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Crohn Disease

  • Author: Leyla J Ghazi, MD; Chief Editor: Julian Katz, MD  more...
 
Updated: Feb 26, 2015
 

Practice Essentials

Crohn disease is an idiopathic, chronic inflammatory process that can affect any part of the gastrointestinal tract from the mouth to the anus (see the image below). Individuals with this condition often experience periods of symptomatic relapse and remission.

Colonoscopic image of a large ulcer and inflammati Colonoscopic image of a large ulcer and inflammation of the descending colon in a 12-year-old boy with Crohn disease.

See Autoimmune Disorders: Making Sense of Nonspecific Symptoms, a Critical Images slideshow, to help identify several diseases that can cause a variety of nonspecific symptoms.

Essential update: Risk stratification model may significantly reduce CT use in Crohn disease patients

A risk-stratification model based on C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR), which are significantly associated with complications of Crohn disease, could reduce the use of computed tomography (CT) scans in patients reporting to the emergency room by 43%, while missing only 0.8% of emergencies, according to a recent retrospective analysis of 613 adult patients. Researchers used logistic regression to model associations between these laboratory values and perforation, abscess, or other serious complications. Further validation studies of the models need to be performed.[1]

Signs and symptoms

The characteristic presentation in Crohn disease is abdominal pain and diarrhea, which may be complicated by intestinal fistulization or obstruction. Unpredictable flares and remissions characterize the long-term course.[2, 3, 4]

Other signs and symptoms of Crohn disease may include the following:

  • Rectal bleeding
  • Fever
  • Weight loss, anorexia
  • Nausea, vomiting
  • Malnutrition, vitamin deficiencies
  • Generalized fatigability
  • Bone loss
  • Psychosocial issues (eg, depression, anxiety, and coping difficulty); pediatric patients may also experience psychological issues regarding quality of life and body image [5, 6]
  • Growth failure in pediatric patients: May precede gastrointestinal symptoms by years

See Clinical Presentation for more detail.

Diagnosis

Examination for Crohn disease includes the following:

  • Vital signs: Normal, but possible presence of tachycardia in anemic or dehydrated patients; possible chronic intermittent fever
  • Gastrointestinal: May vary from normal to those of an acute abdomen; assess for rectal sphincter tone, gross rectal mucosal abnormalities, presence of hematochezia
  • Genitourinary: May include presence of skin tags, fistulae, ulcers, abscesses, and scarring in the perianal region; nephrolithiasis, hydronephrosis, and enterovesical fistulae
  • Musculoskeletal: Possible arthritis and arthralgia, particularly of the large joints [7]
  • Dermatologic: May show pallor or jaundice, mucocutaneous or aphthous ulcers, erythema nodosum, and pyoderma gangrenosum
  • Ophthalmologic: May reveal episcleritis; possible uveitis
  • Growth delay: Decreased growth velocity (eg, height), pubertal delay
  • Hematologic: Hypercoagulable state

Laboratory Tests

Although laboratory results for Crohn disease are nonspecific and are of value principally for facilitating disease management, they may also be used as surrogate markers for inflammation and nutritional status and to screen for deficiencies of vitamins and minerals.

Routine laboratory studies include the following:

  • CBC count
  • Chemistry panel
  • Liver function tests
  • Inflammatory markers
  • Stool studies
  • Serologic tests

Imaging studies

Imaging modalities used for Crohn disease include the following:

  • Plain abdominal radiography
  • Barium contrast studies (eg, small bowel follow-through, barium enema, enteroclysis)
  • CT scanning of the abdomen
  • CT enterography or magnetic resonance enterography: Replacing small bowel follow-through studies
  • MRI of the pelvis
  • Abdominal and/or endoscopic ultrasonography
  • Nuclear imaging (eg, technetium-99m hexamethyl propylene amine oxime, indium-111)
  • Fluorine-18-2-fluoro-2-deoxy-D-glucose scanning combined with positron emission tomography or CT scanning

Procedures

The following procedures may help in the evaluation of Crohn disease:

  • Endoscopic visualization and biopsy (eg, upper gastrointestinal endoscopy, esophagogastroduodenoscopy, endoscopic retrograde cholangiopancreatography)
  • Colonoscopy, ileocolonoscopy
  • Small bowel enteroscopy
  • Interventional radiology: For percutaneous drainages of abscesses

See Workup for more detail.

Management

Pharmacotherapy

Medications used in the treatment of Crohn disease include the following:

  • 5-Aminosalicylic acid derivative agents (eg, mesalamine rectal, mesalamine, sulfasalazine, balsalazide)
  • Corticosteroids (eg, prednisone, methylprednisolone, budesonide, hydrocortisone, prednisolone)
  • Immunosuppressive agents (eg, mercaptopurine, methotrexate, tacrolimus)
  • Monoclonal antibodies (eg, infliximab, adalimumab, certolizumab pegol, natalizumab, vedolizumab)
  • Antibiotics (eg, metronidazole, ciprofloxacin)
  • Antidiarrheal agents (eg, loperamide, diphenoxylate-atropine)
  • Bile acid sequestrants (eg, cholestyramine, colestipol)
  • Anticholinergic agents (eg, dicyclomine, hyoscyamine, propantheline)

Surgery

Unlike ulcerative colitis, Crohn disease has no surgical cure. Most patients with Crohn disease require surgical intervention during their lifetime.

Surgical management of the terminal ileum, ileocolon, and/or upper gastrointestinal tract may include the following[8] :

  • Resection of the affected bowel
  • Ileocolostomy or proximal loop ileostomy
  • Drainage of any septic foci with later definitive resection
  • Strictureplasty
  • Bypass
  • Endoscopic dilatation of symptomatic, accessible strictures

Surgical management of the colon may include the following[8] :

  • Subtotal or total colectomy with end ileostomy (laparoscopic or open approach)
  • Segmental or total colectomy with or without primary anastomosis
  • Total proctocolectomy or proctectomy with stoma creation

See Treatment and Medication for more detail.

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Background

Crohn disease is an idiopathic, chronic inflammatory process of the gastrointestinal (GI) tract that can affect any part of the tract from the mouth to the anus. Individuals with this condition often experience periods of symptomatic relapse and remission.

Crohn disease is believed to be the result of an imbalance between proinflammatory and anti-inflammatory mediators. Although genetic susceptibility, luminal antigenic drive, and environmental triggers are also important factors, animal models demonstrate that no single factor is sufficient to induce intestinal inflammation. (See Pathophysiology.)

Approximately 30% of Crohn disease cases involve the small bowel, particularly the terminal ileum, another 20% involve only the colon, and 45% involve both the small bowel and colon.[9] Once considered rare in the pediatric and black populations, Crohn disease is recognized with increasing frequency in children of all ages and in individuals of varying ethnicities. (See Epidemiology.)

The characteristic presentation is abdominal pain and diarrhea, which may be complicated by intestinal fistulization or obstruction. Unpredictable flares and remissions characterize the long-term course.[2, 3, 4] In addition, individuals can experience rectal bleeding, fever, weight loss, malnutrition, bone loss, and vitamin deficiencies. Psychosocial issues (eg, depression, anxiety, and coping difficulty) are common. Pediatric patients may also experience psychological issues regarding quality of life and body image.[5, 6] (See Presentation.)

Laboratory data for Crohn disease are nonspecific and are of value principally in assisting with management. However, various imaging modalities can aid in diagnosis and management; the choice among them depends upon the clinical question being asked. (See Workup.)

Plain radiography or computed tomography (CT) of the abdomen and pelvis can assess for bowel obstruction or pelvic intra-abdominal abscesses. Small bowel follow-through (SBFT) studies are being supplanted by CT enterography or magnetic resonance (MR) enterography, which is better able to distinguish inflammation from fibrosis. Magnetic resonance imaging (MRI) of the pelvis or endoscopic (transrectal) ultrasonography can identify perianal fistula anatomy and activity and determine the presence or absence of pelvic and perianal abscesses.

Endoscopic visualization and biopsy are essential in the diagnosis of Crohn disease. Colonoscopy is done to assess for colonic or terminal ileal disease. Upper GI endoscopy may be used to diagnose esophageal or gastroduodenal disease and is recommended for all children, regardless of the presence or absence of upper GI symptoms. (See Workup.)

The general goals of treatment are as follows:

  • To achieve the best possible clinical, laboratory, and histologic control of the inflammatory disease with the least adverse effects from medications
  • To permit the patient to function as normally as possible
  • In children, to promote growth with adequate nutrition; the unique problems encountered in the pediatric population necessitate a medical approach that promotes clinical improvement and reverses growth failure with minimal toxicity

Therapy is typically administered in a “step-up” approach, in which patients with mild disease are treated with 5-aminosalicylic acid (5-ASA), antibiotics, and nutritional therapy. If the patient does not respond to this approach or if the disease is more severe than was initially thought, corticosteroid and immunomodulatory therapy with 6-mercaptopurine (6-MP) or methotrexate is attempted. Finally, biologic and surgical therapies, at the tip of the treatment pyramid, are used.[10] (See Treatment.)

A subpopulation of patients with risk factors for complicated disease and rapid progression may benefit from a “top-down” approach. This approach involves early and aggressive use of tumor necrosis factor (TNF) antagonists, which may alter the natural history of the disease, improve treatment response, and decrease the need for steroid therapy. (See Treatment.)

Surgery plays an integral role in controlling medically refractory disease and treating complications of Crohn disease. Because of the high rate of disease recurrence after segmental bowel resection, the guiding principle of surgery is preservation of intestinal length and function.[2] (See Treatment.)

