that of ulcerative colitis, with aminosalicylate and corticosteroid. These drugs are of less value in maintaining remission in Crohn's disease than in ulcerative colitis, although they do help to reduce recurrence of disease at sites of surgical anastamoses. Topical enema preparations are less useful because of the patchy distribution of inflammation and rectal sparing.

In contrast to ulcerative colitis, about 50% of patients with Crohn's colitis will respond to metronidazole given for up to 3 months, although adverse effects including alcohol intolerance, and peripheral neuropathy from such prolonged therapy often limit its use. The drug is also helpful in controlling perianal and small bowel disease and it decreases the incidence of anastamotic recurrence after surgery. Other antimicrobials, particularly ciprofloxacin may also be effective.

Crohn's disease of the small bowel classically affects the ileocaecal region, although any part of the gastrointestinal tract may be involved, from the mouth downwards. Patients with small bowel involvement are frequently malnourished and specialist dietetic input is essential; enteral or parenteral nutrition may be required. Osteoporosis is common, particularly if corticosteroid consumption has been high.

Sulfasalazine, olsalazine and balsalazide are ineffective in small bowel Crohn's disease because these drugs are designed to liberate 5-ASA in the colon. Mesalazine preparations release 5-ASA higher in the gut and control mild to moderate exacerbations of ileocaecal disease in approximately 50% of patients, although high doses are needed (Asacol 2.4 g in divided doses, Pentasa 2 g b.d.).

In more severe disease corticosteroids are needed to induce remission (prednisolone 60 mg/day until remission induced, tailing the dose by 5 mg/week). Approximately 75% of patients respond. Budesonide, a potent topically active corticosteroid, is an alternative which can be administered either orally or as an enema. The oral preparation is presented as a delayed release formulation which delivers drug to the terminal ileum and ascending colon. Extensive first pass metabolism in the liver limits its systemic availability and potential for adverse effects. Budesonide is also useful as maintenance therapy of the 30% of patients with Crohn's disease who are steroid dependent.

Maintenance of remission may require addition of azathioprine or another immunosuppressive drug (see below). Tobacco smoking definitely contributes to relapse and should be strongly discouraged.

Crohn's disease may be complicated by intestinal strictures, fistulae and intra-abdominal abscesses. Surgery is often necessary but strictures may be amenable to endoscopic balloon dilatation and abscesses can be drained under radiographic control.

Dietary therapy

There is evidence that liquid diets based on amino-acids (elemental diets) or oligopeptides for 4-6 weeks are as effective as corticosteroids in controlling Crohn's disease although relapse is common when the treatment stops. Elemental preparations are not particularly palatable and they often have to be administered through a nasogastric tube, which is not popular with patients. They are worth trying in steroid resistant cases, and are particularly favoured by paediatricians who prefer to avoid adrenal steroid because of its adverse effects on growth.

Antibodies to tumour necrosis factor (TNF)

TNFa causes activation of immune cells and release of inflammatory mediators. The inhibitors of TNF, infliximab and etanercept (see p. 293), have been found to benefit Crohn's disease. A single dose of anti-TNFoc will induce remission in approximately one-third of patients with Crohn's disease resistant to conventional therapies, with improvement in a further third. A further dose after 8 weeks appears to produce longer lasting remissions. This treatment is also useful in treating Crohn's fistulae. Adverse reactions include headache, nausea and malaise; repeat infusions after prolonged intervals (1-2 years) may lead to hypersensitivity reactions. Its efficacy and potential for adverse effects in the long term (including development of malignancy) remain to be established. There is no good evidence that anti-TNFa antibodies are effective for ulcerative colitis.

Immunosuppressive drugs

Azathioprine is effective as a steroid sparing agent in maintenance therapy of Crohn's disease. Use of this drug in a dose of up to 2 mg/kg may allow corticosteroid to be withdrawn altogether. It is also used for the same purpose in ulcerative colitis although evidence for its efficacy in this disorder is less persuasive. As the onset of action of azathioprine is delayed for about 8 weeks, it is not effective for inducing remission, and reduction in steroid dose in the first few weeks of azathioprine treatment may lead to relapse. Azathioprine can cause bone marrow suppression and the blood count should be monitored weekly for the first two months of therapy and every 2 months thereafter for as long as the drug is taken.

Intolerance of azathioprine is shown by malaise, abdominal discomfort and sometimes fever. Pancreatitis occurs in up to 5%. These effects are usually due to the imidazole side chain of the molecule, and mercaptopurine (which is azathioprine without the side chain) may be better tolerated. The dose is 1-1.5 mg/kg.

Ciclosporin. There is no good evidence that ciclosporin is effective in Crohn's disease.

Methotrexate can be helpful in controlling relapses of Crohn's disease unresponsive to corticosteroid or azathioprine. It has also been used with benefit in ulcerative colitis. Its short- and long-term use are limited by a wide profile of adverse effects including bone marrow suppression and pulmonary and hepatic fibrosis (see p. 291).

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