The child with multiple short courses of steroid therapy

CASE PRESENTATION

A 10-year-old child in your practice has a three-year history of asthma. You have just seen her in follow-up and noted that her asthma has been worse over the past year. Over the past 15 months she has been to the local emergency department for exacerbations of her asthma four times. Each time, her discharge therapy has included an inhaled bronchodilator and a five-day course of oral methylprednisolone. You wonder when you should be worried about adrenal suppression.

DISCUSSION

Glucocorticosteroids are adrenal steroid hormones that have a variety of biological actions, including energy mobilization, regulation of appetite, suppression of inflammation, blood pressure homeostasis and arousal of the nervous system. The first synthetic glucocorticosteroids were synthesized in the late 1940s and over the past several decades have been increasingly used to control inflammation and alter host responses in a number of disorders. In paediatrics, there has been a dramatic increase in the use of both oral and inhaled glucorticosteroids over the past two decades for the acute and chronic management of asthma.

Glucocorticosteroids are associated with a number of significant adverse effects, including osteopenia, cutaneous atrophy, maldistribution of adipose tissue, hypertension and psychosis, many of which are seen primarily after long term therapy. Two of the most feared complications of glucocorticosteroid therapy are adrenal suppression and immune suppression. These complications are appreciated to be common and important side effects of long term glucocorticosteroid therapy. The question posed relates to when these effects are seen after repeat courses of short term therapy.

Typically, glucocorticosteroids for acute exacerbations of asthma are used either as three- to five-day courses of prendisolone or prednisone in a dose of roughly 1 mg/kg/day or in the form of a variety of inhaled corticosteroids for chronic management. The safety of multiple short courses of steroid therapy has been evaluated in a small number of studies (1,2). With respect to adrenal suppression, this can be demonstrated after two months of a moderate (1 to 2 mg/kg/day) dose of prednisolone or prednisone therapy; this can persist up to one year. Adrenal suppression does not occur after a five-day course of 1 to 2 mg/kg/day of prednisolone or prednisone. As well, there is a small body of evidence that suggests that multiple short courses also do not produce adrenal suppression (3,4). It should be noted that this work has primarily been conducted in adults and there is controversy as to whether it applies to infants. There is a small but growing body of work that suggests that adrenal suppression is not an issue for short courses of therapy in toddlers and older children.

In terms of immune suppression, the current hypothesis with respect to the mechanism of steroid-induced immune suppression is that gene transcription is needed, and, thus, because some time is required to see the beneficial effects of steroids, some time is also needed before steroid-induced immune suppression occurs. Immune suppression can be seen after 14 days of therapy with 2 mg/kg/day (or more than 20 mg/day) of prednisolone or prednisone therapy. Shorter periods of therapy are not associated with immune suppression. Multiple short courses of therapy do not appear to be associated with long term immune suppression, but this question has not been studied in detail.

In the case of inhaled corticosteroids that are often used for chronic therapy, no systemic effects have been demonstrated with low or moderate doses (less than 0.5 mg/day). There are case reports of adrenal suppression when inhaled corticosteroids are used in doses in excess of 0.75 to 1.5 mg/day (3), with the suggestion that there is a higher risk with fluticasone.

With respect to growth in terms of height velocity, although this is a difficult question to address it does appear that in recommended therapeutic doses there may be a slight reduction in height velocity associated with the use of beclomethasone or budesonide but this has not been demonstrated with the use of fluticasone. It should be noted that none of these agents appeared to effect the final height achieved and that the definitive study to address this question has not yet been performed.

SUMMARY

Glucocorticosteroids are potent drugs that are important parts of rational therapy for a number of common diseases in paediatrics. While long term steroid use is associated with both adrenal and immune suppression, short courses of oral steroids (1 to 2 mg/kg of prednisolone or prednisone for three to five days) are not associated with these effects, even when used on several occasions over the course of one year. Chronic low or moderate dose inhaled steroid therapy is not associated with untoward systemic effects.