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Pathophysiology

Chronic inflammation from T-cell activation leading to tissue injury is implicated in the pathogenesis of Crohn disease.

After activation by antigen presentation, unrestrained responses of type 1 T helper (Th1) cells predominate in Crohn disease as a consequence of defective regulation. Th1 cytokines such as interleukin (IL)-12 and TNF-α stimulate the inflammatory response. Inflammatory cells recruited by these cytokines release nonspecific inflammatory substances, including arachidonic acid metabolites, proteases, platelet activating factor, and free radicals, which result in direct injury to the intestine.

In a study from 2012, investigators suggested that genetic predispositions for inflammatory bowel disease (IBD) lead to abnormal epithelial barrier integrity and homeostasis, deficits in autophagy, deficiencies in innate pattern recognition receptors, and problems with lymphocyte differentiation, especially in Crohn disease.[11]

Microscopically, the initial lesion starts as a focal inflammatory infiltrate around the crypts, followed by ulceration of superficial mucosa. Later, inflammatory cells invade the deep mucosal layers and, in that process, begin to organize into noncaseating granulomas (see the image below). The granulomas extend through all layers of the intestinal wall and into the mesentery and the regional lymph nodes.

Colonic granuloma in patient with Crohn disease. H Colonic granuloma in patient with Crohn disease. Hematoxylin-eosin staining. Image courtesy of Dr E. Ruchelli.

Neutrophil infiltration into the crypts forms crypt abscesses, leading to destruction of the crypt and atrophy of the colon. Chronic damage may be seen in the form of villous blunting in the small intestine as well. Ulcerations are common and are often seen on a background of normal mucosa.

Although granuloma formation is pathognomonic of Crohn disease, its absence does not exclude the diagnosis.[12]

Macroscopically, the initial abnormality consists of hyperemia and edema of the involved mucosa. Later, discrete superficial ulcers form over lymphoid aggregates and are seen as red spots or mucosal depressions (see the image below). These can become deep, serpiginous ulcers located transversely and longitudinally over an inflamed mucosa, giving the mucosa a cobblestone appearance. The lesions are often segmental, being separated by healthy areas, and are referred to as skip lesions.[12]

Colonoscopic image of a large ulcer and inflammati Colonoscopic image of a large ulcer and inflammation of the descending colon in a 12-year-old boy with Crohn disease.

Transmural inflammation results in thickening of the bowel wall and narrowing of the lumen. As Crohn disease progresses, it is complicated by obstruction or deep ulceration leading to fistulization by way of the sinus tracts penetrating the serosa, microperforation, abscess formation, adhesions, and malabsorption.[2]

Bowel obstruction is caused initially by significant edema of the mucosa and associated spasm of the bowel. Obstruction is intermittent and can often be reversed by means of conservative measures and anti-inflammatory agents. With further disease progression, the obstruction becomes chronic because of fibrotic scarring, luminal narrowing, and stricture formation.[2]

Fistulae may be enteroenteral, enterovesical, enterovaginal, or enterocutaneous. The inflammation extending through the bowel wall may also involve the mesentery and surrounding lymph nodes. Creeping fat may be seen when the mesentery wraps around the bowel surface (see the following image).[2] Serosal inflammation causes adhesions; thus, free perforations are less common in Crohn disease than in other inflammatory bowel conditions.[2]

Laparoscopic view depicts creeping fat along the m Laparoscopic view depicts creeping fat along the mesentery of the terminal ileum.
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Etiology

The exact cause of Crohn disease remains unknown. Genetic, microbial, immunologic, environmental, dietary, vascular, and psychosocial factors have been implicated, as have smoking and the use of oral contraceptives and nonsteroidal anti-inflammatory agents (NSAIDs). Patients may inherit susceptibility for an aberrant immunologic response to 1 or more of these provoking factors.[12] Interaction between the predisposing genetic factors, environmental factors, host factors, and triggering event is likely necessary for the disease to develop.

Studies have found compelling evidence for an inheritable risk for the development of Crohn disease. However, classic mendelian inheritance is not seen. Most of the genes thought to be involved in the development of the disease play a role in mucosal immunity, and their products are found on the mucosal barrier epithelium.[12]

When the genetics of Crohn disease were first investigated, a strong association was found with chromosome 16 (IBD1 gene), which led to the identification of 3 single nucleotide polymorphisms (SNPs), 2 missense and 1 frameshift, in the NOD2 gene (now called CARD15), the first gene clearly identified as a susceptibility gene for Crohn disease.

NOD2/CARD15 is a polymorphic gene involved in the innate immune system. Of its more than 60 variations, 3 play a role in 27% of patients with Crohn disease, primarily in those with ileal disease. Subsequent studies suggest that CARD15 genotype is associated not only with the onset of disease but also with its natural history. A study in a German and Norwegian cohort showed that patients with 1 of the 3 identified risk alleles for CARD15 were more likely to have either ileal or right-colon disease.[13, 14]

Another early genome-wide association study (GWAS) looked at Jewish and non-Jewish case-control cohorts and identified 2 SNPs in the IL23R gene, which encodes 1 subunit of the IL-23 receptor protein.[15] Interestingly, this study also described the promising nature of certain therapies that block the function of IL-23. Further research suggested that one particular polymorphism in the IL23R gene showed the strongest association in a German population.[16]

However, another study found that the Arg381Gln substitution is associated with childhood onset of IBD in Scotland.[17] Numerous other loci have been identified as conferring susceptibility to Crohn disease. Several large studies found multiple susceptibility loci and confirmed earlier findings.

In a meta-analysis of 3 GWASs, 526 SNPs from 74 distinct genomic loci were found.[18] In addition to loci that have been previously discussed, 21 new loci were found that were associated with an increased risk of developing Crohn disease. Among the new loci were some very interesting implications, including the genes CCR6, IL12B, STAT3, JAK2, LRRK2, CDKAL1, and PTPN22.[18] Most of these genes are involved in signal transduction in certain immune function, as well as genes involved more directly with immune function.

The interlectin gene (ITLN1) is expressed in the small bowel and colon and is involved in recognition of certain microorganisms in the intestine. Other GWASs found associations between susceptibility to Crohn disease and polymorphisms in genes associated with the intestinal milieu. One study, involving nearly 20,000 SNPs in 735 individuals with Crohn disease, found an association in the ATG16L1 gene, which encodes the autophagy-related 16-like protein involved in the autophagosome pathway that processes intracellular bacteria.[19, 20]

SNPs in other autophagy genes have also been associated with susceptibility to Crohn disease, as in one study examining at 2 polymorphisms that flanked the IRGM gene and that may be in the regulatory material for the gene.[21] Subsequently, various other loci have been implicated in the autophagy pathway as being associated with Crohn disease, with mounting evidence that the autophagosome pathway is very important in the pathogenesis of the disease.

Studies have also provided strong support for IBD susceptibility genes on chromosome 5p13.1, which is a gene desert but does modulate expression of the PTGER4 gene. A murine PTGER4 knockout model has been studied and found to exhibit significant susceptibility to severe colitis.[22]

A large genomic study of multiple diseases confirmed many of the findings found in earlier studies and identified several additional loci of interest for Crohn disease.[23, 24] A locus at 3p21 is located within the BSN gene, which encodes a brain-specific scaffold protein involved in neurotransmitter release. However, the MST1 gene is located nearby and encodes a macrophage stimulation gene, and the authors felt that this represented a more plausible explanation for the association.[24]

A locus at 10q24.2 is located near the NKX2-3 gene, which is a homeodomain-containing transcription factor.

Disruption of the homologous gene in a murine model resulted in defective development of the intestine.[25] The investigators hypothesized that changes to expression of this gene could alter the migration of lymphocytes in the intestine and change its inflammatory response. The last locus discussed in this model is immediately upstream of the PTPN2 on chromosome 18p11 and encodes a T cell protein tyrosine phosphatase, which is a negative regulator of inflammation.[25]

Infectious agents such as Mycobacterium paratuberculosis, Pseudomonas species, and Listeria species have all been implicated in the pathogenesis of Crohn disease, suggesting that the inflammation seen with the disease is the result of a dysfunctional, but appropriate, response to an infectious source.[12]

Interleukins and TNF-α have also been implicated in the disease process. Crohn disease is characterized by a Th1 cellular immune response pattern that leads to production of IL-12, TNF-α, and interferon gamma. TNF-α has been shown to play a critical role in the inflammation in this disease. Increased production of TNF-α by macrophages in patients with Crohn disease results in increased concentrations of TNF-α in the stool, blood, and mucosa.[26]

Environmental influences such as tobacco use seem to have an effect on Crohn disease. Smoking has been shown to double the risk of Crohn disease, whereas the risk of developing ulcerative colitis is lower in people who smoke than in those who have never smoked or in those who stopped smoking before their diagnosis.[12, 27]

It has been suggested that a diet high in fatty foods may increase the risk of Crohn disease.[28] Concerns about the measles vaccine and the development of the disease have proved to be unfounded.[29] Although appendectomy has been suggested to be protective in ulcerative colitis, it is not a protective factor in Crohn disease.[30]

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Epidemiology

United States statistics

In 1998, the prevalence of Crohn disease in the United States was estimated on the basis of data from Olmstead County, Minnesota, and was approximated at 8 cases per 100,000 population.[31] A subsequent analysis of a geographically diverse health insurance claims database estimated the prevalence of Crohn disease among US children and adults in 2003-2004 to be closer to 201 cases per 100,000 persons among adults and 43 per 100,000 among children.[32]

Urban areas may have a higher prevalence of IBD than rural areas do.[2, 3] Upper socioeconomic classes are thought to have a higher prevalence than lower socioeconomic classes, a difference that is likely influenced by increased access to health care, though genetic and environmental factors may also play a role.[2, 7]

International statistics

Within Europe and North America, a north-to-south gradient in the frequency of IBD in populations is present. This difference in incidence correlates with the highest frequency of IBD in temperate climates and more industrialized parts of the world, such as Western Europe and North America.[33] As new regions assume Western cultural practices, an increased prevalence of ulcerative colitis is usually found approximately 1 decade before the observed increase in Crohn disease.

