Crohn's disease and cancer

Also known as: Crohn’s disease, ileitis, ileocolitis, regional enteritis, enteritis

Related conditions: Aphthous ulcers, episcleritis, sclero-conjunctivitis, recurrent iritis, uveitis, erythema nodosum, pyoderma gangrenosum, spondyloarthropathy or spondyloarthritis-ankylosing spondylitis and sacroiliitis, peripheral arthritis, hypercoagulability, secondary amyloidosis, primary sclerosing cholangitis, gallstones, perianal disease, malnutrition, malabsorption, osteoporosis, anemia, lymphoma, cholangiocarcinoma, adenocarcinoma of the gastrointestinal tract, colorectal cancer

Definition:Crohn disease is a chronic inflammatory condition of the gastrointestinal tract, anywhere from the mouth to the anus, but most commonly in the end of the small intestine called the ileum and in the adjoining large colon.

Risk factors: Those with a family history of Crohn disease, a genetic predisposition, or a history of smoking are at greatest risk for this disease.

Etiology and the disease process: Crohn disease (CD) belongs to the group of diseases known as inflammatory bowel disease (IBD), a generic term for diseases characterized by inflammation in the small and large bowels. Other IBDs are ulcerative colitis (UC) and indeterminate colitis (lymphocytic colitis and collagenous colitis).

There are many theories about the etiology of Crohn disease, but the exact cause is unknown. It is known to run in families and be more common in certain ethnicities, suggesting a genetic predisposition. However, no specific reason or factor consistently explains the origin of the disease. The current belief relates Crohn disease to an inflammatory process. The human immune system protects people from harmful foreign substances (referred to as antigens) such as bacteria, viruses, and parasites. This protection is provided by cells and various proteins (such as antibodies) through an inflammatory reaction that is a response toward antigens or cell injuries. In Crohn disease, the immune system reacts abnormally against the affected part of the gastrointestinal tract and causes damage. This inappropriate inflammation leads to the clinical manifestations of Crohn disease.

Studies have shown that the inflammation related to Crohn disease is multifactorial and may depend on genetic factors, immune reactions, and environmental cues. A region on the human chromosome 16 was found to possibly contain genes that are involved in the abnormal inflammatory response in Crohn disease. One such gene, known as NOD2 (16q12), was found to be more common in Crohn disease patients than in the general population. An abnormality in this gene causes a mutation in the gene product (protein) that ultimately weakens the immune system’s ability to recognize harmful bacteria. The immune reaction may be a response to antigens or to modified parts of the gastrointestinal tract associated with the inflammation.

The US National Library of Medicine's Genetics Home Reference (GHR) reported in 2014 that Crohn disease is related to chromosomes 5 and 10; the IL23R gene at location 1p31.2 is also connected to the disease. In addition to NOD2, GHR states that changes in ATG16L1 (2q37.1) and IRGM (5q33.1) increase an individual's chances of developing the disease.

Antitumor necrosis factor-alpha (TNF-alpha) is a protein produced by the immune system that enhances the white blood cells’ ability to defend against infections and other foreign substances. TNF-alpha may be a cause of the inflammation associated with Crohn disease; it is abnormally elevated in Crohn disease, causing excessive inflammation and its adverse effects.

IBDs (Crohn disease and ulcerative colitis) have similar symptoms, but they also have significant differences. Crohn disease can affect any part of the gastrointestinal tract, cause inflammation deeply penetrating through the tract linings (full thickness), and show radiographic results suggestive of Crohn disease. Ulcerative colitis affects the colon and rectum; it can also cause a “backwash” ileitis in the junction of the small and large intestines. Ulcerative colitis inflammation is mainly in the superficial linings of the affected gastrointestinal tract. Tissue sampling further identifies the difference between Crohn disease and ulcerative colitis.

Incidence: The incidence of Crohn disease is 7 new cases per 100,000 people per year, and the prevalence is 162 cases per 100,000 people per year. About 20 percent of Crohn disease cases run in families. Men and women are affected equally. Crohn disease is more common in people of European and Jewish heritage than those of other ethnicities. According to GHR in 2014, the prevalence of Crohn disease in western Europe and North America, where it is most common, is 100 to 150 in 100,000 people. The onset of Crohn disease has two peaks: between the ages of fifteen and thirty and the ages of sixty and eighty. However, most patients are diagnosed before the age of thirty.

Symptoms: The manifestations of Crohn disease are heterogeneous, including symptoms within the gastrointestinal tract and outside of it (extraintestinal). Constitutional symptoms of Crohn disease are fatigue, fever, loss of appetite, and weight loss. Most common gastrointestinal tract symptoms are prolonged diarrhea, with or without rectal bleeding, and abdominal pain (tenderness), usually in the lower right area, which can be mistaken for appendicitis. Malabsorption in the gastrointestinal tract can lead to malnutrition and weight loss, which is related to delayed development and poor growth in children. Mouth ulcers may manifest along with pain in the mouth and gums. Problems of the throat such as pain or difficulty with swallowing can occur if the esophagus is involved.

