Crohn's disease

From Wikipedia, the free encyclopedia - View original article

Crohn's disease
Classification and external resources

The three most common sites of intestinal involvement in Crohn's disease are

ileal, ileocolic and colonic.[1]
eMedicinemed/477 ped/507 radio/197
Jump to: navigation, search
Crohn's disease
Classification and external resources

The three most common sites of intestinal involvement in Crohn's disease are

ileal, ileocolic and colonic.[1]
eMedicinemed/477 ped/507 radio/197

Crohn's disease, also known as Crohn syndrome and regional enteritis, is a type of inflammatory bowel disease that may affect any part of the gastrointestinal tract from mouth to anus, causing a wide variety of symptoms. It primarily causes abdominal pain, diarrhea (which may be bloody if inflammation is at its worst), vomiting (can be continuous), or weight loss,[1][2][3] but may also cause complications outside the gastrointestinal tract such as skin rashes, arthritis, inflammation of the eye, tiredness, and lack of concentration.[1] Crohn's disease is caused by interactions between environmental, immunological and bacterial factors in genetically susceptible individuals.[4][5][6] This results in a chronic inflammatory disorder, in which the body's immune system attacks the gastrointestinal tract possibly directed at microbial antigens.[5][7] Crohn's disease has wrongly been described as an autoimmune disease in the past; recent investigators have described it as an immune deficiency state.[7][8][9][10][11][12]

There is a genetic association with Crohn's disease, primarily with variations of the NOD2 gene and its protein, which senses bacterial cell walls. Siblings of affected individuals are at higher risk.[13] Males and females are equally affected. Smokers are two times more likely to develop Crohn's disease than nonsmokers.[14] Crohn's disease affects between 400,000 and 600,000 people in North America.[15] Prevalence estimates for Northern Europe have ranged from 27–48 per 100,000.[16] 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][17] There is no known pharmaceutical or surgical cure for Crohn's disease. Treatment options are restricted to controlling symptoms, maintaining remission, and preventing relapse. The disease was named after gastroenterologist Burrill Bernard Crohn, who, in 1932, together with two other colleagues at Mount Sinai Hospital in New York, described a series of patients with inflammation of the terminal ileum, the area most commonly affected by the illness.[18]



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

Crohn's disease is one type of inflammatory bowel disease (IBD). It typically manifests in the gastrointestinal tract and can be categorized by the specific tract region affected. A disease of both the ileum (the last part of the small intestine that connects to the large intestine), and the large intestine, Ileocolic Crohn's accounts for fifty percent of cases. Crohn's ileitis, manifest in the ileum only, accounts for thirty percent of cases, while Crohn's colitis, of the large intestine, accounts for the remaining twenty percent of cases and may be particularly difficult to distinguish from ulcerative colitis. Gastroduodenal Crohn's disease causes inflammation in the stomach and first part of the small intestine, called the duodenum. Jejunoileitis causes spotty patches of inflammation in the top half of the small intestine, called the jejunum (MedlinePlus 2010). 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, with presentations in other areas.[1]

Crohn's disease may also be categorized by the behavior of disease as it progresses. These categorizations formalized in the Vienna classification of the disease.[19] There are three categories of disease presentation in Crohn's disease: stricturing, penetrating, and inflammatory. Stricturing disease causes narrowing of the bowel that 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 nonstricturing, nonpenetrating disease) causes inflammation without causing strictures or fistulae.[19][20]

Signs and symptoms

Symptoms in Crohn's disease vs. ulcerative colitis (v · d · e)
Crohn's diseaseUlcerative colitis
DefecationOften porridge-like[21],
sometimes steatorrhea
Often mucus-like
and with blood[21]
TenesmusLess common[21]More common[21]
FeverCommon[21]Indicates severe disease[21]
Weight lossOftenMore seldom


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.[23] The usual onset is between 15 and 30 years of age, but can occur at any age.[24] Because of the 'patchy' nature of the gastrointestinal disease and the depth of tissue involvement, initial symptoms can be more subtle than those of ulcerative colitis. People with Crohn's disease experience chronic recurring periods of flare-ups and remission.[25]

Abdominal pain may be the initial symptom of Crohn's disease. It is often accompanied by diarrhea, especially in those who have had surgery. The diarrhea may or may not be bloody. The nature of the diarrhea in Crohn's disease depends on the part of the small intestine or colon 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][17][26][27] 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 color. In the setting of severe Crohn's colitis, bleeding may be copious.[17] Flatulence and bloating may also add to the intestinal discomfort.[17]

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.[17] Although the association is greater in the context of ulcerative colitis, Crohn's disease may also be associated with primary sclerosing cholangitis, a type of inflammation of the bile ducts.[28]

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.[29] Fecal incontinence may accompany perianal 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 (dysphagia), upper abdominal pain, and vomiting.[30]


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.[31] As it 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.[32] 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, 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.[31] People with extensive small intestine disease may also have malabsorption of carbohydrates or lipids, which can further exacerbate weight loss.[33]


Erythema nodosum on the back of a person with Crohn's disease

In addition to systemic and gastrointestinal involvement, Crohn's disease can affect many other organ systems.[34] 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 hands 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.[25]

Pyoderma gangrenosum on the leg of a person with Crohn's disease

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.[16]

Crohn's disease can also cause neurological complications (reportedly in up to 15% of patients).[35] The most common of these are seizures, stroke, myopathy, peripheral neuropathy, headache and depression.[35]

Crohn's patients often also have issues with small bowel bacterial overgrowth syndrome, which has similar symptoms.[36]

In the oral cavity crohn's patients may suffer from cheilitis granulomatosa and other forms of orofacial granulomatosis, pyostomatitis vegetans, recurrent aphthous stomatitis, geographic tongue and migratory stomatitis in higher prevalence than the general population.[37]


Complications of Crohn's disease vs. ulcerative colitis
Crohn's diseaseUlcerative colitis
Nutrient deficiencyHigher risk
Colon cancer riskSlightConsiderable
Prevalence of
extraintestinal complications[38]
Primary sclerosing
Erythema nodosumFemales1.9%2%

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 that 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 is responsible for 10% of vesicoenteric fistulae, and is the most common cause of ileovesical fistulae.[39]

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.[40] Screening for colon cancer with colonoscopy is recommended for anyone who has had Crohn's colitis for at least eight years.[41] Some studies suggest there is a role for chemoprotection in the prevention of colorectal cancer in Crohn's involving the colon; two agents have been suggested, folate and mesalamine preparations.[42]

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.[43]

Crohn's disease can cause significant complications, including bowel obstruction, abscesses, free perforation and hemorrhage.[44]

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.[45]


Risk factors in Crohn's disease vs. ulcerative colitis.
Crohn's diseaseUlcerative colitis
SmokingHigher risk for smokersLower risk for smokers[46]
AgeUsual onset between
15 and 30 years[47]
Peak incidence between
15 and 25 years

Crohn's disease seems to be caused by a combination of environmental factors and genetic predisposition.[48] Crohn's is the first genetically complex disease in which the relationship between genetic risk factors and the immune system is understood in considerable detail.[49] Each individual risk mutation makes a small contribution to the overall risk of Crohn's (approximately 1:200). The genetic data, and direct assessment of patient immunity, indicates a malfunction in the innate immune system.[50] In this view, the chronic inflammation of Crohn's is caused when the adaptive immune system tries to compensate for a deficient innate immune system.[51]


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

Crohn's has a genetic component.[52] The disease runs in families, and siblings are 30 times more likely to develop Crohn's than the general population.

