Pediatric Demodicosis Associated with Gain-of-Function Variant in STAT1 Presenting as Rosacea-Type Rash

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

“…Genetic factors are well-known to influence the risk of rosacea, 83 and the STAT 1 gain-of-function mutation is associated with familial rosacea 84 and demodicosis. 20,22 In our study, most of the pairs of subjects had a genetic link suggesting that genetic background is more important than just close contact with a subject with high Dd. Nevertheless, the fact that individuals with no genetic link but from the same household were also affected suggests that frequent contact with a person with high Dd may lead to transfer of numerous mites, indicating possible contagion.…”

“…Although immunodepression of various origins [18][19][20][21][22][23]64 demodicosis and rosacea generally occur in subjects who are otherwise apparently in good health. 5,30,37,66 Among our Demodex+ subjects, marked immunodepression was rare.…”

“…Age and sex influence Demodex proliferation likely via the production of androgens and their effect on sebaceous glands, where the mites live. 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.…”

“…[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...…”

Chronic demodicosis in patients with immune dysregulation: An unexpected infectious manifestation of Signal transducer and activator of transcription (STAT)1 gain-of-function

“…Recent reports of patients with STAT1 GOF mutations detailed a dermatological phenotype of chronic demodicosis [10][11][12][13]. However, in-depth immune characterization of these patients is lacking.…”