Inflammatory bowel diseases: Crohn's disease and ulcerative colitis
Bruce E. Sands, M.D., M.S.
Medical Co-Director, MGH Crohn's and Colitis Center, Gastrointestinal Unit, Massachusetts General Hospital
Assistant Professor of Medicine, Harvard Medical School
The inflammatory bowel diseases (IBD), Crohn's disease and ulcerative colitis, are immune mediated conditions that affect approximately 1.5 million Americans. These conditions are understood to be caused by an immune system over-responsiveness to bacteria that normally live in the bowel. The resulting immune response leads to inflammation and damage of the intestinal tissues. Crohn’s disease tends to affect the latter part of the small bowel, called the terminal ileum, and the right colon (large bowel). However, any part of the digestive tract may be involved with the inflammation of Crohn’s disease. In ulcerative colitis, the disease is confined to the large bowel alone, and tends to involve the rectum and progress backward toward the right side of the colon. Although these two conditions are distinct in their behavior and complications, both conditions may often be found to run in the same family, suggesting that some of the genetic predisposition for the two conditions may be the same. Other autoimmune conditions, such as rheumatoid arthritis, multiple sclerosis, and autoimmune conditions of the thyroid, such as Graves’ disease and hypothyroidism due to chronic thyroiditis (Hashimoto’s disease), are also more common among individuals with inflammatory bowel disease and their family members.
Diarrhea is the predominant symptom in both Crohn’s disease and ulcerative colitis, and is often accompanied by rectal bleeding in ulcerative colitis. Abdominal pain is more predominant in Crohn’s disease. It should be noted that diarrhea and abdominal pain are very common symptoms, and do not automatically imply a diagnosis of inflammatory bowel disease. Irritable bowel syndrome is a far more common cause of these same symptoms, but is distinctly different from inflammatory bowel disease. If you have irritable bowel syndrome, diarrhea and/or constipation, altered bowel habits and abdominal pain occur in the absence of inflammation of the lining of the bowel—in contrast to inflammatory bowel disease, where inflammation and ulcers can be seen routinely during colonoscopy. In addition, the prognosis of irritable bowel syndrome is benign. The symptoms may wax and wane, but no complications occur beyond the inconvenience of the symptoms themselves.
The symptoms of inflammatory bowel disease may also wax and wane, with periods of flare and of normal health. In contrast to irritable bowel syndrome, however, many of these individuals suffer from complications of their disease, such as stricture (narrowing of the bowel by inflammation and scar tissue), fistula (abnormal communication from the bowel to another organ or to the skin, with leakage of bowel contents), abscess (collection of infected fluid) in the abdomen or on the buttocks, or rarely bowel cancer. Particularly in Crohn’s disease, many patients will require surgery in the course of their disease to treat complications of the disease, or for lack of response to medications. Occasionally, patients with ulcerative colitis will also require surgical removal of the entire colon for disease that fails to respond to medications, or in the rare occasions, when colon cancer complicates the disease.
Fortunately, medical therapy for the inflammatory bowel diseases is highly effective. Medications generally work by reducing inflammation and by decreasing the immune response. Anti-inflammatory medications such as sulfasalazine and mesalamine are often used. Occasionally antibiotics are useful in Crohn’s disease, and may work by altering the bacterial composition of the colon. Corticosteroids are frequently used as short term treatment for flares, but have many possible negative effects, including insomnia, mood disorders, acne, weight gain, adrenal gland suppression, high blood pressure, and thinning of the bones (osteoporosis). In addition, many patients become “steroid-dependent”: unable to taper off of steroids without a rapid return of the symptoms of their disease. For such patients, more powerful medications are used to suppress the immune system’s abnormally vigorous response. These include the medications azathioprine, 6-mercaptopurine, and methotrexate. These medications have a variety of uncommon but important side effects. Azathioprine and 6-mercaptopurine may suppress the bone marrow, and thereby cause a low white blood cell or platelet count. Allergic reactions, including pancreatitis, may rarely occur. There is a very rare risk of lymphoma, a potentially fatal lymph node cancer. Methotrexate may cause liver damage, and liver function tests must be monitored. In addition, it may cause birth defects or abortion, and must not be used during pregnancy. As with any immune suppressing medications, infections, which rarely may be life-threatening, may occur.
More recently, a new class of agents—the anti-TNF antibodies—has been added to the IBD armamentarium. The anti-TNF antibodies can be effective even when the immune modulators have not produced a complete response. TNF, or tumor necrosis factor, is a protein that is produced by activated white blood cells involved in the immune response in a variety of immune mediated diseases, including Crohn’s disease, ulcerative colitis, psoriasis, and rheumatoid arthritis. In all of these conditions, the anti-TNF antibodies have been shown to be highly effective therapies. The anti-TNF antibodies that have been shown to be effective in Crohn’s disease include, inflixamab (Remicade), adalimumab (Humira), and certolizumab pegol (Cimzia). Infliximab has also been shown to be effective in ulcerative colitis. As with the immune modulators, anti-TNF antibodies have rare but potentially serious side effects, including infusion or injection reactions, infections (which may be life-threatening in rare cases), and very rarely, lymphoma or other cancers. Very rare cases of a demyelinating syndrome (such as multiple sclerosis, or MS) have occurred during treatment with anti-TNF antibodies, and therefore these agents should not be used by people who also have MS. Although this list of possible side effects is daunting, the benefits of treatment outweigh the risks in properly selected individuals.
Crohn’s disease and ulcerative colitis are serious and chronic diseases of the intestine. Although no cure exists, considerable progress is being made in understanding the causes and treatments of these conditions. Appropriate and expert medical attention can make a large difference in the health and well-being of individuals who suffer from IBD.
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