Inflammatory bowel disease

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This article is about bowel inflammation. For functional disorder, see Irritable bowel syndrome.
Inflammatory bowel diseases
Classification and external resources

Micrograph showing inflammation of the large bowel in a case of inflammatory bowel disease. Colonic biopsy. H&E stain.
DiseasesDB 31127
eMedicine med/1169 emerg/106 oph/520
MeSH D015212

In medicine, inflammatory bowel disease (IBD) is a group of inflammatory conditions of the colon and small intestine. The major types of IBD are Crohn's disease and ulcerative colitis.[1][2][3]

Contents

Classification [edit]

The main forms of IBD are Crohn's disease and ulcerative colitis (UC). Inflammatory bowel diseases are considered autoimmune diseases, in which the body's own immune system attacks elements of the digestive system.[4]

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

The main 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.[5] Microscopically, ulcerative colitis is restricted to the mucosa (epithelial lining of the gut), while Crohn's disease affects the whole bowel wall ("transmural lesions").

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

Rarely, a definitive diagnosis of neither Crohn's disease nor 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 [edit]

Symptoms in Crohn's disease vs. ulcerative colitis   [ v · d · e ]
Crohn's disease Ulcerative colitis
Defecation Often porridge-like[6],
sometimes steatorrhea		 Often mucus-like
and with blood[6]
Tenesmus Less common[6] More common[6]
Fever Common[6] Indicates severe disease[6]
Fistulae Common[7] Seldom
Weight loss Often More seldom

Although 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.[8] Associated complaints or diseases include arthritis, pyoderma gangrenosum, and primary sclerosing cholangitis. Diagnosis is generally by assessment of inflammatory markers in stool followed by colonoscopy with biopsy of pathological lesions.

Findings in diagnostic workup in Crohn's disease vs. ulcerative colitis   [ v · d · e ]
Sign Crohn's disease Ulcerative colitis
Terminal ileum involvement Commonly Seldom
Colon involvement Usually Always
Rectum involvement Seldom Usually[9]
Involvement around
the anus		 Common[7] Seldom
Bile duct involvement No increase in rate of primary sclerosing cholangitis Higher rate[10]
Distribution of Disease Patchy areas of inflammation (Skip lesions) Continuous area of inflammation[9]
Endoscopy Deep geographic and serpiginous (snake-like) ulcers Continuous ulcer
Depth of inflammation May be transmural, deep into tissues[2][7] Shallow, mucosal
Stenosis Common Seldom
Granulomas on biopsy May have non-necrotizing non-peri-intestinal crypt granulomas[7][11][12] Non-peri-intestinal crypt granulomas not seen[9]


Causes [edit]

Pathophysiology in Crohn's disease vs. ulcerative colitis   [ v · d · e ]
Crohn's disease Ulcerative colitis
Cytokine response Associated with Th17[13] Vaguely associated with Th2
[icon] This section requires expansion. (November 2012)

Concentrated milk fats, a common ingredient of processed foods and confectionery, trigger blooms of otherwise rare gut bacteria in mice that may contribute to inflammatory gut diseases.[14]

Genetic causes

Genes are essential for us as they keep all the information about how the cell should work and IBD is a disease closely related to genetic causes and also subjected to selective pressures, since there is a strong relation between defense and autoimmunity, suggesting a key role for balancing selection in maintaining the genetic relationship between inflammation and infection.

This conclusion has been reached after comparing the genome of healthy people and affected people from the GWAS base. During this research it has also been proved that 25.0575 SNP’s are associated with chron’s disease, ulcerative colitis or combined IBD. Furthermore, both diseases are related by sharing 67% of the loci which are the cause of this illness. This may show a significant risk of being genetically predisposed to have both diseases and also to suffer from others such as diabetes since one locus encodes not only a small piece of information, but also the whole mutation which will affect all this information.

