Ulcerative colitis

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Classification according to ICD-10
K51.- Ulcerative colitis
K51.0 Ulcerative (chronic) enterocolitis
K51.1 Ulcerative (chronic) ileocolitis
K51.2 Ulcerative (chronic) proctitis
K51.3 Ulcerative (chronic) rectosigmoiditis
K51.4 Pseudopolyposis of the colon
K51.5 Proctocolitis of the mucous membrane
K51.8 Other ulcerative colitis
K51.9 Ulcerative colitis, unspecified
ICD-10 online (WHO version 2019)

The ulcerative colitis is in a group of chronic inflammatory bowel disease . It is characterized by an inflammatory attack on the large intestine or colon . In contrast to Crohn's disease , only the large intestine is continuously affected by the inflammation and this is limited to the intestinal mucosa ( mucosa and submucosa ).

frequency

Around 160 to 250 out of 100,000 inhabitants in the western world suffer from ulcerative colitis, with 3 to 3.9 new cases per year in Germany for every 100,000 inhabitants. Women and men are equally affected. The typical age of onset is between the ages of 20 and 40. After the incidence of the disease ( prevalence ) in North America and Europe has increased over decades, it is beginning to stagnate there. In Asia , Africa and South America , where the disease used to be rare, there has been a significant increase in new cases.

Etiology and pathogenesis

The cause of the disease is unknown. Similar to Crohn's disease , a genetically predisposed , pathologically increased immune reaction against the intestinal flora is assumed. Several gene mutations have been identified that are associated with the occurrence of inflammatory bowel disease. As with Crohn's disease is the NF-kB - transcription factor suspected to be consistently active. Environmental factors such as hygiene standards and nutrition should play an equally important role. Stress and strain can contribute significantly to a difficult course and trigger active attacks of the disease.

For a long period of time, ulcerative colitis, like Crohn's disease, was counted among the psychosomatic diseases ; it is one of the Holy Seven . In the meantime, however, it is clear that ulcerative colitis is caused by the organic causes mentioned, and that psychosomatics only influences accompanying and sequelae.

Symptoms / complaints

Clinically, recurring ( recurrent ) diarrhea , intestinal bleeding and colic are in the foreground. The course of ulcerative colitis cannot be predicted. Often the beginning is gradual. But there are also acute phases and the most severe courses.

Fecal incontinence and obsessive bowel movements, the physical weakness itself as well as concomitant diseases and the side effects of the drugs administered are problematic in everyday life . Severe flatulence can lead to increased stool frequency during an attack. The relapse-related flatulence is partly due to a relapse-related sugar intolerance (such as lactose , fructose , sorbitol ). Disease-specific symptoms (such as 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.

Manifestations outside the digestive area (extraintestinal):

Acute episode

The acute episode of ulcerative colitis is characterized by the typical clinical symptoms, i.e. bloody diarrhea and possibly constant painful urge to urinate and defecate ( tenesmus ). Stool frequencies of around 40 times within 24 hours are not uncommon.

X-ray overview of toxic megacolon in ulcerative colitis.

Brilliant thrust

During a severe ( fulminant ) thrust occur frequently bloody diarrhea ( diarrhea ), fever over 38.5 ° C and a performance status and weight loss. In addition, heart palpitations ( tachycardia ) and anemia ( anemia ) can occur. Another complication is the toxic megacolon .

Chronically active course

A chronically active course is characterized by the persistence of the clinical symptoms in spite of an appropriate drug therapy, which brings about an improvement, but not a complete and permanent (fewer than two relapses, i.e. further relapses, per year) remission .

A drug dependency often develops in chronically active disease. After a while, they become weaker or cannot be dosed below a certain value without serious problems arising again immediately. One then speaks of a refractory (unappealing) course.

Remission

From a remission of ulcerative colitis is used when no diarrhea (no more than three stools a day), no visible blood in the stool and not caused by the ulcerative colitis symptoms are present.

Diagnostics / differential diagnoses

  • Endoscopic findings in ulcerative colitis

  • Florid (flowering = active) ulcerative colitis

  • The scar stage of ulcerative colitis

Endoscopy

The diagnosis of ulcerative colitis can only be a colonoscopy ( colonoscopy () with sampling biopsy ) and a histologic ( histological ) examination are provided. Diseases with similar endoscopic findings must be differentiated from the differential diagnosis, in particular Crohn's disease , infectious or drug-related colitis , pseudomembranous colitis , ischemic colitis, or diverticular colitis .

laboratory

Elevated CRP , increased blood sedimentation, and leukocytosis are found to be signs of inflammation , possibly anemia as a result of the bleeding. In 60% of the cases anti- neutrophil cytoplasmic antibodies are found , with a perinuclear fluorescence pattern (p-ANCA).

