Inflammatory Bowel Disease

Practice Essentials

Inflammatory bowel disease (IBD) is an idiopathic disease caused by a dysregulated immune response to host intestinal microflora. The two major types of inflammatory bowel disease are ulcerative colitis (UC), which is limited to the colonic mucosa, and Crohn disease (CD), which can affect any segment of the gastrointestinal tract from the mouth to the anus, involves "skip lesions," and is transmural. There is a genetic predisposition for IBD, and patients with this condition are more prone to the development of malignancy. See the image below.

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Severe colitis noted during colonoscopy in a patient with inflammatory bowel disease. The mucosa is grossly denuded, with active bleeding noted. The p....

Signs and symptoms

Generally, the manifestations of IBD depend on the area of the intestinal tract involved. The symptoms, however, are not specific for this disease. They are as follows:

Abdominal cramping
Irregular bowel habits, passage of mucus without blood or pus
Weight loss
Fever, sweats
Malaise, fatigue
Arthralgias
Growth retardation and delayed or failed sexual maturation in children
Extraintestinal manifestations (10-20%): Arthritis, uveitis, or liver disease
Grossly bloody stools, occasionally with tenesmus: Typical of UC, less common in CD
Perianal disease (eg, fistulas, abscesses): Fifty percent of patients with CD

The World Gastroenterology Organization indicates the following symptoms may be associated with inflammatory damage of the digestive tract^[1]:

Diarrhea: Possible presence of mucus/blood in stool; occurs at night; incontinence
Constipation: May be the primary symptom in UC limited to the rectum; obstipation may occur; may proceed to bowel obstruction
Bowel movement abnormalities: Possible presence of pain or rectal bleeding, severe urgency, tenesmus
Abdominal cramping and pain: Commonly present in the right lower quadrant in CD; occur in the periumbilical or in the left lower quadrant in moderate to severe UC
Nausea and vomiting: More often in CD than in UC

See Clinical Presentation for more detail.

Diagnosis

Examination in patients with IBD may include the following findings, which are directly related to the severity of the attack:

Fever
Tachycardia
Dehydration
Toxicity
Pallor, anemia
Toxic megacolon: Medical emergency; patients appear septic, have high fever, lethargy, chills, and tachycardia, as well as have increasing abdominal pain, tenderness, distention
Mass in the right lower abdominal quadrant: May be present in CD
Perianal complications: May be observed in up to 90% of cases of CD^[2]

Testing

Although several laboratory studies may aid in the management of IBD and provide supporting information, no laboratory test is specific enough to adequately and definitively establish the diagnosis, including the following:

Complete blood count
Nutritional evaluation: Vitamin B12 evaluation, iron studies, red blood cell folate, nutritional markers
Erythrocyte sedimentation rate and C-reactive protein levels
Fecal calprotectin level
Serologic studies: Perinuclear antineutrophil cytoplasmic antibodies (ANCA), anti-Saccharomyces cerevisiae antibodies (ASCA)
Stool studies: Stool culture, ova and parasite studies, bacterial pathogens culture, and evaluation for Clostridium difficile infection^[3]

Imaging studies

The following imaging studies may be used to assess patients with IBD:

Upright chest and abdominal radiography
Barium double-contrast enema radiographic studies
Abdominal ultrasonography
Abdominal/pelvic computed tomography scanning/magnetic resonance imaging
Computed tomography enterography
Colonoscopy, with biopsies of tissue/lesions
Flexible sigmoidoscopy
Upper gastrointestinal endoscopy
Capsule enteroscopy/double balloon enteroscopy

See Workup for more detail.

Management

The medical approach for patients with IBD is symptomatic care (ie, relief of symptoms) and mucosal healing following a stepwise approach to medication, with escalation of the medical regimen until a response is achieved (“step-up” or “stepwise” approach), such as the following:

Step I – Aminosalicylates (oral, enema, suppository formulations): For treating flares and maintaining remission; more effective in UC than in CD
Step IA – Antibiotics: Used sparingly in UC (limited efficacy, increased risk for antibiotic-associated pseudomembranous colitis); in CD, most commonly used for perianal disease, fistulas, intra-abdominal inflammatory masses
Step II – Corticosteroids (intravenous, oral, topical, rectal): For acute disease flares only
Step III – Immunomodulators: Effective for steroid-sparing action in refractory disease; primary treatment for fistulas and maintenance of remission in patients intolerant of or not responsive to aminosalicylates
Step IV – Clinical trial agents: Tend to be disease-specific (ie, an agent works for CD but not for UC, or vice versa)

Pharmacotherapy

The following medications may be used in patients with IBD:

5-Aminosalicylic acid derivatives (eg, sulfasalazine, mesalamine, balsalazide, olsalazine)
Antibiotics (eg, metronidazole, ciprofloxacin, rifaximin)
Corticosteroid agents (eg, hydrocortisone, prednisone, methylprednisolone, prednisolone, budesonide, dexamethasone)
Immunosuppressant agents (eg, azathioprine, 6-mercaptopurine, methotrexate, cyclosporine)
Tumor necrosis factor inhibitors (eg, infliximab, adalimumab, certolizumab pegol)
Monoclonal antibodies (eg, natalizumab)
H2-receptor antagonists (eg, cimetidine, ranitidine, famotidine, nizatidine)
Proton pump inhibitors (eg, omeprazole, lansoprazole, esomeprazole magnesium, rabeprazole sodium, pantoprazole)
Antidiarrheal agents (eg, diphenoxylate and atropine, loperamide, cholestyramine)
Anticholinergic antispasmodic agents (eg, dicyclomine, hyoscyamine)

Surgery

UC is surgically curable. However, surgical resection is not curative in CD, with recurrence being the norm. Consider early consultation with a surgeon in the setting of severe colitis or bowel obstruction and in cases of suspected toxic megacolon.

Surgical intervention in IBD includes the following:

UC: Proctocolectomy with ileostomy, total proctocolectomy with ileoanal anastomosis
Fulminant colitis: Surgical procedure of choice is subtotal colectomy with end ileostomy and creation of a Hartmann pouch
CD: Surgery (not curative) most commonly performed in patients with complications of the disease; generally consists of conservative resection (eg, potential stricturoplasty vs resective surgery) to preserve bowel length in case future additional surgery is needed^[4]
Selected patients with distal ileal or proximal colonic disease: Option for ileorectal or ileocolonic anastomosis
Severe perianal fistulas: Option for diverting ileostomy; generally, resection for symptomatic enteroenteric fistulas

See Treatment and Medication for more detail.

References

Pathophysiology

The common end pathway of ulcerative colitis is inflammation of the mucosa of the intestinal tract, causing ulceration, edema, bleeding, and fluid and electrolyte loss.^[6]In several studies, genetic factors appeared to influence the risk of inflammatory bowel disease (IBD) by causing a disruption of epithelial barrier integrity, deficits in autophagy,^[7]deficiencies in innate pattern recognition receptors, and problems with lymphocyte differentiation, especially in Crohn disease.^[8]

Inflammatory mediators have been identified in IBD, and considerable evidence suggests that these mediators play an important role in the pathologic and clinical characteristics of these disorders. Cytokines, which are released by macrophages in response to various antigenic stimuli, bind to different receptors and produce autocrine, paracrine, and endocrine effects. Cytokines differentiate lymphocytes into different types of T cells. Helper T cells, type 1 (Th-1), are associated principally with Crohn disease, whereas Th-2 cells are associated principally with ulcerative colitis. The immune response disrupts the intestinal mucosa and leads to a chronic inflammatory process.^[9]

In animal studies, a local irritant (eg, acetic acid, trinitrobenzene sulfonic acid) can be inserted via an enema into the colon of rats or rabbits to induce a chemical colitis. An interleukin-10 (IL-10) knockout mouse has been genetically engineered to have some characteristics similar to those of a human with IBD. The cotton-top marmoset, a South American primate, develops colitis very similar to ulcerative colitis when the animal is subjected to stress.

Ulcerative colitis

In ulcerative colitis, the inflammation begins in the rectum and extends proximally in an uninterrupted fashion to the proximal colon and could eventually involve the entire length of the large intestine. The rectum is always involved in ulcerative colitis; and unlike in Crohn disease, there are no "skip areas" (ie, normal areas of the bowel interspersed with diseased areas), unless pretreated with topical rectal therapy (ie, a steroid or 5-aminosalicylic acid [5-ASA] enema).

The disease remains confined to the rectum in approximately 25% of cases, and in the remainder of cases, ulcerative colitis spreads proximally and contiguously. Pancolitis occurs in 10% of patients. The distal terminal ileum may become inflamed in a superficial manner, referred to as backwash ileitis. Even with less than total colonic involvement, the disease is strikingly and uniformly continuous. As ulcerative colitis becomes chronic, the colon becomes a rigid foreshortened tube that lacks its usual haustral markings, leading to the lead-pipe appearance observed on barium enema. (See the images below.)

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Inflamed colonic mucosa demonstrating pseudopolyps in a patient with ulcerative colitis.

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Double-contrast barium enema study shows pseudopolyposis of the descending colon in a patient with ulcerative colitis.

Crohn disease

Crohn disease can affect any portion of the gastrointestinal tract, from the mouth to the anus, and causes 3 patterns of involvement: inflammatory disease, strictures, and fistulas. This disease consists of segmental involvement by a nonspecific granulomatous inflammatory process. The most important pathologic feature of Crohn disease is that it is transmural, involving all layers of the bowel, not just the mucosa and the submucosa, which is characteristic of ulcerative colitis. Furthermore, Crohn disease is discontinuous, with skip areas interspersed between 2 or more involved areas.

Late in the disease, the mucosa develops a cobblestone appearance, which results from deep, longitudinal ulcerations interlaced with intervening normal mucosa (see the images below). In 35% of cases, Crohn disease occurs in the ileum and colon; in 32%, solely in the colon; in 28%, in the small bowel; and in 5%, in the gastroduodenal region.^[10]Diarrhea, cramping, and abdominal pain are common symptoms of Crohn disease in all of the above locations, except for the gastroduodenal region, in which anorexia, nausea, and vomiting are more common.^[10]

Rectal sparing is a typical but not constant feature of Crohn disease. However, anorectal complications (eg, fistulas, abscesses) are common. Much less commonly, Crohn disease involves the more proximal parts of the GI tract, including the mouth, tongue, esophagus, stomach, and duodenum.

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Cobblestone change of the mucosa of the terminal ileum in a patient with Crohn disease. Communicating fissures and crevices in the mucosa separate isl....

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This computed tomography scan from a patient with terminal ileal Crohn disease shows an enteroenteral fistula (arrow) between loops of diseased small ....

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Deep, fissuring ulcer in a patient with Crohn disease. Note the increase in submucosal inflammation and scattered lymphoid aggregates.

Cholelithiasis and nephrolithiasis

The incidence of gallstones and kidney stones is increased in Crohn disease because of malabsorption of fat and bile salts. Gallstones are formed because of increased cholesterol concentration in the bile, which is caused by a reduced bile salt pool.

Patients who have Crohn disease with ileal disease or ileal resection are also likely to form calcium oxalate kidney stones. With the fat malabsorption, unabsorbed long-chain fatty acids bind calcium in the lumen. Oxalate in the lumen is normally bound to calcium. Calcium oxalate is poorly soluble and poorly absorbed; however, if calcium is bound to malabsorbed fatty acids, oxalate combines with sodium to form sodium oxalate, which is soluble and is absorbed in the colon (enteric hyperoxaluria). The development of calcium oxalate stones in Crohn disease requires an intact colon to absorb oxalate. Patients with ileostomies generally do not develop calcium oxalate stones, but they may develop uric acid or mixed stones.^[11]

References

Etiology

Three characteristics define the etiology of inflammatory bowel disease (IBD): (1) genetic predisposition; (2) an altered, dysregulated immune response; and (3) an altered response to gut microorganisms. However, the triggering event for the activation of the immune response in IBD has yet to be identified. Possible factors related to this event include a pathogenic organism (as yet unidentified) or an inappropriate response (ie, failure to downgrade the inflammatory response to an antigen, such as an alteration in barrier function).

No mechanism has been implicated as the primary cause, but many are postulated. The lymphocyte population in persons with IBD is polyclonal, making the search for a single precipitating cause difficult. In any case, an inappropriate activation of the immune system leads to continued inflammation of the intestinal tract, with both an acute (neutrophilic) and chronic (lymphocytic, histiocytic) inflammatory response.

Several environmental risk factors have been proposed as contributing to the IBD pathogenesis, but the results are inconsistent, and the limitations of the studies preclude drawing firm conclusions. The most consistent association described has been smoking, which increases the risk of Crohn disease. However, current smoking protects against ulcerative colitis, whereas former smoking increases the risk of ulcerative colitis. Dietary factors have also been inconsistently described. In some studies, high fiber intake and high intake of fruits and vegetables appear protective against IBD.^[12]The E3N prospective study found that high animal protein intake (meat or fish) carried a higher risk of IBD.^[13]

Genetics

Persons with IBD have a genetic susceptibility for the disease,^[14]and considerable research over the past decade has improved our understanding of the role of these genes. Note that these genes appear to be permissive (ie, allow IBD to occur), but they are not causative (ie, just because the gene is present does not necessarily mean the disease will develop).

