Crohn's disease: Difference between revisions

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{{Infobox_Disease |
{| class="infobox" style="float:right;"
  Name          = Crohn's disease |
|-
  Image          = Patterns of CD.svg|
| [[File:Siren.gif|30px|link=Crohn's disease resident survival guide]]|| <br> || <br>
  Caption        = The three most common sites of intestinal involvement in '''Crohn's disease''' are [[ileum|ileal]], ileocolic and [[colon]]ic.<ref name=Hanauer/>|
| [[Crohn's disease resident survival guide|'''Resident'''<br>'''Survival'''<br>'''Guide''']]
  DiseasesDB    = 3178 |
|}
  ICD10          = {{ICD10|K|50||k|50}} |
  ICD9          = {{ICD9|555}} |
  ICDO          = |
  OMIM          = 266600 |
  MedlinePlus    = 000249 |
  MeshID        = D003424 |
}}
{{Crohn's disease}}
{{Crohn's disease}}


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{{CMG}}
{{CMG}}


{{SK}} Regional enteritis
{{SK}} Regional enteritis; Crohn disease; regional ileitis
==Overview==
''[[Crohn's disease]]'' is a [[Chronic (medical)|chronic]], episodic, [[Inflammation|inflammatory]] [[inflammatory bowel disease|bowel disease]] (IBD) that affects the entire wall of the [[bowel]] or [[intestine]]s. Crohn's disease can affect any part of the [[gastrointestinal tract]] from [[mouth]] to [[anus]]; as a result, the symptoms of Crohn's disease vary among afflicted individuals.
 
The disease is characterized by areas of inflammation with areas of normal lining between in a symptom known as skip [[lesions]]. The main gastrointestinal symptoms are [[abdominal pain]], [[diarrhea]] (which may be bloody or the blood may not be seen by the naked eye), [[constipation]], [[vomiting]], [[weight loss]] or [[weight gain]].  Crohn's disease can also cause complications outside of the gastrointestinal tract such as [[Rash|skin rashes]], [[arthritis]], and [[Uveitis|inflammation of the eye]].<ref name=Hanauer>{{cite journal | last = Hanauer | first = Stephen B. | year = 1996 | month = March | title = Inflammatory bowel disease | journal = New England Journal of Medicine | volume = 334 | issue = 13 | pages = 841-848 | id = PMID 8596552 | url = http://content.nejm.org/cgi/content/extract/334/13/841 | accessdate = 2006-11-10}}</ref>
 
==Historical Perspective==
 
Inflammatory bowel diseases were described by [[Giovanni Battista Morgagni]] (1682-1771), by Polish surgeon Antoni Leśniowski in 1904 (leading to the use of the eponym "'''Leśniowski-Crohn disease'''" in Poland) and by Scottish physician T. Kennedy Dalziel in 1913.<ref>Kirsner JB. Historical aspects of inflammatory bowel disease. ''J Clin Gastroenterol.'' 1988 Jun;10(3):286-97.  PMID 2980764</ref>
 
[[Burrill Bernard Crohn]], an American gastroenterologist at New York City's [[Mount Sinai Hospital, New York|Mount Sinai Hospital]], described fourteen cases in 1932, and submitted them to the [[American Medical Association]] under the rubric of "Terminal ileitis: A new clinical entity".  Later that year, he, along with colleagues Leon Ginzburg and Gordon Oppenheimer published the case series as "Regional ileitis: a pathologic and clinical entity".<ref name=CrohnBB/>
 
The disease was independently described in 1904 by Polish surgeon [[Antoni Lesniowski]] and in 1932 by American [[gastroenterology|gastroenterologist]] [[Burrill Bernard Crohn]], for whom the disease was named.  Crohn, along with two colleagues, described a series of patients with inflammation of the [[terminal ileum]], the area most commonly affected by the illness.<ref name=CrohnBB>Crohn BB, Ginzburg L, Oppenheimer GD.  "Regional ileitis: a pathologic and clinical entity."  ''Mt Sinai J Med'' 2000 May;67(3):263-8.  PMID 10828911</ref>
 
==Classification==
[[Image:Distribution of CD.svg|center|thumb|250px|Distribution of gastrointestinal Crohn's disease.  Based on data from [[American Gastroenterological Association]].]]
Crohn's disease almost invariably affects the gastrointestinal tract. As a result, most gastroenterologists classify the disease by the affected areas. ''Ileocolic Crohn's disease'', which affects both the [[ileum]] (the last part of the [[small intestine]] that connects to the [[large intestine]]) and the large intestine, accounts for fifty percent of cases. ''Crohn's ileitis'', affecting the ileum only, accounts for thirty percent of cases, and ''Crohn's colitis'', affecting the large intestine, accounts for the remaining twenty percent of cases, and may be particularly difficult to distinguish from ulcerative colitis. The disease can attack any part of the digestive tract, from [[mouth]] to [[anus]]. However, individuals affected by the disease rarely fall outside these three classifications, being affected in other parts of the gastrointestinal tract such as the [[stomach]] and [[esophagus]].<ref name=Hanauer/>
Crohn's disease may also be classified by the behaviour of disease as it progresses. This was formalized in the Vienna classification of Crohn's disease.<ref name=Vienna>{{cite journal | author = Gasche C, Scholmerich J, Brynskov J, D'Haens G, Hanauer S, Irvine E, Jewell D, Rachmilewitz D, Sachar D, Sandborn W, Sutherland L | title = A simple classification of Crohn's disease: report of the Working Party for the World Congresses of Gastroenterology, Vienna 1998 | journal = Inflamm Bowel Dis | volume = 6 | issue = 1 | pages = 8-15 | year = 2000 | id = PMID 10701144}}</ref>  There are three categories of disease presentation in Crohn's disease: stricturing, penetrating, and inflammatory. ''Stricturing disease'' causes narrowing of the bowel which may lead to [[bowel obstruction]] or changes in the caliber of the [[feces]]. ''Penetrating disease'' creates abnormal passageways ([[fistula]]e) between the bowel and other structures such as the skin. ''Inflammatory disease'' (or non-stricturing, non-penetrating disease) causes inflammation without causing strictures or fistulae.<ref name=Vienna/><ref name=phenotypes>{{cite journal | author = Dubinsky MC, Fleshner PP. | title = Treatment of Crohn's Disease of Inflammatory, Stenotic, and Fistulizing Phenotypes. | journal = Curr Treat Options Gastroenterol | volume = 6 | issue = 3 | pages = 183-200 | year = 2003 | id = PMID 12744819}}</ref>
 
==Pathophysiology==
 
[[Image:Crohn's transmural path.jpg|thumb|left|120px|H and E section of [[colectomy]] showing transmural inflammation.]]
 
