JAK-inhibitors in the therapy of comorbid diseases – atopic dermatitis and alopecia areata: literature review and experience of clinical practice

Abstract

Atopic dermatitis (AtD) is currently considered as a systemic disease due to the fact, that disorders of innate and adaptive immune response, especially pronounced in severe course, are manifested not only in skin inflammation, but also can be realized in the development of other chronic diseases, including autoimmune profile. One of the autoimmune comorbid diseases in AtD is alopecia areata (AA), which is confirmed by epidemiologic data, clinical features and identification of common immune links of pathogenesis in the case of association of these diseases. Janus-kinase inhibitors, which represent a new class of targeted synthetic basic anti-inflammatory drugs, are currently the main pathogenetic treatments for severe forms of AtD and AA. Acting on several immune axes, these drugs selectively and reversibly modulate the signaling activity of key inflammatory cytokines, which makes them the most promising strategy for systemic therapy of these dermatoses, including in cases of their combination. The article covers the review of pathophysiology and application of first and second generation JAK-inhibitors in AtD and AA, including the analysis of their efficacy in the simultaneous presence of these pathological conditions. We present own observations of two patients with severe comorbid conditions AtD and AA, treated with the JAK-inhibitors abrocitinib and upadacitinib. These examples confirm the efficacy of Janus-kinase inhibitors in AtD and AA in real clinical practice and describe the experience of switching from one JAK-inhibitor of the first generation to another, selective JAK-inhibitor, as well as the effect of of these drugs on the course of both pathologies. Taking into account the necessity of long-term use of JAK-inhibitors, further study of their long-term efficacy and safety remains relevant.