Crohn's disease

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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

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Aditya Ganti M.B.B.S. [2]

Overview

Crohn’s disease is a chronic, episodic, inflammatory bowel disease (IBD) that affects the entire wall of the bowel or intestines. 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 skin rashes, arthritis, and inflammation of the eye. Diagnosis of Crohn’s disease requires an endoscopic evaluation of the colon followed by biopsy. Treatment for Crohn’s disease depends on the location and severity of disease, complications, and the person’s response to previous medical treatments when treated for recurring symptoms. ^[1]

Historical Perspective

The first case of Crohn’s disease was reported by Combe and Sanders, physicians of royal college London in 1806. The first detailed explanation of inflammatory bowel disease (IBD) was done by Giovanni Battista Morgagni and by Scottish physician T. Kennedy Dalziel.^[2]

Classification

Crohn’s disease almost invariably affects the gastrointestinal tract. As a result, most gastroenterologists classify the disease by the affected areas and behavior of disease as it progresses. The disease can attack any part of the digestive tract, from mouth to anus.^[3]^[4]^[5]^[6]

Pathophysiology

Genetic and environmental factors play a key role in the pathogenesis of Crohn’s disease. Mutations in the CARD15 gene (also known as the NOD2 gene) are associated with Crohn’s disease and with susceptibility to certain phenotypes of disease location and activity. Environmental factors include autoimmune disease and dysregulated immune response to commensal bacteria. Characteristic features of the pathology that point toward Crohn’s disease are transmural pattern of inflammation and skip lesions. Under microscopy granulomas are seen, which are aggregates of macrophage derivatives known as giant cells, are found in 50% of cases and are most specific for Crohn’s disease.

Causes

Several theories exist about what causes Crohn’s disease, but none have been proven. The human immune system is made from cells and different proteins that protect people from infection. The most popular theory is that the body’s immune system reacts abnormally in people with Crohn’s disease, mistaking bacteria, foods, and other substances for being foreign. The immune system’s response is to attack these “invaders.” During this process, white blood cells accumulate in the lining of the intestines, producing chronic inflammation, which leads to ulcerations and bowel injury.

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 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.

Epidemiology and Demographics

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 per 100,000 people. Prevalence estimates for Northern Europe have ranged from 27–48 per 100,000. 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. Crohn’s disease affects between 400,000 and 600,000 people in North America. Crohn’s disease has a bimodal distribution in incidence as a function of age. There is no association with gender, social class or occupation.

Risk Factors

Common risk factors in the development of crohns disease include white ancestry, age between 15-40 or 60-80 years, family history of crohns disease and cigarette smoking.

Natural History, Complications and Prognosis

Crohn’s disease 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 intestinal cancer. Similarly, people with Crohn’s colitis have a relative risk of 5.6 for developing colon cancer.There are many complications that can come with Crohn’s disease like: obstructions, abscesses, free perforation, and hemorrhage. With treatment, most people achieve a healthy life, and the mortality rate for the disease is low.^[7]^[8]

Diagnosis

History and Symptoms

Many people with Crohn’s disease have symptoms for years prior to the diagnosis. The usual onset is between 15 and 30 years of age but can occur at any age. Abdominal pain may be the initial symptom of Crohn’s disease. Crohn’s disease, like many other chronic, inflammatory diseases, can cause a variety of systemic symptoms. In addition to systemic and gastrointestinal involvement, Crohn’s disease can affect many other organ systems

Physical Examination

Physical examination findings in crohn’s disease include fever, fatigue, weakness, bloody diarrhea, abdominal pain, hypotension and tachycardia.

Laboratory Findings

The laboratory findings in a patient with Crohn’s disease include anemia, low albumin, elevated ESR, elevated serum alkaline phosphatase, deranged LFTs and electrolyte abnormalities.

Abdominal X Ray

Xray of the abdomen is not required for the diagnosis of Crohn’s disease. Xray may sometimes be one in case colitis is suspected. Xray is normal in mild to moderate disease and can show dilation and/or “thumb printing sign” in fulminant cases.

CT Scan

CT and MRI scans are useful for evaluating the small bowel with enteroclysis protocols. Findings include skip lesions, bowel wall thickening, surrounding inflammation, abscess, and fistulae.

MRI Scan

Magnetic resonance imaging (MRI) is another option for imaging the small bowel as well as looking for complications, though it is more expensive and less readily available.

Other Diagnostic Studies

The diagnosis of Crohn’s disease can sometimes be challenging, and a number of tests are often required to assist the physician in making the diagnosis. 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.

Other Imaging Findings

Other imaging findings for Crohn’s disease can be seen by the help of barium enema. Barium enema may show ulcerations and skip lesions. Barium enema must be avoided in severe cases as it can lead to the manifestation of toxic megacolon.

Treatment

Medical Therapy

Treatment may include drugs, nutrition supplements, surgery, or a combination of these options. The goals of treatment are to control inflammation, correct nutritional deficiencies, and relieve symptoms likeabdominal pain, diarrhea, and rectal bleeding. At this time, treatment can help control the disease by lowering the number of times a person experiences a recurrence, but there is no cure. Treatment for Crohn’s disease depends on the location and severity of disease, complications, and the person’s response to previous medical treatments when treated for recurring symptoms. Some people have long periods of remission, sometimes years, when they are free of symptoms. However, the disease usually recurs at various times over a person’s lifetime. This changing pattern of the disease means one cannot always tell when a treatment has helped. Predicting when a remission may occur or when symptoms will return is not possible.

Surgery

Two-thirds to three-quarters of patients with Crohn’s disease will require surgery at some point in their lives. Surgery becomes necessary when medications can no longer control symptoms. Surgery is used either to relieve symptoms that do not respond to medical therapy or to correct complications such as blockage, perforation, abscess, or bleeding in the intestine. Surgery to remove part of the intestine can help people with Crohn’s disease, but it is not a cure. Surgery does not eliminate the disease, and it is not uncommon for people with Crohn’s Disease to have more than one operation, as inflammation tends to return to the area next to where the diseased intestine was removed.

Prevention

Smoking cessation is the only lifestyle modification shown to have an effect on the prevention of recurrence in Crohn’s disease. There is no specific guidelines for colorectal cancer screening in patients with CD, it is widely accepted to perform surveillance colonoscopy every 1 to 2 years, starting at 8 years after establishing the diagnosis of pancolitis and 15 years in the case of left-sided colitis.

References

↑ Hanauer, Stephen B. (1996). “Inflammatory bowel disease”. New England Journal of Medicine. 334 (13): 841–848. PMID 8596552. Retrieved 2006-11-10. Unknown parameter |month= ignored (help)
↑ Kirsner JB (1988). “Historical aspects of inflammatory bowel disease”. J Clin Gastroenterol. 10 (3): 286–97. PMID 2980764.
↑ Satsangi J, Silverberg MS, Vermeire S, Colombel JF (2006). “The Montreal classification of inflammatory bowel disease: controversies, consensus, and implications”. Gut. 55 (6): 749–53. doi:10.1136/gut.2005.082909. PMC 1856208. PMID 16698746.
↑ Vermeire S, Van Assche G, Rutgeerts P (2012). “Classification of inflammatory bowel disease: the old and the new”. Curr. Opin. Gastroenterol. 28 (4): 321–6. doi:10.1097/MOG.0b013e328354be1e. PMID 22647554.
↑ Vucelic B (2009). “Inflammatory bowel diseases: controversies in the use of diagnostic procedures”. Dig Dis. 27 (3): 269–77. doi:10.1159/000228560. PMID 19786751.
↑ Freeman HJ (2007). “Application of the Montreal classification for Crohn’s disease to a single clinician database of 1015 patients”. Can. J. Gastroenterol. 21 (6): 363–6. PMC 2658118. PMID 17571169.
↑ “Complications of Crohn’s Disease”. Retrieved 2008-01-16.
↑ Ekbom A, Helmick C, Zack M, Adami H (1990). “Increased risk of large-bowel cancer in Crohn’s disease with colonic involvement”. Lancet. 336 (8711): 357–9. PMID 1975343.

