Inflammatory bowel disease

From Infogalactic: the planetary knowledge core
(Redirected from Inflammatory Bowel Disease)
Jump to: navigation, search

<templatestyles src="Module:Hatnote/styles.css"></templatestyles>

This article is about bowel inflammation. For functional disorder, see Irritable bowel syndrome.
Inflammatory bowel diseases
Cryptitis high mag.jpg
Micrograph showing inflammation of the large bowel in a case of inflammatory bowel disease. Colonic biopsy. H&E stain.
Classification and external resources
Specialty Gastroenterology
DiseasesDB 31127
eMedicine med/1169 emerg/106 oph/520
Patient UK Inflammatory bowel disease
MeSH D015212
[[[d:Lua error in Module:Wikidata at line 863: attempt to index field 'wikibase' (a nil value).|edit on Wikidata]]]

Inflammatory bowel disease (IBD) is a group of inflammatory conditions of the colon and small intestine. Crohn's disease and ulcerative colitis are the principal types of inflammatory bowel disease. It is important to note that not only does Crohn's disease affect the small intestine and large intestine, it can also affect the mouth, esophagus, stomach and the anus whereas ulcerative colitis primarily affects the colon and the rectum.[1][2][3]

Inflammatory bowel diseases resulted in 51,000 deaths in 2013 and 55,000 deaths in 1990.[4]

Classification

The chief types of inflammatory bowel disease are Crohn's disease and ulcerative colitis (UC). Inflammatory bowel diseases fall into the class of autoimmune diseases, in which the body's own immune system attacks elements of the digestive system.[5]

Accounting for far fewer cases are other forms of IBD, which are not always classified as typical IBD:

No disease specific markers are currently known in the blood, enabling the reliable separation of Crohn's disease and ulcerative colitis patients.[6] The way doctors can tell the difference between Crohn's disease and UC is the location and nature of the inflammatory changes. Crohn's can affect any part of the gastrointestinal tract, from mouth to anus (skip lesions), although a majority of the cases start in the terminal ileum. Ulcerative colitis, in contrast, is restricted to the colon and the rectum.[7] Microscopically, ulcerative colitis is restricted to the mucosa (epithelial lining of the gut), while Crohn's disease affects the full thickness of the bowel wall ("transmural lesions").

Lastly, Crohn's disease and ulcerative colitis present with extra-intestinal manifestations (such as liver problems, arthritis, skin manifestations and eye problems) in different proportions.

In 10%-15% of cases,[8] a definitive diagnosis neither of Crohn's disease nor of ulcerative colitis can be made because of idiosyncrasies in the presentation. In this case, a diagnosis of indeterminate colitis may be made. Although a recognised definition, not all centres refer to this.

Signs and symptoms

Signs and symptoms
Crohn's disease Ulcerative colitis
Defecation Often porridge-like,[9]
sometimes steatorrhea		 Often mucus-like
and with blood[9]
Tenesmus Less common[9] More common[9]
Fever Common[9] Indicates severe disease[9]
Fistulae Common[10] Seldom
Weight loss Often More seldom

In spite of Crohn's and UC being very different diseases, both may present with any of the following symptoms: abdominal pain, vomiting, diarrhea, rectal bleeding, severe internal cramps/muscle spasms in the region of the pelvis and weight loss. Anemia is the most prevalent extraintestinal complication of inflammatory bowel disease.[11][12] Associated complaints or diseases include arthritis, pyoderma gangrenosum, primary sclerosing cholangitis, and non-thyroidal illness syndrome (NTIS).[13] Associations with deep vein thrombosis (DVT)[14] and Bronchiolitis obliterans organizing pneumonia (BOOP) have also been reported.[citation needed] Diagnosis is generally by assessment of inflammatory markers in stool followed by colonoscopy with biopsy of pathological lesions.

