Treatment of Crohn's disease

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Main article: Crohn's disease

The treatment of 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 people are able to maintain remission with aminosalicylates alone, many require immunosuppressive drugs. [1]

Contents

[edit] 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.[2] 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.[3]

[edit] Corticosteroid anti-inflammatory drugs

Steroid enemas can be used for treatment of rectal disease symptoms
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 availability of effective treatments with less side-effects.[4] 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.[5] Intravenous steroids are used for cases refractory to oral steroids, or where oral steroids cannot be taken.[4] These are administered in the hospital setting. Because corticosteroids reduce the ability to fight infection, care must be used to ensure that there isn't an 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 disease[6] and for maintenance of remission in Crohn's disease.[7] Formulated as Entocort, budesonide is released in the ileum and right colon, and is therefore has a topical effect against disease in that area.[6]

Budesonide is also useful when used in combination with antibiotics for active Crohn's disease.[8]

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.

[edit] Mercaptopurine immunosuppressing drugs

Azathioprine, shown here in tablet form, is a first line steroid-sparing immunosuppressant
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.[9]

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

  • For maintenance therapy for people who are dependent on steroids.[10]
  • Fistulizing disease.[11]
  • Induction of remission in steroid refractory disease.[12]
  • Maintenance of remission after surgery for Crohn's disease.[13]

[edit] Infliximab

Main article: Infliximab, Biological therapy for inflammatory bowel disease

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

Infliximab has found utility as follows:

  • Maintenance of remission for people with Crohn's disease.[14]
  • Induction of remission for people with Crohn's disease.[14]
  • Maintenance for fistulizing Crohn's disease.[15]

Side effects of infliximab include hypersensitivity and allergic reactions, risk of re-activation of tuberculosis, serum sickness, and risk of multiple sclerosis.[16] Serious side effect include lymphoma and severe infections.

[edit] 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.[17] Surgery is often used to manage complications of Crohn's disease, including fistulae, small bowel obstruction, colon cancer, small intestine cancer and fibrostenotic strictures, when strictureplasty (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 type of surgery cures Crohn's disease, as recurrence often reappears in previously unaffected areas of the intestine.[18]

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

[edit] Diet and lifestyle

There is no evidence that diet causes or cures Crohn's disease. If a person with Chron's finds that certain foods increase or decrease the symptoms, then they may adjust their diet accordingly. A food diary is recommended to see what positive or negatives foods have [2]. Fish oil has been found to be effective in reducing the chance of relapse in less severe cases.[19] People 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.[20] A low residue diet may be used to reduce the volume of stools excreted daily. Stress is not proven to aggravate or induce the symptoms of Crohn’s disease. If sufferers observe that Stress Management is a succesful method of suppressing the illness in their bodies, then they may manage stress as they see fit. Conversely, stress is likely to be caused by the flaring up of the disease and this would make day to day life more difficult. Smoking has also been noted to have an association with Crohn's, and smokers with Crohn's are encouraged to quit.

Because the terminal ileum is the most common site of involvement and is the site for vitamin B12 absorption, people with Crohn's disease are at risk for B12 deficiency and may need supplementation. In cases with extensive small intestine involvement, the fat soluble vitamins A, D, E and K can be deficient. Folate deficiency is a risk when being treated with methotrexate.

[edit] Complementary and alternative medicine

More than half of Crohn's disease sufferers have tried complementary or alternative therapy.[21] These include diets, probiotics, fish oil and other herbal and nutritional supplements. The benefit of these medications is uncertain.