First-degree relatives have a 5- to 20-fold increased risk of developing IBD, as compared with persons from unaffected families.^{[6, 8]} The child of a parent with IBD has a 5% risk of developing IBD. Twin studies show a concordance of approximately 70% in identical twins, versus 5%-10% in nonidentical twins. Of patients with IBD, 10%-25% are estimated to have a first-degree relative with the disease. Monozygous twin studies show a high concordance for Crohn disease but less so for ulcerative colitis.

Crohn disease

An early discovery on chromosome 16 (IBD1 gene) led to the identification of 3 single nucleotide polymorphisms (2 missense, 1 frameshift) in the NOD2 gene (now called CARD15) as the first gene (CARD15) clearly associated with IBD (as a susceptibility gene for Crohn disease). CARD15 is a polymorphic gene involved in the innate immune system. The gene has more than 60 variations, of which 3 play a role in 27% of patients with Crohn disease, primarily in patients with ileal disease.

Subsequent studies have suggested that the CARD15 genotype is associated not only with the onset of the disease but also with its natural history. A study on 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 colonic disease.^{[15, 16]}These gene products appear to be involved in the intracellular innate immune pathways that recognize microbial products in the cytoplasm.

Another early genome-wide association study looked at Jewish and non-Jewish case-control cohorts and identified 2 single nucleotide polymorphisms in the IL23R gene, which encodes 1 subunit of the interleukin-23 receptor protein.^[17]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.^[18]However, another study found that the Arg381Gln substitution is associated with childhood onset of IBD in Scotland.^[19]These gene products appear to be involved in regulating adaptive immunity.

Numerous other loci have been identified as conferring susceptibility to Crohn disease, including several large meta-analyses that found multiple novel susceptibility loci and confirmed earlier findings. In one meta-analysis of 3 genome-wide association scans, 526 single nucleotide polymorphisms from 74 distinct genomic loci were found.^[20]In sorting out loci that have been previously discussed, there were 21 new loci that were associated with an increased risk of developing Crohn Disease and have functional implications, including the genes CCR6, IL12B, STAT3, JAK2, LRRK2, CDKAL1, and PTPN22.^[20]Most of these genes are involved in signal transduction in the immune function.

The interlectin gene (ITLN1) is expressed in the small bowel and colon, and it is also involved in the recognition of certain microorganisms in the intestine. Other genome-wide association studies have found associations between susceptibility to Crohn disease and polymorphisms in genes that are associated with the intestinal milieu. One such study examined nearly 20,000 single nucleotide polymorphisms in 735 individuals with Crohn disease.^[21]An association was found with the ATG16L1 gene, which encodes the autophagy-related 16-like protein, which is involved in the autophagosome pathway that processes intracellular bacteria.^[21]

Single nucleotide polymorphisms in other autophagy genes have also shown association with susceptibility to Crohn disease, such as 2 polymorphisms that flanked the IRGM gene and may exert regulatory control for the gene.^[22]Subsequently, there have been a number of other loci implicated in the autophagy pathway that have been associated with Crohn disease.^[7]

There is 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 significant susceptibility to severe colitis.^[23]A large genomic study of multiple diseases confirmed many of the findings that were found in earlier studies, as well as several additional loci of interest for Crohn disease.^[24]

Disruption of a homologous gene in a murine model resulted in defective development of the intestine.^[25]It was hypothesized that changes in the 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]

Ulcerative colitis

The genetic predisposition for ulcerative colitis appears to be lesser in magnitude than Crohn disease but consists of a set of genetic susceptibilities that shows significant overlap with Crohn disease. One genome-wide association study found a previously unknown susceptibility locus at ECM1 and also showed several risk loci that were common to both ulcerative colitis and Crohn disease.^[26]Genes that confer risk for both diseases appear to influence the immune milieu of the intestine, whereas the genes that influence only Crohn disease appear to be involved mainly in autophagy.^{[26, 27]}

Additional susceptibility loci for ulcerative colitis have been found on 1p36 and 12q15. The 1p36 single nucleotide polymorphism is near the PLA2G2E gene, which is involved in releasing arachidonic acid from membrane phospholipids, leading to other proinflammatory lipids. The first 12q15 signal is located near the interferon (IFN)-gamma, interleukin (IL)-26, and IL-22 genes, whereas the second 12q15 signal is located in IL-26 gene. These genes play roles in the immune response to pathogens as well as the tissue inflammation processes.^[28]

Data suggest that genetic influences increase the risk for one form of IBD while decreasing the risk for another. In a Japanese population, the HLA-Cw*1202-B*5201-DRB1*1502 haplotype increases the risk for ulcerative colitis but reduces the risk for Crohn disease.^[29]This finding has not been replicated in other ethnic groups. However, as the authors noted, the human leukocyte antigen (HLA) type in question in this study is relatively common in the Japanese population but relatively rare in European populations. They suggest that the HLA type will favor a T-helper immune response, predisposing toward ulcerative colitis, as opposed to an IFN-predominant response, predisposing more toward Crohn disease.^[29]

Smoking

The risk of developing ulcerative colitis is higher in nonsmokers and former smokers than in current smokers. The onset of ulcerative colitis occasionally appears to coincide with smoking cessation; however, this does not imply that smoking would improve the symptoms of ulcerative colitis. There has been limited success with the use of nicotine patches. Crohn disease patients have a higher incidence of smoking than the general population, and smoking appears to lessen the response to medical therapy.

References

Prognosis

The standardized mortality ratio for inflammatory bowel disease (IBD) ranges from approximately 1.4 times the general population (Sweden) to 5 times the general population (Spain). Most of this increase appears to be in the Crohn disease population; the ulcerative colitis population appears to have the same mortality rate as the general population.^[38]

The majority of studies indicate a small but significant increase in mortality associated with IBD.^[39]A frequent cause of death in persons with IBD is the primary disease^[40]; infections and COPD/respiratory illness are other major causes of death.^[41]IBD is not a risk factor for cardiovascular mortality.^[42]

Patients with IBD are more prone to the development of malignancy. Persons with Crohn disease have a higher rate of small bowel malignancy. Patients with pancolitis, particularly ulcerative colitis, are at a higher risk of developing colonic malignancy after 8-10 years of disease. The current standard of practice is to screen patients with colonoscopy at 1-2 year intervals once they have had the disease for greater than 10 years.

A comprehensive discussion regarding the diagnosis, management, and surveillance of colorectal cancer in patients with IBD is beyond the scope of this article. For more information, see the following 2 guidelines:

AGA medical position statement on the diagnosis and management of colorectal neoplasia in inflammatory bowel disease. 2010.^{[43, 44]} http://www.gastrojournal.org/article/S0016-5085(09)02202-1/fulltext
Colonoscopic surveillance for prevention of colorectal cancer in people with ulcerative colitis, Crohn's disease or adenomas. (National Institute for Health and Clinical Excellence (NICE), London).^[45] http://guideline.gov/content.aspx?id=34830

Morbidity

In addition to long-term, disease-related complications, patients can also experience morbidity from prolonged medical therapy, particularly as a consequence of steroid exposure.

There also appears to be an increased risk for IBD in patients with asthma or chronic obstructive pulmonary disease (COPD). In a population-based retrospective cohort study of 136,178 individuals with asthma and 143,904 individuals with COPD, Brassard and colleagues found a significantly increased incidence of IBD. The average incidences of CD and UC in asthma patients were 23.1 and 8.8/100,000 person-years, respectively. Corresponding figures in COPD patients were 26.2 CD and 17 UC cases/100,000 person-years, respectively.^{[46, 47]}

Compared with the general population, the incidence of CD in asthma and COPD patients was 27% and 55% higher, and the incidence of UC was 30% higher among those with COPD. Among children up to 10 years old in the asthma group and adults aged 50 to 59 in the COPD group, the incidence of CD was more than twice that seen in the general population.^{[46, 47]}

Psychologic morbidity affects patients with IBD, especially younger patients, and are typically associated with depression and anxiety symptoms but also exhibit externalizing behaviors.^[48]Risk factors for psychologic morbidity appear to include increased disease severity, lower socioeconomic status, use of corticosteroids, parental stress, and older age at diagnosis.^[48]

Ulcerative colitis

The average patient with ulcerative colitis has a 50% probability of having another flare during the next 2 years; however, patients may have only one flare over 25 years, and others may have almost persistently active disease. A small percentage of patients with ulcerative colitis have a single attack and no recurrence. Typically, remissions and exacerbations are characteristic of this disease, with acute attacks lasting weeks to months.

Patients with ulcerative colitis limited to the rectum and sigmoid have a 50% chance of progressing to more extensive disease over 10 years^[49]and a 7.5% rate of colectomy over 5 years.^[50]Approximately 10% of patients presenting with proctitis will develop a pancolitis.^{[49, 50]}

Surgical resection for ulcerative colitis is considered “curative” for this disease, although patients may experience symptoms related to the ileal pouch (J-pouch), including acute and chronic pouchitis. Pouchitis is far more common in patients who have had a colectomy for ulcerative colitis than in those who have had a colectomy for familial adenomatous polyposis.

Beyond 8-10 years after diagnosis, the risk of colorectal cancer increases by 0.5%-1.0% per year. Surveillance colonoscopies with random biopsies reduce mortality from colorectal cancer in patients with ulcerative colitis by allowing the detection of low- or high-grade dysplasia and early stage carcinoma.

Crohn disease

The clinical course of Crohn disease is much more variable than that of ulcerative colitis, and it is dependent on the anatomic location and extent of the disease. Periodic remissions and exacerbations are the rule in Crohn disease. The relapse rate over 10 years is 90%, and the cumulative probability of requiring surgery over 10 years is approximately 38%. Terminal ileum location, fistulizing, and structuring disease are all independent risk factors for subsequent surgery.^[51]

A review of the literature indicates that approximately 80% of patients who are in remission for 1 year will remain in remission over subsequent years.^[52]Patients with active disease in the past year have a 70% chance of having clinical disease activity in the following year. Approximately 20% of patients will have annual relapses, and 13% will have a course free of relapses. Less than 5% of patients with Crohn disease will have continually active disease.^[52]

Surgery for Crohn disease is generally performed for complications (eg, stricture, stenosis, obstruction, fistula, bleeding, or abscess). Surgical intervention is an important treatment option for Crohn disease, but patients should be aware that it is not curative and that disease recurrence after surgery is high, mimicking the original disease pattern at the site of the surgical anastomosis.

Recurrence of perianal fistulas after medical or surgical treatment is common (59%-82%).^[52]In one study, one year after surgery for Crohn disease, 20%-37% of patients had symptoms suggestive of clinical recurrence, and endoscopic evidence of recurrent inflammation was in the neoterminal ileum in 48%-93% of patients.^[53]

Overall, the patient's quality of life with Crohn disease is generally lower than that of individuals with ulcerative colitis. Data suggest that in persons with Crohn colitis involving the entire colon, the risk of developing malignancy is equal to that in persons with ulcerative colitis; however, the risk is much smaller (albeit poorly quantified) in most patients with Crohn disease primarily involving the small bowel. Intestinal cancer may become a more important long-term complication in patients with Crohn disease because of longer survival.

Studies support evidence that specific CARD15 mutations are associated with the intestinal location of the disease, as well as course and prognosis,^[8]and are correlated with the propensity for developing ileal strictures and with an early onset of disease.

Complications of IBD disease

Intestinal complications

IBD can be associated with several gastrointestinal complications, including risk of hemorrhage, perforation, strictures, and fistulas—as well as perianal disease and related complications, such as perianal or pelvic abscesses, toxic megacolon (complicating acute severe colitis), and malignancy (colorectal cancer, cholangiocarcinoma complicating primary sclerosing cholangitis).

Extraintestinal complications

Extraintestinal complications occur in approximately 20%-25% of patients with IBD.^[1]In some cases, they may be more symptomatic than the bowel disease itself. These include osteoporosis (usually a consequence of prolonged corticosteroid use), hypercoagulability resulting in venous thromboembolism, anemia, gallstones, primary sclerosing cholangitis, aphthous ulcers, arthritis, iritis (uveitis) and episcleritis, and skin complications (pyoderma gangrenosum, erythema nodosum).

Table 1, below, summarizes the rates of the most common extraintestinal complications in patients with IBD the United States and Europe.

Table 1. Common Extraintestinal Complications of IBD in US and Europe^[54]

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See Table

The Swiss National IBD Cohort Study also demonstrated the risks of extraintestinal complications of IBD; their results are summarized in Table 2, below.^[55]The risk factors of having complications included family history and active disease observed for Crohn disease only; no significant risk factors were noted in patients with ulcerative colitis.^[55]

Table 2. Extraintestinal Complications of IBD in Swiss Patients^[55]

View Table

See Table

References

Laboratory Studies

Hematologic tests

Complete blood cell count

The components of the complete blood cell (CBC) count can be useful indicators of disease activity and iron or vitamin deficiency. An elevated white blood cell (WBC) count is common in patients with active inflammatory disease and does not necessarily indicate infection.