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Historical Perspective

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Aditya Ganti M.B.B.S. [2]

Overview

The first case of Crohn’s disease was reported by Combe and Sanders, physicians of royal college London in 1806. The first detailed explanation of inflammatory bowel disease (IBD) was done by Giovanni Battista Morgagni and by Scottish physician T. Kennedy Dalziel.^[1]

Historical Perspective

In 1806, Combe and Sanders, physicians of royal college london reported the first case of Crohns disease.
In 1913 Giovanni Battista Morgagni (1682-1771) and by Scottish physician T. Kennedy Dalziel described inflammatory bowel diseases in detail for the first time.^[2]
In 1913, Dr.Kennedy reported the surgical evidence in his paper “Chronic Intestinal Entritis”.^[3]
In 1932, American gastroenterologist Burrill Bernard Crohn, after whom the disease was named, along with two colleagues, described a series of patients with inflammation of the terminal ileum, the area most commonly affected by the Crohn’s disease.^[4]
In 1932, Burrill Bernard Crohn at New York City’s Mount Sinai Hospital, described fourteen cases , 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.”^[4]

References

↑ Kirsner JB (1988). “Historical aspects of inflammatory bowel disease”. J Clin Gastroenterol. 10 (3): 286–97. PMID 2980764.
↑ Kirsner JB. Historical aspects of inflammatory bowel disease. J Clin Gastroenterol. 1988 Jun;10(3):286-97. PMID 2980764
↑ [+http://www.jstor.org/stable/25307529 “Chronic Interstitial Enteritis on JSTOR”] Check |url= value (help).
↑ ^4.0 ^4.1 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

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Classification

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Aditya Ganti M.B.B.S. [2]

Overview

Crohn’s disease can affect any part of the gastrointestinal tract expect rectum. Crohn’s disease may be classified based on the area of involvement and based on the behavior of the disease progression.

Classification

Crohn’s disease can affect any part of the gastrointestinal tract expect rectum. It can be classified based on the area of involvement and based on the behavior of the disease progression. Individuals affected by the Crohn’s disease rarely fall outside these classifications.

Based on the area of involvement

Ileocolic Crohn’s disease
- Crohn’s disease involving both the ileum and the large intestine, accounts for 50% of cases.
Crohn’s ileitis
- Crohn’s disease involving ileum only, accounts for 30% of cases.
Crohn’s colitis
- Crohn’s disease involving prendominantly only large intestine. Often difficult to distinguish from ulcerative colitis.

Based on the behavior of disease

Crohn’s disease may also be classified by the behavior of disease as it progresses. This was formalized in the Vienna classification of Crohn’s disease.^[1] There are three categories of disease presentation in Crohn’s disease:

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 (fistulae) 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.^[1]^[2]

References

↑ ^1.0 ^1.1 Gasche C, Scholmerich J, Brynskov J, D’Haens G, Hanauer S, Irvine E, Jewell D, Rachmilewitz D, Sachar D, Sandborn W, Sutherland L (2000). “A simple classification of Crohn’s disease: report of the Working Party for the World Congresses of Gastroenterology, Vienna 1998”. Inflamm Bowel Dis. 6 (1): 8–15. PMID 10701144.
↑ Dubinsky MC, Fleshner PP. (2003). “Treatment of Crohn’s Disease of Inflammatory, Stenotic, and Fistulizing Phenotypes”. Curr Treat Options Gastroenterol. 6 (3): 183–200. PMID 12744819.

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Pathophysiology

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Aditya Ganti M.B.B.S. [2]

Overview

Genetic and environmental factors play a key role in the pathogenesis of Crohn’s disease. Mutations in the CARD15 gene (also known as the NOD2 gene) are associated with Crohn’s disease and with susceptibility to certain phenotypes of disease location and activity. Environmental factors include autoimmune Disease and dysregulated Immune Response to Commensal Bacteria. Characteristic features of the pathology that point toward Crohn’s disease are transmural pattern of inflammation and skip lesions. Under microscopy Granulomas are seen, which are aggregates of macrophage derivatives known as giant cells, are found in 50% of cases and are most specific for Crohn’s disease.

Pathophysiology

The exact pathogenesis of Crohn’s disease is not clearly understood. However, 4 components have been proved to play a key role in the pathogenesis of Crohn’s disease.

Genetic component
Stress and environmental component
Microbial component
Inflammatory component

Genetic Component

There are several genes involved in the pathogenesis of Crohn’s disease. Mutation of any of these genes disrupts the normal function of cells triggering an inflammatory response. Some common and most important genes are as follows:.^[1]^[2]^[3]^[4]

NOD2/CARD15 gene
OCTN1 gene
DLG5 gene
TLR4 gene

The following tables summarizes the most important genes involved in the pathogenesis of Crohn’s disease

Genes	Chromosome		Function	Mutation
NOD2/CARD15	16	16q12.1	Encodes a scaffolding protein important for maintaining epithelial integrity	Disrupts normal epithelial integrity
OCTN1	05	5q31	Ecodes an ion channel	Alters the function of cation transporters and cell-to-cell signaling
DLG5	10	10q22.3	Interact additively with the NOD2/CARD15 gene	Iincrease susceptibility to CD along with CARD15
TLR4	09	9q33.1	Lipopolysaccharide signaling, bacterial recognition, and subsequent immune response	Altered immune response to pathogens and a subsequent increase in inflammation.

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

Stress and Environmental Component

Stress signals are perceived by the central nervous system (CNS), triggering the hypothalamic-pituitary-adrenal axis and the sympathetic-adrenal-medullary axis.
Neuroendocrine mediators released in response to stress not only modulate secretory, absorptive, and barrier functions in the gut but also increase the gut permeability.
Stress increases gut permeability along with other factors which inlude
- Corticotropin-releasing factor
- Autonomic nervous system
- Enteric nervous system

Microbial Component

The possible mechanisms for a bacterial etiology in the development of CD include:

Initial immune response to a specific pathogen resulting in intestinal infection
Alterations in normal bacterial flora of the intestinal tract
Defective mucosal barrier and overwhelming exposure to resident bacteria and their antigens and endotoxins
Alterations to the intestinal immune response

Infectious Pathogens Implicated in Crohn’s Disease
Escherichia coli Listeria monocytogenes Yersinia enterocolitica Mycobacterium avium subspecies paratuberculosis Measles virus

Immune Component

Altered immune response:
- An abnormal antibody response to an unspecified bacterial antigen is mainly responsible for inflammation in Crohn’s disease.
- The inflammatory response is believed to be triggered when elimination of specified microbial antigen was unsuccessful leading to altered immune response
- Dysregulation of normal mucosal immune response results in failure of phagocytosis leading to antigen persistence.
- Antigen persistance leads to antibodies production against all the normal gut flora.
- Activation resulted in secretion of tumor necrosis factor-alpha (TNF-alpha) and subsequent epithelial changes.
Cytokine response:
- The primary precipitating event in Crohn’s disease is T-cell mediated immune response.
- Activated T cells are responsible for the release of cytokines.
- The production of inflammatory cytokines results in ulceration and increased intestinal permeability.
- The characteristic granulomatous lesion seen in Crohn’s disease is evidence of a cell-mediated immune response.
- The early lesions of Crohn’s disease are characterized by elevations in interleukin-4 (IL-4) and decrease in IFN-gamma, a pattern more consistent with an overactive Th2 immune response.
- Chronic lesions are associated with high levels of interleukin-2 (IL-2), interferon gamma (IFN-gamma), TNF-alpha, and interleukin-12 and -18 (IL-12 and IL-18) consistent with an Th1 immune response.
- Tumor necrosis factor appears to play a significant role in the pathogenesis of CD.
  - TNF-alpha induces expression of adhesion factors that allow for inflammatory cells to infiltrate and activates macrophages to promote release of other pro-inflammatory mediators such as IFN-gamma.
  - Neutralization of TNF resulted in significant decrease in inflammation.
  - TNF-alpha concentrations in the stool can be used to monitor disease activity in both CD and UC.

