Crohn disease

Signs and Symptoms

The most common signs and symptoms of Crohn disease are diarrhea and abdominal pain. Symptoms can range from mild to severe.

• Diarrhea (with or without blood)
• Abdominal pain and bloating
• Fatigue
• Poor appetite
• Weight loss
• Fever
• Nausea and vomiting
• Floating stools (caused by poor digestion of fat)
• Anemia (low iron levels)

Crohn disease can also be associated with other medical conditions, including arthritis, osteoporosis, eye infections, blood clots, liver disease, and skin rashes.

What Causes It?

Scientists are not sure what causes Crohn disease. Theories include a faulty immune system response triggered by bacteria or a virus; genetics (about a quarter of people who have Crohn disease also have a close relative with the disease) and a diet high in saturated fat and processed foods. Most likely, several factors are involved.

Risk Factors

Risk factors may include:

• Being of Jewish heritage (3 to 6 times more likely than the general population)
• Being of European (particularly Scandinavian) ancestry
• Family history of inflammatory bowel disease
• Cigarette smoking
• Living in an industrialized country (particularly an urban area)
• Eating a diet high in sugar and saturated fat and low in fruit and vegetables
• Being overweight or obese
• Low exposure to sunlight

What to Expect at Your Provider's Office

Your doctor will perform a thorough physical exam, as well as a series of tests to diagnose Crohn disease. Blood tests may show anemia (due to a significant loss of blood) and a high white blood cell count (a sign of inflammation somewhere in the body). Stool samples may show whether there is bleeding or an infection in the colon or rectum.

The following procedures may help your doctor distinguish between ulcerative colitis, Crohn disease, and other inflammatory conditions.

• Colonoscopy and Sigmoidoscopy. In a colonoscopy, a long, flexible, lighted tube with a camera is used to take pictures of the colon. These pictures can reveal inflammation, bleeding, or ulcers along the entire colon wall. The person is sedated during the procedure. A sigmoidoscopy is similar but is used to examine the rectum and lower part of your colon. It can be done without sedation, but may miss inflammation higher in the colon or the small intestine.
• Capsule endoscopy. In this test, you swallow a small capsule with a camera in it, and the camera takes pictures as it passes through the length of your digestive tract. The capsule then passes out of the body through your stool. The test is generally safe, but if there is an intestinal obstruction the capsule may become trapped. Your doctor will run other tests to make sure you do not have an obstruction before doing this procedure.
• Barium enema. This procedure looks at the large intestine with an x-ray. You will receive barium (a dye) as an enema to coat the lining of your large intestine and rectum. It is generally not as reliable as a colonoscopy.
• CT scans. This imaging technique allows your doctor to look at the entire intestine and can help find intestinal obstructions or fistulas.

Preventive Care

There is no known way to prevent Crohn disease, however, people can usually manage the condition with medication, diet, and lifestyle changes. Exercise can also help prevent the stress and depression that often accompany Crohn disease. Quitting smoking can reduce symptoms. Eating a diet rich in fruit and vegetables can also help ease symptoms.

Treatment Options

The primary goal in treating Crohn disease is to control acute flares of the disease, and to maintain remission for as long as possible. The specific type of treatment often depends on how severe the symptoms are. For example, people with mild-to-moderate symptoms are usually treated with medications that reduce swelling and suppress the immune system. More severe cases may require surgery.

Many people with inflammatory bowel diseases use complementary and alternative (CAM) remedies in addition to prescription medications. Preliminary studies suggest that lifestyle changes, dietary adjustments (such as eating a rich variety of fruits and vegetables and avoiding saturated fat and sugar), and specific herbs and supplements may be useful additions to treatment.

Lifestyle

Stress

Many people with Crohn disease report that stress makes their symptoms worse. Relaxation techniques and mind/body exercises, such as yoga, tai chi, and meditation may be helpful, particularly when used with other forms of treatment. In addition, studies suggest that hypnosis may improve immune function, increase relaxation, reduce stress, and ease feelings of anxiety.

