Crohn's disease

Encyclopedia : C : CR : CRO : Crohn's disease

Endoscopic image of severe Crohn's colitis showing diffuse loss of mucosal architecture, friability of mucosa in sigmoid colon and exudate on wall.

H&E section of non-caseasting granuloma seen in the colon of a patient with Crohn's disease.

Crohn's disease is a type of inflammatory bowel disease (IBD), named for one of the physicians who first described the disease. It is a disease that results in chronic inflammation of the gastrointestinal tract. The disease can affect the entire gastrointestinal tract from mouth to anus. Because it is a systemic disease, it can also cause complications outside of the gastrointestinal tract. The main gastrointestinal symptoms are abdominal pain and diarrhea, which may be bloody.

Crohn's ileitis is a type of Crohn's disease that affects the small intestine; Crohn's colitis, the large intestine (colon). Crohn's colitis is similar to ulcerative colitis, another form of IBD. Extensive testing may be required to distinguish Crohn's from ulcerative colitis. Because of the name, IBD can be confused with irritable bowel syndrome (IBS), an annoying but much less serious condition.

Crohn's disease is a rare disease, affecting fewer than one person in 10,000 in Europe and North America. The disease is believed to be even less common in the rest of the world.

Although Crohn's disease has no known cause, it is widely believed to be an autoimmune disease. There is a genetic component to susceptibility, and the disease may be triggered in a susceptible person by environmental factors. Certain bacteria may also be associated with the disease. Although persons with the disease may need to limit their diet on account of the disease, the disease is not itself caused by dietary factors.

Unlike the other major type of IBD, ulcerative colitis, there is no known medical or surgical cure for Crohn's disease. Many medical treatments are however available for Crohn's disease with a goal of keeping the disease in remission.

Contents

Clinical manifestations

The three most common sites of intestinal involvement in Crohn's disease are ileal, ileocolic and colonic.

Distribution of gastrointestinal Crohn's disease. Based on data from American Gastroenterological Association.

Many patients with Crohn's disease have symptoms for years prior to the diagnosis. Because of the patchy nature of the gastrointestinal disease and the depth of tissue involvement, initial symptoms can be more vague than with ulcerative colitis.

Crohn's disease may be classified according to the extent of involvement of the gastrointestinal tract:

Crohn's ileitis: Crohn's disease usually includes involvement of the ileum, the portion of the small intestine that joins to the large intestine. Thirty percent of cases involve only the illeum.

Crohn's colitis or colonic Crohn's disease: Crohn's disease may affect the large intestine, in which case it becomes particularly difficult to distinguish it from ulcerative colitis. Twenty percent of cases involve only the colon.

Ileocolic Crohn's disease: The disease may affect both the ileum and the large intestine. Fifty percent of cases involve both the ileum and the colon.

Peri-anal Crohn's disease: The disease may affect the area around the anus.

Other: Crohn's disease may affect any portion of the gastrointestinal tract.

Common initial symptoms of Crohn's disease include the following:

Gastrointestinal symptoms

Abdominal pain: A common symptom is abdominal pain of a crampy nature, as the inflammation associated with Crohn's disease can result in stenosis, localized inflammatory strictures, or areas of narrowing of the bowel. Over time, these areas may develop fibrosis, leading to fixed areas of stenosis. The pain may occur anywhere in the abdomen, and, as it is related to areas of stenosis, may be relieved by defecation. In the setting of severe stenosis, vomiting and nausea may indicate the beginnings of small bowel obstruction.
Diarrhea: The nature of the diarrhea in Crohn's disease depends on the part of the small intestine and colon that is involved. Ileitis typically results in large volume watery feces. Colonic Crohn's disease may result in smaller volume feces of higher frequency. Consistency may range from solid to watery. In severe cases, the patient may have more than 20 bowel movements per day, and the need may awaken the patient at night. Fecal incontinence may accompany peri-anal Crohn's disease.
Bloody diarrhea: Gross bleeding in the feces is less common in Crohn's disease than in ulcerative colitis, but may be seen in the setting of Crohn's colitis. Bloody bowel movements are typically intermittent, and may be bright or dark red in colour. In the setting of severe Crohn's colitis, bleeding may be severe.
Peri-anal discomfort: Itchiness or pain around the anus may be suggestive of inflammation, fistulization or abscess around the anal area.
Flatus and bloating.
Rarely, the esophagus, and stomach may be involved in Crohn's disease. These can cause symptoms including odynophagia(difficulty swallowing), upper abdominal pain, and vomiting.

