Ulcerative colitis

Definition: An inflammatory bowel disease that causes open sores in the colon.

Anatomy or system affected: Abdomen, anus, gastrointestinal system, immune system, intestines

Key terms:

antibodies: specialized proteins that bind to those foreign substances in the body that triggered their production, and neutralize them

B-lymphocytes: special white blood cells that make and secrete antibodies in response to stimulation by foreign substances known as antigens

monoclonal antibodies: antibodies made by a single B-lymphocyte clone that are homogeneous and recognize only one antigen

mucosae: the innermost, mucous-secreting layer that lines the gastrointestinal tract

T-lymphocytes: a group of closely related white blood cells that develop in the thymus and regulate the immune system's response to infections and tumors

Causes and Symptoms

Crohn's disease and ulcerative colitis (UC) are the two types of inflammatory bowel diseases (IBDs). UC only affects the large intestine (colon) and its upper mucosal layer, but Crohn's disease can cause lesions anywhere in the gastrointestinal tract and affects all layers of it. According to the Centers for Disease Control and Prevention, UC is the most common type of IBD.

The exact cause of UC remains unknown, but studies with identical twins and families with a history of UC have established a strong genetic component to it. However, environmental and behavioral factors definitely contribute to the severity of the disease. Psychological stress, diet, smoking, the use of nonsteroidal anti-inflammatory drugs, breastfeeding, and isotretinoin (Accutane) have all been implicated as factors that influence the course and onset of UC.

UC presents as an autoimmune disease of the colon, since white blood cells called T-lymphocytes accumulate at the bottom of the mucosal epithelium, attack it, and damage it. Yet another type of white blood cell, B-lymphocytes, which produce and secrete antibodies, release antibodies that bind to the colonic tissues and damage them. The continuous damage to the colon causes ulcers, which are replaced by granulation tissue (a mass of new connective tissue and capillaries that form on the surface of a healing wound). Accumulation of granulation tissue leads to the formation of pseudopolyps.

UC is graded as mild (rectal bleeding and fewer than four bowel movements a day), moderate (rectal bleeding and more than four bowel movements a day), severe (bleeding from the rectum, more than four bowel movements a day and the symptoms of systemic illness, e.g., fever, elevated heart rate, and low blood cell counts), or fulminant (more than ten bowel movements a day, continuous bleeding and a vastly enlarged colon or megacolon).

Another classification scheme for UC depends on the parts of the colon affected by the disease. Proctitis is limited to the rectum; proctosigmoiditis extends from the rectum to the sigmoid colon; left-sided colitis involves the rectum, sigmoid colon, ascending colon and the beginning of the transverse colon; and pancolitis involves the entire colon.

UC patients typically complain of rectal bleeding, frequent bowel movements with mucous discharge, lower abdominal pain, and a constant feeling of needing to pass a stool even though the colon is empty (tenesmus). In the case of severe disease, the patient also shows fever, severe diarrhea, cramps, and abdominal distension. Complete blood counts reveal an elevated white blood cell count (leukocytosis).

Some UC patients show symptoms outside the colon. These include inflammation of the iris of the eye (uveitis), arthritis, skin lesions (erythema nodosum), clubbing at the ends of the fingers, inflammation of the bile ducts (cholangitis), ulcers in the mouth, and blood clots (deep vein thrombosis).

Diagnosis of UC requires a colonoscopy or flexible sigmoidoscopy to rule out Crohn's disease, intestinal cancer, or diverticulitis. The gastroenterologist inserts a colonoscope through the anus and into the colon to view the colon. A colon from a UC patient contains continuous ulcers without the scarring normally observed in Crohn's disease. Biopsies of the colon reveal involvement of the mucosae and not the lower layers.

Treatment and Therapy

Patients with active UC may require hospitalization and treatment with high-dose corticosteroids (e.g., prednisone). These drugs can relieve symptoms and induce remission. Because corticosteroids have significant side effects, they are typically not used long term.

The first-line treatments for managing UC include anti-inflammatory drugs that quell inflammation in the colon. Sulfasalazine (Azulfidine), mesalamine (Asacol, Delzicol, and others), balsalazide (Colazal), and olsalazine (Dipentum) come in oral forms specially formulated so that they release their medicine primarily in the colon, and liquid forms for enemas. Anti-inflammatory drugs have few side effects, but if they do not control the patient's disease, then immunomodulators are added. These drugs include azathioprine (Azasan, Imuran), 6-mercaptopurine (Purinethol), and cyclosporine (Gengraf, Neoral, and Sandimmune). In 2014, the US Food and Drug Administration also approved the use of vedolizumab (Entyvio)—after the completion of clinical trials—for use in the treatment of UC in patients for whom more standard therapies do not work. Because they suppress the immune response, immunomodulators cause severe side effects. Biological immunomodulators, monoclonal antibodies that bind to and inactivate the pro-inflammatory protein tumor necrosis factor-alpha, include infliximab (Remicade), adalimumab (Humira), and golimumab (Simponi). Because of their severe side effects and high cost, these drugs are a last resort.

If medications do not properly manage UC, then surgical options remain. Surgical removal of the colon (colectomy) or colon and rectum (proctocolectomy) can cure UC. A surgical procedure called ileoanal anastomosis reattaches the severed end of the small intestine to the anus and eliminates the need for a colostomy bag. Because UC increases the risk of colon cancer, some long-term UC patients have their colons removed as a preventative measure or when routine colon biopsies show signs of colon cancer.

Perspective and Prospects

Although historical accounts contain several probable descriptions of UC, Sir Samuel Wilks first referred to UC by name in 1859. Some years after Wilk's discovery, the Surgeon General of the Union Army directly referred to UC, and showed microscopic pictures of tissue sections from the colon of a UC patient. In the decades that followed, detailed clinical and pathological descriptions of UC sealed its place as a recognized condition.

Alicaforsen is a first-generation antisense oligonucleotide that binds to the messenger ribonucleic acid (mRNA) for the ICAM-1 gene and inhibits the synthesis of ICAM-1 protein. Increased ICAM-1 expression in the colon correlates with the severity of the disease and inhibition of ICAM-1 decreases inflammation. In the future, antisense oligonucleotide treatments that specifically bind to and inactivate the messenger RNAs expressed by particular pro-inflammatory genes might be used to successfully treat UC.

Bibliography

"Epidemiology of the IBD." Centers for Disease Control and Prevention. CDC, 16 Sept. 2014. Web. 18 Mar. 2015.

"FDA Approves Entyvio to Treat Ulcerative Colitis and Crohn's Disease." US Food and Drug Administration. FDA, 20 May 2014. Web. 18 Mar. 2015.

Russo, Angelo, and Benedetta Gallo, eds. Ulcerative Colitis: Symptoms, Treatment and Complications. Hauppage: Nova Science, 2012. Print.

Saibil, Fred. Crohn's Disease and Ulcerative Colitis: Everything You Need to Know. 3rd ed. Cheektowaga: Firefly, 2011. Print.

"Ulcerative Colitis Basics." Centers for Disease Control and Prevention, 21 June 2024, www.cdc.gov/inflammatory-bowel-disease/about/ulcerative-colitis-uc-basics.html. Accessed 20 Nov. 2024.

Zinser, Stephanie. The Good Gut Guide. New York: Thorsons, 2012. Print.