eMedicine Specialties > Gastroenterology > Colon

Inflammatory Bowel Disease

William A Rowe, MD, Consulting Staff, Gastroenterology, Gastroenterology Associates

Updated: Apr 28, 2008

Introduction

Background

Inflammatory bowel disease (IBD) is an idiopathic disease, probably involving an immune reaction of the body to its own intestinal tract. The 2 major types of IBD are ulcerative colitis and Crohn disease. As the name suggests, ulcerative colitis is limited to the colon; Crohn disease can involve any segment of the gastrointestinal tract from the mouth to the anus.

Inflammatory bowel disease. Severe colitis noted during colonoscopy. The mucosa is grossly denuded, with active bleeding noted. This patient had her colon resected very shortly after this view was obtained.

Inflammatory bowel disease. Stricture in the terminal ileum noted during colonoscopy. Narrowed segment visible upon intubation of the terminal ileum with the colonoscope. Relatively little active inflammation is present, indicating that this is a cicatrix stricture.

Both ulcerative colitis and Crohn disease usually have waxing and waning intensity and severity. When the patient is actively symptomatic, indicating significant inflammation, the disease is considered to be in an active stage; the patient is having a flare of the IBD.

When the degree of inflammation is less (or absent) and the patient is usually asymptomatic, then the patient's disease is considered to be in remission. In most cases, symptoms do correspond well with the degree of inflammation present for either disease, although this is not universally true. In some patients, objective evidence for disease activity should be sought before administering medications with significant adverse effects.

Pathophysiology

Persons with IBD have a genetic predisposition (or perhaps susceptibility) for the disease. The triggering event for the activation of the immune response has yet to be identified. Possible factors related to this event include a pathogenic organism (as yet unidentified), an immune response to an intraluminal antigen (eg, protein from cow milk), or an autoimmune process whereby an appropriate immune response to an intraluminal antigen and an inappropriate response to a similar antigen is present on intestinal epithelial cells (ie, alteration in barrier function).

A great deal of research has been performed to discover potential genes linked to IBD. One of the early linkages discovered was on chromosome 16 (IBD1 gene), which led to the identification of the NOD2 gene (now called CARD15) as the first gene clearly associated with IBD (as a susceptibility gene for Crohn disease). Studies have also provided strong support for IBD susceptibility genes on chromosomes 5 (5q31) and 6 (6p21 and 19p). NOD2/CARD15 is a polymorphic gene involved in the innate immune system. The gene has more than 60 variations. Three of these variations play a role in 27% of patients with Crohn disease, primarily in patients with ileal disease. One important point to note with all of these potential genes is that they appear to be permissive (ie, allow IBD to occur) but 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 compared to subjects from unaffected families. 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. 

None of these mechanisms has been implicated as the primary cause, but they are postulated as potential causes. The lymphocyte population in persons with IBD is polyclonal, making the search for a single precipitating cause difficult. In any case, activation of the immune system leads to inflammation of the intestinal tract, both acute (neutrophilic) and chronic (lymphocytic, histiocytic).

For unclear reasons, research suggests that smoking increases the risk of Crohn disease but reduces the likelihood of ulcerative colitis.  

Appendectomy early in life also reduces the lifetime risk of developing ulcerative colitis.

Many of the mucosal changes seen in persons with IBD are nonspecific in nature; they are seen in any organ system in which active inflammation is occurring. Many inflammatory mediators have been identified; antibodies against these mediators or methods to block the production or receptors for these mediators hold great promise for potential therapy for IBD.

Frequency

United States

An estimated 1-2 million people in the United States have ulcerative colitis or Crohn disease. Before 1960, the incidence of ulcerative colitis was several times higher than that of Crohn disease. The latest data suggest that the current incidence of Crohn disease is approaching that of ulcerative colitis, although this change may reflect improved recognition and diagnosis of Crohn disease.

In the United States, the rates of IBD among persons of European descent have been measured in Olmstead County, Minn. In this population, the incidence of ulcerative colitis is 7.3 cases per 100,000 people per year and the prevalence is 116 cases per 100,000 people; the incidence of Crohn disease is 5.8 cases per 100,000 people per year and the prevalence is 133 cases per 100,000 people.

The prevalence of IBD among Americans of African descent is estimated to be the same as the prevalence among Americans of European descent. The prevalence is lower among Americans of Asian and Hispanic descent.

International

The incidence of IBD is assumed to be highest in developed countries and lowest in the developing regions of the world. A study in Italy showed the incidences of ulcerative colitis and Crohn disease to be similar to those found in the United States. Persons living in colder climates have a greater rate of IBD than persons living in warmer climates. Persons living in urban areas have a greater rate of IBD than persons living in rural areas.

Mortality/Morbidity

Multiple studies have been conducted from regions throughout the world on mortality in patients with IBD. The mortality from ulcerative colitis has decreased over the past 40-50 years.

• One study suggested decreased mortality for ulcerative colitis (standardized mortality ratio of 0.6 in Florence, Italy), but the vast majority of studies indicate a small but significant increase in mortality associated with IBD. The standardized mortality ratio for IBD generally ranges from approximately 1.4 times the general population (Sweden) to 5 times the general population (Spain). In general, the 95% confidence intervals suggest that the increase in relative risk is real. Ulcerative colitis and Crohn disease have approximately equal mortality rates.
• The most frequent cause of death in persons with IBD is the primary disease, followed by malignancy and thromboembolic disease.
• A generally accepted postulation is that the risk of colorectal cancer is not significantly higher in persons with ulcerative colitis compared with the general population until several years after diagnosis. Beyond 8-10 years after diagnosis, the risk of colorectal cancer increases by 0.5-1.0% per year. Data suggest that surveillance colonoscopies with random biopsies reduce mortality from colorectal cancer in patients with ulcerative colitis, primarily by allowing the detection of carcinoma at an earlier Duke stage. Data suggest that persons with Crohn colitis involving the entire colon have a risk of developing malignancy equal to that of persons with ulcerative colitis; however, the risk for most patients with Crohn disease is much smaller (albeit poorly quantified).

Race

The incidence of IBD has been reported to be highest in Jewish populations, followed by non–Jewish white populations. However, data suggest that incidences in non-Jewish, black, and Hispanic populations are increasing. The American Jewish population has one of the highest prevalences of IBD, 4-5 times that of the general population.

Sex

The male-to-female ratio is approximately equal for both ulcerative colitis and Crohn disease.

Age

Ulcerative colitis and Crohn disease are most commonly diagnosed in young adults (ie, late adolescence to the third decade of life). The age distribution of newly diagnosed IBD cases is bell-shaped; the peak incidence occurs in people in the early part of their second decade of life, with the vast majority of new diagnoses made in people aged 15-40 years.¹ However, children younger than 5 years and elderly persons are occasionally diagnosed. Of patients with IBD, 10% are younger than 18 years.

Clinical

History

The manifestations of IBD generally depend on the area of the intestinal tract involved. Patients with ulcerative colitis or Crohn colitis frequently have bloody diarrhea, occasionally with tenesmus. Patients with Crohn disease involving the small intestine frequently have abdominal pain and diarrhea, and occasionally they have symptoms of intestinal obstruction. A variety of intestinal and extraintestinal manifestations of IBD also may be observed in conjunction with either ulcerative colitis or Crohn disease.

• Ulcerative colitis
  • The most typical manifestation of ulcerative colitis is bloody diarrhea. Pain is uncommon but may occur.
  • Patients are commonly fatigued, which is often related to the inflammation and anemia that accompany disease activity.
• Crohn disease
  • The most typical manifestations of Crohn disease are abdominal pain and diarrhea. Not uncommonly, patients have been diagnosed with irritable bowel syndrome before being diagnosed with IBD.
  • Pain is particularly common, especially when some degree of obstruction is present. The pain may be almost anywhere within the abdominal cavity, although the classic location is the lower abdomen or right lower quadrant (appendicitislike).
  • Patients are commonly fatigued, which is often related to the pain, inflammation, and anemia that accompany disease activity.
• Intestinal complications 
  • Strictures and obstructions are not uncommon in persons with Crohn disease (see Media file 2 and Media file 4). These strictures are often inflamed and frequently resolve with medical treatment. Fixed (scarred or cicatrix) strictures may require endoscopic or surgical intervention to relieve obstructions. However, in persons with ulcerative colitis, colonic strictures are of significant concern and should be presumed to be malignant unless proven otherwise (usually by resection).
  • Fistulae and perianal disease are not uncommon in persons with Crohn disease and may be refractory to vigorous medical treatment, including antibiotic therapy (see Media file 3). Surgical intervention is often required for fistulae and perianal disease treatment, but both are associated with a high risk of recurrence.
  • Toxic megacolon is a life-threatening complication of ulcerative colitis and requires urgent surgical intervention.
  • Infectious colitis is in the differential diagnosis of ulcerative colitis and must be excluded before the diagnosis of ulcerative colitis can be made. However, in patients with well-established ulcerative colitis, superimposed infection can occur. Infection with Clostridium difficile is by far most common. Stools of patients hospitalized for a flare of ulcerative colitis should be tested for C difficile toxin. Treatment of C difficile (if present) infection generally helps put the flare into remission.
  • Malignancy is the most dreaded long-term intestinal complication of ulcerative colitis. The risk of colon cancer for persons with ulcerative colitis begins to rise significantly above that of the general population approximately 8-10 years after diagnosis. For cancer prevention, surveillance colonoscopy every 2 years after 8 years of disease is recommended, more frequently if areas of pathologic concern are evident. The risk of cancer in persons with Crohn disease may equal to that of persons with ulcerative colitis if the entire colon is involved, and screening may be beneficial for patients with pancolitis Crohn disease. The risk of small intestine malignancy is increased in persons with Crohn disease, but the malignancy is as likely to arise in a previously normal area as in an inflamed area. No screening protocol has ever been demonstrated to be effective for small bowel Crohn disease.

Physical

• Ulcerative colitis 
  • Presenting signs of ulcerative colitis include diarrhea with occult or frank blood loss (see Media file 1). Weight loss and anemia are also common. Persons with ulcerative colitis typically do not develop fistulae or perianal disease, although they may have perianal abscesses.
  • Diagnosis can be made endoscopically or radiologically, with contrast radiographs typically showing loss of the normal mucosal pattern and, with more advanced disease, loss of colonic haustrae.
  • Sigmoidoscopy or colonoscopy reveals that the rectum is almost always involved. 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 gastrointestinal tract. Colectomy is curative.
• Crohn disease 
  • Presenting signs of Crohn disease include occult blood loss and low-grade fever; weight loss and anemia are common. Growth retardation is seen in children and may be the only presenting sign in young patients. Fistulae and perianal disease are not uncommon.
  • Diagnosis can be made endoscopically or radiologically, with contrast radiographs typically showing a cobblestone pattern to the mucosa and areas of normal mucosa alternating with areas of inflamed mucosa (skip lesions).
  • Sigmoidoscopy or colonoscopy reveals that the rectum is frequently spared and right colonic predominance is common. Ninety percent of patients with Crohn disease have involvement of the terminal ileum and/or right colon. Pediatric patients are more likely (about 20%) to present with disease limited to the small intestine. Occasionally, gastric or duodenal Crohn disease manifests as seemingly refractory ulcer disease.
• Extraintestinal complications: Many complications associated with IBD can occur with either ulcerative colitis or Crohn disease. In addition, many of the medications used to treat IBD may cause significant adverse systemic effects.
  • In addition to medication-induced arthropathies, the arthritides associated with the IBD are of 2 varieties, axial (or central) arthritis and peripheral arthritis.
    • The axial arthritis associated with IBD consists of ankylosing spondylitis and sacroiliitis. Axial arthritis occurs in approximately 5% of patients with IBD (often Crohn disease) and typically is independent of disease activity. Axial arthritis is often associated with HLA-B27.
    • The peripheral arthritides vary with the activity of the underlying IBD. Peripheral arthritis occurs in approximately 10% of patients with IBD; it is a nondestructive arthritis, and patients have seronegative findings for rheumatoid factor. The peripheral arthritis typically is asymmetric, and it can be monoarticular or may involve different joints on different sides of the body. The classic peripheral arthritis affects large weight-bearing joints, although any joint may be involved.
  • Diseases of the eye associated with ulcerative colitis are episcleritis and iritis (uveitis). Treatment of these complications often requires high-dose systemic steroids or infliximab, and either condition can cause significant vision loss if left untreated.
  • The major skin diseases associated with IBD are erythema nodosum and pyoderma gangrenosum.
    • Erythema nodosum is a painful, tender, raised, purplish lesion on the anterior surface of the tibia. Erythema nodosum tends to correlate well with the activity of the underlying bowel disease; with bowel disease treatment, the erythema nodosum usually dissipates.
    • Pyoderma gangrenosum, on the other hand, typically is not associated with disease activity (see Media files 6-7). This skin lesion starts as an inflamed patch of skin ranging from one to several centimeters in diameter that progresses until it ulcerates. Upon ulceration, the lesion may persist for many months before healing. Treatments that have been tried that may have some efficacy include dapsone, metronidazole (MetroGel), cyclosporine, and infliximab. Surgical removal of the diseased bowel (eg, colectomy) does not ameliorate pyoderma gangrenosum.
    • Infectious skin lesions related to immune suppression may also be seen (eg, herpetic lesions)
  • The urinary complications of IBD are more common in persons with Crohn disease. Calcium oxalate stones are the most common type of renal calculi associated with Crohn disease; treatment is to increase hydration and to use oral calcium citrate supplements, which bind the oxalate within the intestinal tract and prevent its excretion in the urinary tract. Because of its proximity to the ureters, inflammation of the small bowel may involve the ureters, causing obstruction and hydronephrosis. Fistulae occasionally occur between the bowel and bladder or ureters.
  • Sclerosing cholangitis is most commonly associated with ulcerative colitis. Sclerosing cholangitis is a disease of the biliary tree. Although sclerosing cholangitis typically manifests as fatigue and, perhaps, jaundice, it is far more commonly sought when abnormal LFT results in a cholestatic pattern are found in a patient with ulcerative colitis.
    • Although ursodeoxycholic acid may help improve serum LFT results, this has not been translated into improved survival. If sclerosing cholangitis is diagnosed in the absence of a known history of ulcerative colitis, colonoscopy is indicated.
    • Ulcerative colitis may be expected to be clinically evident within 2 years of diagnosis of sclerosing cholangitis if the colitis is present and has not been diagnosed first. Sclerosing cholangitis may be indolent for many years but may progress to cirrhosis, for which hepatic transplantation may be necessary. The most dreaded complication of sclerosing cholangitis is the development of cholangiocarcinoma.
  • Gallstones are common in persons with Crohn disease, but these persons are usually asymptomatic; occasionally, cholecystectomy is necessary.
  • The anemia associated with IBD may be of 2 types: (1) iron deficiency anemia secondary to chronic blood loss, and (2) anemia of chronic disease. Because iron is absorbed in the duodenum, patients with Crohn disease involving the proximal small intestine may have difficulty absorbing oral iron; occasionally, parenteral iron replacement is necessary. IBD is a recognized cause of anemia of chronic disease.²
  • A hypercoagulable state is associated with IBD. It is estimated to occur in as many as one third of patients with IBD, but it may go unrecognized until a thrombotic event occurs. Strokes, retinal thrombi, and pulmonary emboli are not uncommon in patients with IBD.

