Role of Topical Treatments in the Modulation of Skin Microbiome in Psoriatic Skin

Overview

Changes in microbiome have been reported recently in psoriasis lesions compared to healthy surround skin. Preliminary data showed that systemic treatments of psoriasis induce modification of the skin microbiome that becomes similar to healthy individuals after successful treatment. The causative role of microbiome in psoriasis remains in debate. The modification of skin microbiome is suspected to be able to activate the innate immune response, namely natural killers (NKs) and immune lymphoid cells (ILCs). Three types of ILCs have been reported. ILC1 (immune lymphoid cells1) that trigger a Th1 response, ILC2 (immune lymphoid cells 2) that stimulate Th2 response and ILC3 (immune lymphoid cells 3) that induce Th17 response. Interestingly, ILC2 have been reported to be increased in atopic dermatitis while ILC3 are increased in psoriasis.

To date, there is no data on the impact of topical treatments in skin microbiome and in innate cells in psoriasis lesions. However, topical treatments remain in most cases the first and the more widely used option for mild psoriasis which represent the more prevalent form of psoriasis. Thus, it appears of great interest to assess the effect of topical psoriasis treatments on skin microbiome. To this respect, topical steroids by their action both on the inflammation but also potentially on bacteria are suspected to induce potent changes in the microbiome in treated psoriasis lesions. calcipotriol has been demonstrated to have a beneficial effect on psoriasis thanks to its action on keratinocyte differentiation and its combination with topical steroids has been shown to be superior in treating psoriasis as compared to topical steroids alone. It could be hypothesized that calcipotriol could also modify the skin microbiome. The main objective of this study intra individual prospective study is to compare the respective effect of betamethasone associated with calcipotriol foam and placebo foam in one hand and betamethasone with calcipotriol foam to betamethasone ointment on the other hand, on skin microbiome after 4 weeks of treatments on knee or elbow lesions. Secondary objectives are to study the impact of the treatments on ILCs (numbers and relative proportion in the 3 types) and NK in the lesions and their potential correlation with the modification of the microbiome (of note ILC can be detected and characterized in situ in skin.) To compare the relative effectiveness of the two products on targets psoriasis lesions. Tolerance and potential side effects will be also studied. Main endpoint: quantitative and qualitative assessment of microbes on psoriasis lesions before and after the treatments compared to surrounding healthy skin control. Secondary endpoints: Presence and types of ILCs and NK in the lesional psoriatic skin before and after treatment compared with control healthy skin assessed using immunohistofluorescence. Targeted PASI or PGA (physician Global Assessment) for the efficacy. Potential side effects. Patients: 30 with mild psoriasis (PASI \<10) affecting elbows and knees in a symmetrical manner aged of at least 18.