Gross Pathology

Characteristic features of Crohn’s disease on gross pathology include:

Creeping fat
Thick/rubbery intestinal wall
Strictures (string sign on barium enema)
Skip areas
Aphthous mucosal ulcers

Microscopic Pathology

On microscopic analysis of the affected colon may show mucosal inflammation. Histo-pathological finding include

Transmural inflammation
Lymphoid aggregates throughout the wall of the colon.
Focal infiltration of neutrophils along with mononuclear cells, may infiltrate into the crypts leading to inflammation (crypititis) or abscess (crypt abscess).
Non- caseating Granulomas (aggregates of macrophage derivatives) known as giant cells, are found in 50% of cases and are most specific for Crohn’s disease.
Blunting of the intestinal villi
Atypical branching of the crypts
Paneth cell metaplasia ^[5]

H and E section of colectomy showing transmural inflammation.
Source:By The original uploader was Samir at English Wikipedia [GFDL (http://www.gnu.org/copyleft/fdl.html) or CC-BY-SA-3.0 (http://creativecommons.org/licenses/by-sa/3.0/)], via Wikimedia Commons

References

↑ Cuthbert A, Fisher S, Mirza M; et al. (2002). “The contribution of NOD2 gene mutations to the risk and site of disease in inflammatory bowel disease”. Gastroenterology. 122 (4): 867–74. PMID 11910337.
↑ 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.
↑ 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.
↑ Cobrin GM, Abreu MT. Defects in mucosal immunity leading to Crohn’s disease. Immunol Rev. 2005 Aug;206:277-95. PMID 16048555
↑ 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.

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Causes

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]

Overview

Several theories exist about what causes Crohn’s disease, but none have been proven. The human immune system is made from cells and different proteins that protect people from infection. The most popular theory is that the body’s immune system reacts abnormally in people with Crohn’s disease, mistaking bacteria, foods, and other substances for being foreign. The immune system’s response is to attack these “invaders.” During this process, white blood cells accumulate in the lining of the intestines, producing chronic inflammation, which leads to ulcerations and bowel injury.^[1] and with susceptibility to certain phenotypes of disease location and activity.^[2]

Causes

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. ^[3] 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.

Scientists do not know if the abnormality in the functioning of the immune system in people with Crohn’s disease is a cause, or a result, of the disease. Research shows that the inflammation seen in the GI tract of people with Crohn’s disease involves several factors: the genes the patient has inherited, the immune system itself, and the environment. Foreign substances, also referred to as antigens, are found in the environment. One possible cause for inflammation may be the body’s reaction to these antigens, or that the antigens themselves are the cause for the inflammation.

Scientists have found that high levels of a protein produced by the immune system, called tumor necrosis factor (TNF), are present in people with Crohn’s disease.

Mutations in the CARD15 gene (also known as the NOD2 gene) are associated with Crohn’s disease. 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. ^[4] and with susceptibility to certain phenotypes of disease location and activity.^[5]

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_h1 of cytokine response in inflammation.^[6] 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.^[7]

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. ^[8] Some studies have linked Mycobacterium avium subsp. paratuberculosis to Crohn’s disease, in part because it causes a very similar disease, Johne’s disease, in cattle. ^[9]

The mannose bearing antigens, mannins, from yeast may also elicit pathogenic anti saccharomyces cerevisiae antibodies.^[10] Newer studies have linked specific strains of enteroadherent E. coli to the disease but failed to find evidence of contributions by other species. ^[11]

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).

Schematic of NOD2 CARD15 gene, which is associated with certain disease patterns in Crohn’s disease

References

↑ 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.
↑ Cuthbert A, Fisher S, Mirza M; et al. (2002). “The contribution of NOD2 gene mutations to the risk and site of disease in inflammatory bowel disease”. Gastroenterology. 122 (4): 867–74. PMID 11910337.
↑ link Crohn’s disease has strong genetic link: study
↑ 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.
↑ Cuthbert A, Fisher S, Mirza M; et al. (2002). “The contribution of NOD2 gene mutations to the risk and site of disease in inflammatory bowel disease”. Gastroenterology. 122 (4): 867–74. PMID 11910337.
↑ Cobrin GM, Abreu MT. Defects in mucosal immunity leading to Crohn’s disease. Immunol Rev. 2005 Aug;206:277-95. PMID 16048555
↑ 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.
↑ Sartor, R. (2006). “Mechanisms of Disease: pathogenesis of Crohn’s disease and ulcerative colitis”. Nature Clinical Practice Gastroenterology & Hepatology (3): 390–407. doi:10.1038 Check |doi= value (help).
↑ 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
↑ Giaffer MH, Clark A, Holdsworth CD (1992). “Antibodies to Saccharomyces cerevisiae in patients with Crohn’s disease and their possible pathogenic importance”. Gut. 33 (8): 1071–5. PMID 1398231.
↑ Baumgart, M.; et al. (2007). “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)”. The ISME Journal. doi:10.1038 Check |doi= value (help).

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Differentiating Crohn’s Disease from other Diseases

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]

Overview

Crohn’s disease should be differentiated from other causes of diarrhea. It is very important to differentiate it from ulcerative colitis as the management of both conditions is different though the initial presentation may be confused for any of these disorders.^[1]^[2]

Differentiating Crohn’s Disease from other Diseases

Differentiating Crohn’s Disease from ulcerative colitis

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 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.^[1]^[2]^[3]^[4]^[5]^[6]

**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^[7]
Involvement around the anus	Common^[8]	Seldom
Bile duct involvement	No increase in rate of primary sclerosing cholangitis	Higher rate^[9]
Distribution of Disease	Patchy areas of inflammation (Skip lesions)	Continuous area of inflammation^[7]
Endoscopy	Deep geographic and serpiginous (snake-like) ulcers	Continuous ulcer
Depth of inflammation	May be transmural, deep into tissues^[8]	Shallow, mucosal
Fistulae	Common^[8]	Seldom
Stenosis	Common	Seldom
Autoimmune disease	Widely regarded as an autoimmune disease	No consensus
Cytokine response	Associated with T_h1	Vaguely associated with T_h2
Granulomas on biopsy	Can have granulomas^[8]	Granulomas uncommon^[7]
Surgical cure	Often returns following removal of affected part	Usually cured by removal of colon
Smoking	Higher risk for smokers	Lower risk for smokers^[7]
Risk of Cancer	Lower than UC	Higher

