp. 208-209, ISSN  0045-205X .
  • SR Targan, SB Hanauer, SJ van Deventer, L. Mayer, DH Present, T. Braakman, KL DeWoody, TF Schaible, PJ Rutgeerts: A short-term study of chimeric monoclonal antibody cA2 to tumor necrosis factor alpha for Crohn's disease. Crohn's Disease cA2 Study Group. In: N Engl J Med. 1997; 337, pp. 1029-1035, PMID 9321530 .
  • J. Wehkamp, ​​J. Harder, M. Weichenthal, M. Schwab, E. Schaffeler, M. Schlee, KR Herrlinger, A. Stallmach, F. Noack, P. Fritz, JM Schroder, CL Bevins, K. Fellermann, EF Stange: NOD2 (CARD15) mutations in Crohn's disease are associated with diminished mucosal a-defensin expression. In: Good . 2004 Nov; 53, pp. 1658-1664, PMID 15479689 .
  • J. Wehkamp, ​​NH Salzman, E. Porter, S. Nuding, M. Weichenthal, RE Petras, B. Shen, E. Schaeffeler, M. Schwab, R. Linzmeier, RW Feathers, H. Chu, H. Lima Jr, K. Fellermann, T. Ganz, EF Stange, CL Bevins: Reduced Paneth cell {alpha} defensins in ileal Crohn's disease. In: Proc Natl Acad Sci USA . 2005 Dec 13; 102, pp. 18129-18134, PMID 16330776 .
  • SR Weiner, J. Clarke, N. Taggart, PD Utsinger: Rheumatic manifestations of inflammatory bowel disease. In: Semin Arthritis Rheum . 1991; 20, p. 353.

Web links

General

Commons : Crohn's Disease  - Collection of images, videos and audio files

Associations

Individual evidence

  1. ↑ Baumgart DC, Carding SR: Inflammatory bowel disease: cause and immunobiology. In: The Lancet . tape 369 , no. 9573 , 2007, p. 1627-1640 , doi : 10.1016 / S0140-6736 (07) 60750-8 , PMID 17499605 .
  2. ↑ Baumgart DC, Sandborn WJ: Crohn's disease. In: The Lancet . 2012, doi : 10.1016 / S0140-6736 (12) 60026-9 , PMID 22914295 .
  3. ↑ RJ Xavier, DK Podolsky: Unraveling the pathogenesis of inflammatory bowel disease . In: Nature . tape 448 , no. 7152 , 2007, p. 427-434 , doi : 10.1038 / nature06005 , PMID 17653185 .
  4. ^ Burrill B. Crohn, Leon Ginzburg, Gordon D. Oppenheimer: Regional ileitis: a pathological and clinical entity. In: Journal of the American Medical Association Volume 99, 1932: pages 1323-1329.
  5. ↑ a b c Sabine Schuchardt: Burrill B. Crohn remained true to his passion for a lifetime. In: Deutsches Ärzteblatt Volume 114, Issue 15 of April 14, 2017, page [52].
  6. ↑ BA Jacobsen a. a .: Increase in incidence and prevalence of inflammatory bowel disease in northern Denmark: a population-based study, 1978-2002 . In: Eur J Gastroenterol Hepatol. 2006 Jun; 18 (6), pp. 601-606, PMID 16702848 .
  7. ↑ a b c Gilaad G. Kaplan, Joseph JY Sung, Francis KL Chan, Justin CY Wu, Subrata Ghosh: Worldwide incidence and prevalence of inflammatory bowel disease in the 21st century: a systematic review of population-based studies . In: The Lancet . tape 390 , no. 10114 , December 23, 2017, ISSN  1474-547X , p. 2769–2778 , doi : 10.1016 / S0140-6736 (17) 32448-0 , PMID 29050646 ( thelancet.com [accessed December 7, 2018]).
  8. ↑ ernaehrung.de: Crohn's disease - clinical picture
  9. ↑ Kenneth Murphy, Casey Weaver: Janeway's Immunobiology . 9th edition. Garland Science, 2017, ISBN 978-0-8153-4551-0 , Chapter 15 Autoimmunity and Transplantation .