At the time of [[colonoscopy]], [[Biopsy|biopsies]] of the colon are often taken in order to confirm the diagnosis.  There are certain characteristic features of the [[pathology]] seen that point toward Crohn's disease. Crohn's disease shows a transmural pattern of [[inflammation]], meaning that the inflammation may span the entire depth of the intestinal wall.<ref name=Hanauer/> Grossly, [[ulcer]]ation is an outcome seen in highly active disease.  There is usually an abrupt transition between unaffected tissue and the ulcer. Under a microscope, biopsies of the affected colon may show [[mucosa]]l inflammation. Transmural inflammation results in formation of lymphoid aggregates throughout the wall of the colon. This inflammation is characterized by focal infiltration of [[neutrophils]], a type of inflammatory cell, into the [[epithelium]]. This typically occurs in the area overlying [[lymphoid tissue|lymphoid]] aggregates. These neutrophils, along with [[lymphocyte|mononuclear cells]], may infiltrate into the [[Crypts of Lieberkühn|crypts]] leading to inflammation (crypititis) or abscess (crypt abscess).  [[Granuloma]]s, aggregates of [[macrophage]] derivatives known as giant cells, are found in 50% of cases and are most specific for Crohn's disease. The granulomas of Crohn's disease do not show "caseation", a cheese-like appearance on microscopic examination that is characteristic of granulomas associated with infections such as [[tuberculosis]]. Biopsies may also show chronic mucosal damage as evidenced by blunting of the intestinal [[villus|villi]], atypical branching of the crypts, and change in the tissue type ([[metaplasia]]). One example of such metaplasia, ''Paneth cell metaplasia'', involves development of Paneth cells (typically found in the small intestine) in other parts of the gastrointestinal system.<ref name=Robbins>Crawford JM.  "The Gastrointestinal tract, Chapter 17".  In Cotran RS, Kumar V, Robbins SL. ''Robbins Pathologic Basis of Disease: 5th Edition''.  W.B. Saunders and Company, Philadelphia, 1994.</ref>
 
==Cause==
 
[[Image:NOD2 CARD15.svg|center|thumb|200px|Schematic of NOD2 CARD15 gene, which is associated with certain disease patterns in Crohn's disease]]
 
The exact cause of Crohn's disease is unknown. However, genetic and environmental factors have been invoked in the [[pathogenesis]] of the disease. Research has indicated that Crohn's disease has a strong genetic link. <ref>[http://www.ccfa.org/reuters/genelic link Crohn's disease has strong genetic link: study]</ref> The disease runs in families and those with a sibling with the disease are 30 times more likely to develop it than the normal population. Ethnic background is also a risk factor. Until very recently, whites and European Jews accounted for the vast majority of the cases in the United States, and in most industrialized countries, this demographic is still true. 
 
[[Mutation]]s in the [[NOD2|CARD15]] gene (also known as the NOD2 [[gene]]) are associated with Crohn's disease<!-- --><ref>Ogura Y, Bonen DK, Inohara N, ''et al.''  A frameshift mutation in NOD2 associated with susceptibility to Crohn's disease.  ''Nature''. 2001 May 31;411(6837):603-6.</ref> and with susceptibility to certain phenotypes of disease location and activity.<ref><!--
-->{{cite journal | author = Cuthbert A, Fisher S, Mirza M, ''et al.'' | title = The contribution of NOD2 gene mutations to the risk and site of disease in inflammatory bowel disease. | journal = Gastroenterology | volume = 122 | issue = 4 | pages = 867-74 | year = 2002 | id = PMID 11910337}}</ref> In earlier studies, only two genes were linked to Crohn's, but scientists now believe there are over eight genes that show genetics play a crucial role in the disease.
 
A handful of cases of Crohn's Disease cases were reported at the turn of the 20th century, but since then, the disease has continued to increase in prevalence dramatically. Some argue that this increase has been the result of a genetic shift in the population caused by conditions favoring individuals carrying the genes linked with the disease. These conditions could be a lower infant mortality rate or better health care in the nations that have the highest incidence of disease (industrialized nations). 
 
Others argue that Crohn's Disease is caused by a combination of environmental and genetic factors. Many environmental factors have also been hypothesized as causes or risk factors for Crohn's disease. Proven environmental risk factors include living in an industrialized country, smoking, and living in an urban area. Diets high in sweet, [[fat]]ty or [[Food processing|refined foods]] may also play a role. A retrospective Japanese study found that those diagnosed with Crohn's disease had higher intakes of sugar, fat, fish and shellfish than controls prior to diagnosis.<!--
--><ref>{{cite journal | author = Sakamoto N, Kono S, Wakai K, ''et al.'' | title = Dietary risk factors for inflammatory bowel disease: a multicenter case-control study in Japan. | journal = Inflamm Bowel Dis | volume = 11 | issue = 2 | pages = 154-63 | year = 2005 | id = PMID 15677909}}</ref> A similar study in Israel also found higher intakes of fats (especially chemically modified fats) and [[sucrose]], with lower intakes of [[fructose]] and fruits, water, [[potassium]], [[magnesium]] and vitamin C in the diets of Crohn's disease sufferers before diagnosis,<!--
--><ref>{{cite journal | author = Reif S, Klein I, Lubin F, Farbstein M, Hallak A, Gilat T | title = Pre-illness dietary factors in inflammatory bowel disease. | journal = Gut | volume = 40 | issue = 6 | pages = 754-60 | year = 1997 | id = PMID 9245929| url = http://gut.bmj.com/cgi/reprint/40/6/754 | format = PDF }}</ref> and cites three large European studies in which sugar intake was significantly increased in people with Crohn's disease compared with controls. Certain chemicals in the diet, known as microparticles, are also hypothesized as a risk factor for the disease, as well as a poor imbalance of omega-6 to healthy omega-3 fatty acids that emerging research shows helps to improve all types of inflammatory disease. The most common forms of microparticles include titanium dioxide, aluminosilicates, anatase, calcium phosphate, and soil residue. These substances are ubiquitous in processed food and most toothpastes and lip glosses. Soil residue is found on fresh fruits and vegetables unless carefully removed.
 
[[Tobacco smoking|Smoking]] has been shown to increase the risk of the return of active disease, or "flares".<ref>{{cite journal | author = Cosnes J | title = Tobacco and IBD: relevance in the understanding of disease mechanisms and clinical practice. | journal = Best Pract Res Clin Gastroenterol | volume = 18 | issue = 3 | pages = 481-96 | year = 2004 | id = PMID 15157822}}</ref>
The introduction of [[hormonal contraception]] in the United States in the 1960's is linked with a dramatic increase in the incidence rate of Crohn's disease. Although a causal linkage has not been effectively shown, there remain fears that these drugs work on the digestive system in similar ways to smoking.<ref><!--
-->{{cite journal | author = Lesko S, Kaufman D, Rosenberg L, ''et al.'' | title = Evidence for an increased risk of Crohn's disease in oral contraceptive users. | journal = Gastroenterology | volume = 89 | issue = 5 | pages = 1046-9 | year = 1985 | id = PMID 4043662}}</ref>
 
Additionally, many in the scientific community believe that early childhood exposure to illness is necessary to the creation of a proper immune system for those with the genetic suseptibility for Crohn's Disease. Like Polio, higher incidences of Crohn's Disease are associated with cleaner living conditions. Throughout the early and mid-20th century in the United States, the disease was strongly associated with upper-class populations, and today the disease does not yet exist in the many Third World countries, despite the fact that it occurs in all races. CD is also associated with first born and single children (because  they would have less exposure to childhood illness from siblings) and in populations that have low incidences of gastric cancer. Gastric cancer is most often caused by the bacterium Helicobacter pylori that flourishes in cramped and unsanitary conditions.<ref>{{cite journal|last=Morris|first= Danielle L|coauthors=Scott M Montgomery|date=2000-11-18|title=Early environmental factors may have role in both Crohn's disease and gastric carcinoma - Letter to the Editor|journal=British Medical Journal|url=http://findarticles.com/p/articles/mi_m0999/is_7271_321/ai_67708495/|accessdate=2008-01-16}}</ref>
 
Abnormalities in the immune system have often been invoked as being causes of Crohn's disease. It has been hypothesized that Crohn's disease involves augmentation of the [[T helper cell#Th1.2FTh2 Model for helper T cells|T<sub>h</sub>1]] of [[cytokine]] response in inflammation.<ref>Cobrin GM, Abreu MT. Defects in mucosal immunity leading to Crohn's disease.  ''Immunol Rev.'' 2005 Aug;206:277-95.  PMID 16048555</ref> The most recent gene to be implicated in Crohn's disease is ATG16L1, which may reduce the effectiveness of [[autophagy]], and hinder the body's ability to attack invasive bacteria.<ref>Prescott NJ, Fisher SA, Franke A, Hampe J, Onnie CM, Soars D, Bagnall R, Mirza MM, Sanderson J, Forbes A, Mansfield JC, Lewis CM, Schreiber S, Mathew CG. A nonsynonymous SNP in ATG16L1 predisposes to ileal Crohn's disease and is independent of CARD15 and IBD5. ''Gastroenterology.'' 2007 May;132(5):1665-71. PMID: 17484864.</ref>
 