Differentiating Crohn’s from other causes of Gastroenteritis

Organism			Age predilection	Travel History	Incubation Size (cell)	Incubation Time	History and Symptoms			Diarrhea type∞				Food source	Specific consideration
Organism			Age predilection	Travel History	Incubation Size (cell)	Incubation Time	Fever	N/V	Cramping Abd Pain	Small Bowel	Large Bowel	Inflammatory	Non-inflammatory	Food source	Specific consideration
Viral	Rotavirus		<2 y	–	<10²	<48 h	+	+	–	+			+	–	Mostly in day cares, most common in winter.
	Norovirus		Any age	–	10 -10³	24-48 h	+	+	+	+			+	–	Most common cause of gastroenteritis, abdominal tenderness,
	Adenovirus		<2 y	–	10⁵ -10⁶	8-10 d	+	+	+	+			+	–	No seasonality
	Astrovirus		<5 y	–		72-96 h	+	+	+	+			+	Seafood	Mostly during winter
Bacterial	Escherichia coli	ETEC	Any age	+	10⁸ -10¹⁰	24 h	–	+	+	+			+	–	Causes travelers diarrhea, contains heat-labile toxins (LT) and heat-stable toxins (ST)
		EPEC	<1 y	–	10^†	6-12 h	–	+	+	+			+	Raw beef and chicken	–
		EIEC	Any ages	–	10^†	24 h	+	+	+		+		+	Hamburger meat and unpasteurized milk	Similar to shigellosis, can cause bloody diarrhea
		EHEC	Any ages	–	10	3-4 d	–	+	+		+	+		Undercooked or raw hamburger (ground beef)	Known as E. coli O157:H7, can cause HUS/TTP.
		EAEC	Any ages	+	10¹⁰	8-18 h	–	–	+		+		+	–	May cause prolonged or persistent diarrhea in children
	Salmonella sp.		Any ages	+	1	6 to 72 h	+	+	+		+	+		Meats, poultry, eggs, milk and dairy products, fish, shrimp, spices, yeast, coconut, sauces, freshly prepared salad.	Can cause salmonellosis or typhoid fever.
	Shigella sp.		Any ages	–	10 – 200	8-48 h	+	+	+		+	+		Raw foods, for example, lettuce, salads (potato, tuna, shrimp, macaroni, and chicken)	Some strains produce enterotoxin and Shiga toxin similar to those produced by E. coli O157:H7
	Campylobacter sp.		<5 y, 15-29 y	–	10⁴	2-5 d	+	+	+		+	+		Undercooked poultry products, unpasteurized milk and cheeses made from unpasteurized milk, vegetables, seafood and contaminated water.	May cause bacteremia, Guillain-Barré syndrome (GBS), hemolytic uremic syndrome (HUS) and recurrent colitis
	Yersinia enterocolitica		<10 y	–	10⁴ -10⁶	1-11 d	+	+	+		+	+		Meats (pork, beef, lamb, etc.), oysters, fish, crabs, and raw milk.	May cause reactive arthritis; glomerulonephritis; endocarditis; erythema nodosum. can mimic appendicitis and mesenteric lymphadenitis.
	Clostridium perfringens		Any ages		> 10⁶	16 h	–	–	+		+		+	Meats (especially beef and poultry), meat-containing products (e.g., gravies and stews), and Mexican foods.	Can survive high heat,
	Vibrio cholerae		Any ages	–	10⁶-10¹⁰	24-48 h	–	+	+	+			+	Seafoods, including molluscan shellfish (oysters, mussels, and clams), crab, lobster, shrimp, squid, and finfish.	Hypotension, tachycardia, decreased skin turgor. Rice-water stools
Parasites	Protozoa	Giardia lamblia	2-5 y	+	1 cyst	1-2 we	–	–	+	+			+	Contaminated water	May cause malabsorption syndrome and severe weight loss
		Entamoeba histolytica	4-11 y	+	<10 cysts	2-4 we	–	+	+		+	+		Contaminated water and raw foods	May cause intestinal amebiasis and amebic liver abscess
		Cryptosporidium parvum	Any ages	–	10-100 oocysts	7-10 d	+	+	+	+			+	Juices and milk	May cause copious diarrhea and dehydration in patients with AIDS especially with 180 > CD₄
		Cyclospora cayetanensis	Any ages	+	10-100 oocysts	7-10 d	–	+	+	+			+	Fresh produce, such as raspberries, basil, and several varieties of lettuce.	More common in rainy areas
	Helminths	Trichinella spp	Any ages	–	Two viable larvae (male and female)	1-4 we	–	+	+		+		+	Undercooked meats	More common in hunters or people who eat traditionally uncooked meats
		Taenia spp	Any ages	–	1 larva or egg	2-4 m	–	+	+	+			+	Undercooked beef and pork	Neurocysticercosis: Cysts located in the brain may be asymptomatic or seizures, increased intracranial pressure, headache.
		Diphyllobothrium latum	Any ages	–	1 larva	15 d	–	–	–	+			+	Raw or undercooked fish.	May cause vitamin B₁₂ deficiency

∞Small bowel diarrhea: watery, voluminous with less than 5 WBC/high power field

Large bowel diarrhea: Mucousy and/or bloody with less volume and more than 10 WBC/high power field
† It could be as high as 1000 based on patient’s immunity system.

Cause			Osmotic gap		History	Physical exam	Gold standard	Treatment
Cause			< 50 mOsm per kg	> 50 mOsm per kg*	History	Physical exam	Gold standard	Treatment
Watery	Secretory	Crohns	+	–	Abdominal pain followed by diarrhea	Abdominal tenderness when palpated in severe disease Blood seen on rectal exam Fever Tachycardia Hypotension	Colonoscopy with biopsy	Topical mucosamine and corticosteroids are preferred Mesalamine and sulfasalazine are used for remission
		Hyperthyroidism	+	–	Excessive sweating Heat intolerance Increased bowel movements	Lump in the neck Proptosis Tremors Increased DTR	TSH with T3 and T4	Carbimazole and methimazole Beta blockers like propylthiouracil Iodine-131
		VIPoma	+	–	Watery diarrhea Dehydration (thirst, dry skin, dry mouth, tiredness, headaches, and dizziness) Lethargy, muscle weakness Nausea, vomiting Crampy abdominal pain Weight loss Flushing	Tachycardia Rash Facial flushing Abdominal distention Abdominal tenderness in the right upper abdominal quadrant	Elevated VIP levels Followed by imaging	Sandostatin or chemotherapy for malignant tumors Surgical removal of the tumor
	Osmotic	Lactose intolerance	–	+	Abdominal pain Bloating Diarrhea Flatulence	Abdominal tenderness	Intestinal biopsy	Avoidance of dietary lactose Substitution to maintain nutrient intake Regulation of calcium intake Use of enzyme lactase
	Osmotic	Celiac disease	–	+	May be asymptomatic Vague abdominal pain Diarrhea Weight loss Malabsorption / steatorrhea Bloatedness	Abdominal pain and cramping Abdominal distention Tetany Mouth ulcers Dermatitis herpetiformis Signs of the fat-soluble vitamins A, D, E, and K deficiency	IgA tissue transglutaminase Ab	Gluten-free diet
	Functional	Irritable bowel syndrome	–	–	Abdominal pain or discomfort recurring at least 3 days per month in the past 3 months and associated with 2 or more of the following: Improves with defecation Onset associated with change in frequency of stool Onset associated with change in appearance of stool 25% of bowel movements are loose stools History of straining is also common	Abdominal tenderness Hard stool in the rectal vault	Clinical diagnosis ROME III criteria Pharmacologic studies based criteria	High dietary fiber Osmotic laxatives such as polyethylene glycol, sorbitol, and lactulose Antispasmodic drugs (e.g. anticholinergics such as hyoscyamine or dicyclomine)

Template:WikiDoc Sources

Differential Diagnosis

Crohn’s disease must be differentiated from:^[10]^[11]^[12]^[13]^[14]^[15]^[16]^[17]^[18]

