Therapeutic progress in rosacea: targeting the neuro-vascular-immune triad

Rosacea is a chronic inflammatory dermatological condition predominantly affecting the facial region. Clinically, rosacea is characterized by paroxysmal flushing, persistent erythema, telangiectasia, papules, pustules, and ocular symptoms. Severe rosacea cases are frequently complicated by anxiety, depression, and sleep disturbances, imposing a heavy psychosocial burden and markedly impairing the quality of life of the patients. Abnormal activation of the neuro-vascular-immune triad has been reported as a crucial pathological mechanism of rosacea. Moreover, dysregulation within the central nervous system might exacerbate disease progression by modulating peripheral nerve activity and neuroendocrine homeostasis. In this review, we summarize the latest advancements in rosacea treatments targeting the neuro-vascular-immune triad, including γ-aminobutyric acid derivatives, antidepressants, anti-calcitonin gene-related peptide agents, physical neuromodulation (transcutaneous auricular vagus nerve and repetitive transcranial magnetic stimulations), botulinum toxin type A, and β-blockers. We provide a comprehensive analysis of their molecular mechanisms, clinical efficacy, and current limitations. While such therapies could specifically regulate different stages of the pathway, their evidence lacks large-scale randomized controlled trials and clarity regarding optimal dosing regimens and treatment durations. Future studies should strengthen basic investigations and clinical translation, explore combined therapeutic strategies, as well as develop personalized therapeutic strategies for the long-term effective control of rosacea.