A variety of pathogenic bacteria were initially suspected of being causative agents of Crohn's disease.  However, the current consensus is that a variety of microorganisms are simply taking advantage of their host's weakened mucosal layer and inability to clear bacteria from the intestinal walls, both symptoms of the disease.  <ref><!--
-->{{cite journal | author = Sartor, R. | title = Mechanisms of Disease: pathogenesis of Crohn's disease and ulcerative colitis | journal = Nature Clinical Practice Gastroenterology & Hepatology | year = 2006 | issue = 3 | pages = 390-407 | doi = 10.1038}}</ref>  Some studies have linked [[Mycobacterium avium subspecies paratuberculosis|''Mycobacterium avium'' subsp. ''paratuberculosis'']] to Crohn's disease, in part because it causes a very similar disease, [[Johne's disease]], in cattle. <ref>Naser SA, Collins MT.  Debate on the lack of evidence of Mycobacterium avium subsp. paratuberculosis in Crohn's disease.  ''Inflamm Bowel Dis.'' 2005 Dec;11(12):1123.  PMID 16306778</ref>
The [[mannose]] bearing antigens, mannins, from yeast may also elicit pathogenic [[anti saccharomyces cerevisiae antibodies]].<ref name="pmid1398231">{{cite journal | author = Giaffer MH, Clark A, Holdsworth CD | title = Antibodies to Saccharomyces cerevisiae in patients with Crohn's disease and their possible pathogenic importance | journal = Gut | volume = 33 | issue = 8 | pages = 1071-5 | year = 1992 | pmid = 1398231}}</ref>  Newer studies have linked specific strains of enteroadherent ''[[E. coli]]'' to the disease but failed to find evidence of contributions by other species.
<ref><!--
-->{{cite journal | author = Baumgart, M., ''et al.'' | title = Culture independent analysis of ileal mucosa reveals a selective increase in invasive Escherichia coli of novel phylogeny relative to depletion of Clostridiales in Crohn's disease involving the ileum (advance online publication) | journal = The ISME Journal | year = 2007 | url = http://www.nature.com/ismej/journal/vaop/ncurrent/abs/ismej200752a.html | doi = 10.1038}}</ref>
 
===Differentiating Crohn's Disease from other Diseases===
The most common disease that mimics the symptoms of Crohn's disease is [[ulcerative colitis]], as both are inflammatory bowel diseases that can affect the [[colon (anatomy)|colon]] with similar symptoms. It is important to differentiate these diseases, since the course of the diseases and treatments may be different. In some cases, however, it may not be possible to tell the difference, in which case the disease is classified as '''indeterminate colitis'''.<ref name=Podolsky/><ref name=Hanauer/><ref name=emed/>
 
{| class="prettytable" cellpadding=1 style="text-align:center"
|+ '''Comparisons of various factors in Crohn's disease and ulcerative colitis'''
|-
!  !! Crohn's disease !! Ulcerative colitis
|-
| [[Terminal ileum]] involvement || Commonly || Seldom
|-
| Colon involvement || Usually || Always
|-
| Rectum involvement || Seldom || Usually<ref name="Kornbluth-Sachar2004">{{cite journal | last = Kornbluth | first = Asher | coauthors = David B. Sachar | year = 2004 | month = July | title = Ulcerative Colitis Practice Guidelines in Adults | journal = American Journal of Gastroenterology | volume = 99 | issue = 7 | pages = 1371-1385 | doi = 10.1111/j.1572-0241.2004.40036.x | id = PMID 15233681 | url = http://www.acg.gi.org/physicians/guidelines/UlcerativeColitisUpdate.pdf | format = PDF | accessdate = 2006-11-08}}</ref>
|-
| Involvement around the [[anus]] || Common<ref name="HanauerCrohns">{{cite journal | last = Hanauer | first = Stephen B. | coauthors = William Sandborn |date=March 1 2001 | title = Management of Crohn's Disease in Adults | journal=American Journal of Gastroenterology | volume = 96 | issue = 3 | pages = 635-643 | doi = 10.1111/j.1572-0241.2001.03671.x | id = PMID 11280528 | url = http://www.acg.gi.org/physicians/guidelines/CrohnsDiseaseinAdults.pdf | format = PDF | accessdate = 2006-11-08}}</ref>
|| Seldom
|-
| Bile duct involvement || No increase in rate of [[primary sclerosing cholangitis]]  || Higher rate<ref>{{cite journal | last = Broomé | first = Ulrika | coauthors = Annika Bergquist | year = 2006 | month = February | title = Primary sclerosing cholangitis, inflammatory bowel disease, and colon cancer | journal = Seminars in Liver Disease | volume = 26 | issue = 1 | pages = 31-41 | doi =10.1055/s-2006-933561 | id = PMID 16496231 }}</ref>
|-
| Distribution of Disease || Patchy areas of inflammation (Skip lesions) || Continuous area of inflammation<ref name="Kornbluth-Sachar2004"/>
|-
| Endoscopy || Deep geographic and serpiginous (snake-like) [[ulcer]]s
|| Continuous ulcer
|-
| Depth of inflammation || May be transmural, deep into tissues<ref name="HanauerCrohns"/><ref name=Hanauer/>
|| Shallow, mucosal
|-
| [[Fistula]]e || Common<ref name="HanauerCrohns"/>
|| Seldom
|-
| [[Stenosis]] || Common || Seldom
|-
| [[Autoimmunity|Autoimmune disease]] || Widely regarded as an autoimmune disease || No consensus
|-
| [[Cytokine]] response || Associated with [[T helper cell#Th1.2FTh2 Model for helper T cells|T<sub>h</sub>1]] || Vaguely associated with T<sub>h</sub>2
|-
| [[Granuloma]]s on biopsy || Can have granulomas<ref name="HanauerCrohns"/>
|| Granulomas uncommon<ref name="Kornbluth-Sachar2004"/>
|-
| Surgical cure || Often returns following removal of affected part || Usually cured by removal of colon
|-
| [[Tobacco smoking|Smoking]] || Higher risk for smokers || Lower risk for smokers<ref name="Kornbluth-Sachar2004"/>
|}
 
==Diagnosis==
===Symptoms===
 
[[Image:CD serpiginous ulcer.jpg|left|thumb|200px|Endoscopy image of [[colon (anatomy)|colon]] showing [[serpiginous]] ulcer, a classic finding in Crohn's disease]]
Many people with Crohn's disease have symptoms for years prior to the diagnosis.<ref name=Pimentel>{{cite journal | last = Pimentel | first = Mark | coauthors = Michael Chang, Evelyn J. Chow, Siamak Tabibzadeh, Viorelia Kirit-Kiriak, Stephan R. Targan, Henry C. Lin | year = 2000 | month = December | title = Identification of a prodromal period in Crohn's disease but not ulcerative colitis | journal = American Journal of Gastroenterology | volume = 95 | issue = 12 | pages = 3458-62 | doi =10.1111/j.1572-0241.2000.03361.x | id = PMID 11151877 }}</ref> The usual onset is between 15 and 30 years of age but can occur at any age.<ref>[http://www.emedicinehealth.com/crohn_disease/article_em.htm Crohn Disease Overview]</ref> Because of the patchy nature of the gastrointestinal disease and the depth of tissue involvement, initial symptoms can be more vague than with [[ulcerative colitis]]. People with Crohn's disease will go through periods of flare-ups and [[remission]]. 
 
