Avoiding steroidal addiction: Consider calcineurin inhibitors first

Sheffield, England - New research data demonstrates that mild, moderate and potent strengths of topical corticosteroids (TCS) cause a thinning of the stratum corneum, particularly when applied for longer periods of time, whereas topical calcineurin inhibitors show no negative change in the integrity of the skin barrier.

This thinning of the stratum corneum, compounded by the already compromised skin barrier seen in atopic dermatitis patients, stresses the importance of the topical use of calcineurin inhibitors in these patients.

Skin barrier damage

"Although topical steroids are an extremely important treatment for atopic eczema, we have known for a long time that if we use them in prolonged courses &$8212 particularly in delicate skin sites, such as the face and flexures, they can damage the skin barrier which can enhance halogen penetration and actually exacerbate rather than improve the atopic eczema," says Michael J. Cork, M.D., head of academic dermatology at the academic unit of biomedical genetics, Dermatology School of Medicine & Biomedical Sciences, University of Sheffield, Sheffield, England.

Clinical study

Dr. Cork and fellow researchers conducted a study comparing the effects of mild, moderate and potent topical corticosteroids with those of either no treatment or the calcineurin inhibitors (pimecrolimus and tacrolimus) on the integrity of the skin barrier in normal skin.

The study included 68 volunteers who were evenly distributed to receive an application of a one finger-tip unit of a potent TCS (betamethasone valerate 0.1 percent), or moderately potent TCS (betamethasone valerate 0.025 percent), or mildly potent TCS (hydrocortisone acetate 0.1 percent) to a 7 cm x 8 cm area on the middle of the right forearm.

A similar area on the left forearm received either no treatment or an application of pimecrolimus cream 1 percent or tacrolimus ointment 0.03 percent.

The effect of the treatments on the integrity of the skin barrier was then assessed using skin-stripping and transepidermal water loss (TEWL) assay.

Results

Results showed that a twice-a-day, two-week and four-week treatment with a potent TCS and a moderately potent TCS, respectively, both caused significantly more damage to the skin barrier than either of the calcineurin inhibitors. The pimecrolimus and tacrolimus-treated sites were similar to the sites receiving no treatment in that there was no negative effect on barrier function.

Additionally, the application of the mildly potent TCS twice a day for six weeks was found to only cause damage to the skin barrier if the volunteer had a previous history of atopic dermatitis.

TCS addiction

According to Dr. Cork, TCS addiction is a common problem that can occur in patients receiving TCS therapy, particularly in long-term use. The addiction may occur in many conditions treated with topical corticosteroids; however, because the barrier is already compromised in eczematous skin, this is the worse-case scenario.

"Topical corticosteroids induce protease production which damages and thins the stratum corneum, and in eczematous skin, there already is an enhanced protease production.

"The thinned stratum corneum allows much more steroid penetration, which makes the eczema worse, as more steroids will allow the barrier to get even thinner allowing more allergens to get through. If the therapy is stopped, the eczema will rebound and worsen, perpetuating the vicious cycle," Dr. Cork explains.

Optimal approach

According to Dr. Cork, an optimal approach in treating atopic dermatitis would be to always use emollients and start with a calcineurin inhibitor *#8212 either tacrolimus or pimecrolimus - in the case of a slight flare, as neither of these topicals negatively impacts the integrity of the skin barrier.

If the patient does suffer a flare that neither of the calcineurin inhibitors are able to control, a short course of TCS could be used in a stepped approach and in combination with either tacrolimus or pimecrolimus. This way, the patient can benefit from the advantages of TCS therapy with the least side effects.

Disease flare

"Calcineurin inhibitors should be used as a first-line therapy for disease flare. They do not damage the skin barrier and, therefore, make an ideal treatment when combined with emollients either to prevent flares or treat early flares.

"In the case of a severe flare, they can be combined with topical steroids until the patient is out of the woods and the disease is under control again," Dr. Cork says. DT

Disclosures: Dr. Cork’s study was partially funded by Novartis.