Crohn's disease

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Crohn's disease
The three most common sites of intestinal involvement in Crohn's disease are ileal, ileocolic and colonic.[1]
ICD-10 K50
ICD-9 555
OMIM 266600
DiseasesDB 3178
MedlinePlus 000249
eMedicine med/477  ped/507 radio/197
MeSH D003424

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Overview

Crohn's disease (also known as regional enteritis) 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.[1]

The disease was independently described in 1904 by Polish surgeon Antoni Lesniowski and in 1932 by American 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.[2] Crohn's disease affects between 400,000 and 600,000 people in North America.[3] Prevalence estimates for Northern Europe have ranged from 27–48 per 100,000.[4] 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.[1][5]

Although the cause of Crohn's disease is not known, it is believed to be an autoimmune disease that is 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 surgical cure for Crohn's disease.[6] Instead, a number of medical treatments are utilized with the goal of putting and keeping the disease in remission. These include 5-aminosalicylic acid (5-ASA) formulations (Pentasa capsules, Asacol tablets, Lialda tablets, Rowasa retention enemas), steroid medications, immunomodulators (such as azathioprine, mercaptopurine (6-MP), and methotrexate), and newer biological medications, such as infliximab (Remicade) and adalimumab (Humira).[7]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.

Classification

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.[1] 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.[8] 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 (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.[8][9]

Symptoms

Endoscopy image of 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.[10] The usual onset is between 15 and 30 years of age but can occur at any age.[11] 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-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 bowel movements per day and may need to awaken at night to defecate.[1][5][7][12] 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.[1] 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.[5] Flatus and bloating may also add to the intestinal discomfort.[5]

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.[5] 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, fistulization or abscess around the anal area[1] or anal fissure. Perianal skin tags are also common in Crohn's disease.[13] 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 ulcers). 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.[14]

Systemic symptoms

Crohn's disease, like many other chronic, inflammatory diseases, can cause a variety of systemic symptoms.[1] Among children, growth failure is common. Many children are first diagnosed with Crohn's disease based on inability to maintain growth.[15] 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.[16] Fever may also be present, though fevers greater than 38.5 ˚C (101.3 ˚F) are uncommon unless there is a complication such as an abscess[1] 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.[15] People with extensive small intestine disease may also have malabsorption of carbohydrates or lipids, which can further exacerbate weight loss.[17]

Extraintestinal symptoms
Erythema nodosum.

In addition to systemic and gastrointestinal involvement, Crohn's disease can affect many other organ systems.[18] 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 episcleritis. Both episcleritis and uveitis can lead to loss of vision if untreated.

Crohn's disease is associated with a type of rheumatologic disease known as seronegative spondyloarthropathy. This group of diseases is characterized by inflammation of one or more joints (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 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 fractures.[4]

Crohn's disease can also cause neurological complications (reportedly in up to 15% of patients).[19] The most common of these are seizures, stroke, myopathy, peripheral neuropathy, headache and depression.[19]

Crohn's patients often also have issues with Small bowel bacterial overgrowth syndrome, which has similar symptoms.

Complications
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 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 intestinal cancer. Similarly, people with Crohn's colitis have a relative risk of 5.6 for developing colon cancer.[20] Screening for colon cancer with colonoscopy is recommended for anyone who has had Crohn's colitis for eight years, or more.[21]

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.[22]

There are many complications that can come with Crohn's disease like: obstructions, abscesses, free perforation, and hemorrhage.[23]

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" [3].

Cause

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. [24] 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.

Mutations in the CARD15 gene (also known as the NOD2 gene) are associated with Crohn's disease[25] and with susceptibility to certain phenotypes of disease location and activity.[26] 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, fatty or 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.[27] 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,[28] 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.

Smoking has been shown to increase the risk of the return of active disease, or "flares".[29] 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.[30]

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.[31]

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 Th1 of cytokine response in inflammation.[32] 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.[33]

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. [34] 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. [35] The mannose bearing antigens, mannins, from yeast may also elicit pathogenic anti saccharomyces cerevisiae antibodies.[36] Newer studies have linked specific strains of enteroadherent E. coli to the disease but failed to find evidence of contributions by other species. [37]

Pathophysiology

H and E section of colectomy showing transmural inflammation.