Exercise

Exercise helps people with Crohn disease maintain health and reduce stress. Talk to your doctor before starting a new exercise or fitness regimen. It is especially important for people with Crohn disease to drink water before and during exercise to prevent dehydration. Avoid extreme changes in body temperature during exercise.

Smoking

Cigarette smoking is a risk factor for Crohn disease, and studies have shown that it may worsen symptoms. If you smoke, you should quit. Ask your doctor for help.

Drug Therapies

Although medicines cannot cure Crohn disease, they can reduce symptoms and help you control your condition. Sometimes, they can bring on remission of the disease. Medicines commonly used to treat Crohn disease include:

• Sulfasalazine (Azulfidine). An older drug that reduces inflammation during acute flare ups and is usually taken with folic acid. Side effects include abdominal discomfort, nausea, and lowered sperm count. Sulfasalazine can be effective, but newer drugs are available.
• Mesalamine (Asacol, Rowasa). This drug reduces inflammation during acute flare ups and helps prevent recurrences. It generally has fewer side effects than sulfasalazine.
• Corticosteroids (such as budesonide, prednisone, and prednisolone). These drugs can reduce inflammation throughout your body but have many side effects, including acne, increased risk of infection, osteoporosis, high blood pressure, excessive hair growth, diabetes, and disorders of the eye, including glaucoma and cataracts. Budesonide (Entocort) may have fewer side effects. Corticosteroids also suppress your body's production of the hormone cortisol and cannot be stopped abruptly. They are not for long-term use, but may be used to control flares.
• Immune system suppressors. These medicines reduce inflammation by suppressing the immune system. They are sometimes used in combination with steroids to lower the dose of the steroid medicine. These drugs can take several months to work, and all may have significant side effects. Drugs include azathioprine (Imuran), methotrexate (Rheumatrex), infliximab (Remicade), adalimumab (Humira), certolizumab pegol (Cimzia), natalizumab (Tysabri), and cyclosporine.
• Antibiotics. Antibiotics may be prescribed to help treat fistulas and ulcers. Ciproflaxin (Cipro) and metronidazole (Flagyl) are most commonly used.
• Antidiarrheal medicines (such as diphenoxylate, loperamide, or psyllium). Medicines used to treat diarrhea must be used only under your doctor's supervision and with extreme caution. They can slow down the normal movements of the gastrointestinal tract and, in severe cases, may cause a life-threatening complication known as toxic megacolon.

Surgical Procedures

Although surgery will not cure Crohn disease, 3 to 4 people with the condition will eventually have resections (parts of their colons removed) to close fistulas, or to remove a severely damaged part of the intestine. In some cases, doctors can perform laparoscopic surgery (which uses a smaller incision), leading to fewer complications. When the intestine has become too narrow from scar tissue, a doctor may perform strictureplasty where a balloon is inserted into the intestine and expanded.

Complementary and Alternative Therapies

People with Crohn disease often cannot absorb all the nutrients their bodies need, due to damage in the intestine. Abdominal pain and nausea may make it hard for them to eat. Some medicines may also block the absorption of important nutrients. For example, sulfasalazine reduces the body's ability to absorb folate, and corticosteroids can reduce calcium levels. Making sure you get enough nutrients is a crucial part of treating Crohn disease. People with significant malnourishment, severe symptoms, or those awaiting surgery may require parenteral (intravenous) nutrition.

Nutrition

Although diet cannot cause or cure Crohn disease, some studies suggest that people who eat foods high in saturated fat and sugar, or who eat a lot of processed foods may be more likely to develop the disease. Certain foods may also reduce symptoms and make recurrences of the disease less likely.