Systemic symptoms

As Crohn's disease involves a greater depth of tissue involvement, it can present with more systemic symptoms. These include the following:

Fever: these are usually low grade (less than 38.5 C), unless there is a complication, such as an abscess
Weight loss: This is usually related to decreased intake since patients with intestinal symptoms feel better when they do not eat. Patients with extensive small intestine disease may have malabsorption of carbohydrates or lipids, which can further exacerbate weight loss.
Growth failure: Many children are first diagnosed with Crohn's disease based on inability to maintain growth. As Crohn's disease may manifest around the growth spurt of puberty, up to 30% of children with Crohn's disease may have retardation of growth.

Extraintestinal symptoms

Crohn's disease is a disease of unknown causation. Many of the following symptoms, which are outside of the gastrointestinal tract, would also be symptoms of a chronic, untreated infection. These symptoms, however, may persist in a patient with Crohn's disease, even after all identifiable infections have been sucessfully treated. If the disease is cause by an infection, that infection remains unknown. The prevalent theory is that the immune system is responding as though there were an infection, even though none is present. Crohn's disease is therefore usually regarded as an auto-immmune disease.

As Crohn's disease is a systemic disease, many other organ systems aside from the gastrointestinal tract can be involved. Extraintestinal symptoms include the following:

aphthous ulcers of the mouth
Ophthalmic (involving the eyes):
*Iritis or uveitis (inflammations of the uvea)
*Episcleritis
Musculoskeletal:
*Seronegative arthritis, which can be a large-joint oligoarthritis (affecting one or two joints), or may affect many small joints of the hands and feet
*Ankylosing spondylitis, arthritis of the spine
*Sacroiliitis, arthritis of the lower spine
Cutaneous (related to the skin):
*Erythema nodosum, which is a painless panniculitis(inflammation of subcutaneous tissue)
* Pyoderma gangrenosum, a painful ulcerating lesion involving the skin
Deep venous thrombosis and pulmonary embolism
autoimmune hemolytic anemia
clubbing, a deformity of the ends of the fingers
Primary sclerosing cholangitis, a type of inflammation of the bile ducts, occurs less commonly than in ulcerative colitis
osteoporosis, or thinning of the bones.

Diagnosis

Endoscopic image of Crohn's colitis showing deep ulceration.

CT scan of patient showing Crohn's disease in the fundus of the stomach

Endoscopy image of colon showing serpiginous ulcer, a classic finding in Crohn's disease

The diagnosis of Crohn's disease can sometimes be challenging, and a number of tests are often required to assist the physician in making the diagnosis:

Blood tests: A complete blood count is useful to check for anemia, which may be caused by blood loss or vitamin B12 deficiency. The latter is common with ileitis because Vitamin B-12 is absorbed in the ileum. Also, erythrocyte sedimentation rate or ESR, and C-reactive protein measurements can be useful to gauge the degree of inflammation. Epub ahead of print
Colonoscopy: A colonoscopy is the best test for making the diagnosis of Crohn's disease as it allows direct visualization of the colon and the terminal ileum, identifying the pattern of disease involvement. During the procedure, the gastroenterologist can also perform a biopsy, taking small samples of tissue for laboratory analysis which may help confirm a diagnosis. As 30% of Crohn's disease involves only the ileum, cannulation of the terminal ileum is required in making the diagnosis. Finding a patchy distribution of disease, with involvement of the ileum but not the rectum, is suggestive of Crohn's disease, as are other endoscopic stigmata.
Small bowel X-ray: Because colonoscopy and gastroscopy allow direct visualization of only the terminal ileum and beginning of the duodenum, they cannot be used to evaluate the remainder of the small intestine. As a result, small bowel x-rays, wherein barium is ingested and fluoroscopic images of the bowel are taken over time, is useful for looking for inflammation and narrowing of the small bowel.
Computed tomography (CT): CT scans are useful for evaluating the small bowel with enteroclysis protocols. They are additionally useful for looking for intra-abdominal complications of Crohn's disease, especially abscesses. Physicians may also order this test to check for other complications such as small bowel obstructions or fistulae.
Magnetic resonance imaging: MRI is additionally useful at imaging the small bowel as well as looking for complications, including abscesses, obstruction or fistulae.
Wireless capsule endoscopy: Capsule camera is a technique where a small capsule with a camera in it is swallowed by the patient. The camera takes serial pictures of the entire gastrointestinal tract and is passed in the patient's feces. It has been used in the search for Crohn's disease in the small bowel, which cannot be reached with colonoscopy or gastroscopy. The utility of capsule endoscopy for this, however, is still uncertain.
Serology: Testing for anti-Saccharomyces cerevisiae antibodies (ASCA) and anti-neutrophil cytoplasmic antibodies (ANCA) has been evaluated to identify inflammatory diseases of the intestine and to differentiate Crohn's disease from ulcerative colitis, but are not routinely used in practice.
Barium enema: With the advent of endoscopy, barium enemas are rarely used in the work-up of Crohn's disease. They remain useful for identifying anatomical abnormalities in patients with strictures of the colon that are too small for a colonoscope to pass through, or in the detection of colonic fistulae.