Between 110 and 163 loci are involved in the down production of T-cells and other less important subsets, which lead to IBD. With our immunologic system weakened, the antibody (also known as immunoglobulin) starts to mark our own cells, going from the circulating system to the bowel. Since T-cells are unable to work, other compounds of the immunologic system starts to work to defeat the inexistent hazard. This reaction leads to the bowel to be inflamed.

Although this high number of mutated loci needed to suffer from IBD, it is also proved that only a minority of the variance ends up in disease risk, which suggests that there are other factors (environmental factors, healthy habits…).

Treatment [edit]

Management in Crohn's disease vs. ulcerative colitis colitis   [ v · d · e ]
Crohn's disease Ulcerative colitis
Mesalamine Less useful[15] More useful[15]
Antibiotics Effective in long-term[16] Generally not useful[17]
Surgery Often returns following
removal of affected part		 Usually cured by removal
of colon

Optimal treatment of inflammatory bowel disease depends on what form it consists of. For example, mesalazine is more useful in ulcerative colitis than in Crohn's disease.[15] 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. More commonly, treatment of IBD requires a form of mesalazine.

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. Alternative medicine treatments for bowel disease exist in various forms, however such methods concentrate on controlling underlying pathology in order to avoid prolonged steroidal exposure or surgical excisement.[18]

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.

A relatively new treatment option is fecal bacteriotherapy (FBT), which has been used to successfully treat IBD in several small studies.[19][20] A memoir of home treatment of IBD with fecal bacteriotherapy, "Ulcerative Colitis from the Bottom Up," has been published as an ebook at Smashwords.com.

There is evidence of an infections contribution to inflammatory bowel disease in some patients and this subgroup of patients may benefit from antibiotic therapy.[21] Anaemia is a common finding in both ulcerative colitis and Crohn's risease. Due to raised levels of inflammatory cytokines such as hepcidin, parenteral iron is the preferred treatment option as it bypasses the gastrointestinal system, has lower incidence of adverse events and enables quicker treatment.

Due to the fact that the disease might be triggered by the blooms of a rare type of gut bacteria[22] some anti-bacterial drugs like chloroxine might be able to dispense the problem. A wider study is needed to confirm this.

Prognosis [edit]

Complications of Crohn's disease vs. ulcerative colitis   [ v · d · e ]
Crohn's disease Ulcerative colitis
Nutrient deficiency Higher risk
Colon cancer risk Slight Considerable
Prevalence of extraintestinal complications[23]
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 unacceptable 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.[24]

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.[25]

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.

Research [edit]

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

Initial reports[26] 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[27] and in some studies have proven to be as effective as prescription drugs.[28]

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.[29]

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.[29]

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.[29]

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.[30] ICAM-1 propagates an inflammatory response promoting the extravasation and activation of leukocytes (white blood cells) into inflamed tissue.[30] 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.[31] This suggests that ICAM-1 is a potential therapeutic target in the treatment of these diseases.[32][33]

References [edit]