Causes

The causes of IBD are currently unknown. See also Pathophysiology.

• Genetics: IBD clearly has a familial tendency.^3,4 First-degree relatives have a 5- to 20-fold increased risk of developing IBD compared to subjects from unaffected families. A parent with IBD has approximately a 5% chance of having a child develop IBD. 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; twin studies show a concordance of approximately 70% in identical twins versus 5-10% in nonidentical twins.
• Animal models: Several animal models are used to study IBD. 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 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 a colitis very similar to ulcerative colitis when the animal is subjected to stress.

Differential Diagnoses

Other Problems to Be Considered

• Backwash ileitis
• C1 esterase deficiency
• Estrogens
• Intestinal tuberculosis

Workup

Laboratory Studies

• Laboratory studies are of value in assisting with the management of IBD but are of minimal help in establishing the diagnosis. Laboratory values may be used as surrogate markers for inflammation and nutritional status and to look for deficiencies of necessary vitamins and minerals. Serologic studies have been proposed to help diagnose IBD and to differentiate Crohn disease from ulcerative colitis.
  • Stool studies: Perform a stool culture (and C difficile toxin assay) on patients before making a definitive diagnosis of idiopathic IBD. Any patient hospitalized with a flare of colitis should, at a minimum, have a C difficile toxin assay performed because, commonly, pseudomembranous colitis is superimposed on ulcerative colitis.
  • Complete blood cell count: The components of the CBC count can be useful indicators of disease activity and iron or vitamin deficiency. An elevated 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). Generally, the platelet count is normal, or, it may be mildly to moderately elevated if active inflammation is occurring, particularly if gastrointestinal blood loss occurs. Note that the MCV can be elevated in patients taking azathioprine (Imuran) or 6-mercaptopurine (6-MP).
  • Erythrocyte sedimentation rate: The erythrocyte sedimentation rate (ESR) is used as a surrogate marker for inflammation; an elevation above normal generally indicates the presence of an inflammatory response. For most, but not all, patients, the ESR can be used to help determine whether active IBD is present. Persons with cicatrix strictures are not expected to have an elevated ESR.
  • Nutritional markers: Blood tests can also be used to help determine nutritional status. The most commonly used marker is serum albumin; prealbumin and transferrin can also be used, although the latter is an acute phase reactant and can be falsely elevated in persons with active IBD. Hypoalbuminemia may reflect malnutrition; it can also develop because of the protein-losing enteropathy that can occur with active IBD.
  • Serum vitamin B-12: Vitamin B-12 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 B-12 is 1000 mcg subcutaneously every month.
  • Serum iron studies: Because active IBD is a source for gastrointestinal blood loss, iron deficiency is common. A microcytic hypochromic anemia suggests iron deficiency; if confirmed with serum iron/total iron-binding capacity, iron can be replaced either enterally or parenterally. For parenteral replacement, intravenous iron dextran can be used and is dosed based on the table in the package insert, with a maximum of 30 mL (1500 mg) at once.
  • Red blood cell folate: While 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. Although some practitioners administer folate supplements in patients taking sulfasalazine, few data demonstrate that this is universally necessary. 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 or more mg/d (rather than the usual 1 mg/d) should be considered.

Imaging Studies

• Abdominal flat plate: For the patient with IBD, kidneys, ureter, and bladder radiography can provide a great deal of information. Evidence of obstruction can be seen. Evidence of inflammatory disease, especially involving the colon, can often be discerned, perforation can be detected, and toxic megacolon can be diagnosed. More subtle findings can include indications of osteopenia and nephrolithiasis.
• Barium enema: This was one of the first studies that allowed characterization of the typical findings associated with IBD. Normal barium enema findings virtually exclude active ulcerative colitis, whereas abnormal findings can be diagnostic. Several terms have been used to describe abnormalities found after barium studies of the colon. These include the following: (1) a "stove-pipe" appearance, which suggests chronic colitis that has resulted in a loss of colonic haustrae; (2) "rectal sparing," which suggests Crohn colitis in the presence of inflammatory changes in other portions of the colon; (3) "thumbprinting," which indicates mucosal inflammation (which can also be seen frequently on the abdominal flat plate); and (4) "skip lesions," which suggest areas of inflammation alternating with normal-appearing areas, again suggesting Crohn colitis. Barium can be refluxed into the terminal ileum in many cases, which can assist in the diagnosis of Crohn disease.
• Small bowel series/small bowel follow-through: The small bowel series, with or without an upper gastrointestinal tract series, provides invaluable information about Crohn disease. This study can reveal if inflammation is present, can assist in the assessment of stricture length and severity, and can help decide the most appropriate surgical approach. Fistulae are often demonstrated on films from a small bowel series, even if they are not suggested based on the clinical evaluation. The small bowel series is usually sufficient for the evaluation of small intestine Crohn disease; rarely, it affords an inadequate view of the terminal ileum and enteroclysis must be performed. Although radiologists may remark on 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 make proper interpretation of colon findings difficult.
• Small bowel enteroclysis: The enteroclysis differs from a small bowel series in that a nasoenteric or oroenteric tube is placed and contrast is instilled directly into the small intestine. This is usually performed when fine detail of the intestinal mucosa is required or the distal small intestine is not adequately seen on the small bowel series because the contrast is diluted as it passes through the (usually dilated) small bowel.
• Computed tomography scan of the abdomen and pelvis: CT scanning of the abdomen and pelvis has limited use in the diagnosis of IBD, but findings may be very suggestive of IBD.⁵ Wall thickening on CT scans is nonspecific and may occur from smooth muscle contraction alone, especially in the absence of other extraintestinal inflammatory changes; however, the presence of inflammatory changes significantly increases the predictive value of the CT scan. CT scanning is the ideal study to determine if the patient has abscesses, and it can be used to guide percutaneous drainage of these abscesses. Fistulae also may be detected on CT scans.
• Fistulogram: Contrast can also be inserted directly into an enterocutaneous fistula in order to help determine the course of the fistula in anticipation of surgical correction and to assist in guiding the surgical approach.

Procedures

• Colonoscopy
  • This is one of the most valuable tools available to the physician for the diagnosis and treatment of 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, nonulcerating, and may occur when a widely patent ileocecal valve is present.
  • Be cautious with colonoscopic intervention in patients with IBD. The usual risks of colonoscopy apply (eg, reaction to medication, bleeding, perforation); the risk of bleeding is increased in the presence of inflammation, and even mucosal biopsies may require cautery to limit bleeding. The risk of perforation is also increased, particularly in patients taking high doses of steroids long-term. Also, weigh the risks and benefits of continuing colonic intubation in a patient with IBD who has significant inflammation.
  • 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 prevent reformation of the stricture, although this has yet to be demonstrated in controlled trials.
• Flexible sigmoidoscopy: This study 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, but not pancolitis. Rarely, Crohn colitis can be diagnosed based on flexible sigmoidoscopy findings; use caution interpreting sigmoid inflammation, particularly in older patients, because Crohn colitis may be confused with diverticulitis or ischemia.
• Upper endoscopy: Esophagogastroduodenoscopy is used for the evaluation of upper gastrointestinal tract symptoms, particularly in patients with Crohn disease. Aphthous ulceration occurs in the stomach and duodenum in 5-10% of patients with Crohn disease. The diagnosis of Crohn disease is occasionally made after gastric or duodenal ulcers fail to heal with acid suppression alone.
• Small bowel enteroscopy: This is of limited use in patients with Crohn disease and is of almost no value in those with ulcerative colitis. Although ulcerations and strictures in the upper half of the jejunum can be demonstrated with enteroscopy, the same information (and often more information) can be demonstrated on the small bowel follow-through x-ray film.
• Capsule enteroscopy: This technique is performed by having the patient swallow an encapsulated video camera that transmits images to a receiver outside the patient. Most commonly used for finding obscure sources of gastrointestinal blood loss, the images can find ulcerations associated with Crohn disease if upper endoscopy and colonoscopy are unrevealing. Its utility for the diagnosis of Crohn disease is currently under evaluation; the current generation of cameras do not allow for treatment. It must be borne in mind that not all small intestinal ulcerations represent manifestations of Crohn disease. The major risk in patients with Crohn disease is the potential for the camera to become lodged at the point of a stricture, which could require operative intervention for removal.

Histologic Findings

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

The entire intestinal wall is involved with inflammation in Crohn disease, not just the mucosa, as in ulcerative colitis. Biopsy specimens frequently demonstrate granulomas (approximately 50% of the time). The presence of granulomas is often helpful for making the diagnosis but is not necessary.

Because biopsy specimens obtained at colonoscopy are generally superficial mucosal tissue samples, the pathologist often has difficulty making a definitive diagnosis of ulcerative colitis or Crohn disease based on histologic findings alone. However, other causes of inflammation may be suggested based on pathology findings (eg, infectious colitis).

Treatment

Medical Care

• The first step in medication therapy is usually aminosalicylates; no advantage has been demonstrated for any particular agent for either ulcerative colitis or Crohn disease. For Crohn disease, metronidazole or ciprofloxacin is occasionally used, particularly for perianal disease or an inflammatory mass.
• If the IBD fails to respond to aminosalicylates, the second step is corticosteroids. Corticosteroids tend to provide rapid relief of symptoms and a significant decrease in inflammation, but they are limited by their adverse effects, particularly for prolonged use. The consensus regarding treatment with corticosteroids is that they should be tapered as rapidly as possible. Corticosteroids do not have a role in maintaining remission.
• If patients have difficulty reducing the dose of corticosteroids, have IBD that is refractory to corticosteroid therapy, or have frequent flares that require corticosteroid therapy, the third step for medication is one of the immunomodulatory agents, either 6-MP or azathioprine. These agents are not used for acute flares because the time from the initiation of treatment to the onset of significant action may be as long as 2-3 months. Response to these agents may be dose dependent; monitoring of blood counts is required to protect the patient from the hematological toxicity associated with these agents. Some authors suggest earlier use of these agents.
• An alternative third step is available for persons with IBD. This alternative is infliximab, a monoclonal antibody against tumor necrosis factor (TNF)–alpha.^6,7 Administer this agent by intravenous infusion. This medication is generally administered in 3 doses over 6 weeks (at weeks 0, 2, and 6) followed by a maintenance regimen. Administering the drug every 8 weeks has been demonstrated to be effective for maintaining remission.
  • The practitioner is advised to have the patient seek insurance approval for the administration of this medication because it is extremely expensive (typically, several thousand dollars per dose). Infliximab has an excellent response rate for Crohn disease (>80%); its response rate for ulcerative colitis is clearly less (approximately 50%).
  • The US Food and Drug Administration (FDA) approved prednisone, budesonide, and infliximab for the treatment of Crohn disease in July 2005. The FDA approved infliximab for the treatment of ulcerative colitis in August 2005.
• The final step for the treatment of IBD involves agents that have less well-demonstrated levels of efficacy but have been shown to be useful in some subsets of patients. For Crohn disease, methotrexate at 12.5-25 mg/wk may fall into this category. For ulcerative colitis, cyclosporine A (usually started intravenously for overwhelming disease) and nicotine patches fall into this category. Finally, a number of clinical trials of biological agents and diets are being conducted and may demonstrate efficacy in persons with IBD.

Surgical Care

The approach to surgical treatment of IBD varies depending on the disease. Most important, ulcerative colitis is a surgically curable disease because the disease is limited to the colon. However, Crohn disease can involve any segment of the gastrointestinal tract from the mouth to the anus; thus, surgical resection is not curative. On the contrary, excessive surgical intervention can leave the patient with a crippling short bowel syndrome. Situations arise in Crohn disease in which surgical intervention without resection can be used to defunctionalize the colon in order to possibly allow healing of distal disease.

• Surgery for ulcerative colitis
  • Surgical intervention for ulcerative colitis is curative for colonic disease and potential colonic malignancy. The indications for colectomy are (1) inflammation that is difficult to control, (2) early changes found during surveillance (high-grade dysplasia, low-grade dysplasia in some instances), (3) strictures, (4) significant adverse medication effects, and/or (5) an unacceptable quality of life referable to the ulcerative colitis.
  • The surgical options for ulcerative colitis vary. While segmental resection is rarely performed, total proctocolectomy is common. Total proctocolectomy with ileostomy creation is the simplest procedure with the lowest overall complication rate. A variation on this is the continent ileostomy or Koch pouch. This procedure creates an ileal reservoir that can be emptied with catheterization several times per day. However, incontinence from the pouch may necessitate use of an ileostomy bag. A colectomy may be performed, leaving a few centimeters of rectum intact; this ensures anal continence, but continued malignancy surveillance is needed for any colonic mucosa that remains and the remaining diseased rectal mucosa can continue to be problematic from a symptomatic standpoint.
  • The most technically demanding option 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 complications of this procedure are anal incontinence and impotence. Occasionally, postoperative pouchitis is a problem. If the diagnosis is incorrect and this procedure is performed on a patient with colonic Crohn disease, the likelihood of disease recurrence at the ileoanal anastomosis is high, which requires takedown, ileostomy creation, and loss of additional small bowel. When performed by a surgeon skilled in this technique, it offers an excellent option for younger patients with ulcerative colitis and concerns about body image.
• Surgery for Crohn disease
  • Surgery in Crohn disease is most commonly performed for complications of the disease (ie, strictures, fistulae, bleeding) rather than for the disease itself.
  • The most straightforward surgery for Crohn disease is the segmental resection, in which a segment of intestine with active Crohn disease or a stricture is resected and the remaining bowel is reanastomosed. This surgery requires margins of resection; in general, as little bowel as possible is resected because the risk of disease recurrence is significant.⁸
  • In patients with a very short cicatrix (scar tissue) 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 vertical 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% septic complication rate (2-3% of patients require reoperation); this can generally 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. This is a variation on the simple segmental resection.
  • In patients with severe perianal fistulae, a diverting ileostomy or colostomy is a surgical option. In this procedure, the distal colon is defunctionalized and a temporary ileostomy or colostomy is created. The defunctionalized rectum is allowed to heal, and the ileostomy or colostomy is then taken down 6 months or a year later. Many patients who pursue this option choose to forego reanastomosis after experiencing 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 fistulae are generally resected, although recurrence is common. Postoperative medical therapy is often used to prevent recurrence, although data are lacking on efficacy.

