INTRODUCTION Crohn's disease is an inflammatory condition of the digestive tract that affects children and adults. The cause of Crohn's disease is unknown, but heredity factors are suspected to contribute. Common symptoms of Crohn's disease include mouth sores, diarrhea, abdominal pain, weight loss, and fever. Patients can also have symptoms outside of the digestive tract, including a skin rash, joint pain, eye redness, and, less commonly, liver problems. This disease is typically diagnosed by the presence of specific symptoms and by tests, such as colonoscopy and imaging tests that use barium.
Although Crohn's disease is usually chronic, medical and surgical treatment can help control the course of the disease and many patients experience long periods of symptom-free remission. Most patients with Crohn's disease have a normal life even though they have to contend with an ongoing problem. Intense research is helping to uncover the cause of the disease and continues to lead to the development of new treatments.
Treatment is individualized and depends upon the area of the digestive tract affected, the type of symptoms, and the activity of the disease. You should take a role in your medical decisions and care by learning as much as you can about the condition, following treatment guidelines, and promptly alerting your doctor to any changes in your condition.
WHAT CAUSES CROHN'S DISEASE? The exact cause of Crohn's disease is unknown. What is known is that the disease tends to run in families and affects certain populations more than others, suggesting that genetic factors are important. Although research has been done to identify environmental factors and infections that might cause the disease, no cause has been consistently found.
The current belief is that some kind of trigger in a genetically susceptible person leads the body's immune system to inappropriately cause inflammation in the digestive tract. Bacteria and food substances in the digestive tract probably also have a role. Once the inflammation begins, it causes damage to the intestines; this damage is mainly responsible for the symptoms of the disease.
WHAT IS THE TYPICAL PATTERN OF CROHN'S DISEASE? Crohn's disease usually follows a pattern of exacerbations and remissions. About 10 to 20 percent of patients will enter remission after their first exacerbation of Crohn's disease. The pattern in other patients can be quite variable, ranging from recurrent periods (weeks to months) of symptoms (such as mild diarrhea and cramping) to, less commonly, severe and disabling symptoms (such as severe abdominal pain and bowel obstruction). Treatment can help drive active disease into remission and then prolong remission.
Most cases of Crohn's disease primarily affect the terminal ileum (a region of the small intestine) and the colon, producing ileitis (inflammation of the ileum) and colitis (inflammation of the colon), respectively (show figure). Inflammation in these areas can lead to the formation of abnormal passages (fistulas), perforation of the intestinal wall, or narrowing of the digestive tract (stricture) and obstruction. Crohn's disease can also affect the perianal area, producing fissures, ulcers, pockets of pus (abscesses), and fistulas.
WHAT DRUGS ARE USED TO TREAT CROHN'S DISEASE? Many different drugs are used to treat Crohn's disease. Your doctor's choice of medications will depend upon the area of the digestive tract affected by the disease and your symptoms. Some of the typical approaches are described below. The following is a summary of some of the drugs that are commonly used.
Sulfasalazine Sulfasalazine was one of the first drugs used to treat Crohn's disease and is still used for treating Crohn's disease restricted to the colon. Sulfasalazine usually begins to reduce symptoms within a few days, but its full effect may require up to four weeks of treatment. A problem with sulfasalazine is that it can cause allergic reactions in a minority of patients and can cause headaches, particularly when given in high doses.
5-Aminosalicylates The 5-aminosalicylate (5-ASA) drugs (such as Asacol and Pentasa) are similar to sulfasalazine but are less likely to cause headaches and allergic reactions. An advantage is that they can be given in relatively high doses compared to sulfasalazine. In addition, they are formulated to be released in the terminal ileum (in the case of Asacol) and throughout the small intestine (in the case of Pentasa), which permits the drugs to be targeted to inflamed areas. Their major disadvantage is their relatively high cost. These drugs are helpful in achieving and maintaining remission. They usually begin to reduce symptoms within a few days, but their full effect may require up to four weeks of treatment.
