Inflammatory Bowel Disease

last authored: Feb 2015, Brandon Cook, David LaPierre
last reviewed:

 

 

Introduction

Inflammatory bowel disease describes two distinct but related diseases - ulcerative colitis (UC) and Crohn's disease (CD). In the US, the prevalence of UC and CD are approximately 234 and 201 per 100,000, respectively (Kappelman et al, 2007). Both sexes are affected, though women have higher rates of CD than men.

 

A bimodal age of presentation exists for UC, with peaks between ages 15-40 and ages 50-80 (Langan et al, 2007). Crohn’s disease has a median age of diagnosis between 20-30 (Wilkens, Jarvis, and Patel, 2011).

 

Worldwide, rates are much higher in Europe and North America, though there is a slowly growing increase in tropical countries as well.

 

 

 

The Case of Mrs C

Mrs C is a 40 year-old woman with a five year history of occasionally bloody diarrhea, abdominal pain, and weight loss. Tests for infectious causes have been negative. Her family doctor considers inflammatory bowel disease.

• Q: how would this diagnosis be explored?
• Q: what are the signs and symptoms of IBD?

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Causes and Risk Factors

Although causes remain elusive, the main theory regarding IBD involves a dysregulation of the normal intestinal immune processes, most likely in response to bacteria, normal flora, or otherwise, or some other environmental component.

Genetics

IBD affects people from every ethnic group, but is more common in people from Northern European ancestry. Approximately 10% of people with IBD have a first degree relative with the disease.

 

A large number of susceptibility loci have been identified, supporting the idea of polygenic effects. The Nod2/CARD15 gene appears especially important (Wilkens, Jarvis, and Patel, 2011).

Immunologic factors

In normal intestine, lymphoid tissue is constantly activated in response to antigenic substances which have crossed the epithelial barrier. A large network of different cell types exists to discriminate harmful from benign stimuli, and regulatory cells are important in attenuating inappropriate responses. In IBD, it appears an over-activation response to benign stimuli may be involved.

 

Environmental Factors

Even though IBD is more common in industrialized countries, the role of the environment remains poorly understood. Many infectious agents, such as Mycobacterium paratuberculosis or measles virus, have been implicated in IBD, but definitive links are unclear.

Smoking leads to a more aggressive Crohn's disease while is seemingly protective in ulcerative colitis.

Elemental diets can reduce inflammation, but no dietary triggers have yet been found to cause IBD.

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Pathophysiology

 

Ulcerative colitis

Ulcerative colitis is characterized by inflammatory changes affecting the colonic mucosa in a continuous superficial fashion, starting in the rectum and spreading proximally to the . Approximately 40-50% have proctitis or proctosigmoiditis, 30-40% have left-sided colitis extending to the splenic flexure, and the remaining 20-25% have pancolitis.
There is an association with primary sclerosing cholangitis.

 

Crohn's Disease

Crohn's disease can involve any segment of the GI tract, often in a discontinuous fashion to form skip lesions. Transmural chronic inflammation, involving cytokines such as IL-1, IL-2, IL-6, and TNFα, results thickening and eventual strictures. The mucosal surface can become cobblestoned, relating to edema with linear ulcerations. Fissures, localized perforations, and abscesses can form fistulas - to other areas of the gut, the bladder, the vagina, or to skin.

The most common form is ileocecal Crohn's, affecting 40% of patients. Thirty percent of patients have disease affecting the small intestine, while 25% of patients have exclusive colonic involvement. Ulcers can be aphthous or more linear.

 

 

Distinguishing UC from CD

While at times distinguishing between UC and CD can be difficult, Crohn's disease is distinguished by:

• small bowel involvement
• rectal sparing
• perianal disease
• skip lesions
• fistulas
• granulomas

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Signs and Symptoms

Diagnosis of IBD is made by incorporating clinical, radiologic, endoscopic, and histologic information. It is often diagnosed during presumptive surgery for appendicitis.

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Investigations

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Differential Diagnosis

The differential diagnosis of chronic abdominal pain is described here. In particular, it is important to consider:

• irritable bowel syndrome (IBS)
• Clostridium difficile colitis
• gastroenteritis
• parasitic infection

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Treatments

IBD is a chronic disease, and this should be communicated to patients to ensure their expectations are appropriate.

 

An ongoing relationship with care providers, including primary care, internal medicine specialists, is important. Allied health professionals that are frequently involved include dietitians and pharmacists.

 

Surgical care may be required for patients with progressive and/or advanced disease.

 

The guiding principle is to use the least toxic treatment regimen possible. Answer three questions - what is it? where is it? how bad is it? - when determining treatment.

