Application of JAK inhibitors in paradoxical reaction through immune-related dermatoses

Abstract

Biologics play a positive and effective role in the treatment of immune-related dermatoses. However, many other immune-related diseases have also manifested along with biologics treatment. Paradoxical reaction through immune-related dermatoses refer to the new onset or exacerbation of other immune-mediated dermatoses (mainly psoriasis and atopic dermatitis) after biologics treatment of inflammatory dermatoses (mainly psoriasis and atopic dermatitis), such as new atopic dermatitis (AD) in psoriasis (PsO) treatment and new PsO in AD treatment. A common genetic background and Inflammatory pathway are possible pathogenesis. Faced with paradoxical reactions, the choice of therapy needs to be directed toward therapies effective for both diseases, such as Janus kinase (JAK) inhibitors. The Janus kinase and signal transducer and activator of transcription (JAK-STAT) pathway plays an important role in the inflammatory pathway, and has been widely used in the treatment of AD and PsO in recent years. This article focuses on JAK inhibitors such as tofacitinib, baricitinib, ruxolitinib, Abrocitinib, upadacitinib, and deucravacitinib, to explore the possible application in treatment of paradoxical reactions. Common side effects, baseline risk factors and safety use of JAK inhibitors were discussed.

Keywords: JAK inhibitors; atopic dermatitis; immune-related dermatoses; paradoxical reaction; psoriasis.

Figure 1

Relationships of T cell polarization and cytokines of AD and PSO on the immune axis. AD is Th22 and Th2 polarized while PsO is Th17 and Th1 polarized. However, AD in Asian populations have both the characteristics of PsO and AD in European and American populations, where Th2, Th17, and Th22 are all activated.

Figure 2

JAK inhibitors target specific JAK kinases to inhibit skin disease-related cytokine downstream signaling pathways. Different cytokines are involved in the pathological processes of different diseases through signals mediated by specific JAK kinases. JAK inhibitors can be used as a therapeutic strategy for cytokine-related diseases by inhibiting specific JAK kinase activity. HS, Hidradenitis suppurativa; SLE, Systemic lupus erythematosus; CLE, Cutaneous lupus erythematosus; AD, Atopic dermatitis; SS, Sjögren’s syndrome.