  1. ^ Baumgart DC, Carding SR (2007). "Inflammatory bowel disease: cause and immunobiology.". The Lancet 369 (9573): 1627–40. doi:10.1016/S0140-6736(07)60750-8. PMID 17499605. 
  2. ^ a b Baumgart DC, Sandborn WJ (2007). "Inflammatory bowel disease: clinical aspects and established and evolving therapies.". The Lancet 369 (9573): 1641–57. doi:10.1016/S0140-6736(07)60751-X. PMID 17499606. 
  3. ^ Xavier RJ, Podolsky DK (2007). "Unravelling the pathogenesis of inflammatory bowel disease.". Nature 448 (7152): 427–34. doi:10.1038/nature06005. PMID 17653185. 
  4. ^ "IBD Facts". 
  5. ^ "Crohn's & Colitis Foundation of America". 
  6. ^ a b c d e f internetmedicin.se > Inflammatorisk tarmsjukdom, kronisk, IBD By Robert Löfberg. Retrieved Oct 2010 Translate.
  7. ^ a b c d Hanauer, Stephen B.; William Sandborn (2001-03-01). "Management of Crohn's disease in adults" (PDF). American Journal of Gastroenterology 96 (3): 635–43. doi:10.1111/j.1572-0241.2001.03671.x. PMID 11280528. Retrieved 2009-11-07. 
  8. ^ Stein, J. R.; Hartmann, F.; Dignass, A. U. (2010). "Diagnosis and management of iron deficiency anemia in patients with IBD". Nature Reviews Gastroenterology & Hepatology. doi:10.1038/nrgastro.2010.151.  edit
  9. ^ a b c Kornbluth, Asher; David B. Sachar (July 2004). "Ulcerative colitis practice guidelines in adults (update): American College of Gastroenterology, Practice Parameters Committee". American Journal of Gastroenterology 99 (7): 1371–85. doi:10.1111/j.1572-0241.2004.40036.x. PMID 15233681. Archived from the original on April 6, 2008. Retrieved 2009-11-07. 
  10. ^ Broomé, Ulrika; Annika Bergquist (February 2006). "Primary sclerosing cholangitis, inflammatory bowel disease, and colon cancer". Seminars in Liver Disease 26 (1): 31–41. doi:10.1055/s-2006-933561. PMID 16496231. 
  11. ^ Shepherd, NA (August 2002). "Granulomas in the diagnosis of intestinal Crohn's disease: a myth exploded?". Histopathology 41 (2): 166–8. doi:10.1046/j.1365-2559.2002.01441.x. PMID 12147095. 
  12. ^ Mahadeva, U; Martin, JP; Patel, NK; Price, AB (July 2002). "Granulomatous ulcerative colitis: a re-appraisal of the mucosal granuloma in the distinction of Crohn's disease from ulcerative colitis". Histopathology 41 (1): 50–5. doi:10.1046/j.1365-2559.2002.01416.x. PMID 12121237. 
  13. ^ Elson, CO; Cong, Y; Weaver, CT; Schoeb, TR; McClanahan, TK; Fick, RB; Kastelein, RA (2007). "Monoclonal Anti–Interleukin 23 Reverses Active Colitis in a T Cell–Mediated Model in Mice". Gastroenterology 132 (7): 2359–70. doi:10.1053/j.gastro.2007.03.104. PMID 17570211. 
  14. ^ Andy Coghlan (2012). "Milk fats clue to inflammatory bowel disease". New Scientist. 
  15. ^ a b c Pages 152-156 (Section: Inflammatory bowel disease(IBD)) in:Elizabeth D Agabegi; Agabegi, Steven S. (2008). Step-Up to Medicine (Step-Up Series). Hagerstwon, MD: Lippincott Williams & Wilkins. ISBN 0-7817-7153-6. 
  16. ^ Feller, M.; Huwiler, K.; Schoepfer, A.; Shang, A.; Furrer, H.; Egger, M. (2010). "Long-term antibiotic treatment for Crohn's disease: systematic review and meta-analysis of placebo-controlled trials". Clinical Infectious Diseases 50 (4): 473–480. doi:10.1086/649923. PMID 20067425.  edit
  17. ^ [1] Section "Antibiotics and Ulcerative Colitis" in: Prantera, C.; Scribano, M. (2009). "Antibiotics and probiotics in inflammatory bowel disease: why, when, and how". Current opinion in gastroenterology 25 (4): 329–333. doi:10.1097/MOG.0b013e32832b20bf. PMID 19444096.  edit
  18. ^ A Phytotherapeutic Approach to Lower Bowel Disease Gaia Garden
  19. ^ Fecal Microbiota Transplants Effective Treatment for C. Difficile, Inflammatory Bowel Disease, Research Finds