Anemia is common and may be either an anemia of chronic disease (usually normal mean corpuscular volume [MCV]) or an iron deficiency anemia (MCV is often low). Anemia may result from acute or chronic blood loss, malabsorption (iron, folate, and vitamin B12) or may reflect the chronic disease state. Note that the MCV can be elevated in patients taking azathioprine (Imuran) or 6-mercaptopurine (6-MP). Generally, the platelet count is normal, or it may be elevated in the setting of active inflammation.

Nutritional evaluation: Vitamin B12 evaluation, iron studies, RBC folate, nutritional markers

Vitamin B12 deficiency can occur in patients with Crohn disease who have significant terminal ileum disease or in patients who have had terminal ileum resection. The standard replacement dose of vitamin B12 is 1000 mg subcutaneously (SC) every month, because oral replacement is often insufficient.

Serum iron studies should be obtained at the time of diagnosis, because active IBD is a source for GI blood loss, making iron deficiency common. A microcytic hypochromic anemia suggests iron deficiency; if confirmed with serum iron/total iron-binding capacity (TIBC), iron should be replaced either enterally or parenterally. For parenteral replacement, intravenous (IV) iron sucrose can be used, and dosing is based on the table in the package insert, with a maximum of 30 mL (1500 mg) at once.

Although folate deficiency is not common in persons with IBD, several concerns have been raised regarding this vitamin. Sulfasalazine (Azulfidine) is a folate reductase inhibitor and may inhibit normal uptake of folate; thus, many practitioners commonly administer folate supplements in patients taking sulfasalazine. Folate supplements are indicated in all women who are pregnant to help prevent neural tube defects; this is particularly true for patients with IBD, and supplementation with 2 mg/day or more (rather than the usual 1 mg/day) should be considered in those on sulfasalazine.

Nutritional status can be assessed by serum albumin, prealbumin, and transferrin levels. However, note that transferrin is an acute-phase reactant that can be falsely elevated in persons with active IBD. Hypoalbuminemia may reflect malnutrition because of poor oral intake or because of protein-losing enteropathy that can coexist with active IBD.

ESR and CRP levels

The erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) level are often used as serologic markers for inflammation, but they are not specific for IBD. However, measuring such inflammatory markers also aids in monitoring disease activity and response to treatment. A small but significant number of patients with Crohn disease or ulcerative colitis may not have elevated ESR or CRP levels even in the setting of significant active inflammation. In addition, inflammatory markers may be elevated in the setting of superimposed intestinal or extraintestinal infections.

Fecal calprotectin levels

Fecal calprotectin has been proposed as a noninvasive surrogate marker of intestinal inflammation in IBD.^[57]As colorectal neoplasia and gastrointestinal infection also increase fecal calprotectin, this marker is not in widespread use. Note that relatives of patients with IBD may also have elevated levels of fecal calprotectin (with unknown degrees of inflammation).^[57]

A study by Henderson et al indicated that fecal calprotectin has a high sensitivity and modest specificity for diagnosing IBD in children. The researchers conducted a systematic review and meta-analysis of 8 studies including 394 pediatric IBD cases and 321 non-IBD controls.^{[58, 59]}The use of fecal calprotectin during the investigation of suspected pediatric IBD was associated with a pooled sensitivity of 97.8%, a pooled specificity of 68.2%, a positive likelihood ratio of 3.07, and a negative likelihood ratio of 0.03.

References

Radiography

Upright chest and abdominal radiography

Abdominal radiography may allow for assessment of the kidneys, ureters, and bladder for nephrolithiasis and the vertebral bodies for osteopenia or osteoporosis and sacroileitis. If severe fulminant colitis is present, abdominal radiography may reveal an edematous, irregular colon with thumbprinting (see the first image below). Occasionally, pneumatosis coli (air in the colonic wall) may be present. Free air and evidence of toxic megacolon, which appears as a long continuous segment of air-filled colon greater than 6 cm in diameter, indicates a surgical emergency. (See the images below.)

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Plain abdominal radiograph of a patient with known ulcerative colitis who presented with an acute exacerbation of his symptoms. This image shows thumb....

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Plain abdominal radiograph in a 26-year-old with a 10-year history of ulcerative colitis shows a long stricture/spasm of the ascending colon/cecum (<i....

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Toxic megacolon. Courtesy of Dr. Pauline Chu.

Toxic megacolon is a life-threatening complication of ulcerative colitis and requires urgent surgical intervention. This condition occurs predominantly in the transverse colon, probably because air collects there in the supine position. The transverse colon is dilated, usually more than 8 cm (dilation more than 6 cm is considered abnormal). A colectomy is required if no improvement occurs within 24-48 hours. Repeat radiographs are required at 12- to 24-hour intervals to monitor the course of dilatation and to assess the need for emergency colectomy.

Barium enema double-contrast radiographic studies

The barium enema imaging technique was one of the first studies that allowed characterization of the typical findings associated with inflammatory bowel disease (IBD). Barium enemas may be useful in cases of limited or no access to endoscopy, in cases of incomplete colonoscopy, or to measure stricture length.^[1]

Several terms have been used to describe abnormalities found after barium studies of the colon, including the following:

A lead-pipe or stove-pipe appearance suggests chronic ulcerative colitis that has resulted in a loss of colonic haustra due to the colon becoming a rigid foreshortened tube (see the following image)

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Double-contrast barium enema study shows pseudopolyposis of the descending colon in a patient with ulcerative colitis.
Rectal sparing suggests Crohn colitis in the presence of inflammatory changes in other portions of the colon (see the image below)

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Double-contrast barium enema study demonstrates marked ulceration, inflammatory changes, and narrowing of the right colon in a patient with Crohn coli....
Thumbprinting indicates mucosal inflammation (which can also be seen frequently on the abdominal flat plate) (see the following image)

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Plain abdominal radiograph of a patient with known ulcerative colitis who presented with an acute exacerbation of his symptoms. This image shows thumb....
Skip lesions indicate areas of inflammation alternating with normal-appearing areas, again suggesting Crohn colitis

Barium can be refluxed into the terminal ileum in many cases (see the first image below), which can assist in the diagnosis of Crohn disease. The string sign (a narrow band of barium flowing through an inflamed or scarred area) in the terminal ileum is typical of one form of ileal Crohn disease observed on radiographs (see the first image below). Barium enema is contraindicated in patients with moderate to severe colitis, because it risks perforation or precipitation of a toxic megacolon (see the second image below).

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Crohn disease involving the terminal ileum. Note the "string sign" in the right lower quadrant (viewer's left).

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Toxic megacolon. Courtesy of Dr. Pauline Chu.

In Crohn disease, areas of segmental narrowing with loss of normal mucosa, fistula formation, and the string sign (a narrow band of barium flowing through an inflamed or scarred area) in the terminal ileum are typically observed on radiographs (see the images below). Some patients with ulcerative colitis also demonstrate inflammatory changes in the terminal ileum (ileitis), but these findings lack the skip pattern that is characteristic of Crohn disease.

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Enteroenteric fistula noted on small bowel series of x-ray films in a patient with inflammatory bowel disease. The narrow-appearing segments filled ou....

The small bowel series, or small bowel follow-through (see the image below), can reveal inflammation, can assist in the assessment of stricture length and severity, and can help determine the most appropriate surgical approach. Fistulas may be demonstrated on films from a small bowel series, even if they are not suggested on the basis of the clinical evaluation.

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Cobblestoning in Crohn disease. Spot views of the terminal ileum from a small bowel follow-through study demonstrates linear longitudinal and transver....

Although radiologists may remark on the abnormalities suggested in the cecum or ascending colon when the barium from a small bowel series enters the colon, independent confirmation must be sought because the presence of stool and dilution of the barium may make proper interpretation of colon findings difficult.

The small bowel series is usually sufficient for the evaluation of small intestine Crohn disease; however, in rare cases, it may not provide an adequate view of the terminal ileum, necessitating an enteroclysis.

References

Colonoscopy and Flexible Sigmoidoscopy

Colonoscopy

Colonoscopy is one of the most valuable tools available to the physician for the diagnosis and treatment of inflammatory bowel disease (IBD), although its limitations must be recognized. Foremost, not all mucosal inflammation is idiopathic IBD. Infectious causes of inflammation must always be considered, as should diverticulitis and ischemia (which are far more common as new diagnoses in an elderly population than IBD, despite the similar colonoscopic and histologic appearance).

When used appropriately, colonoscopy can help determine the extent and severity of colitis, assist in guiding treatment, and provide tissue to assist in the diagnosis. In skilled hands, the colonoscope can frequently reach the terminal ileum and permit assessment of inflammation to assist in the diagnosis or exclusion of Crohn disease. Inflammation may occasionally occur in the terminal ileum in patients with ulcerative colitis; this is referred to as a backwash ileitis and is mild, is nonulcerating, and may occur when a widely patent ileocecal valve is present. (See the following images.)

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Severe colitis noted during colonoscopy in a patient with inflammatory bowel disease. The mucosa is grossly denuded, with active bleeding noted. The p....

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Stricture in the terminal ileum noted during colonoscopy in a patient with inflammatory bowel disease. This image depicts a narrowed segment visible u....

Colonoscopy or sigmoidoscopy reveals that the rectum is almost always involved in ulcerative colitis, but it is frequently spared in Crohn disease. The disease can be limited to the rectum (proctitis); to the rectum, sigmoid, and descending colon (left-sided colitis); or to the entire colon (pancolitis). Ulcerative colitis does not involve any other segment of the GI tract. Colectomy is curative.

Colonoscopy with ileoscopy in the assessment of Crohn disease has a sensitivity of 74% and a specificity of 100%, leading to a positive predictive value of 100% as a diagnostic test.^[67]When paired with small bowel follow-through, the sensitivity of this pair of diagnostic tests is increased to 78%, with a continued positive predictive value of 100%.^[67]

Colonoscopy can also be used for therapeutic intervention in patients with IBD. The most common therapeutic use is stricture dilation in persons with Crohn disease. Colonic, anastomotic, and even small bowel strictures can often be dilated using pneumatic through-the-scope dilators. Intralesional injection of steroids (eg, triamcinolone at 5 mg in 4 quadrants) may help, but it is usually of transient value and has yet to be assessed in controlled trials.

Patients with IBD who are undergoing endoscopic procedures may have higher complication rates than the general population. The risks of colonoscopy apply (eg, reaction to medication, bleeding, perforation), and the risk of bleeding is increased in the presence of inflammation. The risk of perforation is also increased, particularly in patients taking high doses of steroids long term or who have severe colitis.

Colonoscopy also plays an important role in surveillance for colorectal cancer in patients with IBD. The utility of endoscopic surveillance can be further optimized by autofluorescence plus high-resolution endoscopy, chromoendoscopy-guided confocal laser microscopy, and confocal laser microscopy in combination with narrow-band imaging and high-resolution endoscopy, as well as chromoendoscopy with methylene-blue dye and spray-targeted biopsies.^[68]

Flexible sigmoidoscopy

Flexible sigmoidoscopy is useful for a preliminary diagnosis in patients with chronic diarrhea or rectal bleeding; however, because of the limited length of the scope (60 cm), it can only help diagnose distal ulcerative colitis or proctitis. Rarely, Crohn colitis can be diagnosed based on flexible sigmoidoscopy findings. Note that sigmoid inflammation, particularly in older patients, may be confused with diverticulitis or ischemia.

References

Histologic Findings

Ulcerative colitis

Ulcerative colitis is a superficial inflammation of the bowel wall almost entirely limited to the large bowel (when the cecum is involved, there may be some inflammation in the distal-most ileum, the so-called "backwash ileitis"). Only in complicated cases such as evolution into toxic megacolon are the deeper layers of the bowel wall involved with the inflammatory process.

Ulcerative colitis primarily involves the mucosa and the submucosa, with the formation of crypt abscesses and mucosal ulceration. The mucosa typically appears granular and friable. In more severe cases, pseudopolyps form, consisting of areas of hyperplastic growth with swollen mucosa surrounded by inflamed mucosa with shallow ulcers. In severe ulcerative colitis, inflammation and necrosis can extend below the lamina propria to involve the submucosa and the circular and longitudinal muscles.

Inflammation in ulcerative colitis almost always involves the rectum and is contiguous, regardless of the extent of the colon involved. The exception to this rule is that the initial inflammation may appear patchy during colonoscopy that is performed very early in the ulcerative colitis process, although biopsy specimens of the intervening normal-appearing mucosa often do reveal inflammation. The intestinal inflammation of ulcerative colitis only involves the colon. Biopsy specimens demonstrate neutrophilic infiltrate along with crypt abscesses and crypt distortion. Granulomas do not occur in ulcerative colitis. (See the following images.)