Comparison to ulcerative colitis and other diseases

The most common disease that mimics the symptoms of Crohn's disease is ulcerative colitis, as both are inflammatory bowel diseases that can affect the colon with similar symptoms. The following are differences between the two conditions:

Crohn's disease:
*Can occur anywhere in the gastrointestinal tract but commonly involves the terminal ileum
*Has a patchy distribution in the intestine.
*Has transmural inflammation where it spreads deep into the layers of affected tissues.
*Can have granulomata on biopsy
*May spare the rectum on endoscopy
*Has characteristic features on endoscopy including deep, linear and serpiginous (or snake-like) ulcers
*Can be associated with fistulae, abnormal connections or passageways between the intestine and organs or vessels that normally do not connect.
*Can exhibit peri-anal symptoms around the anus.
*Often returns following surgical removal of the affected part of the intestine.

Ulcerative colitis:
*Usually affects only the large intestine and rectum
*Usually exhibits inflammation in a single area in a continuous fashion.
*Usually affects the only the mucosa, or the innermost lining of tissues.
*Has characteristic features on endoscopy including shallow, continuous ulcers and involvement of the rectum.
*Does not usually exhibit peri-anal involvement.
*Not usually associated with fistulae.
*Has a higher rate of primary sclerosing cholangitis
*Can usually be cured by surgical removal of the large intestine.


	Crohn's Disease	Ulcerative Colitis
Involves terminal ileum?	Commonly	Seldom
Involves colon?	Usually	Always
Involves rectum?	Seldom	Usually
Peri-anal involvement?	Commonly	Seldom
Bile duct involvement?	Not associated	Higher rate of Primary sclerosing cholangitis
Distribution of Disease	Patchy areas of inflammation	Continuous area of inflammation
Endoscopy	Linear and serpiginous (snake-like) ulcers	Continuous ulcer
Depth of inflammation	May be transmural, deep into tissues	Shallow, mucosal
Fistulae, abnormal passageways between organs	Commonly	Seldom
Biopsy	Can have granulomata
Surgical cure?	Often returns following removal of affected part	Usually cured by removal of colon
Smoking	Higher risk for smokers	Lower risk for smokers

Epidemiology and causes

The incidence of Crohn's disease has been ascertained from population studies in Norway and the United States and is similar at 6 to 7.1:100,000. It has been established that Crohn's disease is more common in northern countries, and shows a higher preponderance in northern areas of the same country. The incidence of Crohn's disease in North America is 6:100 000, and is thought to be similar in Europe, but lower in Asia and Africa It also has a higher incidence in Ashkenazi Jews.

Crohn's disease has a bimodal distribution in incidence as a function of age. The disease tends to strike people in their teens and twenties, and people in their fifties through seventies.

The exact cause of Crohn's disease is unknown. However, genetic and environmental factors have been invoked in the pathogenesis of the disease:

Schematic of NOD2 CARD15 gene, which is associated with certain disease patterns in Crohn's disease

Heredity: Parents, siblings or children of Crohn's disease are 3 to 20 times more likely to develop the disease.Satsangi J, Jewell DP, Bell JI. The genetics of inflammatory bowel disease. Gut. 1997 May;40(5):572-4. PMID 9203931. Twin studies show a concordance of greater than 55% for Crohn's disease.Tysk C, Lindberg E, Jarnerot G, Floderus-Myrhed B. Ulcerative colitis and Crohn's disease in an unselected population of monozygotic and dizygotic twins. A study of heritability and the influence of smoking. Gut 1988 Jul;29(7):990-6. PMID 3396969 Mutations in a gene called NOD2/CARD15 are associated with Crohn's diseaseOgura Y, Bonen DK, Inohara N, Nicolae DL, Chen FF, Ramos R, Britton H, Moran T, Karaliuskas R, Duerr RH, Achkar JP, Brant SR, Bayless TM, Kirschner BS, Hanauer SB, Nunez G, Cho JH. A frameshift mutation in NOD2 associated with susceptibility to Crohn's disease. Nature. 2001 May 31;411(6837):603-6. and with susceptibility to certain phenotypes of disease location and activity.Cuthbert AP, Fisher SA, Mirza MM, King K, Hampe J, Croucher PJ, Mascheretti S, Sanderson J, Forbes A, Mansfield J, Schreiber S, Lewis CM, Mathew CG. The contribution of NOD2 gene mutations to the risk and site of disease in inflammatory bowel disease. Gastroenterology. 2002 Apr;122(4):867-74. PMID 11910337. Further studies are in progress to delineate the contribution of this gene.

