STAT1 gain‐of‐function and chronic demodicosis

Abstract

Heterozygous STAT1 gain-of-function (GOF) mutations result in a combined form of immunodeficiency which is the most common genetic cause of chronic mucocutaneous candidiasis (CMC). We present a pedigree with a GOF mutation in STAT1, manifesting with chronic demodicosis in the form of a facial papulopustular eruption, blepharitis, and chalazion. So far, demodicosis has been described in only one family with STAT1-GOF mutation. We suggest that chronic demodicosis is an under-recognized feature of the immune dysregulation disorder caused by STAT1 gain-of-function mutations. K E Y W O R D Sblepharitis, demodicosis, gain-of-function mutation, papulopustular rosacea, STAT1 | 155Pediatric Dermatology MOLHO-PESSACH Et AL. in a heterozygous state in patients I-1, II-1, II-2, and II-3 and was not present in the mother (I-2, Figure 1A). How to cite this article: Molho-Pessach V, Meltser A, Kamshov A, Ramot Y, Zlotogorski A. STAT1 gain-of-function and chronic demodicosis. Pediatr Dermatol. 2020;37:153-155. https ://doi.

Rosacea as a striking feature in family members with a STAT1 gain‐of‐function mutation

“…Ruxolitinib, a JAK family tyrosine kinase inhibitor has been a successful therapy in a patient with severe CMC 9 ; its therapeutic response could be explored in STAT1-GOF inflammatory manifestations. The presence of rosacea in the family described in this study, along with the patients reported with early-onset rosacea from two unrelated kindreds, 4,5 and at least the cutaneous phenotype depicted as 'figure 2 D.P104' (erythema, telangiectasias and papulopustules) reported by Toubiana et al, 7 (we may suggest having a rosaceiform dermatosis) supports that STAT1-GOF is a monogenic aetiology of rosacea. Therefore, the presence of early-onset rosacea may be considered as suspected for a STAT1-GOF defect in patients who may display autoimmune, infectious and/or autoinflammatory manifestations.…”

“…3 To date, a genetic cause for early-onset rosacea has only been described in two unrelated families, with a gain-of-function (GOF) mutation in STAT1. 4,5 Here, we report eight family members affected with STAT1-GOF; six of them with rosacea with four of the latter showed early onset.…”

“…Casanova, 3,5,6 N.H. Segura-Mendez, 4 L. Orozco-Covarrubias, 1 S.E. Espinosa-Padilla, 2 A. Puel, 3,5 L. Blancas-Galicia 2, * Dear Editor, During menopause, oestrogen deprivation occurs after the end of ovulation, reduction of ovarian hormones and increased androgen levels which trigger skin ageing. 1 Skin ageing is associated with an increase in extensibility and a reduction in elasticity.…”

“…The skin loses its elasticity and becomes more fragile and susceptible to trauma, leading to more lacerations and bruising and wound healing is impaired. [2][3][4][5] Even though quality of life (QOL) of menopaused women is heavily impacted, current QOL assessing questionnaires only ask about standard skin items such as dryness, hairiness and visual aspect. 6 In 2018, we conducted an internet survey in French women who consented to participate in internet surveys to collect information about their knowledge and concerns of menopause and…”

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

“…[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...…”