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Journal of the American Academy of Dermatology 2013-Oct

Cathelicidin, kallikrein 5, and serine protease activity is inhibited during treatment of rosacea with azelaic acid 15% gel.

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Alvin B Coda
Tissa Hata
Jeremiah Miller
David Audish
Paul Kotol
Aimee Two
Faiza Shafiq
Kenshi Yamasaki
Julie C Harper
James Q Del Rosso

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Abstrak

BACKGROUND

Excess cathelicidin and kallikrein 5 (KLK5) have been hypothesized to play a role in the pathophysiology of rosacea.

OBJECTIVE

We sought to evaluate the effects of azelaic acid (AzA) on these elements of the innate immune system.

METHODS

Gene expression and protease activity were measured in laboratory models and patients with rosacea during a 16-week multicenter, prospective, open-label study of 15% AzA gel.

RESULTS

AzA directly inhibited KLK5 in cultured keratinocytes and gene expression of KLK5, Toll-like receptor-2, and cathelicidin in mouse skin. Patients with rosacea showed reduction in cathelicidin and KLK5 messenger RNA after treatment with AzA gel. Subjects without rosacea had lower serine protease activity (SPA) than patients with rosacea. Distinct subsets of patients with rosacea who had high and low baseline SPA were identified, and patients with high baseline exhibited a statistically significant reduction of SPA with 15% AzA gel treatment.

CONCLUSIONS

Study size was insufficient to predict clinical efficacy based on the innate immune response to AzA.

CONCLUSIONS

These results show that cathelicidin and KLK5 decrease in association with AZA exposure. Our observations suggest a new mechanism of action for AzA and that SPA may be a useful biomarker for disease activity.

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