A comparative exploration of immunohistochemical markers in patients with papulopustular rosacea undergoing treatment with oral isotretinoin versus doxycycline.

Abstract

Rosacea is a chronic inflammatory disease, and doxycycline is a widely recommended treatment for it due to its anti-inflammatory action. Oral isotretinoin reduces sebaceous gland activity and modulates toll-like receptors, reducing inflammation. Our aim was to investigate the effect of these two drugs on the expression of cutaneous immunohistochemical biomarkers related to etiopathogenic factors involved in rosacea. We conducted a randomized, comparative, and evaluator-blinded trial, including 40 participants with moderate and severe papulopustular and ocular rosacea. Participants were treated with doxycycline (DOXY) 100 mg or isotretinoin (ISO) 0.3 mg/kg daily. Immunohistochemistry at baseline and after 4 months was used to demonstrate the expression of the biomarker on the affected skin. The following changes were detected: a reduction in the vessel count after using VEGF with DOXY (P = 0.010); a decrease in VEGF intensity with ISO (P < 0.001) and DOXY (P = 0.020); a reduction of nitric oxide synthase enzyme with both drugs in the inflammatory infiltrate (ISO P < 0.001; DOXY P = 0.003); however, only with ISO was there a significant (P = 0.030) decrease at the level of the sebaceous glands, indicating a reduction of nitric oxide synthesis; a reduction of TRPV-1 expression at the level of the sebaceous glands was observed only with DOXY (P = 0.041); a decrease of cathelicidin LL37 expression, a key antimicrobial peptide in the etiopathogenesis of rosacea, was noted with both drugs, although at the level of sebaceous glands, only with DOXY (P = 0.007). Oral isotretinoin and doxycycline have modified the expression of cutaneous biomarkers related to rosacea etiopathogenesis, demonstrating their role in controlling inflammatory and vascular processes.