Antibiotics Antibiotics can reduce the bacterial contribution to the inflammation of Crohn's disease. The antibiotics most frequently used are metronidazole and ciprofloxacin. Metronidazole is most helpful in patients with Crohn's disease involving the colon and perianal region. A problem with it, however, is that it causes an unpleasant metallic taste, which goes away once the drug is discontinued, and can cause peripheral neuropathy (damage to the nerves responsible for sensation in the hands and feet) with long-term use. Peripheral neuropathy can be permanent. Alcohol should be avoided in patients taking metronidazole because when taken together metronidazole plus alcohol can lead to nausea, headaches, and flushing.
Steroids Steroids (such as prednisone and budesonide) can help drive active, moderate to severe Crohn's disease into remission, but they do not prolong remission and they have many serious side effects when taken for long periods of time.
Immunomodulator drugs Immunomodulator drugs decrease the inflammation associated with Crohn's disease. The most commonly used drugs include azathioprine, 6-mercaptopurine, and methotrexate, although many new drugs continue to be studied and are already used occasionally. These drugs have traditionally been used for patients who have not responded to "first line" therapy with drugs such as antibiotics, sulfasalazine, and 5-aminosalicylates, particularly those who depend upon steroids to control symptoms. These drugs are also very helpful for maintaining remission.
Immunomodulator drugs take a long time (three to six months) to produce a maximal effect and are often prescribed for long-term therapy. The major side effects of these drugs include lowering of the white blood cell count (the cells that help fight off infection in the body), hepatitis (inflammation of the liver), and pancreatitis (inflammation of the pancreas). As a result, your doctor will have to check blood tests regularly.
Another drug that is used occasionally is cyclosporine, which is a strong suppressor of the immune system. Its principal role in Crohn's disease is for patients with active fistulizing disease who have not responded to other types of therapy.
Infliximab Infliximab is an antibody that neutralizes an inflammatory substance in your body that is called tumor necrosis factor. It is a relatively new agent and is generally reserved for patients who do not respond well to "first line" therapy with antibiotics and 5-ASA drugs. It is especially effective in patients with fistulizing Crohn's disease. In one study, for example, closure of all fistulas was observed in 55 and 38 percent of patients receiving the 5 and 10 mg/kg dose of Infliximab, respectively, compared to 13 percent of those receiving placebo (a sugar pill).
The main side effects of infliximab are allergic reactions and infections. Another concern is that a small number of patients who have received Infliximab have developed lymphoma (a cancer of the lymphatic system). While this number is much smaller than the large number of patients who have benefited from Infliximab, it is still not a drug considered to be a "first line" agent. Furthermore, the effects of the drug only last for a few weeks (8 to 10 on average) in most people; thus repeated dosing is usually needed. It is also very expensive (approximately $2500 per dose).
WHAT SHOULD I EAT? Most patients with Crohn's disease can identify foods that tend to exacerbate their symptoms, although the specific foods implicated vary among patients. Many patients with Crohn's disease tend to avoid eating, since eating can worsen diarrhea and cramps. This has potentially serious consequences since it can lead to malnutrition. Thus, it is important that you carefully discuss your dietary concerns with your doctor, who may also arrange for you to have a consultation with a dietitian.
IS THERE ANYTHING ELSE I SHOULD DO? As discussed above, one of the most important things for you to do is to avoid becoming malnourished. In addition, you should exercise regularly to maintain your general health. Smoking worsens Crohn's disease and should be avoided. You should also avoid taking nonsteroidal antiinflammatory drugs (such as ibuprofen and naprosyn), since they can worsen the disease.
CAN I HAVE CHILDREN? Men and women with Crohn's disease can have children. However, several issues, such as the safety of the various drugs used for your treatment, may arise that warrant discussion with your doctor. Thus, you should tell your doctor if you are contemplating pregnancy.
Children of parents with Crohn's disease have been reported to be 3 to 20 times more likely to develop Crohn's disease than the general population. However, there is currently no way to predict the risk in an individual child.
SUPPORT Do not underestimate the value of sharing your concerns with other people with Crohn's disease. Ask your doctor about support groups. The Crohn's and Colitis Foundation of America also has information about support groups. They can be reached on the Internet at http://www.ccfa.org/.
WHAT IS THE MEDICAL TREATMENT FOR CROHN'S DISEASE? In most cases, drugs, nutritional support, and watchful waiting are the first line of treatment for Crohn's disease, although some patients may require surgery. The specific approach depends upon the areas of the digestive tract that are affected and the activity of disease.