The first mutation found to be associated with Crohn's was a frameshift in the NOD2 gene (also known as the CARD15 gene),[53] followed by the discovery of point mutations.[54] By now, over thirty genes have been associated. A biological function is known for most of them. For example, one association is with mutations in the XBP1 gene, which is involved in the unfolded protein response pathway of the endoplasmatic reticulum.[55][56]

Immune system

The prevailing view was that Crohn's disease is a primary T cell autoimmune disorder. A newer view is that Crohn's results from an impaired innate immunity.[57] In the newer view, impaired cytokine secretion by macrophages contributes to impaired innate immunity, and leads to a sustained microbial-induced inflammatory response in the colon, where the bacterial load is high.[5][50] One theory is that the inflammation of Crohn's was caused by an overactive Th1 cytokine response.[58] More recent[when?] studies argue that Th17 is more important.[59]

The most recent (2007) gene to be implicated in Crohn's disease is ATG16L1, which may induce autophagy and hinder the body's ability to attack invasive bacteria.[60] Another recent study has theorized that the human immune system traditionally evolved with the presence of parasites inside the body, and that the lack thereof due to modern hygiene standards has weakened the immune system. Test subjects were reintroduced to harmless parasites, with positive response.[61]


Current thinking is that microorganisms are taking advantage of their host's weakened mucosal layer and inability to clear bacteria from the intestinal walls, which are both symptoms of Crohn's.[62] Different strains found in tissue and different outcomes to antibiotics therapy and resistance suggest Crohn's Disease is not one disease, but an umbrella of diseases related to different pathogens.[63][64]

Some studies have suggested a role for Mycobacterium avium subspecies paratuberculosis (MAP), which causes a similar disease, Johne's disease, in cattle.[65] NOD2, a gene involved in Crohn’s genetic susceptibility, is associated with diminished killing of MAP by macrophages, reduced innate and adaptive immunity in the host and impaired immune responses required for control of intracellular mycobacterial infection.[66][67] Macrophages infected with viable MAP are associated with high production of TNF-α.[68][69]

Other studies have linked specific strains of enteroadherent E. coli to the disease.[70] Adherent-invasive Escherichia coli (AIEC), are much more prevalent in CD patients than in controls[71][72][73] and have the ability to make strong biofilms compared to non-AIEC strains correlating with high adhesion and invasion indices.[74] Inflammation drives the proliferation of AIEC and dysbiosis in the ileum, irrespective of genotype,.[75] AIEC strains replicate extensively into macrophages inducing the secretion of very large amounts of TNF-α.[76] Monocytes from Crohn's disease patients produced markedly higher levels of pro-inflammatory TNF-α (and IL-6) in response to AIEC strain "LF82" than monocytes from normal subjects (p <.001).[77]

Bacterial strains, EC15 and EC10, were found to adhere and invade the Caco2 cell line in pediatric crohn's disease patients, similar to the well-known AIEC strain LF82 (positive control): they upregulated CEACAM6, TNF-α, and IL-8 gene/protein expression, in vitro and in cultured intestinal mucosa; they could also survive inside macrophages and damage the epithelial barrier integrity. Lesions in the inflamed tissues were associated with bacterial infection. [78]

The mannose-bearing antigens (mannins) from yeast may also cause an antibody response.[79]

Mouse studies have suggested some symptoms of Crohn's disease, ulcerative colitis and irritable bowel syndrome have the same underlying cause. Biopsy samples taken from the colons of all three patient groups were found to produce elevated levels of a serine protease.[80] Experimental introduction of the serine protease into mice has been found to produce widespread pain associated with irritable bowel syndrome, as well as colitis, which is associated with all three diseases.[81] Regional and temporal variations in those illnesses follow those associated with infection with the protozoan Blastocystis.[82]

The "cold-chain" hypothesis is that psychrotrophic bacteria such as Yersinia and Listeria species contribute to the disease. A statistical correlation was found between the advent of the use of refrigeration in the United States and various parts of Europe and the rise of the disease.[83][84][85]

There is an apparent connection between Crohn's disease, Mycobacterium, other pathogenic bacteria, and genetic markers.[86][87] In many individuals, genetic factors predispose individuals to Mycobacterium avium subsp. paratuberculosis infection. This bacterium then produces mannins, which protect both itself and various bacteria from phagocytosis, which causes a variety of secondary infections.[88]

Still, this relationship between specific types of bacteria and Crohn's disease remains unclear.[89][90]

Environmental factors

The increased incidence of Crohn's in the industrialized world indicates an environmental component. Crohn's is associated with an increased intake of animal protein, milk protein and an increased ratio of omega-6 to omega-3 polyunsaturated fatty acids.[91] Those who consume vegetable proteins appear to have a lower incidence of Crohn's disease. Consumption of fish protein has no association.[91] Smoking increases the risk of the return of active disease (flares).[14] The introduction of hormonal contraception in the United States in the 1960s is associated with a dramatic increase in incidence, and one hypothesis is that these drugs work on the digestive system in ways similar to smoking.[92] Isotretinoin is associated with Crohn's.[93][94][95] Although stress is sometimes claimed to exacerbate Crohn's disease, there is no concrete evidence to support such claim. [96]


Pathophysiology in Crohn's disease vs. ulcerative colitis
Crohn's diseaseUlcerative colitis
Cytokine responseAssociated with Th17[59]Vaguely associated with Th2
Section of colectomy showing transmural inflammation

During a colonoscopy, biopsies of the colon are often taken to confirm the diagnosis. Certain characteristic features of the pathology seen point toward Crohn's disease; it shows a transmural pattern of inflammation, meaning the inflammation may span the entire depth of the intestinal wall.[1] Ulceration is an outcome seen in highly active disease. There is usually an abrupt transition between unaffected tissue and the ulcer - a characteristic sign known as skip lesions. Under a microscope, biopsies of the affected colon may show mucosal inflammation, 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 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 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 a 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.[97]


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.
Endoscopic biopsy showing granulomatous inflammation of the colon in a case of Crohn's disease. H&E stain.

The diagnosis of Crohn's disease can sometimes be challenging,[23] and a number of tests are often required to assist the physician in making the diagnosis.[17] Even with a full battery of tests, it may not be possible to diagnose Crohn's with complete certainty; a colonoscopy is approximately 70% effective in diagnosing the disease, with further tests being less effective. Disease in the small bowel is particularly difficult to diagnose, as a traditional colonoscopy allows access to only the colon and lower portions of the small intestines; introduction of the capsule endoscopy[98] aids in endoscopic diagnosis. Multinucleated giant cells, a common finding in the lesions of Crohn's disease, are less common in the lesions of lichen nitidus.[99]


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. On occasion, 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.[100] The utility of capsule endoscopy for this, however, is still uncertain.[101] A "cobblestone"-like appearance is seen in approximately 40% of cases of Crohn's disease upon colonoscopy, representing areas of ulceration separated by narrow areas of healthy tissue.

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.[100][102] Barium enemas, in which barium is inserted into the rectum and fluoroscopy is 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 (in this case contrast should be performed with iodate substances).[103]

CT and MRI scans are useful for evaluating the small bowel with enteroclysis protocols.[104]They are also useful for looking for intra-abdominal complications of Crohn's disease, such as abscesses, small bowel obstructions, or fistulae.[105] Magnetic resonance imaging (MRI) is another option for imaging the small bowel as well as looking for complications, though it is more expensive and less readily available[106]

Blood tests

A complete blood count may reveal anemia, which may be caused by blood loss, by vitamin B12 deficiency or, possibly, autoimmune hemolysis. The latter may be seen with ileitis because vitamin B12 is absorbed in the ileum.[107] Erythrocyte sedimentation rate, or ESR, and C-reactive protein measurements can also be useful to gauge the degree of inflammation.[108] It is also true in patients with an ilectomy done in response to the complication. Another cause of anemia is anemia of chronic disease, characterized by its microcytic and hypochromic anemia. There can be various reasons for it, including medication used in treatment of inflammatory bowel disease, like azathioprine, which can lead to cytopenia, and sulfasalazine, which can also result in folate malabsorption, etc. Testing for Saccharomyces cerevisiae antibodies (ASCA) and antineutrophil cytoplasmic antibodies (ANCA) has been evaluated to identify inflammatory diseases of the intestine[109] and to differentiate Crohn's disease from ulcerative colitis.[110] Furthermore, increasing amounts and levels of serological antibodies such as ASCA, antilaminaribioside [Glc(β1,3)Glb(β); ALCA], antichitobioside (GlcNAc(β1,4)GlcNAc(β); ACCA], antimannobioside [Man(α1,3)Man(α)AMCA], antiLaminarin [Glc(β1,3))3n(Glc(β1,6))n; anti-L] and antichitin [(GlcNAc(β1,4)n; anti-C] associate with disease behavior and surgery, and may aid in the prognosis of Crohn's disease.[111][112][113][114]