  20. ^ Borody TJ, Torres M, Campbell J et al. (2011). "Reversal of inflammatory bowel disease (IBD) with recurrent fecal microbiota transplants (FMT)". Am J Gastroenterol 106: 352. 
  21. ^ Ohkusa T, Sato N (March 2005). "Antibacterial and antimycobacterial treatment for inflammatory bowel disease". J. Gastroenterol. Hepatol. 20 (3): 340–51. doi:10.1111/j.1440-1746.2004.03472.x. PMID 15740475. 
  22. ^ Andy Coghlan (2012). "Milk fats clue to inflammatory bowel disease". New Scientist. 
  23. ^ Prevalence defined as at least 5 health care contacts in a 10 year period for the condition, according to: Greenstein, A. J.; Janowitz, H. D.; Sachar, D. B. (1976). "The extra-intestinal complications of Crohn's disease and ulcerative colitis: a study of 700 patients". Medicine 55 (5): 401–412. doi:10.1097/00005792-197609000-00004. PMID 957999.  edit
  24. ^ Roifman I, Sun YC, Fedwick JP, Panaccione R, Buret AG, Liu H, Rostom A, Anderson TJ, Beck PL (February 2009). [linkinghub.elsevier.com/retrieve/pii/S1542-3565(08)01109-9 "Evidence of endothelial dysfunction in patients with inflammatory bowel disease"] Check |url= scheme (help). Clin. Gastroenterol. Hepatol. 7 (2): 175–82. doi:10.1016/j.cgh.2008.10.021. PMID 19121648. Retrieved 2009-11-04. 
  25. ^ Gandhi S, Narula N, Marshall JK, Farkouh M. "Are patients with inflammatory bowel disease at increased risk of coronary artery disease?". American Journal of Medicine. doi:10.1016/j.amjmed.2012.03.015. PMID 22840916. Retrieved 2012-08-14. 
  26. ^ Summers RW, Elliott DE, Qadir K, Urban JF, Thompson R, Weinstock JV (2003). "Trichuris suis seems to be safe and possibly effective in the treatment of inflammatory bowel disease". Am. J. Gastroenterol. 98 (9): 2034–41. doi:10.1111/j.1572-0241.2003.07660.x. PMID 14499784. 
  27. ^ Furrie E, Macfarlane S, Kennedy A, et al. (2005). "Synbiotic therapy (Bifidobacterium longum/Synergy 1) initiates resolution of inflammation in patients with active ulcerative colitis: a randomised controlled pilot trial". Gut 54 (2): 242–9. doi:10.1136/gut.2004.044834. PMC 1774839. PMID 15647189. 
  28. ^ Kruis W, Fric P, Pokrotnieks J, et al. (2004). "Maintaining remission of ulcerative colitis with the probiotic Escherichia coli Nissle 1917 is as effective as with standard mesalazine". Gut 53 (11): 1617–23. doi:10.1136/gut.2003.037747. PMC 1774300. PMID 15479682. 
  29. ^ a b c Wright K, Rooney N, Feeney M, et al. (2005). "Differential expression of cannabinoid receptors in the human colon: cannabinoids promote epithelial wound healing". Gastroenterology 129 (2): 437–53. doi:10.1053/j.gastro.2005.05.026. PMID 16083701. 
  30. ^ a b Bennett CF, Condon TC, Grimm S, Chan H, Chiang MY (1994). "Inhibition of endothelial cell-leukocyte adhesion molecule expression with antisense oligonucleotides". J Immunol 152 (1): 3530–40. 
  31. ^ Jones SC, Banks RE, Haider A et al (1995). "Adhesion molecules in inflammatory bowel disease". Gut 36: 724–30. 
  32. ^ Van Deventer SJH, Wedel MK, Baker BF, Xia S, Chuang E, Miner Jr PB (2006). "A Phase II dose ranging, double-blind, placebo-controlled study of alicaforsen enema in subjects with acute exacerbation of mild to moderate left-sided ulcerative colitis". Alimentary Pharmacology & Therapeutics 23: 1415–25. 
  33. ^ Baumgart DC, Thomas S, (2012). "Targeting leukocyte migration and adhesion in Crohn's disease and ulcerative colitis.". Inflammopharmacology 20: 1–18.  Text "issue 1 " ignored (help)

External links [edit]

Inflammatory bowel disease: Crohn's disease and ulcerative colitis
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