Pathology / morphology

Histological examination: active stage of ulcerative colitis. HE staining .
As above figure, cross section.

Carcinoma risk

After a long period of illness and an extensive course of the disease (8–10 years if the entire colon is affected, 12–15 years after left-sided colitis) there is an increased risk of malignant degeneration. In addition to the duration of the disease, the extent of ulcerative colitis represents a clear risk factor for the development of colon cancer (colorectal carcinoma) and is therefore also regarded as a so-called precancerous condition .

Endoscopic tumor screening

With regular colonoscopic controls with step biopsies (tissue sampling from several sections of the colon), the colitis carcinoma is rare (2.1% after a disease duration of ten years, in 8.5% after 20 years and in 17.8% after 30 years) . An annual colonoscopy with step biopsies should therefore be performed in patients with (sub) total ulcerative colitis that has existed for more than eight years or left-sided colitis that has existed for more than 15 years.

therapy

Basically, the existing guidelines should be used. Drugs normally used in treating ulcerative colitis are given either orally or rectally to reduce inflammation. In particularly severe cases, when the intestine cannot absorb the active ingredients or cannot absorb them sufficiently, most fast-acting drugs can be given intravenously .

Medical therapy

For the treatment of ulcerative colitis, as for the treatment of Crohn's disease, a number of drugs are available, which, however, can sometimes have severe or at least unpleasant side effects, especially with prolonged use.

According to the current guidelines for the treatment of ulcerative colitis, mesalazine or another 5-ASA preparation is recommended for long-term treatment, as it reduces the risk of colon cancer at the same time as it reduces inflammation . Mesalazine is considered to have quite few side effects. If you have mesalazine intolerance, you usually switch to sulfasalazine . If the 5-ASA is insufficient, the glucocorticoid is first applied locally (rectally as an enema or foam or orally as a tablet with MMX galenics) or systemically (orally or intravenously) for a short time. If the disease is limited to the rectum and the sigmoid colon , budesonide foam has the advantage over other glucocorticoid preparations that it only has a local effect and hardly affects the rest of the organism. It is broken down during the first passage through the liver. Mesalazine can also be administered rectally (suppositories, enemas or as a foam).

E-Coli - Alfred Nissle -1917 bacteria: These probiotic bacteria areavailable in pharmaciesunder the name Mutaflor and have been shown in several studies to be an effective substitute for 5-ASA preparations in maintaining remission. Mutaflor is covered by health insurances in the event of mesalazine intolerance. The preparation has to be kept refrigerated, even during transport, and can only be kept for a few months.

If long-term immunosuppression makes sense, azathioprine should be used first . In the event of intolerance, 6-mercaptopurine can be used. Other reserve drugs from the group of antimetabolites ( methotrexate (MTX), ciclosporin and tacrolimus ) are also available for therapy. These can be considered in patients who do not respond or do not respond adequately to glucocorticoids and in whom azathioprine shows no effect, as well as in severe cases or at the start of therapy with azathioprine.

Studies (ACT 1 and ACT 2) have also shown that the TNF blocker infliximab is effective in treating ulcerative colitis. This drug is also used clinically for ulcerative colitis. Ulcerative colitis, which cannot be cured by medication, is a disease that (apart from the extraintestinal symptoms) can be cured by a total removal of the large intestine ( colectomy ). As a rule of thumb, infliximab can be used in patients who are reluctant to have surgery and when ciclosporin is contraindicated . Infliximab is an immunosuppressive drug. If possible, the treatment should be combined with another immunosuppressive drug (such as azathioprine). As with Crohn's disease, administration is every two and four weeks, if long-term therapy is necessary, every eight weeks.