Immune system: Abnormalities in the immune system have often been invoked as causes of Crohn's disease. It has been hypothesized that Crohn's disease involves augmentation of the Th1 system of cytokine response in inflammation.Cobrin GM, Abreu MT. Defects in mucosal immunity leading to Crohn's disease. Immunol Rev. 2005 Aug;206:277-95. PMID 16048555 Also, as the colon is rich in bacteria, many infectious agents have been invoked as causes of Crohn's disease, including Mycobacterium avium subspecies paratuberculosis.Naser SA, Collins MT. Debate on the lack of evidence of Mycobacterium avium subsp. paratuberculosis in Crohn's disease. Inflamm Bowel Dis. 2005 Dec;11(12):1123. PMID 16306778
Environment: Many environmental factors have also been hypothesized as causes or risk factors for Crohn's disease. These include the following:
*A diet high in fatty or refined foods, may play a role, but this is anecdotal and based on the fact that Crohn's disease has a higher incidence in industrialized countries.
*Smoking, which may increase the risk of Crohn's flares.Cosnes J, Beaugerie L, Carbonnel F, Gendre JP. Smoking cessation and the course of Crohn's disease: an intervention study. Gastroenterology. 2001 Apr;120(5):1093-9. PMID 11266373
*Oral contraceptives have shown an association with the development of Crohn's disease.Lesko SM, Kaufman DW, Rosenberg L, Helmrich SP, Miller DR, Stolley PD, Shapiro S. Evidence for an increased risk of Crohn's disease in oral contraceptive users. Gastroenterology. 1985 Nov;89(5):1046-9. PMID 4043662.

Pathology

Because very little of the small intestine can be visualized through colonoscopy or gastroscopy, the following discussion is focused on Crohn's colitis.

At the time of colonoscopy, biopsies of the colon are often taken in order to confirm the diagnosis. There are certain characteristic features of the pathology seen that point toward Crohn's disease. Crohn's disease shows a transmural pattern of inflammation, meaning that the inflammation may span the entire depth of the intestinal wall. Biopsies of the affected colon may show the following features:Crawford JM. "The Gastrointestinal tract, Chapter 17". In Cotran RS, Kumar V, Robbins SL. Robbins Pathologic Basis of Disease: 5th Edition. W.B. Saunders and Company, Philadelphia, 1994.

Mucosal inflammation: focal infiltration of neutrophils, a type of inflammatory cell, into the epithelium, usually the area overlying lymphoid aggregates
This proceeds to the infiltration of neutrophils and mononuclear cells into the crypts resulting in inflammation, termed cryptitis, or the formation of small abscesses, termed crypt abscesses.
Ulceration is an outcome seen in highly active disease. Typically, there is an abrupt transition between unaffected tissue and the ulcer.
Chronic mucosal damage results in blunting of the intestinal villi, atypical branching of the crypts, and metaplasia or change in the tissue type
Paneth cells, which is a cell type normally found in the small intestine, but rarely in the distal colon, may develop in a process called Paneth cell metaplasia
Transmural inflammation results with inflammation and the formation of lymphoid aggregates throughout the wall of the colon
Granulomas, aggregates of macrophage derivatives known as giant cells, are found in 50% of cases. The granulomas of Crohn's disease do not show "caseation", a cheese-like appearance on microscopic examination that is characteristic of granulomas associated with infections such as tuberculosis.

Treatment

The therapeutic approach to Crohn's disease is sequential: to treat acute disease, and then to maintain remission. Treatment initially involves the use of medications to treat any infection and to reduce inflammation. This usually involves the use of aminosalicylate anti-inflammatory drugs and corticosteroids, and may include antibiotics. Surgery may be required for complications such as obstructions or abcesses, or if the disease does not respond to drugs within a reasonable time.

Once remission is induced, the goal of treatment becomes maintenance of remission, avoiding the return of active disease, or "flares". Because of side-effects, the prolonged use of corticosteroids must be avoided. Although some patients are able to maintain remission with aminosalicylates alone, many require immunosuppressive drugs. Management of Crohn's Disese in Adults, Am. J. Gastroenterology, Vol 96, No. 3[link]

Aminosalicylate anti-inflammatory drugs

5-aminosalicylates (5-ASA) include the following:

Mesalazine or mesalamine, which is marketed in the forms Asacol, Pentasa, Salofalk, Dipentum and Rowasa.
Sulfasalazine, which is converted to 5-ASA and sulfapyridine by intestinal bacteria. The sulfapyridine may have some therapeutic effect in addition to the 5-ASA, although this is not entirely clear.