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.[1][17][26]

Findings in diagnostic workup in Crohn's disease vs. ulcerative colitis
SignCrohn's diseaseUlcerative colitis
Terminal ileum involvementCommonlySeldom
Colon involvementUsuallyAlways
Rectum involvementSeldomUsually[46]
Involvement around
the anus
Bile duct involvementNo increase in rate of primary sclerosing cholangitisHigher rate[115]
Distribution of DiseasePatchy areas of inflammation (Skip lesions)Continuous area of inflammation[46]
EndoscopyDeep geographic and serpiginous (snake-like) ulcersContinuous ulcer
Depth of inflammationMay be transmural, deep into tissues[1][22]Shallow, mucosal
Granulomas on biopsyMay have non-necrotizing non-peri-intestinal crypt granulomas[22][116][117]Non-peri-intestinal crypt granulomas not seen[46]


Management in Crohn's disease vs. ulcerative colitis
Crohn's diseaseUlcerative colitis
MesalamineLess useful[118]More useful[118]
AntibioticsEffective in long-term[119]Generally not useful[120]
SurgeryOften returns following
removal of affected part
Usually cured by
removal of colon

There is no cure for Crohn's disease and remission may not be possible or prolonged if achieved. In cases where remission is possible, relapse can be prevented and symptoms controlled with medication, lifestyle and dietary changes, changes to eating habits (eating smaller amounts more often), reduction of stress, moderate activity and exercise, . Surgery is generally counter-indicated and has not been shown to prevent remission. Adequately controlled, Crohn's disease may not significantly restrict daily living.[121] Treatment for Crohn's disease is only when symptoms are active and involve first treating the acute problem, then maintaining remission.

Lifestyle changes

Certain lifestyle changes can reduce symptoms, including dietary adjustments, elemental diet, proper hydration, and smoking cessation. Smoking may increase Crohn's disease; stopping is recommended. Eating small meals frequently instead of big meals may also help with a low appetite. To manage symptoms have a balanced diet with proper portion control. Fatigue can be helped with regular exercise, a healthy diet, and enough sleep. A food diary may help with identifying foods that trigger symptoms. Some people should follow a low dietary fiber diet to control symptoms especially if fibrous foods cause symptoms.[121] Some find relief in eliminating casein (protein found in cow's milk) and gluten (protein found in wheat, rye and barley) from their diets. They may suffer from specific dietary intolerances (not allergies).[122]


Acute treatment uses medications to treat any infection (normally antibiotics) and to reduce inflammation (normally aminosalicylate anti-inflammatory drugs and corticosteroids). When symptoms are in remission, treatment enters maintenance, with a goal of avoiding the recurrence of symptoms. Prolonged use of corticosteroids has significant side-effects; as a result, they are, in general, not used for long-term treatment. Alternatives include aminosalicylates alone, though only a minority are able to maintain the treatment, and many require immunosuppressive drugs.[22] It has been also suggested that antibiotics change the enteric flora, and their continuous use may pose the risk of overgrowth with pathogens such as Clostridium difficile.[123]

Medications used to treat the symptoms of Crohn's disease include 5-aminosalicylic acid (5-ASA) formulations, prednisone, immunomodulators such as azathioprine (given as the prodrug for 6-mercaptopurine), methotrexate, infliximab, adalimumab,[26] certolizumab[124] and natalizumab.[125][126] Hydrocortisone should be used in severe attacks of Crohn's disease.[127]

The gradual loss of blood from the gastrointestinal tract, as well as chronic inflammation, often leads to anemia, and professional guidelines suggest routinely monitoring for this. Adequate disease control usually improves anemia of chronic disease, but iron deficiency may require treatment with oral iron supplements. Occasionally, parenteral iron is required.[128]


Crohn's cannot be cured by surgery, though it is used when partial or a full blockage of the intestine occurs. Surgery may also be required for complications such as obstructions, fistulas and/or abscesses, or if the disease does not respond to drugs. After the first surgery, Crohn's usually shows up at the site of the resection, however it can appear in other locations. After a resection, scar tissue builds up, which can cause strictures, which form when the intestines become 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.[129] For patients with an obstruction due to a stricture, two options for treatment are strictureplasty and resection of that portion of bowel. There is no statistical significance between strictureplasty alone versus strictureplasty and resection 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.[130]

Short bowel syndrome (SBS, also short gut syndrome or simply short gut) can be caused by the surgical removal of the small intestines. It usually develops in those having had half or more of their small intestines removed.[131] Diarrhea is the main symptom of short bowel syndrome, however other symptoms may include cramping, bloating, and heartburn. Short bowel syndrome is treated with changes in diet, intravenous feeding, vitamin and mineral supplements, and treatment with medications. Another complication following surgery for Crohn's disease in which the terminal ileum has been removed is the development of excessive watery diarrhea. This is due to an inability of the ileum to reabsorb bile acids after resection of the terminal ileum.[citation needed]

In some cases of SBS, intestinal transplant surgery may be considered; though the number of transplant centres offering this procedure is quite small and it comes with a high risk due to the chance of infection and rejection of the transplanted intestine.[132]

Alternative medicine

More than half of people with Crohn's disease have tried complementary or alternative therapy.[133] These include diets, probiotics, fish oil and other herbal and nutritional supplements. Some scientists have suggested more research into these is needed to discriminate between effective therapies and "pseudo" therapies that can be ineffective.[134]


Crohn's disease is a chronic condition for which there is no cure. It is characterised by periods of improvement followed by episodes when symptoms flare up. With treatment, most people achieve a healthy weight, and the mortality rate for the disease is relatively low. However, Crohn's disease is associated with an increased risk of small bowel and colorectal carcinoma, including bowel cancer.[138] It can vary from being benign to very severe and patients could experience just one episode or have continuous symptoms. It usually reoccurs, although some patients can remain disease free for years or decades. Most sufferers live a normal lifespan.[139]


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. The Crohn's and Colitis Foundation of America cites this number as approx 149:100,000; NIH cites 28 to 199 per 100,000.[140][141] Crohn's disease is more common in northern countries, and shows a higher preponderance in northern areas of the same country.[142] The incidence of Crohn's disease is thought to be similar in Europe but lower in Asia and Africa.[140] It also has a higher incidence in Ashkenazi Jews[26] and smokers.[143]

Crohn's disease has a bimodal distribution in incidence as a function of age: the disease tends to strike people in their teens and 20s, and people in their 50s through to their 70s, and ages in between due to not being diagnosed with Crohn's and being diagnosed instead with irritable bowel syndrome (IBS).[1][17] It is rarely diagnosed in early childhood. It usually strikes females who are pediatric patients more severely than males.[144] However, only slightly more women than men have Crohn's disease.[145] Parents, siblings or children of people with Crohn's disease are 3 to 20 times more likely to develop the disease.[146] Twin studies show a concordance of greater than 55% for Crohn's disease.[147]


Inflammatory bowel diseases were described by Giovanni Battista Morgagni (1682–1771) and by Scottish physician T. Kennedy Dalziel in 1913.[148]

Ileitis terminalis was first described by Polish surgeon Antoni Leśniowski in 1904, however, due to the precedence of Crohn's name in the alphabet, it became later to be known in the worldwide literature as Crohn's disease.[citation needed] Only in Poland it continues to be named Leśniowski-Crohn's disease. 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".[18]


The Crohn's Allogeneic Transplant Study's investigation team of Seattle is currently undergoing a Phase 2 clinical trial to cure Crohn's disease, involving bone marrow transplant, noting that cases in which bone marrow transplant had been done for a secondary purpose effectively cured the patient of Crohn's.[149]