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Chronic architectural changes in ulcerative colitis. Note the crypt branching and irregularity of size and shape, with an increase in chronic inflamma....

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Low-power image of a colon biopsy specimen in a patient with ulcerative colitis illustrates changes limited to the mucosa. These changes include chron....

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Chronic architectural changes in ulcerative colitis. Note the trifid crypt.

The typical histologic findings of ulcerative colitis include expansion of chronic inflammation in the mucosa and, in active cases, the presence of acute inflammation. In mildly active cases, there is an acute cryptitis that progresses to crypt abscesses in moderately active cases. In severe cases, mucosal ulcers develop as a result of the ongoing acute inflammatory process. Areas of relatively preserved mucosa between ulcerated areas may have a polypoid appearance grossly and are referred to as "pseudopolyps." In cases of many years’ duration, dysplasia of the large bowel mucosa may develop and signifies an increased risk for the development of colorectal adenocarcinoma. (See the images below.)

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High-power view of a crypt abscess in ulcerative colitis shows the crypt to be dilated and filled with neutrophils and debris.

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This is an example of low-grade glandular dysplasia in a patient with longstanding ulcerative colitis. Note the loss of mucin, nuclear hyperchromasia,....

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High-grade dysplasia in the same patient as the previous image. There is significant cytologic atypia, with rounding of the nuclei and a greater degre....

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Histologic section from another location in the same patient as the previous image. This field shows glands that are suspicious for invasive carcinoma....

Crohn disease

The entire intestinal wall is involved with inflammation in Crohn disease. Biopsy specimens may demonstrate granulomas (approximately 50% of the time). The presence of granulomas is often helpful in making the diagnosis but is not necessary.

Because biopsy specimens obtained at colonoscopy are generally superficial mucosal samples, the pathologist may have difficulty making a definitive diagnosis of ulcerative colitis or Crohn disease based on histologic findings alone. However, histology also helps rule out other causes of inflammation, including infectious colitis and ischemic colitis. The characteristic pattern of inflammation in Crohn disease is a transmural involvement of the bowel wall by lymphoid infiltrates that contains sarcoidlike granulomas in about half of the cases (most commonly in the submucosa). Also characteristic are proliferative changes in the muscularis mucosa and in the nerves scattered in the bowel wall and myenteric plexus. In the involved foci of the small and large bowel, Paneth cell hyperplasia is frequent and areas of pyloric metaplasia may be seen. In full-blown cases, long and deep fissurelike ulcers form. (See the following images.)

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Deep knifelike, fissuring, transmural ulcer in Crohn disease.

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Granuloma in the mucosa in a Crohn disease patient.

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Colonic granuloma in a patient with Crohn disease (arrow). Hematoxylin-eosin staining. Courtesy of Dr E. Ruchelli.

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A crypt abscess demonstrating active, neutrophilic inflammation in Crohn disease.

References

Step II – Corticosteroids

Corticosteroids are rapid-acting anti-inflammatory agents used in the treatment of inflammatory bowel disease (IBD). These drugs are indicated for acute flares of disease only and have no role in the maintenance of remission.

Corticosteroids may be administered by various routes depending on the location and severity of disease; they may be administered intravenously (ie, methylprednisolone, hydrocortisone), orally (ie, prednisone, prednisolone, budesonide, dexamethasone), or topically (ie, enema, suppository, or foam preparations).Corticosteroids are limited by their adverse effects, particularly with prolonged use.

The potential complications of corticosteroid use include fluid and electrolyte abnormalities, osteoporosis, avascular bone necrosis, peptic ulcers, cataracts, glaucoma, neurologic and endocrine dysfunctions, infectious complications, and occasional psychiatric disorders (including psychosis).

The consensus regarding treatment with these agents is that they should be tapered once remission has been induced. (see Surgical Intervention, below, for information on Tapering corticosteroids in the postoperative setting). Corticosteroids do not have a role in maintaining remission.

Patients who are concerned about immunosuppressive therapies, including immunomodulators or anti–tumor necrosis factor (TNF) agents, should be educated about the potential greater incidence of complications occurring with long-term steroid use and with undertreated disease. Patients with prolonged use of steroids may also require ophthalmologic examination because of the risk of development of glaucoma and cataracts.

Periodic assessment of bone mineral density is recommended for patients taking steroids for more than 3 months.^[90]Agents used for osteoporosis prevention and treatment (eg, the bisphosphonates) are useful for preventing the bone loss associated with corticosteroid use.

Intravenous corticosteroids

Intravenous corticosteroids are often used in patients who are severely ill and hospitalized; few data have been published on the optimum dosage of IV or oral corticosteroids. The upper end of dosing generally includes IV methylprednisolone at 20 mg every 6 hours or IV hydrocortisone at 100 mg every 8 hours. Typically, once a clinical response is observed (usually within 3-5 days), the dose of the IV corticosteroid can be tapered. Before hospital discharge, conversion to an oral corticosteroid is made with dosage tapering in an outpatient setting.

Oral corticosteroids

When oral corticosteroids are used, dosing is variable, and few data have been published to guide optimal dosing. The most common range for moderate flares of IBD is prednisone at 10-40 mg/day. For more severe flares, doses up to 60 mg/day may be used, but there are no supportive data. Once a clinical response is seen, the dose is tapered. Most patients who use oral corticosteroids can occasionally tolerate a relatively rapid taper after a response is achieved; a prolonged steroid taper is rarely necessary to prevent relapse. When the latter situation occurs, consider escalation of therapy with the use of alternative drugs (immune modifiers or anti-TNF therapy).

Budesonide (Entocort EC), a synthetic corticosteroid, is available for Crohn disease with ileal or ileocecal involvement.^[70]Budesonide has extensive first-pass metabolism, which limits systemic adverse effects.^[90]However, some absorption occurs over a prolonged period of exposure. Budesonide is also less effective than other standard glucocorticosteroids for the treatment of ileal Crohn disease and has not demonstrated efficacy in maintaining therapy beyond 12 months.^[89]

According to the American Gastroenterological Association (AGA) guidelines, ileal-release preparations of budesonide are indicated for the treatment of patients with mild to moderate ileal and right-sided colonic Crohn disease.^[90]These preparations have not been demonstrated to be effective in patients with ulcerative colitis, but clinical trials in this setting are under way.^[90]

Topical corticosteroids

Topical corticosteroids are used in persons with distal colonic disease in a manner similar to that of topical mesalamine; the major difference is that even though topical mesalamine may be used to help maintain remission, topical corticosteroids are used for active disease and have only a small role in the maintenance of remission. According to AGA guidelines, topical therapy with either hydrocortisone (grade A recommendation) or budesonide (grade B recommendation) is effective for distal colonic inflammation in patients with mild to moderate IBD.^[90]

Patients with ulcerative colitis with predominantly distal disease may be treated with topical budesonide, a synthetic steroid which has local anti-inflammatory effects and limited systemic effects.^[91]Although topical budesonide is effective, novel oral controlled-release formulations have been developed to enable treatment of the entire colon.^[91]

Rectal corticosteroids

Cortenema, Cortifoam, and Anusol-HC suppositories are useful in treating distal disease (proctitis and proctosigmoiditis).

References

Step III – Immunomodulators

Immune modifiers have a slower onset of action (typically, a 2- to 3-month lag) and, consequently, are not used for induction of remission. However, these agents have shown effectiveness for their steroid-sparing action in persons with refractory disease; they are also used as primary treatment for fistulas and maintenance of remission in patients intolerant of or not responsive to aminosalicylates.

The immunomodulators 6-mercaptopurine (6-MP) and azathioprine (AZA) are used in patients with inflammatory bowel disease (IBD) in whom remission is difficult to maintain with the aminosalicylates alone. Calcineurin inhibitors such as cyclosporin A (CSA) and tacrolimus, as well as methotrexate (MTX), are also immune-modifying agents^[1]; CSA is almost exclusively limited to acute severe colitis, whereas tacrolimus has been used in both perianal Crohn disease and ulcerative colitis.^[1]

Data on MTX support the use of intramuscular MTX in Crohn disease, but such data are lacking in ulcerative colitis. The only trial of MTX in ulcerative colitis used a low-dose oral therapy^[92]; whether a higher-dose oral MTX or parenteral MTX (IM or SQ) may be effective in ulcerative colitis has not been studied. Several clinical trials showed that AZA continuation in patients with ulcerative colitis prevented relapse, as compared to those who discontinued the medication. However, other trials have shown trends but no statistically significant benefit of AZA in ulcerative colitis.^[93]

Thiopurine agents

The American Gastroenterological Association (AGA), in accordance with the US Food and Drug Administration (FDA), recommends that patients undergo assessment of the thiopurine methyltransferase (TPMT) genotype or phenotype before starting therapy with AZA or 6-MP.^[90]Individuals who have low enzyme activity or are homozygous deficient in the TPMT mutation are at risk of very severe leukopenia, with potential septic complications, and may not be good candidates for therapy with these drugs.^[90]

About 11% of individuals with heterozygous TPMT activity respond well to therapy but are prone to myelotoxicity, although this can be minimized with the use of lower doses. These patients, as well as those with wild-type TPMT activity, require monitoring for complications.^[90]

Adverse effects and monitoring

Use of immune modifiers mandates monitoring of blood parameters; they can cause significant neutropenia or pancytopenia that warrants a dose reduction or discontinuation. Routine complete blood cell (CBC) counts with differentials and platelet counts are checked monthly, and liver function tests (LFTs) can be performed intermittently. After a year of stable dosing with no difficulties with blood counts (except the expected lymphopenia), the interval between blood count monitoring can be increased.

The cytopenic effect is typically dose dependent, although some patients are more sensitive than others. The typical AZA dose is 2-2.5 mg/kg/day, whereas the dose of 6-MP is 1-1.5 mg/kg/day. In some studies, blood levels of 6-thioguanine has been shown to guide dosing, but such tests offer little advantage, at a much greater cost for routine monitoring and dose adjustment, over CBC counts and liver function tests. In independent studies, metabolite levels have not shown any correlation with clinical efficacy, but they may help in monitoring compliance.

Other adverse effects of the immune modifiers include fever, rash, infectious complications, hepatitis, pancreatitis, and bone marrow depression. The most common reason for discontinuing the immune modifiers within the first few weeks is the development of abdominal pain; occasionally, a biochemically demonstrable pancreatitis occurs.

Concerns have been raised about the development of malignancy in patients taking 6-MP and azathioprine. These agents have been associated with a 2- to 4-fold greater incidence of lymphoma and an increase in nonmelanoma skin cancers, but curiously, there is a 3.5-fold decrease in colorectal carcinoma.

Anti-TNF-alpha monoclonal antibodies

Infliximab

Infliximab (Remicade) is an anti-TNF-alpha monoclonal antibody that is administered by infusion for the treatment of Crohn disease. Infliximab is FDA approved for both ulcerative colitis and Crohn disease; it appears to have a higher efficacy rate in Crohn disease. Infliximab is generally administered as 3 separate infusions of 5 mg/kg for the induction of remission of moderate to severe IBD at weeks 0, 2, and 6, followed by infusions every 8 weeks for maintenance of remission. Vande Casteele et al found that targeting the trough concentrations of infliximab to levels of 3-7 μg/mL results in a more efficient use of this agent in patients with IBD.^[94]

A systemic review of the efficacy of biologic therapies in IBD confirmed that anti-TNF-alpha agents and natalizumab were effective in inducing remission of active Crohn disease.^[95]For Crohn disease, the response rate may be as high as 80% (the usual response rate to natalizumab is about 60%), and the induction of remission rate is 30%-50% after a single dose; with multiple dosing, higher rates of remission are attained. For ulcerative colitis, the response rates may be as high as 50%-70%.

Patients with moderate to severe Crohn disease who have documented active inflammation, dependence on corticosteroids and an inability to taper these agents, or disease refractory to steroids are most likely to benefit from anti-TNF therapy.^[96]Before anti-TNF agents are administered, screening should be done for coexistent infection with perianal and abdominal abscess (including Mycobacterium tuberculosis), and caution is advised if a patient is a carrier for the hepatitis B virus.^[96]

Cessation of infliximab therapy, even in patients who are in prolonged remission, is associated with high rates of disease flare. In a study of 115 patients with Crohn disease who were treated for a minimum of 1 year with infliximab and an antimetabolite, who had at least 6 months of corticosteroid-free remission, and who subsequently stopped infliximab therapy, 45% (52/115) had a relapse at a median of 28 months’ follow-up, with a 1-year relapse rate of 43.9%.^[97]Risk factors for relapse included male sex, leukocyte count greater than 6.0 × 10⁹/L, C-reactive protein level of 5.0 mg/L or greater, and a fecal calprotectin level of 300 µg/g or more. Re-treatment with infliximab was successful in 88% of patients who had a relapse.^[97]

Infliximab is also indicated for the treatment of fistulizing Crohn disease. For this indication, the fistula responds (closes) in 68% of patients treated with infliximab, although 12% may develop an abscess. The response can be maintained by continuing regular dosing (ie, every 8 weeks) after the induction dose.