Diagnostic findings
Crohn's disease Ulcerative colitis
Terminal ileum involvement Commonly Seldom
Colon involvement Usually Always
Rectum involvement Seldom Usually[15]
Involvement around
the anus		 Common[10] Seldom
Bile duct involvement No increase in rate of primary sclerosing cholangitis Higher rate[16]
Distribution of disease Patchy areas of inflammation (skip lesions) Continuous area of inflammation[15]
Endoscopy Deep geographic and serpiginous (snake-like) ulcers Continuous ulcer
Depth of inflammation May be transmural, deep into tissues[10][2] Shallow, mucosal
Stenosis Common Seldom
Granulomas on biopsy May have non-necrotizing non-peri-intestinal crypt granulomas[10][17][18] Non-peri-intestinal crypt granulomas not seen[15]


Causes

Pathophysiology
Crohn's disease Ulcerative colitis
Cytokine response Associated with Th17[19] Vaguely associated with Th2

IBD is a complex disease which arises as a result of the interaction of environmental and genetic factors. It is increasingly thought that alterations to interal bacteria can contribute to inflammatory gut diseases[20][21] IBD affected individuals have been found to have 30-50 percent reduced biodiversity of commensalism bacteria such as a decrease in Firmicutes (namely Lachnospiraceae) and Bacteroidetes. Further evidence of the role of gut flora in the cause of inflammatory bowel disease is that IBD affected individuals are more likely to have been prescribed antibiotics in the 2-5 year period before their diagnosis than unaffected individuals.[22] The enteral bacteria can be altered by environmental factors, such as Concentrated milk fats (a common ingredient of processed foods and confectionery) or oral medications such as antibiotics and oral iron preparations.[23]

Diet

High protein intake, specifically animal protein via meat and fish consumption has been significantly associated with inflammatory bowel disease as well as ulcerative colitis.[24] There was no such association related to plant proteins in the prospective study consisting of over 65,000 patients over a 10-year period.[25] Animal proteins have greater amounts of sulphur containing amino acids such as methionine, which the colonic microflora accrues into hydrogen sulfide, resulting in the pathogenesis of IBD and ulcerative colitis.[25][26] Such bacterial derived cell poisons in the form of hydrogen sulfide are specifically elaborated by animal or meat and fish intake, and not by plant foods.[27]

Genetics

Associated loci pane. Pink genes are in IBD associated loci, blue are not.

The genetic contribution is poorly understood and seems to arise from the small contribution of dozens of genes. In 2012 163 IBD susceptibility loci were confirmed which means that 163 alleles that can increase the susceptibility to the disease. These 163 loci explain from an 8.2% to a 13.6% of variance in Crohn’s disease and 4.1% to 7.5% in ulcerative colitis.

The 163 loci were related with 300 known genes. The functional enrichment analysis of this group of genes using gene ontology showed that there are many genes related with cytokine production, lymphocyte activation and the response to bacterial infection. In an effort to identify likely causal genes a probabilistic causal gene network was constructed. Here a sub-network including NOD2, Il10 and CARD9 seems to indicate a close relationship between IBD and genes related with host interaction with bacteria. Of particular relevance is the presence of the gene HCK which seems to play an important role anti-inflammation. In the figure beside there is a NOD2-focused cluster in the causal gene sub-network.[28]

Diagnosis

Diagnosis is usually confirmed by biopsy on colonoscopy. In children fecal calprotectin is useful.[29]

Treatment

Management
Crohn's disease Ulcerative colitis
Mesalazine Less useful[30] More useful[30]
Antibiotics Effective in long-term[31] Generally not useful[32]
Surgery Often returns following
removal of affected part		 Usually cured by removal
of colon

CD and UC are inflammatory diseases, and are not medically curable. Surgery can essentially cure ulcerative colitis if the large intestine is removed (though medical treatment and endoscopic surveillance may be necessary if a stump of rectum is left behind). A pouch can be created from the small intestine, this serves as the rectum and prevents the need for a permanent ileostomy. Further complications can arise with a pouch in the form of pouchitis which manifests itself by symptoms, somewhat similar to UC. Surgery cannot cure Crohn's disease.[33]