• Eating fruits and vegetables, lowering fat, and eliminating sugar may reduce the risk of developing Crohn disease. Although a low-fiber diet is one of the risk factors for developing Crohn disease, some people with Crohn disease find that fiber makes symptoms worse. If fiber bothers you, steam or bake your vegetables rather than eating them raw, and avoid high-fiber fruits, such as apples.
• Certain foods may aggravate symptoms of Crohn disease, most often dairy products, fats, and spicy foods. People with Crohn disease may want to avoid these foods. Work with a dietician who is familiar with Chron disease.
• Eat antioxidant foods, including fruits (such as blueberries, cherries, and tomatoes) and vegetables (such as squash and bell peppers).
• Eat foods high in B vitamins, calcium, and magnesium, such as whole grains (if not bothered by fiber), dark leafy greens (such as spinach and kale), and sea vegetables.
• Avoid refined foods, such as white breads and pastas.
• Eat 5 to 6 small meals a day.
• Avoid caffeine, alcohol, and tobacco.
• If symptoms are severe, an elemental diet may be recommended. Elemental formulas are liquid diets that contain only the basic building blocks of food and do not need to be broken down into smaller substances along the digestive tract. Some people find it hard to stick to an elemental diet, but after a period of time, other foods can often be reintroduced. One study suggests that adding omega-3 fatty acids to an elemental diet may boost its nutritional content and make it more likely that people with Crohn disease will stick with it. Only try elemental diets under the supervision of a physician.

Vitamins and Minerals

Because of decreased appetite, malabsorption, chronic diarrhea, side effects of medication, and surgical removal of parts of the intestine, many people with Crohn disease do not get enough of some vitamins and minerals. In particular, people with Crohn disease may lack adequate vitamin D, B12, and K, plus folic acid, calcium, and zinc. Your doctor may recommend that you take a multivitamin daily.

• Zinc (25 mg), folic acid (800 mcg), vitamin B12 (800 mcg). The body uses these vitamins and minerals to repair cells in the intestine. In addition, drugs such as sulfasalazine and methotrexate may cause levels of folic acid in the body to drop, so that you need a supplement. Getting too much zinc can weaken the immune system. Folic acid in high doses over long periods of time may be associated with certain illnesses. Nevertheless, studies suggest that people with Crohn disease often suffer from vitamin B12 and/or folate deficiency. Speak with your doctor to determine the proper type and level of supplementation for your individual case.
• Vitamin D (1,000 IU per day). The body needs vitamin D to maintain strong bones. People with Crohn disease, especially those who take corticosteroids, often have low levels of vitamin D putting them at risk for osteoporosis.
• Calcium (1,000 to 1,200 mg per day). Calcium is also needed for strong bones. Ask your doctor if you need a calcium supplement.
• Omega-3 fatty acids, such as those found in fish oil. These fats may help fight inflammation and reduce the chances of recurrence, but studies have been mixed. The study with the most positive results used a special type of fish oil, "enteric coated free fatty acid form," that is not sold commercially. Some researchers suggest that measuring the blood levels of different types of fatty acids may help determine if fish oil would be useful. DO NOT take high doses of a fish oil supplement if you take blood-thinning medication. Fish oil may interact with blood-thinning medications, such as warfarin (Coumadin) and aspirin.
• Probiotics, especially Saccharomyces boulardi. One small study indicated that this type of "friendly" bacteria helped people with Crohn disease reduce the incidence of diarrhea. However, other studies have shown mixed results. People with allergies to yeast should avoid Saccharomyces boulardi. People with very weak immune systems should check with their doctor before using probiotics.
• N-acetyl glucosamine (NAG). Preliminary research suggests that N-acetyl glucosamine supplements or enemas may improve symptoms of inflammatory bowel disease, but more studies are needed to determine whether glucosamine would have any effect on Crohn disease. There is some concern that NAG may raise blood sugar (or insulin) in people with diabetes and may worsen asthma symptoms. NAG may interact with blood-thinning medications, such as warfarin (Coumadin) as well as certain cancer drugs.
• Glutamine. Glutamine is an amino acid found in the body that that helps the intestine function properly. While there is no evidence that glutamine specifically helps reduce symptoms of Crohn disease, it may be good for overall intestinal health. It is best to take glutamine on an empty stomach. DO NOT take glutamine if you are diabetic or have seizures, suffer from bouts of mania, severe liver disease with difficulty thinking or confusion, or if you are sensitive to monosodium glutamate (MSG).

Herbs

Because of the presence of inflammation and the nature of the disease, Crohn disease should not be treated with herbs alone. However, herbs may be a useful complement to traditional medical treatment. Herbs can trigger side effects and interact with other herbs, supplements, or medicines. For these reasons, you should take herbs with care, under the supervision of a health care provider.

