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 that presents distinct cutaneous manifestations and various degrees of potentially life-threatening systemic involvement,¹ such as pulmonary diseases or malignancies. The first-line therapy for managing dermatomyositis is systemic corticosteroids. However, in cases where psoriasis coexists with dermatomyositis, the administration of systemic corticosteroids may pose a dilemma due to concerns regarding the potential exacerbation of psoriasis after corticosteroid withdrawal.

In order to figure out the possible solution for this dilemma, we prepared a comprehensive full strategic electronic search of the PubMed, Scopus, Google Scholar and EBSCO databases, using the following keywords ‘psoriasis’, ‘dermatomyositis’ and covering the period 2003–2022. Over 200 articles were found. After reviewing these articles, fourteen cases^2–13 were concluded (Table 1). The treatment of these cases concluded methotrexate, corticosteroids, cyclosporin, ustekinumab, mycophenolate mofetil and azathioprine.

Table 1 Cases of Psoriasis Concurrent with Dermatomyositis

Among the available treatments for psoriasis concurrent with dermatomyositis, methotrexate has shown promise and was utilized in seven out of fourteen cases. However, the use of methotrexate to treat this condition carries certain risks, such as the potential for interstitial lung disease, which raises concerns that the treatment may trigger or exacerbate the interstitial lung disease associated with dermatomyositis. In some cases, corticosteroids were used in the treatment of psoriasis concurrent with dermatomyositis, despite their known potential to exacerbate psoriasis. Of the six cases in which corticosteroids were used, four were administered concomitantly with other immunosuppressants, including methotrexate, cyclosporin, mycophenolate mofetil, and azathioprine. However, the possibility of psoriasis exacerbation remained. Inkeles MS reported the effectiveness of cyclosporine monotherapy in the treatment of psoriasis concurrent with dermatomyositis, noting that its selection was based on its documented efficacy and safety in treating dermatomyositis, as well as its FDA-approved status for treating psoriasis. Nonetheless, limitations exist, such as the concern that during the SARS-CoV-2 pandemic, immunosuppressants like cyclosporine may increase the risk of infection. Furthermore, biologics such as ustekinumab, which target Interleukin(IL)-12/23p40 and are effective in treating psoriasis, have shown promise in treating psoriasis concurrent with dermatomyositis. However, there have been reports of secukinumab, an interleukin 17 antagonist, acting as a precipitating factor for psoriasis concurrent with dermatomyositis, which has led to caution in using biologics that target the IL23-IL17 pathway in the treatment of this condition.

Then, what could be a solution for this treatment dilemma of psoriasis concurrent with dermatomyositis? We thought the same pathogenetic pathway might give us a hint. Thus, we download the skin transcriptomic data of psoriasis¹⁴ (GSM5216154, GSM5216170, GSM5216195, GSM5216211, GSM5216226, GSM5216244, GSM5216272 as lesion samples and GSM5216067, GSM5216071, GSM5216086, GSM5216102, GSM5216106, GSM5216114, GSM5216118 as control samples) and dermatomyositis¹⁵ (GSM3671281, GSM3671282, GSM3671285, GSM3671287 as lesion samples and GSM3671288, SM3671289, GSM3671290, GSM3671291, GSM3671292 as control samples). We used R studio in the analyses of the downloaded psoriasis (DESeq2 and clusterProfiler package) and dermatomyositis data (limma and clusterProfiler package). We found type II interferon-mediated signaling pathway (GO: 0060333) was enriched in both psoriasis (P = 0.003144649) and dermatomyositis (P = 1.37E-07).

Based on our data above, the medication targeting type II interferon-mediated signaling pathway could be a potential solution for the psoriasis concurrent with dermatomyositis dilemma. Type II interferon-mediated signaling pathway is controlled by Janus Kinase (JAK) 1 and JAK2 which several JAK inhibitors targeting this pathway including tofacitinib,¹⁶ ruxolitinib,¹⁷ baricitinib,¹⁶ abrocitinib¹⁸ and etc. There were several JAK inhibitors proved effective in the treatment of dermatomyositis. Meanwhile, these JAK inhibitors were also used in the treatment of psoriasis. These facts made JAK inhibitors eligible for the treatment of psoriasis concurrent with dermatomyositis. As mentioned above, in the SARS-CoV-2 era whether a treatment might aggravate SARS-CoV-2 should be taken into consideration. Baricitinib, one of the JAK inhibitors was approved by FDA for the treatment of adult patients hospitalized with COVID-19. While another JAK inhibitor, tofacitinib were also appeared to benefit attenuating SARS-CoV-2 infection. Thus, based on the psoriasis and dermatomyositis transcriptomic data as well as the lines above, we believe that JAK inhibitors could be the potential therapeutic strategy for the dilemma of psoriasis concurrent with dermatomyositis in the SARS-CoV-2 era.