Consultations

In addition to possible studies performed by an endoscopist or radiologist, patients with IBD who are admitted to a medical facility typically require consultation with a surgeon.

• Colorectal surgeon (where available) or general surgeon: Early consultation with a surgeon is particularly useful in patients with stricturing or fistulizing disease and in patients with ulcerative colitis who experience frequent flares, have significant adverse effects from medications, or have an unacceptable quality of life.
• Radiologist: An interventional radiologist may be consulted when percutaneous drainage of an abscess is desired.

Diet

• Lactose intolerance is common in persons with Crohn disease or ulcerative colitis and some patients with other types of IBD.
• Diet has been well demonstrated to have little or no influence on inflammatory activity in persons with ulcerative colitis. However, diet may influence symptoms. For this reason, patients are often advised to make a variety of diet modifications, especially the adaptation of a low-residue diet. Evidence does not support a low-residue diet as beneficial in the treatment of ulcerative colitis, although it might decrease the frequency of bowel movements.
• Unlike in persons with ulcerative colitis, diet can influence inflammatory activity in persons with Crohn disease. Nothing by mouth (status NPO) can hasten the reduction of inflammation, as might the use of a liquid or predigested formula for enteral feeding. Although a meta-analysis in 1993 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.⁶

Activity

Generally, patients do not need to limit activity when IBD is quiescent. Even during flares of disease activity, activity is limited only by the extent of fatigue and the abdominal pain or diarrhea the patient is experiencing.

• Abdominal pain may limit the ability of the patient to work productively during flares of disease. When abdominal pain persists beyond medical therapy–induced resolution of the active inflammation, other causes of pain must be considered, including nephrolithiasis, abscess, stricture, irritable bowel syndrome, 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. This can often be resolved with employers. Occasionally, dehydration may be an issue, requiring intravenous hydration or the use of oral rehydration solutions.

Medication

While several drugs have been used successfully for the treatment of IBD for many years, medical treatment has advanced rapidly. The medications used are broken down into several classes based on the chemical similarities of the individual agents and similarities in the mechanisms of action. A step-wise approach may be taken. With this approach, the most benign (or temporary) drugs are used first. As they fail to provide relief, drugs from a higher step are used.

The aminosalicylates and symptomatic agents are step I drugs under this scheme; the antibiotics are a step IA, given the limited situations in which they are used. The corticosteroids constitute the step II drugs to be used if the step I drugs fail to adequately control the IBD. The immune-modifying agents are step III drugs and are used if corticosteroids fail or are required for prolonged periods. Infliximab is also a step III drug that can be used in some situations in patients with Crohn disease and ulcerative colitis. The experimental agents are step IV drugs and are used only after the previous steps fail and, then, are administered only by physicians familiar with their use.

Note that drugs from all steps may be used additively; in general, the goal is to wean the patient off steroids as soon as possible to prevent long-term adverse effects from these agents. Opinions differ regarding the use of certain agents in this step-wise approach.

The 5 oral aminosalicylate preparations available for use in the United States are sulfasalazine (Azulfidine), mesalamine (Asacol, Pentasa), balsalazide (Colazal), and olsalazine (Dipentum). Enema and suppository formulations are also available. All of these are derivatives of 5-aminosalicylic acid (5-ASA); the major differences are in the mechanism of delivery. Some of these also have unique adverse effects that other agents of this class lack. All of the aminosalicylates are useful for treating flares of IBD and for maintaining remission. None of the aminosalicylates has been proven to have greater efficacy for the treatment of ulcerative colitis or Crohn disease over any of the others. All of them are clearly more effective in persons with ulcerative colitis than in persons with Crohn disease; in persons with Crohn disease, the primarily utility is for colonic disease.

Step IA (antibiotics)

The antibiotics metronidazole and ciprofloxacin are the most commonly used antibiotics in persons with IBD. Antibiotics are used only sparingly in persons with ulcerative colitis because ulcerative colitis increases the risk of developing antibiotic-associated pseudomembranous colitis. When used in persons with ulcerative colitis, antibiotics are most commonly administered in the perioperative setting. However, in persons with Crohn disease, antibiotics are used for a variety of indications, most commonly for perianal disease. They are also used for fistulae and inflammatory masses in the abdomen, and they may have some efficacy in treating ileitis. The antibiotics have potential adverse effects, including nausea, anorexia, diarrhea, and monilial (candidal) infections; peripheral neuropathy can be observed in association with metronidazole use and, when present, requires discontinuation of therapy with that drug.

Corticosteroids are rapid-acting anti-inflammatory agents used in the treatment of IBD. Indications are for acute flares of disease only; corticosteroids have no role in the maintenance of remission. Corticosteroids may be administered by a variety of 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).

Intravenous corticosteroids are often used for patients who are severely ill and hospitalized; few data have been published on the optimum dosage of intravenous (or oral form) corticosteroids. The generally used upper ends of dosing are methylprednisolone at 40 mg intravenously every 6 hours or hydrocortisone at 100 mg intravenously every 8 hours. Some situations mandate a higher initial intravenous dose, but many practitioners start hospitalized patients at lower intravenous doses.

In general, once a clinical response is observed (typically within a 1-2 d, occasionally longer), the dose of the intravenous corticosteroid can be tapered. Before hospital discharge, conversion to an oral corticosteroid is made; further dosage tapering can be accomplished in an outpatient setting. When oral corticosteroids are used, dosing is highly 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/d; for more severe flares, the higher end of the range is used (occasionally even higher doses are used). Again, once a clinical response is seen, the dose is tapered. Most patients who use oral corticosteroids can only occasionally tolerate a relatively rapid taper after a response is achieved; occasionally, a very prolonged steroid taper is necessary to prevent relapse. When the latter situation occurs, consider the use of alternative drugs (immune modifiers or anti-TNF therapy).

Topical corticosteroids are used in persons with distal colonic disease in a manner similar to 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. The potential complications of corticosteroid use are multiple and include fluid and electrolyte abnormalities, osteoporosis, aseptic necrosis, peptic ulcers, cataracts, neurologic and endocrine dysfunctions, infectious complications, and occasional psychiatric disorders (including psychosis). Patients who are taking corticosteroids, especially for longer than a few weeks, must be warned about the associated complications; this discussion should be documented in the medical record. Some data assert that some agents used for osteoporosis prevention and treatment (eg, the bisphosphonates) are useful for preventing the bone loss associated with corticosteroid use.

The immune modifiers 6-MP and azathioprine are used in patients with IBD in whom remission is difficult to maintain with the aminosalicylates alone. Immune modifiers work by causing a reduction in the lymphocyte count, and because of that mechanism of action, their onset of action is relatively slow (typically 2-3 mo). They are used most commonly for their steroid-sparing action in persons with refractory disease; they are also used as primary treatment for fistulae and the maintenance of remission in patients intolerant of aminosalicylates. Use of these agents mandates monitoring of blood parameters; they can cause significant neutropenia or pancytopenia that would warrant a dose reduction or discontinuation. Routine CBC counts with differentials and platelet counts are checked monthly, and LFTs can be performed intermittently. After a year of stable dosing with no difficulties with blood counts (except the expected lymphopenia), the intervals between blood count monitoring can be increased.

The cytopenic effect is typically dose dependent, although some patients are more sensitive than others. Typical dosing of the immune modifiers (either 6-MP or azathioprine) is 1-2 mg/kg/d. If needed, the dose can be increased to the point when cytopenia occurs; obviously, at higher doses, closer monitoring is warranted. Blood tests are available to measure metabolite levels, but the results have not been shown in independent studies to have any correlation with clinical efficacy. These blood tests for monitoring toxicity offer little advantage (but much greater expense) over monitoring CBC counts and LFT results.

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 azathioprine and 6-MP. Because the population that requires these medications is already at higher risk for the development of malignancy, the author believes that the available data on the use of azathioprine or 6-MP are insufficient and do not demonstrate a significant increase in the risk of malignancy.

Additional step III agents work by a different mechanism. Infliximab (Remicade) is an anti–TNF-alpha monoclonal antibody administered by infusion for the treatment of Crohn disease. Infliximab is FDA approved for both ulcerative colitis and Crohn disease, although it does appear to have a higher efficacy rate in the latter. Infliximab is generally administered as infusions of 5 mg/kg for the treatment of moderate-to-severe IBD. It is administered as 3 separate infusions of 5 mg/kg at weeks 0, 2, and 6, often followed by doses every 8 weeks for maintenance of remission. For Crohn disease, the response rate is 80% and the induction of remission rate is 50% after a single dose; with multiple dosing, higher rates of remission are attained. For ulcerative colitis, the response rates are 50-70%.

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% develop an abscess. The response can be maintained by continuing regular dosing (ie, every 8 wk) after the induction dose.

The adverse effects of infliximab commonly include hypersensitivity and flulike symptoms; the latter can often be avoided by pretreatment with acetaminophen and diphenhydramine. Rare reports of lupuslike reactions and lymphoproliferative malignancies have been reported, although whether the malignancies are related to the drug or to the underlying disease process remains uncertain.

Other newer anti-TNF agents include adalimumab (Humira), which is given by subcutaneous injection every 2 weeks after a loading dose of 6 injections, and certolizumab pegol (Cimzia), which is given by subcutaneous injection every 4 weeks.

Natalizumab (Tysabri; formerly called Antegrin), an agent aimed at preventing the accumulation of lymphocytes in the diseased bowel by blocking the effects of integrin, has been approved but is only available through a restricted distribution program. Natalizumab is an intravenous medication that has shown efficacy in Crohn disease but is not as effective as anti-TNF agents. Natalizumab has been linked to reports of progressive multifocal leukoencephalopathy (a potentially fatal opportunistic viral infection) in 3 patients.

Generally, use these agents as part of an experimental protocol or in a setting in which the toxicities of the agents can be rapidly recognized and managed. Examples of some agents are provided, but a review of the literature is warranted before using them. In most cases, some subsets of patients respond; in general, large placebo-controlled trials have not yet established efficacy for these agents for the treatment of IBD.

Various experimental agents tend to be more disease-specific, ie, an agent works for Crohn disease but not ulcerative colitis, or vice versa. Experimental agents used in persons with Crohn disease include methotrexate (12.5-25 mg/wk orally or intramuscularly), thalidomide (50-300 mg/d orally), and interleukin 11 (1 mg/wk subcutaneously). Experimental agents used in persons with ulcerative colitis include cyclosporine A at a dose of 2-4 mg/kg/d intravenously (measure level; convert to oral dosing at 2-3 times the intravenous dose), nicotine patch (14-21 mg/d via topical patch), butyrate enema (100 mL per rectum twice daily), and heparin (10,000 U subcutaneously twice daily). Multiple contraindications, interactions, and precautions are associated with these drugs.

Because patients report symptoms (eg, diarrhea, spasm/pain, epigastric discomfort) and not inflammation per se, symptomatic relief is appropriate when indicated. This includes therapy with antidiarrheal agents, bile acid–binding agents, antispasmodics, and acid suppressants, as needed. These medications are not without complications, and caution is necessary.

Aminosalicylates (step I)

Effective in reducing inflammatory reactions.

Sulfasalazine (Azulfidine, Azulfidine EN-tabs)

Considered best for colonic disease, although also considered first-line therapy for Crohn disease. Used for acute disease and for maintenance of remission. Sulfasalazine is 5-ASA connected to sulfapyridine by an azo bond; colonic bacteria break the azo bond, releasing the active 5-ASA. Sulfapyridine moiety also may have some small therapeutic effect.

Dosing

Adult

500 mg PO bid, may increase to 1000 mg PO qid (usual dose)

Pediatric

<2 years: Not established
>2 years: 30-50 mg/kg/d PO divided qid, may increase to 75 mg/kg/d divided doses

Interactions

Decreases effects of iron, digoxin, and folic acid; conversely, increases effect of oral anticoagulants, oral hypoglycemic agents, and methotrexate

Contraindications

Documented hypersensitivity to sulfa drugs or any component; GI or GU obstruction

Precautions

Pregnancy

B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals

Precautions

Caution in renal or hepatic impairment, blood dyscrasias, or urinary obstruction; frequently causes reversible decrease in sperm count and motility; stop if rash or hemolytic anemia occur

Mesalamine (Asacol, Pentasa, Canasa, Rowasa, Lialda)

A 5-ASA acts systemically and also has activity as a topical anti-inflammatory. The currently approved oral mesalamine products in the United States differ only in the mechanism of drug delivery. Asacol has mesalamine within a Eudragit-S coating that dissolves and releases the mesalamine at pH 7, which typically occurs in the terminal ileum. Pentasa is 5-ASA in ethylcellulose and has a time-release coating. Release of mesalamine from Pentasa begins at the pylorus; because of this, the drug is often used when proximal intestinal Crohn disease is suggested. Despite its proximal release, no convincing data indicate the site of release translates into clinical superiority.
Lialda is indicated to induce remission in active ulcerative colitis. It has a proprietary release mechanism that is referred to as MMX technology. This is actually a combination of the release mechanisms of Asacol (with a pH dependent coating) and Pentasa (a water-soluble matrix). Available as a 1.2 g tab.
Rectal dosage forms deliver high concentrations of mesalamine to the left colon as high as the splenic flexure (enema with 30 min retention) or to the rectum for use in proctitis (suppository). Although effective, associated with relatively high relapse rate upon discontinuation. Widespread use of topical agents is limited by patient acceptance in many cases; often, patients with active rectal disease have difficulty holding in enema.

Dosing

Adult

Asacol: 400 mg PO bid to 1200 mg PO qid, usual 800 mg PO tid
Pentasa: 500 mg PO bid to 1000 mg PO qid (usual dose)
Usual maximum dose is 4.8 g/d, but even higher doses have been used
Lialda: 1.2-4.8 g (ie, 1-4 tabs) PO qd pc
Canasa: Insert 1 supp PR bid
Rowasa, rectal: 1 enema (4 g/60-mL) PR qd/bid; alternatively, 1 supp (500-mg) PR qd/bid

Pediatric

PO: 30-50 mg/kg/d divided bid/qid, not to exceed 3.2 g/d
PR: Administer as in adult

Interactions

Decreases effects of iron, digoxin, and folic acid; increases effects of oral anticoagulants, methotrexate, and oral hypoglycemic agents

Contraindications

Documented hypersensitivity

Precautions

Pregnancy

B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals

Precautions

Most common adverse effects are rash, occasional fever, and flulike syndrome; rare reports of interstitial nephritis at high doses; also rare reports of pancreatitis and pericarditis; diarrhea may occur; caution in patients with renal or hepatic impairment; elderly patients may have difficulty administering and retaining rectal suppository

Balsalazide (Colazal)

Prodrug 5-ASA connected to a 4-aminobenzoyl-(beta)-alanine carrier by an azo bond; colonic bacteria break the azo bond, releasing the active 5-ASA. Metabolites of drug may decrease inflammation by blocking production of arachidonic acid metabolites in colon mucosa.
Considered best for colonic disease. Used for acute disease and for maintenance of remission; some studies suggest better at maintaining remission than sulfasalazine.