Disease	Cause	Symptoms									Diagnosis	Other findings
		Pain			Nausea & Vomiting	Heartburn	Belching or Bloating	Weight loss	Loss of Appetite	Stools	Endoscopy findings
		Location	Aggravating Factors	Alleviating Factors	Nausea & Vomiting	Heartburn	Belching or Bloating	Weight loss	Loss of Appetite	Stools	Endoscopy findings
Acute gastritis	H. pylori NSAIDS Corticosteroids Alcohol Spicy food Viral infections Crohn’s disease Autoimmune diseases Bile reflux Cocaine use Breathing machine or ventilator Ingestion of corrosives	Epigastric pain	Food	Antacids	?	?	?	–	?	Black stools	Pangastritis or antral gastritis Erosive (Superficial, deep, hemorrhagic) Nonerosive (H. pylori)	–
Chronic gastritis	H. pylori Alcohol Medications Autoimmune diseases Chronic stress	Epigastric pain	Food	Antacids	?	?	?	?	?	–	H. pylori gastritis Atrophy Intestinal metaplasia Lymphocytic gastritis Enlarged folds Aphthoid erosions	–
Atrophic gastritis	H. pylori Autoimmune disease	Epigastric pain	–	–	?	–		?	?	–	H. pylori Mucosal atrophy Autoimmune Mucosal atrophy	Iron deficiency anemia Autoimmune gastritis diagnosis include: Antiparietal and anti-IF antibodies Achlorhydria and hypergastrinemia Low serum cobalamine
Crohn’s disease	Autoimmune disease	Abdominal pain	–	–	–	–	–	?	?	Chronic diarrhea often bloody with pus or mucus Rectal bleeding	Mucosal nodularity with cobblestoning Multiple aphthous ulcers Linier or serpiginous ulcerations Thickened antral folds Antral narrowing Hypoperistalsis Duodenal strictures	Fever Fatigue Anemia (pernicious anemia)
GERD	Lower esophageal sphincter abnormalities Hiatal hernia Abnormal esophageal contractions Prolonged emptying of stomach Gastrinomas	Epigastric pain	Spicy food Tight fitting clothing	Antacids Head elevation during sleep	? (Suspect delayed gastric emptying)	?	–	–	–	–	Esophagitis Barrette esophagus Strictures	Other symptoms: Dysphagia Regurgitation Nocturnal cough Hoarseness Complications Esophagitis Strictures Barrette esophagus
Peptic ulcer disease	H. pylori Smoking Alcohol Radiation therapy Medications Zollinger-ellison syndrome	Epigastric pain sometimes extending to back Right upper quadrant pain	Duodenal ulcer Pain aggravates with empty stomach Gastric ulcer Pain aggravates with food	Antacids Duodenal ulcer Pain alleviates with food	?	?	–	–	–	Black stools	Gastric ulcers Discrete mucosal lesions with a punched-out smooth ulcer base with whitish fibrinoid base Most ulcers are at the junction of fundus and antrum 0.5-2.5cm Duodenal ulcers Well-demarcated break in the mucosa that may extend into the muscularis propria of the duodenum Found in the first part of duodenum <1cm	Other diagnostic tests Serum gastrin levels Secretin stimulation test Biopsy
Gastrinoma	Associated with MEN type 1	Abdominal pain	–	–	? (suspect gastric outlet obstruction)	?	–	–	–	Black stools	Useful in collecting the tissue for biopsy	May present with symptoms of GERD or peptic ulcer disease Associated with MEN type 1 Diagnostic tests Serum gastrin levels Somatostatin receptor scintigraphy CT and MRI
Gastric Adenocarcinoma	H. pylori infection Smoked and salted food	Abdominal pain	–	–	?	?	?	?	?	Black stools, or blood in stools	Esophagogastroduodenoscopy Multiple biopsies are taken to establish the diagnosis	Other symptoms Dysphagia Early satiety Frequent burping
Primary gastric lymphoma	H. pylori infection	Abdominal pain Chest pain	–	–	–	–	–	?	–	–	Useful in collecting the tissue for biopsy	Other symptoms Painless swollen lymph nodes in neck and armpit Night sweats Fatigue Fever Cough or trouble breathing

Oral Crohn’s lesions must be differentiated from other diseases causing oral lesions such as leukoplakia and herpes simplex virus infection.

