JAK Inhibitors as Potential Therapeutic Strategy for the Dilemma of Psoriasis Concurrent with Dermatomyositis in the SARS-CoV-2 Era.

Dermatomyositis is a rare inflammatory disease with potentially life-threatening systemic involvement that is treated with systemic corticosteroids. However, when psoriasis coexists with dermatomyositis, the administration of corticosteroids may exacerbate psoriasis after withdrawal, posing a treatment dilemma. Our search of the literature revealed 14 cases where various treatments were used, including methotrexate, corticosteroids, cyclosporin, ustekinumab, mycophenolate mofetil, and azathioprine. While methotrexate showed promise, it carries risks, and corticosteroids were used despite their potential to exacerbate psoriasis. Based on transcriptomic data analysis of psoriasis and dermatomyositis, the type II interferon-mediated signaling pathway was enriched in both diseases. Medication targeting this pathway, such as JAK inhibitors, could be a potential solution for the psoriasis concurrent with dermatomyositis dilemma, as JAK inhibitors have been proven effective in treating both dermatomyositis and psoriasis, with some being FDA-approved for treating COVID-19. Therefore, JAK inhibitors may be a potential therapeutic strategy for psoriasis concurrent with dermatomyositis in the SARS-CoV-2 era.

SARS-CoV-2 might transmit through the skin while the skin barrier function could be the mediator.

During the coronavirus disease 2019 (COVID-19) pandemic, it were reported that COVID-19 patients could have cutaneous symptoms, and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was observed on the skin of COVID-19 patients, which indicated that the skin is one target of SARS-CoV-2. Meanwhile, reports about SARS-CoV-2 transmission through food cold-chain overpacks emerged. With the fact that SARS-CoV-2 could survive on the skin for more than 9 h, the skin could be implicated in SARS CoV-2 transmission. Angiotensin-converting enzyme 2 (ACE2), a critical membrane protein for SARS-CoV-2 that enters a host cell, was recognized to be associated with the risk of SARS-CoV-2 infection. Therefore, tissues that express ACE2 might have the potential to be infected by and transmit SARS-CoV-2. The skin is one such tissue that expresses ACE2. However, unlike the lung that expresses ACE2 on the upper-most epithelial layer, the skin is composed of different layers of cells that function as a barrier, and cells under the top epidermal layer express ACE2. Since the skin barrier is the first line of protection, the typical position of ACE2-expressing cells in the skin implies that the skin barrier function could be the mediator of SARS-CoV-2. In our study, we found that ACE2 could be expressed in the skin, and its expression level is increased in psoriasis, an inflammatory disease of the skin with barrier dysfunction. Additionally, by applying the SARS-CoV-2 pseudovirus on mouse models with or without deteriorated skin barrier, we found that the SARS-CoV-2 pseudovirus could infect the skin and lungs of mouse models, and when the skin barrier was impaired, more SARS-CoV-2-infected cells could be found. Thus, we hypothesized that a deteriorated condition of the skin barrier might increase the risk of SARS-CoV-2 infection through the skin.