Dosing

Adult

3 cap (2.25 g) PO tid for 8-12 wk

Pediatric

Not established

Interactions

None known, but oral antibiotics may interfere with 5-ASA release in colon

Contraindications

Documented hypersensitivity to 5-ASA or any component; GI or GU obstruction

Precautions

Pregnancy

B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals

Precautions

Caution in renal impairment; gastric retention may be prolonged in pyloric stenosis; safety and efficacy of long-term use (>12 wk) not established; headache, abdominal pain, and nausea may occur, but not more than with placebo; rare hepatitis reported

Olsalazine (Dipentum)

Aminosalicylate is useful for active disease and maintenance of remission in ulcerative colitis. Dipentum is 5-ASA connected to a 5-ASA by an azo bond; colonic bacteria break the azo bond, releasing the active 5-ASA.

Dosing

Adult

500-1000 mg PO bid

Pediatric

30 mg/kg/d PO divided bid

Interactions

None reported

Contraindications

Documented hypersensitivity

Precautions

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

Major common adverse effect is diarrhea; other adverse effects are similar to those of mesalamine; occasional exacerbation of disease

Antibiotics (step IA)

Antimicrobial therapy must cover all likely pathogens in the context of the clinical setting.

Metronidazole (Flagyl)

Widely available inexpensive antibiotic and antiprotozoal agent.

Dosing

Adult

250-500 mg PO tid

Pediatric

35-50 mg/kg/d PO divided tid

Interactions

Cimetidine may increase toxicity; may increase effects of anticoagulants; may increase toxicity of lithium and phenytoin; disulfiramlike reaction may occur with orally ingested ethanol

Contraindications

Documented hypersensitivity

Precautions

Pregnancy

B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals

Precautions

Adjust dose in hepatic disease; monitor for seizures and development of peripheral neuropathy; metronidazole should be discontinued immediately and permanently if significant signs of peripheral neuropathy develop, as the neuropathy may be progressive and irreversible if the agent is not discontinued

Ciprofloxacin (Cipro)

Fluoroquinolone antibiotic commonly used for treatment of urinary, skin, and respiratory tract infections.

Dosing

Adult

500 mg PO bid

Pediatric

<18 years: Not recommended
>18 years: Administer as in adults

Interactions

Antacids, iron salts, and zinc salts may reduce serum levels; administer antacids 2-4 h before or after taking fluoroquinolones; cimetidine may interfere with metabolism; reduces therapeutic effects of phenytoin; probenecid may increase serum concentrations; may increase toxicity of theophylline, caffeine, cyclosporine, and digoxin (monitor digoxin levels); may increase effects of anticoagulants (monitor PT)

Contraindications

Documented hypersensitivity

Precautions

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

In prolonged therapy, perform periodic evaluations of organ system functions (eg, renal, hepatic, hematopoietic); adjust dose in renal function impairment; superinfections may occur with prolonged or repeated antibiotic therapy

Rifaximin (Xifaxan)

Nonabsorbed (<0.4%), broad-spectrum antibiotic specific for enteric pathogens of the gastrointestinal tract (ie, gram-positive, gram-negative, aerobic, anaerobic). Rifampin structural analog. Binds to beta-subunit of bacterial DNA-dependent RNA polymerase, thereby inhibiting RNA synthesis.

Dosing

Adult

200 mg PO tid

Pediatric

<12 years: Not established
>12 years: Administer as in adults

Interactions

Induces CYP450 3A4 in vitro; limited data exist; no significant interactions shown in single dose studies with midazolam and oral contraceptives

Contraindications

Documented hypersensitivity to rifaximin or rifamycin antimicrobial agents (eg, rifampin)

Precautions

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

May promote intestinal bacterial overgrowth and cause superinfection; discontinue if diarrhea persists more than 24-48 h or worsens; seek immediate medical care if fever and/or bloody stools emerge (tablets not effective); not effective for travelers' diarrhea due to suspected pathogens other than E coli; postmarketing reports include allergic dermatitis, rash, angioneurotic edema, urticaria, and pruritus

Corticosteroids

Have anti-inflammatory properties and cause profound and varied metabolic effects. Modify the body's immune response to diverse stimuli.

Hydrocortisone (Solu-Cortef, Cortenema, Cortifoam, Anusol-HC)

Adrenocortical steroids act as potent inhibitors of inflammation. May cause profound and varied metabolic effects, particularly in relation to salt, water, and glucose tolerance, in addition to their modification of the immune response of the body. Alternative adrenocortical steroids may be used in equivalent dosage.
Topical corticosteroid similar to IV and PO corticosteroids; significant amounts of corticosteroids can be absorbed systemically when administered via enema or suppository. Various products containing hydrocortisone are available for PR use.

Dosing

Adult

Solu-Cortef: 100 mg IV tid
Cortenema (100-mg hydrocortisone): 1 enema PR bid
Cortifoam (80-mg hydrocortisone): 1 applicator PR bid
Anusol-HC supp: 1 suppository PR bid; others available

Pediatric

Similar to low end of adult dose, depending on clinical response; typically equivalent to 1-2 mg/kg/d of PO prednisone

Interactions

Clearance may decrease with estrogens; may increase digitalis toxicity secondary to hypokalemia

Contraindications

Documented hypersensitivity; viral infection; peptic ulcer disease; hepatic dysfunction; connective tissue infections; fungal or tubercular skin infections

Precautions

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

Avoid immunization during steroid use; impaired wound healing; other precautions noted above apply but generally are of less severity; as much as 75% of administered topical dose may be absorbed if the lower colon is severely inflamed; caution in hyperthyroidism, osteoporosis, peptic ulcer, cirrhosis, nonspecific ulcerative colitis, diabetes, and myasthenia gravis

Prednisone (Deltasone, Orasone, Sterapred)

Acts as potent inhibitor of inflammation. May cause profound and varied metabolic effects, particularly in relation to salt, water, and glucose tolerance, in addition to their modification of the immune response of the body. Alternative corticosteroids may be used in equivalent dosage. PO corticosteroids are generally tapered over days to weeks, depending on duration and dose of administration to control disease.

Dosing

Adult

40-60 mg PO qd

Pediatric

1-2 mg/kg/d PO in single or divided doses, taper after response

Interactions

Coadministration with estrogens may decrease clearance; concurrent use with digoxin may cause digitalis toxicity secondary to hypokalemia; phenobarbital, phenytoin, and rifampin may increase metabolism (consider increasing maintenance dose); monitor for hypokalemia with coadministration of diuretics

Contraindications

Documented hypersensitivity; viral infection; peptic ulcer disease; hepatic dysfunction; connective tissue infections; fungal or tubercular skin infections

Precautions

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

Abrupt discontinuation of may cause adrenal crisis; hyperglycemia, edema, osteonecrosis, myopathy, peptic ulcer disease, hypokalemia, osteoporosis, euphoria, psychosis, myasthenia gravis, growth suppression, and infections may occur; avoid immunization during steroid use

Methylprednisolone (Solu-Medrol, Depo-Medrol)

Adrenocortical steroids act as potent inhibitors of inflammation. They may cause profound and varied metabolic effects, particularly in relation to salt, water, and glucose tolerance, in addition to their modification of the immune response of the body. Alternative adrenocortical steroids may be used in equivalent dosage.

Dosing

Adult

20-40–mg IV q6h

Pediatric

Similar to low end of adult dose, depending upon clinical response; typically equivalent to 1-2 mg/kg/d of oral prednisone

Interactions

Coadministration with digoxin, may increase digitalis toxicity secondary to hypokalemia; estrogens may increase levels of methylprednisolone; phenobarbital, phenytoin and rifampin may decrease levels of methylprednisolone (adjust dose); monitor patients for hypokalemia when taking medication concurrently with diuretics; grapefruit juice increases prednisolone concentrations; methylprednisolone and cyclosporine mutually inhibit one another resulting in increased plasma levels of each drug

Contraindications

Documented hypersensitivity; viral, fungal or tubercular skin infections

Precautions

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

Hyperglycemia, edema, osteonecrosis, peptic ulcer disease, hypokalemia, osteoporosis, euphoria, psychosis, growth suppression, myopathy, and infections are possible complications of glucocorticoid use; Depo-Medrol contains benzyl alcohol, which is potentially toxic when administered locally to neural tissue; administration of Depo-Medrol by other than indicated routes, including the epidural route, has been associated with reports of serious medical events, including arachnoiditis, meningitis, paraparesis/paraplegia, sensory disturbances, bowel/bladder dysfunction, seizures, and visual impairment, including blindness, ocular and periocular inflammation, and residue or slough at injection site

Prednisolone (AK-Pred, Pred Forte)

Corticosteroids act as potent inhibitors of inflammation. They may cause profound and varied metabolic effects, particularly in relation to salt, water, and glucose tolerance, in addition to their modification of the immune response of the body. Alternative corticosteroids may be used in equivalent dosage. Oral corticosteroids generally are tapered off over days to weeks, depending upon duration and dose of administration to control disease.

Dosing

Adult

32-40 mg PO qd

Pediatric

Not established

Interactions

Decreases effects of salicylates and toxoids (for immunizations); phenytoin, carbamazepine, barbiturates, and rifampin decrease effects of corticosteroids

Contraindications

Documented hypersensitivity; viral, fungal, or tubercular skin lesions

Precautions

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

Caution in hyperthyroidism, osteoporosis, cirrhosis, nonspecific ulcerative colitis, peptic ulcer, diabetes, and myasthenia gravis

Budesonide EC (Entocort)

Alters level of inflammation in tissues by inhibiting multiple types of inflammatory cells and decreasing production of cytokines and other mediators involved in inflammatory reactions.
Corticosteroids may cause profound and varied metabolic effects, particularly in relation to salt, water, and glucose tolerance, in addition to their modification of the immune response of the body. Alternative corticosteroids may be used in equivalent dosage. Oral corticosteroids generally are tapered off over days to weeks, depending upon duration and dose of administration to control disease.
Formulation contains granules coated to protect against dissolution in gastric juice, but which dissolve at pH 5.5 in the duodenum. Drug is released into the intestinal lumen in a time dependent manner.

Dosing

Adult

9-15 mg PO qam

Pediatric

Not established

Interactions

Ketoconazole, itraconazole, ritonaivir, indinavir, saquinavir, erythromycin, and other CYP3A4 enzyme inhibitors may significantly increase serum levels of budesonide

Contraindications

Documented hypersensitivity; systemic fungal infections; ileocolostomy during immediate or early postoperative period

Precautions

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

If improvement fails to occur within 2-3 wk, discontinue therapy; symptomatic improvement may be misleading and should not be used as sole criterion in judging efficacy (sigmoidoscopic examination and x-ray visualization are essential for adequate monitoring); caution where there is a probability of impending perforation or abscess, pyogenic infections, intestinal anastomoses, obstruction, extensive fistulas, and sinus tracts

Immune modifiers (step III)

These agents modify immune reactions resulting from diverse stimuli.

Azathioprine (Imuran)

Antagonizes purine metabolism and inhibits synthesis of DNA, RNA, and proteins. May decrease proliferation of immune cells, which results in lower autoimmune activity.

Dosing

Adult

1-2 mg/kg PO qd

Pediatric

Administer as in adults

Interactions

Toxicity increases with allopurinol; concurrent use with ACE inhibitors may induce severe leukopenia; may increase levels of methotrexate metabolites and decrease effects of anticoagulants, neuromuscular blockers, and cyclosporine

Contraindications

Documented hypersensitivity

Precautions

Pregnancy

D - Fetal risk shown in humans; use only if benefits outweigh risk to fetus

Precautions

Publications suggest may be continued safely during pregnancy; may increase risk of neoplasia; caution with liver disease and renal impairment; hematologic toxicities may occur

6-Mercaptopurine (Purinethol)

Purine analog that inhibits DNA and RNA synthesis, causing cell proliferation to arrest.

Dosing

Adult

1-2 mg/kg PO qd

Pediatric

Administer as in adults

Interactions

Toxicity increases when administered with allopurinol; hepatic toxicity increases when used in combination with doxorubicin

Contraindications

Documented hypersensitivity

Precautions

Pregnancy

D - Fetal risk shown in humans; use only if benefits outweigh risk to fetus

Precautions

Publications suggest may be continued safely during pregnancy; exercise caution in patients with renal or hepatic impairment; patients have a high risk of developing pancreatitis; monitor for myelosuppression

Tumor necrosis factor inhibitors (step IIIa)

These agents inhibit the activity of TNF.

Infliximab (Remicade)

Neutralizes cytokine TNF-alpha and inhibits its binding to TNF-alpha receptor. Mix in 250 mL NS for infusion over 2 h.

Dosing

Adult

5 mg/kg IV infusion over 2 h
Although single doses can be used, most efficacious is a dosing schedule of induction at weeks 0, 2, and 6, followed by q8wk dosing
For fistulizing Crohn disease, 3-dose induction is almost always needed, and q8wk dosing clearly helps maintain fistula closure; dose may be increased to 10 mg/kg IV if patient is not responding or only incompletely responding to 5 mg/kg dose

Pediatric

Induction: 5 mg/kg IV infusion; repeat for a total of 3 doses at 2 and 6 wk
Maintenance: 5 mg/kg IV infusion q6wk

Interactions

None reported

Contraindications

Documented hypersensitivity

Precautions

Pregnancy

B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals

Precautions

TNF-alpha modulates cellular immune responses; anti-TNF therapies, such as infliximab, may adversely affect normal immune responses and allow development of superinfections; if desired, patients may be premedicated with acetaminophen at 650 mg PO and diphenhydramine at 25 mg IV immediately prior to infusion, but this is generally not necessary; during administration and for 30 min after, monitor patient for fever or chills, pruritus or urticaria, chest pain, hypotension, hypertension, and dyspnea; more cases of lymphoma were observed in TNF alpha-blockers compared to controlled groups; may increase risk of reactivation of tuberculosis in patients with particular granulomatous infections; high cost makes insurance coverage almost universally necessary

Adalimumab (Humira)

Recombinant human IgG1 monoclonal antibody specific for human TNF. Binds specifically to TNF-alpha and blocks interaction with p55 and p75 cell-surface TNF receptors.