Medical treatment of IBD is individualized to each patient. The choice of which drugs to use and by which route to administer them (oral, rectal, injection, infusion) depends on factors including the type, distribution, and severity of the patient's disease, as well as other historical and biochemical prognostic factors, and patient preferences. For example, mesalazine is more useful in ulcerative colitis than in Crohn's disease.[30] Generally, depending on the level of severity, IBD may require immunosuppression to control the symptom, such as prednisone, TNF inhibition, azathioprine (Imuran), methotrexate, or 6-mercaptopurine.

Often, anti-inflammatory steroids are used to control disease flares and were once acceptable as a maintenance drug. In use for several years in Crohn's disease patients and recently in patients with ulcerative colitis, biologicals have been used such as TNF inhibitors. Severe cases may require surgery, such as bowel resection, strictureplasty or a temporary or permanent colostomy or ileostomy. Ulcerative colitis can in most cases be cured by proctocolectomy, however this may not eliminate extra-intestinal symptoms. A small percentage of patients with ileo-anal pouches do have to manage occasional or even chronic pouchitis.[34] In Crohn's disease, surgery involves removing the worst inflamed segments of the intestine and connecting the healthy regions, but unfortunately, it does not cure Crohn's or eliminate the disease, as at some point after the first surgery, Crohn's disease recurs in the healthy parts of the intestine, usually at the resection site. (For example, if a patient with Crohn's disease has an ileocecal anastomosis, in which the caecum and terminal ileum are removed and the ileum is joined to the ascending colon, their Crohn's will nearly always flare-up near the anastomosis or in the rest of the ascending colon).

Usually the treatment is started by administering drugs with high anti-inflammatory effects, such as prednisone. Once the inflammation is successfully controlled, the patient is usually switched to a lighter drug to keep the disease in remission, such as Asacol, a mesalazine. If unsuccessful, a combination of the aforementioned immunosuppression drugs with a mesalazine (which may also have an anti-inflammatory effect) may or may not be administered, depending on the patient. Budesonide is the easiest medication for the elderly and children.

A number of naturopathists and holistic medicine practitioners claim to have found a cure for inflammatory bowel conditions. The treatments are natural, based on herbal supplements that help revitalize the area inflicted by IBD. There is a strong argument against traditional medical healing, claiming that to treat IBD you need to repair the gastrointestinal tract in two ways: a) Replace the mucosal lining that protects the tender intestinal wall. b) Repair the damage that has been done to the intestinal wall. This is achieved by feeding your GI tract the natural ingredients it is made of, not antibiotics and synthetic drugs, according to naturopathists' opinions.[35]

There is no question that nutritional deficiencies play a prominent role in IBD. Malabsorption, diarrhea and GI blood loss are common features of IBD, and therefore deficiencies of B vitamins, fat soluble vitamins and essential fatty acids, and key minerals such as magnesium, zinc and selenium are extremely common.

A traditional naturopathic remedy for bowel disorders, Bastyr (Robert’s) Formula B, consists of marshmallow, wild indigo, geranium, goldenseal, slippery elm, ginger, okra powder, niacinamide and duodenum powder. A safer and even more attractive therapeutic alternative is offered by probiotics, with or without the addition of prebiotics, a ‘natural’ approach to IBD treatment.[36] Natural treatments for IBD are not proven by research to be effective.