At the time of colonoscopy, 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.[1] Grossly, ulceration 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 mucosal 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 aggregates. These neutrophils, along with mononuclear cells, may infiltrate into the crypts leading to inflammation (crypititis) or abscess (crypt abscess). Granulomas, 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 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.[38]









Diagnosis

Endoscopic image of Crohn's colitis showing deep ulceration.
CT scan showing Crohn's disease in the fundus of the stomach
Crohn's disease can mimic ulcerative colitis on endoscopy. This endoscopic image is of Crohn's colitis showing diffuse loss of mucosal 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,[10] and a number of tests are often required to assist the physician in making the diagnosis.[5] 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,[1] cannulation 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.[39]

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.[40]The utility of capsule endoscopy for this, however, is still uncertain.[41]

Radiologic tests

A 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 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 fluoroscopic images of the bowel are taken over time, is useful for looking for inflammation and narrowing of the small bowel.[40][42] 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.[43]

CT and MRI scans are useful for evaluating the small bowel with enteroclysis protocols.[44]They are additionally useful for looking for intra-abdominal complications of Crohn's disease such as abscesses, small bowel obstruction, or fistulae.[45] 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[46]

Images shown below are courtesy of RadsWiki and copylefted

  • Abdominal x-ray of a patient with Crohn disease

    Abdominal x-ray of a patient with Crohn disease

  • Pseudosacculations in Crohn's disease

    Pseudosacculations in Crohn's disease

  • Pseudosacculations in Crohn's disease

    Pseudosacculations in Crohn's disease

  • Pseudosacculations in Crohn's disease

    Pseudosacculations in Crohn's disease

Blood tests

A complete blood count may reveal anemia, which may be caused either by blood loss or [[Cyanocobalamin|vitamin BTemplate:Ssub]] deficiency. The latter may be seen with ileitis because vitamin BTemplate:Ssub is absorbed in the ileum.[47] Erythrocyte sedimentation rate, or ESR, and C-reactive protein measurements can also be useful to gauge the degree of inflammation.[48] 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 antibodies (ANCA) has been evaluated to identify inflammatory diseases of the intestine[49] and to differentiate Crohn's disease from ulcerative colitis.[50]

Comparison with 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.[7][1][5]

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[51]
Involvement around the anus Common[52] Seldom
Bile duct involvement No increase in rate of primary sclerosing cholangitis Higher rate[53]
Distribution of Disease Patchy areas of inflammation (Skip lesions) Continuous area of inflammation[51]
Endoscopy Deep geographic and serpiginous (snake-like) ulcers Continuous ulcer
Depth of inflammation May be transmural, deep into tissues[52][1] Shallow, mucosal
Fistulae Common[52] Seldom
Stenosis Common Seldom
Autoimmune disease Widely regarded as an autoimmune disease No consensus
Cytokine response Associated with Th1 Vaguely associated with Th2
Granulomas on biopsy Can have granulomas[52] Granulomas uncommon[51]
Surgical cure Often returns following removal of affected part Usually cured by removal of colon
Smoking Higher risk for smokers Lower risk for smokers[51]

Treatment

Main articles: Treatment of Crohn's disease and Biological therapy for inflammatory bowel disease

Treatment is only needed for people exhibiting symptoms. The therapeutic approach to Crohn's disease is sequential: to treat 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.[52]

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 (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.[54].As of late December 2007, more than 21,000 MS patients were receiving natalizumab mono-therapy without a single incidence of PML occurring.[55].