Researchers at University College London have questioned the wisdom of suppressing the immune system in Crohn's, as the problem may be an underactive rather than an overactive immune system: Their study found that Crohn's patients showed an abnormally low response to an introduced infection, marked by a poor flow of blood to the wound, and the response improved when the patients were given sildenafil citrate.[50]

Recent studies using helminthic therapy or hookworms to treat Crohn's Disease and other (non-viral) auto-immune diseases seem to yield promising results.[150]

Numerous preclinical studies demonstrate that activation of the CB1 and CB2 cannabinoid receptors exert biological functions on the gastrointestinal tract.[151] Activation of CB1 and CB2 receptors in animals has shown a strong anti-inflammatory effect.[152] Cannabinoids and/or modulation of the endocannabinoid system is a novel therapeutic means for the treatment of numerous GI disorders, including inflammatory bowel diseases like Crohn's disease.[153]

Notable cases


  1. ^ a b c d e f g h i j k l m n o Baumgart, Daniel C; Sandborn, William J (2012). "Crohn's disease". The Lancet. doi:10.1016/S0140-6736(12)60026-9. PMID 22914295.
  2. ^ Crohn's Disease Mayo Clinic[full citation needed]
  3. ^ Crohn's Disease National Digestive Diseases Information Clearinghouse
  4. ^ Cho, Judy H.; Brant, Steven R. (2011). "Recent Insights into the Genetics of Inflammatory Bowel Disease". Gastroenterology 140 (6): 1704–12. doi:10.1053/j.gastro.2011.02.046. PMID 21530736.
  5. ^ a b c Dessein, Rodrigue; Chamaillard, Mathias; Danese, Silvio (2008). "Innate Immunity in Crohnʼs Disease". Journal of Clinical Gastroenterology 42: S144–7. doi:10.1097/MCG.0b013e3181662c90. PMID 18806708.
  6. ^ Stefanelli, Tommaso; Malesci, Alberto; Repici, Alessandro; Vetrano, Stefania; Danese, Silvio (2008). "New Insights into Inflammatory Bowel Disease Pathophysiology: Paving the Way for Novel Therapeutic Targets". Current Drug Targets 9 (5): 413–8. doi:10.2174/138945008784221170. PMID 18473770.
  7. ^ a b Marks, DJ; Rahman, FZ; Sewell, GW; Segal, AW (2010). "Crohn's disease: An immune deficiency state". Clinical reviews in allergy & immunology 38 (1): 20–31. doi:10.1007/s12016-009-8133-2. PMID 19437144.
  8. ^ Lalande, JD; Behr, MA (2010). "Mycobacteria in Crohn's disease: How innate immune deficiency may result in chronic inflammation". Expert review of clinical immunology 6 (4): 633–41. doi:10.1586/eci.10.29. PMID 20594136.
  9. ^ Yamamoto-Furusho, Jesus K; Korzenik, Joshua R (2006). "Crohn's disease: Innate immunodeficiency?". World Journal of Gastroenterology 12 (42): 6751–5. PMID 17106921.
  10. ^ What's in a name? The (mis)labelling of Crohn's as an autoimmune disease
  11. ^ Defective IL-1A expression in patients with Crohn's disease is related to attenuated MAP3K4 signaling.
  12. ^ Revisiting Crohn's disease as a primary immunodeficiency of macrophages
  13. ^ a b Cosnes, Jacques (2004). "Tobacco and IBD: Relevance in the understanding of disease mechanisms and clinical practice". Best Practice & Research Clinical Gastroenterology 18 (3): 481. doi:10.1016/j.bpg.2003.12.003.
  14. ^ Loftus, E. V.; Schoenfeld, P.; Sandborn, W. J. (2002). "The epidemiology and natural history of Crohn's disease in population-based patient cohorts from North America: A systematic review". Alimentary Pharmacology and Therapeutics 16 (1): 51–60. doi:10.1046/j.1365-2036.2002.01140.x. PMID 11856078.
  15. ^ a b Bernstein, Charles N.; Wajda, Andre; Svenson, Lawrence W.; MacKenzie, Adrian; Koehoorn, Mieke; Jackson, Maureen; Fedorak, Richard; Israel, David et al. (2006). "The Epidemiology of Inflammatory Bowel Disease in Canada: A Population-Based Study". The American Journal of Gastroenterology 101 (7): 1559–68. doi:10.1111/j.1572-0241.2006.00603.x. PMID 16863561.
  16. ^ a b c d e f g h i Crohn Disease at eMedicine
  17. ^ a b Crohn, BB; Ginzburg, L; Oppenheimer, GD (2000). "Regional ileitis: A pathologic and clinical entity. 1932". The Mount Sinai journal of medicine, New York 67 (3): 263–8. PMID 10828911.
  18. ^ a b Gasche, Christoph; Scholmerich, Jurgen; Brynskov, Jorn; d'Haens, Geert; Hanauer, Stephen B.; Irvine, E. Jan; Jewell, Derek P.; Rachmilewitz, Daniel et al. (2007). "A simple classification of Crohn's disease: Report of the Working Party for the World Congresses of Gastroenterology, Vienna 1998". Inflammatory Bowel Diseases 6 (1): 8–15. doi:10.1002/ibd.3780060103. PMID 10701144.
  19. ^ Dubinsky, Marla C.; Fleshner, Phillip P. (2003). "Treatment of Crohn's disease of inflammatory, stenotic, and fistulizing phenotypes". Current Treatment Options in Gastroenterology 6 (3): 183–200. doi:10.1007/s11938-003-0001-1. PMID 12744819.
  20. ^ a b c d e f > Inflammatorisk tarmsjukdom, kronisk, IBD By Robert Löfberg. Retrieved Oct 2010 Translate.
  21. ^ a b c d e Hanauer, Stephen B.; William Sandborn (2001-03-01). "Management of Crohn's disease in adults" (PDF). American Journal of Gastroenterology 96 (3): 635–43. doi:10.1111/j.1572-0241.2001.03671.x. PMID 11280528. Retrieved 2009-11-07.
  22. ^ a b Pimentel, Mark; Chang, Michael; Chow, Evelyn J.; Tabibzadeh, Siamak; Kirit-Kiriak, Viorelia; Targan, Stephan R.; Lin, Henry C. (2000). "Identification of a prodromal period in Crohn's disease but not ulcerative colitis". The American Journal of Gastroenterology 95 (12): 3458–62. doi:10.1111/j.1572-0241.2000.03361.x. PMID 11151877.
  23. ^ Crohn's Disease Overview
  24. ^ a b Zieve, David; George F Longstreth (October 18, 2009). "Crohn's Disease". ADAM Health Illustrated Encyclopedia. Retrieved 2010-08-16.[verification needed]
  25. ^ a b c d Podolsky, Daniel K. (2002). "Inflammatory Bowel Disease". New England Journal of Medicine 347 (6): 417–29. doi:10.1056/NEJMra020831. PMID 12167685.
  26. ^ Mueller, M. H.; Kreis, M. E.; Gross, M. L.; Becker, H. D.; Zittel, T. T.; Jehle, E. C. (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.
  27. ^ Kumar, Vinay; Abbas, Abul K.; Fausto, Nelson (July 30, 2004). "The Gastrointestinal Tract". Robbins and Cotran: Pathologic Basis of Disease (7th ed.). Philadelphia, Pennsylvania: Elsevier Saunders. pp. 847. ISBN 0-7216-0187-1.
  28. ^ Taylor, B. A.; Williams, G. T.; Hughes, L. E.; Rhodes, J. (1989). "The histology of anal skin tags in Crohn's disease: An aid to confirmation of the diagnosis". International Journal of Colorectal Disease 4 (3): 197–9. doi:10.1007/BF01649703. PMID 2769004.