The overall incidence of Crohn disease in Europe is about 5.6 per 100,000 inhabitants (7.0 per 100,000 person-years in northern centers vs 3.9 in southern centers).[34] In most Western European countries, the incidence has stabilized or slightly increased. Increases are reported from some high-incidence areas (eg, Denmark and Sweden). Earlier studies from the 1980s reported an incidence of 4.1 per 100,000 person-years, whereas data for 2003-2005 indicate an incidence of 8.6 per 100,000 person-years.[35]

Incidence figures in Asia range from 0.5 to 4.2 cases per 100,000 persons.[36] The lowest recorded rates of new cases appear to be in South Africa (0.3-2.6 cases per 100,000 persons) and Latin America (0-0.03 cases per 100,000 persons).[2, 3]

A systematic review revealed that the highest prevalence for Crohn disease in North America was 319 per 100,000 persons, compared with 322 per 100,000 persons in Europe.[37] The highest annual incidence figures were 20.2 per 100,000 person-years in North America, 12.7 per 100,000 person-years in Europe, and 5.0 per 100,000 person-years in Asia and the Middle East. In time-trend analyses, 75% of the epidemiologic studies showed statistically significant increases in the incidence of Crohn disease over time.[37]

Age-, sex-, and race-related demographics

The age of onset of Crohn disease has a bimodal distribution. The first peak occurs between the ages of 15 and 30 years (late adolescence and early adulthood), and the second occurs mainly in women between the ages of 60 and 70 years. However, most cases begin before age 30 years, and approximately 20-30% of all patients with Crohn disease are diagnosed before age 20 years. A greater proportion of colonic and distal Crohn disease has been diagnosed in older patients, whereas younger patients have predominantly ileal disease.[2]

In general, the frequency of IBD is similar in males and females, with some studies showing a very slight female predominance. The rate of Crohn disease is 1.1-1.8 times higher in women than in men.[38] This pattern is reversed with pediatric IBD, which has a higher incidence in boys than in girls (pediatric male-to-female ratio, ~1.6:1).

Crohn disease is reported to be more common in white patients than in black patients and rare in Asian and Hispanic children. Approximately 20% of all IBD patients are of black descent. Rates are higher in people of Jewish descent, particularly in Ashkenazi Jews and Jews of middle European origin as compared with Sephardic or eastern European Jews.[39]

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Prognosis

Crohn disease is a chronic inflammatory condition with an indolent course. Appropriate medical and surgical therapy helps patients to have a reasonable quality of life, with an overall good prognosis and an extremely low risk of a fatal outcome.[2]

Several earlier studies estimated a slight decrease in life expectancy associated with certain prognostic indicators, such as female sex, long disease duration, and disease location. The increased mortality was related to pulmonary malignancies, genitourinary tract diseases, and GI, liver, and biliary diseases.

In contrast, other studies have reported normal survival in patients with Crohn disease. With the advent of new medical therapies, population-based studies have shown that overall survival for North American patients with IBD is similar to that expected in the US white population.[40] Individuals with Crohn disease were at increased risk of death from complications of GI disease, GI malignancy, and chronic obstructive pulmonary disease (COPD).[40]

In a Danish study that evaluated trends in mortality from 1982 to 2010, investigators observed a 50% higher mortality in patients with Crohn disease relative to the general population; this percentage did not change over time.[41]

Crohn disease is typically characterized by periods of remission and relapse. In the first year after diagnosis, the relapse rate approaches 50%, with 10% of patients having a chronic relapsing course.[2] Most patients develop complications that require surgery, and postoperative clinical relapse occurs in a significant proportion.[2] The risk of surgery at 5-year intervals after diagnosis is as follows[42] :

  • 5 years after diagnosis – The cumulative probability of having only 1 surgical procedure is 37%; 2 or more surgical procedures, 12%; and no surgical procedures, 51%
  • 10 years after diagnosis – The cumulative probability of having only 1 surgical procedure is 39%; 2 or more surgical procedures, 23%; and no surgical procedures, 39%
  • 15 years after diagnosis – The cumulative probability of having only 1 surgical procedure is 34%; 2 or more surgical procedures, 36%; and no surgical procedures, 30%

Patients with proximal small bowel disease have a higher risk of mortality than those who have ileal or ileocecal disease. The excess mortality may be ascribed to complications of Crohn disease.[2]

Acute Crohn disease of the terminal ileum is often discovered during laparotomy for suspected appendicitis and has an excellent prognosis. The acute episode is usually treated conservatively, and as many as two thirds of patients may show no subsequent evidence of regional enteritis.[2]

Discussion of the diagnosis, management, and surveillance of colorectal cancer in patients with IBD is beyond the scope of this article. Current data suggest that with the advent of improved therapies for patients with IBD, there is a trend toward decreasing risk of colorectal cancer. For more information, see the following 2 guidelines:

Genetic studies are yielding evidence associating particular variants of the CARD15 gene with the prognosis of Crohn disease.[11] Specific CARD15 mutations have been linked with the intestinal site of the disease (eg, ileal site), and certain variants have been found to be associated with the propensity for developing strictures and with an early onset of disease.[11] In the future, these variants may be helpful in predicting the course of the disease in affected individuals.

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Patient Education

Education of patients and their families is encouraged and is extremely important in the treatment process. Useful education materials can be obtained from the following organization:

  • Crohn’s and Colitis Foundation of America, 386 Park Avenue South, 17th floor, New York, NY 10016; (800) 932-2423; http://www.ccfa.org; e-mail: info@ccfa.org

In addition, see the Digestive Disorders Center, as well as Inflammatory Bowel Disease, Crohn’s Disease, Crohn’s Disease FAQs, and Ulcerative Colitis.

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Contributor Information and Disclosures
Author

Leyla J Ghazi, MD Assistant Professor, Department of Medicine, Associate Program Director, Division of Gastroenterology and Hepatology, University of Maryland School of Medicine

Leyla J Ghazi, MD is a member of the following medical societies: American College of Gastroenterology, American Gastroenterological Association, American Society for Gastrointestinal Endoscopy, Crohn's and Colitis Foundation of America

Disclosure: Received honoraria from Abbvie for consulting; Received cme development of educational material from UCB for speaking and teaching.

Specialty Editor Board

BS Anand, MD Professor, Department of Internal Medicine, Division of Gastroenterology, Baylor College of Medicine

BS Anand, MD is a member of the following medical societies: American Association for the Study of Liver Diseases, American College of Gastroenterology, American Gastroenterological Association, American Society for Gastrointestinal Endoscopy

Disclosure: Nothing to disclose.

Chief Editor

Julian Katz, MD Clinical Professor of Medicine, Drexel University College of Medicine

Julian Katz, MD is a member of the following medical societies: American College of Gastroenterology, American College of Physicians, American Gastroenterological Association, American Geriatrics Society, American Medical Association, American Society for Gastrointestinal Endoscopy, American Society of Law, Medicine & Ethics, American Trauma Society, Association of American Medical Colleges, Physicians for Social Responsibility

Disclosure: Nothing to disclose.

Acknowledgements

BS Anand, MD Professor, Department of Internal Medicine, Division of Gastroenterology, Baylor College of Medicine

BS Anand, MD is a member of the following medical societies: American Association for the Study of Liver Diseases, American College of Gastroenterology, American Gastroenterological Association, and American Society for Gastrointestinal Endoscopy

Disclosure: Nothing to disclose.

Priyankha Balasundaram, MD Director, Kovai Heart Foundation, India; Resident Physician, Department of Surgery, Tulane University School of Medicine

Disclosure: Nothing to disclose.

Marcy L Coash, DO Staff Physician, Department of Internal Medicine, University of Connecticut

Marcy L Coash, DO is a member of the following medical societies: American Medical Student Association/Foundation and American Osteopathic Association

Disclosure: Nothing to disclose.

Senthil Nachimuthu , MD, FACP

Disclosure: Nothing to disclose.

Waqar A Qureshi, MD Associate Professor of Medicine, Chief of Endoscopy, Department of Internal Medicine, Division of Gastroenterology, Baylor College of Medicine and Veterans Affairs Medical Center

Waqar A Qureshi, MD is a member of the following medical societies: American College of Gastroenterology, American College of Physicians, American Gastroenterological Association, and American Society for Gastrointestinal Endoscopy

Disclosure: Nothing to disclose.

Priya Rangasamy, MD Fellow, Department of Gastroenterology/Hepatology, University of Connecticut Health Center

Priya Rangasamy, MD is a member of the following medical societies: American College of Gastroenterology, American Gastroenterological Association, and American Society for Gastrointestinal Endoscopy

Disclosure: Nothing to disclose.

