Crohn's disease
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A chronic inflammatory bowel disorder characterized by transmural involvement, skip lesions, cobblestoning, and granuloma formation that can affect any part of the bowel from the mouth to the anus. Incidence ranges from 1.6-14.6 cases/100,000/year in Western populations usually in the second to fourth decade[1]
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History
First described in 1932 by Burrill Bernard Crohn, Leon Ginzberg and Gordon D. Oppenheimer; who published a series of fourteen cases of "Terminal Ileitis: A new clinical entity". It later became known as Regional Enteritis and acquired the Crohn's appellation.
Aetiology
- Genetic[2]
- More common in Ashkenazi Jews
- Lowest rates in Hispanics and Asians
- Monozygotic twin concordance at 20-50% is significantly higher than dizygotic twin concordance 0%-7%[3]
- Nod2 gene associated with ileal involvement
- HLA-DRB1*0103 associated with colonic involvement
- ATG16L1 gene (codes for part of the autophagosome pathway)
- Prostaglandin receptor EP4 modulation seems likely to be important from several SNP studies.
- Positive association with early childhood hygiene
- Smoking doubles risk
- Tumour necrosis factor alpha is a key inflammatory cytokine as demonstrated by its successful specific antibody modulation. Modulation of interleukin 12, interleukin 23 (IL23R is a susceptibility gene for inflammatory bowel disease) and chemokine receptor CCR9 is investigational[4].
Symptoms
- Weight loss
- Abdominal Pain
- Diarrhoea, often bloodstained
 | Consider when:
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Features
Histological
- Transmural intestinal inflamation
Gastro-intestinal
- Cobblestone mucosa;
- Skip lesions;
- String sign of Kantor;
- Mouth ulcers;
- Fistula formation
- Perianal involvment
- Small intestine involvment - stricture formation
- Malabsorption
- Terminal ileitis
- Primary sclerosing cholangitis
- Pancreatitis
Non-GI
eyes
Joints
- Arthropathy
- Inflammatory back pain
Skin
Lung
Differential diagnosis
Investigations
- Sigmoidoscopy& biopsy
- Colonoscopy&biopsy
- Barium enema
- Small bowel meal ("barium follow through") or enteroclysis (small bowel enema)
Treatment
Medical
- Are likely to be beneficial for initial induction of remission[5]
- Azathioprine is beneficial for maintaining remission[6]
- Methotrexate is unknown effectiveness [7]
- 6-mercaptopurine (6-MP) is beneficial for maintaining remission[8]
- Ciclosporin is likely to be ineffective or harmful[9]
Aminosalicylate anti-inflammatory drugs
- Mesalazine is unknown effectiveness or little better than placebo in mild or moderately active disease[10] or to maintain medical therapy attained remission[11]
- Useful after surgery
- Sulfasalazine
Therapeutic antibody They are corticosteroid sparing. The strong indications where they are beneficial[12][13]
- Infliximab
- Induction of remission in severe cases
- Maintenance of remission and maintenance of fistula healing after response to infliximab induction
- Adalimumab
- Induction of remission in severe cases
- Maintenance of remission
- Certolizumab pegol (license refused EU as of 2008)
- Induction of remission in severe cases
- Maintenance of remission
- Natalizumab while effective, has questionable risk/benefit because of progressive multifocal leukoencephalopathy (license refused EU as of 2008)
Anti-mycobacterial antibiotics are unlikely to be benefical[14] With infective complications consider:
Others
- Thalidomide
- Enteral nutrition is unlikely to be benefical compared to corticosteroids in induction of remission[15]
Surgical
Historically was part of management in over 80%
- Localised resection
- Stricturoplasty
Regional Ileitis (Crohn's) is a persistent disease and if serial episodes of stricture are dealt with by resection the patient may run out of bowel. Incising the strictures longitudinally and closing them transversely is more demanding but preserves gut length.
References
- ↑ Cummings JR, Keshav S, Travis SP. Medical management of Crohn's disease. BMJ (Clinical research ed.). 2008 May 10; 336(7652):1062-6.(Link to article – subscription may be required.)
- ↑ Cho JH. Inflammatory bowel disease: genetic and epidemiologic considerations. World journal of gastroenterology : WJG. 2008 Jan 21; 14(3):338-47.
- ↑ Cho JH. Inflammatory bowel disease: genetic and epidemiologic considerations. World journal of gastroenterology : WJG. 2008 Jan 21; 14(3):338-47.
- ↑ Kaser A, Tilg H. Novel therapeutic targets in the treatment of IBD. Expert opinion on therapeutic targets. 2008 May; 12(5):553-63.(Link to article – subscription may be required.)
- ↑ Benchimol EI, Seow CH, Steinhart AH, Griffiths AM. Traditional corticosteroids for induction of remission in Crohn's disease. Cochrane database of systematic reviews (Online). 2008; (2):CD006792.(Epub) (Link to article – subscription may be required.)
- ↑ 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 of systematic reviews (Online). 2000; (2):CD000545.(Link to article – subscription may be required.)
- ↑ Chande N, MacDonald JK, McDonald JW. Methotrexate for induction of remission in ulcerative colitis. Cochrane database of systematic reviews (Online). 2007; (4):CD006618.(Epub) (Link to article – subscription may be required.)
- ↑ 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 of systematic reviews (Online). 2000; (2):CD000545.(Link to article – subscription may be required.)
- ↑ McDonald JW, Feagan BG, Jewell D, Brynskov J, Stange EF, Macdonald JK. Cyclosporine for induction of remission in Crohn's disease. Cochrane database of systematic reviews (Online). 2005; (2):CD000297.(Epub) (Link to article – subscription may be required.)
- ↑ Cummings JR, Keshav S, Travis SP. Medical management of Crohn's disease. BMJ (Clinical research ed.). 2008 May 10; 336(7652):1062-6.(Link to article – subscription may be required.)
- ↑ Akobeng AK, Gardener E. Oral 5-aminosalicylic acid for maintenance of medically-induced remission in Crohn's Disease. Cochrane database of systematic reviews (Online). 2005; (1):CD003715.(Epub) (Link to article – subscription may be required.)
- ↑ Behm BW, Bickston SJ. Tumor necrosis factor-alpha antibody for maintenance of remission in Crohn's disease. Cochrane database of systematic reviews (Online). 2008; (1):CD006893.(Epub) (Link to article – subscription may be required.)
- ↑ Lewis JD. Anti-TNF antibodies for Crohn's disease--in pursuit of the perfect clinical trial. The New England journal of medicine. 2007 Jul 19; 357(3):296-8.(Link to article – subscription may be required.)
- ↑ Selby W, Pavli P, Crotty B, Florin T, Radford-Smith G, Gibson P, Mitchell B, Connell W, Read R, Merrett M, Ee H, Hetzel D. Two-year combination antibiotic therapy with clarithromycin, rifabutin, and clofazimine for Crohn's disease. Gastroenterology. 2007 Jun; 132(7):2313-9.(Link to article – subscription may be required.)
- ↑ Zachos M, Tondeur M, Griffiths AM. Enteral nutritional therapy for induction of remission in Crohn's disease. Cochrane database of systematic reviews (Online). 2007; (1):CD000542.(Epub) (Link to article – subscription may be required.)