Dosing

Adult

Induction dose: 160 mg SC once (administer by either dividing dose into 4 injections on day 1 or over 2 days), then follow with 80 mg SC once at week 2
Maintenance: 40 mg SC q2wk beginning at week 4

Pediatric

Not established

Interactions

May interfere with immune response to live virus vaccine (eg, MMR) and reduce efficacy; methotrexate (MTX) decreases clearance (available data do not support adjusting dose of either adalimumab or MTX); coadministration with anakinra (an IL-1 antagonist that also blocks TNF) may cause additive adverse effects, particularly development of serious infections

Contraindications

Documented hypersensitivity; active infection

Precautions

Pregnancy

B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals

Precautions

Causes immunosuppression; may be associated with serious infections (some fatal), including reactivation of tuberculosis, sepsis, or opportunistic infections; increases risk for lymphoma development; associated with CNS demyelination (rare); discontinue if serious infection develops; autoantibody development may occur causing lupus-like syndrome; may cause hypersensitivity reactions, including anaphylaxis and hematologic adverse effects (ie, pancytopenia, aplastic anemia); exacerbation of CHF or new onset CHF has been observed with TNF-blocking agents

Certolizumab pegol (Cimzia)

Pegylated antitumor necrosis factor (TNF)–alpha blocker, which results in disruption of the inflammatory process. Indicated for moderate-to-severe Crohn disease in individuals who have not responded to conventional therapies.

Dosing

Adult

400 mg SC initially; repeat at weeks 2 and 4; if favorable response occurs, initiate maintenance dose of 400 mg SC q4wk
Administer as 2 separate 200-mg SC injections at 2 separate sites in abdomen or thigh

Pediatric

Not established

Interactions

May interfere with immune response to live-virus vaccine (eg, MMR) and reduce efficacy; coadministration with anakinra (an interleukin-1 antagonist that also blocks TNF) may cause additive adverse effects, particularly development of serious infections

Contraindications

Documented hypersensitivity

Precautions

Pregnancy

B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals

Precautions

Common adverse effects include headache, upper respiratory tract infections, abdominal pain, injection site reactions, and nausea; increases risk of serious infections, including infections that may result in hospitalization or death; may increase risk of opportunistic infections (eg, tuberculosis [TB], invasive fungal), so test for latent TB, and, if positive, initiate TB treatment prior to starting certolizumab; if infection occurs, patients should contact their physician immediately; may cause reactivation of hepatitis B virus; may increase risk of lymphoma and other malignancies because of immune suppression; anaphylaxis or serious allergic reactions, demyelinating disease, cytopenias, pancytopenia, heart failure, and lupuslike syndrome have been reported with TNF blockers

Anti-integrin antibody (step IIIb)

Inhibits integrins effects on leukocyte adhesion to their receptors.

Natalizumab (Tysabri)

Recombinant humanized IgG4-1C monoclonal antibody produced in murine myeloma cells. Binds to alpha-4 subunits of alpha-4-beta-1 and alpha-4-beta-7 integrins expressed on leukocyte surface, which inhibits alpha-4-mediated leukocyte adhesion to their receptors. In Crohn disease, the interaction of the alpha-4-beta-7 integrin with the endothelial receptor MAdCAM-1 has been implicated as an important contributor to the chronic inflammation that is a hallmark of the disease.
Indicated to induce and maintain a clinical response and remission for moderate-to-severe Crohn disease with evidence of inflammation. Use is reserved for patients who have had an inadequate response to, or are unable to tolerate, conventional Crohn disease therapies and TNF-alpha inhibitors. Patients must be enrolled in a special restricted distribution program called the Crohn Disease–Tysabri Outreach Unified Commitment to Health (CD TOUCH) Prescribing Program.
Also investigated under the name Antegrin.

Dosing

Adult

300 mg IV q4wk; dilute in 100 mL 0.9% NaCl and infuse over 1 h

Pediatric

Not established/contraindicated

Interactions

Interferon beta-1a decreases clearance by 30%, however no dosage adjustment is needed; because of the potential for increased risk of PML and other infections, patients with Crohn disease should not receive concomitant treatment with immunosuppressants (eg, 6-mercaptopurine, azathioprine, cyclosporine, methotrexate) or TNF-alpha inhibitors (eg, infliximab, adalimumab), and if on chronic corticosteroids when initiating natalizumab, corticosteroids should be tapered; patients with multiple sclerosis receiving chronic immunosuppressant or immunomodulatory therapy typically should not be treated with natalizumab

Contraindications

Documented hypersensitivity; progressive multifocal leukoencephalopathy (PML)

Precautions

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

Author advises against its use in pregnant women (no data available); uncommon serious adverse effects include infections (eg, pneumonia), hypersensitivity reactions, severe depression, and gallstones; common adverse effects include mild infections (eg, UTI, lower respiratory tract, GI, vaginal), headache, mild depression, joint pain, and menstrual disorders; excreted in breast milk; infusion-related adverse effects include urticaria, pruritus, and rigors (discontinue infusion and treat accordingly); monitor closely for PML

Histamine2-receptor antagonists

H2-receptor antagonists are reversible competitive blockers of histamines at the H2 receptors, particularly those in the gastric parietal cells, where they inhibit acid secretion. The H2 antagonists are highly selective, do not affect the H1 receptors, and are not anticholinergic agents.

Cimetidine (Tagamet)

Inhibit histamine at H2 receptors of gastric parietal cells, which results in reduced gastric acid secretion, gastric volume, and hydrogen concentrations.

Dosing

Adult

800 mg PO bid

Pediatric

Not established
Suggested dose is 10-20 mg/kg/d PO/IV divided q6h; not to exceed 40 mg/d

Interactions

Can increase blood levels of theophylline, warfarin, tricyclic antidepressants, triamterene, phenytoin, quinidine, propranolol, metronidazole, procainamide, and lidocaine

Contraindications

Documented hypersensitivity

Precautions

Pregnancy

B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals

Precautions

Elderly may experience confusional states; may cause impotence and gynecomastia in young males; may increase levels of many drugs; adjust dose or discontinue treatment if changes in renal function occur; may increase risk of necrotizing enterocolitis in premature infants

Ranitidine (Zantac)

Inhibits histamine stimulation of the H2 receptor in gastric parietal cells, which, in turn, reduces gastric acid secretion, gastric volume, and hydrogen ion concentrations.

Dosing

Adult

150 mg PO bid

Pediatric

<12 years: Not established
>12 years:
1.25-2.5 mg/kg/dose PO q12h; not to exceed 300 mg/d
0.75-1.5 mg/kg/dose IV/IM q6-8h; not to exceed 400 mg/d

Interactions

Inhibits CYP450 3A4 and 2D6; may decrease effects of ketoconazole and itraconazole; may alter serum levels of ferrous sulfate, diazepam, nondepolarizing muscle relaxants, and oxaprozin

Contraindications

Documented hypersensitivity

Precautions

Pregnancy

B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals

Precautions

Caution in renal or liver impairment; if changes in renal function occur during therapy, consider adjusting dose or discontinuing treatment; may increase risk of necrotizing enterocolitis in premature infants

Famotidine (Pepcid)

Competitively inhibits histamine at H2 receptor of gastric parietal cells, resulting in reduced gastric acid secretion, gastric volume, and hydrogen ion concentrations.

Dosing

Adult

20-40 mg PO bid

Pediatric

Not established; suggested dose is as follows:
<3 months: 0.5 mg/kg/dose PO qd
3 months to <1 year: 0.5 mg/kg PO bid
1-16 years: 1 mg/kg/d PO divided bid; may increase if needed, not to exceed 40 mg PO divided bid
>16 years: Administer as in adults

Interactions

May decrease effects of ketoconazole and itraconazole

Contraindications

Documented hypersensitivity

Precautions

Pregnancy

B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals

Precautions

If changes in renal function occur during therapy, consider adjusting dose or discontinuing treatment; may increase risk of necrotizing enterocolitis in premature infants

Nizatidine (Axid)

Competitively inhibits histamine at the H2 receptor of the gastric parietal cells, resulting in reduced gastric acid secretion, gastric volume, and reduced hydrogen concentrations.

Dosing

Adult

150 mg PO bid

Pediatric

Not established

Interactions

None reported

Contraindications

Documented hypersensitivity

Precautions

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

Caution in renal or liver impairment; if changes in renal function occur during therapy, consider adjusting dose or discontinuing treatment; may increase risk of necrotizing enterocolitis in premature infants

Proton pump inhibitors

Proton pump inhibitors inhibit gastric acid secretion by inhibition of the H⁺ -K⁺ -ATPase enzyme system in the gastric parietal cells. Used in cases of severe esophagitis and in patients not responsive to H2-antagonist therapy.

Omeprazole (Prilosec)

Decreases gastric acid secretion by inhibiting the parietal cell H⁺/K⁺ -ATPase pump.

Dosing

Adult

20 mg PO qd/bid

Pediatric

Not established

Interactions

May decrease effects of itraconazole and ketoconazole; may increase toxicity of warfarin, digoxin, and phenytoin

Contraindications

Documented hypersensitivity

Precautions

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

Bioavailability may increase in the elderly

Lansoprazole (Prevacid)

Suppresses gastric acid secretion by specific inhibition of the (H⁺, K⁺)-ATPase enzyme system (ie, proton pump) at the secretory surface of the gastric parietal cell. It blocks the final step of acid production. The effect is dose-related and inhibits both basal and stimulated gastric acid secretion, thus increasing gastric pH.

Dosing

Adult

30 mg PO qd/bid

Pediatric

Not established

Interactions

Cytochrome P450 isoenzyme CYP2C19 and CYP3A3/4 substrate; increases theophylline clearance mildly (approximately 10%); may increase warfarin effects; may interfere with the absorption of ketoconazole, ampicillin, iron salts, and digoxin; sucralfate delays and decreases lansoprazole absorption by 30%; cranberry juice significantly reduces gastric pH and may reduce proton pump inhibitors effectiveness

Contraindications

Documented hypersensitivity

Precautions

Pregnancy

B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals

Precautions

Consider adjusting dose in liver impairment; Prevacid® SoluTabs™ contain aspartame, which is metabolized to phenylalanine and must be used with caution in patients with phenylketonuria

Esomeprazole magnesium (Nexium)

S-isomer of omeprazole. Inhibits gastric acid secretion by inhibiting H⁺/K⁺ -ATPase enzyme system at secretory surface of gastric parietal cells.
Used in severe cases of and patients not responding to H2 antagonist therapy.
Used for up to 4 wk to treat and relieve symptoms of active duodenal ulcers; may be used up to 8 wk to treat all grades of erosive esophagitis.

Dosing

Adult

20-40 mg PO qd for 4-8 wk

Pediatric

Not established

Interactions

Extensively metabolized by CYP2C19 and CYP3A4, also inhibits CYP2C19; coadministration with CYP2C19 and CYP3A4 inhibitors (eg, voriconazole) may increase esomeprazole levels, but dosage adjustment is not normally required; may decrease atazanavir plasma levels; decreases diazepam clearance by 45%; postmarketing surveillance found coadministration with warfarin may increase INR and prothrombin time; amoxicillin or clarithromycin may increase plasma levels of esomeprazole when used concurrently; may reduce absorption of dapsone; may increase levels of diazepam and GI absorption of digoxin; may decrease absorption of iron, ketoconazole and itraconazole

Contraindications

Documented hypersensitivity

Precautions

Pregnancy

B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals

Precautions

Symptomatic relief with proton pump inhibitors may mask symptoms of gastric malignancy; frequently occurring (>1%) adverse effects include headache, diarrhea, nausea, flatulence, abdominal pain, constipation, and xerostomia

Rabeprazole sodium (Aciphex)

Decreases gastric acid secretion by inhibiting the parietal cell H⁺/K⁺ ATP pump.

Dosing

Adult

20-40 mg PO qd for 4-8 wk

Pediatric

Not established

Interactions

May decrease effects of itraconazole and ketoconazole; may increase toxicity of warfarin, digoxin, and phenytoin; inhibits cyclosporine metabolism

Contraindications

Documented hypersensitivity

Precautions

Pregnancy

B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals

Precautions

Symptomatic relief with proton pump inhibitors may mask symptoms of gastric malignancy

Pantoprazole (Pantoloc, Protonix)

Suppresses gastric acid secretion by specifically inhibiting H+/K+ ATPase enzyme system at the secretory surface of gastric parietal cells.

Dosing

Adult

40 mg PO bid; may increase if needed, not to exceed 240 mg/d
Alternatively, 80 mg IV q12h; may increase to 80 mg IV q8h if needed; treatment duration not to exceed 6 d

Pediatric

Not established

Interactions

May decrease effects of ketoconazole and iron salts

Contraindications

Documented hypersensitivity

Precautions

Pregnancy

B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals

Precautions

Decrease dose in hepatic impairment, half-life can increase 7- to 9-fold; no dose adjustment required in patients with renal impairment

Antidiarrheal agents

Reduce prevalence of diarrhea.

Diphenoxylate and atropine (Lomotil)

Antidiarrheal agent chemically related to narcotic analgesic meperidine. Acts on intestinal muscles to inhibit peristalsis and slow intestinal motility. Prolongs movement of electrolytes and fluid through bowel, and increases viscosity and loss of fluids and electrolytes. Also, diphenoxylate and atropine, a drug combination. A subtherapeutic dose of anticholinergic atropine sulfate is added to discourage overdosage, in which case diphenoxylate may clinically mimic the effects of codeine.
Each tab of Lomotil or 5 cc of elixir contains 2.5 mg diphenoxylate hydrochloride and 0.025 mg atropine sulfate.

Dosing

Adult

1-2 tab (or 10 ml elixir) PO tid/qid ac (as high as 8/d)until diarrhea controlled; then use smallest effective dose
Maintenance dose: 2-6 tab/d (10-30 ml) PO

Pediatric

<2 years: Not recommended
2-5 years: 2 mg of diphenoxylate PO tid
5-8 years: 2 mg of diphenoxylate PO qid
8-12 years: 2 mg of diphenoxylate 5 times/d
>12 years: Administer as in adults
Alternatively, 0.3-0.4 mg/kg/d PO divided qid; adjust dose downward according to overall nutritional status and degree of dehydration
Children <12 years: Use liquid Lomotil and not tab
>12 years: Administer as in adults

Interactions

Lomotil may delay metabolism of drugs in liver; CNS depressants, MAO inhibitors, and antimuscarinic agents may increase toxicity of this drug combination

Contraindications

Documented hypersensitivity; narrow-angle glaucoma or hepatic insufficiency

Precautions

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

In young children, dehydration may influence variability of response and predispose patient to delayed diphenoxylate intoxication; exercise caution in patients with ulcerative colitis; a decrease in intestinal motility may be detrimental to patients with diarrhea resulting from Shigella, Salmonella, and toxigenic strains of E coli

Loperamide (Imodium)

Acts on intestinal muscles to inhibit peristalsis and slow intestinal motility. Prolongs movement of electrolytes and fluid through bowel, and increases viscosity and loss of fluids and electrolytes.