Kathleen M Raynor, MD Staff Physician, Department of Internal Medicine, University of Connecticut School of Medicine

Disclosure: Nothing to disclose.

Francisco Talavera, PharmD, PhD Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Medscape Salary Employment

George Y Wu, MD, PhD Professor, Department of Medicine, Director, Hepatology Section, Herman Lopata Chair in Hepatitis Research, University of Connecticut School of Medicine

George Y Wu, MD, PhD is a member of the following medical societies: American Association for the Study of Liver Diseases, American Gastroenterological Association, American Medical Association, American Society for Clinical Investigation, and Association of American Physicians

Disclosure: Springer Consulting fee Consulting; Gilead Consulting fee Review panel membership; Gilead Honoraria Speaking and teaching; Bristol-Myers Squibb Honoraria Speaking and teaching; Springer Royalty Review panel membership

References
  1. Govani SM, Guentner AS, Waljee AK, Higgins PD. Risk stratification of emergency department patients with Crohn's disease could reduce computed tomography use by nearly half. Clin Gastroenterol Hepatol. 2014 Oct. 12(10):1702-1707.e3. [Medline]. [Full Text].

  2. Kornbluth A, Sachar DB, Salomon P. Crohn's disease. Feldman M, Scharschmidt BF, Sleisenger MH, eds. Sleisenger & Fordtran's Gastrointestinal and Liver Disease: Pathophysiology, Diagnosis, and Management. 6th. Philadelphia, Pa: WB Saunders Co; 1998. Vol 2: 1708-34.

  3. Panes J, Gomollon F, Taxonera C, et al. Crohn's disease: a review of current treatment with a focus on biologics. Drugs. 2007. 67(17):2511-37.

  4. Tierney LM. Crohn's disease. Tierney LM, McPhee SJ, Papadakis MA, eds. Current Medical Diagnosis and Treatment. 40th ed. New York, NY: McGraw-Hill Professional Publishing; 2001. 638-42.

  5. Mackner LM, Bickmeier RM, Crandall WV. Academic achievement, attendance, and school-related quality of life in pediatric inflammatory bowel disease. J Dev Behav Pediatr. 2012 Feb. 33(2):106-11. [Medline].

  6. Rabbett H, Elbadri A, Thwaites R, Northover H, Dady I, Firth D, et al. Quality of life in children with Crohn's disease. J Pediatr Gastroenterol Nutr. 1996 Dec. 23(5):528-33. [Medline].

  7. Nikolaus S, Schreiber S. Diagnostics of inflammatory bowel disease. Gastroenterology. Nov 2007. 133(5):1670-89. [Full Text].

  8. Strong SA, Koltun WA, Hyman NH, Buie WD. Practice parameters for the surgical management of Crohn's disease. Dis Colon Rectum. 2007 Nov. 50(11):1735-46. [Medline].

  9. Farmer RG, Hawk WA, Turnbull RB Jr. Clinical patterns in Crohn's disease: a statistical study of 615 cases. Gastroenterology. 1975 Apr. 68(4 Pt 1):627-35. [Medline].

  10. D'Haens G, Baert F, van Assche G, et al. Early combined immunosuppression or conventional management in patients with newly diagnosed Crohn's disease: an open randomised trial. Lancet. Feb 23 2008. 371(9613):660-7.

  11. Tsianos EV, Katsanos KH, Tsianos VE. Role of genetics in the diagnosis and prognosis of Crohn's disease. World J Gastroenterol. 2012 Jan 14. 18(2):105-18. [Medline]. [Full Text].

  12. Thoreson R, Cullen JJ. Pathophysiology of inflammatory bowel disease: an overview. Surg Clin North Am. Jun 2007. 87(3):575-85.

  13. Hampe J, Grebe J, Nikolaus S, Solberg C, Croucher PJ, Mascheretti S, et al. Association of NOD2 (CARD 15) genotype with clinical course of Crohn's disease: a cohort study. Lancet. 2002 May 11. 359(9318):1661-5. [Medline].

  14. Hugot JP, Chamaillard M, Zouali H, Lesage S, Cézard JP, Belaiche J, et al. Association of NOD2 leucine-rich repeat variants with susceptibility to Crohn's disease. Nature. 2001 May 31. 411(6837):599-603. [Medline].

  15. Duerr RH, Taylor KD, Brant SR, Rioux JD, Silverberg MS, Daly MJ, et al. A genome-wide association study identifies IL23R as an inflammatory bowel disease gene. Science. 2006 Dec 1. 314(5804):1461-3. [Medline].

  16. Glas J, Seiderer J, Wetzke M, Konrad A, Török HP, Schmechel S, et al. rs1004819 is the main disease-associated IL23R variant in German Crohn's disease patients: combined analysis of IL23R, CARD15, and OCTN1/2 variants. PLoS One. 2007 Sep 5. 2(9):e819. [Medline]. [Full Text].

  17. Van Limbergen J, Russell RK, Nimmo ER, Drummond HE, Smith L, Davies G, et al. IL23R Arg381Gln is associated with childhood onset inflammatory bowel disease in Scotland. Gut. 2007 Aug. 56(8):1173-4. [Medline]. [Full Text].

  18. Barrett JC, Hansoul S, Nicolae DL, Cho JH, Duerr RH, Rioux JD, et al. Genome-wide association defines more than 30 distinct susceptibility loci for Crohn's disease. Nat Genet. 2008 Aug. 40(8):955-62. [Medline]. [Full Text].

  19. Hampe J, Franke A, Rosenstiel P, Till A, Teuber M, Huse K, et al. A genome-wide association scan of nonsynonymous SNPs identifies a susceptibility variant for Crohn disease in ATG16L1. Nat Genet. 2007 Feb. 39(2):207-11. [Medline].

  20. Rioux JD, Xavier RJ, Taylor KD, Silverberg MS, Goyette P, Huett A, et al. Genome-wide association study identifies new susceptibility loci for Crohn disease and implicates autophagy in disease pathogenesis. Nat Genet. 2007 May. 39(5):596-604. [Medline]. [Full Text].

  21. Parkes M, Barrett JC, Prescott NJ, Tremelling M, Anderson CA, Fisher SA, et al. Sequence variants in the autophagy gene IRGM and multiple other replicating loci contribute to Crohn's disease susceptibility. Nat Genet. 2007 Jul. 39(7):830-2. [Medline]. [Full Text].

  22. Libioulle C, Louis E, Hansoul S, Sandor C, Farnir F, Franchimont D, et al. Novel Crohn disease locus identified by genome-wide association maps to a gene desert on 5p13.1 and modulates expression of PTGER4. PLoS Genet. 2007 Apr 20. 3(4):e58. [Medline]. [Full Text].

  23. Wellcome Trust Case Control Consortium. Genome-wide association study of 14,000 cases of seven common diseases and 3,000 shared controls. Nature. 2007 Jun 7. 447(7145):661-78. [Medline]. [Full Text].

  24. Hedin C, Whelan K, Lindsay JO. Evidence for the use of probiotics and prebiotics in inflammatory bowel disease: a review of clinical trials. Proc Nutr Soc. 2007 Aug. 66(3):307-15. [Medline].

  25. Baumgart DC. Endoscopic surveillance in Crohn's disease and ulcerative colitis: who needs what and when?. Dig Dis. 2011. 29 Suppl 1:32-5. [Medline].

  26. Sandborn WJ, Hanauer SB, Rutgeerts P, et al. Adalimumab for maintenance treatment of Crohn's disease: results of the CLASSIC II trial. Gut. Sep 2007. 56(9):1232-9. [Full Text].

  27. Lindberg E, Järnerot G, Huitfeldt B. Smoking in Crohn's disease: effect on localisation and clinical course. Gut. Jun 1992. 33(6):779-82.

  28. D'Souza S, Levy E, Mack D, Israel D, Lambrette P, Ghadirian P. Dietary patterns and risk for Crohn's disease in children. Inflamm Bowel Dis. Mar 2008. 14(3):367-73.

  29. Davis RL, Kramarz P, Bohlke K, Benson P, Thompson RS, Mullooly J, et al. Measles-mumps-rubella and other measles-containing vaccines do not increase the risk for inflammatory bowel disease: a case-control study from the Vaccine Safety Datalink project. Arch Pediatr Adolesc Med. Mar 2001. 155(3):354-9.

  30. Reif S, Lavy A, Keter D, Broide E, Niv Y, Halak A, et al. Appendectomy is more frequent but not a risk factor in Crohn's disease while being protective in ulcerative colitis: a comparison of surgical procedures in inflammatory bowel disease. Am J Gastroenterol. Mar 2001. 96(3):829-32.

  31. Loftus EV Jr, Silverstein MD, Sandborn WJ, Tremaine WJ, Harmsen WS, Zinsmeister AR. Crohn's disease in Olmsted County, Minnesota, 1940-1993: incidence, prevalence, and survival. Gastroenterology. 1998 Jun. 114(6):1161-8. [Medline].

  32. Kappelman MD, Rifas-Shiman SL, Kleinman K, Ollendorf D, Bousvaros A, Grand RJ, et al. The prevalence and geographic distribution of Crohn's disease and ulcerative colitis in the United States. Clin Gastroenterol Hepatol. 2007 Dec. 5(12):1424-9. [Medline].

  33. Shivananda S, Lennard-Jones J, Logan R, Fear N, Price A, Carpenter L, et al. 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. 1996 Nov. 39(5):690-7. [Medline]. [Full Text].