  10. ↑ Weakness in the immune system: New findings on the cause of inflammatory bowel disease ( Memento of November 24, 2011 in the Internet Archive ); dccv.de, press conference for Crohn & Colitis Day 2011, on September 15, 2011 in Leipzig.
  11. ↑ Gut flora: Dysbacteria marks the beginning of Crohn's disease aerzteblatt.de, March 13, 2014
  12. ↑ Gene variant protects against Crohn's disease. (No longer available online.) Aerzteblatt.de, October 27, 2006, archived from the original on February 12, 2007 ; Retrieved August 1, 2010 . Info: The archive link was inserted automatically and has not yet been checked. Please check the original and archive link according to the instructions and then remove this notice. @1@ 2Template: Webachiv / IABot / www.aerzteblatt.de
  13. ↑ Andre Franke, Jochen Hampe, Philip Rosenstiel, Christian Becker, Florian Wagner, Robert Häsler, Randall D. Little, Klaus Huse, Andreas Ruether, Tobias Balschun, Michael Wittig, Abdou ElSharawy, Gabriele Mayr, Mario Albrecht, Natalie J. Prescott, Clive M. Onnie, Helene Fournier, Tim Keith, Uwe Radelof, Matthias Platzer, Christopher G. Mathew, Monika Stoll, Michael Krawczak, Peter Nürnberg, Stefan Schreiber, Greg Gibson: Systematic Association Mapping Identifies NELL1 as a Novel IBD Disease Gene. In: PLoS ONE. 2, 2007, p. E691, doi: 10.1371 / journal.pone.0000691 , PMC 1933598 (free full text).
  14. ^ K. Fellermann, DE Stange, E. Schaeffeler, H. Schmalzl, J. Wehkamp, ​​CL Bevins, W. Reinisch, A. Teml, M. Schwab, P. Lichter, B. Radlwimmer, EF Stange: A chromosome 8 gene cluster polymorphism with low human beta-defensin 2 gene copy number predisposes to Crohn's disease of the colon. In: Am. J. Hum. Genet. 79 (2006), pp. 439-448.
  15. ↑ Crohn's disease: One gene copy too little weakens the defense. dkfz.de, July 17, 2006, accessed on August 1, 2010 (Press Release No. 59 of the German Cancer Research Center).
  16. ^ K. Fellermann, DE Stange, E. Schaeffeler, H. Schmalzl, J. Wehkamp, ​​CL Bevins, W. Reinisch, A. Teml, M. Schwab, P. Lichter, B. Radlwimmer, EF Stange: A chromosome 8 gene cluster polymorphism with low human beta-defensin 2 gene copy number predisposes to Crohn's disease of the colon. In: Am. J. Hum. Genet. 79 (2006), pp. 439-448.
  17. ↑ VN Drozdov, AI Parfenov, AA Lishchinskaia, KK Noskova, EV Tkachenko, GG Varvanina: [Clinical and diagnostic significance of gepsidin level in the regulation of iron metabolism in patients with inflammatory bowel disease] . In: Ėksperimental'nai ͡ a i klinicheskai ͡ a gastroėnterologii ͡ a (= Experimental & clinical gastroenterology) . No. 10 , 2011, p. 18-22 , PMID 22629694 .
  18. ↑ Zühre Kaya u. a .: Serum prohepcidin levels in children with solid tumors, inflammatory bowel disease and iron deficiency anemia . In: Journal of tropical pediatrics . tape 57 , no. 2 , April 2011, p. 120-125 , doi : 10.1093 / tropej / fmq058 , PMID 20601378 .
  19. ↑ Gaith Semrin et al. a .: Impaired intestinal iron absorption in Crohn's disease correlates with disease activity and markers of inflammation . In: Inflammatory Bowel Diseases . tape 12 , no. December 12 , 2006, pp. 1101-1106 , doi : 10.1097 / 01.mib.0000235097.86360.04 , PMID 17119383 .
  20. ↑ Pantelis Oustamanolakis, Ioannis E. Koutroubakis, Ippokratis Messaritakis, Niki Malliaraki, Aekaterini Sfiridaki, Elias A. Kouroumalis: Serum hepcidin and prohepcidin concentrations in inflammatory bowel disease . In: European journal of gastroenterology & hepatology . tape 23 , no. 3 , March 2011, p. 262-268 , doi : 10.1097 / MEG.0b013e328343b885 , PMID 21285884 .
