ABSTRACT

Background:

Itch control is important in improving the atopic dermatitis patients’ quality of life, reducing the damage to the skin barrier, and, thereby, adding to the downregulation of skin inflammation. We aimed to investigate the efficacy of calcineurin inhibition by cyclosporine versus phosphodiesterase-4 inhibition by apremilast in controlling pruritus and reversing skin pathology in an experimental model of atopic dermatitis (AD) induced by oxazolone in mice.

Materials and Methods:

Forty BALB/c female mice were randomly assigned to four groups. AD-like lesions were induced in groups 2, 3, and 4 by repetitive application of oxazolone to the mouse skin. Group 2 mice were left untreated receiving vehicle placebo, whereas those in groups 3 and 4 received cyclosporine (2 mg/kg PO daily) and apremilast (2.5 mg/kg PO twice daily), respectively. Studied mice were subjected to weekly assessment of skin inflammation and scratching behavior for 6 weeks. The oxazolone-treated right ear thickness and skin hydration were measured at the end of the study. Serum immunoglobulin E (IgE) and interleukin (IL)-31 were measured, and biopsies of lesional back skin were obtained for histopathologic evaluation.

Results:

Both cyclosporine and apremilast significantly reduced scratching behavior in treated mice, accompanied by a significant decrease in the elevated levels of IL-31 and IgE by both drugs. IL-31 and IgE suppressions were significantly greater with apremilast. A significant reduction of mean itching started earlier at week 3 with apremilast versus week 4 with cyclosporine.

Conclusion:

We propose that the earlier control of itch observed with apremilast is clinically significant as this will lead to less epidermal damage and that will interrupt the itch-scratch cycle and progression of dermatitis.