  34. Loftus EV Jr. Clinical epidemiology of inflammatory bowel disease: Incidence, prevalence, and environmental influences. Gastroenterology. 2004 May. 126(6):1504-17. [Medline].

  35. Lovasz BD, Golovics PA, Vegh Z, Lakatos PL. New trends in inflammatory bowel disease epidemiology and disease course in Eastern Europe. Dig Liver Dis. 2012 Sep 22. [Medline].

  36. Economou M, Zambeli E, Michopoulos S. Incidence and prevalence of Crohn’s disease and its etiological influences. Ann Gastroenterol. 2009;22(3):158-67. Available at http://www.annalsgastro.gr/index.php/annalsgastro/article/view/743. Accessed: December 11, 2012.

  37. Molodecky NA, Soon IS, Rabi DM, Ghali WA, Ferris M, Chernoff G, et al. Increasing incidence and prevalence of the inflammatory bowel diseases with time, based on systematic review. Gastroenterology. 2012 Jan. 142(1):46-54.e42; quiz e30. [Medline].

  38. Calkins BM, Lilienfeld AM, Garland CF, Mendeloff AI. Trends in incidence rates of ulcerative colitis and Crohn's disease. Dig Dis Sci. 1984 Oct. 29(10):913-20. [Medline].

  39. Duerr RH. Update on the genetics of inflammatory bowel disease. J Clin Gastroenterol. Nov-Dec 2003. 37(5):358-67.

  40. Jess T, Loftus EV Jr, Harmsen WS, Zinsmeister AR, Tremaine WJ, Melton LJ 3rd, et al. Survival and cause specific mortality in patients with inflammatory bowel disease: a long term outcome study in Olmsted County, Minnesota, 1940-2004. Gut. 2006 Sep. 55(9):1248-54. [Medline]. [Full Text].

  41. Jess T, Frisch M, Simonsen J. Trends in overall and cause-specific mortality among patients with inflammatory bowel disease from 1982 to 2010. Clin Gastroenterol Hepatol. 2013 Jan. 11(1):43-8. [Medline].

  42. Munkholm P, Langholz E, Davidsen M, Binder V. Intestinal cancer risk and mortality in patients with Crohn's disease. Gastroenterology. 1993 Dec. 105(6):1716-23. [Medline].

  43. Fiocchi C. Inflammatory bowel disease: etiology and pathogenesis. Gastroenterology. Jul 1998. 115(1):182-205.

  44. Friedman S, Blumberg RS. Inflammatory bowel disease. Braunwald E, Fauci AS, Kasper DS, et al, eds. Harrison's Principles of Internal Medicine. 15th ed. New York, NY: McGraw-Hill Professional Publishing; 2001. Vol 2: 1679-91.

  45. Wilkins T, Jarvis K, Patel J. Diagnosis and management of Crohn's disease. Am Fam Physician. 2011 Dec 15. 84(12):1365-75. [Medline].

  46. Danese S, Semeraro S, Papa A, et al. Extraintestinal manifestations in inflammatory bowel disease. World J Gastroenterol. Dec 14 2005. 11(46):7227-36. [Full Text].

  47. Canavan C, Abrams KR, Mayberry J. Meta-analysis: colorectal and small bowel cancer risk in patients with Crohn's disease. Aliment Pharmacol Ther. 2006 Apr 15. 23(8):1097-104. [Medline].

  48. Jess T, Simonsen J, Jørgensen KT, Pedersen BV, Nielsen NM, Frisch M. Decreasing risk of colorectal cancer in patients with inflammatory bowel disease over 30 years. Gastroenterology. 2012 Aug. 143(2):375-81.e1; quiz e13-4. [Medline].

  49. Herrinton LJ, Liu L, Levin TR, Allison JE, Lewis JD, Velayos F. Incidence and mortality of colorectal adenocarcinoma in persons with inflammatory bowel disease from 1998 to 2010. Gastroenterology. 2012 Aug. 143(2):382-9. [Medline].

  50. Bernstein CN, Blanchard JF, Rawsthorne P, Yu N. The prevalence of extraintestinal diseases in inflammatory bowel disease: a population-based study. Am J Gastroenterol. 2001 Apr. 96(4):1116-22. [Medline].

  51. Isaacs KL. How prevalent are extraintestinal manifestations at the initial diagnosis of IBD?. Inflamm Bowel Dis. 2008 Oct. 14 Suppl 2:S198-9. [Medline].

  52. Aghazadeh R, Zali MR, Bahari A, Amin K, Ghahghaie F, Firouzi F. Inflammatory bowel disease in Iran: a review of 457 cases. J Gastroenterol Hepatol. 2005 Nov. 20(11):1691-5. [Medline].

  53. Gasche C, Scholmerich J, Brynskov J, D'Haens G, Hanauer SB, Irvine EJ, et al. A simple classification of Crohn's disease: report of the Working Party for the World Congresses of Gastroenterology, Vienna 1998. Inflamm Bowel Dis. 2000 Feb. 6(1):8-15. [Medline].

  54. Silverberg MS, Satsangi J, Ahmad T, Arnott ID, Bernstein CN, Brant SR, et al. Toward an integrated clinical, molecular and serological classification of inflammatory bowel disease: Report of a Working Party of the 2005 Montreal World Congress of Gastroenterology. Can J Gastroenterol. 2005 Sep. 19 Suppl A:5-36. [Medline].

  55. Leach ST, Nahidi L, Tilakaratne S, Day AS, Lemberg DA. Development and assessment of a modified Pediatric Crohn Disease Activity Index. J Pediatr Gastroenterol Nutr. 2010 Aug. 51(2):232-6. [Medline].

  56. Kappelman MD, Crandall WV, Colletti RB, Goudie A, Leibowitz IH, Duffy L, et al. Short pediatric Crohn's disease activity index for quality improvement and observational research. Inflamm Bowel Dis. 2011 Jan. 17(1):112-7. [Medline]. [Full Text].

  57. Newnham E, Hawkes E, Surender A, James SL, Gearry R, Gibson PR. Quantifying exposure to diagnostic medical radiation in patients with inflammatory bowel disease: are we contributing to malignancy?. Aliment Pharmacol Ther. 2007 Oct 1. 26(7):1019-24. [Medline].

  58. Desmond AN, O'Regan K, Curran C, McWilliams S, Fitzgerald T, Maher MM, et al. Crohn's disease: factors associated with exposure to high levels of diagnostic radiation. Gut. 2008 Nov. 57(11):1524-9. [Medline].

  59. Kambadakone AR, Prakash P, Hahn PF, Sahani DV. Low-dose CT examinations in Crohn's disease: Impact on image quality, diagnostic performance, and radiation dose. AJR Am J Roentgenol. 2010 Jul. 195(1):78-88. [Medline].

  60. Craig O, O'Neill S, O'Neill F, McLaughlin P, McGarrigle A, McWilliams S, et al. Diagnostic accuracy of computed tomography using lower doses of radiation for patients with Crohn's disease. Clin Gastroenterol Hepatol. 2012 Aug. 10(8):886-92. [Medline].

  61. Panés J, Bouzas R, Chaparro M, García-Sánchez V, Gisbert JP, Martínez de Guereñu B, et al. Systematic review: the use of ultrasonography, computed tomography and magnetic resonance imaging for the diagnosis, assessment of activity and abdominal complications of Crohn's disease. Aliment Pharmacol Ther. 2011 Jul. 34(2):125-45. [Medline].

  62. Gisbert JP, McNicholl AG. Questions and answers on the role of faecal calprotectin as a biological marker in inflammatory bowel disease. Dig Liver Dis. 2009 Jan. 41(1):56-66. [Medline].

  63. D'Incà R, Dal Pont E, Di Leo V, Ferronato A, Fries W, Vettorato MG, et al. Calprotectin and lactoferrin in the assessment of intestinal inflammation and organic disease. Int J Colorectal Dis. 2007 Apr. 22(4):429-37. [Medline].

  64. [Guideline] World Gastroenterology Organisation. World Gastroenterology Organisation global guideline: inflammatory bowel disease: a global perspective. Munich, Germany: World Gastroenterology Organisation; 2009. Available at http://guideline.gov/content.aspx?id=15231. Accessed: December 12, 2012.

  65. Mackalski BA, Bernstein CN. New diagnostic imaging tools for inflammatory bowel disease. Gut. May 2006. 55(5):733-41.

  66. Saibeni S, Rondonotti E, Iozzelli A, et al. Imaging of the small bowel in Crohn's disease: a review of old and new techniques. World J Gastroenterol. Jun 28 2007. 13(24):3279-87.

  67. Schreyer AG, Seitz J, Feuerbach S, Rogler G, Herfarth H. Modern imaging using computer tomography and magnetic resonance imaging for inflammatory bowel disease (IBD) AU1. Inflamm Bowel Dis. Jan 2004. 10(1):45-54.

  68. [Guideline] Kidd R, Mezwa DG, Ralls PW, Balfe DM, Bree RL, DiSantis DJ, et al. Imaging recommendations for patients with newly suspected Crohn's disease, and in patients with known Crohn's disease and acute exacerbation or suspected complications. American College of Radiology. ACR Appropriateness Criteria. Radiology. 2000 Jun. 215 Suppl:181-92. [Medline].

  69. Fidler JL, Rosen MP, Blake MA, et al, for the Expert Panel on Gastrointestinal Imaging. ACR Appropriateness Criteria: Crohn disease. [online publication]. Reston, Va: American College of Radiology; 2011. Available at http://guideline.gov/content.aspx?id=35137. Accessed: April 5, 2011.