 
; Gastrointestinal symptoms
[[Abdominal pain]] may be the initial symptom of Crohn's disease. The pain is commonly [[cramp|cramp-like]] and may be relieved by [[defecation]]. It is often accompanied by [[diarrhea]], which may or may not be bloody, though diarrhea is not uncommon especially in those who have had surgery.  People who have had surgery or multiple surgeries often end up with [[short bowel syndrome]] of the gastrointestinal tract. The nature of the diarrhea in Crohn's disease depends on the part of the small intestine or colon that is involved. Ileitis typically results in large-volume watery feces. Colitis may result in a smaller volume of feces of higher frequency. Fecal consistency may range from solid to watery. In severe cases, an individual may have more than 20 [[Defecation|bowel movements]] per day and may need to awaken at night to defecate.<ref name=Hanauer/><ref name=emed/><ref name=Podolsky/><ref>{{cite journal | last = Mueller | first = M. H. | coauthors = M. E. Kreis, M. L. Gross, H. D. Becker, T. T. Zittel & E. C. Jehle | year = 2002 | month = August | title = Anorectal functional disorders in the absence of anorectal inflammation in patients with Crohn's disease | journal = British Journal of Surgery | volume = 89 | issue = 8 | pages = 1027-31 | doi =10.1046/j.1365-2168.2002.02173.x  | id = PMID 12153630 }}</ref> Visible bleeding in the feces is less common in Crohn's disease than in ulcerative colitis, but may be seen in the setting of Crohn's colitis.<ref name=Hanauer/> Bloody bowel movements are typically intermittent, and may be bright or dark red in colour. In the setting of severe Crohn's colitis, bleeding may be copious.<ref name=emed/> [[Flatulence|Flatus]] and bloating may also add to the intestinal discomfort.<ref name=emed/>
 
Symptoms caused by intestinal [[stenosis]] are also common in Crohn's disease. Abdominal pain is often most severe in areas of the bowel with stenoses. In the setting of severe stenosis, [[vomiting]] and [[nausea]] may indicate the beginnings of small [[bowel obstruction]].<ref name=emed>{{cite web|first= Latha|last= Gopal|coauthors=Senthil Nachimuthu|publisher=eMedicine|title=Crohn Disease|url=http://www.emedicine.com/MED/topic477.htm|accessdate=2006-07-02|date=2006-05-23}}</ref> Crohn's disease may also be associated with [[primary sclerosing cholangitis]], a type of inflammation of the bile ducts.
 
Perianal discomfort may also be prominent in Crohn's disease. Itchiness or pain around the [[anus]] may be suggestive of inflammation, [[fistula|fistulization]] or [[abscess]] around the anal area<ref name=Hanauer/> or [[anal fissure]]. Perianal skin [[acrochordon|tags]] are also common in Crohn's disease.<ref>{{cite journal | author = Taylor B, Williams G, Hughes L, Rhodes J | title = The histology of anal skin tags in Crohn's disease: an aid to confirmation of the diagnosis | journal = Int J Colorectal Dis | volume = 4 | issue = 3 | pages = 197-9 | year = 1989 | id = PMID 2769004}}</ref> [[Fecal incontinence]] may accompany peri-anal Crohn's disease. At the opposite end of the gastrointestinal tract, the mouth may be affected by non-healing sores ([[aphthous ulcer]]s). Rarely, the [[esophagus]], and [[stomach]] may be involved in Crohn's disease. These can cause symptoms including  difficulty swallowing ([[odynophagia]]), upper abdominal pain, and vomiting.<ref>{{cite journal | last = Fix | first = Oren K. | coauthors = Jorge A. Soto, Charles W. Andrews and Francis A. Farraye | year = 2004 | month = December | title = Gastroduodenal Crohn's disease | journal = Gastrointestinel Endoscopy | volume = 60 | issue = 6 | pages = 985 | doi = doi:10.1016/S0016-5107(04)02200-X | id = PMID 15605018 }}</ref>
 
;Systemic symptoms
Crohn's disease, like many other chronic, inflammatory diseases, can cause a variety of [[B symptoms|systemic symptoms]].<ref name=Hanauer/> Among children, [[growth failure]] is common. Many children are first diagnosed with Crohn's disease based on [[failure to thrive|inability to maintain growth]].<ref name=Beattie/>  As Crohn's disease may manifest at the time of the growth spurt in [[puberty]], up to 30% of children with Crohn's disease may have retardation of growth.<ref>{{cite journal | last = Büller | first = H.A. | year = 1997 | month = February | title = Problems in diagnosis of IBD in children | journal = The Netherlands Journal of Medicine  | volume = 50 | issue = 2 | pages = S8-S11 | doi =10.1016/S0300-2977(96)00064-2 | id = PMID 9050326 }}</ref> Fever may also be present, though fevers greater than 38.5&nbsp;[[Celsius|˚C]] (101.3&nbsp;[[Fahrenheit|˚F]]) are uncommon unless there is a complication such as an [[abscess]]<ref name=Hanauer/> Among older individuals, Crohn's disease may manifest as weight loss. This is usually related to decreased food intake, since individuals with intestinal symptoms from Crohn's disease often feel better when they do not eat and might lose their appetite.<ref name=Beattie>{{cite journal | last = Beattie | first = R.M. | coauthors = N. M. Croft, J. M. Fell, N. A. Afzal and R. B. Heuschkel | year = 2006 | month = May | title = Inflammatory bowel disease | journal = Archives of Disease in Childhood | volume = 91 | issue = 5 | pages = 426-32 | doi =10.1136/adc.2005.080481 | id = PMID 16632672 }}</ref>  People with extensive [[small intestine]] disease may also have [[malabsorption]] of [[carbohydrate]]s or [[lipid]]s, which can further exacerbate weight loss.<ref>{{cite journal | last = O'Keefe | first = S. J. | year = 1996 | title = Nutrition and gastrointestinal disease | journal = Scandinavian Journal of Gastroenterology Supplement | issue = 220 | pages = 52-9 | id = PMID 8898436 }}</ref>
 
;Extraintestinal symptoms
[[Image:Crohnie sores 4.JPG|thumb|left|150px|Erythema nodosum.]]
In addition to systemic and gastrointestinal involvement, Crohn's disease can affect many other organ systems.<ref name=Danese>{{cite journal | last = Danese | first = Silvio  | coauthors = Stefano Semeraro, Alfredo Papa, Italia Roberto, Franco Scaldaferri, Giuseppe Fedeli, Giovanni Gasbarrini, Antonio Gasbarrini | year = 2005 | month = December | title = Extraintestinal manifestations in inflammatory bowel disease | journal = World Journal of Gastroenterology | volume = 11 | issue = 46 | pages = 7227-7236 | id = PMID 16437620 | url = http://www.wjgnet.com/1007-9327/11/7227.asp | accessdate = 2006-07-02 }}</ref> Inflammation of the interior portion of the eye, known as [[uveitis]], can cause eye pain, especially when exposed to light ([[photophobia]]). Inflammation may also involve the white part of the eye ([[sclera]]), a condition called [[Scleritis|episcleritis]]. Both episcleritis and uveitis can lead to loss of vision if untreated.
 