Dosing

Adult

1-2 scoop PO prn (as high as 8/d)

Pediatric

<2 years: Not established
2-6 years: 1 mg PO tid
6-8 years: 2 mg PO bid
8-12 years: 2 mg PO tid
Maintenance: 0.1 mg/kg PO after each loose stool, not to exceed initial dose
Chronic diarrhea: 0.08-0.24 mg/kg/d divided bid/tid; not to exceed 2 mg/dose

Interactions

Phenothiazines, tricyclic antidepressants, and CNS depressants may increase loperamide toxicity; loperamide increases bioavailability and absorption of desmopressin, thus potentially increasing effect

Contraindications

Documented hypersensitivity; diarrhea resulting from infections; pseudomembranous colitis

Precautions

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

Discontinue use if no clinical improvement in 48 h; because primarily metabolized in liver, monitor for CNS toxicity in patients with hepatic insufficiency; do not use if high fever or blood in stool coincides with diarrhea

Cholestyramine (Questran)

Binds bile acids, thus reduces damage to the intestinal mucosa. Also reduces induction of colonic fluid secretion. Forms a nonabsorbable complex with bile acids in the intestine, which, in turn, inhibits enterohepatic reuptake of intestinal bile salts.

Dosing

Adult

3-4 g PO bid/qid mixed with fluid or food

Pediatric

240 mg/kg/d PO divided tid ac as slurry in water, juice, or milk

Interactions

Inhibits absorption of numerous drugs, including warfarin, thyroid hormone, amiodarone, NSAIDs, methotrexate, digitalis glycosides, glipizide, phenytoin, imipramine, niacin, methyldopa, tetracyclines, clofibrate, hydrocortisone, and penicillin G

Contraindications

Documented hypersensitivity

Precautions

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

Caution in constipation and phenylketonuria

Antispasmodic agents

Treat spastic disorders of the GI tract.

Dicyclomine (Bentyl)

Treats GI motility disturbances. Blocks action of acetylcholine at parasympathetic sites in secretory glands, smooth muscle, and CNS. Alternatively, hyoscyamine exerts similar antispasmodic effects.

Dosing

Adult

10-40 mg PO qid

Pediatric

10 mg/dose PO tid/qid

Interactions

Effects are weakened when administered with anti-Parkinson drugs, haloperidol, and phenothiazines; toxicity increases when administered concurrently with amantadine, antihistamines, type I antiarrhythmics, phenothiazines, TCAs, or narcotic analgesics

Contraindications

Documented hypersensitivity; myasthenia gravis; narrow-angle glaucoma

Precautions

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

Caution when administering to patients with hepatic or renal insufficiency, cardiovascular disease, urinary tract obstruction, ulcerative colitis, GI obstruction, hyperthyroidism, or hypertension

Hyoscyamine (Levbid, Levsin, Levsin-SL)

Blocks action of acetylcholine at parasympathetic sites in smooth muscle, secretory glands, and CNS, which, in turn, has antispasmodic effects. SL tabs may be administered orally, sublingually, or chewed.

Dosing

Adult

Levsin: 1 PO qid
Levbid: 1 PO bid
Levsin-SL: 1-2 SL prn

Pediatric

<2 years: 12.5 mcg/2.3 kg (maximum 75 mg/d) to 45.8 mcg/15 kg (maximum 275 mcg/d)
2-10 years: 32.0 mcg/10 kg to 125/50 kg; not to exceed 0.75 mg/dose
>10 years: Administer as in adults

Interactions

Effects decrease when used concurrently with antacids; toxicity increases when used concurrently with phenothiazines, amantadine, haloperidol, MAO inhibitors, and tricyclic antidepressants

Contraindications

Documented hypersensitivity; obstructive uropathy, narrow-angle glaucoma, myasthenia gravis, and obstructive GI tract disease

Precautions

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

Caution in elderly patients; some products contain sodium metabisulfite, which can cause allergic type reactions

Follow-up

Further Inpatient Care

• Day of admission
  • Admit the patient to the hospital if surgical intervention is anticipated or if he or she does not respond to outpatient treatment, is dehydrated, or has uncontrolled pain or diarrhea.
  • Start intravenous hydration. If indicated, obtain an abdominal flat plate image to exclude obstruction or megacolon. If the patient is nauseated or vomiting or has evidence of obstruction or megacolon, nasogastric intubation is indicated. Consider consultation with a surgeon.
  • If the patient has colitis, send a stool sample for C difficile toxin titer testing; also send one for routine culture and sensitivity testing if the patient has a new diagnosis of IBD. Laboratory studies to be considered include CBC count with differential, albumin level, ESR, glucose value, calcium level, magnesium level, phosphate value, electrolyte status, BUN/creatinine values, and a pregnancy test in females of childbearing age.
  • Initiate treatment with an oral aminosalicylate, intravenous corticosteroids, and metronidazole or ciprofloxacin (if antibiotics are indicated). Electrolyte correction and, potentially, transfusion, can be performed if indicated based on laboratory findings.
  • Keep patients NPO, except for medications (Crohn disease only); patients with ulcerative colitis may maintain a regular diet unless megacolon is present or surgery is being contemplated. Consider additional consultations with a registered dietitian and a stoma nurse if indicated. Consider line placement of central venous access.
• Hospital day 1
  • If the abdominal flat plate findings were not diagnostic or if diagnostic concerns remain, order a barium study (small bowel series or barium enema). Although a colonoscopic evaluation also may be contemplated, consider the increased risk of perforation in persons with acute colitis.
  • Assess and correct the posthydration CBC count and electrolyte values, as indicated. Depending on the response to the initial interventions, advancement of the diet may be considered.
• Hospital days 2 and 3
  • By the second hospital day, most patients should be showing clear evidence of clinical improvement. Assess the electrolyte status if intravenous 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. Consider skipping to interventions typically enacted on day 3 or 4 (or discharge).
  • Hospital day 3 is similar to day 2. The corticosteroid dose can be reduced, and a switch to oral forms of all medications can be contemplated. If home treatments are needed (eg, home hyperalimentation), initiate arrangements for these. The diet can be advanced as tolerated. Consider skipping to day 4 or 5 interventions.
• Hospital day 4
  • Continue to advance the diet, as tolerated. 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 intravenous therapy.
  • If no progress has been made in the patient's condition since admission, additional treatments are necessary, including surgery 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.
• Day of discharge/hospital day 5
  • 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 may be obtained to assist in future disease assessment but is unlikely to alter current management.
  • Discharge the patient on oral medications, with appropriate follow-up as an outpatient, typically within a few weeks.

Further Outpatient Care

• Outpatient medical care follows the approach outlined earlier in the article (see Medical Care) using the medications described (see Medication).
• Most outpatients' disease is in remission and requires little or no medication other than aminosalicylates (perhaps). Flares of IBD can generally be managed in an outpatient setting, primarily by stepping up the medication as described in the step-wise approach (see Medication).
• The biggest concern for outpatients is the duration and dosing of oral corticosteroids. This author uses a dose that is adequate to suppress inflammation (and thus symptoms), typically in the range of 20-40 mg of prednisone per day. Once symptoms are controlled, a rapid taper of the steroid follows. Patients in whom flares are frequent (>1-2 times/y), in whom the duration of steroid use is long (more than a few weeks each year), in whom reduction of the steroid dose causes recurrence of symptoms, or in whom steroids do not appear to be working are candidates for more intensive therapy. This higher step would include immune-modifying agents, infliximab, or experimental agents.
• One health maintenance issue of particular importance to patients with IBD is a reduction in bone density, either from decreased calcium absorption (because of the underlying disease process) or because of corticosteroid use. Crippling osteoporosis can be a very serious complication for patients with IBD. The threshold for obtaining bone density studies should be low, and treatment (with bisphosphonates and calcium supplements) can be initiated in patients with significantly low bone density.

Inpatient & Outpatient Medications

• If a step-wise approach is observed, the least amount of medication that is effective can be used (see Medication). A general rule of thumb is that once remission is achieved, the medications used to achieve remission (except for steroids, which should be tapered off) are continued. Despite the widespread availability of home infusion, intravenous corticosteroids are still used only in hospital settings because of potential problems and the dosing schedule.
• Home infusion of intravenous hyperalimentation is increasingly available for rare patients with Crohn disease in whom prolonged bowel rest is necessary. The short bowel may require prolonged hyperalimentation. Home intravenous antibiotics can also be arranged in this setting, if necessary.

Transfer

• The decision to transfer care of a patient (inpatient or outpatient) depends on the expertise and comfort level of the treating physician. Outpatient requests for a tertiary opinion should occur when patients have disease that is difficult to control with aminosalicylates and occasional brief courses of corticosteroids.
• Relatively infrequent use and the monitoring necessary for azathioprine, 6-MP, and infliximab prompt some physicians to choose to refer patients to tertiary care centers when the need for these agents becomes apparent; others are comfortable handling these agents themselves.
• For patients with refractory disease or those in whom corticosteroids cannot be weaned, referral for a second opinion generally is wise. Transfer inpatients for a tertiary opinion if the patient is not responding to intravenous steroids within a few days of admission; alternatively, strongly consider surgical intervention.

Deterrence/Prevention

• No known dietary or lifestyle changes prevent IBD.
• Dietary manipulation may help symptoms in persons with ulcerative colitis, and it actually may help reduce inflammation in persons with Crohn disease (see Diet). However, no evidence indicates that consuming or avoiding any particular food item causes or avoids flares of IBD.
• Smoking cessation is the only lifestyle change that may benefit patients with Crohn disease. Smoking has been linked to increases in the number and severity of flares of Crohn disease. Smoking cessation is occasionally sufficient to achieve remission in a patient with refractory Crohn disease.

Complications

• See the subtopics in Clinical for the various complications that occur with IBD.

Prognosis

• Prognosis is discussed in Mortality/Morbidity. The typical course of IBD (for the vast majority of patients) includes periods of remission interspersed with occasional flares.
• Ulcerative colitis
  • The average patient with ulcerative colitis has a 50% probability of having another flare during the next 2 years. However, the range of experiences is very broad; some patients may only have one flare over 25 years (as many as 10%), and others may have almost constant flares (much less common).
  • Patients with ulcerative colitis limited to the rectum and sigmoid at the time of diagnosis have a greater than 50% chance of progressing to more extensive disease and a 12% rate of colectomy over 25 years. More than 70% of patients presenting with proctitis alone continue to have disease limited to the rectum over 20 years. Most patients who develop more extensive disease do so within 5 years of diagnosis. Of patients with ulcerative colitis involving the entire colon, 60% eventually require colectomy, whereas very few of those with proctitis require colectomy. Of interest, most surgical interventions are required in the first year of disease; the annual colectomy rate after the first year is 1% for all patients.
  • Surgical resection for ulcerative colitis is considered curative for that disease, although postoperative pouchitis may occur in some patients. Of note, pouchitis is far more common in patients who have had a colectomy for ulcerative colitis than in those who have had a colectomy for other reasons (eg, familial adenomatous polyposis).
• Crohn disease
  • The clinical course of Crohn disease is much more variable than that of ulcerative colitis. The clinical activity of Crohn disease is independent of the anatomic location and extent of disease. A patient in remission has a 42% likelihood of being free of relapse for 2 years and only a 12% likelihood of being free of relapse for 10 years. Over a 4-year period, approximately one quarter of patients remain in remission, one quarter have frequent flares, and one half have a course that fluctuates between periods of flares and remissions.
  • Surgery for Crohn disease is generally performed for complications (eg, stricture, stenosis, obstruction, fistula, bleeding) rather than for the inflammatory disease itself. After operation, the frequency of recurrence of Crohn disease is high, generally in a pattern mimicking the original disease pattern, often on one or both sides of the surgical anastomosis. Approximately one third of patients with Crohn disease who require surgery require surgery again within 5 years, and two thirds require surgery again within 15 years. Endoscopic evidence of recurrent inflammation is present in 93% of patients 1 year after surgery for Crohn disease. Surgery 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 the rule.

Patient Education

• Patients with IBD benefit tremendously from education about their disease. As a chronic, often life-long disease that is frequently diagnosed in young adulthood, increasing patient knowledge improves medical compliance and assists in the management of symptoms.
• The Crohn's & Colitis Foundation of America is the most prominent organization in the United States that can directly provide educational materials for patients. This organization also supplies physicians with educational brochures at no cost upon request.
• For excellent patient education resources, visit eMedicine's Crohn Disease Center and Esophagus, Stomach, and Intestine Center. Also, see eMedicine's patient education articles Inflammatory Bowel Disease, Crohn Disease, Crohn Disease FAQs, and Irritable Bowel Syndrome.

Miscellaneous

Medicolegal Pitfalls

• Physicians may be at risk in certain areas of the treatment of patients with IBD. In general, these may be easily avoided by documenting appropriate education of the patient in the patient's medical record.
• Patients with IBD are more prone to the development of malignancy. Persons with Crohn disease have a higher rate of small bowel malignancy. Because no effective screening protocol is available, this should not be an issue. 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 these patients with colonoscopy at 2-year intervals once they have had the disease for that duration. If a patient refuses appropriate screening, document it in the medical record.
• Use of corticosteroids may lead to debilitating illness, particularly after long-term use. Warn patients who refuse to try more aggressive therapies and insist on continuing to take corticosteroids of the potential for long-term harm with these drugs, and take care to document these warnings and the alternatives offered in the medical record. Recommend to any patient who requires more than the rare short course of steroids that a yearly ophthalmologic examination is warranted because of the risk of cataract development.
• Patients with IBD who are undergoing endoscopic procedures have higher complication rates than the general population; the informed consent obtained for endoscopic procedures should always mention bleeding and perforation as potential complications. The single factor cited in most lawsuits involving endoscopy is failure to obtain adequate informed consent; missed malignancy and perforation are secondary.
• Ulcerative colitis is a surgically curable disease. Keep this in mind in patients who are having significant difficulty with their disease or are having significant adverse effects from medications (particularly those related to long-term steroid use). This author makes certain to mention this (and document it) when first meeting any patient with ulcerative colitis.
• If a decision is made to use or to continue immunosuppressant agents (ie, azathioprine, 6-MP) in a pregnant patient with IBD, the physician should be aware of the latest literature⁹ and should document the discussion of such with the patient, particularly given that these agents are still rated pregnancy class D by the US FDA.

