Precision Medicine Approaches in Dermatology

A true translational revolution can be witnessed in dermatology with development of many targeted therapies, which has been possible due to novel ways of analysing the tissue (figure 1). Detection of immune pathways has been key to develop targeted therapies.

T-cells can differentiate in different subsets (Th1, Th2, and others). On the other hand, there are innate pathways driven by dendritic and other immune presenting cells and a second pathway that is driven by inflammasome activation (figure 2). “These are simplified core immune pathways that are directly associated with certain skin diseases”, Prof. Gilliet, Université de Lausanne, Lausanne (Switzerland) explained (figure 3).

“Although targeted therapies give some very efficacious responses, there are still some non -responders”, Prof. Gilliet said. It is not known, whether a wrong immune pathway is targeted, or whether there are immune escape pathways or even paradoxical reactions. To answer this question, Prof. Gilliet and his team started to use a precision medicine approach in all patients with inflammatory skin diseases.  They take 4-mm skin punch biopsies from skin lesions, perform RNA extraction and probe hybridisation for transcriptional profiling: As a result, different immune modules can be identified (figure 4). “What we came up to is that in psoriasis there are predominantly Th17 genes whereas if we do this for atopic dermatitis (AD) we come up with Th2 related genes or type I IFN genes in cutaneous lupus”, Prof. Gilliet said. These immune models can be used to identify diseases.

According to Prof. Gilliet´s experience, these immune models help to improve the diagnosis of inflammatory skin diseases. In his department, only 61% of patients can be diagnosed clinically, 85% if a histological examination is performed. However, when a molecular signature is added to the clinical examination and histology, the predictive value of the diagnosis is 100%.

At the end of the lecture, Prof. Gilliet presented three case reports that highlight the clinical consequences of a precision medicine approach in dermatology.

A personalized approach is also important in the context of so-called paradoxical reactions under targeted therapy: about 5,8% of anti-IL17A -treated patients get eczematous skin lesions. “Once we profile these lesions, we get a clear Th2 profile indicating a switch from Th17 to Th2”, Prof. Gilliet explained.

“I think in all these cases [of immune switches] the optimal new treatment is a JAK1/2 inhibitor that blocks a broader spectrum”, Prof. Gilliet concluded.