Crohn's disease is associated with a type of [[Rheumatology|rheumatologic disease]] known as [[spondyloarthropathy|seronegative spondyloarthropathy]]. This group of diseases is characterized by inflammation of one or more [[joint]]s ([[arthritis]]) or muscle insertions ([[enthesitis]]). The arthritis can affect larger joints such as the knee or shoulder or may exclusively involve the small joints of the hand and feet. The arthritis may also involve the spine, leading to [[ankylosing spondylitis]] if the entire spine is involved or simply [[sacroiliitis]] if only the lower spine is involved. The symptoms of arthritis include painful, warm, swollen, stiff [[Arthralgia|joints]] and loss of joint mobility or function.
 
Crohn's disease may also involve the skin, blood, and [[endocrine system]]. One type of skin manifestation, [[erythema nodosum]], presents as red nodules usually appearing on the shins. Erythema nodosum is due to inflammation of the underlying subcutaneous tissue and is characterized by septal [[panniculitis]]. Another skin lesion, [[pyoderma gangrenosum]], is typically a painful ulcerating nodule. Crohn's disease also increases the risk of blood clots; painful swelling of the lower legs can be a sign of [[deep venous thrombosis]], while difficulty breathing may be a result of [[pulmonary embolism]]. [[Autoimmune hemolytic anemia]], a condition in which the immune system attacks the [[red blood cells]], is also more common in Crohn's disease and may cause fatigue, pallor, and other symptoms common in [[anemia]]. [[Clubbing]], a deformity of the ends of the fingers, may also be a result of Crohn's disease. Finally, Crohn's disease may cause [[osteoporosis]], or thinning of the bones. Individuals with osteoporosis are at increased risk of [[bone fracture]]s.<ref name=Bernstein>{{cite journal | last = Bernstein | first = Michael | coauthors = Sue Irwin and Gordon R. Greenberg | year = 2005 | month = September | title = Maintenance infliximab treatment is associated with improved bone mineral density in Crohn's disease | journal = The American Journal of Gastroenterology | volume = 100 | issue = 9 | pages = 2031-5. | doi =10.1111/j.1572-0241.2005.50219.x | id = PMID 16128948 }}</ref>
 
Crohn's disease can also cause neurological complications (reportedly in up to 15% of patients).<ref name="pro">[http://professionals.epilepsy.com/page/inflammatory_crohn.html Crohn's disease]. professionals.epilepsy.com. Retrieved on [[July 13]], [[2007]].</ref> The most common of these are seizures, stroke, myopathy, peripheral neuropathy, headache and depression.<ref name="pro"/>
 
Crohn's patients often also have issues with [[Small bowel bacterial overgrowth syndrome]], which has similar symptoms.
 
==Natural History , Complications and Prognosis==
;Complications
[[Image:Colorectal cancer endo 2.jpg|center|thumb|200px|[[Colonoscopy|Endoscopic]] image of '''colon cancer''' identified in the sigmoid [[colon (anatomy)]] on screening [[colonoscopy]] for Crohn's disease.]] 
Crohn's disease can lead to several mechanical complications within the intestines, including obstruction, fistulae, and abscesses. Obstruction typically occurs from strictures or adhesions which narrow the lumen, blocking the passage of the intestinal contents. Fistulae can develop between two loops of bowel, between the bowel and bladder, between the bowel and vagina, and between the bowel and skin. Abscesses are walled off collections of [[infection]], which can occur in the [[abdomen]] or in the [[wiktionary:perianal|perianal]] area in Crohn's disease sufferers.
 
Crohn's disease also increases the risk of cancer in the area of inflammation. For example, individuals with Crohn's disease involving the [[small bowel]] are at higher risk for [[Small intestine cancer|small intestinal cancer]]. Similarly, people with Crohn's colitis have a [[relative risk]] of 5.6 for developing [[colon cancer]].<ref>{{cite journal |author=Ekbom A, Helmick C, Zack M, Adami H |title=Increased risk of large-bowel cancer in Crohn's disease with colonic involvement |journal=Lancet |volume=336 |issue=8711 |pages=357-9 |year=1990 |pmid=1975343}}</ref> Screening for colon cancer with [[colonoscopy]] is recommended for anyone who has had Crohn's colitis for eight years, or more.<ref>{{cite journal | author = Collins P, Mpofu C, Watson A, Rhodes J | title = Strategies for detecting colon cancer and/or dysplasia in patients with inflammatory bowel disease | journal = Cochrane Database Syst Rev | volume = | issue = | pages = CD000279 | year = | id = PMID 16625534}}</ref>
 
Individuals with Crohn's disease are at risk of [[malnutrition]] for many reasons, including decreased food intake and [[malabsorption]]. The risk increases following resection of the [[small bowel]]. Such individuals may require oral supplements to increase their caloric intake, or in severe cases, [[total parenteral nutrition]] (TPN). Most people with moderate or severe Crohn's disease are referred to a [[dietitian]] for assistance in nutrition.<ref>{{cite journal | author = Evans J, Steinhart A, Cohen Z, McLeod R | title = Home total parenteral nutrition: an alternative to early surgery for complicated inflammatory bowel disease | journal = J Gastrointest Surg | volume = 7 | issue = 4 | pages = 562–6 | year = 2003 | id = PMID 12763417}}</ref>
 
There are many complications that can come with Crohn's disease like: obstructions, abscesses, free perforation, and hemorrhage.<ref>{{cite web|url=https://www.livingwithcrohnsdisease.com/livingwithcrohnsdisease/crohns_disease/complications_of_crohns.html|title=Complications of Crohn's Disease|accessdate=2008-01-16}}</ref>
 
Women with Inflammatory bowel disease shows that they "face a higher risk of adverse outcomes related to pregnancy, according to a report in the October issue of Gastroenterology" [http://www.ccfa.org/reuters/pregnancyoutcomes].
 
===Prognosis===
 
Crohn's disease is a [[Chronic (medicine)|chronic]] condition for which there is currently no cure. It is characterized by periods of improvement followed by episodes when symptoms flare up. With treatment, most people achieve a healthy height and weight, and the mortality rate for the disease is low. Crohn's disease is associated with an increased risk of small bowel and colorectal carcinoma.<ref name=Canavan>{{cite journal | last = Canavan | first = C. | coauthors = K. R. Abrams, J. Mayberry | year = 2006 | month = August? | title = Meta-analysis : colorectal and small bowel cancer risk in patients with Crohn's disease | journal = Alimentary pharmacology & therapeutics  | volume = 23 | issue = 8 | pages = 1097-1104 | id = ISSN 0269-2813 | url = http://cat.inist.fr/?aModele=afficheN&cpsidt=17660183 | accessdate = 2007-05-23 }}</ref>
 
Crohn's cannot be cured by surgery, though surgery does happen with blockages, whether partial or a full blockage occurs.  After the first surgery, the Crohn's usually shows up at the site of the resection though it can appear in other locations.  After a resection, scar tissue builds up which causes strictures.  A stricture is when the intestines becomes too small to allow excrement to pass through easily which can lead to a blockage. After the first resection, another resection may be necessary within five years of the first surgery.  [http://ibdcrohns.about.com/od/surgeryprocedures/a/resectioncrohns.htm]
 
Many patients will have temporary stoma formations together with possible associated complications. [http://www.answers.com/topic/crohn-s-disease?cat=health]
 
==Diagnosis==
 
[[Image:CD colitis.jpg|150px|thumb|left|[[Colonoscopy|Endoscopic]] image of Crohn's colitis showing deep ulceration.]]
[[Image:CT scan gastric CD.jpg|150px|thumb|left|[[CT scan]] showing Crohn's disease in the fundus of the [[stomach]]]]
[[Image:CD colitis 2.jpg|thumb|left|150px|Crohn's disease can mimic [[ulcerative colitis]] on endoscopy.  This [[Colonoscopy|endoscopic]] image is of Crohn's colitis showing diffuse loss of [[mucosa]]l architecture, friability of mucosa in sigmoid colon and exudate on wall, all of which can be found with ulcerative colitis.]]
 