Special Concerns

• Because patients with IBD are often diagnosed in the peak of childbearing years, issues related to fertility, pregnancy, and childbearing are always a concern with the disease and its treatment.
• Reproduction  
  • In women, fertility is normal or only minimally impaired. Women considering pregnancy should not take immune modifiers (ie, 6-MP, azathioprine). Although some case reports and small series show no adverse outcomes of pregnancies in patients with IBD who are taking immune modifiers, birth defects are also reported. If a patient is taking an immune modifier and becomes pregnant, stopping the immune modifier and using steroids, as needed, is advisable in most instances. Vigilance for birth defects is appropriate.
  • For men with IBD, the major concern is the medications needed for treatment. Sulfasalazine can decrease sperm counts and sperm motility, causing a functional azoospermia; the other aminosalicylates do not seem to 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 more birth defects, although this has been suggested.
• Pregnancy  
  • Most infants are born healthy. The prevalence of prematurity, stillbirth, and birth defects is similar to that of the general population. The prevalence of spontaneous abortion is slightly higher in patients with IBD (12.2% vs 9.9% in the general population). Prior proctocolectomy or ileostomy is not an impediment to successful pregnancy.
  • In general, 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. The literature suggests that continuation of immune modifiers (ie, azathioprine, 6-MP) may be safe in pregnancy. Metronidazole (Flagyl) and ciprofloxacin (Cipro) are safe in pregnancy. The topical agents are generally safe in pregnancy.
• Breastfeeding  
  • Mothers who require medication to control of their IBD should strongly consider bottle feeding their infants. Sulfasalazine metabolites can be detected in breast milk; exercise caution. Low concentrations of mesalamine and higher concentrations of its metabolites can be detected in breast milk. The significance of this is unknown. Corticosteroids can also be detected in breast milk. Immune modifiers are excreted in breast milk; either the immune modifier should be discontinued or the infant should be bottle fed. Metronidazole (Flagyl) and ciprofloxacin (Cipro) are excreted in breast milk; discontinue breastfeeding or discontinue the drugs.
  • Although small amounts of the topical agents are absorbed, and thus may be excreted in breast milk, the concentrations are much lower than with the oral forms of the same medications. These medications are probably reasonably safe in breastfeeding.
• Medications, safety in pregnancy 
  • All of the aminosalicylates and the corticosteroids appear to be safe in women in all phases of fertility, pregnancy, and lactation. Men should avoid sulfasalazine (Azulfidine) during periods when they and their mates are attempting to become pregnant.
  • The antibiotics (ie, metronidazole, ciprofloxacin) should generally be avoided during lactation; they are probably safe for fertility and during pregnancy.
  • The immune-modifying agents (ie, 6-MP, azathioprine) should be considered only on a case-by-case basis.
• Aspirin and nonsteroidal anti-inflammatory agents in IBD  
  • Substantial controversy has been raised in the medical/IBD community regarding the effects of aspirin or nonsteroidal anti-inflammatory drugs (NSAIDs) on IBD. Published data and recommendations indicate that aspirin and NSAIDs cause a number of flares of IBD and, thus, should be avoided in all patients with IBD. On the other hand, studies also indicate that only a very minor link exists between the use of aspirin or NSAIDs and flares of IBD.
  • This author's practice is to administer aspirin or NSAIDs judiciously when indicated (eg, with arthritis and/or arthralgias associated with IBD), with the caveat that the patient is warned of the possibility that the medication may cause a flare of the IBD. If, shortly after starting the NSAID, a flare occurs, then the NSAID should be discontinued. If the patient's disease remains in remission, the patient can be maintained on the NSAID as necessary.

Multimedia

Media file 1: Inflammatory bowel disease. Severe colitis noted during colonoscopy. The mucosa is grossly denuded, with active bleeding noted. This patient had her colon resected very shortly after this view was obtained.

Media file 2: Inflammatory bowel disease. Stricture in the terminal ileum noted during colonoscopy. Narrowed segment visible upon intubation of the terminal ileum with the colonoscope. Relatively little active inflammation is present, indicating that this is a cicatrix stricture.

Media file 3: Inflammatory bowel disease. Enteroenteric fistula noted on small bowel series of x-ray films. The narrow-appearing segments filled out relatively normally on subsequent films. Note that barium is just starting to enter the cecum in the right lower quadrant (viewer's left), but that barium has also started to enter the sigmoid colon toward the bottom of the picture, thus indicating the presence of a fistula from the small bowel to the sigmoid colon.

Media file 4: Inflammatory bowel disease. Crohn disease involving the terminal ileum. Note the "string sign" in the right lower quadrant (viewer's left).

Media file 5: Inflammatory bowel disease. Inflammation in the terminal ileum noted during colonoscopy. Areas of inflammation, friability, and ulceration in the terminal ileum are consistent with mild-to-moderate Crohn disease.

Media file 6: Inflammatory bowel disease. Severe advanced pyoderma gangrenosum of the medial aspect of the left ankle.

Media file 7: Inflammatory bowel disease. Early pyoderma gangrenosum, before skin breakdown. Medial aspect of the right ankle. Same day and same patient as in Media file 6.

References

1. Ananthakrishnan AN, Binion DG. Treatment of ulcerative colitis in the elderly. Dig Dis. 2009;27(3):327-34. [Medline].

2. Garcia-Erce JA, Gomollon F, Munoz M. Blood transfusion for the treatment of acute anaemia in inflammatory bowel disease and other digestive diseases. World J Gastroenterol. Oct 7 2009;15(37):4686-94. [Medline].

3. Bengtson MB, Solberg IC, Aamodt G, et al. Relationships between inflammatory bowel disease and perinatal factors: Both maternal and paternal disease are related to preterm birth of offspring. Inflamm Bowel Dis. Sep 30 2009;epub ahead of print. [Medline].

4. Scherr R, Essers J, Hakonarson H, Kugathasan S. Genetic determinants of pediatric inflammatory bowel disease: is age of onset genetically determined?. Dig Dis. 2009;27(3):236-9. [Medline].

5. Pickhardt PJ. Noninvasive radiologic imaging of the large intestine: a valuable complement to optical colonoscopy. Curr Opin Gastroenterol. Sep 25 2009;[Medline].

6. Yamamoto T, Nakahigashi M, Umegae S, Matsumoto K. Prospective clinical trial: enteral nutrition during maintenance infliximab in Crohn's disease. J Gastroenterol. Oct 2 2009;[Medline].

7. Leso V, Leggio L, Armuzzi A, et al. Role of the tumor necrosis factor antagonists in the treatment of inflammatory bowel disease: an update. Eur J Gastroenterol Hepatol. Sep 25 2009;epub ahead of print. [Medline].

8. Lazarev M, Ullman T, Schraut WH, et al. Small bowel resection rates in Crohn's disease and the indication for surgery over time: Experience from a large tertiary care center. Inflamm Bowel Dis. Oct 1 2009;epub ahead of print. [Medline].

9. Dignass AU, Hartmann F, Sturm A, Stein J. Management of inflammatory bowel diseases during pregnancy. Dig Dis. 2009;27(3):341-6. [Medline].

10. Adachi JD, Rostom A. Metabolic bone disease in adults with inflammatory bowel disease. Inflamm Bowel Dis. Aug 1999;5(3):200-11. [Medline].

11. American Society for Gastrointestinal Endoscopy. The role of colonoscopy in the management of patients with inflammatory bowel disease. Gastrointest Endosc. Dec 1998;48(6):689-90. [Medline].

12. American Society for Parenteral and Enteral Nutrition. Intestinal dysfunction/failure: Inflammatory Bowel Disease in: Guidelines for the use of parenteral and enteral nutrition in adult and pediatric patients. JPEN J Parenter Enteral Nutr. Jul-Aug 1993;17(4 Suppl):18SA-19SA. [Medline].

13. Andres PG, Friedman LS. Epidemiology and the natural course of inflammatory bowel disease. Gastroenterol Clin North Am. Jun 1999;28(2):255-81, vii. [Medline].

14. Ardizzone S, Petrillo M, Imbesi V, et al. Is maintenance therapy always necessary for patients with ulcerative colitis in remission?. Aliment Pharmacol Ther. Mar 1999;13(3):373-9. [Medline].

15. Becker JM. Surgical therapy for ulcerative colitis and Crohn's disease. Gastroenterol Clin North Am. Jun 1999;28(2):371-90, viii-ix. [Medline].

16. Bergman L, Djarv L. A comparative study of loperamide and diphenoxylate in the treatment of chronic diarrhoea caused by intestinal resection. Ann Clin Res. Dec 1981;13(6):402-5. [Medline].

17. Bernstein CN, Boult IF, Greenberg HM, van der Putten W, Duffy G, Grahame GR. A prospective randomized comparison between small bowel enteroclysis and small bowel follow-through in Crohn's disease. Gastroenterology. Aug 1997;113(2):390-8. [Medline].

18. Bonner GF, Walczak M, Kitchen L, Bayona M. Tolerance of nonsteroidal antiinflammatory drugs in patients with inflammatory bowel disease. Am J Gastroenterol. Aug 2000;95(8):1946-8. [Medline].

19. Breuer RI, Soergel KH, Lashner BA, et al. Short chain fatty acid rectal irrigation for left-sided ulcerative colitis: a randomised, placebo controlled trial. Gut. Apr 1997;40(4):485-91. [Medline].

20. Brynskov J, Freund L, Rasmussen SN, et al. A placebo-controlled, double-blind, randomized trial of cyclosporine therapy in active chronic Crohn's disease. N Engl J Med. Sep 28 1989;321(13):845-50. [Medline].

21. Buchman AL. Bones and Crohn's: problems and solutions. Inflamm Bowel Dis. Aug 1999;5(3):212-27. [Medline].

22. Burakoff R, Opper F. Pregnancy and nursing. Gastroenterol Clin North Am. Sep 1995;24(3):689-98. [Medline].

23. Caulfield ME, Michener WM. Ulcerative colitis. In: Wyllie R, Hyams JS, eds. Pediatric Gastrointestinal Disease: Pathophysiology, Diagnosis, and Management. Philadelphia: WB Saunders; 1993:765-87.

24. Choi PM, Nugent FW, Schoetz DJ Jr, Silverman ML, Haggitt RC. Colonoscopic surveillance reduces mortality from colorectal cancer in ulcerative colitis. Gastroenterology. Aug 1993;105(2):418-24. [Medline].

25. Colombel JF, Lemann M, Cassagnou M, et al. A controlled trial comparing ciprofloxacin with mesalazine for the treatment of active Crohn's disease. Groupe d'Etudes Thérapeutiques des Affections Inflammatoires Digestives (GETAID). Am J Gastroenterol. Mar 1999;94(3):674-8. [Medline].

26. Egan LJ, Sandborn WJ, Tremaine WJ, et al. A randomized dose-response and pharmacokinetic study of methotrexate for refractory inflammatory Crohn's disease and ulcerative colitis. Aliment Pharmacol Ther. Dec 1999;13(12):1597-604. [Medline].

27. Ewe K, Press AG, Singe CC, Stufler M, et al. Azathioprine combined with prednisolone or monotherapy with prednisolone in active Crohn's disease. Gastroenterology. Aug 1993;105(2):367-72. [Medline].

28. Fazio VW, Marchetti F, Church M, et al. Effect of resection margins on the recurrence of Crohn's disease in the small bowel. A randomized controlled trial. Ann Surg. Oct 1996;224(4):563-71; discussion 571-3. [Medline].

29. Felder JB, Korelitz BI, Rajapakse R, et al. Effects of nonsteroidal antiinflammatory drugs on inflammatory bowel disease: a case-control study. Am J Gastroenterol. Aug 2000;95(8):1949-54. [Medline].

30. Ferry GD. Aminosalicylates in the treatment of children with inflammatory bowel disease. Summary of the workshop on aminosalicylate pharmacology. Inflamm Bowel Dis. May 1998;4(2):113-4; discussion 114-6. [Medline].

31. Francella A, Dyan A, Bodian C, et al. The safety of 6-mercaptopurine for childbearing patients with inflammatory bowel disease: a retrospective cohort study. Gastroenterology. Jan 2003;124(1):9-17. [Medline].

32. Gaffney PR, Doyle CT, Gaffney A, et al. Paradoxical response to heparin in 10 patients with ulcerative colitis. Am J Gastroenterol. Feb 1995;90(2):220-3. [Medline].

33. Gendre JP, Mary JY, Florent C, et al. Oral mesalamine (Pentasa) as maintenance treatment in Crohn's disease: a multicenter placebo-controlled study. The Groupe d'Etudes Thérapeutiques des Affections Inflammatoires Digestives (GETAID). Gastroenterology. Feb 1993;104(2):435-9. [Medline].

34. Ginsberg AL. Topical salicylate therapy (4-ASA and 5-ASA enemas). Gastroenterol Clin North Am. Mar 1989;18(1):35-42. [Medline].

35. Gitnick G, ed. Inflammatory Bowel Disease: Diagnosis and Treatment. New York: Igaku-Shoin Medical; 1995.

36. Griffiths AM, Ohlsson A, Sherman PM, Sutherland LR. Meta-analysis of enteral nutrition as a primary treatment of active Crohn's disease. Gastroenterology. Apr 1995;108(4):1056-67. [Medline].

37. Hanauer S, Schwartz J, Robinson M, et al. Mesalamine capsules for treatment of active ulcerative colitis: results of a controlled trial. Pentasa Study Group. Am J Gastroenterol. Aug 1993;88(8):1188-97. [Medline].

38. Hanauer SB. Review article: safety of infliximab in clinical trials. Aliment Pharmacol Ther. Sep 1999;13 Suppl 4:16-22; discussion 38. [Medline].

39. Hanauer SB, Meyers S. Management of Crohn's disease in adults. Am J Gastroenterol. Apr 1997;92(4):559-66. [Medline].

40. Hurst RD, Cohen RD. The role of laparoscopy and strictureplasty in the management of inflammatory bowel disease. Semin Gastrointest Dis. Jan 2000;11(1):10-7. [Medline].

41. Hyams JS. Crohn's disease. In: Wyllie R, Hyams JS, eds. Pediatric Gastrointestinal Disease: Pathophysiology, Diagnosis, and Management. Philadelphia: WB Saunders; 1993:742-64.

42. International Mesalazine Study Group. Coated oral 5-aminosalicylic acid versus placebo in maintaining remission of inactive Crohn's disease. Aliment Pharmacol Ther. Feb 1990;4(1):55-64. [Medline].

