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Crohn's disease

2007 Schools Wikipedia Selection. Related subjects: Health and medicine

   CAPTION: Crohn's disease
   Classifications and external resources

   The three most common sites of intestinal involvement in Crohn's
   disease are ileal, ileocolic and colonic.
     ICD- 10   K 50.
     ICD- 9    555
      OMIM     266600
   DiseasesDB  3178
   MedlinePlus 000249
    eMedicine  med/477  ped/507 radio/197
   H&E section of non-caseating granuloma seen in the colon of someone
   affected by Crohn's disease.
   Enlarge
   H&E section of non-caseating granuloma seen in the colon of someone
   affected by Crohn's disease.

   Crohn's disease (also known as regional enteritis) is a chronic,
   episodic, inflammatory condition of the gastrointestinal tract
   characterized by transmural inflammation (affecting the entire wall of
   the involved bowel) and skip lesions (areas of inflammation with areas
   of normal lining in between). Crohn's disease is a type of inflammatory
   bowel disease (IBD) and can affect any part of the gastrointestinal
   tract from mouth to anus; as a result, the symptoms of Crohn's disease
   can vary between affected individuals. The main gastrointestinal
   symptoms are abdominal pain, diarrhea, which may be bloody, and weight
   loss. Crohn's disease can also cause complications outside of the
   gastrointestinal tract such as skin rashes, arthritis, and inflammation
   of the eye.

   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 often develops in the teenage years,
   though individuals in their 60s and 70s are also at increased risk.
   There is a genetic component to susceptibility, affecting males and
   females equally. The disease may be triggered by environmental factors.

   Although the cause of Crohn's disease is not known, it is widely
   believed to be an autoimmune disease. The condition occurs when the
   immune system contributes to damage of the gastrointestinal tract by
   causing inflammation. Many cytokines in the Th1 classification,
   including TNF-α, interleukin-2, and interferon γ are elevated in
   Crohn's disease, and are involved in mediating the inflammation.

   Unlike the other major type of IBD, ulcerative colitis, there is no
   known medical or surgical cure for Crohn's disease. Instead, a number
   of medical treatments are utilized with the goal of putting and keeping
   the disease in remission. These include steroid medications,
   immunomodulators (such as azathioprine and methotrexate), and newer
   biological medications, such as infliximab.

   The disease was named after Burrill Bernard Crohn, an American
   gastroenterologist. In 1932, Crohn and two colleagues first described a
   series of patients with inflammation of the terminal ileum, the area
   most commonly affected in Crohn's disease.

Classification

   Distribution of gastrointestinal Crohn's disease. Based on data from
   American Gastroenterological Association.
   Enlarge
   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.

   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. 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
   Enlarge
   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, with no
   difference between men and women. 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.

   Gastrointestinal symptoms

   Abdominal pain may be the initial symptom of Crohn's disease. The pain
   is commonly crampy and may be relieved by defecation. It is often
   accompanied by diarrhea, which may be bloody. 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. Flatus 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.

   Peri-anal 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 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. People with
   extensive small intestine disease may also have malabsorption of
   carbohydrates or lipids, which can further exacerbate weight loss.

   Extraintestinal symptoms

   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 anaemia, 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 anaemia. 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.

   Complications

   Endoscopic image of colon cancer identified in the sigmoid colon
   (anatomy) on screening colonoscopy for Crohn's disease.
   Enlarge
   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 and 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 are at a higher risk for colon
   cancer. Screening for colon cancer with colonoscopy is recommended for
   anyone who has had Crohn's colitis for eight years, or more.

   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 severe
   Crohn's disease are referred to a dietitian for assistance in
   nutrition.

Cause

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

   Many environmental factors have also been hypothesized as causes or
   risk factors for Crohn's disease. Diets high in sweet, fatty or refined
   foods may 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.

   Smoking has been shown to increase the risk of the return of active
   disease, or "flares". Oral contraceptives have also shown an
   association with the development of Crohn's disease.

   Abnormalities in the immune system have often been invoked as causes of
   Crohn's disease. It has been hypothesized that Crohn's disease involves
   augmentation of the T[h]1 of cytokine response in inflammation. Also,
   as the colon is rich in bacteria, many infectious agents have been
   suggested as causes of Crohn's disease, including Mycobacterium avium
   subspecies paratuberculosis.

Pathophysiology

   H and E section of colectomy showing transmural inflammation.
   Enlarge
   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.
   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.

Diagnosis

   Endoscopic image of Crohn's colitis showing deep ulceration.
   Enlarge
   Endoscopic image of Crohn's colitis showing deep ulceration.
   CT scan showing Crohn's disease in the fundus of the stomach
   Enlarge
   CT scan showing Crohn's disease in the fundus of the stomach
   Crohn's disease can mimic ulcerative colitis on endoscopy. This
   endoscopic image of 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.
   Enlarge
   Crohn's disease can mimic ulcerative colitis on endoscopy. This
   endoscopic image of 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, and a
   number of tests are often required to assist the physician in making
   the diagnosis.

   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. 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,
   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.

   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.The utility of
   capsule endoscopy for this, however, is still uncertain.

   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. 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.