5-ASA compounds have been shown to be useful in the treatment of mild-to-moderate Crohn's disease.Hanauer SB, Stromberg U. Oral Pentasa in the treatment of active Crohn's disease: A meta-analysis of double-blind, placebo-controlled trials. Clin Gastroenterol Hepatol. 2004 May;2(5):379-88. PMID 15118975 They are usually considered to be first line therapy for disease in the ileum and right side of the colon particularly due to their low side effect profile.Prantera C, Cottone M, Pallone F, Annese V, Franze A, Cerutti R, Bianchi Porro G. Mesalamine in the treatment of mild to moderate active Crohn's ileitis: results of a randomized, multicenter trial. Gastroenterology. 1999 Mar;116(3):521-6. PMID 10029609.

Corticosteroid anti-inflammatory drugs

Steroid enemas can be used for treatment of rectal disease symptoms

Corticosteroids are a class of anti-inflammatory drug that are used primarily for treatment of moderate to severe flares of Crohn's disease. They are used more sparingly due to the available of effective treatments with less side-effects. The side effects of corticosteroids include Cushing's syndrome, mania, insomnia, hypertension, high blood glucose, osteoporosis, and avascular necrosis of long bones. These should not be confused with the anabolic steroids used to enhance athletic performance.

The most commonly prescribed oral steroid is prednisone, which is typically dosed at 0.5 mg/kg for induction of remission.Hanauer SB. Sulfasalazine vs. steroids in Crohn's disease: David vs. Goliath? Gastroenterology. 1991 Oct;101(4):1130-1. PMID 1679735. Intravenous steroids are used for cases refractory to oral steroids, or where the patient cannot take oral steroids. These are administered in the hospital setting. Because corticosteroids reduce the ability to fight infection, care must be used to ensure that the patient does not have active infection, particularly an intra-abdominal abscess before the initiation of steroids.

Budesonide is an oral corticosteroid with limited absorption and high level of first-pass metabolism, meaning that less quantities of steroid enter into the bloodstream. It has been shown to be useful in the treatment of mild-to-moderate Crohn's diseaseGreenberg GR, Feagan BG, Martin F, Sutherland LR, Thomson AB, Williams CN, Nilsson LG, Persson T. Oral budesonide for active Crohn's disease. Canadian Inflammatory Bowel Disease Study Group. N Engl J Med. 1994 Sep 29;331(13):836-41. and for maintenance of remission in Crohn's disease.Sandborn WJ, Lofberg R, Feagan BG, Hanauer SB, Campieri M, Greenberg GR. Budesonide for maintenance of remission in patients with Crohn's disease in medically induced remission: a predetermined pooled analysis of four randomized, double-blind, placebo-controlled trials. Am J Gastroenterol. 2005 Aug;100(8):1780-7. PMID 16086715 Formulated as Entocort, budesonide is released in the ileum and right colon, and is therefore has a topical effect against disease in that area.

Budesonide is also useful when used in combination with antibiotics for active Crohn's disease.Steinhart AH, Feagan BG, Wong CJ, Vandervoort M, Mikolainis S, Croitoru K, Seidman E, Leddin DJ, Bitton A, Drouin E, Cohen A, Greenberg GR. Combined budesonide and antibiotic therapy for active Crohn's disease: a randomized controlled trial. Gastroenterology. 2002 Jul;123(1):33-40. PMID 12105831.

Steroid enemas can also be used for disease of the lower colon and rectum, in order to treat symptoms. Hydrocortisone and budesonide liquid and foam enemas are being marketed for these reasons.

Mercaptopurine immunosuppressing drugs

Azathioprine, shown here in tablet form, is a first line steroid-sparing immunosuppressant

Azathioprine and 6-mercaptopurine (6-MP) are the most used immunosuppressants for maintenance therapy of Crohn's disease. They are purine anti-metabolites, meaning that they interfere with the synthesis of purines required for inflammatory cells. They have a duration of action of months, making it unwieldy to use them for induction of remission. Both drugs are dosed at 1.5 to 2.5 mg/kg, with literature supporting the use of higher doses.