43. Issenman RM. Bone mineral metabolism in pediatric inflammatory bowel disease. Inflamm Bowel Dis. Aug 1999;5(3):192-9. [Medline].

44. Jacobsen O, Hojgaard L, Hylander Moller E, et al. Effect of enterocoated cholestyramine on bowel habit after ileal resection: a double blind crossover study. Br Med J (Clin Res Ed). May 4 1985;290(6478):1315-8. [Medline].

45. Katz J. Treatment of Crohn's disease with 5-ASA. Am J Gastroenterol. Sep 1993;88(9):1315-7. [Medline].

46. Kirschner BS. Ulcerative colitis and Crohn's disease in children. Diagnosis and management. Gastroenterol Clin North Am. Mar 1995;24(1):99-117. [Medline].

47. Kornbluth A, Present DH, Lichtiger S, Hanauer S. Cyclosporin for severe ulcerative colitis: a user's guide. Am J Gastroenterol. Sep 1997;92(9):1424-8. [Medline].

48. Kornbluth A, Sachar DB. Ulcerative colitis practice guidelines in adults. American College of Gastroenterology, Practice Parameters Committee. Am J Gastroenterol. Feb 1997;92(2):204-11. [Medline].

49. Kornbluth AA, Salomon P, Sacks HS, Mitty R, Janowitz HD. Meta-analysis of the effectiveness of current drug therapy of ulcerative colitis. J Clin Gastroenterol. Apr 1993;16(3):215-8. [Medline].

50. Kozarek RA, Patterson DJ, Gelfand MD, et al. Methotrexate induces clinical and histologic remission in patients with refractory inflammatory bowel disease. Ann Intern Med. Mar 1 1989;110(5):353-6. [Medline].

51. Lamers CB, Griffioen G, van Hogezand RA, Veenendaal RA. Azathioprine: an update on clinical efficacy and safety in inflammatory bowel disease. Scand J Gastroenterol Suppl. 1999;230:111-5. [Medline].

52. Lewis JD, Schwartz JS, Lichtenstein GR. Azathioprine for maintenance of remission in Crohn's disease: benefits outweigh the risk of lymphoma. Gastroenterology. Jun 2000;118(6):1018-24. [Medline].

53. Lichtenstein GR. Treatment of fistulizing Crohn's disease. Gastroenterology. Oct 2000;119(4):1132-47. [Medline].

54. Lichtiger S, Present DH. Preliminary report: cyclosporin in treatment of severe active ulcerative colitis. Lancet. Jul 7 1990;336(8706):16-9. [Medline].

55. Lichtiger S, Present DH, Kornbluth A, et al. Cyclosporine in severe ulcerative colitis refractory to steroid therapy. N Engl J Med. Jun 30 1994;330(26):1841-5. [Medline].

56. Lochs H, Mayer M, Fleig WE, et al. Prophylaxis of postoperative relapse in Crohn's disease with mesalamine: European Cooperative Crohn's Disease Study VI. Gastroenterology. Feb 2000;118(2):264-73. [Medline].

57. Lofberg R, Danielsson A, Suhr O, et al. Oral budesonide versus prednisolone in patients with active extensive and left-sided ulcerative colitis. Gastroenterology. Jun 1996;110(6):1713-8. [Medline].

58. Mathew CG, Lewis CM. Genetics of inflammatory bowel disease: progress and prospects. Hum Mol Genet. Apr 1 2004;13 Spec No 1:R161-8. [Medline].

59. Meinzer U, Idestrom M, Alberti C, et al. Ileal involvement is age dependent in pediatric Crohn's disease. Inflamm Bowel Dis. Jul 2005;11(7):639-44. [Medline].

60. Mekhjian HS, Switz DM, Melnyk CS, Rankin GB, Brooks RK. Clinical features and natural history of Crohn's disease. Gastroenterology. Oct 1979;77(4 Pt 2):898-906. [Medline].

61. Mesalamine Study Group. An oral preparation of mesalamine as long-term maintenance therapy for ulcerative colitis. A randomized, placebo-controlled trial. Ann Intern Med. Jan 15 1996;124(2):204-11. [Medline].

62. Michetti P, Peppercorn MA. Medical therapy of specific clinical presentations. Gastroenterol Clin North Am. Jun 1999;28(2):353-70, viii. [Medline].

63. Munakata A, Yoshida Y, Muto T, et al. Double-blind comparative study of sulfasalazine and controlled-release mesalazine tablets in the treatment of active ulcerative colitis. J Gastroenterol. Nov 1995;30 Suppl 8:108-11. [Medline].

64. O'Brien J. Nonsteroidal anti-inflammatory drugs in patients with inflammatory bowel disease. Am J Gastroenterol. Aug 2000;95(8):1859-61. [Medline].

65. Oostenbrug LE, van Dullemen HM, te Meerman GJ, Jansen PL. IBD and genetics: new developments. Scand J Gastroenterol Suppl. 2003;63-8. [Medline].

66. Oren R, Moshkowitz M, Odes S, et al. Methotrexate in chronic active Crohn's disease: a double-blind, randomized, Israeli multicenter trial. Am J Gastroenterol. Dec 1997;92(12):2203-9. [Medline].

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

68. Poritz LS, Rowe WA, Swenson BR, Hollenbeak CS, Koltun WA. Intravenous cyclosporine for the treatment of severe steroid refractory ulcerative colitis: what is the cost?. Dis Colon Rectum. Sep 2005;48(9):1685-90. [Medline].

69. Prantera C, Cottone M, Pallone F, et al. Mesalamine in the treatment of mild to moderate active Crohn's ileitis: results of a randomized, multicenter trial. Gastroenterology. Mar 1999;116(3):521-6. [Medline].

70. Present DH. Review article: the efficacy of infliximab in Crohn's disease--healing of fistulae. Aliment Pharmacol Ther. Sep 1999;13 Suppl 4:23-8; discussion 38. [Medline].

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

72. Rankin GB, Watts HD, Melnyk CS, Kelley ML Jr. National Cooperative Crohn's Disease Study: extraintestinal manifestations and perianal complications. Gastroenterology. Oct 1979;77(4 Pt 2):914-20. [Medline].

73. Rowe WA, Bayless TM. Colonic short-chain fatty acids: fuel from the lumen?. Gastroenterology. Jul 1992;103(1):336-8. [Medline].

74. Rutgeerts P, Feagan BG, Lichtenstein GR, et al. Comparison of scheduled and episodic treatment strategies of infliximab in Crohn's disease. Gastroenterology. Feb 2004;126(2):402-13. [Medline].

75. Rutgeerts PJ. Review article: efficacy of infliximab in Crohn's disease--induction and maintenance of remission. Aliment Pharmacol Ther. Sep 1999;13 Suppl 4:9-15; discussion 38. [Medline].

76. Sandborn WJ. Azathioprine: state of the art in inflammatory bowel disease. Scand J Gastroenterol Suppl. 1998;225:92-9. [Medline].

77. Sandborn WJ, Tremaine WJ, Offord KP, et al. Transdermal nicotine for mildly to moderately active ulcerative colitis. A randomized, double-blind, placebo-controlled trial. Ann Intern Med. Mar 1 1997;126(5):364-71. [Medline].

78. Sands BE, Bank S, Sninsky CA, et al. Preliminary evaluation of safety and activity of recombinant human interleukin 11 in patients with active Crohn's disease. Gastroenterology. Jul 1999;117(1):58-64. [Medline].

79. Scheppach W. Treatment of distal ulcerative colitis with short-chain fatty acid enemas. A placebo-controlled trial. German-Austrian SCFA Study Group. Dig Dis Sci. Nov 1996;41(11):2254-9. [Medline].

80. Scheppach W, Sommer H, Kirchner T, et al. Effect of butyrate enemas on the colonic mucosa in distal ulcerative colitis. Gastroenterology. Jul 1992;103(1):51-6. [Medline].

81. Scotiniotis I, Rubesin SE, Ginsberg GG. Imaging modalities in inflammatory bowel disease. Gastroenterol Clin North Am. Jun 1999;28(2):391-421, ix. [Medline].

82. Shaffer EA, Corenblum EB. Osteonecrosis, corticosteroid use and Crohn's disease: evidence-based medicine versus civil law. Can J Gastroenterol. Feb 2000;14(2):91-3. [Medline].

83. Silvennoinen JA, Karttunen TJ, Niemela SE, Manelius JJ, Lehtola JK. A controlled study of bone mineral density in patients with inflammatory bowel disease. Gut. Jul 1995;37(1):71-6. [Medline].

84. Stein RB, Hanauer SB. Medical therapy for inflammatory bowel disease. Gastroenterol Clin North Am. Jun 1999;28(2):297-321. [Medline].

85. Stein RB, Lichtenstein GR. Complications after ileal pouch-anal anastomosis. Semin Gastrointest Dis. Jan 2000;11(1):2-9. [Medline].

86. Sutherland LR, May GR, Shaffer EA. Sulfasalazine revisited: a meta-analysis of 5-aminosalicylic acid in the treatment of ulcerative colitis. Ann Intern Med. Apr 1 1993;118(7):540-9. [Medline].

87. Thomsen OO, Cortot A, Jewell D, et al. A comparison of budesonide and mesalamine for active Crohn's disease. International Budesonide-Mesalamine Study Group. N Engl J Med. Aug 6 1998;339(6):370-4. [Medline].

88. Tremaine WJ. Inflammatory bowel disease workshop. Vail, Colorado, March 22 and 23, 1998. Maintenance therapy in IBD. Inflamm Bowel Dis. Nov 1998;4(4):292-5; discussion 295-301. [Medline].

89. Yamamoto T, Keighley MR. Smoking and disease recurrence after operation for Crohn's disease. Br J Surg. Apr 2000;87(4):398-404. [Medline].

Keywords

inflammatory bowel disease, IBD, Crohn disease, Crohn's disease, terminal ileitis, granulomatous enteritis, ulcerative colitis, gastrointestinal tract disease, GI tract disease, gastrointestinal disease, GI disease, Clostridium difficile,

irritable bowel syndrome, IBS, irritable bowel disease, pyoderma gangrenosum, bloody diarrhea, inflamed colon, colonoscopy, proctocolectomy, continent ileostomy, Koch pouch, colonic disease, ileoanal anastomosis, segmental colon resection, colorectal cancer, Crohn colitis, intestinal obstruction, intestinal strictures, scarred strictures, cicatrix strictures, colonic strictures, fistulae, perianal disease, toxic megacolon, colon cancer,pancolitis, perianalabscesses, loss of colonic haustrae, sigmoidoscopy, proctitis

colectomy, occult blood loss, growth retardation, gastric Crohn disease, duodenal Crohn disease, medication-induced arthropathies, axial arthritis, ankylosing spondylitis, sacroiliitis, episcleritis, iritis, uveitis, erythema nodosum, herpetic lesions, calcium oxalate stones, hydronephrosis, sclerosing cholangitis, cholangiocarcinoma, cirrhosis, gallstones, iron deficiency anemia, anemia of chronic disease, strokes, retinal thrombi, pulmonary emboli

Contributor Information and Disclosures

Author

William A Rowe, MD, Consulting Staff, Gastroenterology, Gastroenterology Associates
William A Rowe, MD is a member of the following medical societies: American Gastroenterological Association, American Society for Gastrointestinal Endoscopy, and Crohns and Colitis Foundation of America
Disclosure: Nothing to disclose.

Medical Editor

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

Pharmacy Editor

Francisco Talavera, PharmD, PhD, Senior Pharmacy Editor, eMedicine
Disclosure: eMedicine Salary Employment

Managing Editor

Oscar S Brann, MD, FACP, Associate Clinical Professor, Department of Medicine, University of California at San Diego; Consulting Staff, Mecklenburg Medical Group
Oscar S Brann, MD, FACP is a member of the following medical societies: American Gastroenterological Association
Disclosure: Nothing to disclose.

CME Editor

Alex J Mechaber, MD, FACP, 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.

Chief Editor

Julian Katz, MD, Clinical Professor of Medicine, Drexel University College of Medicine; Consulting Staff, Department of Medicine, Section of Gastroenterology and Hepatology, Hospital of the Medical College of Pennsylvania
Julian Katz, MD is a member of the following medical societies: American College of Gastroenterology, American College of Physicians, American Gastroenterological Association, American Geriatrics Society, American Medical Association, American Society for Gastrointestinal Endoscopy, American Society of Law Medicine and Ethics, American Trauma Society, Association of American Medical Colleges, and Physicians for Social Responsibility
Disclosure: Nothing to disclose.

Related eMedicine Topics

• Crohn Disease
• Crohn Disease [in the Pediatrics: General Medicine section]
• Inflammatory Bowel Disease [in the Emergency Medicine section]
• Inflammatory Bowel Disease [in the Ophthalmology section]
• Ulcerative Colitis
• Ulcerative Colitis [in the Pediatrics: General Medicine section]

Clinical Trials

• Collection of Specimens for Study of Inflammatory Bowel Disease
• Infliximab to Treat Crohn's-like Inflammatory Bowel Disease in Chronic Granulomatous Disease
• Interactions Between Immune Cells of Intestinal Mucosa or Peripheral Blood With the Extracellular Matrix in Inflammatory Bowel Disease (IBD)
• Managing Inflammatory Bowel Disease
• Pediatric Inflammatory Bowel Disease Collaborative Research Group Registry
• Study Registry to Evaluate the Long-Term Safety of Infliximab and Clinical Status of Pediatric Patients With Inflammatory Bowel Disease.
• Surgical Decision Making Among People With Inflammatory Bowel Disease
• Vitamin D levels in Children With IBD

Clinical Guidelines

• ACR Appropriateness Criteria® Crohn's disease. American College of Radiology - Medical Specialty Society. 1998 (revised 2005). 11 pages. NGC:004772
• American Gastroenterological Association Institute medical position statement on corticosteroids, immunomodulators, and infliximab in inflammatory bowel disease. American Gastroenterological Association Institute - Medical Specialty Society. 2006 Mar. 5 pages. NGC:004873
• ASGE guideline: endoscopy in the diagnosis and treatment of inflammatory bowel disease. American Society for Gastrointestinal Endoscopy - Medical Specialty Society. 2006 Apr. 8 pages. NGC:004977
• Evidence-based care guideline for management of pediatric moderate/severe inflammatory bowel disease (IBD). Cincinnati Children's Hospital Medical Center - Hospital/Medical Center. 2007 Apr 5. 29 pages. NGC:005604
• Guidelines for osteoporosis in inflammatory bowel disease and coeliac disease. British Society of Gastroenterology - Medical Specialty Society. 2007 Jun. 18 pages. NGC:007149

© 1994- by Medscape.
All Rights Reserved
(http://www.medscape.com/public/copyright)