The precise cause of Crohn's disease is not known. The disease occurs when the immune system attacks the gastrointestinal tract and for this reason, Crohn's disease is considered an autoimmune disease. This autoimmune activity produces inflammation in the gastrointestinal tract, and therefore Crohn's disease is classified as an inflammatory bowel disease. Research in 2007 has suggested that intestinal bacteria are theorized to drive immune activation.

 Like many other autoimmune diseases, Crohn's disease is believed to be genetically linked. The highest risk occurs in individuals with siblings who have the disease. Males and females are equally affected. Smokers are three times more likely to develop Crohn's disease. Crohn's disease affects between 400,000 and 600,000 people in North America. 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. Unlike the other major types of inflammatory bowel disease, there is no known drug based or surgical cure for Crohn's disease. Treatment options are restricted to controlling symptoms, putting and keeping the disease in remission and preventing relapse.

The disease was independently described in 1904 by Polish surgeon Antoni Leśniowski 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.[12] For this reason, the disease has also been called regional ileitis or regional enteritis.

Crohn's disease is generally classified as an autoimmune disease. It invariably affects the gastrointestinal tract, and most gastroenterologists categorize the presenting 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.Crohn's disease may also be categorized by the behavior of disease as it progresses. This was formalized in the Vienna classification of Crohn's disease.[13] 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.

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. The usual onset is between 15 and 30 years of age but can occur at any age. 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 is not relieved by defecation.[citation needed] 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.[ 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. 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. Flatulence and bloating may also add to the intestinal discomfort.

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. 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 or anal fissure. Perianal skin tags are also common in Crohn's disease. 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.
 

Systemic symptoms

Crohn's disease, like many other chronic, inflammatory diseases, can cause a variety of systemic symptoms. Among children, growth failure is common. Many children are first diagnosed with Crohn's disease based on inability to maintain growth. 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. 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. 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. People with extensive small intestine disease may also have malabsorption of carbohydrates or lipids, which can further exacerbate weight loss.
 

Extraintestinal symptoms

Erythema nodosum
In addition to systemic and gastrointestinal involvement, Crohn's disease can affect many other organ systems. 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.
 

Crohn's disease can also cause neurological complications (reportedly in up to 15% of patients). The most common of these are seizures, stroke, myopathy, peripheral neuropathy, headache and depression. 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 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. Screening for colon cancer with colonoscopy is recommended for anyone who has had Crohn's colitis for eight years, or more. Some study suggest that there is a role for chimioprotection in the prevention of colorectal cancer in Crohn's involving the colon; two agents have been suggested, folate and mesalamine preparations.
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

Crohn's disease can cause significant complications including bowel obstruction, abscesses, free perforation and hemorrhage.
Crohn's disease can be problematic during pregnancy, and some medications can cause adverse outcomes for the fetus or mother. Consultation with an obstetrician and gastroenterologist about Crohn's disease and all medications allows preventative measures to be taken. In some cases, remission can occur during pregnancy. Certain medications can also impact sperm count or may otherwise adversely affect a man's ability to conceive.
 

Cause
The exact cause of Crohn's disease is unknown. However, environmental and genetic factors have been invoked in the pathogenesis of the disease. Others argue that Crohn's disease is caused by a combination of environmental and genetic factors.
 

Genetics
Schematic of NOD2 CARD15 gene, which is associated with certain disease patterns in Crohn's disease.
Research has indicated that Crohn's disease has a strong genetic link.[33] 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. However, the European Commission makes an interesting point:
A review of the literature suggests that Crohn's disease is more prevalent in Western populations with northern European and Anglo-Saxon ethnic derivation, than in populations of southern Europe, Asia and Africa. However, when the Asian people migrate to urban-industrial societies of the West, they become as susceptible to the disease as the population of their host countries, suggesting environmental factors in the aetiology of Crohn's disease143.

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. 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 role in the disease, either directly through causation or indirectly as with a mediator variable. Anomalies in the XBP1 gene have recently been identified as a factor, pointing towards a role for the unfolded protein response pathway of the endoplasmatic reticulum in inflammatory bowel diseases.
 

Environmental factors

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). Another explanation is that modern industrial practices have given rise to increased disease prevalence via infectious diseases. A common recurrent theory is that a specific species of Mycobacterium, Mycobacterium avium subspecies paratuberculosis, is responsible for both Johne's disease and Crohn's disease, and modern industrial farming practices have led to the spread of Mycobacterium avium subspecies paratuberculosis.

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. 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, and cites three large European studies in which sugar intake was significantly increased in people with Crohn's disease compared with controls. 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". The introduction of hormonal contraception in the United States in the 1960s 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.

Some scientific studies and court rulings have posited that Accutane is a probable cause of IBD, a group of diseases including Crohn's Disease and Ulcerative colitis, in some individuals. Three cases in the United States have gone to trial thus far, with all three resulting in multi-million dollar judgments against the makers of isotretinoin; there are an additional 425 cases pending.
Immune system

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 susceptibility for Crohn's Disease. 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.

Abnormalities in the immune system have often been invoked as being causes of Crohn's disease. Crohn's disease is thought to be an autoimmune disease, with inflammation stimulated by an over-active Th1 cytokine response. However, more recent evidence has shown that Th17 is of greater importance in the disease. 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.

Contrary to the prevailing view that Crohn's diseaes is a primary T cell autoimmune disorder, there is an increasing body of evidence in favour of the hypothesis that Crohn's disease results from an impaired innate immunity. The immunodeficiency, which has been shown to be due to (at least in part) impaired cytokine secretion by macrophages, is thought to lead to a sustained microbial-induced inflammatory response, particularly in the colon where the bacterial load is especially high.

http://en.wikipedia.org/wiki/Crohn's_disease