  21. ↑ Robert J. Basseri et al. a .: Hepcidin is a key mediator of anemia of inflammation in Crohn's disease . In: Journal of Crohn's and Colitis . tape 7 , no. 8 , September 1, 2013, p. e286 – e291 , doi : 10.1016 / j.crohns.2012.10.013 , PMID 23219355 .
  22. ↑ Tyler Burpee et al. a .: Intestinal ferroportin expression in pediatric Crohn's disease . In: Inflammatory bowel diseases . tape 17 , no. 2 , February 2011, p. 524-531 , doi : 10.1002 / ibd . 21367 , PMID 20564534 .
  23. ↑ KK Noskova, AA Lishchinskaia, AI Parfenov, OV Kniazev, GG Varvanina, VN Drozdov: [Risk of development of clinical and pathogenetic features of anemia on the background of basic therapy of inflammatory bowel disease] . In: Ėksperimental'nai ͡ a i klinicheskai ͡ a gastroėnterologii ͡ a = Experimental & clinical gastroenterology . No. 10 , 2011, p. 12-17 , PMID 22629693 .
  24. ↑ Lijian Wang et al. a .: The bone morphogenetic protein-hepcidin axis as a therapeutic target in inflammatory bowel disease . In: Inflammatory bowel diseases . tape 18 , no. 1 , January 2012, p. 112-119 , doi : 10.1002 / ibd . 21675 , PMID 21351217 .
  25. ↑ a b Crohn's disease caused by mycobacteria: A suspicion becomes a certainty. European Institute of Food and Nutritional Sciences, 2/2009, pp. 21–24.
  26. ↑ Mpofu et al. a .: Microbial mannan inhibits bacterial killing by macrophages: a possible pathogenic mechanism for Crohn's disease. In: Gastroenterology. 2007 Nov; 133 (5), pp. 1487-1498.
  27. ↑ Crohn's patients should stop smoking. ( Memento of the original from February 28, 2014 in the Internet Archive ) Info: The archive link was inserted automatically and has not yet been checked. Please check the original and archive link according to the instructions and then remove this notice. DCCV , May 15, 2001, accessed February 24, 2014. @1@ 2Template: Webachiv / IABot / www.dccv.de
  28. ↑ Hubert Feiereis: Crohn's disease . In: Thure von Uexküll u. a. (Ed.): Psychosomatic Medicine . 3. Edition. Urban & Fischer, Elsevier 1986, ISBN 3-541-08843-5 , pp. 803-805 .
  29. ↑ K.-M. Keller, D. Weitzel, U. Lörcher: Diagnostics of chronic inflammatory bowel diseases . In: Monthly Pediatrics. Vol. 152, No. 2, 2004, pp. 122-132.
  30. ↑ a b K. Kemp, J. Griffiths, K. Lovell: Understanding the health and social care needs of people living with IBD: a meta-synthesis of the evidence. In: World journal of gastroenterology. 2012; 18 (43), pp. 6240-6249, PMID 23180944 .
  31. ^ LA Graff, JR Walker, L. Lix, I. Clara, P. Rawsthorne, L. Rogala, N. Miller, L. Jakul, C. McPhail, J. Ediger, CN Bernstein: The relationship of inflammatory bowel disease type and activity to psychological functioning and quality of life. In: Clinical gastroenterology and hepatology. 2006; 4 (12), pp. 1491-1501, PMID 17162241 .
    LA Graff, JR Walker, CN Bernstein: Depression and anxiety in inflammatory bowel disease: a review of comorbidity and management. In: Inflammatory bowel diseases. 2009; 15 (7), pp. 1105-1118, PMID 19161177 .
  32. ↑ MS Sajadinejad, K. Asgari, K. Molavi, M. Kalantari, P. Adibi: Psychological issues in inflammatory bowel disease: an overview. In: Gastroenterology research and practice. 2012; doi: 10.1155 / 2012/106502 , PMID 22778720 .
  33. ↑ Online questionnaire for people with inflammatory bowel disease . Editor: Senior Professorship for Population Medicine; University of Lübeck. Retrieved January 10, 2015.