  29. ^ Fix, Oren K.; Soto, Jorge A.; Andrews, Charles W.; Farraye, Francis A. (2004). "Gastroduodenal Crohn's disease". Gastrointestinal Endoscopy 60 (6): 985. doi:10.1016/S0016-5107(04)02200-X. PMID 15605018.
  30. ^ a b Beattie, R M; Croft, NM; Fell, JM; Afzal, NA; Heuschkel, RB (2006). "Inflammatory bowel disease". Archives of Disease in Childhood 91 (5): 426–32. doi:10.1136/adc.2005.080481. PMC 2082730. PMID 16632672. //
  31. ^ Büller, H (1997). "Problems in diagnosis of IBD in children". The Netherlands Journal of Medicine 50 (2): S8–11. doi:10.1016/S0300-2977(96)00064-2. PMID 9050326.
  32. ^ O'Keefe, S. J. D. (1996). "Nutrition and Gastrointestinal Disease". Scandinavian Journal of Gastroenterology 31: 52. doi:10.3109/00365529609094750.
  33. ^ Danese, Silvio; Semeraro, Stefano; Papa, Alfredo; Roberto, Italia; Scaldaferri, Franco; Fedeli, Giuseppe; Gasbarrini, Giovanni; Gasbarrini, Antonio (2005). "Extraintestinal manifestations in inflammatory bowel disease". World Journal of Gastroenterology 11 (46): 7227–36. PMID 16437620.
  34. ^ a b Crohn's disease. Retrieved July 13, 2007.
  35. ^ MedlinePlus Encyclopedia Small bowel bacterial overgrowth
  36. ^ Zadik, Yehuda; Drucker, Scott; Pallmon, Sarit (2011). "Migratory stomatitis (ectopic geographic tongue) on the floor of the mouth". Journal of the American Academy of Dermatology 65 (2): 459–60. doi:10.1016/j.jaad.2010.04.016. PMID 21763590.
  37. ^ Prevalence defined as at least 5 health care contacts in a 10 year period for the condition, according to: Greenstein, A. J.; Janowitz, H. D.; Sachar, D. B. (1976). "The extra-intestinal complications of Crohn's disease and ulcerative colitis: a study of 700 patients". Medicine 55 (5): 401–412. doi:10.1097/00005792-197609000-00004. PMID 957999. edit
  38. ^ Enterovesical Fistula at eMedicine
  39. ^ 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. doi:10.1016/0140-6736(90)91889-I. PMID 1975343.
  40. ^ Collins P, Mpofu C, Watson A, Rhodes J (2006). Watson, Alastair J. ed. "Strategies for detecting colon cancer and/or dysplasia in patients with inflammatory bowel disease". Cochrane Database Syst Rev (2): CD000279. doi:10.1002/14651858.CD000279.pub3. PMID 16625534.
  41. ^ Zisman, Timothy L; Rubin, David T (2008). "Colorectal cancer and dysplasia in inflammatory bowel disease". World Journal of Gastroenterology 14 (17): 2662–9. doi:10.3748/wjg.14.2662. PMC 2709054. PMID 18461651. //
  42. ^ Evans, J; Steinhart, AH; Cohen, Z; McLeod, RS (2003). "Home Total Parenteral Nutrition an Alternative to Early Surgery for Complicated Inflammatory Bowel Disease". Journal of Gastrointestinal Surgery 7 (4): 562–6. doi:10.1016/S1091-255X(02)00132-4. PMID 12763417.
  43. ^ "Complications of Crohn's Disease". Centocor Ortho Biotech. Retrieved 2009-11-07.
  44. ^ Kaplan, C (2005-10-21). "IBD and Pregnancy: What You Need to Know". Crohn's and Colitis Foundation of America. Retrieved 2009-11-07.
  45. ^ a b c d Kornbluth, Asher; David B. Sachar (July 2004). "Ulcerative colitis practice guidelines in adults (update): American College of Gastroenterology, Practice Parameters Committee". American Journal of Gastroenterology 99 (7): 1371–85. doi:10.1111/j.1572-0241.2004.40036.x. PMID 15233681. Archived from the original on April 6, 2008. Retrieved 2009-11-07.
  46. ^ Crohn's Disease Overview
  47. ^ Braat H, Peppelenbosch MP, Hommes DW (August 2006). "Immunology of Crohn's disease". Ann. N. Y. Acad. Sci. 1072: 135–54. doi:10.1196/annals.1326.039. PMID 17057196.
  48. ^ Henckaerts L, Figueroa C, Vermeire S, Sans M (May 2008). "The role of genetics in inflammatory bowel disease". Curr Drug Targets 9 (5): 361–8. doi:10.2174/138945008784221161. PMID 18473763.
  49. ^ a b c Marks DJ, Harbord MW, MacAllister R, Rahman FZ, Young J, Al-Lazikani B, Lees W, Novelli M, Bloom S, Segal AW (2006). "Defective acute inflammation in Crohn's disease: a clinical investigation". Lancet 367 (9511): 668–78. doi:10.1016/S0140-6736(06)68265-2. PMC 2092405. PMID 16503465. //
  50. ^ Comalada M, Peppelenbosch MP (September 2006). "Impaired innate immunity in Crohn's disease". Trends Mol Med 12 (9): 397–9. doi:10.1016/j.molmed.2006.07.005. PMID 16890491.
  51. ^ "Crohn's disease has strong genetic link: study". Crohn's and Colitis Foundation of America. 2007-04-16. Retrieved 2009-11-07.
  52. ^ Ogura, Y; Bonen, DK; Inohara, N; Nicolae, DL; Chen, FF; Ramos, R; Britton, H; Moran, T et al. (2001). "A frameshift mutation in NOD2 associated with susceptibility to Crohn's disease". Nature 411 (6837): 603–6. doi:10.1038/35079114. PMID 11385577.
  53. ^ 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. doi:10.1053/gast.2002.32415. PMID 11910337.
  54. ^ Kaser, A; Lee, AH; Franke, A; Glickman, JN; Zeissig, S; Tilg, H; Nieuwenhuis, EES; Higgins, DE et al. (5 September 2008). "XBP1 links ER stress to intestinal inflammation and confers genetic risk for human inflammatory bowel disease". Cell 134 (5): 743–56. doi:10.1016/j.cell.2008.07.021. PMC 2586148. PMID 18775308. //
  55. ^ Clevers, H (2009). "Inflammatory Bowel Disease, Stress, and the Endoplasmic Reticulum". New England Journal of Medicine 360 (7): 726–27. doi:10.1056/NEJMcibr0809591. PMID 19213688.
  56. ^ Marks DJ, Segal AW. (January 2008). "Innate immunity in inflammatory bowel disease: a disease hypothesis". J Pathol. 214 (2): 260–6. doi:10.1002/path.2291. PMC 2635948. PMID 18161747. //
  57. ^ Cobrin GM, Abreu MT (2005). "Defects in mucosal immunity leading to Crohn's disease". Immunol. Rev. 206: 277–95. doi:10.1111/j.0105-2896.2005.00293.x. PMID 16048555.
  58. ^ a b Elson, CO; Cong, Y; Weaver, CT; Schoeb, TR; Mcclanahan, TK; Fick, RB; Kastelein, RA (2007). "Monoclonal Anti–Interleukin 23 Reverses Active Colitis in a T Cell–Mediated Model in Mice". Gastroenterology 132 (7): 2359–70. doi:10.1053/j.gastro.2007.03.104. PMID 17570211.
  59. ^ Prescott NJ, Fisher SA, Franke A et al. (2007). "A nonsynonymous SNP in ATG16L1 predisposes to ileal Crohn's disease and is independent of CARD15 and IBD5". Gastroenterology 132 (5): 1665–71. doi:10.1053/j.gastro.2007.03.034. PMID 17484864.
  60. ^ Moises Velasquez-Manoff (June 29, 2008). "The Worm Turns". The New York Times.
  61. ^ Sartor, R Balfour (2006). "Mechanisms of Disease: Pathogenesis of Crohn's disease and ulcerative colitis". Nature Clinical Practice Gastroenterology & Hepatology 3 (7): 390. doi:10.1038/ncpgasthep0528.
  62. ^ Multidrug resistance is common in Escherichia coli associated with ileal Crohn's disease.
  63. ^ The many faces of Crohn’s Disease: Latest concepts in etiology
