Faculty Bibliography

Background/Purpose : About 30% of patients with skin psoriasis (PsO) develop psoriatic arthritis (PsA). The reasons for why only some progress to synovio-enthesial disease from skin involvement remains unknown. Genetic, environmental and clinical-demographic factors have been implicated, but are yet to be characterized in specialized, combined care centers. We aim to describe clinical phenotypes differentiating patients with PsO from those with PsA at a large, urban tertiary care PsO-PsA clinic. Methods : Consecutive adult patients meeting CASPAR criteria for PsA (n= 448) or with dermatologist diagnosed skin psoriasis only (n=161) were prospectively recruited at the NYU Psoriatic Arthritis Center and the NYU Psoriasis and Psoriatic Arthritis Clinic. All data was collected utilizing clinical visit notes and additional on-site questionnaires. Type of psoriasis and body surface area (BSA) was determined by dermatologists or rheumatologists specializing in psoriatic disease. Data was analyzed using statistical software SPSS using chi squared test with Yates Continuity Correction for dichotomous/categorical variables and t-test for continuous variables. Results : Patients with PsO were more likely to be older (52.7 vs. 48.9, p=.032) and have hypertension, obesity, diabetes, and history of myocardial infarction (Figure 1). Patients with PsO had a statistically higher BSA than those with PsA (5.8% vs 3.1%, p=.003). While the type of psoriasis was similar, the site of psoriasis involvement (specifically the scalp and nail) differentiated the populations (Table 1). In PsA compared to PsO, the odds ratio of scalp involvement was 2.96 (95% Confidence Interval [CI] 2.02, 4.34) and that of nail involvement was 14.66 (95% CI 8.21, 26.16). Inverse psoriasis was not different between groups. Additionally, those with PsA were much more likely to have a first degree relative (FDR) with psoriasis compared to those with cutaneous disease alone (31.9% vs. 12.0%, p=.007) (Figure 1). Conclusion : We report for the first time the comorbidities and psoriasis features of PsA and PsO populations in a large, combined center. We found that scalp involvement and any nail involvement was more prevalent in the PsA as compared to PsO. Only one previous study has identified scalp psoriasis[1] as a possible risk factor for progression, while previous studies looking at nail psoriasis reported much lower odds ratios[1,2]. Patients with PsA also demonstrated a higher number of FDRs with skin psoriasis, reinforcing the notion of strong heritability in PsA. The identification of risk factors for progression is of critical importance to study natural history of psoriatic disease and to inform the adequate design of prevention trials in psoriasis patients who have enriched features associated with future transition to synovio-enthesial disease

Background/Purpose : Psoriatic arthritis (PsA) is a heterogenous inflammatory disease affecting skin, joints, and other domains. While psychiatric diseases (i.e., depression and anxiety) are known comorbidities, little is known about their impact on disease severity and patient reported outcomes (PROs). The objective of this study was to characterize the prevalence of psychiatric comorbidities in an academic combined psoriasis-psoriatic arthritis center and determine their impact on PsA clinical and patient derived outcomes. Methods : Consecutive adult patients meeting CASPAR criteria for PsA (n=436) were prospectively recruited at the NYU Psoriatic Arthritis Center. All data was collected from clinical visits utilizing a standardized EPIC template. Depression was defined by established diagnosis and/or use of anti-depressant medications. Objective measures of disease severity included swollen and tender joint counts (SJC/TJC) and PROs including RAPID3 scores. Data was analyzed using statistical software R. Results : Our cohort was comprised of 436 patients: 54% male, mean age of 47 years, and mostly Caucasians (74.1%). Within our population, 19.5% had depression, 15.6% had anxiety, and 4.8% had ADHD (Table 1). Of those with depression, 71% were on anti-depressive medication. At the initial visit, patients with PsA and depression were more likely to be on medication(s) for PsA (80% vs 65%, p=.01) and had a trend towards higher rates of biologic use (47.5% vs 40.4%, p=.126). Those with depression had a similar TJC to their non-depressed counterparts, but had a trend towards fewer swollen joints and concomitant higher RAPID3 scores (Table 2). When analyzing repeated outcome measures over subsequent visits, individuals with depression were similarly more likely to have a higher TJC, a lower SJC, and a higher RAPID3 score (although only RAPID3 was found to be statistically significant, p=.004). Importantly, these findings persisted when analyzing participants that were matched with propensity scores to adjust for age, sex, comorbidities, and medication use. In addition to joint activity, psoriasis activity measured by body surface area (BSA) was lower in those who were depressed (1.4% vs 3.03%, p=.001) and these differences were maintained over subsequent visits. Conclusion : Our results expand on prior reports of significantly elevated rates of depression in PsA. Notably, individuals with depression were more likely to be on medication(s) for their PsA, had fewer swollen joints, and a lower BSA but, paradoxically reported higher RAPID3 scores. This discrepancy is likely a manifestation of how depression could affect the way patients experience their PsA despite apparent improvement in skin and joint symptoms. Depression should, therefore, be considered a critical comorbidity when addressing PsA care in routine visits. Further work is needed to understand whether modulation of psychiatric comorbidities can lead to improved PsA outcomes