Azathioprine and 6-MP have been found to be useful for the following indications:

For maintenance therapy in patients who are dependent on steroids.Rosenberg JL, Levin B, Wall AJ, Kirsner JB. A controlled trial of azathioprine in Crohn's disease. Am J Dig Dis. 1975 Aug;20(8):721-6. PMID 1098449
Fistulizing disease.Dejaco C, Harrer M, Waldhoer T, Miehsler W, Vogelsang H, Reinisch W. Antibiotics and azathioprine for the treatment of perianal fistulas in Crohn's disease. Aliment Pharmacol Ther. 2003 Dec;18(11-12):1113-20. PMID 14653831
Induction of remission in steroid refractory disease.Sandborn W, Sutherland L, Pearson D, May G, Modigliani R, Prantera C. Azathioprine or 6-mercaptopurine for inducing remission of Crohn's disease. Cochrane Database Syst Rev. 2000;(2):CD000545. PMID 10796557
Maintenance of remission after surgery for Crohn's disease.Hanauer SB, Korelitz BI, Rutgeerts P, Peppercorn MA, Thisted RA, Cohen RD, Present DH. Postoperative maintenance of Crohn's disease remission with 6-mercaptopurine, mesalamine, or placebo: a 2-year trial. Gastroenterology. 2004 Sep;127(3):723-9. PMID 15362027.

Infliximab

Infliximab, marketed as Remicade, is a mouse-human chimeric antibody that targets tumour necrosis factor, a cytokine in the inflammatory response. It is administed intravenously and dosed per weight.

Infliximab has found utility as follows:

Maintenance of remission in patients with Crohn's disease.Hanauer SB, Feagan BG, Lichtenstein GR, Mayer LF, Schreiber S, Colombel JF, Rachmilewitz D, Wolf DC, Olson A, Bao W, Rutgeerts P; ACCENT I Study Group. Maintenance infliximab for Crohn's disease: the ACCENT I randomised trial. Lancet. 2002 May 4;359(9317):1541-9. PMID. 12047962
Induction of remission in patients with Crohn's disease.
Maintenance for fistulizing Crohn's disease.Sands BE, Anderson FH, Bernstein CN, Chey WY, Feagan BG, Fedorak RN, Kamm MA, Korzenik JR, Lashner BA, Onken JE, Rachmilewitz D, Rutgeerts P, Wild G, Wolf DC, Marsters PA, Travers SB, Blank MA, van Deventer SJ. Infliximab maintenance therapy for fistulizing Crohn's disease. N Engl J Med. 2004 Feb 26;350(9):876-85. PMID 14985485

Side effects of infliximab include hypersensitivity and allergic reactions, risk of re-activation of tuberculosis, serum sickness, and risk of multiple sclerosis.Rutgeerts P, Van Assche G, Vermeire S. Review article: Infliximab therapy for inflammatory bowel disease--seven years on. Aliment Pharmacol Ther. 2006 Feb 15;23(4):451-63. PMID 16441465.

Other medications

Methotrexate is a folate anti-metabolite drug which is also used for chemotherapy. It is useful in maintenance of remission off of corticosteroids.Feagan BG, Fedorak RN, Irvine EJ, Wild G, Sutherland L, Steinhart AH, Greenberg GR, Koval J, Wong CJ, Hopkins M, Hanauer SB, McDonald JW. A comparison of methotrexate with placebo for the maintenance of remission in Crohn's disease. North American Crohn's Study Group Investigators. N Engl J Med. 2000 Jun 1;342(22):1627-32. PMID 10833208
Metronidazole and ciprofloxacin are antibiotics which are used to treat Crohn's that have colonic or perianal involvement, although this use is non-Food and Drug Administration (FDA) approved.Ursing B, Alm T, Barany F, Bergelin I, Ganrot-Norlin K, Hoevels J, Huitfeldt B, Jarnerot G, Krause U, Krook A, Lindstrom B, Nordle O, Rosen A. A comparative study of metronidazole and sulfasalazine for active Crohn's disease: the cooperative Crohn's disease study in Sweden. II. Result. Gastroenterology. 1982 Sep;83(3):550-62. PMID 6124474 They are also used for treatment of complications, including abscesses and other infections accompanying Crohn's disease.
Thalidomide has shown response in reversing endoscopic evidence of disease.Cohen LB. Re: Disappearance of Crohn's ulcers in the terminal ileum after thalidomide therapy. Can J Gastroenterol 2004; 18(2): 101-104. Can J Gastroenterol. 2004 Jun;18(6):419. PMID 15230268.

Research on medications in progress

Egg of Trichuris spp. whipworm. Trichuris suis or pig whipworm has been investigated for treatment of Crohn's disease.