The diagnosis of Crohn's disease can sometimes be challenging,<ref name=Pimentel/> and a number of tests are often required to assist the physician in making the diagnosis.<ref name=emed/>  Sometimes even with all the tests the Crohn's does not show itself.  A colonoscopy has about a 70% chance of showing the disease and the rest of the tests go down in percentage.  Disease in the small bowel can not be seen through some of the regular tests; for example, a colonoscopy can't get there.
 
;Endoscopy
A [[colonoscopy]] is the best test for making the diagnosis of Crohn's disease as it allows direct visualization of the colon and the [[terminal ileum]], identifying the pattern of disease involvement. Occasionally, the colonoscope can travel past the terminal ileum but it varies from patient to patient. During the procedure, the [[gastroenterologist]] can also perform a [[biopsy]], taking small samples of tissue for laboratory analysis which may help confirm a diagnosis.  As 30% of Crohn's disease involves only the ileum,<ref name=Hanauer/> [[cannula]]tion of the terminal ileum is required in making the diagnosis. Finding a patchy distribution of disease, with involvement of the colon or ileum but not the [[rectum]], is suggestive of Crohn's disease, as are other endoscopic stigmata.<!--
  --><ref>{{cite journal | last = Lee | first = S. D. | coauthors = R. D. Cohen | year = 2002 | month = march | title = Endoscopy in inflammatory bowel disease | journal = Gastroenterology Clinics of North America | volume = 31 | issue = 1 | pages = 119-32 | id = PMID 12122727 }}</ref>
 
[[Wireless capsule endoscopy]] is a technique where a small capsule with a built-in camera is swallowed, the camera takes serial pictures of the entire gastrointestinal tract and is passed in the patient's faeces.  It has been used in the search for Crohn's disease in the small bowel, which cannot be reached with colonoscopy or gastroscopy.<!--
  --><ref name="Hara2006"/><!--
-->The utility of capsule endoscopy for this, however, is still uncertain.<!--
  --><ref>{{cite journal | last = Triester | first = Stuart L. | coauthors = Jonathan A. Leighton, Grigoris I. Leontiadis, Suryakanth R. Gurudu, David E. Fleische, Amy K. Hara, Russell I. Heigh, Arthur D. Shiff, and Virender K. Sharma | year = 2006 | month = May | title = A meta-analysis of the yield of capsule endoscopy compared to other diagnostic modalities in patients with non-stricturing small bowel Crohn's disease | journal = The American Journal of Gastroenterology | volume = 101 | issue = 5 | pages = 954-64 | doi =10.1111/j.1572-0241.2006.00506.x | id = PMID 16696781 }}</ref>
 
;Radiologic tests
A [[barium follow-through|small bowel follow-through]] may suggest the diagnosis of Crohn's disease and is useful when the disease involves only the small intestine. Because colonoscopy and [[Esophagogastroduodenoscopy|gastroscopy]] allow direct visualization of only the terminal ileum and beginning of the [[duodenum]], they cannot be used to evaluate the remainder of the small intestine. As a result, a [[barium follow-through]] x-ray, wherein [[barium sulfate]] suspension is ingested and [[fluoroscopy|fluoroscopic]] images of the bowel are taken over time, is useful for looking for inflammation and narrowing of the small bowel.<!--
  --><ref name="Hara2006">{{cite journal | last = Hara | first = Amy K.  | coauthors = Jonathan A. Leighton, Russell I. Heigh, Virender K. Sharma, Alvin C. Silva, Giovanni De Petris, Joseph G. Hentz and David E. Fleischer | year = 2006 | month = January | title = Crohn disease of the small bowel: preliminary comparison among CT enterography, capsule endoscopy, small-bowel follow-through, and ileoscopy | journal = Radiology | volume = 238 | issue = 1 | pages = 128-34 | doi =10.1148/radiol.2381050296 | id = PMID 16373764 }}</ref><!--
  --><ref>{{cite journal | last = Dixon | first = P.M.  | coauthors = M.E. Roulston and D.J. Nolan | year = 1993 | month = January | title = The small bowel enema: a ten year review | journal = Clinical Radiology | volume = 47 | issue = 1 | pages = 46-8 | doi =10.1016/S0009-9260(05)81213-9 | id = PMID 8428417 }}</ref> Barium enemas, in which barium is inserted into the rectum and fluoroscopy used to image the bowel, are rarely used in the work-up of Crohn's disease due to the advent of colonoscopy. They remain useful for identifying anatomical abnormalities when strictures of the colon are too small for a colonoscope to pass through, or in the detection of colonic fistulae.<!--
  --><ref>{{cite journal | last = Carucci | first = L. R. | coauthors = M. S. Levine | year = 2002 | month = march | title = Radiographic imaging of inflammatory bowel disease | journal = Gastroenterology Clinics of North America | volume = 31 | issue = 1 | pages = 93-117 | id = PMID 12122746 }}</ref>
 
[[Computed tomography|CT]] and [[MRI]] scans are useful for evaluating the small bowel with [[enteroclysis]] protocols.<!--
  --><ref>{{cite journal | last = Rajesh | first = A.  | coauthors = D.D.T. Maglinte | year = 2006 | month = January | title = Multislice CT enteroclysis: technique and clinical applications | journal = Clinical Radiology | volume = 61 | issue = 1 | pages = 31-9 | doi =10.1016/j.crad.2005.08.006  | id = PMID 16356814 }}</ref><!--
-->They are additionally useful for looking for intra-abdominal complications of Crohn's disease such as [[abscess]]es, small bowel obstruction, or fistulae.<!--
  --><ref>{{cite journal | last = Zissin | first = Rivka | coauthors = Marjorie Hertz, Alexandra Osadchy, Ben Novis and Gabriela Gayer | year = 2005 | month = February | title = Computed Tomographic Findings of Abdominal Complications of Crohn’s Disease—Pictorial Essay | journal = Canadian Association of Radiologists Journal | volume = 56 | issue = 1 | pages = 25-35 | id = PMID 15835588 | url =http://www.carj.ca/issues/2005-Feb/25/pg25.pdf | format = PDF | accessdate = 2006-07-02 }}</ref> [[Magnetic resonance imaging]] (MRI) are another option for imaging the [[small bowel]] as well as looking for complications, though it is more expensive and less readily available<!--
  --><ref>{{cite journal | last = MacKalski | first = B. A. | coauthors = C. N. Bernstein | year = 2005 | month = May | title = New diagnostic imaging tools for inflammatory bowel disease | journal = Gut | volume = 55 | issue = 5 | pages = 733-41 | doi =10.1136/gut.2005.076612 | id = PMID 16609136 }}</ref>
 
Images shown below are courtesy of RadsWiki and copylefted
 
<div align="center">
<gallery heights="175" widths="175">
Image:Crohns-pseudosacculations-001.jpg|Abdominal x-ray of a patient with Crohn disease
Image:Crohns-pseudosacculations-002.jpg|Pseudosacculations in Crohn's disease
Image:Crohns-pseudosacculations-003.jpg|Pseudosacculations in Crohn's disease
Image:Crohns-pseudosacculations-004.jpg|Pseudosacculations in Crohn's disease
</gallery>
</div>
 
<gallery>
Image:
Active Crohn's disease CT 002.jpg|Active Crohn's disease CT
Image:


Active Crohn's disease MRI 003.jpg|Active Crohn's disease MRI
== [[Crohn's disease overview|Overview]] ==
==[[Crohn's disease historical perspective|Historical Perspective]] ==


Image:
== [[Crohn's disease classification|Classification]] ==
Active Crohn's disease MRI 004.jpg|Active Crohn's disease MRI
Image:
Active Crohn's disease small bowel series 001.jpg|Active Crohn's disease small bowel series