The evidence for using herbs to treat Crohn disease is mostly lacking. Herbs that have been used traditionally to treat inflammation within the digestive tract include:

• Slippery elm (Ulmus fulva) is a demulcent (a substance that protects irritated tissues and promotes their healing). One tsp. powder may be mixed with water and drunk 3 to 4 times a day. Take slippery elm at least one hour after taking other medicines.
• Marshmallow (Althaea officinalis) is a demulcent and emollient (a substance that soothes mucous membranes). Drink one cup of tea 3 times per day. To make tea, steep 2 to 5 g of dried leaf or 5 g dried root in one cup boiling water. Strain and cool. Avoid marshmallow if you have diabetes. Marshmallow may interact with lithium. It may also interfere with drugs taken by mouth. Take Marshmallow at least one hour after taking oral medications.
• Curcumin or turmeric shows anti-inflammatory properties in test tubes. One small study found that people with inflammatory bowel disease who took curcumin reduced their symptoms and their need for medicines. More research is needed. Curcumin may make gallbladder illnesses worse and may interact with blood-thinning medications. Curcumin may have effects similar in action to hormones, so people who have hormone-sensitive conditions should speak to their physicians before taking curcumin. Curcumin may also interfere with iron absorption.
• Cat's claw (Uncaria tomentosa) 250 mg per day may help fight inflammation. Cat's claw may make leukemia, as well as autoimmune disorders, worse, and may worsen low blood pressure.
• Boswellia (Boswellia serrata) has anti-inflammatory properties, and a few small studies suggest that it may help treat Crohn disease. More research is needed. DO NOT take Boswelia for more than eight weeks consecutively. Boswellia may interact with other drugs and supplements, so talk to your doctor before taking it.

Homeopathy

Although few studies have examined the effectiveness of specific homeopathic therapies, professional homeopaths may consider the following remedies for the treatment of Crohn disease symptoms (such as diarrhea) based on their knowledge and experience. Before prescribing a remedy, homeopaths take into account a person's constitutional type, includes your physical, emotional, and psychological makeup. An experienced homeopath assesses all of these factors when determining the most appropriate treatment for each person.

• Mercurius. For foul-smelling diarrhea that may have streaks of blood accompanied by a sensation of incomplete emptying. This remedy is most appropriate for individuals who tend to feel exhausted following bowel movements, experience fluctuations in body temperature, perspire frequently, and have a thirst for cold fluids.
• Podophyllum. For explosive, gushing, painless diarrhea that worsens after eating or drinking. Exhaustion often follows bowel movements. The individuals for whom this remedy is appropriate may experience painful cramps in the lower legs and feet.
• Veratrum album. For profuse, watery diarrhea accompanied by stomach cramps, bloated abdomen, vomiting, exhaustion, and chills. The diarrhea tends to worsen as a result of eating fruit. The individual for whom this therapy is appropriate tends to crave cold liquids.

Acupuncture

Acupuncture has long been used in Traditional Chinese Medicine to treat inflammatory bowel disease. One study in Germany found that acupuncture and moxibustion were effective specifically for treating Crohn disease. Acupuncturists treat people with inflammatory bowel disease based on an individualized assessment of the excesses and deficiencies of qi located in various meridians. Some practioners use moxibustion (a technique in which the herb mugwort is burned over specific acupuncture points) because they believe it reaches deeper into the body than using needles alone.

Other Considerations

Pregnancy

Women who are in remission at the time of conception generally have normal pregnancies and healthy babies. However, women with active disease are more prone to miscarriages, spontaneous abortions, and stillbirths. Symptoms often get worse during pregnancy. For this reason, women with active Crohn disease who are or wish to become pregnant should continue medications under the guidance of their doctor. Pregnant women should avoid high doses of vitamins. An obstetrician and/or a nutritionally-oriented physician can provide instructions about taking multivitamins during pregnancy and while breastfeeding. Specifically, the herbs cat's claw (Uncaria tomentosa) and turmeric (Curcuma longa) should never be used while breastfeeding, but any herb or supplement should only be used by a nursing mother under the guidance of her physician.