  64. ^ Naser, Saleh A; Collins, Michael T (2006). "Debate on the lack of evidence of Mycobacterium avium subsp. Paratuberculosis in Crohn's disease". Inflammatory Bowel Diseases 11 (12): 1123. doi:10.1097/01.MIB.0000191609.20713.ea.
  65. ^[full citation needed]
  66. ^ Glubb, Dylan M; Gearry, Richard B; Barclay, Murray L; Roberts, Rebecca L; Pearson, John; Keenan, Jacqui I; McKenzie, Judy; Bentley, Robert W (2011). "NOD2 and ATG16L1 polymorphisms affect monocyte responses in Crohn's disease". World Journal of Gastroenterology 17 (23): 2829–37. doi:10.3748/wjg.v17.i23.2829. PMC 3120942. PMID 21734790. //
  67. ^ Clancy, R; Ren, Z; Turton, J; Pang, G; Wettstein, A (2007). "Molecular evidence for Mycobacterium avium subspecies paratuberculosis (MAP) in Crohn's disease correlates with enhanced TNF-alpha secretion". Digestive and liver disease : official journal of the Italian Society of Gastroenterology and the Italian Association for the Study of the Liver 39 (5): 445–51. doi:10.1016/j.dld.2006.12.006. PMID 17317344.
  68. ^ Nakase, H; Tamaki, H; Matsuura, M; Chiba, T; Okazaki, K (2011). "Involvement of mycobacterium avium subspecies paratuberculosis in TNF-α production from macrophage: Possible link between MAP and immune response in Crohn's disease". Inflammatory bowel diseases 17 (11): E140–2. doi:10.1002/ibd.21750. PMID 21990211.
  69. ^ Baumgart, Martin; Dogan, Belgin; Rishniw, Mark; Weitzman, Gil; Bosworth, Brian; Yantiss, Rhonda; Orsi, Renato H; Wiedmann, Martin 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". The ISME Journal 1 (5): 403–18. doi:10.1038/ismej.2007.52. PMID 18043660.
  70. ^ Sasaki, M; Sitaraman, SV; Babbin, BA; Gerner-Smidt, P; Ribot, EM; Garrett, N; Alpern, JA; Akyildiz, A et al. (2007). "Invasive Escherichia coli are a feature of Crohn's disease". Laboratory investigation; a journal of technical methods and pathology 87 (10): 1042–54. doi:10.1038/labinvest.3700661. PMID 17660846.
  71. ^ Darfeuille-Michaud, A; Boudeau, J; Bulois, P; Neut, C; Glasser, AL; Barnich, N; Bringer, MA; Swidsinski, A et al. (2004). "High prevalence of Adherent-invasive Escherichia coli associated with ileal mucosa in Crohn's disease". Gastroenterology 127 (2): 412–21. doi:10.1053/j.gastro.2004.04.061. PMID 15300573.
  72. ^ Baumgart, M; Dogan, B; Rishniw, M; Weitzman, G; Bosworth, B; Yantiss, R; Orsi, RH; Wiedmann, 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". The ISME journal 1 (5): 403–18. doi:10.1038/ismej.2007.52. PMID 18043660.
  73. ^ Martinez-Medina, Margarita; Naves, Plínio; Blanco, Jorge; Aldeguer, Xavier; Blanco, Jesus E; Blanco, Miguel; Ponte, Carmen; Soriano, Francisco et al. (2009). "Biofilm formation as a novel phenotypic feature of adherent-invasive Escherichia coli (AIEC)". BMC Microbiology 9: 202. doi:10.1186/1471-2180-9-202. PMC 2759958. PMID 19772580. //
  74. ^ Inflammation Drives Dysbiosis and Bacterial Invasion in Murine Models of Ileal Crohn’s Disease
  75. ^ Adherent-invasive Escherichia coli and Crohn's disease.
  76. ^ Adherent Invasive E.coli (LF82) are Potently PRO-Inflammatory for Monocytes, but Not Intestinal Macrophages, in Patients With Crohn's Disease
  77. ^ Characterization of adherent-invasive Escherichia coli isolated from pediatric patients with inflammatory bowel disease.
  78. ^ Giaffer, M H; Clark, A; Holdsworth, C D (1992). "Antibodies to Saccharomyces cerevisiae in patients with Crohn's disease and their possible pathogenic importance". Gut 33 (8): 1071–5. doi:10.1136/gut.33.8.1071. PMC 1379444. PMID 1398231. //
  79. ^ Cenac N, Andrews CN, Holzhausen M et al. (March 2007). "Role for protease activity in visceral pain in irritable bowel syndrome". J. Clin. Invest. 117 (3): 636–47. doi:10.1172/JCI29255. PMC 1794118. PMID 17304351. //
  80. ^ Cenac N, Coelho AM, Nguyen C et al. (November 2002). "Induction of Intestinal Inflammation in Mouse by Activation of Proteinase-Activated Receptor-2". Am. J. Pathol. 161 (5): 1903–15. doi:10.1016/S0002-9440(10)64466-5. PMC 1850779. PMID 12414536.
  81. ^ Boorom KF, Smith H, Nimri L et al. (October 2008). "Oh my aching gut: irritable bowel syndrome, Blastocystis, and asymptomatic infection". Parasit Vectors 1 (1): 40. doi:10.1186/1756-3305-1-40. PMC 2627840. PMID 18937874. //
  82. ^ Hugot, Jean-Pierre; Alberti, Corinne; Berrebi, Dominique; Bingen, Edouard; Cézard, Jean-Pierre (2003). "Crohn's disease: The cold chain hypothesis". The Lancet 362 (9400): 2012. doi:10.1016/S0140-6736(03)15024-6.
  83. ^ "Fridges blamed for Crohn's disease rise". Medical News Today. 2003-12-12.
  84. ^ Forbes, Alastair; Kalantzis, Tommy (2005). "Crohn's disease: The cold chain hypothesis". International Journal of Colorectal Disease 21 (5): 399–401. doi:10.1007/s00384-005-0003-7. PMID 16059694.
  85. ^ Subramanian, S.; Roberts, C. L.; Hart, C. A.; Martin, H. M.; Edwards, S. W.; Rhodes, J. M.; Campbell, B. J. (2007). "Replication of Colonic Crohn's Disease Mucosal Escherichia coli Isolates within Macrophages and Their Susceptibility to Antibiotics". Antimicrobial Agents and Chemotherapy 52 (2): 427–34. doi:10.1128/AAC.00375-07. PMC 2224732. PMID 18070962. //
  86. ^ Mpofu, Chiedzo M.; Campbell, Barry J.; Subramanian, Sreedhar; Marshall–Clarke, Stuart; Hart, C. Anthony; Cross, Andy; Roberts, Carol L.; McGoldrick, Adrian et al. (2007). "Microbial Mannan Inhibits Bacterial Killing by Macrophages: A Possible Pathogenic Mechanism for Crohn's Disease". Gastroenterology 133 (5): 1487–98. doi:10.1053/j.gastro.2007.08.004. PMID 17919633.
  87. ^ "New insights into Crohn's Disease".
  88. ^ "Possible links between Crohn's disease and Paratuberculosis". European Commission Directorate-General Health & Consumer Protection. Retrieved 2009-11-07.
  89. ^ Gui, G. P.; Thomas, P. R.; Tizard, M. L.; Lake, J.; Sanderson, J. D.; Hermon-Taylor, J. (1997). "Two-year-outcomes analysis of Crohn's disease treated with rifabutin and macrolide antibiotics". Journal of Antimicrobial Chemotherapy 39 (3): 393–400. doi:10.1093/jac/39.3.393. PMID 9096189.
  90. ^ a b Shoda, R; Matsueda, K; Yamato, S; Umeda, N (1996). "Epidemiologic analysis of Crohn disease in Japan: increased dietary intake of n-6 polyunsaturated fatty acids and animal protein relates to the increased incidence of Crohn disease in Japan". The American journal of clinical nutrition 63 (5): 741–5. PMID 8615358.
  91. ^ 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.
  92. ^ Reddy D, Siegel CA, Sands BE, Kane S (July 2006). "Possible association between isotretinoin and inflammatory bowel disease". The American journal of gastroenterology 101 (7): 1569–73. doi:10.1111/j.1572-0241.2006.00632.x. PMID 16863562.