Adverse effects of infliximab

The adverse effects of infliximab are uncommon but can include hypersensitivity and flulike symptoms; the latter can often be avoided by pretreatment with acetaminophen and diphenhydramine. There have been rare reports of lupus-like reactions and lymphoproliferative malignancies, although whether the malignancies are related to the drug or to the underlying disease process remains uncertain; they are more likely to be due to the concomitant use of immunomodulators.

Adalimumab, certolizumab, golimumab

Other anti-TNF agents include adalimumab (Humira), which is given by subcutaneous (SC) injection every 2 weeks after a loading dose of 6 injections over 4 weeks^[98]; certolizumab pegol (Cimzia), which is given by SC injection every 4 weeks (only approved for Crohn diesase); and golimumab (Simponi), which is given by subcutaneous (SC) injection every 4 weeks after two loading doses (only approved for ulcerative colitis).

Natalizumab

Natalizumab (Tysabri), an agent aimed at preventing the accumulation of lymphocytes in the diseased bowel by blocking the effects of both α4β7 integrin (gut specific) and α4β1 integrin (CNS specific), has been approved by the FDA, but it is only available through a restricted distribution program. Natalizumab is an intravenous medication that has shown efficacy in Crohn disease, but there have been 3 reports of progressive multifocal leukoencephalopathy, a potentially fatal opportunistic viral infection. Risk is typically apparent in those with prior immunosuppressant exposure or with a duration of infusion for longer than 2 years.^[99]

Vedolizumab

Vedolizumab (Entyvio), another integrin antagonist, is approved for Crohn disease and ulcerative colitis.^[100]It is specific for α4β7 integrin. Approval was based on several phase 3 clinical trials that simultaneously evaluated vedolizumab for both ulcerative colitis and Crohn disease and involved patients in nearly 40 countries. Among patients with Crohn disease who had a response to induction therapy with vedolizumab, 39.0% of those assigned to vedolizumab every 8 weeks were in clinical remission at week 52, compared with 21.6% assigned to placebo.

In patients with ulcerative colitis who had a response to vedolizumab induction, 41.8% continued to be in clinical remission at 52 weeks compared with 15.9% of patient taking placebo.

References

Inpatient Management

Patients should be admitted to the hospital if surgical intervention is anticipated or if their condition does not respond to outpatient treatment, if they are dehydrated, or if they have uncontrolled pain or diarrhea. Start IV hydration. If indicated, obtain an abdominal flat-plate image to exclude obstruction or megacolon. If the patient is nauseous or vomiting or has evidence of obstruction or megacolon, nasogastric intubation may be helpful. Consider early consultation with a surgeon in the setting of severe colitis or bowel obstruction.

If the patient has active colitis, send a stool sample for Clostridium difficile toxin assay and routine microbiologic culture. Laboratory studies to be considered include a complete blood cell (CBC) count with differential; erythrocyte sedimentation rate; levels of albumin, glucose, calcium, magnesium, phosphate, and BUN/creatinine; electrolyte status; and a pregnancy test in females of childbearing age.

Patients with acute severe colitis are treated with IV corticosteroids. Antibiotics are not routinely used but may be indicated in select patients. Electrolyte correction and, potentially, blood transfusion can be administered if indicated on the basis of laboratory findings. The IBD Sydney Organisation and the Australian Inflammatory Bowel Diseases Consensus Working Group recommendations include the following for patients with acute severe ulcerative colitis^[101]:

Hospitalization
Unprepared flexible sigmoidoscopy to assess severity and exclude cytomegalovirus colitis
Intravenous thromboembolism prophylaxis
IV hydrocortisone 100 mg tid/qid and close monitoring
If insufficient response by day 3, initiate rescue therapy with infliximab or cyclosporine
If no response by day 7 of rescue therapy or if clinical deterioration occurs, consider colectomy

Author information

Patients with suspected bowel obstruction should be given nothing by mouth (NPO), except for medications. Most patients with ulcerative colitis may maintain a regular (or low-fiber) diet, unless megacolon is present or surgery is being contemplated.

Although a colonoscopic evaluation may also be contemplated, consider the increased risk of perforation in persons with acute colitis. Assess and correct the posthydration CBC count and electrolyte levels, as indicated. Depending on the response to the initial interventions, advancement of the diet may be considered.

By the second or third hospital day, most patients should be showing clear evidence of clinical improvement with IV steroids. Assess the electrolyte status if IV fluids are still being administered. Consider advancement of the diet. The corticosteroid dose can be tapered. If the patient is not improving, consider other treatment options; these may include hyperalimentation, other medical therapies, surgical intervention, or transfer to a tertiary care facility.

Continue to advance the diet, as tolerated, on hospital day 4. Continue the switch to oral medications. Many patients with a flare of Crohn disease or ulcerative colitis may be discharged by this time (occasionally even sooner); some may require another day of IV therapy.

If no progress has been made in the patient's condition since admission, additional treatments are necessary, including surgery (see Surgical Intervention, below) or more aggressive medical treatments. Again, consider transfer to a tertiary care facility. If the patient has been unable to tolerate an oral diet, initiate hyperalimentation and/or reconsider surgical intervention.

Most patients should be able to be discharged on or before the fifth hospital day. A regular diet should be tolerated, with some restrictions if strictures are present. An ESR level may be obtained to assist in future disease assessment, but its result is unlikely to alter current management.

Discharge the patient on oral medications, with appropriate follow-up as an outpatient, typically within a few weeks.

References

Surgical Intervention

Ulcerative colitis is a surgically curable disease. However, Crohn disease can involve any segment of the gastrointestinal tract from the mouth to the anus; surgical resection is not curative, as recurrence is the norm. In addition, repeated need for surgery and bowel resection may result in short gut syndrome and dependence on parenteral nutrition.

Ulcerative colitis

Consider surgical intervention for patients in whom medical therapy fails, as it is curative for colonic disease, and for those with colonic dysplasia or malignancy.^[3]Approximately 25%-30% of patients may require operative management.^[1]The indications for colectomy are the following:

Intractable inflammation
Precancerous changes (high-grade dysplasia or proven multicentric, low-grade dysplasia confirmed by 2 expert pathologists)
Intolerance to medical therapy
Toxic megacolon
Perforation

The surgical options for ulcerative colitis vary. Currently, the 2 most common choices are proctocolectomy with ileostomy and total proctocolectomy with ileoanal anastomosis.

The most common operation performed to treat ulcerative colitis is ileal pouch/anal anastomosis (IPAA). In this multistage procedure, a diverting ileostomy is performed and an ileal pouch is created and anastomosed directly to the anus, with complete removal of the rectal mucosa. After the ileoanal anastomosis is healed, the ileostomy is taken down, and flow through the anus is reestablished.

The major complication of this procedure is postoperative development of acute or chronic pouchitis. Very rarely, particularly in those with a preoperative diagnosis of indeterminate colitis, Crohn disease of the pouch may develop. IPAA offers an excellent option for younger patients with ulcerative colitis and those with concerns with body image. However, IPAA is also associated with a substantial rate of infertility (due to pelvic dissection).

Elective surgery can sometimes be performed laparoscopically. For fulminant colitis, the surgical procedure of choice consists of a subtotal colectomy with end ileostomy and creation of a Hartmann pouch.

A population-based study by de Silva et al showed that the primary predictors of severe postoperative complications are age and multiple comorbidities. Furthermore, the worst outcomes occurred when surgery was performed 14 or more days after hospital admission under emergency conditions in patients who had no response to medical treatment.^[106]

For patients who plan to become pregnant, a subtotal colectomy is preferred to avoid the 48% decrease in fecundity with the IPAA procedure.

Crohn disease

Surgery for Crohn disease is most commonly performed in patients with complications of the disease (ie, strictures, fistulas). Approximately 70% of patients with ileocolonic Crohn disease require surgical intervention.^[1] In general, conservative resection is advocated (including potential stricturoplasty, as opposed to resective surgery) to preserve bowel length in case additional surgery is needed in the future.^[4]

Although surgery is an important treatment option for Crohn disease, patients should be aware that it is not curative and that disease recurrence after surgery is the rule. Disease recurrence generally mimics the original disease pattern at the surgical anastomosis. Endoscopic evidence of recurrent inflammation is present in 93% of patients 1 year after surgery.

In segmental resection, a segment of intestine with active Crohn disease or a stricture is resected, and the remaining bowel is reanastomosed. In general, as little bowel as possible is resected, because the risk of disease recurrence is significant.^[107]

In patients with a very short cicatrix stricture, a bowel-sparing stricturoplasty can be performed. In this procedure, a longitudinal incision is made across the stricture, and then the incision is repaired with a horizontal suture. All mucosa is spared, and the obstruction is relieved. As many as 6-8 stricturoplasties can be performed in a single operative session.

Stricturoplasty is associated with a 6%-8% rate of septic complications (2%-3% of patients require reoperation); this may be prevented with optimal preoperative management to control the inflammatory component of the stricture before surgical intervention.

Ileorectal or ileocolonic anastomosis is an option available to some patients who have distal ileal or proximal colonic disease. In patients with severe perianal fistulas, a diverting ileostomy or colostomy is an option. In this procedure, the distal colon is defunctionalized and a temporary ileostomy or colostomy is created. The ileostomy or colostomy is then taken down after 6 months or longer. Many patients who pursue this option choose to forego reanastomosis after placement of a stoma and a consequent improvement in quality of life. Approximately 50% of patients who have the reanastomosis performed have recurrences of perianal disease.

Symptomatic enteroenteric fistulas are generally resected, although recurrence is common. Postoperative medical therapy often prevents recurrence, although data are lacking regarding efficacy. A meta-analysis of 9 randomized trials suggested that 5-ASA preparations provide a very modest benefit for maintenance.^[85]The preferred program of prevention varies between immunomodulators and biologic therapy.

Contraception in the perioperative setting

Before undergoing major elective surgery, women with IBD should stop using combined oral contraception for a minimum of 4 weeks before the surgery, and alternative methods of contraception should be used.^[108]Advise each patient when oral contraception can be restarted.

If a woman with IBD is considering sterilization, counsel her and her partner regarding alternative contraceptive methods (eg, long-acting reversible contraception, vasectomy). Note that in women with a history of pelvic or abdominal surgery, laparoscopic sterilization may not be considered an appropriate contraceptive method.^[108]

Tapering corticosteroids in the postoperative setting

If possible, the use of corticosteroids should be minimized before surgery. Poor postoperative outcomes have been associated with prednisone doses greater than 30 mg/day.^[1]

The World Gastroenterology Organization (WGO) recommendations for tapering corticosteroids depend on the duration of corticosteroid use, as follows^[1]:

Less than 1 month: abrupt cessation postoperatively is allowed
1-3 months, with a dose of 20 mg/day or greater: taper by 5 mg/day per week after surgery
3-6 months: taper by 2.5 mg/day per week
More than 6 months: taper slowly, at 1 mg/wk or less once the dose is 10 mg/day

References

Diet, Lifestyle Modifications, and Activity

No known dietary or lifestyle changes prevent inflammatory bowel disease (IBD), and no known dietary substances have been consistently shown to cause activation of IBD. Tobacco use has been linked to increases in the number and severity of flares of Crohn disease, and smoking cessation can help achieve remission in patients with Crohn disease. Lactose intolerance is common in persons with Crohn disease or ulcerative colitis and can mimic symptoms of IBD.

Diet

Although diet has been well demonstrated to have little or no influence on inflammatory activity in persons with ulcerative colitis, it may influence symptoms. For this reason, patients are often advised to make a variety of dietary modifications, especially adaptation of a low-residue diet, although the evidence does not support a low-residue diet as beneficial in the treatment of ulcerative colitis. Such a diet, however, might decrease the frequency of bowel movements.

Unlike in patients with ulcerative colitis, diet can influence inflammatory activity in persons with Crohn disease. Nothing by mouth (NPO) can hasten the reduction of inflammation, as may the use of a liquid or predigested formula for enteral feeding. Although a meta-analysis in 1995 demonstrated that steroids were superior to liquid diet alone for Crohn disease, a liquid diet seemed superior to a regular diet for reducing inflammation. The problem with using enteral liquid diets, especially the predigested formulations, is that palatability limits the intake of adequate energy (calories) to meet patient requirements. Parenteral alimentation may be needed.