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

   Blood tests

   A complete blood count may reveal anaemia, which may be caused either
   by blood loss or vitamin B[12] deficiency. The latter may be seen with
   ileitis because vitamin B[12] is absorbed in the ileum. Erythrocyte
   sedimentation rate, or ESR, and C-reactive protein measurements can
   also be useful to gauge the degree of inflammation. Testing for anti-
   Saccharomyces cerevisiae antibodies (ASCA) and anti-neutrophil
   cytoplasmic antibodies (ANCA) has been evaluated to identify
   inflammatory diseases of the intestine and to differentiate Crohn's
   disease from ulcerative colitis.

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.

   CAPTION: Comparisons of various factors in Crohn's disease and
   ulcerative colitis

   Crohn's disease Ulcerative colitis
   Terminal ileum involvement Commonly Never
   Colon involvement Usually Always
   Rectum involvement Seldom Usually
   Involvement around the anus Common Seldom
   Bile duct involvement Lower rate of primary sclerosing cholangitis
   Higher rate
   Distribution of Disease Patchy areas of inflammation Continuous area of
   inflammation
   Endoscopy Deep geographic and serpiginous (snake-like) ulcers
   Continuous ulcer
   Depth of inflammation May be transmural, deep into tissues Shallow,
   mucosal
   Fistulae Common Seldom
   Stenosis Common Seldom
   Autoimmune disease Widely regarded as an autoimmune disease No
   consensus
   Cytokine response Associated with T[h]1 Vaguely associated with T[h]2
   Granulomas on biopsy Can have granulomas Granulomas uncommon
   Surgical cure Often returns following removal of affected part Usually
   cured by removal of colon
   Smoking Higher risk for smokers Lower risk for smokers

Treatment

   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. Surgery may be required for complications such as
   obstructions or abscesses, or if the disease does not respond to drugs
   within a reasonable time.

   Once remission is induced, the goal of treatment becomes maintenance of
   remission, 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.

   Drugs

   The anti-TNF-α monoclonal antibody infliximab is a mainstay of the
   biological therapy for inflammatory bowel disease
   Enlarge
   The anti- TNF-α monoclonal antibody infliximab is a mainstay of the
   biological therapy for inflammatory bowel disease

   Various drug approaches may be used in Crohn's disease to both obtain
   and maintain remission. Aminosalicylate anti-inflammatory drugs
   commonly prescribed are mesalazine (mesalamine, 5-ASA) and the
   derivative sulfasalazine. The corticosteroids prednisone and budesonide
   are immunosuppressants, as well as azathioprine (Imuran),
   6-mercaptopurine (6-MP), infliximab (Remicade®), methotrexate. Rarely,
   atypical medications such as thalidomide can be used. The antibiotics
   metronidazole and ciprofloxacin may also be used for people with
   colonic disease.

   Surgery

   Surgery is generally reserved for complications of Crohn's disease, or
   when disease that resists treatment with drugs is confined to one
   location that can be removed. Surgery is often used to manage
   complications of Crohn's disease, including fistulae, small bowel
   obstruction, colon cancer, small intestine cancer and fibrostenotic
   strictures, when strictureplasty (expansion of the stricture) is
   sometimes performed. Otherwise, and for other complications, resection
   and anastomosis - the removal of the affected section of intestine and
   the rejoining of the healthy sections - is the surgery usually
   performed for Crohn's disease (e.g., ileocolonic resection). Neither
   type of surgery cures Crohn's disease, as recurrence often reappears in
   previously unaffected areas of the intestine.

   Small intestine transplants are experimental, and are usually only
   performed when there is a risk of short bowel syndrome due to repeated
   resection surgeries.

   Diet and lifestyle

   There is no evidence that diet causes or cures Crohn's disease, but
   many people with Crohn's disease note that certain foods improve or
   worsen their symptoms. Fish oil has been found to be effective in
   reducing the chance of relapse in less severe cases. People with
   lactose intolerance due to small bowel disease may benefit from
   avoiding lactose-containing foods. Many diets have been proposed for
   treatment of Crohn's disease, and many do improve symptoms, but none
   have been proven to actually cure Crohn's disease. A low residue diet
   may be used to reduce the volume of stools excreted daily. Stress can
   make symptoms of Crohn's disease worse. People with Crohn's disease can
   find that their symptoms improve with effective stress management.

   Because the terminal ileum is the most common site of involvement and
   is the site for vitamin B[12] absorption, people with Crohn's disease
   are at risk for B[12] deficiency and may need supplementation. In cases
   with extensive small intestine involvement, the fat soluble vitamins A,
   D, E and K can be deficient. Folate deficiency is a risk when being
   treated with methotrexate.

   Complementary and alternative medicine

   More than half of Crohn's disease sufferers have tried complementary or
   alternative therapy. These include diets, probiotics, fish oil and
   other herbal and nutritional supplements. The benefit of these
   medications is uncertain.

Prognosis

   Crohn's disease is a chronic condition that cannot be cured. 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.

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

   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. 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. Twin
   studies show a concordance of greater than 55% for Crohn's disease.

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.

   Burrill Bernard Crohn, an American gastroenterologist at Mount Sinai
   Hospital, described fourteen cases in 1932, and submitted them to the
   American Medical Association under the rubrick 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".

   Retrieved from " http://en.wikipedia.org/wiki/Crohn%27s_disease"
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