In addition, the TNF-alpha blocker adalimumab (trade name Humira ® ; manufacturer AbbVie ) has been approved as a further form of therapy since April 2012 . This is a human monoclonal antibody of the IgG1 type, which, like infliximab, binds highly specifically to the cytokine tumor necrosis factor-alpha (TNF-α) and neutralizes its effect. In contrast to many other antibodies, adalimumab was identified from a library of human immunoglobulin sequences by phage display . Adalimumab is therefore a "completely human" antibody. In 2013, the approval of the likewise human golimumab (trade name Simponi ® ; manufacturer Centocor ) followed. Both TNF-alpha blockers are injected subcutaneously and offer this advantage over infliximab, which can only be administered via infusion.

Since May 2014 Vedolizumab (trade name Entyvio ® , a product of Takeda ), a humanized monoclonal antibody from the group of integrin - antagonists , for the treatment of ulcerative colitis or Crohn's disease admitted.

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Numerous other drugs are currently being approved and are therefore currently (2008) only used in the context of studies, many initially for Crohn's disease and possibly later for ulcerative colitis, such as biologics that are supposed to be more tolerable than infliximab and in some cases also easier are to be administered (approximately subcutaneously and without weight adjustment), as well as some active ingredients that have been known for a long time, the effectiveness of which for colitis is only being recognized: Certolizumab , Etanercept , Basiliximab , Daclizumab , Visilizumab , Mycophenolat-Mofetil (MMF), 6- thioguanine , heparin , Dehydroepiandrosterone (DHEA). Thalidomide is also being discussed as a possible drug .

Antibiotics are rarely used. Only ciprofloxacin and metronidazole were able to bring relief in certain cases in studies. In hospitals, severe relapses are often treated with a combination of antibiotics and high-dose cortisone in addition to the previous medication.

Surgical therapy

In more severe cases and with complications such as the toxic megacolon , surgery may be necessary. This usually means a complete removal of the colon followed by an operation called an ileoanal pouch surgery . A kind of artificial rectum is constructed from the small intestine, which takes over the reservoir function of the removed rectum. The small intestine is then connected to the anus so that patients have normal bowel movements. In particularly severe cases or if an artificial anus has been around for a long time, only the pouch is put on in an intermediate step so that it can come to rest after the second severe operation. If fecal incontinence is foreseeable , a kind of funnel is used to rinse the pouch every two to three days (taking into account that the fluid is retained) in order to train the sphincter muscle. This training is continued independently after the hospital stay and requires some discipline and at the beginning also overcoming. In the subsequent (relatively harmless) operation, both ends ( ileostomy and pouch access) are connected to one another. Although the operations can have considerable side effects (such as incontinence at night), they can actually cure the disease.

Extracorporeal therapy method

The leukocyte apheresis , i.e. the extracorporeal removal of an excess of granulocytes and monocytes , which are said to be responsible for maintaining the inflammatory reaction, is a standard procedure in Japan for the treatment of ulcerative colitis. The guidelines for Germany recommend leukocyte apheresis in exceptional cases. However, the high costs will only be covered by the statutory health insurances after a case-by-case examination and if all drug therapy options have failed.

Deficiency symptoms

Symptoms of deficiency can occur in the episode as well as in remission as an interaction with medication. Even if the inflammation in ulcerative colitis is always limited to the large intestine, in severe diarrhea many nutrients are not absorbed in the small intestine. Defects can therefore be pronounced in the thrust.

Potassium / Sodium : Due to severe (especially watery) diarrhea, the salts are excreted quickly. In most cases, a diet rich in sodium (containing salt) or high in potassium (e.g. bananas) is sufficient.

Water: Because of the increased stool frequency (with aqueous diarrhea), it may dry out ( dehydration come).

Iron : Due to the constant loss of blood, iron deficiency can occur. That is why the iron balance is checked regularly and iron supplements are prescribed if necessary. Iron supplements, however, are sometimes poorly tolerated because they irritate the intestinal mucosa. Intravenous iron supply is also possible.

Calcium : Changes in bone density often occur as a result of the metabolic disorder caused by cortisone therapy in the form of osteoporosis . With longer cortisone therapy, the bone density should therefore be measured annually ( osteodensitometry ). In the context of long-term, systemic steroid medication, calcium and vitamin D must be substituted . The most suitable are calcium / vitamin D combination preparations.

Folic acid : By sulfasalazine, the folic acid resorption are disturbed.