Patients with Crohn disease may develop perianal diseases such as fissure in ano (fissures or tears in the lining of the anus) and fistula-in-ano (abnormal connection between the anal intestinal lining and another part of the body, such as the skin, bladder, vagina, or another part of the gastrointestinal tract). Fistulas are most common in the anal region; abscesses (pockets of pus) may be present as a complication. Blockage (obstruction) and perforation of the gastrointestinal tract may occur. Extraintestinal symptoms include eye disorders, skin problems, arthritis, and liver and gallbladder diseases.

Screening and diagnosis: Screening is done through a comprehensive physical examination and a complete blood count to evaluate for anemia and infection. A stool test will be performed if there is gastrointestinal tract bleeding or infection. Special tests for antibodies, such as antineutrophil cytoplasmic antibodies and anti-Saccharomyces cerevisiae antibodies, may be used if the diagnosis of Crohn disease is uncertain. Radiographic studies can include upper and lower gastrointestinal series (barium enema). Upper or lower gastrointestinal endoscopy can identify the affected site, allow tissue sampling (biopsy), and confirm the diagnosis of Crohn disease. The severity of Crohn disease is diverse, and its activity is described as mild-moderate, moderate-severe, severe-fulminant, and remission.

Treatment and therapy: Crohn disease has no cure; however, symptoms can be alleviated. Management of Crohn disease and its complications may include medications for treatment of symptoms such as antidiarrheal agents (loperamide and diphenoxylate), nutritional support, surgery, or a combination of these modalities. Medications for Crohn disease include antibiotics such as ciprofloxacin and metronidazole; anti-inflammatory drugs such as corticosteroids, sulfasalazine, and 5-aminosalicylate (5-ASA); immunomodulators that inhibit the immune response such as azathioprine, 6-mercaptopurine, and methotrexate; and biological therapies such as infliximab (Remicade) and adalimumab (Humira), which are antibodies that block TNF-alpha activity. All of these medications may have side effects ranging from nausea, vomiting, and headaches to infection susceptibility. The risks and benefits of medications are assessed and modifications implemented on an individual basis.

Regular nutritional assessments are necessary to prevent malnutrition, which can result from malabsorption in the inflamed small and large bowels. Surgical intervention is needed in some cases, such as failure of medical treatment and complications such as obstruction, perforation, nonstop bleeding, abscess, and fistula.

Prognosis, prevention, and outcomes: Crohn disease is a chronic medical condition. It can manifest in recurrent episodes of the active disease (flares) or remain in remission for variable time periods. Patients with Crohn disease are monitored closely for related conditions such as associated cancers. Regular cancer screening using colonoscopy is recommended for patients with Crohn disease because of its association with colorectal cancer.

Bibliography

Amer. Cancer Soc. "What Are the Risk Factors for Bile Duct Cancer?" Cancer.org. ACS, 30 Oct. 2013. Web. 19 Aug. 2014.

Amer. Gastroenterological Assn. Clinical Practice Committee. “Perianal Crohn’s Disease.” Gastroenterology 125.5 (2003): 1503–1507. Print.

Amer. Soc. of Clinical Oncology. "Small Bowel Cancer: Risk Factors." Cancer.Net. ASCO, June 2013. Web. 19 Aug. 2014.

Eyre, Harmon J., Dianne Partie Lange, and Lois B. Morris. Informed Decisions: The Complete Book of Cancer, Diagnosis, Treatment, and Recovery. 2d ed. Atlanta: Amer. Cancer Soc., 2002. Print.

Genetics Home Reference. "Crohn Disease." Genetics Home Reference. US NLM, 18 Aug. 2014. Web. 19 Aug. 2014.

Hanauer, Stephen B., William Sandborn, and the Practice Parameters Committee of the American College of Gastroenterology. “Management of Crohn’s Disease in Adults.” American Journal of Gastroenterology 96.3 (2001): 635–643. Print.

Hemminki, K., X. Li, J. Sundquist, and K. Sundquist. "Cancer Risks in Crohn Disease Patients." Annals of Oncology 20.3 (2009): 574–580. Print.

Litin, Scott C., Jr., ed. Mayo Clinic Family Health Book. 4th ed. New York: Time, 2010. Print.

Natl. Cancer Inst., Natl. Insts. of Health. "Colorectal Cancer Screening (PDQ®)." Cancer.gov. NCI/NIH, 6 June 2013. Web. 19 Aug. 2014.

Natl. Digestive Diseases Information Clearinghouse. "Crohn's Disease." National Digestive Diseases Information Clearinghouse (NDDIC). NIH/NIDDK, 10 July 2013. Web. 19 Aug. 2014.