Many clinical trials have been recently completed or are ongoing for new therapies for Crohn's disease. They include the following:

adalimumab, like infliximab is an antibody that targets tumour necrosis factor.Hanauer SB, Sandborn WJ, Rutgeerts P, Fedorak RN, Lukas M, MacIntosh D, Panaccione R, Wolf D, Pollack P. Human anti-tumor necrosis factor monoclonal antibody (adalimumab) in Crohn's disease: the CLASSIC-I trial. Gastroenterology. 2006 Feb;130(2):323-33. PMID 16472588
sargramostim, or granulocyte-monocyte stimulating factor.Korzenik JR, Dieckgraefe BK, Valentine JF, Hausman DF, Gilbert MJ; Sargramostim in Crohn's Disease Study Group. Sargramostim for active Crohn's disease. N Engl J Med. 2005 May 26;352(21):2193-201. PMID 15917384.
Trichuris suis is a pig whipworm that been shown in one study to improve Crohn's disease symptoms.Summers RW, Elliott DE, Urban JF Jr, Thompson R, Weinstock JV. Trichuris suis therapy in Crohn's disease. Gut. 2005 Jan;54(1):87-90. PMID 15591509.
Autologous stem cell transplant has also been evaluated .Oyama Y, Craig RM, Traynor AE, Quigley K, Statkute L, Halverson A, Brush M, Verda L, Kowalska B, Krosnjar N, Kletzel M, Whitington PF, Burt RK. Autologous hematopoietic stem cell transplantation in patients with refractory Crohn's disease. Gastroenterology. 2005 Mar;128(3):552-63.PMID 15765390

Surgery

Surgery is generally reserved for complications of Crohn's disease, or when disease that resists treatment with drugs is confined to one location that can be removed. Oftentimes surgery is used to manage:

fibrostenotic strictures
fistulae
small bowel obstruction
colon cancer and small intestine cancer

In the case of fibrostenotic strictures, strictureplasty - the expansion of the stricture - is sometimes performed. Otherwise, and for other complications, resection and anastomosis - the removal of the affected section of intestine and the rejoining of the healthy sections - is the surgery usually performed for Crohn's disease (e.g., ileocolonic resection). Neither surgery cures Crohn's disease, as recurrence often reappear in previously unaffected areas of the intestine.

Small intestine transplants are experimental as of yet, and are usually only done when the patient is at risk of short bowel syndrome due to repeated resection surgeries.

Diet and lifestyle

There is no evidence that diet causes or cures Crohn's disease, but many patients with Crohn's disease note that certain foods worsen their symptoms. For example, patients with lactose intolerance due to small bowel disease may benefit from avoiding lactose-containing foods. Many diets have been proposed for treatment of Crohn's disease, and many do improve symptoms, but none have been proven to actually cure Crohn's disease.Gottschall E. Breaking the Vicious Cycle: Intestinal health through diet. Kirkton Press Ltd, Baltimore Ontario, 2005. Similarly, stress can worsen symptoms of Crohn's disease. Patients with Crohn's disease can find that their symptoms improve if they control the stress in their lives.

Because the terminal ileum is the most common site of involvement and is the site for vitamin B₁₂ absorption, it is generally advised that patients receive bi-weekly or monthly intramuscular vitamin B₁₂ injections.

Complementary and alternative medicine

More than half of patients with Crohn's disease have tried complementary or alternative therapy.Caprilli R, Gassull MA, Escher JC, Moser G, Munkholm P, Forbes A, Hommes DW, Lochs H, Angelucci E, Cocco A, Vucelic B, Hildebrand H, Kolacek S, Riis L, Lukas M, de Franchis R, Hamilton M, Jantschek G, Michetti P, O'Morain C, Anwar MM, Freitas JL, Mouzas IA, Baert F, Mitchell R, Hawkey CJ; European Crohn's and Colitis Organisation. European evidence based consensus on the diagnosis and management of Crohn's disease: special situations. Gut. 2006 Mar;55 Suppl 1:i36-58. PMID. 16481630 These include diets, probiotics, fish oil and other herbal and nutritional supplements. The benefit of these medications is uncertain.

Complications

Crohn's disease can lead to the following complications:

Obstruction: Crohn's disease may have a fibrostenotic phenotype, meaning that patients have a tendency to form fibrous tissue. This may result in strictures, and small bowel obstruction. Often, surgical treatment is required.
Fistulae: Patients with Crohn's disease can develop fistulas or passageways between two structures that are ordinarily not attached. These can be between two loops of bowel, between the bowel and bladder, between the bowel and vagina, and between the bowel and skin. Treatment of fistulae may be medical (with azathioprine, infliximab and parenteral nutrition) or may require surgery. This can be a cause of significant discomfort for patients.
Abscesses are walled off collections of infection and can occur in the abdomen or in the peri-anal area in patients with Crohn's disease. They typically present with fevers or abdominal pain. These require treatment with antibiotics and may require drainage or surgery in order to evacuate the infected focus.