Image:
== [[Crohn's disease pathophysiology|Pathophysiology]] ==
Comb3.jpg|Comb sign in Crohn's disease


</gallery>
== [[Crohn's disease causes|Causes]] ==


;Blood tests
== [[Crohn's disease differential diagnosis|Differentiating Crohn's Disease from other Diseases]] ==
A [[complete blood count]] may reveal [[anemia]], which may be caused either by blood loss or [[Cyanocobalamin|vitamin B{{ssub|12}}]] deficiency. The latter may be seen with ileitis because vitamin B{{ssub|12}} is absorbed in the [[ileum]].<!--
  --><ref name=Goh>{{cite journal | last = Goh | first = Jason | coauthors = C. A. O'Morain | year = 2003 | month = February | title = Review article: nutrition and adult inflammatory bowel disease | journal = Alimentary Pharmacology & Therapeutics | volume = 17 | issue = 3 | pages = 307-20 | doi =10.1046/j.1365-2036.2003.01482.x | id = PMID 12562443 }}</ref><!--
--> [[Erythrocyte sedimentation rate]], or ESR, and [[C-reactive protein]] measurements can also be useful to gauge the degree of inflammation.<!--
  --><ref>{{cite journal | last = Chamouard | first = Patrick  | coauthors = Zoe Richert, Nicolas Meyer, Gabriel Rahmi, René Baumann | year = April | month = 2006 | title = Diagnostic Value of C-Reactive Protein for Predicting Activity Level of Crohn's Disease | journal = Clinical Gastroenterology and Hepatology | doi =10.1016/j.cgh.2006.02.003 | id = PMID 16630759 }} Epub ahead of print</ref> It is also true in patient with ilectomy done in response to the complication. Another cause of anaemia is anaemia of chronic disease, characterized by its microcytic and hypochromic anaemia. There are reasons in anaemia, including medication in treatment of inflammatory bowel disease like azathioprine can lead to cytopenia and sulfasalazine can also result in folate malabsorption, etc. Testing for anti-''[[Saccharomyces cerevisiae]]'' antibodies (ASCA) and [[anti-neutrophil cytoplasmic antibody|anti-neutrophil cytoplasmic antibodies]] (ANCA) has been evaluated to identify inflammatory diseases of the intestine<!--
  --><ref>{{cite journal | last = Kaila | first = B. | coauthors = K. Orr and C. N. Bernstein | year = 2005 | month = December | title = The anti-Saccharomyces cerevisiae antibody assay in a province-wide practice: accurate in identifying cases of Crohn's disease and predicting inflammatory disease | journal = The Canadian Journal of Gastroenterology | volume = 19 | issue = 12 | pages = 717-21 | id = PMID 16341311 | url =http://www.pulsus.com/Gastro/19_12/kail_ed.htm | accessdate = 2006-07-02 }}</ref><!--
--> and to differentiate Crohn's disease from ulcerative colitis.<!--
  --><ref>{{cite journal | last = Israeli | first = E. | coauthors = I. Grotto, B. Gilburd, R. D. Balicer, E. Goldin, A. Wiik and Y. Shoenfeld | year = 2005 | month = September | title = Anti-Saccharomyces cerevisiae and antineutrophil cytoplasmic antibodies as predictors of inflammatory bowel disease | journal = Gut | volume = 54 | issue = 9 | pages = 1232-6 | doi =10.1136/gut.2004.060228 | id = PMID 16099791 }}</ref>


==Epidemiology and Demographics==
==[[Crohn's disease epidemiology and demographics|Epidemiology and Demographics]]==
Crohn's disease affects between 400,000 and 600,000 people in North America.<ref name=Loftus>{{cite journal | last = Loftus | first = E. V. | coauthors = P. Schoenfeld, W. J. Sandborn | year = 2002 | month = January | title = The epidemiology and natural history of Crohn's disease in population-based patient cohorts from North America: a systematic review | journal = Alimentary Pharmacology & Therapeutics | volume = 16 | issue = 1 | pages = 51-60 | doi =10.1046/j.1365-2036.2002.01140.x | id = PMID 11856078 }}</ref>
Prevalence estimates for Northern Europe have ranged from 27–48 per 100,000.<ref name=Bernstein>{{cite journal | last = Bernstein | first = Charles N. | year = 2006 | month = July | title = The Epidemiology of Inflammatory Bowel Disease in Canada: A Population-Based Study | journal =The American Journal of Gastroenterology | volume = 101 | issue = 7 | pages = 1559–1568 | doi =10.1111/j.1572-0241.2006.00603.x | id = PMID 16863561 }}</ref> Crohn's disease tends to present initially in the teens and twenties, with another peak incidence in the fifties to seventies, although the disease can occur at any age.<ref name=Hanauer/><ref name=emed>{{cite web|first= Latha|last= Gopal|coauthors=Senthil Nachimuthu|publisher=eMedicine|title=Crohn Disease|url=http://www.emedicine.com/MED/topic477.htm|accessdate=2006-07-02|date=2006-05-23}}</ref>


The incidence of Crohn's disease has been ascertained from population studies in Norway and the United States and is similar at 6 to 7.1:100,000.<ref name=Hiatt>{{cite journal | last = Hiatt | first = Robert A. | coauthors = Leon Kaufman | year = 1988 | month = November | title = Epidemiology of inflammatory bowel disease in a defined northern California population | journal = Western Journal of Medicine | volume = 149 | issue = 5 | pages = 541-6 | id = PMID 3250100 | url =http://www.pubmedcentral.gov/articlerender.fcgi?tool=pubmed&pubmedid=3250100 | accessdate = 2006-07-02 }}</ref><ref>{{cite journal | last = Moum | first = B. | coauthors =M. H. Vatn, A. Ekbom, E. Aadland, O. Fausa, I. Lygren, N. Stray, J. Sauar, T. Schulz | year = 1996 | month = April | title = Incidence of Crohn's disease in four counties in southeastern Norway, 1990-93. A prospective population-based study. The Inflammatory Bowel South-Eastern Norway (IBSEN) Study Group of Gastroenterologists. | journal = Scandinavian Journal of Gastroenterology | volume = 31 | issue = 4 | pages = 355-61 | id = PMID 8726303 }}</ref>  Crohn's disease is more common in northern countries, and shows a higher preponderance in northern areas of the same country.<ref>{{cite journal | last = Shivananda | first = S. | coauthors =  J. Lennard-Jones, R. Logan, N. Fear, A. Price, L. Carpenter and M. van Blankenstein | year = 1996 | month = November | title = Incidence of inflammatory bowel disease across Europe: is there a difference between north and south? Results of the European Collaborative Study on Inflammatory Bowel Disease (EC-IBD) | journal = Gut | volume = 39 | issue = 5 | pages = 690-7 | id = PMID 9014768 }}</ref> The incidence of Crohn's disease in North America is 6:100,000, and is thought to be similar in Europe, but lower in Asia and Africa.<ref name=Hiatt/> It also has a higher incidence in Ashkenazi Jews.<ref name=Podolsky/>
== [[Crohn's disease risk factors|Risk Factors]] ==


Crohn's disease has a [[bimodal distribution]] in [[incidence (epidemiology)|incidence]] as a function of age: the disease tends to strike people in their teens and twenties, and people in their fifties through seventies.<ref name=Hanauer/><ref name=emed/> It is rare in early childhood. There is no association with gender, social class or occupation. Parents, siblings or children of people with Crohn's disease are 3 to 20 times more likely to develop the disease.<ref>Satsangi J, Jewell DP, Bell JI.  The genetics of inflammatory bowel disease and they are sick and we too.  Gut. 1997 May;40(5):572-4.  PMID 9203931.</ref> Twin studies show a concordance of greater than 55% for Crohn's disease.<ref>Tysk C, Lindberg E, Jarnerot G, Floderus-Myrhed B.  Ulcerative colitis and Crohn's disease in an unselected population of monozygotic and dizygotic twins. A study of heritability and the influence of smoking.  ''Gut'' 1988 Jul;29(7):990-6.  PMID 3396969</ref>
==[[Crohn's disease screening|Screening]]==


==Risk Factors==
== [[Crohn's disease natural history, complications and prognosis|Natural History, Complications and Prognosis]] ==
Although the cause of Crohn's disease is not known, it is believed to be an [[autoimmunity|autoimmune disease]] that is [[genetics|genetically]] linked. The highest relative risk occurs in siblings, affecting males and females equally. Smokers are three times more likely to get Crohn's disease.


