Managing a Burning Face: Clinical Manifestations and Therapeutic Approaches for Neurogenic Rosacea

Abstract

Rosacea is a common chronic inflammatory condition primarily affecting middle-aged women. It presents with flushing, erythema, telangiectasia, papules, pustules, phymatous changes, and ocular involvement. Although typically grouped into four subtypes-erythematotelangiectatic, papulopustular, ocular, and phymatous-overlapping features often favor a phenotypic diagnostic approach. Neurogenic rosacea (NR) has emerged as a distinct subgroup featuring distinguishing features such as peripheral facial erythema, severe burning and stinging sensations, and resistance to standard rosacea therapies. Recent insights into the pathophysiology of NR propose neural dysregulation as the main driver of the condition. Specifically, the activation of TRP channels at cutaneous sensory nerve endings in the dermis triggers the release of vasoactive peptides, driving neuroinflammation and resulting in burning and stinging. Additionally, there is a marked association with neuropsychiatric comorbidities, which would further mediate the pathogenesis of the condition. In line with this pathophysiological model, NR often fails to respond to conventional rosacea treatments. Instead, patients benefit more from antidepressants and neuroleptic agents that help modulate neuronal activity and alleviate symptoms. This review explores and summarizes the scientific evidence regarding the new insights on disease pathogenesis, clinical manifestations, and proposed treatments for NR.

Keywords: neurogenic inflammation; neurogenic rosacea; refractory erythema; rosacea.

Figure 1

Proposed driver pathophysiological mechanisms in neurogenic rosacea. Activation of TRPA1, TRPV1, and TRPV4 channels on sensory nerve endings triggers the release of vasoactive peptides (substance P, PACAP, and CGRP) into the post-synaptic space, contributing to the symptoms of neurogenic rosacea. The presence of Demodex mites and bacteria exacerbates this condition through the interaction of their proteases with PAR2 and TLR2 channels, enhancing the inflammatory response. Note that the release of vasoactive peptides is not exclusive to any single channel but is depicted in the figure for illustrative purposes. Moreover, these mechanisms have also been previously described in other rosacea subtypes, leading to an overlap of symptoms and clinical presentations.