  70. Pilleul F, Godefroy C, Yzebe-Beziat D, Dugougeat-Pilleul F, Lachaux A, Valette PJ. Magnetic resonance imaging in Crohn's disease. Gastroenterol Clin Biol. Aug-Sep 2005. 29(8-9):803-8.

  71. Florie J, Horsthuis K, Hommes DW, Nio CY, Reitsma JB, van Deventer SJ. Magnetic resonance imaging compared with ileocolonoscopy in evaluating disease severity in Crohn's disease. Clin Gastroenterol Hepatol. Dec 2005. 3(12):1221-8.

  72. Rimola J, Ordás I, Rodriguez S, García-Bosch O, Aceituno M, Llach J, et al. Magnetic resonance imaging for evaluation of Crohn's disease: validation of parameters of severity and quantitative index of activity. Inflamm Bowel Dis. 2011 Aug. 17(8):1759-68. [Medline].

  73. Lee SS, Kim AY, Yang SK, et al. Crohn disease of the small bowel: comparison of CT enterography, MR enterography, and small-bowel follow-through as diagnostic techniques. Radiology. Jun 2009. 251(3):751-61.

  74. Low RN, Francis IR, Politoske D, Bennett M. Crohn's disease evaluation: comparison of contrast-enhanced MR imaging and single-phase helical CT scanning. J Magn Reson Imaging. 2000 Feb. 11(2):127-35. [Medline].

  75. Fiorino G, Bonifacio C, Peyrin-Biroulet L, Minuti F, Repici A, Spinelli A, et al. Prospective comparison of computed tomography enterography and magnetic resonance enterography for assessment of disease activity and complications in ileocolonic Crohn's disease. Inflamm Bowel Dis. 2011 May. 17(5):1073-80. [Medline].

  76. Hafeez R, Punwani S, Boulos P, Bloom S, McCartney S, Halligan S, et al. Diagnostic and therapeutic impact of MR enterography in Crohn's disease. Clin Radiol. 2011 Dec. 66(12):1148-58. [Medline].

  77. Guidi L, Ratto C, Semeraro S, Roberto I, De Vitis I, Papa A. Combined therapy with infliximab and seton drainage for perianal fistulizing Crohn's disease with anal endosonographic monitoring: a single-centre experience. Tech Coloproctol. Jun 2008. 12(2):111-7.

  78. Schwartz DA, White CM, Wise PE, Herline AJ. Use of endoscopic ultrasound to guide combination medical and surgical therapy for patients with Crohn's perianal fistulas. Inflamm Bowel Dis. 2005 Aug. 11(8):727-32. [Medline].

  79. Wise PE, Schwartz DA. The evaluation and treatment of Crohn perianal fistulae: EUA, EUS, MRI, and other imaging modalities. Gastroenterol Clin North Am. 2012 Jun. 41(2):379-91. [Medline].

  80. Leighton JA, Shen B, Baron TH, Adler DG, Davila R, Egan JV, et al. ASGE guideline: endoscopy in the diagnosis and treatment of inflammatory bowel disease. Gastrointest Endosc. 2006 Apr. 63(4):558-65. [Medline].

  81. Rubin DT, Panaccione R, Chao J, Robinson AM. A practical, evidence-based guide to the use of adalimumab in Crohn's disease. Curr Med Res Opin. 2011 Sep. 27(9):1803-13. [Medline].

  82. Robinson M. Optimizing therapy for inflammatory bowel disease. Am J Gastroenterol. Dec 1997. 92(12 suppl):12S-17S.

  83. Helwick C. Stem Cell Transplantation Halts Crohn's Disease. Medscape Medical News. Available at http://www.medscape.com/viewarticle/804570. Accessed: June 4, 2013.

  84. Colombel JF, Sandborn WJ, Reinisch W, Mantzaris GJ, Kornbluth A, Rachmilewitz D, et al. Infliximab, azathioprine, or combination therapy for Crohn's disease. N Engl J Med. 2010 Apr 15. 362(15):1383-95. [Medline].

  85. Lim WC, Hanauer S. Aminosalicylates for induction of remission or response in Crohn's disease. Cochrane Database Syst Rev. 2010 Dec 8. CD008870. [Medline].

  86. Ford AC, Bernstein CN, Khan KJ, Abreu MT, Marshall JK, Talley NJ, et al. Glucocorticosteroid therapy in inflammatory bowel disease: systematic review and meta-analysis. Am J Gastroenterol. 2011 Apr. 106(4):590-9. [Medline].

  87. Turner D, Grossman AB, Rosh J, et al. Methotrexate following unsuccessful thiopurine therapy in pediatric Crohn's disease. Am J Gastroenterol. Dec 2007. 102(12):2804-12 quiz 2803, 2813.

  88. Ford AC, Sandborn WJ, Khan KJ, Hanauer SB, Talley NJ, Moayyedi P. Efficacy of biological therapies in inflammatory bowel disease: systematic review and meta-analysis. Am J Gastroenterol. 2011 Apr. 106(4):644-59. [Medline].

  89. US Food and Drug Administration. Tumor necrosis factor-alpha (TNFα) blockers: label change - boxed warning updated for risk of infection from Legionella and Listeria. Posted September 7, 2011. Available at http://www.fda.gov/Safety/MedWatch/SafetyInformation/SafetyAlertsforHumanMedicalProducts/ucm270977.htm. Accessed: April 5, 2012.

  90. [Guideline] Lichtenstein GR, Abreu MT, Cohen R, Tremaine W. American Gastroenterological Association Institute medical position statement on corticosteroids, immunomodulators, and infliximab in inflammatory bowel disease. Gastroenterology. 2006 Mar. 130(3):935-9. [Medline]. [Full Text].

  91. Present DH, Rutgeerts P, Targan S, Hanauer SB, Mayer L, van Hogezand RA, et al. Infliximab for the treatment of fistulas in patients with Crohn's disease. N Engl J Med. 1999 May 6. 340(18):1398-405. [Medline].

  92. Targan SR, Hanauer SB, van Deventer SJ, et al. A short-term study of chimeric monoclonal antibody cA2 to tumor necrosis factor alpha for Crohn's disease. Crohn's Disease cA2 Study Group. N Engl J Med. Oct 9 1997. 337(15):1029-35. [Full Text].

  93. Present DH, Rutgeerts P, Targan S, et al. Infliximab for the treatment of fistulas in patients with Crohn's disease. N Engl J Med. May 6 1999. 340(18):1398-405. [Full Text].

  94. Louis E, Mary JY, Vernier-Massouille G, Grimaud JC, Bouhnik Y, Laharie D, et al. Maintenance of remission among patients with Crohn's disease on antimetabolite therapy after infliximab therapy is stopped. Gastroenterology. 2012 Jan. 142(1):63-70.e5; quiz e31. [Medline].

  95. Peyrin-Biroulet L, Laclotte C, Bigard MA. Adalimumab maintenance therapy for Crohn's disease with intolerance or lost response to infliximab: an open-label study. Aliment Pharmacol Ther. Mar 15 2007. 25(6):675-80. [Full Text].

  96. Hanauer SB, Sandborn WJ, Rutgeerts P, Fedorak RN, Lukas M, MacIntosh D, et al. Human anti-tumor necrosis factor monoclonal antibody (adalimumab) in Crohn's disease: the CLASSIC-I trial. Gastroenterology. 2006 Feb. 130(2):323-33; quiz 591. [Medline].

  97. Colombel JF, Sandborn WJ, Rutgeerts P, Enns R, Hanauer SB, Panaccione R, et al. Adalimumab for maintenance of clinical response and remission in patients with Crohn's disease: the CHARM trial. Gastroenterology. 2007 Jan. 132(1):52-65. [Medline].

  98. Mannon PJ, Fuss IJ, Mayer L, Elson CO, Sandborn WJ, Present D, et al. Anti-interleukin-12 antibody for active Crohn's disease. N Engl J Med. 2004 Nov 11. 351(20):2069-79. [Medline].

  99. Sandborn WJ, Rutgeerts P, Enns R, et al. Adalimumab induction therapy for Crohn disease previously treated with infliximab: a randomized trial. Ann Intern Med. Jun 19 2007. 146(12):829-38. [Full Text].

  100. Peppercorn MA. Clinical manifestations, diagnosis, and prognosis of ulcerative colitis in adults. UpToDate. September 15, 2008. [Full Text].

  101. Sandborn WJ, Feagan BG, Stoinov S, Honiball PJ, Rutgeerts P, Mason D, et al. Certolizumab pegol for the treatment of Crohn's disease. N Engl J Med. 2007 Jul 19. 357(3):228-38. [Medline].

  102. Schreiber S, Khaliq-Kareemi M, Lawrance IC, Thomsen OØ, Hanauer SB, McColm J, et al. Maintenance therapy with certolizumab pegol for Crohn's disease. N Engl J Med. 2007 Jul 19. 357(3):239-50. [Medline].

  103. Lichtenstein GR, Thomsen OØ, Schreiber S, Lawrance IC, Hanauer SB, Bloomfield R, et al. Continuous therapy with certolizumab pegol maintains remission of patients with Crohn's disease for up to 18 months. Clin Gastroenterol Hepatol. 2010 Jul. 8(7):600-9. [Medline].

  104. Biogen Idec Elan. TYSABRI (natalizumab) Safety Update: (17 August 2012). Available at http://www.tapp.com.au/members/Tysabri_Safety_Update_160812.pdf. Accessed: December 14, 2012.

