Glucocorticoids

The general immunosuppression caused by glucocorticoids often induces symptomatic remission in patients with left-sided UC. However, avoiding glucocorticoid therapy has become the mantra of the gastroenterologist caring for IBD patients. Many questions focus on the cost of the short term benefit of steroids in terms of changing the character of disease and the iatrogenic medical complications that arise from steroid use. Glucocorticoids follow mesalamine in the "induction of remission" treatment algorithm. Their use should be accompanied by a strategy to minimize the cumulative systemic exposure to steroids. Topical rectal therapy applies the steroid dose to the area of the inflammation with the same distribution characteristics demonstrated for mesalamine enemas. The inflamed mucosa poorly absorbs steroids and systemic glucocorticoid effects are least likely with topical rectal therapy. As the mucosa heals, glucocorticoid absorption improves and systemic effects of steroids may occur.

Role of Eosinophils in Relapses

Seasonal or infectious relapses can be linked to high numbers of eosinophils by identifying increased numbers of fecal eosinophils, Charcot-Layden crystals in the stool, or with biopsy evidence of eosinophilic mucosal migration. When eosinophils are implicated in the symptomatic relapse of disease, high dose, short-term steroids are often effective. The diurnal variation of eosinophil function often provides a useful clinical clue that eosinophil activation is related to the current flare of colitis. Eosinophils are most active between 11 pm and 2 am, thus a patient with dominant colitis symptoms during this time likely has active eosinophils that should be modulated. Eosinophils are usually sensitive to high plasma levels of steroids, thus an intravenous (IV) dose of steroids (eg, solumedrol 60 mg IV) or a rapidly tapering daily dose of oral steroids (eg, 60, 50, 40,30,20 and 10 mg of prednisone) may induce a durable remission lasting weeks, months, or until a new stimulus activates the colitis. Even without documented eosinophilic activation of a colitis flare, an excellent clinical response to the first 48 hours of steroids suggests eosinophils are pivotal in the current flare of the disease and a short course of steroid may be all that is required for inducing remission. Lessons from the tryptophan-eosinophil-myalgia syndrome include the recognition that approximately 15% of eosinophils are resistant to steroids making this subgroup of patients difficult to manage.

When chronic glucocorticoids appear necessary, I favor moving as quickly as possible to every other day dosing as this often controls the colonic inflammation with less acute prednisone toxicity. If continuous steroids are required to control a relapse, immunomodulation therapy should be considered because there is no place in the treatment of IBD for maintenance steroids.

Budenoside/Beclomethasone

Early in the development of budesonide, an enema formulation (2 mg) was determined to be beneficial, however, budesonide is only commercially available in an ileal release form for CD (Entocort EC, AstraZeneca LP, Wilmington, DE). The theoretical advantage of budesonide revolves around the efficient first pass hepatic clearance of this steroid from the portal blood. This should decrease the systemic availability of the steroid and permit local steroid suppression of the disease without systemic toxicity. It is unfortunate that further studies were not conducted with topical rectal budesonide, however, approximately 15% of the blood flow from the distal colon escapes the portal system increasing the amount of drug that may be available in the systemic circulation. Oral beclometasone in a delayed release formulation was successful in treating left-sided uC. The same principle of high first pass clearance resulted in few systemic side effects (Campieri et al, 2003).

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