Prognosis and Complications

A number of complications may develop from Crohn disease. Many can be treated successfully. These include:

• Narrowing of the colon, which may cause obstruction
• Perforation of the colon
• Abscesses (pus-filled pockets of infection) in the colon
• Toxic megacolon (swollen colon that may rupture)
• Fistulas (abnormal hollow passages that lead from one part of the intestine to another, or to other organs)
• Infection of the blood (sepsis)
• Colon cancer
• Nutritional problems (including weight loss and reduced muscle mass)
• Joint pain and arthritis
• Osteoporosis (bone loss)
• Gallstones
• Eye infections/inflammation
• Mouth ulcers, gum inflammation, and dental cavities
• Liver damage
• Blood clots
• Depression and anxiety
• Anemia

Although there is no cure for Crohn disease, many people with the disease lead active lives by controlling their symptoms with medicine. Over time, however, Crohn disease is less responsive to treatment. It is estimated that 75% of people with Crohn disease will eventually undergo surgery. Up to 38% of people who have surgery for Crohn disease experience a recurrence in the first year after surgery. Smoking is the strongest risk factor for postoperative recurrence. In general, morbidity and mortality rates are higher for people who have Crohn disease compared to the unaffected population.

Supporting Research

Abela MB. Hypnotherapy for Crohn's disease: a promising complementary/alternative therapy. Integr Med. 2000;2(2/3):127-131.

Ahmed T, Rieder F, Fiocchi C, Achkar JP. Pathogenesis of postoperative recurrence in Crohn's disease. Gut. 2011; 60(4):553-62.

Ammon HP. Boswellic acids in chronic inflammatory diseases. Planta Med. 2006 Oct;72(12):1100-16.

Anton PA. Stress and mind-body impact on the course of inflammatory bowel diseases. Semin Gastrointest Dis. 1999;10(1):14-19.

Ball E. Exercise guidelines for patients with inflammatory bowel disease. Gastroenterol Nurs. 1998;21(3):108-111.

Belluzzi A, Boschi S, Brignola C, Munarini A, Cariani G, Miglio F. Polyunsaturated fatty acids and inflammatory bowel disease. Am J Clin Nutr. 2000;71(suppl):339S-342S.

Belluzzi A, Brignola C, Campieri M, Pera A, Boschi S, Miglioli M. Effect of an enteric-coated fish-oil preparation on relapses in Crohn's disease. N Engl J Med. 1996;334(24):1557-1560.

Bermejo F, Algaba A, Guerra I, et al. Should we monitor vitamin B12 and folate levels in Crohn's disease patients? Scand J Gastroenterol. 2013;48(11):1272-7.

Bernell O, Lapidus A, Hellers G. Risk factors for surgery and postoperative recurrence in Crohn's disease. Ann Surg. 2000;231(1):38-45.

Blumenthal M, ed. Herbal Medicine. Expanded Commission E Monographs. Newton, Mass: Integrative Medicine Communications; 2000.

Bock S. Integrative medical treatment of inflammatory bowel disease. Int J Integr Med. 2000;2(5):21-29.

Brignola C, Belloli C, De Simone G, et al. Zinc supplementation restores plasma concentrations of zinc and thymulin in patients with Crohn's disease. Aliment Pharmacol Ther. 1993;7:275-280.

Butterworth AD, Thomas AG, Akobeng AK. Probiotics for induction of remission in Crohn's disease. Cochrane Database Syst Rev. 2008 Jul 16;(3):CD006634. Review.

Cho S, Cho S, Regueiro M. Postoperative Management of Crohn's Disease. Gastroenterology Clinics. 2009;38(4).

Chowers Y, Sela B, Holland R, Fidder H, Simoni FB, Bar-Meir S. Increased levels of homocysteine in patients with Crohn's disease are related to folate levels. Am J Gastroenterol. 2000;95(12):3498-3502.

Cosnes J, Beaugerie L, Carbonnel F, Gendre JP. Smoking cessation and the course of Crohn's disease: an intervention study. Gastroenterology. 2001;120(5):1093-1099.

Dear KL, Hunter JO. Colonoscopic hydrostatic balloon dilation of Crohn's strictures. J Clin Gastroenterol. 2001;33(4):315-318.