Disease	Presentation	Risk Factors	Diagnosis	Affected Organ Systems	Important features	Picture
Diseases predominantly affecting the oral cavity
Oral Candidiasis	Dysphagia or odynophagia White patches on the mouth and tongue	Newborn babies Denture users Poorly controlled diabetes As a side effect of medication, most commonly having taken antibiotics. Inhaled corticosteroids for the treatment of lung conditions (e.g, asthma or COPD) may also result in oral candidiasis which may be reduced by regularly rinsing the mouth with water after taking the medication. People with poor nutrition, specifically vitamin A, iron and folate deficiencies. People with an immune deficiency (e.g. as a result of AIDS/HIV or chemotherapy treatment). Women undergoing hormonal changes, like pregnancy or those on birth control pills. Organ transplantation patients	Clinical diagnosis Confirmatory tests rarely needed	Localized candidiasis Oral and esophageal candidasis Candida vulvovaginitis Chronic mucocutaneous candidiasis Invasive candidasis Candidaemia Candida endocarditis Candida osteoarticular disease	Oral candidiaisis is a benign self limiting disease unless accompanied by immunosuppression.	Tongue infected with oral candidiasis – By James Heilman, MD – Own work, CC BY-SA 3.0, httpscommons.wikimedia.orgwindex.phpcurid=11717223.jpg
Herpes simplex oral lesions	Fever Sore throat Painful ulcers	Stress Recent URTI Female sex	Physical examination Viral culture Tzanck smear	Orofacial Infection Anogenital Infection Ocular Infection Herpes Encephalitis Neonatal Herpes Herpetic Whitlow Herpes Gladiatorum	The symptoms of primary HSV infection generally resolve within two weeks	Oral herpes simplex infection – By James Heilman, MD – Own work, CC BY-SA 3.0, httpscommons.wikimedia.orgwindex.phpcurid=19051042.jpg
Aphthous ulcers	Painful, red spot or bump that develops into an open ulcer	Being a female Between the ages of 10-40 Family history of aphthous ulcers	Physical examination Diagnosis of exclusion	Oral cavity	Self-limiting , Pain decreases in 7 to 10 days, with complete healing in 1 to 3 weeks	Apthous ulcer on the lower surface of the tongue – By Ebarruda – Own work, CC BY-SA 3.0, httpscommons.wikimedia.orgwindex.phpcurid=7903358
Squamous cell carcinoma	Non healing ulcer, nodule, indurated plaque or mass May involve skin, lips, inside the mouth, throat or esophagus	Chronic sun or UV exposure Fair skin Elderly age (>45 yrs) Male sex Smoking	Physical exam Biopsy	Oral Cavity Floor of mouth Lateral tongue Throat Esophagus	Malignant Can spread to TMJ Some times associated with leukoplakia	Squamous cell carcinoma – By Luca Pastore, Maria Luisa Fiorella, Raffaele Fiorella, Lorenzo Lo Muzio – http://www.plosmedicine.org/article/showImageLarge.action?uri=info%3Adoi%2F10.1371%2Fjournal.pmed.0050212.g001, CC BY 2.5, https://commons.wikimedia.org/w/index.php?curid=15252632
Leukoplakia	White leathery spots on the mucous membranes of the tongue and inside of the mouth Lateral borders of tongue	Atypical Tobacco use Chronic irritation Immunodeficiency Bloodroot (sanguinaria)	Physical exam Diagnosis of exclusion Biopsy	Vulvar lesions occur independent of oral lesions	Associated with HIV Persistant white spots Benign but can progress to carcinoma after almost 10 years Oral proliferative verrucous leukoplakia is an aggressive sub type with multiple lesions and higher conversion to warts or carcinoma^[19]	Leukoplakia – By Aitor III – Own work, Public Domain, https://commons.wikimedia.org/w/index.php?curid=9873087
Melanoma	A lesion with ABCD Asymmetry Border irregularity Color variation Diameter changes Bleeding from the lesion	UV radiations Genetic predisposition Old age Male gender Family or personal history of melanoma Multiple benign or atypical nevi	ABCD characteristics Bleeding or ulceration may show malignancy Serum LDH may be elevated in case of malignancy Biopsy	Can metastasize All UV radiation or sun exposed areas can be effected independently 1-2 to hundreds of granules	Neural crest cell derivative Development begins with disruption of nevus growth control Progression involves MAPK/ERK pathway N-RAS or BRAF oncogene also involved	Oral melanoma – By Emmanouil K Symvoulakis, Dionysios E Kyrmizakis, Emmanouil I Drivas, Anastassios V Koutsopoulos, Stylianos G Malandrakis, Charalambos E Skoulakis and John G Bizakis – Symvoulakis et al. Head & Face Medicine 2006 2:7 doi:10.1186/1746-160X-2-7 (Open Access), [1], CC BY-SA 2.0, https://commons.wikimedia.org/w/index.php?curid=9839811
Fordyce spots	Rice-like granules or spots Small, painless, raised, pale, red or white 1 to 3 mm in diameter	Greasy skin types Some rheumatic disorders Hereditary nonpolyposis colorectal cancer Lower gingiva (gums) Vestibular mucosa	Physical exam Small keratin-filled pseudocysts May be seen on incidental mucosal biopsy Biopsy not done for them primarily	Oral cavity Vermilion border of the lips Oral mucosa of the upper lip Buccal mucosa in the commissural region often bilaterally Genitals	Benign neoplasms with sebaceous features Visible sebaceous glands No surrounding mucosal change Several adjacent glands may coalesce into a larger cauliflower-like cluster	Fordyce spots – Por Perene – Obra do próprio, CC BY-SA 3.0, https://commons.wikimedia.org/w/index.php?curid=19772899
Burning mouth syndrome	Burning or tingling on the lips, tongue, or entire mouth	Nutritional deficiencies Chronic anxiety or depression Diabetes type 2 Menopause Oral thrush or dry mouth, or damaged nerves transmitting taste Female gender Menopause	Presentation Physical exam	Oral cavity	Pain typically is low in the morning and builds up over the day Low dosages of benzodiazepines, tricyclic antidepressants or anticonvulsants may be effective
Torus palatinus	Bony growth on midline of the hard palate Nodular mass covered with normal mucosa	Genetic predisposition Autosomal dominant	Physical exam Types Flat tori Spindle tori Nodular tori Lobular tori	Hard palate	More common in Asian and Inuit populations Twice more common in females Repeated trauma can cause bleeding Surgery may be required in symptomatic	Torus palatinus – By Photo taken by dozenist, CC BY-SA 3.0, https://commons.wikimedia.org/w/index.php?curid=846591
Diseases involving oral cavity and other organ systems
Behcet’s disease	Painful mouth sores Acne like skin lesions Headache, fever, poor balance, disorientation Abdominal pain, diarrhea or bleeding Uveitis Joint swelling and joint pain Genital sores wit pain and scaring Aneurysms	Over active immune system	Physical examination	Mouth Genitals GIT Eye Joints Skin Vascular system Brain	Outbreaks of exaggerated inflammation Affects smaller blood vessels	Behcet’s disease – By Ahmet Altiner MD, Rajni Mandal MD – http://dermatology.cdlib.org/1611/articles/18_2009-10-20/2.jpg, CC BY-SA 3.0, https://commons.wikimedia.org/w/index.php?curid=17863021
Crohn’s disease	Chronic, episodic diarrhea or constipation Abdominal pain Vomiting Weight loss or weight gain	Smoking Whites and European Jews Hormonal contraception Diets high in microparticles, sweet, fatty or refined foods Industrialized country	Typical history and symptoms Skip lesions on biopsy Anti-Saccharomyces cerevisiae antibodies (ASCA) Anti-neutrophil cytoplasmic antibodies (ANCA)	Eyes Joints Skin	May lead to Obstructions Abscesses Free perforation Hemorrhage
Agranulocytosis	Fever or chills Frequent infections Unusual redness, pain, or swelling around a wound Mouth ulcers Abdominal pain Burning sensation when urinating Sore throat	Medications^[20] Cytotoxic chemotherapy Hematologic malignancies Autoimmune disorders	Neutropenia <100 cells per micro litre Eosinopenia Basopenia	Oral cavity Skin GIT Urinary system Conjunctiva	Immunocompromization Types Drug-induced Malignant Autoimmune
Syphilis^[21]	Chancre Regional lymphadenopathy	Multiple sexual partners Illicit drug use Unprotected sex Men who have sex with men Residence in highly prevalent areas HIV infection Presence of other STIs Previous history of STIs Intravenous drug use	Darkfield microscopy Non treponemal tests like VDRL and RPR test) Treponemal testsFTA-ABS tests, (TP-PA) assay, enzyme immunoassays, and chemiluminescence immunoassays)	Oral cavity Penis Cervix Labia Anal canal Rectum CNS CVS	Primary syphilis Chancre Secondary syphilis Condylomata lata Latent syphilis Asymptomatic Tertiary syphilis Gummas Neurosyphilis	oral syphilis – By CDC/Susan Lindsley – http://phil.cdc.gov/phil_images/20021114/34/PHIL_2385_lores.jpg, Public Domain, https://commons.wikimedia.org/w/index.php?curid=2134349
Coxsackie virus	Fever Sores in the mouth Rash with blisters Aches	Pregnancy immunodeficiency	History and Physical exam Throat swabs Swabs from the lesion Tzanck test	Oral cavity Skin	Symptomatic treatment	Coxsackie virus stomatitis – Adapted from Dermatology Atlas.^[22]
Chicken pox	Conjunctival symptoms Catarrhal symptoms Characteristic spots on the trunk appearing in two or three waves Itching	Pregnancy Premature infants born to susceptible mothers All infants born at less than 28 weeks gestation or who weigh =1000 grams Immunocompromised	History and physical exam PCR to detect VZV in skin lesions (vesicles, scabs, maculopapular lesions)	Oral cavity Skin	Sodium bicarbonate in baths or antihistamines for itching Paracetamol (acetaminophen) for fever Prednisolone is contraindicated	Chickenpox – By James Heilman, MD – Own work, CC BY-SA 4.0, https://commons.wikimedia.org/w/index.php?curid=52872565
Measles	Fever Rash Cough Coryza (runny nose) Conjunctivitis (pink eye) Malaise Koplick spots in mouth	Unvaccinated individuals^[23]^[24] Crowded and/or unsanitary conditions Traveling to less developed and developing countries Immunocompromized Winter and spring seasons Born after 1956 and never fully vaccinated Health care workers	History and examination PCR for Measles-specific IgM antibody PCR for Measles RNA	Oral cavity Skin Respiratory tract Eyes Throat	Caused by Morbillivirus Primary site of infection is the respiratory epithelium of the nasopharynx Transmitted in respiratory secretions, via aerosol droplets containing virus particles	Koplick spots (Measles) – By CDC – http://phil.cdc.gov/PHIL_Images/20040908/4f54ee8f0e5f49f58aaa30c1bc6413ba/6111_lores.jpg, Public Domain, https://commons.wikimedia.org/w/index.php?curid=824483

Crohn’s disease must be differentiated from diseases that cause abdominal pain and chronic diarrhea. The table below summarizes the findings that differentiate watery causes of chronic diarrhea:^[25]^[26]^[27]^[28]^[29]

