The Pathogenic Role of Demodex Mites in Rosacea: A Potential Therapeutic Target Already in Erythematotelangiectatic Rosacea?

Abstract

Rosacea is an inflammatory continuum, with all characteristics being already present from the onset of the disease, even if not clinically visible. Demodex proliferation also appears to be a continuum process in rosacea, and high Demodex density is beginning to be accepted as an important trigger of the inflammatory cascade and as a marker of rosacea: moreover, papulopustules of rosacea can be treated using acaricides. Immunological studies are providing new hypotheses according to which Demodex may induce tolerogenic dendritic cells and collaborate with VEGF to induce T cell exhaustion favoring its own proliferation. This proliferation may not be clinically visible initially. The interactions among VEGF, Demodex, and immunity need to be explored, and the nosology of rosacea definitions adapted accordingly. The effectiveness of treating any patient who only has visible vascular symptoms with an acaricidal cream needs to be confirmed in prospective controlled clinical trials with long-term follow-up, but it is already important to detect patients with pityriasis folliculorum among those with only vascular symptoms of rosacea in order to treat at least these patients with an acaricidal cream. DIGITAL FEATURES This article is published with digital features to facilitate understanding of the article. You can access the digital features on the article's associated Figshare page. To view digital features for this article go to

Which factors influence Demodex proliferation? A retrospective pilot study highlighting a possible role of subtle immune variations and sebaceous gland status

“…Thus, in addition to severe immunodepression, subtle immune defects (as seen in pregnancy, in hypothyroidism, and with age, not forgetting the likely immunosuppressive action of VEGF 12,29 associated with ETR 75 ), which are more frequently encountered in daily practice, can also favor Demodex proliferation.…”

“…Immune defects (ID) of various origins seem to be another major factor favoring Demodex proliferation: marked immunodepression (rare, e.g., associated with human immunodeficiency virus [HIV] infection), [18][19][20][21][22][23] and, more frequently, more subtle IDs, e.g., associated with thymic stromal lymphopoietin (TSLP, increased in sebaceous gland rich areas), 54 glucocorticoids (of which abnormal endogenous synthesis is encountered in rosacea), 85 vascular endothelial growth factor 12 (VEGF, which is increased in rosacea 75 and may induce T-cell exhaustion as in tumor pathology), 29 Staphylococcus epidermidis, 10,81 and, potentially, pregnancy and hypothyroidism. Corticosteroids may favor proliferation when Demodex densities (Dd) are low, via an immunosuppressive effect, 4,12,34,50,65,76,77 and could limit its excessive proliferation when Dd are high, by an atrophic action on the pilosebaceous follicles. 3,78 Good facial hygiene may also potentially reduce mite proliferation, 30,50,63 and some topical treatments are clearly acaricidal (ivermectin, 86 benzyl benzoate 41 ).…”

“…[1][2][3][4][5][6][7] They are acquired progressively by direct contact with the skin of other humans, 3 mainly within families, 2 and then slowly proliferate over time, under probable control of the host immune system, which they can modulate for their own survival. [8][9][10][11][12] The Demodex density (Dd) thus increases with age. 3,[13][14][15][16][17] Many factors have been reported to favor proliferation of the Demodex mite, including immunosuppression, [18][19][20][21][22][23] hypervascularizationrelated factors 10,[24][25][26][27][28] (likely via vascular endothelial growth factor [VEGF], 12 which has immunosuppressive properties 29 ), lack of use of soap combined with cosmetic overuse, 30 male sex, 13,31 high concentration of sebaceous glands 7,16 (such as on the cheeks 4,14,32,33 ), sebaceous hyperplasia, 3,6 and poor blood glucose control.…”

“…[8][9][10][11][12] The Demodex density (Dd) thus increases with age. 3,[13][14][15][16][17] Many factors have been reported to favor proliferation of the Demodex mite, including immunosuppression, [18][19][20][21][22][23] hypervascularizationrelated factors 10,[24][25][26][27][28] (likely via vascular endothelial growth factor [VEGF], 12 which has immunosuppressive properties 29 ), lack of use of soap combined with cosmetic overuse, 30 male sex, 13,31 high concentration of sebaceous glands 7,16 (such as on the cheeks 4,14,32,33 ), sebaceous hyperplasia, 3,6 and poor blood glucose control. 21 Other factors (e.g., low skin moisture, 14,33 low sebum quantity, 33,34 altered sebum composition, 33,35 and skin alkalinity 35 ) may be more a consequence of Demodex proliferation than a cause, because Demodex proliferation probably disturbs sebaceous gland function in the same way it induces Meibomian gland dysfunction on the eyelas...…”

“…36 When the mites proliferate excessively, they become pathogenic, inducing demodicosis 10,24,30,[36][37][38] and probably, although still controversial, 38,39 the inflammatory symptoms of rosacea. 9,10,12,24,25,[40][41][42] The concept that the mite is a trigger 43 for rosacea and that high Demodex densities (Dd) may be a marker of the disease 6,44 is beginning to be accepted.…”