In a prospective study of 56 patients with quiescent Crohn disease on maintenance infliximab therapy (5 mg/kg, q 8 wk), Yamamoto et al found that concomitant enteral nutrition did not significantly improve the maintenance rate of clinical remission in patients with Crohn disease.^[109]In the study, 32 patients received concomitant enteral nutrition (elemental diet infusion at night; a low-fat diet during the day), and 24 patients did not receive enteral nutrition and had no dietary restrictions.^[109]

Multivitamin supplementation is recommended in patients with IBD.^[1]For patients with vitamins B12 or vitamin D deficiency, supplementation of these vitamins should be given. The results of 2 studies suggest that the link between vitamin D and IBD may be of particular importance.^{[110, 111, 112]}

In one of the studies, 3217 patients with Crohn disease or ulcerative colitis and low vitamin D levels had an increased risk of surgery and hospitalization.^[111]Crohn disease patients with 25-hydroxyvitamin D levels lower than 20 ng/ml had an increased risk of surgery and IBD-related hospitalization than those with levels higher than 30 ng/ml. Similar estimates were seen for ulcerative colitis. In the other study, Crohn disease patients who took 2000 IU of vitamin D daily for 3 months gained muscle strength and improved quality of life.^[112]

Patients receiving steroid therapy should receive vitamin D and calcium supplementation. Parenteral iron (IM weekly or IV) may be used in patients with chronic iron-deficiency anemia who are unable to tolerate the oral formulation.^[1]

Activity

Generally, patients do not need to limit activity when IBD is quiescent. During disease flares, physical activity is limited only by the extent of fatigue and the abdominal pain or diarrhea the patient is experiencing. When abdominal pain persists beyond medical therapy-induced resolution of the active inflammation, other causes of pain must be considered, including abscess, stricture, nephrolithiasis, IBS, and psychiatric disease.

In most instances, diarrhea limits activity primarily because of the lack of immediate access to toilet facilities in many locations and/or occupations. Dehydration may be an issue, often requiring IV hydration or the use of oral rehydration solutions.

Moderate to vigorous physical activity for as long as 12 weeks has been shown to improve symptom scores and many specific quality-of-life dimensions, including energy, sleep, emotion, and physical functioning.^[113]This degree of activity was defined as 20-60 minutes of intense exercise 3-5 days per week. The improvements occur despite lack of change in body weight, oral-anal transit time, bowel movements per week, or stool consistency. This study also highlights that symptomatic deterioration is more likely in physically inactive individuals.

References

Reproduction and Pregnancy

Clinicians are advised to review the prescribing information for medications in women who are attempting to conceive, are pregnant, or are breastfeeding.^[108]All of the aminosalicylates (sulfasalazine, mesalamine, olsalazine, balsalazide) and corticosteroids appear to be safe in women in all phases of fertility, pregnancy, and lactation. Men should avoid sulfasalazine during periods when they and their mates are attempting to become pregnant.

Reproduction

In women with IBD, fertility is normal or only minimally impaired. The majority of case reports and small series show no adverse outcomes of pregnancies in patients with IBD who are taking immune modifiers. Birth defects have not been reported at a rate higher than that of the general population. If a patient is taking an immune modifier and becomes pregnant, current data support the consensus that continuing the immune modifier throughout the pregnancy is the safest course of action for both the mother and the fetus.^[114]

The only agent that is contraindicated in women considering pregnancy is methotrexate (MTX), which has demonstrated teratogenic effects. MTX should be discontinued 3 months prior to planned conception.

For men with IBD, sulfasalazine can decrease sperm counts and sperm motility, causing a functional azoospermia; the other aminosalicylates do not have this effect. The sperm effects are reversible by discontinuing the sulfasalazine. No firm evidence indicates that the use of immune modifiers in the father leads to increased birth defects, although this has been suggested in one Spanish study.

Pregnancy

Most infants born to parents with IBD are healthy. The prevalence of prematurity, stillbirth, and birth defects is similar to that in the general population. The prevalence of spontaneous abortion is slightly higher in patients with IBD (12.2%) than in the general population (9.9%). Previous proctocolectomy or ileostomy is not an impediment to successful pregnancy; however, controversy exists regarding the type of delivery (cesarean or vaginal) that is most appropriate when a woman has had ileal pouch/anal anastomosis surgery.^[108]Women who have undergone such a procedure should consult with their obstetricians and gastroenterologists.^[108]

The aminosalicylates, including sulfasalazine, are safe during pregnancy. Folate supplements should be taken. Corticosteroids are also safe, but if high doses are needed near the end of the pregnancy, monitor the infant for signs of adrenal suppression. Continuation of immune modifiers (ie, 6-MP, azathioprine) appears to be safe in pregnancy,^{[105, 115]}as well as metronidazole (Flagyl) and ciprofloxacin (Cipro).

It is considered safe to continue TNF-alpha inhibitors during pregnancy (FDA category B), but concerns have been raised about high levels of maternally administered anti-TNF agents being found in the fetal circulation.^{[116, 117, 118, 119]}The manufacturers of infliximab and adalimumab recommend that these 2 agents be discontinued during the third trimester of pregnancy, although there is no documentation of fetal harm. Certolizumab does not cross the placenta.^{[116, 117, 118, 119]}

In a retrospective, multicenter study, treatment of IBD with thiopurines and anti-TNF-alpha drugs did not increase the risk of complications during pregnancy or neonatal complications.^[120]The rate of unfavorable Global Pregnancy Outcome and the rate of neonatal complications were lower in pregnant women treated with thiopurines alone than in those exposed to anti-TNF-alpha drugs or those not exposed to either group of agents.

Effective contraception must be used with certain drug therapy.^[108]Both male and female partners receiving methotrexate should use effective contraception for a minimum of 3 months following treatment with this agent.

Other concerns that have been raised include the potential reduction of fertility with total abdominal colectomy with ileal pouch/anal anastomosis (IPAA) surgery (primarily because of adhesions).^{[121, 122]}This possibility can likely be avoided by using a laparoscopic approach, and if infertility occurs, fertility can often be normalized by lysis of adhesions.

According to the Faculty of Sexual and Reproductive Healthcare Clinical Effectiveness Unit in the United Kingdom, women with IBD should plan for conception when their disease is stable and well controlled.^[108]Male and female patients require prepregnancy counseling to help them with the best management of their condition before conception occurs.^[108]

Contraception precautions

Advise women who have Crohn disease with small bowel disease and malabsorption that oral contraception may have reduced effectiveness.^[108]Additional contraception is recommended for women on combined hormonal contraception who are also receiving antibiotic regimens for less than 3 weeks, as well as for 7 weeks following cessation of the antibiotic. Note that certain medications prescribed for rectal or genital use may adversely affect the efficacy of condoms.^[108]In addition, consider whether contraceptive agents may have an effect on diseases associated with IBD (eg, osteoporosis, venous thromboembolism, primary sclerosing cholangitis).

In women with IBD who will undergo major elective surgery, combined oral contraception should be discontinued for a minimum of 4 weeks before the procedure.^[108]These women should use alternative contraception.

Breastfeeding

Sulfasalazine metabolites can be detected in the breast milk. Low concentrations of mesalamine and higher concentrations of its metabolites can also be detected in breast milk, but the significance of this is unknown. In addition, corticosteroids can also be detected in breast milk.

Immune modifiers are excreted in breast milk and should be considered only on a case-by-case basis; either the immune modifier should be discontinued or the infant should be bottle fed.

Antibiotics (metronidazole [Flagyl], ciprofloxacin [Cipro]) should generally be avoided during lactation, because they are excreted in breast milk; either breastfeeding or the drugs should be discontinued. These agents are probably safe for fertility and during pregnancy.

Anti-TNF agents (ie, infliximab, adalimumab) traverse the placenta, whereas certolizumab does not, because of the absence of the Fc fragment. They are found in the cord blood but not in breast milk.

Although small amounts of the topical agents are absorbed and thus may be excreted in breast milk, the concentrations are much lower than those with the oral forms of the same medications. These medications are probably reasonably safe in breastfeeding.

