Abstract
Accumulating data on cellular and molecular pathways help to develop novel therapeutic strategies in skin inflammation and autoimmunity. Examples are psoriasis and atopic dermatitis, two clinically and immunologically well-defined disorders. Here, the elucidation of key pathogenic factors such as IL-17A/IL-23 on the one hand and IL-4/IL-13 on the other hand profoundly changed our therapeutic practice. The knowledge on intracellular pathways and governing factors is shifting our attention to new druggable molecules. Multiple cytokine receptors signal through Janus kinases (JAKs) and associated signal transducer and activators of transcription (STATs). Inhibition of JAKs can simultaneously block the function of multiple cytokines. Therefore, JAK inhibitors (JAKi) are emerging as a new class of drugs, which in dermatology can either be used systemically as oral drugs or locally in topical formulations. Inhibition of JAKs has been shown to be effective in various skin disorders. The first oral JAKi have been recently approved for the treatment of rheumatoid arthritis and psoriatic arthritis. Currently, multiple inhibitors of the JAK/STAT pathway are being investigated for skin diseases like alopecia areata, atopic dermatitis, dermatomyositis, graft-versus-host-disease, hidradenitis suppurativa, lichen planus, lupus erythematosus, psoriasis, and vitiligo. Here, we aim to discuss the immunological basis and current stage of development of JAKi in dermatology.
Highlights
The classification of skin diseases and their treatment options are becoming more and more complex
We aim to present the current position of JAK inhibitors (JAKi) in dermatology focusing on inflammatory skin diseases for which JAKi are at least in phase II investigation according to announced trials at clinicaltrials.gov
One example is the increase in cholesterol levels by tofacitinib [144, 206,207,208], which could be a paradox effect induced by the reduction of inflammation [209]
Summary
The classification of skin diseases and their treatment options are becoming more and more complex. While for a long period of time the morphology of diseased skin was prominent for disease classification and therapeutic procedures, we have the methodologies for a deep analysis of molecular processes and immunological pattern analysis responsible for the pathophysiological alterations. These advances enlarged our therapeutic repertoire in dermatology remarkably. Deep analysis of skin biopsies allows us to define pathophysiological factors like cytokines, receptors or signaling molecules that are present at different levels in distinct skin diseases [1,2,3] This leads to the identification of new targets and, if these targets are druggable, to new treatments. Our better understanding of further inflammatory skin diseases such as lupus erythematosus
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