Objective- Psoriasis is an inflammatory skin disease which heightens the risk of cardiovascular disease. This study directly investigated vascular endothelial health and systemically altered pathways in psoriasis and matched controls. Approach and Results- Twenty patients (mean age, 40 years; 50% male) with active psoriasis and 10 age-, sex-matched controls were recruited. To investigate systemically alerted pathways, a deep sequencing omics approach was applied, including unbiased blood transcriptomic and targeted proteomic analysis. Vascular endothelial health was assessed by transcriptomic profiling of endothelial cells obtained from the brachial veins of recruited participants. Blood transcriptomic profiling identified inflammasome signaling as the highest differentially expressed canonical pathway ( Z score 1.6; P=1×10^-7) including upregulation of CASP5 and interleukin ( IL) -1β. Proteomic panels revealed IL-6 as a top differentially expressed cytokine in psoriasis with pathway analysis highlighting IL-1β( Z score 3.7; P=1.02×10^-23) as an upstream activator of the observed upregulated proteins. Direct profiling of harvested brachial vein endothelial cells demonstrated inflammatory transcript (eg, IL-1β, CXCL10, VCAM-1, IL-8, CXCL1, Lymphotoxin beta, ICAM-1, COX-2, and CCL3) upregulation between psoriasis versus controls. A linear relationship was seen between differentially expressed endothelial inflammatory transcripts and psoriasis disease severity. IL-6 levels correlated with inflammatory endothelial cell transcripts and whole blood inflammasome-associated transcripts, including CASP5 and IL-1β. Conclusions- An unbiased sequencing approach demonstrated the inflammasome as the most differentially altered pathway in psoriasis versus controls. Inflammasome signaling correlated with psoriasis disease severity, circulating IL-6, and proinflammatory endothelial transcripts. These findings help better explain the heightened risk of cardiovascular disease in psoriasis. Clinical Trial Registration- URL: http://www.clinicaltrials.gov . Unique identifier: NCT03228017.

PURPOSE/OBJECTIVE:Injectable biologics (IB) are important in dermatology and we sought to examine the distribution of U.S. IB-prescribing dermatologists. MATERIALS AND METHODS/METHODS:We used Centers for Medicare and Medicaid Services Medicare Provider Utilization and Payment Data: Part D for 2013-2015. Density of dermatologists who prescribe IB (etanercept, adalimumab, ustekinumab, secukinumab) in each U.S. county, represented as number of dermatologists per 100,000 Medicare Part D beneficiaries, was calculated. RESULTS:2,992 dermatologists (26.3% of dermatologists) prescribed IB in this study. The national density of IB-prescribing dermatologists was 7.22. Only 778 counties (24.8%) have at least one IB-prescribing dermatologist. The densities of IB-prescribing dermatologists in metropolitan counties were 8.07-8.12. The densities of IB-prescribing dermatologists were 4.55 and 6.51 for urban populations of greater than 20,000 people adjacent and non-adjacent to metropolitan areas, respectively. Urban counties with populations between 2,500-19,999 and adjacent to a metropolitan area had a density of 2.03 and urban counties with the same population and not adjacent to a metropolitan area had a density of 2.84. Completely rural or urban counties with populations under 2,500 people had densities between 2.31-2.35. CONCLUSIONS:There are disparities in the availability of IB-prescribing dermatologists across urban-rural geographic settings in the U.S.