References

What is inflammatory bowel disease (IBD)?What are the symptoms of inflammatory bowel disease (IBD)?Which symptoms of inflammatory bowel disease (IBD) may be associated with inflammatory damage of the digestive tract?Which physical findings are related to the severity of inflammatory bowel disease (IBD)?What is the role of lab testing in the diagnosis and management of inflammatory bowel disease (IBD)?What is the role of imaging in the evaluation of inflammatory bowel disease (IBD)?What is the medical approach to treatment of inflammatory bowel disease (IBD)?Which medications are used in the treatment of inflammatory bowel disease (IBD)?What is the role of surgery in the management of inflammatory bowel disease (IBD)?What are the surgical options for treatment of inflammatory bowel disease (IBD)?What is inflammatory bowel disease (IBD)?What is the overlap in extraintestinal symptoms of ulcerative colitis (UC) and Crohn disease (CD)?What is the role of inflammation in the manifestation of inflammatory bowel disease (IBD)?When is surgical intervention curative for inflammatory bowel disease (IBD)?What is the pathophysiology of Crohn disease (CD)?What is the role of genetics in the pathogenesis of inflammatory bowel disease (IBD)?What is the role of inflammatory mediators in the pathogenesis of inflammatory bowel disease (IBD)?How is inflammatory bowel disease (IBD) studied in animals?How do the characteristics of inflammation vary between ulcerative colitis (UC) and Crohn disease?What is the pathophysiology of ulcerative colitis (UC)?How is the rectum involvement in Crohn disease (CD)?Why is the incidence of gallstones and kidney stones increased in Crohn disease (CD)?Which characteristics define the etiology of inflammatory bowel disease (IBD)?What is the primary cause of inflammatory bowel disease (IBD)?What are the environmental risk factors of inflammatory bowel disease (IBD)?What are the genic risks of inflammatory bowel disease (IBD)?Which genes are associated with inflammatory bowel disease (IBD)?Which genetic loci are involved in the etiology of Crohn disease (CD)?What is the role of the interlectin gene (ITLN1) in the etiology of Crohn disease (CD)?What is the role of single nucleotide polymorphisms in the etiology of inflammatory bowel disease (IBD)?Where are inflammatory bowel disease (IBD)-susceptibility genes?What is the genetic predisposition for ulcerative colitis (UC)?Where have susceptibility genetic loci been found for ulcerative colitis (UC)?How much do genetic influences increase the risk for ulcerative colitis (UC)?What is the role of smoking in the etiology of inflammatory bowel disease (IBD)?How does the incidence of ulcerative colitis compare to Crohn disease?What is the prevalence of inflammatory bowel disease (IBD) in the US?What are the racial predilections for inflammatory bowel disease (IBD) in the US?How does the prevalence of inflammatory bowel disease (IBD) vary by sex?How does the incidence of inflammatory bowel disease (IBD) vary by age?What is the global prevalence of inflammatory bowel disease (IBD)?What are the extraintestinal complications of inflammatory bowel disease (IBD)?What is the mortality rate for inflammatory bowel disease (IBD)?What is the likelihood of malignancy in patients with inflammatory bowel disease (IBD)?Where can more information on malignancy in inflammatory bowel disease (IBD) be found?What are the morbidities associated with inflammatory bowel disease (IBD)?What is the incidence of inflammatory bowel disease (IBD) in patients with asthma or COPD?What are the risk factors for psychologic morbidity in inflammatory bowel disease (IBD)?What is the recurrence rate of ulcerative colitis (UC)?What is the probability of progression of ulcerative colitis (UC)?What treatment is considered curative for ulcerative colitis (UC)?What is the risk of colorectal cancer in patients with ulcerative colitis (UC)?What is the clinical course of Crohn disease (CD)?What is the rate of remission in patients with Crohn disease (CD)?When is surgery indicated for Crohn disease (CD)?What is the likelihood of recurrence of perianal fistulas in Crohn disease (CD)?What is the quality of life in patients with Crohn disease (CD) compared to those with ulcerative colitis?What are the intestinal complications of inflammatory bowel disease (IBD)?What are the rates of the most common extraintestinal complications inflammatory bowel disease (IBD)?What are the extraintestinal complications of inflammatory bowel disease (IBD) in Swiss patients?What are the benefits of patient education about inflammatory bowel disease (IBD)?What is the Crohn's & Colitis Foundation of America and how can it assist patients with inflammatory bowel disease (IBD)?What are the clinical manifestations of inflammatory bowel disease (IBD)?What are the systemic symptoms associated with inflammatory bowel disease (IBD)?How are symptoms of inflammatory bowel disease (IBD) associated with inflammatory damage?What are the physical findings characteristic of inflammatory bowel disease (IBD)?What are the physical findings characteristic of Crohn disease (CD)?What should be included in the physical exam of patients with inflammatory bowel disease (IBD)?What is the involvement of the small intestine in inflammatory bowel disease (IBD)?Why should eating disorders be included in the differential diagnoses of inflammatory bowel disease (IBD)?Why are so many conditions included in the differential diagnoses of inflammatory bowel disease (IBD)?When is Crohn disease (CD) frequently diagnosed?Which conditions should be included in the differential diagnoses of inflammatory bowel disease (IBD) when diarrhea is a dominant symptom?Which conditions should be included in the differential diagnoses of inflammatory bowel disease (IBD) when abdominal pain, GI bleeding, and/or intestinal ulceration are predominant symptoms?What are the differential diagnoses for Inflammatory Bowel Disease?What is the role of lab studies in the evaluation of inflammatory bowel disease (IBD)?What tests should be included in the evaluation of inflammatory bowel disease (IBD) in patients who are immunosuppressed or from developing countries?What is the role of CBC count in the diagnosis of inflammatory bowel disease (IBD)?What is the diagnostic significance of anemia in the evaluation of inflammatory bowel disease (IBD)?What is the diagnostic significance of vitamin B12 deficiency in the evaluation of inflammatory bowel disease (IBD)?What is the role of serum iron studies in the evaluation of inflammatory bowel disease (IBD)?When are folate supplements indicated in the management of inflammatory bowel disease (IBD)?How is nutritional status assessed in patients with inflammatory bowel disease (IBD)?What is the role of the erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) levels in the diagnosis of inflammatory bowel disease (IBD)?What is the role of fecal calprotectin levels in the diagnosis of inflammatory bowel disease (IBD)?What is the role of perinuclear antineutrophil cytoplasmic antibodies (pANCA) in the diagnosis of inflammatory bowel disease (IBD)?What is the diagnostic significance of positive perinuclear antineutrophil cytoplasmic antibodies (pANCA) results in the evaluation of inflammatory bowel disease (IBD)?What is the significance of a greater number of positive anti-Saccharomyces cerevisiae antibodies (ASCA) in the evaluation of inflammatory bowel disease (IBD)?What is the role of stool culture in the diagnosis of inflammatory bowel disease (IBD)?When is the assessment of cytomegalovirus colitis indicated in the evaluation of inflammatory bowel disease (IBD)?What is the most common cause of acute terminal ileitis in inflammatory bowel disease (IBD)?What is the role of radiography in the diagnosis of inflammatory bowel disease (IBD)?What is toxic megacolon in inflammatory bowel disease (IBD)?What is the role of barium enema imaging for the diagnosis of inflammatory bowel disease (IBD)?How are abnormalities of inflammatory bowel disease (IBD) described on barium studies?What are findings of barium enema suggestive of inflammatory bowel disease (IBD)?What radiographs findings are characteristic of inflammatory bowel disease (IBD)?What are findings of a small bowel radiography series characteristic of inflammatory bowel disease (IBD)?Why must independent confirmation of the diagnosis of inflammatory bowel disease (IBD) be sought after barium enema?When is a small bowel radiography series used for the diagnosis of inflammatory bowel disease (IBD)?What is the role of small bowel enteroclysis in the diagnosis of inflammatory bowel disease (IBD)?What is the role of fistulographic studies in the diagnosis of inflammatory bowel disease (IBD)?What is the role of ultrasonography in the diagnosis of inflammatory bowel disease (IBD)?What is the role of CT scanning in the diagnosis of inflammatory bowel disease (IBD)?When is CT scanning used in the diagnosis of inflammatory bowel disease (IBD)?What is the role of MRI in the diagnosis of inflammatory bowel disease (IBD)?What is the role of CT enterography in the diagnosis of inflammatory bowel disease (IBD)?What is the role of a colonoscopy in the diagnosis of inflammatory bowel disease (IBD)?What are the colonoscopy or sigmoidoscopy findings characteristic of inflammatory bowel disease (IBD)?What is the accuracy of a colonoscopy with ileoscopy in the assessment of Crohn disease (CD)?What is the role of colonoscopy in the treatment of inflammatory bowel disease (IBD)?What are the complications associated with endoscopic procedures for the evaluation of inflammatory bowel disease (IBD)?What is the role of colonoscopy in the surveillance of inflammatory bowel disease (IBD)?What is the role of flexible sigmoidoscopy in the diagnosis of inflammatory bowel disease (IBD)?What is the role of esophagogastroduodenoscopy (EGD) in the diagnosis of inflammatory bowel disease (IBD)?How is capsule enteroscopy used for the diagnosis of inflammatory bowel disease (IBD)?What is the major risk associated with enteroscopy for the diagnosis of inflammatory bowel disease (IBD)?What is double balloon enteroscopy and how is it used in the diagnosis of inflammatory bowel disease (IBD)?Where is inflammation seen in ulcerative colitis (UC)?What are the histologic characteristics of ulcerative colitis (UC)?What is involved in the inflammation of the colon in inflammatory bowel disease (IBD)?What are the typical histologic findings of ulcerative colitis (UC)?What is the histology of Crohn disease (CD)?What are the histologic findings characteristic of Crohn disease (CD)?What are the goals of therapy for inflammatory bowel disease (IBD)?What are the treatment options for inflammatory bowel disease (IBD)?What are the benefits of deep mucosal healing in the treatment of inflammatory bowel disease (IBD)?What is included in the symptomatic therapy of inflammatory bowel disease (IBD)?How should corticosteroid therapy for inflammatory bowel disease (IBD) flares be administered?When are immunomodulators and biologic agents indicated in the treatment of inflammatory bowel disease (IBD)?What are the treatment options for low bone density in inflammatory bowel disease (IBD)?What is the best approach for the treatment of mild to moderate inflammatory bowel disease (IBD?)What is the first step in medication therapy for inflammatory bowel disease (IBD)?What is the second step in medication therapy for inflammatory bowel disease (IBD)?When are immune modifying agents indicated in the treatment of inflammatory bowel disease (IBD)?When is a step-down approach used in the treatment of inflammatory bowel disease (IBD)?Why is weaning off steroid therapy a priority in the treatment of inflammatory bowel disease (IBD)?What are the oral aminosalicylates used in the US for the treatment of inflammatory bowel disease (IBD)?What is the role of oral aminosalicylates in the treatment of inflammatory bowel disease (IBD)?Which probiotic agents are used in the diagnosis of inflammatory bowel disease (IBD)?What are the most commonly used antibiotics in the treatment of inflammatory bowel disease (IBD)?What is the role of antibiotics in the treatment of inflammatory bowel disease (IBD)?What are the potential adverse effects of antibiotics in the treatment of inflammatory bowel disease (IBD)?When are corticosteroids indicated for treatment of inflammatory bowel disease (IBD)?How are corticosteroids administered for the treatment of inflammatory bowel disease (IBD)?What are the potential complications of corticosteroid in the treatment of inflammatory bowel disease (IBD)?When should patients be weaned off of corticosteroid therapy for inflammatory bowel disease (IBD)?What are the risks of long-term use of corticosteroids for the treatment of inflammatory bowel disease (IBD)?How often should bone mineral density be assessed in patients with inflammatory bowel disease (IBD)?What is the role of IV corticosteroids in the treatment of inflammatory bowel disease (IBD)?What is the optimal dosing of oral corticosteroids for the treatment of inflammatory bowel disease (IBD)?What is the role of budesonide in the treatment of inflammatory bowel disease (IBD)?What is the role of topical corticosteroids in the treatment of inflammatory bowel disease (IBD)?When are corticosteroid suppositories indicated the treatment of inflammatory bowel disease (IBD)?What is the effectiveness of immune modifiers in the treatment of inflammatory bowel disease (IBD)?What is the role of 6-mercaptopurine (6-MP) and azathioprine (AZA) in the treatment of inflammatory bowel disease (IBD)?What is the role of intramuscular MTX in the treatment of inflammatory bowel disease (IBD)?What are the American Gastroenterological Association (AGA) recommendations for the use of 6-mercaptopurine (6-MP) and azathioprine (AZA) in the treatment of inflammatory bowel disease (IBD)?What are possible hematologic adverse effects of immune modifiers for the treatment of inflammatory bowel disease (IBD)?What monitoring is needed during immune modifier therapy for inflammatory bowel disease (IBD)?What are possible adverse effects of immune modifiers for the treatment of inflammatory bowel disease (IBD)?What is the role of infliximab (Remicade) in the treatment of inflammatory bowel disease (IBD)?What is the effectiveness of anti-TNF-alpha agents for the treatment of inflammatory bowel disease (IBD)?Which patients are most likely to benefit for anti-TNF-alpha monoclonal antibodies for the treatment of inflammatory bowel disease (IBD)?What are the risk factors for relapse of inflammatory bowel disease (IBD) following cessation of infliximab therapy?What is the role of infliximab in the treatment Crohn disease fistula?What are the adverse effects of infliximab for the treatment of inflammatory bowel disease (IBD)?Which anti-TNF-alpha agents are used in the treatment of inflammatory bowel disease (IBD)?What is the role of natalizumab in the treatment of inflammatory bowel disease (IBD)?What is the role of vedolizumab in the treatment of inflammatory bowel disease (IBD)?Which experimental agents have shown efficacy in the treatment of inflammatory bowel disease (IBD)?When is inpatient treatment indicated for inflammatory bowel disease (IBD)?How is suspected bowel obstruction managed in inflammatory bowel disease (IBD)?What needs to be considered prior to performing a colonoscopic evaluation in hospitalized patients with inflammatory bowel disease (IBD)?Which treatment modifications are made upon clinical improvement of hospitalized patients with inflammatory bowel disease (IBD?)What treatments should be considered for hospitalized patients with inflammatory bowel disease (IBD) who have not progressed with initial therapy?What are the discharge requirements for patients with inflammatory bowel disease (IBD)?When should step-down therapy be considered in the management of inflammatory bowel disease (IBD)?What are the treatment options for refractory inflammatory bowel disease (IBD)?What is the role of monoclonal antibodies in the treatment of refractory inflammatory bowel disease (IBD)?How does smoking cessation affect patients with inflammatory bowel disease (IBD)?What is included in the top-down approach to the treatment of inflammatory bowel disease (IBD)?What are common comorbidities in older patients with inflammatory bowel disease (IBD)?How are adverse medication interactions managed in older patients with inflammatory bowel disease (IBD)?Which drugs commonly used to treat cardiovascular and rheumatologic disorders may trigger inflammatory bowel disease (IBD) flares?When are anti-TNF agents contraindicated in the treatment of inflammatory bowel disease (IBD)?What is the role of surgery in the treatment of inflammatory bowel disease (IBD)?When is colectomy indicated in the treatment of inflammatory bowel disease (IBD)?What are the most common surgical options for the treatment of inflammatory bowel disease (IBD)?What is the role of ileal pouch/anal anastomosis (IPAA) in the treatment of inflammatory bowel disease (IBD)?What is the major complication of the ileal pouch/anal anastomosis (IPAA) in the treatment of inflammatory bowel disease (IBD)?What are the surgical options for fulminant colitis in inflammatory bowel disease (IBD)?What are risk factors for postoperative complications in inflammatory bowel disease (IBD)?What are the surgical options for patients with inflammatory bowel disease (IBD) who plan on becoming pregnant?What are the indications for surgical intervention in Crohn disease (CD)?What are the limitations to surgical treatment of Crohn disease (CD)?What is the role of segmental resection in the treatment of inflammatory bowel disease (IBD)?What is the role of bowel-sparing stricturoplasty in the treatment of inflammatory bowel disease (IBD)?What are the indications for ileostomy or colostomy in the treatment of inflammatory bowel disease (IBD)?How are symptomatic enteroenteric fistulas treated in inflammatory bowel disease (IBD)?What are contraception options for women with inflammatory bowel disease (IBD)?Which medications should be minimized prior to surgery for inflammatory bowel disease (IBD)?What are the World Gastroenterology Organization (WGO) recommendations for tapering corticosteroids prior to surgery for inflammatory bowel disease (IBD)?What is the role of dietary or lifestyle changes in the treatment of inflammatory bowel disease (IBD)?Which dietary modifications may be beneficial in the management of inflammatory bowel disease (IBD)?What is the role of vitamin supplementation in the management of inflammatory bowel disease (IBD)?What is the role of activity modification in the management of inflammatory bowel disease (IBD)?How is inflammatory bowel disease (IBD) managed during pregnancy?How is fertility affected in women with inflammatory bowel disease (IBD)?Which agent is contraindicated in women with inflammatory bowel disease (IBD) who are considering pregnancy?How does sulfasalazine affect the fertility of men with inflammatory bowel disease (IBD)?How does parental inflammatory bowel disease (IBD) affect infant health?Which treatments are considered safe for pregnant patients with inflammatory bowel disease (IBD)?When is effective contraception required during the treatment of inflammatory bowel disease (IBD)?What is the effect of abdominal colectomy with ileal pouch/anal anastomosis (IPAA) for inflammatory bowel disease (IBD) on fertility?When should women with inflammatory bowel disease (IBD) plan conception?What causes reduced effectiveness of oral contraceptives in women with inflammatory bowel disease (IBD)?Which agents used to treat inflammatory bowel disease (IBD) can be detected in breast milk?What are the options for infant feeding in women taking immune modifiers for inflammatory bowel disease (IBD)?Which antibiotics are contraindicated in breast-feeding women with inflammatory bowel disease (IBD)?Which anti-TNF agents are not found in the breast milk of women with inflammatory bowel disease (IBD)?What is the significance of topical agents excreted in breast milk of women with inflammatory bowel disease (IBD)?Which specialist consultations are needed for the diagnosis and treatment of inflammatory bowel disease (IBD)?Which experimental treatments hold promise in the treatment of inflammatory bowel disease (IBD)?What is the effectiveness of treatments for Crohn disease (CD)?What is the stepwise approach to treating inflammatory bowel disease (IBD)?Which medications in the drug class Anticholinergic, Antispasmodic Agents are used in the treatment of Inflammatory Bowel Disease?Which medications in the drug class Antidiarrheals are used in the treatment of Inflammatory Bowel Disease?Which medications in the drug class Proton Pump Inhibitors are used in the treatment of Inflammatory Bowel Disease?Which medications in the drug class Histamine H2 Antagonists are used in the treatment of Inflammatory Bowel Disease?Which medications in the drug class Alpha 4 Integrin Inhibitors are used in the treatment of Inflammatory Bowel Disease?Which medications in the drug class TNF Inhibitors are used in the treatment of Inflammatory Bowel Disease?Which medications in the drug class Immunosuppressants are used in the treatment of Inflammatory Bowel Disease?Which medications in the drug class Corticosteroids are used in the treatment of Inflammatory Bowel Disease?Which medications in the drug class Antibiotics, Other are used in the treatment of Inflammatory Bowel Disease?Which medications in the drug class 5-Aminosalicylic Acid Derivatives are used in the treatment of Inflammatory Bowel Disease?