A relatively new treatment option is fecal bacteriotherapy (FBT), which has been used to successfully treat IBD in several small studies.[37][38] There is evidence from case series of patients with ulcerative colitis responding favourably to fecal microbiota transplant with cure or significant remission persisting for up to 13 years post treatment. Individuals whose onset of ulcerative colitis is associated with antibiotic use or colonic infection are the most likely to benefit from fecal microbiota transplant.[22]

There is evidence of an infectious contribution to inflammatory bowel disease in some patients and this subgroup of patients may benefit from antibiotic therapy.[39] Anaemia is a common finding in both ulcerative colitis and Crohn's disease. Due to raised levels of inflammatory cytokines which lead to the increased expression of hepcidin, parenteral iron is the preferred treatment option as it bypasses the gastrointestinal system, has lower incidence of adverse events and enables quicker treatment. Hepcidin itself is also an anti-inflammatory agent. In the murine model very low levels of iron restrict hepcidin synthesis, worsening the inflammation that is present.[40] Enteral nutrition has been found to be efficient to improve hemoglobin level in patients with inflammatory bowel disease, especially combined with erythropoietin.[41]

Due to the fact that the disease might be triggered by the blooms of a rare type of gut bacteria[20] some anti-bacterial drugs like chloroxine might be able to dispense the problem. A wider study is needed to confirm this.

In February 2013 researchers identified adult stem cells in the bone marrow that could one day be used to treat inflammatory bowel disease (IBD).[42]

Prognosis

Complications
Crohn's
disease		 Ulcerative
colitis
Nutrient deficiency Higher risk
Colon cancer risk Slight Considerable
Prevalence of extraintestinal complications[43]
Iritis/uveitis Females 2.2% 3.2%
Males 1.3% 0.9%
Primary sclerosing
cholangitis		 Females 0.3% 1%
Males 0.4% 3%
Ankylosing
spondylitis		 Females 0.7% 0.8%
Males 2.7% 1.5%
Pyoderma
gangrenosum		 Females 1.2% 0.8%
Males 1.3% 0.7%
Erythema nodosum Females 1.9% 2%
Males 0.6% 0.7%

While IBD can limit quality of life because of pain, vomiting, diarrhea, and other socially undesired symptoms, it is rarely fatal on its own. Fatalities due to complications such as toxic megacolon, bowel perforation and surgical complications are also rare.

While patients of IBD do have an increased risk of colorectal cancer, this is usually caught much earlier than the general population in routine surveillance of the colon by colonoscopy, and therefore patients are much more likely to survive.

New evidence suggests that patients with IBD may have an elevated risk of endothelial dysfunction and coronary artery disease.[44]

A recent literature review by Gandhi et al. described that IBD patients over the age of 65 and females are at increased risk of coronary artery disease despite the lack of traditional risk factors.[45]

The goal of treatment is toward achieving remission, after which the patient is usually switched to a lighter drug with fewer potential side effects. Every so often, an acute resurgence of the original symptoms may appear; this is known as a "flare-up". Depending on the circumstances, it may go away on its own or require medication. The time between flare-ups may be anywhere from weeks to years, and varies wildly between patients - a few have never experienced a flare-up.

Life with IBD can be challenging, however, it should not impede your ability to live a normal life. Patients with IBD can go to college, hold a normal job, get married, have children etc. As is the nature of any chronic, unpredictable disease, there will be ups and downs. The progress made in IBD research and treatment is astounding and will only improve in the years to come.

Although living with IBD can be difficult, there are numerous resources available to help families navigate the ins and out of IBD. The Crohn's and Colitis Foundation of America (CCFA) is an excellent resource. CCFA is a vital resource to getting questions answered and finding support about life with IBD.

Epidemiology

IBD resulted in 51,000 deaths in 2013 and 55,000 deaths in 1990.[4] The increased incidence of IBD has followed a sharp increase in meat consumption worldwide since World War 2. This supports the claim that animal protein intake is strongly associated with IBD incidence.[25]

Research

The following treatment strategies are not used routinely, but appear promising in some forms of inflammatory bowel disease.

Initial reports[46] suggest that "helminthic therapy" may not only prevent but even control IBD: a drink with roughly 2,500 ova of the Trichuris suis helminth taken twice monthly decreased symptoms markedly in many patients. It is even speculated that an effective "immunization" procedure could be developed—by ingesting the cocktail at an early age.