Cause	Osmotic gap		History	Physical exam	Gold standard for diagnosis
Cause	< 50 mOsm per kg	> 50 mOsm per kg*	History	Physical exam	Gold standard for diagnosis
Zollinger-Ellison syndrome	+	–	Abdominal pain and diarrhea Dyspepsia Upper or Lower gastrointestinal bleeding	Abdominal tenderness Hematochezia Hematemesis Tachycardia Hypotension	Gastrin levels
Crohn’s disease	+	–	Abdominal pain followed by diarrhea	Abdominal tenderness when palpated in severe disease Blood seen on rectal exam Fever Tachycardia Hypotension	Colonoscopy with biopsy
Hyperthyroidism	+	–	Excessive sweating Heat intolerance Increased bowel movements	Lump in the neck Proptosis Tremors Increased DTR	TSH with T3 and T4
VIPoma	+	–	Watery diarrhea Dehydration (thirst, dry skin, dry mouth, tiredness, headaches, and dizziness) Lethargy, muscle weakness Nausea, vomiting Cramping abdominal pain Weight loss Flushing	Tachycardia Rash Facial flushing Abdominal distention Abdominal tenderness in the right upper abdominal quadrant	Elevated VIP levels Followed by imaging
Lactose intolerance	–	+	Abdominal pain Bloating Diarrhea Flatulence	Abdominal tenderness	Intestinal biopsy
Celiac disease	–	+	May be asymptomatic Vague abdominal pain Diarrhea Weight loss Malabsorption/steatorrhea Bloatedness	Abdominal pain and cramping Abdominal distention Tetany Mouth ulcers Dermatitis herpetiformis Signs of the fat-soluble vitamins A, D, E, and K deficiency	IgA tissue transglutaminase Ab
Irritable bowel syndrome	–	–	Abdominal pain or discomfort recurring at least 3 days per month in the past 3 months and associated with 2 or more of the following: Improves with defecation Onset associated with change in frequency of stool Onset associated with change in appearance of stool 25% of bowel movements are loose stools History of straining is also common.	Abdominal tenderness Hard stool in the rectal vault	Clinical diagnosis ROME III criteria Pharmacologic studies based criteria

References

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↑ Silverberg MS, Satsangi J, Ahmad T, Arnott ID, Bernstein CN, Brant SR; et al. (2005). “Toward an integrated clinical, molecular and serological classification of inflammatory bowel disease: report of a Working Party of the 2005 Montreal World Congress of Gastroenterology”. Can J Gastroenterol. 19 Suppl A: 5A–36A. PMID 16151544.
↑ Sauter GH, Moussavian AC, Meyer G, Steitz HO, Parhofer KG, Jüngst D (2002). “Bowel habits and bile acid malabsorption in the months after cholecystectomy”. Am J Gastroenterol. 97 (7): 1732–5. doi:10.1111/j.1572-0241.2002.05779.x. PMID 12135027.
↑ Maiuri L, Raia V, Potter J, Swallow D, Ho MW, Fiocca R; et al. (1991). “Mosaic pattern of lactase expression by villous enterocytes in human adult-type hypolactasia”. Gastroenterology. 100 (2): 359–69. PMID 1702075.
↑ RUBIN CE, BRANDBORG LL, PHELPS PC, TAYLOR HC (1960). “Studies of celiac disease. I. The apparent identical and specific nature of the duodenal and proximal jejunal lesion in celiac disease and idiopathic sprue”. Gastroenterology. 38: 28–49. PMID 14439871.

Epidemiology and Demographics

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] ; Associate Editor(s)-in-Chief: Aditya Ganti M.B.B.S. [2]

Overview

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. Prevalence estimates for Northern Europe have ranged from 27–48 per 100,000. 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. Crohn’s disease affects between 400,000 and 600,000 people in North America. Crohn’s disease has a bimodal distribution in incidence as a function of age. There is no association with gender, social class or occupation.

Epidemiology and Demographics

Prevalence

Prevalence estimates for Northern Europe have ranged from 27–48 per 100,000.^[1]
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. Crohn’s disease affects between 400,000 and 600,000 people in North America.^[2]

Incidence

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.^[3]^[4]
Crohn’s disease is more common in northern countries, and shows a higher preponderance in northern areas of the same country.^[5]
The incidence of Crohn’s disease in North America is 6 per 100,000 population and is similar in Europe, but the incidence rates are lower in Asia and Africa.

Demographics

Age

Crohn’s disease has a bimodal distribution in incidence as a function of age.
The disease tends to strike people in their teens and twenties, and people in their fifties through seventies. It is rare in early childhood.
Parents, siblings or children of people with Crohn’s disease are 3 to 20 times more likely to develop the disease.^[6]
Twin studies show a concordance of greater than 55% for Crohn’s disease.^[7]

Gender

There is no association with gender, social class or occupation.

Race

Whites and European Jews accounted for the vast majority of the cases in the United States, and in most industrialized countries. ^[8]

References

↑ Bernstein, Charles N. “The Epidemiology of Inflammatory Bowel Disease in Canada: A Population-Based Study”. The American Journal of Gastroenterology. 101 (7): 1559–1568. doi:10.1111/j.1572-0241.2006.00603.x. PMID 16863561.
↑ Loftus, E. V. “The epidemiology and natural history of Crohn’s disease in population-based patient cohorts from North America: a systematic review”. Alimentary Pharmacology & Therapeutics. 16 (1): 51–60. doi:10.1046/j.1365-2036.2002.01140.x. PMID 11856078.
↑ Hiatt, Robert A. “Epidemiology of inflammatory bowel disease in a defined northern California population”. Western Journal of Medicine. 149 (5): 541–6. PMID 3250100. Retrieved 2006-07-02.
↑ Moum, B. “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”. Scandinavian Journal of Gastroenterology. 31 (4): 355–61. PMID 8726303.
↑ Shivananda, S. “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)”. Gut. 39 (5): 690–7. PMID 9014768.
↑ 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.
↑ 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
↑ Podolsky, Daniel K. “Inflammatory bowel disease”. New England Journal of Medicine. 346 (6): 417–29. PMID 12167685. Retrieved 2006-07-02.

Template:WH Template:WS

Risk Factors

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]

Overview

Common risk factors in the development of crohns disease include white ancestry, age 15-40 or 60-80 years, family history of crohns disease and cigarette smoking.

Risk Factors

Common risk factors in the development of crohns disease include ^[1]^[2]^[3]

White ancestry
Age 15-40 or 60-80 years
Family history of CD
Cigarette smoking, smokers are three times more likely to get Crohn’s disease.
Diet rich in sugars
Oral contraceptives
NSAIDS
Living in an industrialized country
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.
Gastric cancer is most often caused by the bacterium Helicobacter pylori that flourishes in cramped and unsanitary conditions.

References

↑ Cosnes J (2004). “Tobacco and IBD: relevance in the understanding of disease mechanisms and clinical practice”. Best Pract Res Clin Gastroenterol. 18 (3): 481–96. PMID 15157822.
↑ Morris, Danielle L (2000-11-18). “Early environmental factors may have role in both Crohn’s disease and gastric carcinoma – Letter to the Editor”. British Medical Journal. Retrieved 2008-01-16.
↑ Lesko S, Kaufman D, Rosenberg L; et al. (1985). “Evidence for an increased risk of Crohn’s disease in oral contraceptive users”. Gastroenterology. 89 (5): 1046–9. PMID 4043662.

Template:WH Template:WS

Screening

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] ; Associate Editor(s)-in-Chief: Aditya Ganti M.B.B.S. [2]

Overview

There are no screening recommendations for Crohn’s disease.

Screening

There are no screening recommendations for Crohn’s disease.

References

Template:WH Template:WS

Natural History, Complications and Prognosis

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] ; Associate Editor(s)-in-Chief: Aditya Ganti M.B.B.S. [2]

Overview

If left untreated, patients with Crohn’s disease can progress into colorectal cancer depending upon the region involved. The common complication of Crohn’s disease include obstructions, abscesses, free perforation, and hemorrhage. With treatment, most people achieve a healthy life, and the mortality rate for the disease is low.