Farmer M, Petras RE, Hunt LE, Janosky JE, Galadiuk S. The importance of diagnostic accuracy in colonic inflammatory bowel disease. Am J Gastroenterol. 2000;95(11):3184-3188.

Favier C, Neut C, Mizon C, Cortot A, Colombel JF, Mizon J. Fecal ß-D-Galactosidase production and Bifidobacteria are decreased in Crohn's disease. Dig Dis Sci. 1997;42(4):817-822.

Feagan BG, Fedorak RN, Irvine EJ, et al. A comparison of methotrexate with placebo for the maintenance of remission in Crohn's disease. N Engl J Med. 2000;342:1627-1632.

Feagan BG, Sandborn WJ, Mittmann U, Bar-Meir S, D'Haens G, Bradette M, et al. Omega-3 free fatty acids for the maintenance of remission in Crohn disease: the EPIC Randomized Controlled Trials. JAMA. 2008 Apr 9;299(14):1690-7.

Ferri: Practical Guide to the Care of the Medical Patient, 8th ed. St. Louis, MO: Elsevier Mosby; 2010.

Ferri: Ferri's Clinical Advisor 2015. St. Louis, MO: Elsevier Mosby; 2014.

Freeman HJ. Natural history and long-term clinical course of Crohn's disease. World J Gastroenterol. 2014;20(1):31-6.

Geerling BJ, Badart-Smook A, Stockbrügger RW, Brummer R-JM. Comprehensive nutritional status in recently diagnosed patients with inflammatory bowel disease compared with population controls. Eur J Clin Nutr. 2000;54:514-521.

Geerling BJ, Houwelingen AC, Badart-Smook A, Stockbrügger RW, Brummer R-JM. The relation between antioxidant status and alterations in fatty acid profile in patients with Crohn disease and controls. Scand J Gastroenterol. 1999a;34:1108-1116.

Geerling BJ, Stockbrugger RW, Brummer R-JM. Nutrition and inflammatory bowel disease: an update. Scand J Gastroenterol. 1999c;34(suppl 230):95-105.

Gilman J, Shanahan F, Cashman KD. Determinants of vitamin D status in adult Crohn's disease patients, with particular emphasis on supplemental vitamin D use. Eur J Clin Nutr. 2006 Jul;60(7):889-96.

Gionchetti P, Rizzello F, Venturi A, Campieri M. Probiotics in infective diarrhea and inflammatory bowel diseases. J Gastroenterol Hepatol. 2000;15:489-493.

Gupta I, Parihar A, Malhotra P, Singh GB, Ludtke R, Safayhi H, Ammon HPT. Effects of Boswellia serrata gum resin in patients with ulcerative colitis. Eur J Med Res. 1997;2:37-43.

Haas l, McClain C, Varilek G. Complementary and alternative medicine and gastrointestinal diseases. Curr Opin Gastroenterol. 2000;16:188-196.

Hampe J, Cuthbert A, Croucher JP, et al. Association between insertion mutation in NOD2 gene Crohn's disease in German and British populations. Lancet. 2001;357:1925-1928.

Harper JWW, Welch MP, Sinanan MN, Wahbeh GT, Lee SD. Co-morbid diabetes in patients with Crohn's disease predicts a greater need for surgical intervention. Aliment Pharmacol Ther. 2012;35(1):126-32.

Heilpern D, Szilagyi A. Manipulation of intestinal microbial flora for therapeutic benefit in inflammatory bowel diseases: review of clinical trials of probiotics, pre-biotics and synbiotics. Rev Recent Clin Trials. 2008 Sep;3(3):167-84. Review.

Heuschkel RB, Menache CC, Megerian JT, Baird AE. Enteral nutrition and corticosteroids in the treatment of acute Crohn's disease in children. J Pediatr Gastroenterol Nutr. 2000;31(1):8-15.

Joachim G. The relationship between habits of food consumption and reported reactions to food in people with inflammatory bowel disease—testing the limits. Nutr Health. 1999;13(2):69-83.

Jonas WB, Jacobs J. Healing with Homeopathy: The Doctors' Guide. New York, NY: Warner Books; 1996:220.

