Characterization of the Cytokine Profile and the Microbiome in Darier's Disease

A study carried out in 75 patients showed the presence of Staphylococcus aureus in lesional skin in 68% of cases, this percentage being correlated with the affected surface and the severity of the disease. Histologically, there is a characteristic appearance of acantholytic dyskeratosis and the underlying dermis is the site of inflammation. On the physiopathological level, the mutations cause disturbances in calcium metabolism, causing a loss of cell adhesion and a disruption of keratinocyte differentiation. The mechanisms leading to inflammatory skin lesions and frequent superinfections are poorly understood and could be the consequence of the abnormality of the skin barrier, causing disturbances in the cytokine profile and the microbiota.

This has been shown in hereditary ichthyoses, another group of diseases with keratinization disorders, in which microbiota abnormalities and a TH17 cytokine profile have been demonstrated.

In Darier disease, a study published in 2023 also showed the presence of a TH17 profile in 6 patients.

In 2 patients, clinical improvement was also noted when using biotherapy targeting interleukin 17 or 23. Also in 2023, Amar et al. studied the skin microbiota of 14 patients and showed the presence of Staphylococcus aureus and Staphylococcus warneri in the inflammatory areas, the abundance of which correlated with the severity of the disease.

Our study will provide additional data to this recent work, by highlighting differential cytokine and microbiota signatures between the two skin areas studied, in order to validate our hypothesis of the involvement of cytokines and the microbiota in chronic skin inflammation.

Inclusion criteria

• Patients aged 18 or over,
• MD (clinical diagnosis),
• MD moderate to severe,
• Person affiliated or beneficiary of a social security scheme,
• Free, informed and written consent signed by the participant and the investigator (at the latest on the day of inclusion and before any examination required by the research).

Exclusion criteria

• Other inflammatory dermatological diseases : atopic dermatitis, psoriasis and lichen planus,
• Skin superinfection (clinical diagnosis),
• Treatment with a biotherapy, in progress or in the 12 weeks preceding inclusion,
• Treatment with oral retinoids introduced in the 6 months preceding inclusion,
• Application of tacrolimus to the areas or to more than 30% of the body surface,
• Application of topical corticosteroids to the areas or to more than 30% of the body surface, within 2 weeks preceding inclusion,
• Oral corticosteroid therapy in the 2 weeks preceding inclusion,
• Application of topical retinoids to the areas in the 2 weeks prior to inclusion,
• Oral and/or topical antibiotic therapy in the 2 weeks preceding inclusion,
• Local antiseptic in the 2 weeks preceding inclusion,
• Local keratolytics on areas within 5 days preceding inclusion.