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.[56]

Recent studies using Helminthic therapy or Hookworms to treat Crohn's Disease and other (non-viral) auto-immune diseases seem to yield promising results.[57][58][59]

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 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.[60]

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. [4]

Many patients will have temporary stoma formations together with possible associated complications. [5]

Epidemiology

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.[61][62] Crohn's disease is more common in northern countries, and shows a higher preponderance in northern areas of the same country.[63] 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.[61] It also has a higher incidence in Ashkenazi Jews.[7]

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.[1][5] 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.[64] Twin studies show a concordance of greater than 55% for Crohn's disease.[65]

History

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.[66]

Burrill Bernard Crohn, an American gastroenterologist at New York City's 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".[2]

See also

References

  1. ↑ 1.00 1.01 1.02 1.03 1.04 1.05 1.06 1.07 1.08 1.09 1.10 1.11 1.12 1.13 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)
  2. ↑ 2.0 2.1 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
  3. ↑ Loftus, E. V. (2002). "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. Unknown parameter |coauthors= ignored (help); Unknown parameter |month= ignored (help)
  4. ↑ 4.0 4.1 Bernstein, Charles N. (2006). "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. Unknown parameter |month= ignored (help)
  5. ↑ 5.0 5.1 5.2 5.3 5.4 5.5 5.6 5.7 Gopal, Latha (2006-05-23). "Crohn Disease". eMedicine. Retrieved 2006-07-02. Unknown parameter |coauthors= ignored (help)
  6. ↑ Al-Ataie, M Bashar (2005-10-04). "Ulcerative colitis". eMedicine. Retrieved 2006-07-02. Unknown parameter |coauthors= ignored (help)
  7. ↑ 7.0 7.1 7.2 7.3 Podolsky, Daniel K. (2002). "Inflammatory bowel disease". New England Journal of Medicine. 346 (6): 417–29. PMID 12167685. Retrieved 2006-07-02. Unknown parameter |month= ignored (help)
  8. ↑ 8.0 8.1 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.
  9. ↑ 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.
  10. ↑ 10.0 10.1 Pimentel, Mark (2000). "Identification of a prodromal period in Crohn's disease but not ulcerative colitis". American Journal of Gastroenterology. 95 (12): 3458–62. doi:10.1111/j.1572-0241.2000.03361.x. PMID 11151877. Unknown parameter |coauthors= ignored (help); Unknown parameter |month= ignored (help)
  11. ↑ Crohn Disease Overview
  12. ↑ Mueller, M. H. (2002). "Anorectal functional disorders in the absence of anorectal inflammation in patients with Crohn's disease". British Journal of Surgery. 89 (8): 1027–31. doi:10.1046/j.1365-2168.2002.02173.x. PMID 12153630. Unknown parameter |coauthors= ignored (help); Unknown parameter |month= ignored (help)
  13. ↑ Taylor B, Williams G, Hughes L, Rhodes J (1989). "The histology of anal skin tags in Crohn's disease: an aid to confirmation of the diagnosis". Int J Colorectal Dis. 4 (3): 197–9. PMID 2769004.
  14. ↑ Fix, Oren K. (2004). "Gastroduodenal Crohn's disease". Gastrointestinel Endoscopy. 60 (6): 985. doi:doi:10.1016/S0016-5107(04)02200-X Check |doi= value (help). PMID 15605018. Unknown parameter |coauthors= ignored (help); Unknown parameter |month= ignored (help)
  15. ↑ 15.0 15.1 Beattie, R.M. (2006). "Inflammatory bowel disease". Archives of Disease in Childhood. 91 (5): 426–32. doi:10.1136/adc.2005.080481. PMID 16632672. Unknown parameter |coauthors= ignored (help); Unknown parameter |month= ignored (help)
  16. ↑ Büller, H.A. (1997). "Problems in diagnosis of IBD in children". The Netherlands Journal of Medicine. 50 (2): S8–S11. doi:10.1016/S0300-2977(96)00064-2. PMID 9050326. Unknown parameter |month= ignored (help)