Joos S, Brinkhaus B, Maluche C, Maupai N, Kohnen R, Kraehmer N, Hahn EG, Schuppan D. Acupuncture and moxibustion in the treatment of active Crohn's disease: a randomized controlled study. Digestion. 2004;69(3):131-9.

Julsgaard M, Norgaard M, Hvas CL, Grosen A, Hasseriis S, Christensen LA. Influence of medical treatment, smoking and disease activity on pregnancy outcomes in Crohn's disease. Scand J Gastroenterol. 2014;49(3):302-8.

Keane J, Gershon S, Wise RP et al. Tuberculosis associated with infliximab, a tumor necrosis factor alpha-neutralizing agent. N Engl J Med. 2001;345(15):1098-1104.

Kozuch PL, Hanauer SB. Treatment of inflammatory bowel disease: a review of medical therapy. World J Gastroenterol. 2008 Jan 21;14(3):354-77. Review.

Kuroki F, Iida M, Tominaga M, et al. Multiple vitamin status in Crohn's disease. Dig Dis Sci. 1993;38(9):1614-1618.

Latella G, Sferra R, Vetuschi A, Zanninelli G, D'Angelo A, Catitti V, Caprilli R, Gaudio E. Prevention of colonic fibrosis by Boswellia and Scutellaria extracts in rats with colitis induced by 2,4,5-trinitrobenzene sulphonic acid. Eur J Clin Invest. 2008 Jun;38(6):410-20.

Levy E, Rizwan Y, Thibault L, et al. Altered lipid profile, lipoprotein composition, and oxidant and antioxidant status in pediatric Crohn disease. Am J Clin Nutr. 2000;71:807-815.

Lewis JD, Fisher RL. Nutrition support in inflammatory bowel disease. Med Clin North Am. 1994;78(6):1443-1456.

Loudon CP, Corroll V, Butcher J, Rawsthorne P, Bernstein CN. The effects of physical exercise on patients with Crohn's disease. Am J Gastroenterol. 1999;94(3):697-703.

Macdonald A. Omega-3 fatty acids as adjunctive therapy in Crohn's disease. Gastroenterol Nurs. 2006 Jul-Aug;29(4):295-301.

Malin M, Suomalainen H, Saxelin M, Isolauri E. Promotion of IgA immune response in patients with Crohn's disease by oral bacteriotherapy with Lactobacillus GG. Ann Nutr Metab. 1996;40:137-145.

Marrero F, Qadeer M, Lashner B. Severe Complications of Inflammatory Bowel Disease. Medical Clinics of North America. 2008;92(3).

Mendall MA, Gunasekera AV, John BJ, Kumar D. Is obesity a risk for Crohn's disease. Dig Dis Sci. 2011;56(3):837-44.

Messaris E, Chandolias N, Grand D, Pricolo V. Role of magnetic resonance enterography in the management of Crohn's disease. Arch Surg. 2010;145(5):471-5.

Msika S, Iannelli A, Deroide G, et al. Can laparoscopy reduce hospital stay in the treatment of Crohn's disease? Dis Colon Rectum. 2001;44(11):1661-1666.

Mulder TPJ, Van Der Sluys Veer A, Verspaget HW, et al. Effect of oral zinc supplementation on metallothionein and superoxide dismutase concentrations in patients with inflammatory bowel disease. J Gastroenterol Hepatol. 1994;9:472-477.

Nerich V, Jantchou P, Boutron-Ruault MC, et al. Low exposure to sunlight is a risk factor for Crohn's disease. Aliment Pharmacol Ther. 2011;33(8):940-5.

Nielsen AA, Jorgensen LG, Nielsen JN, Eivindson M, Gronbaek H, Vind I, et al. Omega-3 fatty acids inhibit an increase of proinflammatory cytokines in patients with active Crohn's disease compared with omega-6 fatty acids. Aliment Pharmacol Ther. 2005 Dec;22(11-12):1121-8.

Onken JE, Greer PK, Calingaert B, Hale LP. Bromelain treatment decreases secretion of pro-inflammatory cytokines and chemokines by colon biopsies in vitro. Clin Immunol. 2008 Mar;126(3):345-52.

