A case of trichodysplasia spinulosa related to ruxolitinib treated successfully with oral acitretin

Abstract Trichodysplasia spinulosa (TS) is a rare disease that affects immunocompromised patients, characterized by hair‐like growths caused by TS‐associated polyomavirus infection. Little is known about specific immunosuppressive drugs that can precipitate the condition. We report a case of TS presenting after initiating the oral Janus‐associated kinase inhibitor (JAKi) ruxolitinib. A 67‐year‐old female with a history of allogeneic bone marrow transplant requiring immunosuppression with tacrolimus, prednisone and, more recently, ruxolitinib 5 mg twice daily due to Graft versus Host Disease presented to the clinic with a facial rash. The clinical and histopathological findings in the setting of immunosuppression were consistent with TS. Initial treatments were ineffective, but oral acitretin showed significant improvement after 3 months. Due to the close temporal relationship between the initiation of ruxolitinib and the development of TS, this case suggests that JAKis may contribute to TS development by suppressing the JAK‐signal transducer and activator of the transcription pathway's antiviral functions

Cutaneous Squamous Cell Carcinoma Arising in Immunosuppressed Patients: A Systematic Review of Tumor Profiling Studies.

As solid organ transplantation becomes more prevalent, more individuals are living as members of the immunosuppressed population with an elevated risk for cutaneous squamous cell carcinoma (cSCC). Although great progress has been made in understanding the pathogenesis of cSCC in general, little is known about the drivers of tumorigenesis in immunosuppressed patients and organ-transplant recipients, specifically. This systematic review sought to synthesize information regarding the genetic and epigenetic alterations as well as changes in protein and mRNA expression that place this growing population at risk for cSCC, influence treatment response, and promote tumor aggressiveness. This review will provide investigators with a framework to identify future areas of investigation and clinicians with additional insight into how to best manage these patients

ENTPD1(CD39) expression inhibits ultraviolet radiation-induced DNA damage repair via purinergic signaling and is associated with metastasis in human cutaneous squamous cell carcinoma

Ultraviolet radiation (UVR) and immunosuppression are major risk factors for cutaneous squamous cell carcinoma (cSCC). Regulatory T cells (Tregs) promote cSCC carcinogenesis and in other solid tumors, infiltrating Tregs and CD8+ T cells express ENTPD1 (also known as CD39), an ecto-enzyme that catalyzes the rate-limiting step in converting extracellular ATP to extracellular adenosine. We previously demonstrated that extracellular purine nucleotides influence DNA Damage Repair (DDR). Here we investigate whether DDR is modulated via purinergic signaling in cSCC. We found increased ENTPD1 expression on T cells within cSCCs when compared to T cells from blood or non-lesional skin and accordingly, concentrations of derivative extracellular ADP, AMP, and adenosine are increased in tumors compared to normal skin. Importantly, ENTPD1 expression is significantly higher in human cSCCs that metastasize compared to those that are non-metastatic. We also identify in a mouse model that ENTPD1 expression is induced by UVR in an IL27-dependent manner. Finally, increased extracellular adenosine is shown to downregulate the expression of NAP1L2, a nucleosome assembly protein we show to be important for DDR secondary to UVR. Together, these data suggest a novel role for ENTPD1 expression on skin-resident T cells to regulate DDR via purinergic signaling to promote skin carcinogenesis and metastasis