Mouth sores The often painful mouth sores of Crohn's disease usually respond to treatment of intestinal disease. Topical drugs (such as hydrocortisone or sucralfate) may help heal these sores.
Inflammation of the stomach and upper small intestine Crohn's disease of the upper part of the digestive tract may respond to drugs used to treat stomach and intestinal ulcers. In severe cases, steroids and immunomodulator drugs may be necessary to control inflammation.
Ileitis Active ileitis is first treated with 5-aminosalicylate drugs; antibiotics, steroids, and immunomodulator drugs may be required in patients with moderate to severe symptoms. Antidiarrheal drugs can also help relieve diarrhea. Severe ileitis may require close monitoring, bowel rest (avoiding solid food), enteral feeding (feeding by a nasogastric tube) or total parenteral feeding (intravenous feeding), and surgery. The remission of ileitis can be maintained with 5-aminosalicylate drugs in some patients.
Ileocolitis and colitis Active Crohn's disease that affects the ileum and colon or the colon alone is first treated with sulfasalazine or a 5-ASA drug. In some patients, treatment will also include antibiotics and steroids. Severe ileocolitis or colitis may require hospitalization, bowel rest, enteral feeding or parenteral feeding, and long-term treatment with immunomodulator drugs. The 5-ASA drugs are usually used to maintain remission of ileocolitis and colitis.
Perianal complications About 35 to 45 percent of patients with Crohn's disease will develop perianal complications at some time during their disease. If abscesses, fissures, or fistulas do not produce symptoms, they may not require treatment. Some will spontaneously heal, but others will require treatment with antibiotics, steroid suppositories, immunomodulator drugs, or surgery. Sitz baths and careful, gentle cleaning of the perianal area can also promote healing. Although treatment resolves most perianal complications, recurrence is frustratingly common and may require long-term treatment.
Chronic disease of the perianal area can also lead to narrowing of the anal canal. This narrowing can be partially reversed by gentle therapeutic dilation, which is often started in the hospital and continued at home.
WHAT SECONDARY PROBLEMS ARE ASSOCIATED WITH CROHN'S DISEASE? Over time, the intestinal problems of Crohn's disease and the ongoing inflammation can lead to secondary health problems. Fortunately, many of these problems can be anticipated and prevented; if they do occur, most can be successfully treated.
Malnutrition Between 50 and 70 percent of patients with Crohn's disease develop malnutrition or are underweight. There may be many consequences of malnutrition, including delayed growth and puberty in children, osteoporosis, a decreased ability to withstand surgery, and psychosocial problems.
Malnutrition can often be prevented by regular nutritional assessments. Typically, a doctor or dietitian reviews a patient's diet, checks a patient's body composition, and orders laboratory tests to detect deficiencies. In most patients, caloric and nutrient supplementation can reverse the malnutrition associated with Crohn's disease. Although patients with Crohn's disease often have a poor appetite, they should not restrict their dietary intake unless they are instructed to do so by their doctor.
Enteral feeding (feeding by a nasogastric tube) with special, elemental, or polymeric diets and total parenteral feeding (intravenous feeding) can provide nutrients when the digestive tract cannot tolerate normal food or has been effectively shortened by disease or surgery. In some cases, parenteral feeding can also help achieve remission. However, for the majority of patients with Crohn's disease, neither feeding procedure is a practical option for long-term nutrition.
Bone complications Up to 30 percent of patients with Crohn's disease develop osteoporosis, which can lead to bone fractures. Patients who take steroids for long periods of time and postmenopausal women are particularly at risk. Regular bone mineral density tests can detect early osteoporosis in patients with Crohn's disease.
Osteoporosis usually results from deficiencies of vitamin D, calcium, and sex hormones (estrogen and testosterone). Regular blood tests will detect deficiencies, and supplements and drugs can be used to restore the levels to normal. Patients can further strengthen their bones by performing low-impact, weight-bearing exercises at least twice a week.
Liver and gallbladder complications Crohn's disease can lead to inflammation of the liver, which often responds to the drugs also used to treat intestinal Crohn's disease. Crohn's disease can rarely cause inflammation of the bile ducts (a disease called primary sclerosing cholangitis). Crohn's disease can also increase the likelihood of gallstones, which may not require treatment or may require surgical removal.