Prebiotics and probiotics are showing increasing promise as treatments for IBD[47] and in some studies have proven to be as effective as prescription drugs.[48]

In 2005 New Scientist published a joint study by Bristol University and the University of Bath on the apparent healing power of cannabis on IBD. Reports that cannabis eased IBD symptoms indicated the possible existence of cannabinoid receptors in the intestinal lining, which respond to molecules in the plant-derived chemicals. CB1 cannabinoid receptors – which are known to be present in the brain – exist in the endothelial cells which line the gut, it is thought that they are involved in repairing the lining of the gut when damaged.[49]

The team deliberately damaged the cells to cause inflammation of the gut lining and then added synthetically produced cannabinoids; the result was that gut started to heal: the broken cells were repaired and brought back closer together to mend the tears. It is believed that in a healthy gut, natural endogenous cannabinoids are released from endothelial cells when they are injured, which then bind to the CB1 receptors. The process appears to set off a wound-healing reaction, and when people use cannabis, the cannabinoids bind to these receptors in the same way.[49]

Previous studies have shown that CB1 receptors located on the nerve cells in the gut respond to cannabinoids by slowing gut motility, therefore reducing the painful muscle contractions associated with diarrhea. The team also discovered another cannabinoid receptor, CB2, in the guts of IBD sufferers, which was not present in healthy guts. These receptors, which also respond to chemicals in cannabis, appear to be associated with apoptosis – programmed cell death – and may have a role in suppressing the overactive immune system and reducing inflammation by mopping up excess cells.[49]

Alicaforsen is a first generation antisense oligodeoxynucleotide designed to bind specifically to the human ICAM-1 messenger RNA through Watson-Crick base pair interactions in order to subdue expression of ICAM-1.[50] ICAM-1 propagates an inflammatory response promoting the extravasation and activation of leukocytes (white blood cells) into inflamed tissue.[50] Increased expression of ICAM-1 has been observed within the inflamed intestinal mucosa of ulcerative colitis, pouchitis and Crohn's sufferers where ICAM-1 over production correlated with disease activity.[51] This suggests that ICAM-1 is a potential therapeutic target in the treatment of these diseases.[52][53]

In 2014, an alliance among the Broad Institute, Amgen and Massachusetts General Hospital formed with the intention to "collect and analyze patient DNA samples to identify and further validate genetic targets."[54]

In a recent meta-analysis on 938 IBD patients and 953 controls, IBD was significantly associated with having higher odds of vitamin D deficiency.[55]