 

Treatment During Flares

During acute worsening, provide IV fluids and electrolyte replacement as needed. Pain control frequently requires opioids.

Assess for, and treat, infections.

Immunosuppresants are frequently needed in high doses during flares.

 

Lifestyle treatments

The most important lifestyle modification for patients with Crohn's is smoking cessation.

There is no clear link between IBD and specific foods; some foods are that are easily tolerated by one person can cause discomfort in other individuals. Lactose intolerance is common. Eating a balanced diet that follows the Canada Food Guide is important to ensure adequate nutritional intake.

 

There is some evidence that probiotics, including non-pathogenic Escherichia coli and Lactobacillus, may be of some benefic.

 

 

Medications

Immunosuppresants include:

• 5-ASA is a mild anti-inflammatory that is a first line treatment for mild to moderate ulcerative colitis and Crohn's disease. It can be given by suppository, enema, or orally.
• glucocorticoids such as prednisone are useful for flares, but with multiple serious side effects, not useful for long term. Avoid in patients with bleeding before ruling out C. difficile
• Immunosuppressants, including azathioprine, methotrexate and 6-mercaptopurine, are used for inducing remission of moderate to severe Crohn’s disease
• Anti-TNF biologics, such as infliximab or adalimumab, can be effective at inducing remission in moderate to severe disease, but with a tremendous price tag

Antidiarrheals, including loperamide and cholestyramine, should be avoided during flares to avoid toxic megacolon (described below).

 

Antibiotics such as ciprofloxacin and metronidazole can help decrease severity during flares.

 

Surgery

Crohn’s: Surgery is generally used for complications of Crohn's disease, such as perforation, obstruction, bleeding, fistulas, and cancer. Surgery after failed medical management is rare. Surgery is to control, not to cure, and the least amount of bowel required should be taken out. Recurrence and the need for repeat operations is very common. Female fertility can be affected by colectomy.

 

Ulcerative colitis: Indications for surgery includes failed medical management, obstruction, toxic megacolon, or longstanding disease causing increased risk of malignancy.

Curative UC surgery involves excision of the rectum and colon and re-anastomosis of the anus to the terminal ileum by forming a J-pouch, or pelvic pouch. In patients who are very sick, or who have co-morbidities, the procedure is done as a sequence of two operations. The first step is to staple off the rectum and form a temporary stoma as the tissues heal, and the pouch is anastomosed to the anus during a second, later operation.

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Consequences and Course

IBD can follow patterns of relapse and remission, but serious episodes of disease worsening can occur. Obstruction, perforation, or bleeding can be catastrophic and at times life-threatening.

 

Strictures, abscesses, fistulas, and perianal disease can occur with IBD, and especially Crohn’s.

Psychosocial impact: The symptoms of IBD can lead to loss of work, hobbies, and socialization, and this can be profound.

Colorectal cancer: Both Crohn's and ulcerative colitis carry an increased risk of colorectal cancer. Disease severity does not appear to correlate with risk. Initial screening for colorectal cancer by colonoscopy should occur 8 years after onset of pancolitis or 12 to 15 years after onset of left-sided disease, and should be repeated every 1 to 3 years thereafter. During these colonoscopies, random biopsies of colon mucosa should be taken every 10 cm.

Anemia can result from bleeding and bone marrow suppression from the inflammatory condition.

Primary sclerosing cholangitis can occur, potentially leading to cancer as well as hepatic failure.

 

Toxic megacolon can occur with UC, and is characterized by gross dilation of the large bowel, associated with fever, pain, dehydration, tachycardia, and bloody diarrhea. Perforation can result, and can require urgent surgical intervention.

 

Vitamin deficiency can result from ileal Crohn’s. This can include vitamin B12 deficiency, fat malabsorption (bile salts) and deficiency of fat-soluble vitamins A, D, E and K.

Chronic fat malabsorption leads to fat binding to calcium and thereby oxalate to be absorbed. This can increase the risk for urinary oxalate stone formation. Small bowel obstructions can also occur.

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Resources and References

Kappelman MD et al. 2007. The prevalence and geographic distribution of Crohn’s disease and ulcerative colitis in the United States. Clin Gastro Hepatol. 5(12):1424-9.

Langan RC et al. 2007. Ulcerative Colitis: Diagnosis and Treatment. Am Fam Physician. 76(9):1323-1330.

Wilkins T, Jarvis K, Patel J. 2011. Diagnosis and Management of Crohn's Disease. Am Fam Physician. 84(12):1365-1375.

 

Crohn's and Colitis Foundation of Canada - many educational resources, community chapters, and volunteer opportunities.

 

American Association of Crohn's and Colitis

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Topic Development

authors: David LaPierre, Brandon Cook

reviewers:

 

 

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