Traditional Chinese medicine can be used to help manage the symptoms of Crohn's disease.[22]

[edit] Other medications

[edit] Research on medications in progress

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

[edit] See also

Topics related to Crohn's disease
Main Inflammatory bowel disease | Biological therapy for inflammatory bowel disease | Treatment of Crohn's disease | Crohn's Disease Activity Index
Related terms Abdominal pain | Anal abscess | Erythema nodosum | Fistula | Granuloma | Ileum | Ileitis | Malabsorption | Proctitis | Protein losing enteropathy | Pyoderma gangrenosum | Sacroiliitis | Short bowel syndrome | Small bowel obstruction | Stenosis
History Giovanni Battista Morgagni | Burrill Bernard Crohn
Organizations Crohn's and Colitis Foundation of America | National Society for Colitis and Crohn's Disease
People List of notable people diagnosed with Crohn's disease

[edit] References

  1. ^ Management of Crohn's Disease in Adults, Am. J. Gastroenterology, Vol 96, No. 3[1]
  2. ^ 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
  3. ^ 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.
  4. ^ a b c Gopal, Latha; Senthil Nachimuthu (2006-05-23). Crohn Disease. eMedicine. Retrieved on July 2, 2006.
  5. ^ Hanauer SB. Sulfasalazine vs. steroids in Crohn's disease: David vs. Goliath? Gastroenterology. 1991 Oct;101(4):1130-1. PMID 1679735.
  6. ^ a b Greenberg 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.
  7. ^ Sandborn WJ, Lofberg R, Feagan BG, Hanauer SB, Campieri M, Greenberg GR. Budesonide for maintenance of remission for people 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
  8. ^ 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.
  9. ^ Podolsky, Daniel K. (August 2002). "Inflammatory bowel disease". New England Journal of Medicine 346 (6): 417-29. PMID 12167685. Retrieved on 2006-07-02. 
  10. ^ 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
  11. ^ 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
  12. ^ 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
  13. ^ 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.
  14. ^ a b 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
  15. ^ 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
  16. ^ 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.
  17. ^ Hanauer, Stephen B. (March 1996). "Inflammatory bowel disease". New England Journal of Medicine 334 (13): 841-848. PMID 8596552. Retrieved on 2006-11-10. 
  18. ^ Surgery for Crohn's Disease. Crohn's and Colitis Foundation of America (March 2006). Retrieved on June 8, 2006.
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  20. ^ Gottschall, Elaine (1994). Breaking the Vicious Cycle: Intestinal Health Through Diet. Baltimore: Kirkton Press. ISBN 0-9692768-1-8. 
  21. ^ Caprilli R, Gassull M, Escher J et al. "European evidence based consensus on the diagnosis and management of Crohn's disease: special situations". Gut 55 Suppl 1: i36-58. PMID 16481630. 
  22. ^ http://www.acupuncturetoday.com/archives2001/jan/01chen.html Two part reveiw of Western approach versus Eastern approach to managing Crohn's disease
  23. ^ 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
  24. ^ 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
  25. ^ 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.
  26. ^ 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.
  27. ^ B. Dieckgraefe (2006). Improving Mucosal Barrier Function - A Novel Therapeutic Strategy for Crohn's Disease.
  28. ^ 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
  29. ^ Schreiber S, Rutgeerts P, Fedorak R, Khaliq-Kareemi M, Kamm M, Boivin M, Bernstein C, Staun M, Thomsen O, Innes A (2005). "A randomized, placebo-controlled trial of certolizumab pegol (CDP870) for treatment of Crohn's disease.". Gastroenterology 129 (3): 807-18. PMID 16143120. 
  30. ^ Sandborn W, Colombel J, Enns R, Feagan B, Hanauer S, Lawrance I, Panaccione R, Sanders M, Schreiber S, Targan S, van Deventer S, Goldblum R, Despain D, Hogge G, Rutgeerts P (2005). "Natalizumab induction and maintenance therapy for Crohn's disease.". N Engl J Med 353 (18): 1912-25. PMID 16267322. 
  31. ^ Van Assche G, Van Ranst M, Sciot R, Dubois B, Vermeire S, Noman M, Verbeeck J, Geboes K, Robberecht W, Rutgeerts P (2005). "Progressive multifocal leukoencephalopathy after natalizumab therapy for Crohn's disease.". N Engl J Med 353 (4): 362-8. PMID 15947080. 
  32. ^ 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.
  33. ^ 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 for people with refractory Crohn's disease. Gastroenterology. 2005 Mar;128(3):552-63.PMID 15765390
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