  93. ^ Borobio E, Arín A, Valcayo A, Iñarrairaegui M, Nantes O, Prieto C (2004). "[Isotretinoin and ulcerous colitis]" (in Spanish; Castilian). An Sist Sanit Navar 27 (2): 241–3. doi:10.4321/S1137-66272004000300009. PMID 15381956.
  94. ^ Reniers DE, Howard JM (October 2001). "Isotretinoin-induced inflammatory bowel disease in an adolescent". Ann Pharmacother 35 (10): 1214–6. doi:10.1345/aph.10368. PMID 11675849.
  95. ^ "Crohn's Disease". National Digestive Diseases Information Clearinghouse. Retrieved 13 November 2012.
  96. ^ 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.
  97. ^ HCP: Pill Cam, Capsule Endoscopy, Esophageal Endoscopy
  98. ^ Scheinfeld, NS; Teplitz, E; McClain, SA (November 2001). "Crohn's disease and lichen nitidus: a case report and comparison of common histopathologic features". Inflammatory Bowel Diseases 7 (4): 314–8. doi:10.1097/00054725-200111000-00006. PMID 11720321.
  99. ^ a b Hara, A. K.; Leighton, J. A.; Heigh, R. I.; Sharma, V. K.; Silva, A. C.; De Petris, G.; Hentz, J. G.; Fleischer, D. E. (2005). "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.
  100. ^ Triester, SL; Leighton, JA; Leontiadis, GI; Gurudu, SR; Fleischer, DE; Hara, AK; Heigh, RI; Shiff, AD et al. (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.
  101. ^ Dixon, P.M.; Roulston, M.E.; Nolan, D.J. (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.
  102. ^ Carucci, Laura R; Levine, Marc S (2002). "Radiographic imaging of inflammatory bowel disease". Gastroenterology Clinics of North America 31 (1): 93–117, ix. doi:10.1016/S0889-8553(01)00007-3. PMID 12122746.
  103. ^ Rajesh, A; Maglinte DD (2006). "Multislice CT enteroclysis: technique and clinical applications". Clinical Radiology 61 (1): 31–9. doi:10.1016/j.crad.2005.08.006. PMID 16356814.
  104. ^ Zissin, R; Hertz M; Osadchy A; Novis B; Gayer G (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. Archived from the original on April 6, 2008. Retrieved 2009-11-07.
  105. ^ MacKalski, BA; Bernstein CN (2005). "New diagnostic imaging tools for inflammatory bowel disease". Gut 55 (5): 733–41. doi:10.1136/gut.2005.076612. PMC 1856109. PMID 16609136. //
  106. ^ Goh, J.; O'Morain, C. A. (2003). "Nutrition and adult inflammatory bowel disease". Alimentary Pharmacology and Therapeutics 17 (3): 307–20. doi:10.1046/j.1365-2036.2003.01482.x. PMID 12562443.
  107. ^ Chamouard, Patrick; Richert, Zoe; Meyer, Nicolas; Rahmi, Gabriel; Baumann, René (2006). "Diagnostic Value of C-Reactive Protein for Predicting Activity Level of Crohn's Disease". Clinical Gastroenterology and Hepatology 4 (7): 882–7. doi:10.1016/j.cgh.2006.02.003. PMID 16630759.
  108. ^ Kaila, B; K Orr and C N Bernstein (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.
  109. ^ Israeli, E.; I. Grotto, B. Gilburd, R. D. Balicer, E. Goldin, A. Wiik and Y. Shoenfeld (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. PMC 1774672. PMID 16099791. //
  110. ^ Ferrante, M.; L. Henckaerts, M. Joossens, M. Pierik, S. Joossens, N. Dotan, G.L. Norman , R.T. Altstock , K. Van Steen , P. Rutgeerts , G. Van Assche and S.Vermeire (2007). "New serological markers in inflammatory bowel disease are associated with complicated disease behaviour". Gut 56 (10): 1394–403. doi:10.1136/gut.2006.108043. PMC 2000264. PMID 17456509. //
  111. ^ Papp, M; Altorjay, I; Dotan, N; Palatka, K; Foldi, I; Tumpek, J; Sipka, S; Udvardy, M et al. (2008). "New serological markers for inflammatory bowel disease are associated with earlier age at onset, complicated disease behavior, risk for surgery, and NOD2/CARD15 genotype in a Hungarian IBD cohort". The American Journal of Gastroenterology 103 (3): 665–81. doi:10.1111/j.1572-0241.2007.01652.x. PMID 18047543.
  112. ^ Seow, C.H.; J.M. Stempak, W. Xu, H. Lan, A.M. Griffiths, G.R. Greenberg, A.H. Steinhart, N. Dotan and M.S. Silverberg (2009). "Novel anti-glycan antibodies related to inflammatory bowel disease diagnosis and phenotype". Am J Gastroenterol 104 (6): 1426–34. doi:10.1038/ajg.2009.79. PMID 19491856.
  113. ^ Dotan, I. (2007). "Serologic markers in inflammatory bowel disease: tools for better diagnosis and disease stratification". Expert Rev Gastroenterol Hepatol 1 (2): 265–74. doi:10.1586/17474124.1.2.265. PMID 19072419.
  114. ^ Broomé, Ulrika; Annika Bergquist (February 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.
  115. ^ Shepherd, NA (August 2002). "Granulomas in the diagnosis of intestinal Crohn's disease: a myth exploded?". Histopathology 41 (2): 166–8. doi:10.1046/j.1365-2559.2002.01441.x. PMID 12147095.
  116. ^ Mahadeva, U; Martin, JP; Patel, NK; Price, AB (July 2002). "Granulomatous ulcerative colitis: a re-appraisal of the mucosal granuloma in the distinction of Crohn's disease from ulcerative colitis". Histopathology 41 (1): 50–5. doi:10.1046/j.1365-2559.2002.01416.x. PMID 12121237.
  117. ^ a b Pages 152-156 (Section: Inflammatory bowel disease(IBD)) in:Elizabeth D Agabegi; Agabegi, Steven S. (2008). Step-Up to Medicine (Step-Up Series). Hagerstwon, MD: Lippincott Williams & Wilkins. ISBN 0-7817-7153-6.
  118. ^ Feller, M.; Huwiler, K.; Schoepfer, A.; Shang, A.; Furrer, H.; Egger, M. (2010). "Long-term antibiotic treatment for Crohn's disease: systematic review and meta-analysis of placebo-controlled trials". Clinical Infectious Diseases 50 (4): 473–480. doi:10.1086/649923. PMID 20067425. edit
  119. ^ [1] Section "Antibiotics and Ulcerative Colitis" in: Prantera, C.; Scribano, M. (2009). "Antibiotics and probiotics in inflammatory bowel disease: why, when, and how". Current opinion in gastroenterology 25 (4): 329–333. doi:10.1097/MOG.0b013e32832b20bf. PMID 19444096. edit
  120. ^ a b Fries, WS; Nazario, B (2007-05-16). "Crohn's Disease: 54 Tips to Help You Manage". WebMD. Retrieved 2008-02-14.
  121. ^ Escott-Stump, Sylvia (2008). Nutrition and Diagnosis-Related Care, 7th edition. Baltimore, MD: Lippincott Williams & Wilkins. pp. 1020 (pp 431). ISBN 978-1-60831-017-3.
  122. ^ Shanahan, Fergus (January 2002). "Crohn's disease". The Lancet (Elsevier Science) 359 (9300): 62–9. doi:10.1016/S0140-6736(02)07284-7.
  123. ^ "FDA Approves Cimzia to Treat Crohn's Disease" (Press release). U.S. Food and Drug Administration (FDA). April 22, 2008. Retrieved 2009-11-05.
  124. ^ Sandborn, William J.; Colombel, Jean Frédéric; Enns, Roberts; Feagan, Brian G.; Hanauer, Stephen B.; Lawrance, Ian C.; Panaccione, Remo; Sanders, Martin et al. (2005). "Natalizumab Induction and Maintenance Therapy for Crohn's Disease". New England Journal of Medicine 353 (18): 1912–25. doi:10.1056/NEJMoa043335. PMID 16267322.