  17. ↑ O'Keefe, S. J. (1996). "Nutrition and gastrointestinal disease". Scandinavian Journal of Gastroenterology Supplement (220): 52–9. PMID 8898436.
  18. ↑ Danese, Silvio (2005). "Extraintestinal manifestations in inflammatory bowel disease". World Journal of Gastroenterology. 11 (46): 7227–7236. PMID 16437620. Retrieved 2006-07-02. Unknown parameter |month= ignored (help); Unknown parameter |coauthors= ignored (help)
  19. ↑ 19.0 19.1 Crohn's disease. professionals.epilepsy.com. Retrieved on July 13, 2007.
  20. ↑ 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.
  21. ↑ 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.
  22. ↑ 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.
  23. ↑ "Complications of Crohn's Disease". Retrieved 2008-01-16.
  24. ↑ link Crohn's disease has strong genetic link: study
  25. ↑ 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.
  26. ↑ 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.
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  28. ↑ Reif S, Klein I, Lubin F, Farbstein M, Hallak A, Gilat T (1997). "Pre-illness dietary factors in inflammatory bowel disease" (PDF). Gut. 40 (6): 754–60. PMID 9245929.
  29. ↑ 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.
  30. ↑ 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.
  31. ↑ 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. Unknown parameter |coauthors= ignored (help)
  32. ↑ Cobrin GM, Abreu MT. Defects in mucosal immunity leading to Crohn's disease. Immunol Rev. 2005 Aug;206:277-95. PMID 16048555
  33. ↑ 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.
  34. ↑ 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).
  35. ↑ 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
  36. ↑ 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.
  37. ↑ 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).
  38. ↑ 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.
  39. ↑ Lee, S. D. (2002). "Endoscopy in inflammatory bowel disease". Gastroenterology Clinics of North America. 31 (1): 119–32. PMID 12122727. Unknown parameter |coauthors= ignored (help); Unknown parameter |month= ignored (help)
  40. ↑ 40.0 40.1 Hara, Amy K. (2006). "Crohn disease of the small bowel: preliminary comparison among CT enterography, capsule endoscopy, small-bowel follow-through, and ileoscopy". Radiology. 238 (1): 128–34. doi:10.1148/radiol.2381050296. PMID 16373764. Unknown parameter |coauthors= ignored (help); Unknown parameter |month= ignored (help)
  41. ↑ Triester, Stuart L. (2006). "A meta-analysis of the yield of capsule endoscopy compared to other diagnostic modalities in patients with non-stricturing small bowel Crohn's disease". The American Journal of Gastroenterology. 101 (5): 954–64. doi:10.1111/j.1572-0241.2006.00506.x. PMID 16696781. Unknown parameter |coauthors= ignored (help); Unknown parameter |month= ignored (help)
  42. ↑ Dixon, P.M. (1993). "The small bowel enema: a ten year review". Clinical Radiology. 47 (1): 46–8. doi:10.1016/S0009-9260(05)81213-9. PMID 8428417. Unknown parameter |coauthors= ignored (help); Unknown parameter |month= ignored (help)
  43. ↑ Carucci, L. R. (2002). "Radiographic imaging of inflammatory bowel disease". Gastroenterology Clinics of North America. 31 (1): 93–117. PMID 12122746. Unknown parameter |coauthors= ignored (help); Unknown parameter |month= ignored (help)
  44. ↑ Rajesh, A. (2006). "Multislice CT enteroclysis: technique and clinical applications". Clinical Radiology. 61 (1): 31–9. doi:10.1016/j.crad.2005.08.006. PMID 16356814. Unknown parameter |coauthors= ignored (help); Unknown parameter |month= ignored (help)
  45. ↑ Zissin, Rivka (2005). "Computed Tomographic Findings of Abdominal Complications of Crohn's Disease—Pictorial Essay" (PDF). Canadian Association of Radiologists Journal. 56 (1): 25–35. PMID 15835588. Retrieved 2006-07-02. Unknown parameter |month= ignored (help); Unknown parameter |coauthors= ignored (help)
  46. ↑ MacKalski, B. A. (2005). "New diagnostic imaging tools for inflammatory bowel disease". Gut. 55 (5): 733–41. doi:10.1136/gut.2005.076612. PMID 16609136. Unknown parameter |coauthors= ignored (help); Unknown parameter |month= ignored (help)