  105. FDA. FDA Drug Safety Communication: New risk factor for progressive multifocal leukoencephalopathy (PML) associated with Tysabri (natalizumab) [safety announcement]. January 20, 2012. Available at http://www.fda.gov/Drugs/DrugSafety/ucm288186.htm. Accessed: December 14, 2012.

  106. Sandborn WJ, Colombel JF, Enns R, Feagan BG, Hanauer SB, Lawrance IC, et al. Natalizumab induction and maintenance therapy for Crohn's disease. N Engl J Med. 2005 Nov 3. 353(18):1912-25. [Medline].

  107. Targan SR, Feagan BG, Fedorak RN, Lashner BA, Panaccione R, Present DH, et al. Natalizumab for the treatment of active Crohn's disease: results of the ENCORE Trial. Gastroenterology. 2007 May. 132(5):1672-83. [Medline].

  108. Sandborn WJ, Feagan BG, Rutgeerts P, Hanauer S, Colombel JF, Sands BE, et al. Vedolizumab as induction and maintenance therapy for Crohn's disease. N Engl J Med. 2013 Aug 22. 369(8):711-21. [Medline].

  109. McSharry K, Dalzell AM, Leiper K, El-Matary W. Systematic review: the role of tacrolimus in the management of Crohn's disease. Aliment Pharmacol Ther. 2011 Dec. 34(11-12):1282-94. [Medline].

  110. Solomon MJ, McLeod RS, O’Connor BI, Steinhart H, Greenberg GR, Cohen Z. Combination ciprofloxacin and metronidazole in severe perianal Crohn’s disease. Can J Gastroenterol. 1993. 7:571-3.

  111. Borrelli O, Cordischi L, Cirulli M, et al. Polymeric diet alone versus corticosteroids in the treatment of active pediatric Crohn's disease: a randomized controlled open-label trial. Clin Gastroenterol Hepatol. Jun 2006. 4(6):744-53.

  112. Harpavat M, Keljo DJ, Regueiro MD. Metabolic bone disease in inflammatory bowel disease. J Clin Gastroenterol. Mar 2004. 38(3):218-24.

  113. Heuschkel R. Enteral nutrition in Crohn disease: more than just calories. J Pediatr Gastroenterol Nutr. Mar 2004. 38(3):239-41.

  114. Razack R, Seidner DL. Nutrition in inflammatory bowel disease. Curr Opin Gastroenterol. Jul 2007. 23(4):400-5.

  115. Whitten KE, Rogers P, Ooi CY, Day AS. International survey of enteral nutrition protocols used in children with Crohn's disease. J Dig Dis. 2012 Feb. 13(2):107-12. [Medline].

  116. Markowitz J, Markowitz JE, Bousvaros A, Crandall W, Faubion W, Kirschner BS. Workshop report: prevention of postoperative recurrence in Crohn's disease. J Pediatr Gastroenterol Nutr. Aug 2005. 41(2):145-51.

  117. Ewe K, Herfarth C, Malchow H, Jesdinsky HJ. Postoperative recurrence of Crohn's disease in relation to radicality of operation and sulfasalazine prophylaxis: a multicenter trial. Digestion. 1989. 42(4):224-32.

  118. Alós R, Hinojosa J. Timing of surgery in Crohn's disease: a key issue in the management. World J Gastroenterol. Sep 28 2008. 14(36):5532-9.

  119. Simillis C, Yamamoto T, Reese GE, Umegae S, Matsumoto K, Darzi AW. A meta-analysis comparing incidence of recurrence and indication for reoperation after surgery for perforating versus nonperforating Crohn's disease. Am J Gastroenterol. Jan 2008. 103(1):196-205.

  120. Shen B. Managing medical complications and recurrence after surgery for Crohn's disease. Curr Gastroenterol Rep. Dec 2008. 10(6):606-11.

  121. Cobb WS IV. Finney pyloroplasty. In: Rosen MJ, ed. Chapter 13. Atlas of Surgical Techniques for the Upper Gastrointestinal Tract and Small Bowel. Philadelphia, Pa: Saunders Elsevier; 2010.

  122. Angel CA. Finney pyloroplasty. Townsend CM Jr, Evers MB, eds. Atlas of General Surgical Techniques. Philadelphia, Pa: Saunders Elsevier; 2010. chapter 24.

  123. Yamamoto T, Fazio VW, Tekkis PP. Safety and efficacy of strictureplasty for Crohn's disease: a systematic review and meta-analysis. Dis Colon Rectum. Nov 2007. 50(11):1968-86.

  124. Couckuyt H, Gevers AM, Coremans G, Hiele M, Rutgeerts P. Efficacy and safety of hydrostatic balloon dilatation of ileocolonic Crohn's strictures: a prospective longterm analysis. Gut. Apr 1995. 36(4):577-80.

  125. Garcia JC, Persky SE, Bonis PA, Topazian M. Abscesses in Crohn's disease: outcome of medical versus surgical treatment. J Clin Gastroenterol. May-Jun 2001. 32(5):409-12.

  126. Berg DF, Bahadursingh AM, Kaminski DL, Longo WE. Acute surgical emergencies in inflammatory bowel disease. Am J Surg. Jul 2002. 184(1):45-51.

  127. Kiran RP, Nisar PJ, Church JM, Fazio VW. The role of primary surgical procedure in maintaining intestinal continuity for patients with Crohn's colitis. Ann Surg. 2011 Jun. 253(6):1130-5. [Medline].

  128. Kamm MA, Ng SC. Perianal fistulizing Crohn's disease: a call to action. Clin Gastroenterol Hepatol. Jan 2008. 6(1):7-10.

  129. Bode M, Eder S, Schürmann G. Perianal fistulas in Crohn's disease--biologicals and surgery: is it worthwhile?. Z Gastroenterol. Dec 2008. 46(12):1376-83.

  130. Poritz LS, Rowe WA, Koltun WA. Remicade does not abolish the need for surgery in fistulizing Crohn's disease. Dis Colon Rectum. Jun 2002. 45(6):771-5.

  131. Liu CD, Rolandelli R, Ashley SW, Evans B, Shin M, McFadden DW. Laparoscopic surgery for inflammatory bowel disease. Am Surg. Dec 1995. 61(12):1054-6.

  132. Sardinha TC, Wexner SD. Laparoscopy for inflammatory bowel disease: pros and cons. World J Surg. Apr 1998. 22(4):370-4.

  133. Georgeson KE, Cohen RD, Hebra A, Jona JZ, Powell DM, Rothenberg SS. Primary laparoscopic-assisted endorectal colon pull-through for Hirschsprung's disease: a new gold standard. Ann Surg. Ann Surg. May 1999. 229(5):678-82; discussion 682-3.

  134. Lowney JK, Dietz DW, Birnbaum EH, Kodner IJ, Mutch MG, Fleshman JW. Is there any difference in recurrence rates in laparoscopic ileocolic resection for Crohn's disease compared with conventional surgery? A long-term, follow-up study. Dis Colon Rectum. Jan 2006. 49(1):58-63.

  135. Chen HH, Wexner SD, Iroatulam AJ, Pikarsky AJ, Alabaz O, Nogueras JJ. Laparoscopic colectomy compares favorably with colectomy by laparotomy for reduction of postoperative ileus. Dis Colon Rectum. Jan 2000. 43(1):61-5.

  136. Eshuis EJ, Polle SW, Slors JF, Hommes DW, Sprangers MA, Gouma DJ. Long-term surgical recurrence, morbidity, quality of life, and body image of laparoscopic-assisted vs. open ileocolic resection for Crohn's disease: a comparative study. Dis Colon Rectum. Jun 2008. 51(6):858-67.

  137. Eshuis EJ, Bemelman WA, van Bodegraven AA, Sprangers MA, Bossuyt PM, van Milligen de Wit AW. Laparoscopic ileocolic resection versus infliximab treatment of distal ileitis in Crohn's disease: a randomized multicenter trial (LIR!C-trial). BMC Surg. 2008. 8:15.

  138. Khan KJ, Ullman TA, Ford AC, Abreu MT, Abadir A, Marshall JK, et al. Antibiotic therapy in inflammatory bowel disease: a systematic review and meta-analysis. Am J Gastroenterol. 2011 Apr. 106(4):661-73. [Medline].

  139. Feagan BG, Rutgeerts PJ, Sands BE, et al. Induction therapy for ulcerative colitis: results of GEMINI I, a randomized, placebo-controlled, double-blind, multicenter phase 3 trial [abstract 943b]. Gastroenterology. 2012. 142:S160.

  140. Sakuraba A, Keyashian K, Correia C, Melek J, Cohen RD, Hanauer SB, et al. Natalizumab in Crohn's Disease: Results From a US Tertiary Inflammatory Bowel Disease Center. Inflamm Bowel Dis. 2013 Mar. 19(3):621-6. [Medline].

  141. Savarino E, Bodini G, Dulbecco P, et al. Adalimumab Is More Effective Than Azathioprine and Mesalamine at Preventing Postoperative Recurrence of Crohn's Disease: A Randomized Controlled Trial. Medscape [serial online]; MEDLINE database. Available at http://www.medscape.com/viewarticle/814758. Accessed: January 6, 2014.

  142. Valentine JF, Fedorak RN, Feagan B, Fredlund P, Schmitt R, Ni P, et al. Steroid-sparing properties of sargramostim in patients with corticosteroid-dependent Crohn's disease: a randomised, double-blind, placebo-controlled, phase 2 study. Gut. Oct 2009. 58(10):1354-62.