  34. ↑ A. Hueppe, J. Langbrandtner, H. Raspe: Inviting patients with inflammatory bowel disease to active involvement in their own care: a randomized controlled trial. In: Inflammatory bowel diseases. 2014; 20 (6), pp. 1057-1069, PMID 24788217 .
  35. ↑ WR Best, JM Becktel, JW Singleton, F. Kern Jr .: Development of a Crohn's disease activity index. National Cooperative Crohn's Disease Study . In: Gastroenterology . tape 70 , no. 3 , March 1976, p. 439-444 , PMID 1248701 .
  36. ^ R. Harvey, J. Bradshaw: A simple index of Crohn's disease activity . In: Lancet . tape 1 , no. 8167 , 1980, pp. 514 , doi : 10.1016 / S0140-6736 (80) 92767-1 , PMID 6102236 .
  37. ↑ janssenmedicalinformation.ca ( Memento of the original from January 2, 2015 in the Internet Archive ) Info: The archive link has been inserted automatically and has not yet been checked. Please check the original and archive link according to the instructions and then remove this notice. @1@ 2Template: Webachiv / IABot / www.janssenmedicalinformation.ca
  38. ↑ G. Pineton de Chambrun, L. Peyrin-Biroulet, M. Lémann, JF Colombel: Clinical implications of mucosal healing for the management of IBD. In: Nat Rev Gastroenterol Hepatol Volume 7, Number 1, January 2010, pp. 15-29, ISSN  1759-5053 , doi: 10.1038 / nrgastro.2009.203 , PMID 19949430 . (Review).
  39. ↑ JC Hoffmann, JC Preiß, F. Autschbach, HJ Buhr, W. Häuser, K. Herrlinger, W. Höhne, S. Koletzko, CF Krieglstein, W. Kruis, H. Matthes, G. Moser, M. Reinshagen, G Rogler, S. Schreiber, AG Schreyer, B. Sido, B. Siegmund, A. Stallmach, B. Bokemeyer, EF Stange, M. Zeitz: S3 guideline "Diagnostics and Therapy of Crohn's Disease". In: Z Gastroenterol. Volume 46, Number 9, September 2008, pp. 1094-1146, ISSN  0044-2771 , doi: 10.1055 / s-2008-1027796 , PMID 18810679 .
  40. ↑ G. Van Assche, A. Dignass, J. Panes, L. Beaugerie, J. Karagiannis, M. Allez, T. Ochsenkühn, T. Orchard, G. Rogler, E. Louis, L. Kupcinskas, G. Mantzaris, S. Travis, E. Stange: The second European evidence-based consensus on the diagnosis and management of Crohn's disease: Definitions and diagnosis. In: J Crohn's Colitis. Volume 4, number 1, February 2010, pp. 7-27, ISSN  1876-4479 , doi: 10.1016 / j.crohns.2009.12.003 , PMID 21122488 .
  41. ↑ A. Dignass, G. Van Assche, JO Lindsay, M. Lémann, J. Söderholm, JF Colombel, S. Danese, A. D'Hoore, M. Gassull, F. Gomollón, DW Hommes, P. Michetti, C O'Morain, T. Oresland, A. Windsor, EF Stange, SP Travis: The second European evidence-based consensus on the diagnosis and management of Crohn's disease: Current management. In: J Crohn's Colitis. Volume 4, Number 1, February 2010, pp. 28-62, ISSN  1876-4479 , doi: 10.1016 / j.crohns.2009.12.002 , PMID 21122489 .
  42. ↑ G. Van Assche, A. Dignass, W. Reinisch, CJ van der Woude, A. Sturm, M. De Vos, M. Guslandi, B. Oldenburg, I. Dotan, P. Marteau, A. Ardizzone, DC Baumgart , G. D'Haens, P. Gionchetti, F. Portela, B. Vucelic, J. Söderholm, J. Escher, S. Koletzko, KL Kolho, M. Lukas, C. Mottet, H. Tilg, S. Vermeire, F. Carbonnel, A. Cole, G. Novacek, M. Reinshagen, E. Tsianos, K. Herrlinger, B. Oldenburg, Y. Bouhnik, R. Kiesslich, E. Stange, S. Travis, J. Lindsay: The second European evidence-based consensus on the diagnosis and management of Crohn's disease: Special situations. In: J Crohn's Colitis. Volume 4, Number 1, February 2010, pp. 63-101, ISSN  1876-4479 , doi: 10.1016 / j.crohns.2009.09.009 , PMID 21122490 .