  47. ↑ Goh, Jason (2003). "Review article: nutrition and adult inflammatory bowel disease". Alimentary Pharmacology & Therapeutics. 17 (3): 307–20. doi:10.1046/j.1365-2036.2003.01482.x. PMID 12562443. Unknown parameter |coauthors= ignored (help); Unknown parameter |month= ignored (help)
  48. ↑ Chamouard, Patrick (April). "Diagnostic Value of C-Reactive Protein for Predicting Activity Level of Crohn's Disease". Clinical Gastroenterology and Hepatology. doi:10.1016/j.cgh.2006.02.003. PMID 16630759. Unknown parameter |coauthors= ignored (help); Unknown parameter |month= ignored (help); Check date values in: |year= (help) Epub ahead of print
  49. ↑ Kaila, B. (2005). "The anti-Saccharomyces cerevisiae antibody assay in a province-wide practice: accurate in identifying cases of Crohn's disease and predicting inflammatory disease". The Canadian Journal of Gastroenterology. 19 (12): 717–21. PMID 16341311. Retrieved 2006-07-02. Unknown parameter |month= ignored (help); Unknown parameter |coauthors= ignored (help)
  50. ↑ Israeli, E. (2005). "Anti-Saccharomyces cerevisiae and antineutrophil cytoplasmic antibodies as predictors of inflammatory bowel disease". Gut. 54 (9): 1232–6. doi:10.1136/gut.2004.060228. PMID 16099791. Unknown parameter |coauthors= ignored (help); Unknown parameter |month= ignored (help)
  51. ↑ 51.0 51.1 51.2 51.3 Kornbluth, Asher (2004). "Ulcerative Colitis Practice Guidelines in Adults" (PDF). American Journal of Gastroenterology. 99 (7): 1371–1385. doi:10.1111/j.1572-0241.2004.40036.x. PMID 15233681. Retrieved 2006-11-08. Unknown parameter |month= ignored (help); Unknown parameter |coauthors= ignored (help)
  52. ↑ 52.0 52.1 52.2 52.3 52.4 Hanauer, Stephen B. (March 1 2001). "Management of Crohn's Disease in Adults" (PDF). American Journal of Gastroenterology. 96 (3): 635–643. doi:10.1111/j.1572-0241.2001.03671.x. PMID 11280528. Retrieved 2006-11-08. Unknown parameter |coauthors= ignored (help); Check date values in: |date= (help)
  53. ↑ Broomé, Ulrika (2006). "Primary sclerosing cholangitis, inflammatory bowel disease, and colon cancer". Seminars in Liver Disease. 26 (1): 31–41. doi:10.1055/s-2006-933561. PMID 16496231. Unknown parameter |coauthors= ignored (help); Unknown parameter |month= ignored (help)
  54. ↑ "FDA Approves Tysabri to Treat Moderate-to-Severe Crohn's Disease" (Press release). U.S. Food and Drug Administration. 2008-01-14. Retrieved 2008-01-16.
  55. ↑ .http://www.elan.com/News/full.asp?ID=1091942
  56. ↑ Ozuner G, Fazio VW, Lavery IC, Milsom JW, Strong SA (1996). "Reoperative rates for Crohn's disease following strictureplasty. Long-term analysis". Dis. Colon Rectum. 39 (11): 1199–203. PMID 8918424.
  57. ↑ British Medical Journal A proof of concept study establishing Necator americanus in Crohn’s patients and reservoir donors
  58. ↑ Daily Mail. The bloodsucking worm that fights allergies from inside your tummy 14-09-2007.
  59. ↑ How to cure your asthma or hayfever using hookworm - a practical guide. 01-05-2006.
  60. ↑ 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. Unknown parameter |month= ignored (help); Unknown parameter |coauthors= ignored (help)
  61. ↑ 61.0 61.1 Hiatt, Robert A. (1988). "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. Unknown parameter |month= ignored (help); Unknown parameter |coauthors= ignored (help)
  62. ↑ Moum, B. (1996). "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. Unknown parameter |coauthors= ignored (help); Unknown parameter |month= ignored (help)
  63. ↑ Shivananda, S. (1996). "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. Unknown parameter |coauthors= ignored (help); Unknown parameter |month= ignored (help)
  64. ↑ 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.
  65. ↑ 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
  66. ↑ Kirsner JB. Historical aspects of inflammatory bowel disease. J Clin Gastroenterol. 1988 Jun;10(3):286-97. PMID 2980764

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