Endoscopic image of colon cancer identified in sigmoid colon on screening colonoscopy for Crohn's disease.

Cancer: Having Crohn's disease increases the risk of cancer in the area of inflammation. For example, patients with Crohn's disease involving the small bowel are at higher risk for small intestinal cancer. Similarly, patients with Crohn's colitis are at a higher risk for colon cancer. As colonoscopy is an excellent tool to detect precursor lesions to colon cancer, screening for colon cancer is recommended for all patients who have had Crohn's colitis for at least eight years.Collins PD, Mpofu C, Watson AJ, Rhodes JM. Strategies for detecting colon cancer and/or dysplasia in patients with inflammatory bowel disease. Cochrane Database Syst Rev. 2006 Apr 19;(2):CD000279. PMID: 16625534.
Malnutrition: Patients with Crohn's disease are at risk for malnutrition, due to many reasons, including decreased intake, and malabsorption. They are especially at risk if they have had previous resection of the small bowel. Patients may require oral supplements to increase their caloric intake, or, in severe cases, may require total parenteral nutrition or TPN. Most patients with severe Crohn's disease are referred to a dietician for assistance in nutrition.Evans JP, Steinhart AH, Cohen Z, McLeod RS. Home total parenteral nutrition: an alternative to early surgery for complicated inflammatory bowel disease. J Gastrointest Surg. 2003 May-Jun;7(4):562-6.
Other health problems:
*Anal fissures.Whiteford MH, Kilkenny J 3rd, Hyman N, Buie WD, Cohen J, Orsay C, Dunn G, Perry WB, Ellis CN, Rakinic J, Gregorcyk S, Shellito P, Nelson R, Tjandra JJ, Newstead G; The Standards Practice Task Force; The American Society of Colon and Rectal Surgeons. Practice parameters for the treatment of perianal abscess and fistula-in-ano (revised). Dis Colon Rectum. 2005 Jul;48(7):1337-42. PMID. 15933794.
*Kidney stones, especially oxalate stones.Buno Soto A, Torres Jimenez R, Olveira A, Fernandez-Blanco Herraiz I, Montero Garcia A, Mateos Anton F. Lithogenic risk factors for renal stones in patients with Crohn's disease. Arch Esp Urol. 2001 Apr;54(3):282-92. PMID 11432047.
*Osteoporosis

History and name

Inflammatory bowel diseases were described by Giovanni Battista Morgagni (1682-1771), by Polish surgeon Antoni Leśniowski in 1904 (leading to the use of the eponym "Leśniowski-Crohn disease" in Poland) and by Scottish physician T. Kennedy Dalziel in 1913.Kirsner JB. Historical aspects of inflammatory bowel disease. J Clin Gastroenterol. 1988 Jun;10(3):286-97. PMID 2980764

Burrill Bernard Crohn, an American gastroenterologist at Mount Sinai Hospital, described fourteen cases in 1932, and submitted them to the American Medical Association under the rubrick of "Terminal ileitis: A new clinical entity". Later that year, he, along with colleagues Leon Ginzburg and Gordon Oppenheimer published the case series as "Regional ileitis: a pathologic and clinical entity",Crohn BB, Ginzburg L, Oppenheimer GD. Regional ileitis: a pathologic and clinical entity. Mt Sinai J Med. 2000 May;67(3):263-8. PMID 10828911 which became the first published work to describe the pathology of Crohn's disease.Baron JH. Inflammatory bowel disease up to 1932. Mt Sinai J Med. 2000 May;67(3):174-89. PMID 10828902.

External links

General Information

[Crohn's Disease] US National Institute of Diabetes and Digestive and Kidney Diseases
[Crohn's Disease] MayoClinic.com
[Crohn's Disease] WebMed
[Crohn's Disease Clinical and Alternative Treatment]
[IBD Directory - Listings for Crohn's and colitis resources]
[Crohn's Disease] HealthAtoZ
[Crohns Disease Resource Site]
[How the disease came to be known as Crohn's disease]
[Jigsaw Health IBD]

Organizations

Communities

[TeenCrohns.co.nr] A community for teenagers with Crohn's Disease
[Teens with Crohn's Disease] Support for teenagers with Crohn's Disease
[CrohnsZone.org] UK based Crohn's and colitis support network
[Paratuberculosis Awareness and Research Association, inc.] subscribes to the view that Crohn's is caused by infectious agents
() [Israeli online community about Crohn's Disease]
() [French online community about Crohn's Disease]
[IBD Sucks - an online forum for people with Colitis, Crohn's, and IBS]

References

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