Rosacea: Molecular Mechanisms and Management of a Chronic Cutaneous Inflammatory Condition (Open access free pdf)
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3.2. Demodex Colonization
Demodex folliculorum is a species of facial mite readily found in the pilosebaceous units of humans.
Individuals with rosacea exhibit a markedly increased density of demodex on their skin compared to
controls in studies with skin surface biopsy specimen [50,51]. In addition, a higher population density
of demodex was also observed in patients with rosacea in quantification studies using a polymerase
chain reaction amplification method and a reflectance confocal microscopy [52,53]. Furthermore,
a reduction in the density of demodex mites was observed after treatment, which was correlated with
clinical improvement as measured by skin surface biopsy [54]. This reduction was also observed by
reflectance confocal microscopy [55].
The increased number of demodex mite exoskeletons might themselves act as pathogen-associated
molecular patterns, with the chitin released from demodex mites potentially prompting inflammatory
responses from keratinocytes through a TLR-2 pathway [56]. A recent study has shown that skin
samples with higher demodex densities exhibited enhanced expression of genes for interleukin (IL)-8,
IL-1, tumor necrosis factor (TNF)-α, cyclooxygenase-1, and the inflammasome [52]. Consistent with
this,
Demodex folliculorum has been shown to facilitate the activation of the NLRP3 inflammasome,
which subsequently associates with caspase-1 and results in the release of the proinflammatory cytokine
IL-1 [57].
Furthermore, the inflammatory reactions might also be aggravated when dead mites release their
resident bacteria, which would likely further induce the chemotaxis of neutrophils [58]. Chemotactic
factors such as IL-8 and TNF-α in turn attract more neutrophils to the tissue and thereby aggravate
the inflammatory reaction [59]. Moreover, activated neutrophils induce the release of cathelicidin and
MMP-9, which cause further tissue damage.
Researchers have suggested various mechanisms to explain the association between demodex
mites and rosacea. For example, a genetic susceptibility effected by HLA-Cw2 and HLA-Cw4
might alter the local immune reaction pattern to demodex mites and promote their proliferation
and survival [60], suggested by the finding of Akilov et al. [16] that these haplotypes were associated
with increased demodex mite density. The frequent occurrence of demodecidosis in patients with
immunodeficiency and vascular insufficiency suggests that an abnormal vascularized surface as well
as a compromised patient immune status along with genetic predisposition might be suspected as
factors promoting the proliferation of demodex in rosacea [61–63]. Thus, demodex proliferation
facilitated by compromised tissue in rosacea may lead to exacerbation of the pathologic condition
through enhanced inflammation mediated by host response to both the mites themselves and their
harbored microorganisms.
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