Targeted Treatment of TREX1 Chilblain Lupus and Other Interferonopathies

Targeted, or pathogenesis-based, therapies are revolutionizing medicine. For the past decade and a half, as science has honed in on the primary events in psoriasis pathogenesis, treatment has evolved from that of a hammer to that of a laser. The discovery that helper T-cell subtype 17 (TH17) immunity (and related cytokines interleukin-17 [IL-17] and IL-23) plays a central role in psoriasis pathogenesis has led to the development of effective treatments with agents targeting IL-17 and IL-23 (eg, secukinumab and guselkumab, respectively). More recently our understanding of atopic dermatitis pathogenesis has advanced and we now have targeted therapy for this common dermatosis. The cytokines IL-4 and IL-13 have been identified as drivers of atopic dermatitis pathogenesis, leading to the development of dupilumab, a monoclonal antibody targeting IL-4 and IL-13. Even more recently, the identification of interferon-γ (IFN-γ) as a pathogenic driver in alopecia areata has led to the development of Janus kinase (JAK) inhibitors to treat this disease. In each of these cases, as science has revealed the underpinnings of disease, targeted therapy has followed.

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