  125. ^ MacDonald, JK; McDonald, JWD (2007). MacDonald, John K. ed. "Natalizumab for induction of remission in Crohn's disease". Cochrane Database of Systematic Reviews (1): CD006097. doi:10.1002/14651858.CD006097.pub2. PMID 17253580. CD006097.
  126. ^ Longmore, Murray; Ian Wilkinson, Tom Turmezei, Chee Kay Cheung (2007). Oxford Handbook of Clinicial Medicine (7th ed.). Oxford University Press. pp. 266–7. ISBN 0-19-856837-1.
  127. ^ Mowat C, Cole A, Windsor A, et al. (May 2011). "Guidelines for the management of inflammatory bowel disease in adults". Gut 60 (5): 571–607. doi:10.1136/gut.2010.224154. PMID 21464096.
  128. ^ Tresca, AJ (2007-01-12). "Resection Surgery for Crohn's Disease". Retrieved 2008-02-14.
  129. ^ 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. doi:10.1007/BF02055108. PMID 8918424.
  130. ^ Short Bowel Syndrome as defined by the National Institute of Diabetes and Digestive and Kidney Diseases
  131. ^ Rhodes, M (2006-10-24). "Intestinal transplant for Crohn's disease". Everyday Health. Retrieved 2009-03-22.
  132. ^ Caprilli, R; Gassull, MA; Escher, JC; Moser, G; Munkholm, P; Forbes, A; Hommes, DW; Lochs, H et al. (2006). "European evidence based consensus on the diagnosis and management of Crohn's disease: special situations". Gut 55 Suppl 1 (Suppl 1): i36–58. doi:10.1136/gut.2005.081950c. PMC 1859996. PMID 16481630. //
  133. ^ "Use of complementary and alternative medicine in Germany – a survey of patients with inflammatory bowel disease". BioMed Central. Retrieved 21 September 2010. "At the same time, further clinical studies assessing the most commonly used CAM therapies are urgently needed. Research in CAM offers the chance to discover new treatment options in the management of IBD but may also protect patients from ineffective and expensive 'pseudo'-therapies."
  134. ^ Joos S, Brinkhaus B, Maluche C et al. (2004). "Acupuncture and moxibustion in the treatment of active Crohn's disease: a randomized controlled study". Digestion 69 (3): 131–9. doi:10.1159/000078151. PMID 15114043.
  135. ^ Caprilli, R; Gassull, MA; Escher, JC; Moser, G; Munkholm, P; Forbes, A; Hommes, DW; Lochs, H et al. (2006). "The second European evidence-based Consensus on the diagnosis and management of Crohn's disease: Special situations". Gut 55 (Suppl 1): i36–i58. doi:10.1136/gut.2005.081950c. PMC 1859996. PMID 16481630. "the colitis activity index fell significantly in the treatment group compared to the sham acupuncture group. However, recruitment did not reach its target and the number of patients was small."[verification needed]
  136. ^ Smart, H L; Mayberry, J F; Atkinson, M (1986). "Alternative medicine consultations and remedies in patients with the irritable bowel syndrome". Gut 27 (7): 826–8. doi:10.1136/gut.27.7.826. PMC 1433575. PMID 3755416. //
  137. ^ Canavan, C.; Abrams, K. R.; Mayberry, J. (2006). "Meta-analysis: Colorectal and small bowel cancer risk in patients with Crohn's disease". Alimentary Pharmacology and Therapeutics 23 (8): 1097–104. doi:10.1111/j.1365-2036.2006.02854.x. PMID 16611269.
  138. ^ "Crohn's disease - Prognosis". University of Maryland Medical Centre. Retrieved 19 October 2012.
  139. ^ a b Hiatt, Robert A.; Leon Kaufman (1988). "Epidemiology of inflammatory bowel disease in a defined northern California population". Western Journal of Medicine 149 (5): 541–6. PMC 1026530. PMID 3250100. //
  140. ^ Moum, B.; M. H. Vatn, A. Ekbom, E. Aadland, O. Fausa, I. Lygren, N. Stray, J. Sauar, T. Schulz (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. doi:10.3109/00365529609006410. PMID 8726303.
  141. ^ Shivananda, S.; J. Lennard-Jones, R. Logan, N. Fear, A. Price, L. Carpenter and M. van Blankenstein (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. doi:10.1136/gut.39.5.690. PMC 1383393. PMID 9014768. //
  142. ^ Effects of light smoking consumption on the clinical course of Crohn's disease. Seksik P, Nion-Larmurier I, Sokol H, Beaugerie L, Cosnes J. Inflamm Bowel Dis. 2009
  143. ^ "Crohn's disease manifests differently in boys and girls". Crohn's and Colitis Foundation of America.
  144. ^ "Who is affected by Crohn's disease". Healthwise.
  145. ^ Satsangi J, Jewell DP, Bell JI (1997). "The genetics of inflammatory bowel disease". Gut 40 (5): 572–4. PMC 1027155. PMID 9203931. //
  146. ^ Tysk C, Lindberg E, Järnerot G, Flodérus-Myrhed B (1988). "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 29 (7): 990–6. doi:10.1136/gut.29.7.990. PMC 1433769. PMID 3396969. //
  147. ^ Kirsner JB (1988). "Historical aspects of inflammatory bowel disease". J. Clin. Gastroenterol. 10 (3): 286–97. doi:10.1097/00004836-198806000-00012. PMID 2980764.
  148. ^
  149. ^ Croese J, O'neil J, Masson J et al. (2006). "A proof of concept study establishing Necator americanus in Crohn's patients and reservoir donors". Gut 55 (1): 136–7. doi:10.1136/gut.2005.079129. PMC 1856386. PMID 16344586. //
  150. ^ *Massa and Monory; Monory, K (2007). "Endocannabinoids and the gastrointestinal tract". Journal of Endocrinological Investigation 29 ((Suppl)): 47–57. PMID 16751708.
  151. ^ Massa, F; Storr, M; Lutz, B (2005). "The endocannabinoid system in the physiology and pathophysiology of the gastrointestinal tract". Journal of Molecular Medicine 83 (12): 944–54. doi:10.1007/s00109-005-0698-5. PMID 16133420.
  152. ^ Izzo, AA; Coutts, AA (2005). "Cannabinoids and the digestive tract". Handbook of Experimental Pharmacology. Handbook of Experimental Pharmacology 168 (168): 573–98. doi:10.1007/3-540-26573-2_19. ISBN 3-540-22565-X. PMID 16596788.
  153. ^ Feagan, BG; Fedorak, RN; Irvine, EJ; Wild, G; Sutherland, L; Steinhart, AH; Greenberg, GR; Koval, J et al. (2000). "A comparison of methotrexate with placebo for the maintenance of remission in Crohn's disease. North American Crohn's Study Group Investigators". New England Journal of Medicine 342 (22): 1627–32. doi:10.1056/NEJM200006013422202. PMID 10833208.
  154. ^ Ursing B, Alm T, Bárány F et al. (1982). "A comparative study of metronidazole and sulfasalazine for active Crohn's disease: the cooperative Crohn's disease study in Sweden. II. Result". Gastroenterology 83 (3): 550–62. PMID 6124474.
  155. ^ Cohen LB (2004). "Re: Disappearance of Crohn's ulcers in the terminal ileum after thalidomide therapy. Can J Gastroenterol 2004; 18(2): 101-104". Can. J. Gastroenterol. 18 (6): 419; author reply 419. PMID 15230268.

External links