Philipsen-Geerling BJ, Brummer RJM. Nutrition in Crohn's disease. Curr Opin Clin Nutr Metab Care. 2000;3:305-309.

Rahimi R, Nikfar S, Rahimi F, Elahi B, Derakhshani S, Vafaie M, Abdollahi M. A meta-analysis on the efficacy of probiotics for maintenance of remission and prevention of clinical and endoscopic relapse in Crohn's disease. Dig Dis Sci. 2008 Sep;53(9):2524-31.

Rajapakse R, Korelitz BI. Inflammatory bowel disease during pregnancy. Current Treatment Options in Gastroenterology. 2001;4(3):245-251.

Rawsthorne P, Shanahan F, Cronin NC, et al. An international survey of the use and attitudes regarding alternative medicine by patients with inflammatory bowel disease. Am J Gastroenterol. 1999;94(5):1298-1303.

Ringel Y, Drossman DA. Psychosocial aspects of Crohn's disease. Surg Clin North Am. 2001;81(1):231-252.

Rioux JD, Daly MJ, Silverberg MS, et al. Genetic variation in the 5q31 cytokine gene cluster confers susceptibility to Crohn disease. Nat Genet. 2001;29:223-228.

Rolfe VE, Fortun PJ, Hawkey CJ, Bath-Hextall F. Probiotics for maintenance of remission in Crohn's disease. Cochrane Database Syst Rev. 2006 Oct 18;(4):CD004826.

Russel MG. Changes in the incidence of inflammatory bowel disease: what does it mean? Eur J Intern Med. 2000;11(4):191-196.

Salvatore S, Heuschkel R, Tomlin S, et al. A pilot study of N-acetyl glucosamine, a nutritional substrate for glycosaminoglycan synthesis, in pediatric chronic inflammatory bowel disease. Aliment Pharmacol Ther. 2000;14:1567-1579.

Shanahan F. Probiotics and inflammatory bowel disease: is there a scientific rationale? Inflamm Bowel Dis. 2000;6(2):107-115.

Steger GG, Mader RM, Vogelsang H, Schöfl R, Lochs H, Ferenci P. Folate absorption in Crohn's disease. Digestion. 1994;55:234-238.

Stein RB, Lichtenstein GR, Rombeau JL. Nutrition in inflammatory bowel disease. CurrOpin Clin Nutr Metab Care. 1999;2:367-371.

Szulc P, Meunier PJ. Is vitamin K deficiency a risk factor for osteoporosis in Crohn's disease? [commentary]. Lancet. 2001;357(9273):1995-1996.

Tamaka S, Matsuo K, Sasaki T, Nakano M, Shimura H, Yamashita Y. Clinical outcomes and advantages of laparoscopic surgery for primary Crohn's disease: are they significant? Hepatogastroenterology. 2009;56(90):416-20.

Teahon K, Bjarnason I, Pearson M, Levi AJ. Ten years' experience with an elemental diet in the management of Crohn's disease. Gut. 1990;31(10):1133-1137.

Tsujikawa T, Satoh J, Katsuhiro U, et al. Clinical importance of n-3 fatty acid-rich diet and nutritional education for the maintenance of remission in Crohn's disease. Gastroenterol. 2000;35:99-104.

Ullman D. The Consumer's Guide to Homeopathy. New York, NY: Penguin Putnam; 1995:76-77.

van Heel DA, McGovern DPB, Jewell DP. Crohn's disease: a genetic susceptibility, bacteria, and innate immunity [commentary]. Lancet. 2001;357:1902-1903.

Wilkins T, Jarvis K, Patel J. Diagnosis and management of Crohn's disease. Am Fam Physician. 2011;84(12):1365-75.

Zachos M, Tondeur M, Griffiths AM. Enteral nutritional therapy for inducing remission of Crohn's disease (Cocrane Review). In: The Cochrane Library, 4, 2001. Oxford: Update Software.

Zurita VF, Rawls DE, Dyck WP. Nutritional support in inflammatory bowel disease. Dig Dis. 1995;13:92-107.