The basics - Crohn's disease

An overview of the presentation, diagnosis, treatment options and likely outcomes, by Dr Taqi Hashmi.

Crohn's disease, named after Dr Bernard Crohn, is a chronic relapsing and remitting inflammatory disease of unknown aetiology. It primarily affects the GI tract but has systemic effects as well.

The incidence per 100,000 varies by geography: Asia 0.5, UK 6.6, USA 8 and some parts of Canada as high as 20. It has a bimodal age distribution, with peaks at 15-30 and 60-80 years. Risk factors include smoking, family history, use of oral contraceptives and low-fibre diets.

The male-to-female ratio, previously in favour of females, is now undergoing reversal with current estimates around 1.5 male: 1 female. No cause for this change in gender ratio has been identified.

No clear aetiological factor has been identified, but mutations in the NOD genes on chromosome 16, involved in recognising bacterial lipopolysaccharides, point to the involvement of environmental factors.

Presentation
The inflammatory process involves the full thickness of the bowel wall, and can affect any part along the length of the bowel, in discontinuous areas known as 'skip lesions'. In the initial phases, mucosal oedema results in subtle signs of obstruction: postprandial bloating, cramping and constipation.

As the inflammatory process spreads, the loss of absorptive surface results in persistent (>6 weeks) diarrhoea.

Diarrhoea is not a usual feature of Crohn's in children, but it can present insidiously as unexplained growth failure. Abdominal pain is periumbilical or in the right iliac fossa.

The most commonly affected sites are the terminal ileum and colon. Upper GI tract (oesophagus, mouth, stomach) disease is rare. Ulceration of the superficial mucosa occurs in a grid-like pattern, resulting in a cobblestone appearance. The superficial nature of ulceration may explain the lower than expected incidence of bloody diarrhoea. Bloody diarrhoea occurs in 50 per cent of cases, and is more likely with colonic involvement.

As the disease progresses the loss of absorptive surface leads to a poor nutritional status. Disease of the terminal ileum, involved in the reabsorption of bile salts and vitamin B12, results in decreased fat and vitamin B12 absorption. This gives rise to steatorrhoea, low fat soluble vitamin levels (A, D, E and K) and anaemia. Other contributing factors to the anaemia include GI blood loss, anaemia of chronic disease and side-effects of medication.

With chronic inflammation, fibrosis leads to obstruction. Other complications include fissures and fistulae. Extra-GI manifestations include aphthous ulcers, eye involvement (uveitis, recurrent iritis), asymmetric large joint arthritis, skin manifestations such as pyoderma gangrenosum and erythema nodosum, and hepatobiliary and renal complications. These usually parallel the course of the disease and can predate GI symptoms.

Diagnosis
Diagnosis is achieved through a combination of modalities. Traditional blood markers of disease include CRP and ESR, the latter is more useful for colitis and the former for ileitis.

Other markers include serum orosomucoid, faecal calprotectin and lactoferrin levels. A stool culture will exclude infective causes. Positive serological markers for ASCA (anti-scereisiae) antibodies and negativity for pANCA (peri-nuclear anti-neutrophil cytoplasmic antibodies) offer supportive evidence and help differentiate from ulcerative colitis (UC) where the opposite is generally true.

Sigmoidoscopy allows for a rectal biopsy. Small bowel follow through, barium enema for colonic disease and endoscopy are also useful investigations. The presence of noncaseating granulomas on biopsy is pathognomonic but only present in 50 per cent of cases.

Research tools such as the Crohn's Disease Activity Index are of limited use in clinical practice. Endoscopic examination and biopsy provide direct monitoring of disease activity.

Treatment
Treatment aims to deal with symptoms and modify the underlying inflammatory process. Diarrhoea is treated with loperamide, which is contraindicated where active colitis is present, because this may result in toxic megacolon. Where steatorrhoea is present, bile acid sequestrants such as cholestyramine are of use. If extensive ileal disease is present, a low-fat diet can help. Abdominal cramping is relieved with hyoscine or dicyclomine. Elemental diets are effective but the induced remission is short lived.

Acute cases are treated with IV fluids and bowel rest. The addition of antibiotics (metronidazole +/- ciprofloxacin) is beneficial if infection is thought to be likely.

Anti-inflammatory agents include sulfasalazine and related rectal preparations.

Where there is no response to anti-inflammatory agents a short steroid course is of use. The clinician should be alert to the possibility of an abscess prior to using steroids.

Other immunomodulatory agents include azathioprine and anti-TNF agents such as infliximab. Infliximab has shown good results, with a third of cases showing remission and effects lasting up to three months. Its use is limited by immunogenicity and the tendency to induce lupus.

Fistulae are difficult to treat and tend to recur. Treatment options include prolonged bowel rest with total parenteral nutrition, surgical intervention and anti-TNF agents. Around 60-80 per cent of patients will eventually require surgical intervention. Indications for surgical treatment include severe haemorrhage, toxic megacolon, obstructions and failure of medical therapy.

Recurrence of fistulae post-surgery is common and segmental resections have a greater recurrence rate than total colectomies or ileostomies.

It was thought that UC increased the risk of colorectal cancer whereas Crohn's did not. The risk of colorectal cancer in both is related to the duration and extent of the disease.1 Screening for colorectal cancer is indicated in Crohn's as for UC.

Around 10 per cent of patients will have unremitting disease. For a given age and sex, Crohn's will increase mortality by 50 per cent giving a standardised mortality ratio of 1.5.2

Dr Hashmi is a former GP in London working as a consultant in family medicine in Jeddah, Saudi Arabia References

1. Sachar D. Cancer in Crohn's disease: dispelling the myths. Gut 1994; 35: 1,507-8.

2. Canavan C, Abrams K, Mayberry J. Meta-analysis: mortality in Crohn's disease. Aliment Pharmacol Ther 2007; 25: 861-70.

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