Lifestyle, demographic and Skindex measures associated with cutaneous T-cell lymphoma: a single institution cohort study.

Cutaneous T-cell lymphoma (CTCL) risk factors and associated quality of life are poorly understood. Previous studies of CTCL risk factors explored patient comorbidities and lifestyle exposures, but not in conjunction with disease stage, subtype, severity, or health-related quality of life (HRQoL). We investigated lifestyle exposures and demographic factors associated with advanced-stage disease, increased disease severity, and poorer HRQoL outcomes in this single-center cohort study. A cohort survey study was conducted at Northwestern's Multidisciplinary Cutaneous Lymphoma specialty clinic between April 2019 and June 2021. REDCap surveys were administered to 140 patients with CTCL, investigating patients' demographics, lifestyle and chemical exposures. QoL was evaluated using the Skindex survey; pain and itch with ten-point Likert scales. Modified Severity Weighted Assessment Tool (mSWAT), disease stage, and disease subtype were confirmed upon enrollment in the study by a single board-certified dermatologist specializing in CTCL. Factors were compared by t test or Fischer's exact test. Median age was 63 years (range 14-92) with male-to-female ratio of 1.2:1. The most common diagnosis was CD4 + MF (n = 94, 67.1%). Common lifestyle exposures included smoking (past or current) (52.3%) and chemical exposure history (all sources [53.7%]; industrial only [33.0%]). History of chemical exposures were associated with advanced stage disease (p = 0.003) and worse QoL outcomes (p = 0.001). There were significant racial differences, respectively, in early (I-IIA) vs late (IIB-IV) stage disease (p = 0.003). Obesity, hygiene, smoking, recent sun exposure, education and atopy were not significantly associated with disease stage or severity. We provide an analysis of lifestyle and demographic factors in the context of CTCL disease severity, stage, and HRQoL. We identified race as a potential risk factor for advanced stage disease and both skin phototype and chemical exposures as a risk factor for increased disease severity as measured by mSWAT. QoL outcomes were multifactorial and significantly associated with history of chemical exposure, severe pain/itch, race, disease stage and subtype. An improved understanding of these associations may lead to better individualized care. As chemical exposure and race were found to be significant factors associated with advanced-stage disease, taking exposure histories and addressing racial disparities may improve care for CTCL patients.

Nasal Dysbiosis in Cutaneous T-Cell Lymphoma Is Characterized by Shifts in Relative Abundances of Non-Staphylococcus Bacteria.

The nasal microbiome of patients with cutaneous T-cell lymphoma (CTCL) remains unexplored despite growing evidence connecting nasal bacteria to skin health and disease. Nasal swabs from 45 patients with CTCL (40 with mycosis fungoides, 5 with Sézary syndrome) and 20 healthy controls from the same geographical region (Chicago Metropolitan Area, Chicago, IL) were analyzed using sequencing of 16S ribosomal RNA and tuf2 gene amplicons. Nasal α-diversity did not differ between mycosis fungoides/Sézary syndrome and healthy controls (Shannon index, genus level, P = 0.201), but distinct microbial communities were identified at the class (R2 = 0.104, P = 0.023) and order (R2 = 0.0904, P = 0.038) levels. Increased relative abundance of the genera Catenococcus, Vibrio, Roseomonas, Acinetobacter, and unclassified Clostridiales was associated with increased skin disease burden (P < 0.005, q < 0.05). Performed to accurately resolve nasal Staphylococcus at the species level, tuf2 gene amplicon sequencing revealed no significant differences between mycosis fungoides/Sézary syndrome and healthy controls. Although S. aureus has been shown to worsen CTCL through its toxins, no increase in the relative abundance of this taxon was observed in nasal samples. Despite the lack of differences in Staphylococcus, the CTCL nasal microbiome was characterized by shifts in numerous other bacterial taxa. These data add to our understanding of the greater CTCL microbiome and provide context for comprehending nasal-skin and host‒tumor‒microbial relationships.

Targeting the IL-17 Receptor Using Liposomal Spherical Nucleic Acids as Topical Therapy for Psoriasis.

The activation of T helper 17 signaling plays a critical role in psoriasis pathogenesis, and systemically-administered IL-17 inhibitors are highly effective therapy for moderate-to-severe disease. We generated topically-delivered gene-regulating nanoconstructs, comprised of spherically-arrayed antisense DNA (liposomal spherical nucleic acids [L-SNAs]), which are able to penetrate human skin to knock down cutaneous gene targets. Topically-applied L-SNAs targeting the gene encoding the mouse IL-17A receptor (Il17ra) reversed the development of psoriasis clinically, histologically, and transcriptionally in imiquimod-treated psoriasis-like mouse skin. Il17ra L-SNAs reduced the modified PASI by 74% versus controls and decreased epidermal thickness by 56%. Il17ra L-SNA reduced Il17ra protein expression by 75% and significantly decreased the mRNA expression of psoriasis markers, including Defb4, Il17c, S100a7, Pi3, Krt16, and Tnfa versus scrambled spherical nucleic acid (Scr SNA) controls. A human IL17RA L-SNA penetrates 3-dimensional cultures and normal human explants to knock down IL17RA mRNA by 63% and 66%, respectively. After topical application to psoriatic 3-dimensional rafts, anti-human IL17RA L-SNAs reduced the expression of IL17RA (by 72%) and the IL-17-induced genes IL17C (by 85%), DEFB4 (by 83%), TNFA (by 77%), and PI3 (by 65%) versus scrambled L-SNA and vehicle controls (all P < 0.001). Taken together, these data suggest that targeted suppression of IL17RA is a promising new topical treatment strategy for psoriasis.