Natural History

If left untreated, patients with Crohn’s disease can progress into colorectal cancer depending upon the region involved. For example, individuals with Crohn’s disease involving the small bowel are at higher risk for small intestinal cancer. Similarly, people with Crohn’s colitis have a relative risk of 5.6 for developing colon cancer.^[1] Screening for colon cancer with colonoscopy is recommended for anyone who has had Crohn’s colitis for eight years, or more.^[2]^[3]^[4]

Complications

Common complications of Crohn’s disease include:^[5]

Abscess – Abscesses are walled off collections of infection, which can occur in the abdomen or in the perianal area in Crohn’s disease sufferers.
Bowel obstructions – Obstruction typically occurs from strictures or adhesions which narrow the lumen, blocking the passage of the intestinal contents.
Complications of corticosteroid therapy
Erythema nodosum
Fistulae can develop between two loops of bowel, between the bowel and bladder, between the bowel and vagina, and between the bowel and skin.
Impaired growth and sexual development in children
Inflammation of the joints
Lesions in the eye
Nutritional deficiencies (particularly vitamin B12 deficiency)
Pyoderma gangrenosum
Development of cancer
Malnutrition^[6]

Prognosis

Crohn’s disease is a 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 life, and the mortality rate for the disease is low.
Crohn’s disease is associated with an increased risk of small bowel and colorectal carcinoma.^[7]
Many patients will have temporary stoma formations together with possible associated complications.^[8]

References

↑ Ekbom A, Helmick C, Zack M, Adami H (1990). “Increased risk of large-bowel cancer in Crohn’s disease with colonic involvement”. Lancet. 336 (8711): 357–9. PMID 1975343.
↑ Collins P, Mpofu C, Watson A, Rhodes J. “Strategies for detecting colon cancer and/or dysplasia in patients with inflammatory bowel disease”. Cochrane Database Syst Rev: CD000279. PMID 16625534.
↑ “Complications of Crohn’s Disease”. Retrieved 2008-01-16.
↑ Ekbom A, Helmick C, Zack M, Adami H (1990). “Increased risk of large-bowel cancer in Crohn’s disease with colonic involvement”. Lancet. 336 (8711): 357–9. PMID 1975343.
↑ “Complications of Crohn’s Disease”. Retrieved 2008-01-16.
↑ Evans J, Steinhart A, Cohen Z, McLeod R (2003). “Home total parenteral nutrition: an alternative to early surgery for complicated inflammatory bowel disease”. J Gastrointest Surg. 7 (4): 562–6. PMID 12763417.
↑ Canavan, C. (2006). “Meta-analysis : colorectal and small bowel cancer risk in patients with Crohn’s disease”. Alimentary pharmacology & therapeutics. 23 (8): 1097–1104. ISSN 0269-2813. Retrieved 2007-05-23.
↑ http://www.answers.com/topic/crohn-s-disease?cat=health

Template:WH Template:WS

Diagnosis

Treatment

Medical Therapy | Surgery | Prevention | Cost-Effectiveness of Therapy | Future or Investigational Therapies

Case Studies

Case #1

Related Chapters

Template:Crohn’s Template:Gastroenterology

Template:WikiDoc Sources

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[3] Crohn’s disease has strong genetic link: study

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[pmid1702075-28] Maiuri L, Raia V, Potter J, Swallow D, Ho MW, Fiocca R; et al. (1991). “Mosaic pattern of lactase expression by villous enterocytes in human adult-type hypolactasia”. Gastroenterology. 100 (2): 359–69. PMID 1702075.

[pmid14439871-29] RUBIN CE, BRANDBORG LL, PHELPS PC, TAYLOR HC (1960). “Studies of celiac disease. I. The apparent identical and specific nature of the duodenal and proximal jejunal lesion in celiac disease and idiopathic sprue”. Gastroenterology. 38: 28–49. PMID 14439871.

[Bernstein-1] Bernstein, Charles N. “The Epidemiology of Inflammatory Bowel Disease in Canada: A Population-Based Study”. The American Journal of Gastroenterology. 101 (7): 1559–1568. doi:10.1111/j.1572-0241.2006.00603.x. PMID 16863561.

[Loftus-2] Loftus, E. V. “The epidemiology and natural history of Crohn’s disease in population-based patient cohorts from North America: a systematic review”. Alimentary Pharmacology & Therapeutics. 16 (1): 51–60. doi:10.1046/j.1365-2036.2002.01140.x. PMID 11856078.

[Hiatt-3] Hiatt, Robert A. “Epidemiology of inflammatory bowel disease in a defined northern California population”. Western Journal of Medicine. 149 (5): 541–6. PMID 3250100. Retrieved 2006-07-02.

[4] Moum, B. “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”. Scandinavian Journal of Gastroenterology. 31 (4): 355–61. PMID 8726303.

[5] Shivananda, S. “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)”. Gut. 39 (5): 690–7. PMID 9014768.

[6] 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.

[7] 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

[Podolsky-8] Podolsky, Daniel K. “Inflammatory bowel disease”. New England Journal of Medicine. 346 (6): 417–29. PMID 12167685. Retrieved 2006-07-02.

[1] Cosnes J (2004). “Tobacco and IBD: relevance in the understanding of disease mechanisms and clinical practice”. Best Pract Res Clin Gastroenterol. 18 (3): 481–96. PMID 15157822.

[2] Morris, Danielle L (2000-11-18). “Early environmental factors may have role in both Crohn’s disease and gastric carcinoma – Letter to the Editor”. British Medical Journal. Retrieved 2008-01-16.

[3] Lesko S, Kaufman D, Rosenberg L; et al. (1985). “Evidence for an increased risk of Crohn’s disease in oral contraceptive users”. Gastroenterology. 89 (5): 1046–9. PMID 4043662.

[1] Ekbom A, Helmick C, Zack M, Adami H (1990). “Increased risk of large-bowel cancer in Crohn’s disease with colonic involvement”. Lancet. 336 (8711): 357–9. PMID 1975343.

[2] Collins P, Mpofu C, Watson A, Rhodes J. “Strategies for detecting colon cancer and/or dysplasia in patients with inflammatory bowel disease”. Cochrane Database Syst Rev: CD000279. PMID 16625534.

[3] “Complications of Crohn’s Disease”. Retrieved 2008-01-16.

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[5] “Complications of Crohn’s Disease”. Retrieved 2008-01-16.

[6] Evans J, Steinhart A, Cohen Z, McLeod R (2003). “Home total parenteral nutrition: an alternative to early surgery for complicated inflammatory bowel disease”. J Gastrointest Surg. 7 (4): 562–6. PMID 12763417.

[Canavan-7] Canavan, C. (2006). “Meta-analysis : colorectal and small bowel cancer risk in patients with Crohn’s disease”. Alimentary pharmacology & therapeutics. 23 (8): 1097–1104. ISSN 0269-2813. Retrieved 2007-05-23.

[8] ttp://www.answers.com/topic/crohn-s-disease?cat=health

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Crohn's disease

Overview

Historical Perspective

Classification

Pathophysiology

Causes

Differentiating Crohn’s Disease from Other Diseases

Epidemiology and Demographics

Risk Factors

Natural History, Complications and Prognosis

Diagnosis

History and Symptoms

Physical Examination

Laboratory Findings

Abdominal X Ray

CT Scan

MRI Scan

Other Diagnostic Studies

Other Imaging Findings

Treatment

Medical Therapy

Surgery

Prevention

References

Overview

Historical Perspective

References

Overview

Classification

Based on the area of involvement

Based on the behavior of disease

References

Overview

Pathophysiology

Genetic Component

Stress and Environmental Component

Microbial Component

Immune Component

Gross Pathology

Microscopic Pathology

References

Overview

Causes

References

Overview

Differentiating Crohn’s Disease from other Diseases

Differentiating Crohn’s Disease from ulcerative colitis

Differentiating Crohn’s from other causes of Gastroenteritis

Differential Diagnosis

References

Overview

Epidemiology and Demographics

Prevalence

Incidence

Demographics

Age

Gender

Race

References

Overview

Risk Factors

References

Overview

Screening

References

Overview

Natural History

Complications

Prognosis

References

Diagnosis

Treatment

Case Studies

Related Chapters

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