Complementary therapies

  • Myrrh : Myrrh is also anti-inflammatory. Myrrh has long been used in naturopathy against inflammation internally and externally. In addition to pure myrrh (which is bitter when chewed), tasteless preparations are also available. The old medicinal plant reduces the tension in the smooth intestinal muscles. This will reduce the number of bowel contractions and relieve bowel cramps. In addition, myrrh reduces inflammatory processes in the intestine and has the ability to reduce the formation of free radicals there and thus strengthen the antioxidant protection system. Combined with other medicinal plants such as coffee charcoal and chamomile, an even greater anti-inflammatory effect can be observed. Studies at the Charité Berlin have shown that the medicinal plant myrrh stabilizes the intestinal barrier and protects it from harmful influences through the inflammation-promoting protein TNFalpha. The combination with coffee charcoal and chamomile is also used in Crohn's disease. A clinical study has shown that this herbal therapy for maintaining the relapse-free phase in ulcerative colitis is as effective as the standard therapy with mesalazine. The mode of action is also different: Evidence has been found that the herbal therapy only works on the intestinal mucosa and does not affect the entire immune system. Further studies showed that plant therapy in the acute ulcerative colitis flare-up ensures a higher concentration of health-promoting short-chain fatty acids in the intestine than the standard synthetic drug mesalazine. Also based on these studies, the current S3 guideline "Ulcerative colitis" of the German Society for Gastroenterology, Digestive and Metabolic Diseases (DGVS) recommends: "A combination of myrrh, chamomile flower extract and coffee charcoal can be used as a complement in remission-maintaining treatment."
  • Frankincense ( Boswellia serrata ): Studies indicate that the boswellic acids contained in frankincense have anti-inflammatory effects and can provide relief from inflammatory bowel diseases such as ulcerative colitis.
  • Psyllium husks : Studies show an effect similar to the use of aminosalicylates (e.g. mesalazine ) when ingesting the seed husks of the plantain family Plantago ovata . In animal experiments, a reduction in various inflammatory mediators such as leukotrienes and TNF-α was demonstrated. A growth-promoting effect on Lactobacillus acidophilus and bifidobacteria , which are pathologically reduced in the intestinal flora of ulcerative colitis sufferers, was also demonstrated .
  • Lecithin : Healthy intestinal mucosa in the large intestine contains lecithin, and this lecithin plays an important role in the barrier function of the intestine, i.e. the ability to distinguish it from bacteria and pollutants and to tolerate them without an immune reaction. Studies have shown that the intestinal mucosa of people with ulcerative colitis contains significantly less lecithin than that of healthy people. However, since lecithin is broken down by pancreatic enzymes for digestion, lecithin administered normally does not reach the affected colon. To intact lecithin convey orally to the large intestine, is a lecithin granules for this new approach with the polymer resin Eudragit S100 enteric microencapsulated so that the lecithin only in the lower small intestine and is released in the colon. However, an approval study for a drug that was started in 2014 was discontinued at the end of 2016 due to ineffectiveness compared to a placebo.
  • Trichuris suis : Pig whipworm eggs (TSO eggs) taken orally have shown promise in initial studies. It is based on the theory that dealing with these parasites distracts the immune system from unwanted attacks on the intestinal mucosa. The worms apparently also secrete effective substances themselves, which can be extracted and can already alleviate autoimmune diseases (e.g. asthma) in animal experiments. A registration study is being planned, at the moment treatment is possible at the risk of the attending physician, whereby the treatment costs of approx. 3000 EUR per treatment cycle have to be borne by the patient. The pig whipworms die in the human body within 14 days and cannot be passed on to other people.
  • Diet: Anti-inflammatory foods like omega-3 fatty acids and berries containing anthocyanins , especially blueberries or blueberry juice , can also help somewhat. Often times, omitting certain foods also helps. However, which foods are not well tolerated varies from patient to patient. In addition, foods that are tolerated in remission (such as milk, cream, apples, vegetables with peel) are often not tolerated in the acute episode, or only in small quantities. Accordingly, it is recommended to limit the consumption of aggressive, inflammatory foods.
  • Turmeric : The curcumin containing turmeric ( Curcuma longa ) is administered together with mesalazine or sulfasalazine , suitable for maintaining remission. It is not known whether the administration of turmeric alone is sufficient to maintain remission.
  • Nicotine : Ulcerative colitis is significantly more common in non-smokers than in smokers. Randomized controlled studies demonstrated the significant effectiveness of nicotine patches.

