Are Demodex mites principal, conspirator, accomplice, witness or bystander in the cause of rosacea?

As the only permanent human ectoparasite, the role of human Demodex mites in health and diseases remains largely unclarified. In view of the ecological interaction between organisms of two different species, a type of commensalism between Demodex mites and humans (the former benefit, the latter unaffected) is most likely, while parasitism occurs temporarily and spatially in the diseased state (the former benefit, the latter harmed). As part of normal skin microbiota, the causal role of Demodex mites in the initiation of rosacea can neither fulfill the classical Henle-Koch's principal nor the advanced criteria proposed by Fredericks and Relman for molecular detection of non-cultivatable microorganisms. Epidemiological analysis using Hill's criteria fails to support the causative role of Demodex mites in rosacea regarding the strength of association, specificity and temporality of association, biological gradient and plausibility as well as clinical coherence, therapeutic experimentation and medical analogy. In application of Rothman's sufficient cause model to evaluate the contribution of Demodex mites to rosacea on a population basis, Demodex mites can be regarded as a non-necessary, non-sufficient causal factor for certain forms of rosacea. Further strategies to dissect the association between Demodex mites and rosacea may include studying the possible existence of more virulent forms of mites with a higher pathogenicity, the endosymbiotic bacteria in certain life periods of mites, the interactions between mites and human hosts or between mites and environment, and to set up ex vivo culture models for Demodex mites.