Colorectal cancer Overall, patients with Crohn's disease have an increased risk of developing colorectal cancer in areas of active inflammation. However, cancer usually does not arise until a patient has had Crohn's disease for many years. Some doctors recommend a regular screening colonoscopy to identify premalignant and malignant changes in the colon.
CAN CROHN'S DISEASE AFFECT OTHER AREAS OF THE BODY? Crohn's disease can lead to inflammation of other tissues, commonly called "extraintestinal" disease. Possible symptoms include reddening and swelling of the skin, eye pain and irritation or vision problems, and coughing, wheezing, or difficulty breathing.
Skin inflammation Crohn's disease can lead to skin inflammation in up to 15 percent of patients. This inflammation often subsides when the intestinal symptoms are treated, but steroids may be required.
Eye inflammation Inflammation of the eyes occurs in up to 5 percent of patients with Crohn's disease. This inflammation often responds to the drugs used to treat Crohn's disease, but careful monitoring is necessary to prevent complications such as glaucoma.
Lung and airway inflammation Rarely, Crohn's disease may lead to inflammation of the airways and lungs. This inflammation may be treated with nonsteroidal anti-inflammatory drugs, inhaled steroids, or oral steroids.
WHEN IS SURGERY NECESSARY? Medical treatment can help control the symptoms and complications of Crohn's disease and may delay the need for surgery. Surgery is usually used as a last resort since it does not cure the disease, although in some patients it may be the fastest way to restore health. About 80 percent of patients with Crohn's disease will require an operation at some time, usually for serious problems. Surgery is used to stop bleeding, to close fistulas and bypass obstructions, and often simply to remove the affected areas of the intestine.
WHAT CAN I EXPECT AFTER SURGERY? It is important to have realistic expectations of surgery. Surgery can improve a patient's medical condition and can even be lifesaving. However, surgery does not cure Crohn's disease, and recurrence is likely.
Between 85 and 90 percent of patients are symptom-free during the year following surgery, and up to 20 percent of patients are still symptom-free 15 years after surgery. If Crohn's disease is confined to the colon and the colon is removed, only 10 percent of patients will have a recurrence within 10 years. Prompt and long-term drug treatment started at the time of surgery decreases the risk of recurrence in many patients with Crohn's disease.
If the surgery creates an ileostomy or colostomy (an opening for collecting intestinal contents), a stomal therapist can answer questions about the procedure. Patients with ostomies usually lead a normal life.
HOW IS CROHN'S DISEASE TREATED IF IT RECURS AFTER REMISSION OR SURGERY? Recurrent Crohn's disease is usually treated according to the same guidelines used to treat the initial episode of Crohn's disease. In some cases, stronger drugs are used to treat a recurrence.
WHAT ARE SPECIAL CONCERNS WHEN CROHN'S DISEASE OCCURS IN CHILDREN AND ADOLESCENTS? Crohn's disease appears before the age of 18 in about 20 percent of patients. If the disease is not treated, about one-half of these children will have short stature or delayed growth. Aggressive nutritional therapy can help normalize growth. This therapy may include supplements, a high-calorie diet, and sometimes enteral feeding.
Because steroids can also retard growth and lead to osteoporosis in children, these agents are often the last used if a child's Crohn's disease requires long-term therapy. Height, weight, and bone mineral density must be closely monitored in children who take steroids.
Children with Crohn's disease may experience significant psychosocial problems because their condition interferes with day-to-day functioning and affects their interaction with peers. If your child seems withdrawn or is experiencing school or social difficulties, be sure to bring these matters to your doctor's attention.
WHAT TREATMENTS ARE ON THE HORIZON? Several investigational therapies show promise for the treatment of Crohn's disease. The majority of the new drugs that are being developed help quiet inflammation. Many of these drugs are currently undergoing clinical trials. As of yet, none have been proven to be better than currently available treatments. You should tell your doctor if you are interested in participating in a clinical trial. You can also contact your nearest academic medical center (a medical center affiliated with a medical school) and ask for the gastroenterology department to see if they are conducting clinical research in Crohn's disease.