References

Author

William A Rowe, MD, President, Gastroenterology Associates of Central Pennsylvania, PC; Manager, Endoscopy Center of Central Pennsylvania, LLC; Clinical Associate Professor of Surgery, Division of Colon and Rectal Surgery, Milton S Hershey Medical Center, Pennsylvania State University College of Medicine

Disclosure: Nothing to disclose.

Coauthor(s)

Gary R Lichtenstein, MD, Professor of Medicine, Director, Center for Inflammatory Bowel Disease, Department of Medicine, Division of Gastroenterology, Perelman School of Medicine at the University of Pennsylvania

Disclosure: Serve(d) as a director, officer, partner, employee, advisor, consultant or trustee for: Abbott Corp/Abbvie; Actavis; Alaven; CellCeutrix; Celgene; Ferring; Gilead; Hospira; Janssen Orthobiotech; Luitpold/American Regent; Pfizer Pharm; Prometheus Labs; Romark; Salix Pharma/Valeant; Santarus/Receptos/Celgene; Shire Pharma; Takeda; UCB<br/>Received research grant from: Salix Pharm/Valeant; Santarus/Receptos/Celgene; Shire Pharm; UCB<br/>Received author or editor honorarium or book royalty from for: Clinical Advances in Gastroenterology; Gastroenterology and Hepatology; Gastro-Hep Communications; Ironwood; Luitpold/American Regent; Merck; McMahon Publishing; Romark; SLACK Inc; Springer Science and Business Media; Up-To-Date.

Specialty Editors

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

Disclosure: Received salary from Medscape for employment. for: Medscape.

Chief Editor

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

Disclosure: Nothing to disclose.

Acknowledgements

Mounir Bashour, MD, CM, FRCS(C), PhD, FACS Assistant Professor of Ophthalmology, McGill University; Clinical Assistant Professor of Ophthalmology, Sherbrooke University; Medical Director, Cornea Laser and Lasik MD

Mounir Bashour, MD, CM, FRCS(C), PhD, FACS is a member of the following medical societies: American Academy of Ophthalmology, American Association for Pediatric Ophthalmology and Strabismus, American College of International Physicians, American College of Surgeons, American Medical Association, American Society of Cataract and Refractive Surgery, American Society of Mechanical Engineers, American Society of Ophthalmic Plastic and Reconstructive Surgery, Biomedical Engineering Society, Canadian Medical Association,Canadian Ophthalmological Society, Contact Lens Association of Ophthalmologists, International College of Surgeons US Section, Ontario Medical Association, Quebec Medical Association, and Royal College of Physicians and Surgeons of Canada

Disclosure: Nothing to disclose.

William K Chiang, MD Associate Professor, Department of Emergency Medicine, New York University School of Medicine; Chief of Service, Department of Emergency Medicine, Bellevue Hospital Center

William K Chiang, MD is a member of the following medical societies: American Academy of Clinical Toxicology, American College of Medical Toxicology, and Society for Academic Emergency Medicine

Disclosure: Nothing to disclose.

Andrew A Dahl, MD Director of Ophthalmology Teaching, Mid-Hudson Family Practice Institute, The Institute for Family Health; Assistant Professor of Surgery (Ophthalmology), New York College of Medicine

Andrew A Dahl, MD is a member of the following medical societies: Alpha Omega Alpha, American Academy of Ophthalmology, American College of Surgeons, American Medical Association, American Society of Cataract and Refractive Surgery, and Wilderness Medical Society

Disclosure: Nothing to disclose.

Steven C Dronen, MD, FAAEM Chair, Department of Emergency Medicine, LeConte Medical Center

Steven C Dronen, MD, FAAEM is a member of the following medical societies: American Academy of Emergency Medicine and Society for Academic Emergency Medicine

Disclosure: Nothing to disclose.

Eugene Hardin, MD, FAAEM, FACEP Former Chair and Associate Professor, Department of Emergency Medicine, Charles Drew University of Medicine and Science; Former Chair, Department of Emergency Medicine, Martin Luther King Jr/Drew Medical Center

Disclosure: Nothing to disclose.

Sarvotham Kini, MD Assistant Professor of Emergency Medicine, Emory University School of Medicine, Atlanta, GA

Sarvotham Kini, MD is a member of the following medical societies: American College of Emergency Physicians, American College of Surgeons, and South Carolina Medical Association

Disclosure: Nothing to disclose.

Alex J Mechaber, MD, FACP Senior Associate Dean for Undergraduate Medical Education, Associate Professor of Medicine, University of Miami Miller School of Medicine

Alex J Mechaber, MD, FACP is a member of the following medical societies: Alpha Omega Alpha, American College of Physicians-American Society of Internal Medicine, and Society of General Internal Medicine

Disclosure: Nothing to disclose.

Hampton Roy Sr, MD Associate Clinical Professor, Department of Ophthalmology, University of Arkansas for Medical Sciences

Hampton Roy Sr, MD is a member of the following medical societies: American Academy of Ophthalmology, American College of Surgeons, and Pan-American Association of Ophthalmology

Disclosure: Nothing to disclose.

William Shapiro, MD Consulting Staff, Department of Urgent Care and Emergency Medicine, Scripps Clinic and Research Foundation

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

Rajeev Vasudeva, MD, FACG Clinical Professor of Medicine, Consultants in Gastroenterology, University of South Carolina School of Medicine

Rajeev Vasudeva, MD, FACG is a member of the following medical societies: American College of Gastroenterology, American Gastroenterological Association, American Society for Gastrointestinal Endoscopy, Columbia Medical Society, South Carolina Gastroenterology Association, and South Carolina Medical Association

Disclosure: Pricara Honoraria Speaking and teaching; UCB Consulting fee Consulting

R Christopher Walton, MD Professor, Director of Uveitis and Ocular Inflammatory Disease Service, Department of Ophthalmology, Assistant Dean for Graduate Medical Education, University of Tennessee College of Medicine; Consulting Staff, Regional Medical Center, Memphis Veterans Affairs Medical Center, St Jude Children's Research Hospital

R Christopher Walton, MD is a member of the following medical societies: American Academy of Ophthalmology, American College of Healthcare Executives, American Uveitis Society, Association for Research in Vision and Ophthalmology, and Retina Society

Disclosure: Nothing to disclose.

Complication	Prevalence
Scleritis	18%
Anterior uveitis	17%
Gall stones (particularly in Crohn disease)	13%-34%
Inflammatory arthritis	10%-35%
Anemia	9%-74%
Aphthous stomatitis	4%-20%
Osteoporosis	2%-20%
Erythema nodosum	2%-20%
Source: Larson S, Bendtzen K, Nielsen OH. Extraintestinal manifestations of inflammatory bowel disease: epidemiology, diagnosis and management. Ann Med. 2010;42:97-114.

Complication	Crohn Disease	Ulcerative Colitis
Arthritis	33%	4%
Aphthous stomatitis	10%	4%
Uveitis	6%	3%
Erythema nodosum	6%	3%
Ankylosing spondylitis	6%	2%
Psoriasis	2%	1%
Pyoderma gangrenosum	2%	2%
Primary sclerosing cholangitis	1%	4%
Source: Vavricka SR, Brun L, Ballabeni P, et al. Frequency and risk factors for extraintestinal manifestations in the Swiss inflammatory bowel disease cohort. Am J Gastroenterol. 2011;106:110-9.

Inflammatory Bowel Disease

Practice Essentials

Severe colitis noted during colonoscopy in a patient with inflammatory bowel disease. The mucosa is grossly denuded, with active bleeding noted. The p....

Signs and symptoms

Diagnosis

Management

Background

Severe colitis noted during colonoscopy in a patient with inflammatory bowel disease. The mucosa is grossly denuded, with active bleeding noted. The p....

Stricture in the terminal ileum noted during colonoscopy in a patient with inflammatory bowel disease. This image depicts a narrowed segment visible u....

Distinguishing features of Crohn disease (CD) and ulcerative colitis (UC).

Pathophysiology

Ulcerative colitis

Inflamed colonic mucosa demonstrating pseudopolyps in a patient with ulcerative colitis.

Double-contrast barium enema study shows pseudopolyposis of the descending colon in a patient with ulcerative colitis.

Crohn disease

Cobblestone change of the mucosa of the terminal ileum in a patient with Crohn disease. Communicating fissures and crevices in the mucosa separate isl....

This computed tomography scan from a patient with terminal ileal Crohn disease shows an enteroenteral fistula (arrow) between loops of diseased small ....

Deep, fissuring ulcer in a patient with Crohn disease. Note the increase in submucosal inflammation and scattered lymphoid aggregates.

Etiology

Genetics

Smoking

Epidemiology

United States statistics

International statistics

Prognosis

Morbidity

Ulcerative colitis

Crohn disease

Complications of IBD disease

See Table

See Table

Patient Education

History

Physical Examination

Approach Considerations

Laboratory Studies

Hematologic tests

Serologic Studies

pANCA and ASCA tests

Stool Studies

Radiography

Upright chest and abdominal radiography

Plain abdominal radiograph of a patient with known ulcerative colitis who presented with an acute exacerbation of his symptoms. This image shows thumb....

Plain abdominal radiograph in a 26-year-old with a 10-year history of ulcerative colitis shows a long stricture/spasm of the ascending colon/cecum (<i....

Toxic megacolon. Courtesy of Dr. Pauline Chu.

Barium enema double-contrast radiographic studies

Double-contrast barium enema study shows pseudopolyposis of the descending colon in a patient with ulcerative colitis.

Double-contrast barium enema study demonstrates marked ulceration, inflammatory changes, and narrowing of the right colon in a patient with Crohn coli....

Plain abdominal radiograph of a patient with known ulcerative colitis who presented with an acute exacerbation of his symptoms. This image shows thumb....

Crohn disease involving the terminal ileum. Note the "string sign" in the right lower quadrant (viewer's left).

Toxic megacolon. Courtesy of Dr. Pauline Chu.

Enteroenteric fistula noted on small bowel series of x-ray films in a patient with inflammatory bowel disease. The narrow-appearing segments filled ou....

Cobblestoning in Crohn disease. Spot views of the terminal ileum from a small bowel follow-through study demonstrates linear longitudinal and transver....

Small Bowel Enteroclysis and Fistulography

Ultrasonography

CT Scanning and MRI

This computed tomography scan from a patient with terminal ileal Crohn disease shows an enteroenteral fistula (arrow) between loops of diseased small ....

A teenaged patient with Crohn disease underwent a contrast-enhanced upper gastrointestinal computed tomography study with small-bowel follow-through. ....

Computed tomography scan depicting Crohn disease in the fundus of the stomach.

CT enterography

Colonoscopy and Flexible Sigmoidoscopy

Colonoscopy

Severe colitis noted during colonoscopy in a patient with inflammatory bowel disease. The mucosa is grossly denuded, with active bleeding noted. The p....

Stricture in the terminal ileum noted during colonoscopy in a patient with inflammatory bowel disease. This image depicts a narrowed segment visible u....

Flexible sigmoidoscopy

Upper GI Endoscopy

Enteroscopy

Capsule enteroscopy

Double balloon enteroscopy

Histologic Findings

Ulcerative colitis

Chronic architectural changes in ulcerative colitis. Note the crypt branching and irregularity of size and shape, with an increase in chronic inflamma....

Low-power image of a colon biopsy specimen in a patient with ulcerative colitis illustrates changes limited to the mucosa. These changes include chron....

Chronic architectural changes in ulcerative colitis. Note the trifid crypt.

High-power view of a crypt abscess in ulcerative colitis shows the crypt to be dilated and filled with neutrophils and debris.

This is an example of low-grade glandular dysplasia in a patient with longstanding ulcerative colitis. Note the loss of mucin, nuclear hyperchromasia,....

High-grade dysplasia in the same patient as the previous image. There is significant cytologic atypia, with rounding of the nuclei and a greater degre....

Histologic section from another location in the same patient as the previous image. This field shows glands that are suspicious for invasive carcinoma....

Crohn disease

Deep knifelike, fissuring, transmural ulcer in Crohn disease.