Unlike the other major type of IBD, [[ulcerative colitis]], there is no known medical or [[surgery|surgical]] cure for Crohn's disease.<ref>{{cite web|first= M Bashar|last= Al-Ataie|coauthors=Vishwanath N Shenoy|publisher=eMedicine|title=Ulcerative colitis|url=http://www.emedicine.com/med/topic2336.htm|accessdate=2006-07-02|
== Diagnosis ==
date=2005-10-04}}</ref>  Instead, a number of medical treatments are utilized with the goal of putting and keeping the disease in [[remission (medicine)|remission]].  These include [[mesalazine|5-aminosalicylic acid]] (5-ASA) formulations (Pentasa capsules, Asacol tablets, Lialda tablets, Rowasa retention enemas), [[prednisone|steroid]] medications, immunomodulators (such as [[azathioprine]], [[mercaptopurine]] (6-MP), and [[methotrexate]]), and newer [[biological therapy for inflammatory bowel disease|biological]] medications, such as [[infliximab]] (Remicade) and [[adalimumab]] (Humira).<ref name=Podolsky>{{Cite journal|last=Podolsky|first= Daniel K.|title=Inflammatory bowel disease|journal=New England Journal of Medicine|month=August|year=2002|volume=346|issue=6|pages=417-29
|url=http://content.nejm.org/cgi/content/extract/347/6/417|accessdate=2006-07-02|id=PMID 12167685}}</ref>Also in January 2008 the U.S. Food and Drug Administration approved a new biologic known as [[natalizumab]] (Tysabri) for both induction of remission and maintenance of remission in moderate and severe Crohns Disease.


==Treatment==
[[Crohn's disease history and symptoms|History and Symptoms]] | [[Crohn's disease physical examination|Physical Examination]] | [[Crohn's disease laboratory findings|Laboratory Findings]] | [[Crohn's disease CT|CT]] | [[Crohn's disease MRI|MRI]] | [[Crohn's disease other imaging findings|Other Imaging Findings]] | [[Crohn's disease other diagnostic studies|Other Diagnostic Studies]]


{{main|Treatment of Crohn's disease|Biological therapy for inflammatory bowel disease}}
== Treatment ==
Treatment is only needed for people exhibiting symptoms. The therapeutic approach to Crohn's disease is sequential: to treat [[acute (medical)|acute]] disease and then to maintain [[remission]]. Treatment initially involves the use of medications to treat any infection and to reduce inflammation. This usually involves the use of aminosalicylate anti-inflammatory drugs and corticosteroids, and may include antibiotics. 


Once remission is induced, the goal of treatment becomes maintaining remission and avoiding flares. Because of side-effects, the prolonged use of corticosteroids must be avoided. Although some people are able to maintain remission with aminosalicylates alone, many require immunosuppressive drugs.<ref name="HanauerCrohns"/>
[[Crohn's disease medical therapy|Medical Therapy]] | [[Crohn's disease surgery|Surgery]] | [[Crohn's disease prevention|Prevention]] | [[Crohn's disease cost-effectiveness of therapy|Cost-Effectiveness of Therapy]] | [[Crohn's disease future or investigational therapies|Future or Investigational Therapies]]


On 14 January 2008 the U.S. Food and Drug Administration approved [[natalizumab]] (Tysabri) for both induction of remission and maintenance of remission in Crohns. Natalizumab is humanised monoclonal antibody (MAb), and the first alpha-4 antagonist in a new class of agents called selective adhesion-molecule (SAM) inhibitors. Alpha-4 integrin is required for leukocytes to adhere to the walls of blood vessels and migrate into the gut; natalizumab prevents leukocytes from doing that. Natalizumab was previously approved for multiple sclerosis. However, because it suppresses the immune system, natalizumab has been linked to a very rare adverse effect that is usually fatal if undetected. Leukocytes also protect the body from viruses, and 2 patients on natalizumab, who were also receiving other immuno-suppressive drugs ([[Interferon beta-1a|Avonex]] and Immuran), died of a rare brain infection, [[progressive multifocal leukoencephalopathy]]. Because of this danger, patients must be in a special monitoring program, and natalizumab is given as a mono-therapy.<ref name="FDA-Tysbari">{{cite press release|title=FDA Approves Tysabri to Treat Moderate-to-Severe Crohn's Disease|publisher=U.S. Food and Drug Administration|date=2008-01-14|url=http://www.fda.gov/bbs/topics/NEWS/2008/NEW01775.html|accessdate=2008-01-16
==Case Studies==
}}</ref>.As of late December 2007, more than 21,000 MS patients were receiving natalizumab mono-therapy without a single incidence of PML occurring.<ref>.http://www.elan.com/News/full.asp?ID=1091942</ref>.
[[Crohn's disease case study one|Case #1]]


[[Surgery]] may be required for complications such as obstructions, fistulas and/or abscesses, or if the disease does not respond to drugs within a reasonable time. For patients with an obstruction due to a stricture, two options for treatment are strictureplasty and resection of that portion of bowel.  According to a retrospective review at the Cleveland Clinic, there is no [[statistical significance]] between strictureplasty alone versus strictureplasty and resection specifically in cases of duodenal involvement. In these cases, re-operation rates were 31% and 27%, respectively, indicating that strictureplasty is a safe and effective treatment for selected patients with duodenal involvement.<ref name="pmid8918424">{{cite journal | author = Ozuner G, Fazio VW, Lavery IC, Milsom JW, Strong SA | title = Reoperative rates for Crohn's disease following strictureplasty. Long-term analysis | journal = Dis. Colon Rectum | volume = 39 | issue = 11 | pages = 1199-203 | year = 1996 | pmid = 8918424 | doi = }}</ref>
==Related Chapters==
 
Recent studies using [[Helminthic therapy]] or [[Hookworm]]s to treat Crohn's Disease and other (non-viral) auto-immune diseases seem to yield promising results.<ref>British Medical Journal [http://gut.bmj.com/cgi/content/full/55/1/136 A proof of concept study establishing Necator americanus in Crohn’s patients and reservoir donors]</ref><ref name="Daily Mail">Daily Mail. [http://www.dailymail.co.uk/pages/live/articles/technology/technology.html?in_article_id=481875&in_page_id=1965  The bloodsucking worm that fights allergies from inside your tummy] 14-09-2007.</ref><ref>[http://www.kuro5hin.org/story/2006/4/30/91945/8971 How to cure your asthma or hayfever using hookworm - a practical guide]. 01-05-2006.</ref>
 
==See also==
* [[Small bowel bacterial overgrowth syndrome]]
* [[Small bowel bacterial overgrowth syndrome]]
 
* [[Ulcerative colitis]]
== References ==
{{reflist|2}}


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Latest revision as of 21:09, 29 July 2020
Resident
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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]

Synonyms and keywords: Regional enteritis; Crohn disease; regional ileitis

Overview

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