  43. ↑ Hubert Feiereis: Crohn's disease . In: Thure von Uexküll u. a. (Ed.): Psychosomatic Medicine . 3. Edition. Urban & Fischer, Elsevier 1986, ISBN 3-541-08843-5 , pp. 806 .
  44. ^ Azathioprine # Clinical information
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  46. ↑ Kakodkar, S .; Farooqui, AJ; Mikolaitis, SL; Mutlu, EA: The Specific Carbohydrate Diet for Inflammatory Bowel Disease: A Case Series In: Journal of the Academy of Nutrition and Dietetics 2015; 115/8 p1226-1232
  47. ↑ Cohen, SA; Gold, BD; Oliva, S .; Lewis, J .; Stallworth, A .; Koch, B .; Eshee, L .; Mason, D .: Clinical and Mucosal Improvement With Specific Carbohydrate Diet in Pediatric Crohn Disease In: Journal of Pediatric Gastroenterology & Nutrition 2014; 59/4 p516-521
  48. ↑ Suskind, DL; Wahbeh, G., Gregory, N .; Vendettuoli, H .; Christie, D .: Nutritional Therapy in Pediatric Crohn Disease: The Specific Carbohydrate Diet In: Journal of Pediatric Gastroenterology & Nutrition 2014; 58/1, p87-91
  49. ^ Fridge, JL; Kerner, J .; Cox, K .: The Specific Carbohydrate Diet - A Treatment for Crohn's Disease? In: Journal of Pediatric Gastroenterology & Nutrition 2004; 39 p299-300
  50. ↑ BC Olendzki, TD Silverstein, GM Persuitte, Y. Ma, KR Baldwin, D. Cave: An anti-inflammatory diet as treatment for inflammatory bowel disease: a case series report. In: Nutrition journal. Volume 13, 2014, p. 5, doi: 10.1186 / 1475-2891-13-5 , PMID 24428901 , PMC 3896778 (free full text).
  51. ^ T. Naftali, LB Lev, D. Yablekovitz, E. Half, FM Konikoff: Treatment of Crohn's disease with cannabis: an observational study. In: Isr Med Assoc J. 2011; 13 (8), pp. 455-458.
  52. ↑ AC Kaliora, MG Stathopoulou, JK Triantafillidis, GV Dedoussis, NK Andrikopoulos: Chios mastic treatment of patients with active Crohn's disease. In: World J Gastroenterol. 2007; 13 (5), pp. 748-753.
  53. ↑ PTA FORUM. Intestinal disease treatment with parasites
  54. ↑ The Medicines Letter. Intestinal microflora and the immune system AMB 2011, 45, 32a
  55. ↑ RW Summers, DE Elliott, K. Qadir, JF Urban, R. Thompson, JV Weinstock: Trichuris suis seems to be safe and possibly effective in the treatment of inflammatory bowel disease. In: Am. J. Gastroenterol. Volume 98, Number 9, September 2003, pp. 2034-2041, ISSN  0002-9270 , doi: 10.1111 / j.1572-0241.2003.07660.x , PMID 14499784 .
  56. ↑ Double-blind, randomized, placebo-controlled, multicenter phase II study to investigate the efficacy and safety of three different doses of orally taken Trichuris suis ova (TSO) suspension in active Crohn's disease ( Memento from March 1, 2011 in the Internet Archive )
  57. ↑ Therapy with Trichuris suis ova (TSO) suspension (worm eggs)
  58. ↑ D. Ďuricová, N. Pedersen, M. Elkjaer, M. Gamborg, P. Munkholm, T. Jess: Overall and cause-specific mortality in Crohn's disease: a meta-analysis of population-based studies. In: Inflamm. Bowel Dis. Volume 16, Number 2, February 2010, pp. 347-353, ISSN  1536-4844 , doi: 10.1002 / ibd . 21007 , PMID 19572377 .