References

  1. ↑ Lua error in package.lua at line 80: module 'strict' not found.
  2. ↑ 2.0 2.1 Lua error in package.lua at line 80: module 'strict' not found. Cite error: Invalid <ref> tag; name "Baumgart" defined multiple times with different content
  3. ↑ Lua error in package.lua at line 80: module 'strict' not found.
  4. ↑ 4.0 4.1 Lua error in package.lua at line 80: module 'strict' not found.
  5. ↑ Lua error in package.lua at line 80: module 'strict' not found.
  6. ↑ Lua error in package.lua at line 80: module 'strict' not found.
  7. ↑ Lua error in package.lua at line 80: module 'strict' not found.
  8. ↑ http://jcp.bmj.com/content/57/12/1233.long
  9. ↑ 9.0 9.1 9.2 9.3 9.4 9.5 internetmedicin.se > Inflammatorisk tarmsjukdom, kronisk, IBD By Robert Löfberg. Retrieved Oct 2010 Translate.
  10. ↑ 10.0 10.1 10.2 10.3 Lua error in package.lua at line 80: module 'strict' not found.
  11. ↑ Lua error in package.lua at line 80: module 'strict' not found.
  12. ↑ Lua error in package.lua at line 80: module 'strict' not found.
  13. ↑ Lua error in package.lua at line 80: module 'strict' not found.
  14. ↑ Lua error in package.lua at line 80: module 'strict' not found.
  15. ↑ 15.0 15.1 15.2 Lua error in package.lua at line 80: module 'strict' not found.
  16. ↑ Lua error in package.lua at line 80: module 'strict' not found.
  17. ↑ Lua error in package.lua at line 80: module 'strict' not found.
  18. ↑ Lua error in package.lua at line 80: module 'strict' not found.
  19. ↑ Lua error in package.lua at line 80: module 'strict' not found.
  20. ↑ 20.0 20.1 Lua error in package.lua at line 80: module 'strict' not found.
  21. ↑ Lua error in package.lua at line 80: module 'strict' not found.
  22. ↑ 22.0 22.1 Lua error in package.lua at line 80: module 'strict' not found.
  23. ↑ Lua error in package.lua at line 80: module 'strict' not found.
  24. ↑ Lua error in package.lua at line 80: module 'strict' not found.
  25. ↑ 25.0 25.1 25.2 Lua error in package.lua at line 80: module 'strict' not found.
  26. ↑ Lua error in package.lua at line 80: module 'strict' not found.
  27. ↑ Lua error in package.lua at line 80: module 'strict' not found.
  28. ↑ Lua error in package.lua at line 80: module 'strict' not found.
  29. ↑ Lua error in package.lua at line 80: module 'strict' not found.
  30. ↑ 30.0 30.1 30.2 Pages 152–156 (Section: Inflammatory bowel disease (IBD)) in: Lua error in package.lua at line 80: module 'strict' not found. Cite error: Invalid <ref> tag; name "agabegi2nd" defined multiple times with different content
  31. ↑ Lua error in package.lua at line 80: module 'strict' not found.
  32. ↑ Section "Antibiotics and Ulcerative Colitis" in: Lua error in package.lua at line 80: module 'strict' not found.
  33. ↑ Lua error in package.lua at line 80: module 'strict' not found.
  34. ↑ http://www.mayoclinic.org/diseases-conditions/pouchitis/care-at-mayo-clinic/treatment/con-20036404
  35. ↑ http://www.gicure.com/gastrointestinal-health-blog
  36. ↑ http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2291363/
  37. ↑ Fecal Microbiota Transplants Effective Treatment for C. Difficile, Inflammatory Bowel Disease, Research Finds
  38. ↑ Lua error in package.lua at line 80: module 'strict' not found.
  39. ↑ Lua error in package.lua at line 80: module 'strict' not found.
  40. ↑ Lua error in package.lua at line 80: module 'strict' not found.
  41. ↑ Lua error in package.lua at line 80: module 'strict' not found.
  42. ↑ Lua error in package.lua at line 80: module 'strict' not found.
  43. ↑ Lua error in package.lua at line 80: module 'strict' not found.
  44. ↑ Lua error in package.lua at line 80: module 'strict' not found.
  45. ↑ Lua error in package.lua at line 80: module 'strict' not found.
  46. ↑ Lua error in package.lua at line 80: module 'strict' not found.
  47. ↑ Lua error in package.lua at line 80: module 'strict' not found.
  48. ↑ Lua error in package.lua at line 80: module 'strict' not found.
  49. ↑ 49.0 49.1 49.2 Lua error in package.lua at line 80: module 'strict' not found.
  50. ↑ 50.0 50.1 Lua error in package.lua at line 80: module 'strict' not found.
  51. ↑ Lua error in package.lua at line 80: module 'strict' not found.
  52. ↑ Lua error in package.lua at line 80: module 'strict' not found.
  53. ↑ Lua error in package.lua at line 80: module 'strict' not found.
  54. ↑ Lua error in package.lua at line 80: module 'strict' not found.
  55. ↑ Lua error in package.lua at line 80: module 'strict' not found.

External links

Retrieved from "https://infogalactic.com/w/index.php?title=Inflammatory_bowel_disease&oldid=1041159"