 
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Colonoscopic image of a large ulcer and inflammation of the descending colon in a 12-year-old boy with Crohn disease.
Laparoscopic view depicts creeping fat along the mesentery of the terminal ileum.
On this laparoscopic photograph, the mesentery of the terminal ileum is being coagulated with a sealing device (LigaSure; Valley Lab, Boulder, Colo). Note that the ligation of the mesentery proceeds near the border of the ileum rather than at the base of the mesentery.
This postoperative photograph depicts incisions used for laparoscopic ileocolectomy in a 14-year-old male adolescent with obstruction of terminal ileum. Note 2-cm incision in right lower abdomen, through which the specimen was extracted and extracorporeal anastomosis performed. 12-mm umbilical incision is nicely hidden in the depths of the umbilicus. 5-mm incision is visible in left lower abdomen, and another is in left suprapubic region just above the top of the pants.
Colonic granuloma in patient with Crohn disease. Hematoxylin-eosin staining. Image courtesy of Dr E. Ruchelli.
Aphthous ulcers. Double-contrast barium enema examination in Crohn colitis demonstrates numerous aphthous ulcers.
Double-contrast barium enema study demonstrates marked ulceration, inflammatory changes, and narrowing of right colon in patient with Crohn colitis.
Cobblestoning in Crohn disease. Spot view of the terminal ileum from a small bowel follow-through study demonstrates linear longitudinal and transverse ulcerations that create a cobblestone appearance. Also, note the relatively greater involvement of the mesenteric side of the terminal ileum and the displacement of the involved loop away from the normal small bowel secondary to mesenteric inflammation and fibrofatty proliferation.
Crohn disease of terminal ileum. Small bowel follow-through study demonstrates the string sign in terminal ileum. Also, note pseudodiverticula of the antimesenteric wall of terminal ileum, secondary to greater distensibility of this less-involved wall segment.
Spot view of the terminal ileum from a small bowel follow-through study in a patient with Crohn disease demonstrates the string sign, consistent with narrowing and stricturing. Also, note a sinus tract originating from the medial wall of the terminal ileum and the involvement of the medial wall of the cecum.
Enterocolic fistula in patient with Crohn disease. Double-contrast barium enema study demonstrates multiple fistulous tracts between terminal ileum and right colon adjacent to the ileocecal valve (so-called double-tracking of ileocecal valve).
Active small bowel inflammation in a patient with Crohn disease. This CT scan demonstrates small bowel wall thickening, mesenteric inflammatory stranding, and mesenteric adenopathy.
This computed tomography scan from a patient with terminal ileal Crohn disease shows an enteroenteral fistula (arrow) between loops of diseased small intestine.
A teenaged patient with Crohn disease underwent contrast-enhanced upper gastrointestinal CT with small-bowel follow-through. Several loops of small bowel are in the pelvis. Note loop of distal bowel with thickened wall (solid arrow), which is contrasted with less-involved loop of bowel in which intestinal wall is not thickened at all (dotted arrow).
CT scan depicts Crohn disease in fundus of stomach.
MRI demonstrates inflamed terminal ileum in 10-year-old girl with Crohn disease.
Granuloma in mucosa of a patient with Crohn disease.
Table 1. Characteristics Differentiating Crohn Disease and Ulcerative Colitis
Characteristic
  Crohn Disease Ulcerative Colitis
Distribution Entire gastrointestinal tract Colon only, though gastritis is recognized
Skip lesions Continuous involvement proximally from rectum
Pathology Full thickness Mucosa only
Granulomas (15-30% in biopsy specimens; 40-60% in surgically resected bowel) No granulomas
Radiology Entire gastrointestinal tract Colon only
Skip lesions Continuous involvement proximally from rectum
Fistulae, abscesses, fibrotic strictures Mucosal disease only
Cancer risk Increased Estimated to be 3% at 10 years, 8% at 30 years, and 18% at 30 years after diagnosis[47] ; risk is higher in patients with primary sclerosing cholangitis and long-standing colitis (> 8-10 y); may be lower in subsequent studies (see Intestinal Manifestations).
Presentation
  Crohn Disease Ulcerative Colitis
Bleeding Occasional Very common
Obstruction Common Uncommon
Fistulae Common None
Weight loss Common Uncommon
Perianal disease Common Rare
Table 2. ASCRS Indications for Surgical Management of Crohn Disease
Operative Indication Factors for Considering Surgery
Failed medical therapy
  • Presence of disease-related symptoms not responsive to medical management; condition demonstrates an inadequate response
  • When first- and second-line therapies do not induce remission safely in severe disease
  • Before escalating medical therapy in severe or steroid-dependent disease with limited extent (eg, disease with stricturing behavior, patients who have contraindications or risk factors for further medical therapy)
Perforation
  • Presence of symptoms or signs of free perforation
  • Immediate resection of perforated segment (has a relatively high mortality)
  • After small bowel resection or perforation, other procedures can be performed, as needed (eg, end stoma, diverted or nondiverted anastomosis)
  • When large anteroparietal, interloop, intramesenteric, or retroperitoneal abscesses cannot be or are unsuccessfully managed with antibiotics and percutaneous drainage
  • Perform surgical drainage in such cases, with or without resection
  • Persistent enteric fistulae and symptoms or signs of localized or systemic sepsis despite appropriate medical management
  • Persistent sepsis warrants excision of the diseased bowel, whether or not an abscess is present
For target or “innocent bystander” organs, diseased bowel is typically resected, noninflamed bowel primarily closed, and other internal organs primarily closed or allowed to heal by secondary intention



Note: Operative intervention may be avoided for asymptomatic internal fistulae



Obstruction
  • Presence of symptomatic strictures in regions not amenable or responsive to medical therapy
  • Presence of asymptomatic colonic strictures that cannot be adequately surveyed by biopsy or cytology brushing
Inflammation
  • Presence of acute colitis and symptoms or signs of impending or actual perforation (eg, transverse colon distention > 6 cm on abdominal x-ray or persistent gaseous colonic distention indicate toxic megacolon, pneumatosis coli, evolving local peritonitis, multiple organ failure)
  • Presence of severe or fulminant colitis
  • Worsening acute colitis or failure to significantly improve despite 48-96 hours of appropriate medical therapy
Hemorrhage
  • Presence of massive hemorrhaging of any origin that (1) cannot be or fails to be managed with interventional or endoscopic techniques and (2) occurs in hemodynamically unstable patients
Mesenteric angiography with embolization may be attempted when adequate endoscopic visualization is not possible or when the bleeding source cannot be identified; if this technique is not successful or the patient is hemodynamically unstable, laparotomy with or without intraoperative endoscopy and resection of the responsible bowel segment may be required
Neoplasia
  • Presence of chronic Crohn disease of the ileocolon or colon (endoscopic surveillance)
  • Presence of adenomatous-appearing polyps (excision)
  • Presence of carcinoma, DALM, high-grade dysplasia, multifocal colonic or rectal low-grade dysplasia (resection)
  • Presence of chronic Crohn disease of the terminal ileum, ileocolon, or upper GI region
Growth retardation and EIMs
  • Presence of significant growth retardation in prepubertal patients despite appropriate medical therapy
  • Presence of symptomatic dermatologic, oral, ophthalmologic, or joint disorders refractory to medical therapy (resection of diseased intestine)
ASCRS = American Society of Colon and Rectal Surgeons; DALM = dysplasia-associated lesion or mass; EIM = extraintestinal manifestation; GI = gastrointestinal.



Source:  Strong SA, Koltun WA, Hyman NH, Buie WD, for the Standards Practice Task Force of The American Society of Colon and Rectal Surgeons. Practice parameters for the surgical management of Crohn’s disease. Dis Colon Rectum. 2007;50(11):1735-46.[8]



Table 3. ASCRS Recommendations for Site-Specific Operative Management of Crohn Disease
Site Surgical Intervention
Terminal ileum, ileocolon, upper GI tract
  • Resection of the affected bowel for jejunal, proximal ileal, terminal ileal, or ileocolic disease in the absence of existing or impending short bowel syndrome
  • Ileocolostomy or proximal loop ileostomy in cases where there is concern about damage to nondiseased bowel, superior mesenteric vessels, retroperitoneal structures
  • Drainage of any septic foci with later definitive resection (after several months’ delay)
  • Strictureplasty for nonphlegmonous jejunal, ileal, or ileocolic strictures in the absence of existing or impending short bowel syndrome
  • Strictureplasty when multiple jejunal or proximal/terminal ileum strictures are present
  • Bypass or strictureplasty for symptomatic gastric or duodenal disease
  • Endoscopic dilatation of symptomatic, accessible strictures of the intestinal tract
Note: Surgical services should be available in case of perforation
Colon
  • Subtotal or total colectomy with end ileostomy for colonic disease requiring emergency or urgent surgery (via laparoscopic or open approach)
  • Segmental or total colectomy with or without primary anastomosis for colonic disease requiring elective surgery
  • Total proctocolectomy or proctectomy with stoma creation for rectal disease requiring surgery
ASCRS = American Society of Colon and Rectal Surgeons; GI = gastrointestinal.



Source:  Strong SA, Koltun WA, Hyman NH, Buie WD, for the Standards Practice Task Force of The American Society of Colon and Rectal Surgeons. Practice parameters for the surgical management of Crohn’s disease. Dis Colon Rectum. 2007;50(11):1735-46.[8]



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