Crohn_disease is a chronic transmural inflammation that may involve any part of the DIGESTIVE TRACT from MOUTH to ANUS, mostly found in the ILEUM, the CECUM, and the COLON. In Crohn disease, the inflammation, extending through the intestinal wall from the MUCOSA to the serosa, is characteristically asymmetric and segmental. Epithelioid GRANULOMAS may be seen in some patients."
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 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 vary between affected individuals. The main gastrointestinal symptoms are abdominal pain, diarrhea (which may be bloody) or constipation, 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 .
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.
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.
Influence of age at diagnosis on site and clinical type of disease
Familial aggregation in Crohn disease:increased age-adjusted risk and concordance in clinical characteristics
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 a slight increase in prevalence in women (1:1.2).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 constipation is not uncommon especially in those who have had surgery. 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.
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"http://www.ncbi.nlm.nih.gov/pubmed/17269417?ordinalpos=1&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_RVDocSum ). 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.
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.
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.
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, and a number of tests are often required to assist the physician in making the diagnosis. Sometimes even with all the tests the Crohn's does not show itself. A colonoscopy has about a 70% chance of showing the disease and the rest of the tests go down in percentage. Disease in the small bowel can not be seen through some of the regular tests; for example, a colonoscopy can't get there.
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, 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.
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.
A complete blood count may reveal anemia, which may be caused either by blood loss or vitamin B12 deficiency . The latter may be seen with ileitis because vitamin B12 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. 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 and to differentiate Crohn's disease from ulcerative colitis.
The most common disease that mimics the symptoms of Crohn's disease is ulcerative colitis, as both are inflammatory bowel diseases that can affect the colon with similar symptoms. It is important to differentiate these diseases, since the course of the diseases and treatments may be different. In some cases, however, it may not be possible to tell the difference, in which case the disease is classified as indeterminate colitis.
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.
Familial occurrence and inheritance studies in inflammatory bowel disease
Investigation of inheritance of chronic inflammatory bowel diseases by complex segregation analysis
Contribution of genes of the major histocompatibility complex to susceptibility and disease phenotype in inflammatory bowel disease
PATIENT RISK FACTOR
Recently, research has indicated that Crohn's disease has a strong genetic link. In earlier studies, only two genes were linked to Crohn's, scientists now believe there are over eight genes that show genetics play a crucial role in the disease, although environmental factors also are involved.
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. 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.
Because Crohn's disease occurs more often among people living in cities and industrial nations, it's possible that environmental factors, including a diet high in fat or refined foods, may play a role.
Among the environmental factors:
- Diets high in sweet, fatty or refined foods may play a role.
- Smoking has been shown to increase the risk of the return of active disease, or "flares".
- Methods of hormonal contraception have also shown an association with the development of Crohn's disease.
- People living in Northern climates also seem to have a greater risk of the disease.
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. 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. The mannose bearing antigens, mannins, from yeast may also elicit pathogenic anti saccharomyces cerevisiae antibodies. Newer studies have linked specific strains of enteroadherent E. coli to the disease but failed to find evidence of contributions by other species.
Seroprevalence of Helicobacter pylori infection in inflammatory bowel disease:is Helicobacter pylori infection a protective factor?
Role of thrombotic vascular risk factors
Theraphy insight:vascular complications in patients with 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.
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.
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.
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.
Many patients will have temporary stoma formations together with possible associated complications.
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.
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.
Effect of exclusion diet with nutraceutical therapy in juvenile Crohn's disease. 2009
Most moderate-severe juvenile Crohn's disease (CD) patients are in a constant catabolic state resulting in poor weight gain and growth failure. Anti-inflammatory, immunomodulatory, and monoclonal antibody drugs, as well as growth hormone (GH), frequently fail to achieve sustained remission or reverse growth failure.
To test whether an exclusion diet with nutraceutical therapy (DNT) could induce sustained clinical remission and weight gain, and if so does this enhance the ability for GH to reverse growth failure.
An uncontrolled prospective case study was undertaken in six moderate- severe CD patients, two of whom had completed growth. All were treated with DNT. Adequate caloric and protein ( >or= 3g/kg/d) intake for catch up weight was prescribed. Dairy products, certain grains and carrageenan containing foods were eliminated. Nutraceuticals, consisting of fish peptides, bovine colostrum, boswellia serrata, curcumin and a multivitamin were administered daily. Lactobacillus GG, a probiotic, was administered twice weekly. Recombinant human GH (rhGH) was administered daily.
Within 2 months of starting DNT all six patients went into remission, with discontinuation of all pharmacological drugs. Three patients have remained in sustained remission for 4 to 8 years. One patient with very severe CD had recurrence of CD symptoms after being in complete remission for 18 months, one patient was in remission for 3 years but symptoms recurred when she became less compliant to DNT and one recently treated patient remains in remission after 6 months. With the addition of rhGH, the 4 growing patients had good-excellent growth response
DNT engendered prolonged remission and restoration of normal weight in moderate-severe juvenile CD patients, providing conditions that enabled rhGH to stimulate growth. These findings justify larger controlled trials to evaluate the long-term benefit of compliance to DNT in both juvenile and adult CD patients.