Rosacea, an infectious disease: why rosacea with papulopustules should be considered a demodicosis. A narrative review

Rosacea and demodicosis are common facial conditions in dermatology practice. While demodicosis is clearly the result of Demodex mite infestation, the pathogenicity of rosacea is still not sufficiently explained, so that it is defined by its symptoms, and not by its cause. It is usually considered as a disease of the immune system associated with neurogenic inflammation triggered by various factors (ultraviolet light, heat, spicy food, alcohol, stress and microorganisms). Its links with demodicosis remain controversial, although there is increasing evidence that Demodex mites may play a key role in the inflammatory process. Indeed, high Demodex densities are observed in nearly all cases of rosacea with papulopustules (PPR) and the papulopustules of rosacea can be effectively treated with topical acaricidal agents. Recent studies suggest that Demodex induces two opposite actions on host immunity: a defensive immune response aimed at eliminating the mite and an immunosuppressive action aimed at favouring its own proliferation. Moreover, the initial defensive immune response is likely diverted towards benefit for the mite, via T-cell exhaustion induced by the immunosuppressive properties of vascular endothelial growth factor, which may also explain the favourable influence that the altered vascular background of rosacea seems to exert on Demodex proliferation. In this review, the evidence for and against a causal role of Demodex in rosacea is discussed, applying three systems traditionally used to attribute causality to a disease (modified Koch criteria, Hill criteria for causality and Rothman model). The findings suggest that PPR can reasonably be attributed to Demodex proliferation, which appears to be a necessary factor in the centre of a causal network in which multiple co-factors interact and influence the occurrence and severity of inflammatory symptoms, from limited (pityriasis folliculorum) to more marked (PPR). PPR could, therefore, be considered as a chronic infection by Demodex mites with associated T-cell exhaustion.