Cooperation of the patient

For a better understanding of their own situation and current complaints, affected patients can be given a comprehensive overview of their current health situation and their personal problem profile with the help of a questionnaire. If necessary, those affected receive suggestions for suitable and promising support offers. Following the evaluation, the results of the questionnaire can be used as a starting point for a medical consultation. The benefit of the questionnaire and its effectiveness on the quality of life of those affected were confirmed in a randomized controlled study.

literature

Guidelines

Technical article

  • S. Danese, C. Fiocchi: Ulcerative colitis. In: New England Journal of Medicine. 365, 2011, pp. 1713-1725, doi: 10.1056 / NEJMra1102942 .
  • J. Meier, A. Sturm: Current treatment of ulcerative colitis. In: World journal of gastroenterology: WJG. Volume 17, Number 27, July 2011, pp. 3204-3212, ISSN  1007-9327 . doi: 10.3748 / wjg.v17.i27.3204 . PMID 21912469 . PMC 3158396 (free full text). (Review).
  • D. Baumgart: Diagnosis and therapy of Crohn's disease and ulcerative colitis . In: Dtsch Arztebl Int . No. 106 (8) , 2009, pp. 123-133 ( aerzteblatt.de ).

Web links

Commons : Ulcerative Colitis  - Collection of pictures, videos and audio files

Supraregional associations

Individual evidence

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  4. ↑ S3 guideline for diagnosis and treatment of ulcerative colitis of the German Society for Digestive and Metabolic Diseases (DGVS). In: AWMF online (as of 2011)
  5. ↑ Hetbert Renz-Polster, Steffen Krautzig: Basic textbook internal medicine . Elsevier, Munich 2013, ISBN 978-3-437-41114-4 , pp. 553f.
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  10. ↑ S-3 guideline "Ulcerative Colitis" ( Memento of the original from August 19, 2019 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. of the German Society for Gastroenterology, Digestive and Metabolic Diseases , accessed on August 19, 2019 @1@ 2Template: Webachiv / IABot / www.awmf.org
  11. ↑ S-3 Guideline Ulcerative Colitis ( Memento of the original from August 19, 2019 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. of the DGVS (AWMF guideline register 021/009), accessed on August 19, 2019 @1@ 2Template: Webachiv / IABot / www.awmf.org
  12. ↑ BJ Rembacken u. a .: Non-pathogenic Escherichia coli versus mesalazine for the treatment of ulcerative colitis: a randomized trial. In: Lancet. 1999 Aug 21; 354 ​​(9179), pp. 635-639. PMID 10466665
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  19. ↑ AJ Fatani et al .: Myrrh attenuates oxidative and inflammatory processes in acetic acid-induced ulcerative colitis. In: Experimental and therapeutic medicine 12: 730-738, (2016).
  20. ↑ C. Vissiennon et al .: Synergistic interactions of chamomile flower, myrrh and coffee charcoal in inhibiting pro-inflammatory chemokine release from activated human macrophages. In: Synergy , Volume 4, June 2017, pp. 13-18.
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  22. ^ J. Langhorst, I. Varnhagen, SB Schneider, U. Albrecht, A. Rueffer, R. Stange, A. Michalsen, GJ Dobos: Randomized clinical trial: a herbal preparation of myrrh, chamomile and coffee charcoal compared with mesalazine in maintaining remission in ulcerative colitis - a double-blind, double-dummy study. In: Aliment Pharmacol Ther. 2013 Jul 4
  23. ↑ Jost Langhorst, Anna K. Koch, Andreas Rueffer, Gustav Dobos: Distinct Patterns of Short Chain Fatty Acids in Patients with Ulcerative Colitis Experiencing a Flare during Treatment with Mesalamine or a Herbal Combination of Myrrh, Chamomile Flowers and Coffee Charcoal. In: Gastroenterology , April 2017, Volume 152, Issue 5, Supplement 1, page S616. doi: 10.1016 / S0016-5085 (17) 32186-8 .
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  25. ↑ Hermann PT Ammon: Salai-Guggal (Indian frankincense) gum resin from Boswellia serrata: Boswellic acids as non-redox inhibitors of leukotriene biosynthesis - New therapeutic option? In: Deutsches Ärzteblatt . tape 95 , no. 1-2 . Deutscher Ärzte-Verlag , January 5, 1998, p. A-30 / B-21 / C-21 ( aerzteblatt.de [accessed on February 2, 2015]).
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