Background/Purpose: Psoriatic arthritis (PsA) and Psoriasis (PsO) are chronic inflammatory diseases associated with vascular inflammation and increased CVD risk. Few studies have examined vascular inflammatory differences between PsO and PsA and how these differences may impart a different CVD risk profile. We directly investigated the vascular endothelium of patients with PsA, PsO and compared to controls to better understand the inflammatory mechanism(s) that predispose psoriatic patients to CVD risk.
Method(s): Twenty patients with psoriatic disease (PD) (mean age 45 years, 55% male, 11.2 +/- 19% body surface area (BSA) involvement) were first compared to 10 matched controls. Next, comparisons were made between PsO (n = 14, average age 50 years, 57% male, 11 +/- 22% BSA) and active PsA (n = 6, average age 36 years, 50% male, 11 +/- 10% BSA, average 2 - 3 tender/swollen joints per individual). To measure vascular endothelial health, venous endothelial cells were collected from the brachial vein using guidewires inserted through an angiocatheter and isolated with CD146-conjugated magnetic beads. Following collection, endothelial mRNA was isolated, converted to cDNA and inflammatory gene profiling performed by RT-qPCR with Taqman probes and primers. Transcripts were chosen based on in vitro gene arrays of human aortic endothelial cells co-stimulated with IL-17 and TNF-alpha.
Result(s): PD patients compared to controls showed a trend towards higher levels of hs-CRP (2.4 +/- 4 mg/dl vs. 0.8 +/- 2 mg/ dl, p = 0.08) with no overall difference noted between PsA and PsO patients (2.8 +/- 2 mg/dl vs. 2.7 +/- 4 mg/dl, p = 0.24). Transcriptomic profiling of venous endothelial cells comparing PD (PsO and PsA) to controls revealed upregulation of inflammatory cytokine- and chemokine- associated transcripts (lymphotoxin beta [4 - fold], CCL3 [11 - fold], CXCL10 [16 - fold], IL-8 [10 - fold] and IL-1beta [4 - fold], P < 0.05 for all) and transcripts related to intracellular adhesion (ICAM1 [2.4 - fold] and inflammation COX-2 [3 - fold], P < 0.05). Increased expression of the chemokine fractalkine (CX3CL1 [2.8 - fold], p < 0.05) and lymphotoxin beta [2 - fold, p = 0.10] were found in patients with active PsA compared to PsO. No differences in CCL3, CXCL10, IL-8, IL-1B, ICAM1 and COX-2 where seen between PsA and PsO patients.
Conclusion(s): Endothelial cell pro-inflammatory transcripts are upregulated in patients with active PD compared with controls. Levels of lymphotoxin beta and fractalkine, a chemokine present in inflamed arthritic synovial tissue, are greater in endothelial cells of patients with PsA than PsO. These findings may underlie increased CVD risk in patients with PD and highlight the inflammatory vascular differences between PsO and PsA

Background/Purpose: The microbiome serves a number of important functions, including modulation of the immune system and protection from pathogenic microorganisms1. Many autoimmune diseases have been associated with intestinal microbial dysbiosis1. Recent studies have also demonstrated that microbiota can affect the lifetime, bioavailability and efficacy of drugs2. Conversely, even drugs designed to specifically target human cells have been associated with changes in microbial composition3. To date, most research has focused on bacterial microorganisms and little is known about the role that fungal microorganisms (the mycobiome) play, including their interactions with bacteria. In this study, we characterized the ecological effects of biologic therapies on the intestinal mycobiome.
Method(s): Fecal samples were collected from SpA patients pre- and post-treatment with either tumor necrosis factor inhibitors (TNFi; n=15) or secukinumab (n=14), an anti-IL-17A monoclonal antibody (IL-17i). Subjects treated with TNFi were naive to biologic therapy, whereas those treated with secukinumab previously failed or had incomplete response to TNFi. Samples underwent DNA extraction, amplification, and gene sequencing of the ITS1 region conserved in fungi. In parallel, gene sequencing of the 16S rRNA gene region conserved in bacteria was also performed. Sequences were analyzed with R and Quantitative Insights into Microbial Ecology (QIIME).
Result(s): ITS fungal data reveled that, on average, subjects treated with TNFi and IL-17i did not have major differences in overall microbial alpha or beta diversity pre- and post-treatment. However, there were dramatic shifts in the relative abundance of specific taxa, such as Candida albicans, which were more prominent in the IL-17i cohort compared to the TNFi cohort (p=0.04). The IL-17i cohort also demonstrated similar changes in certain 16S bacterial taxa, including Clostridia (p=0.02) and Clostridiales (p=0.02).
Conclusion(s): We characterized, for the first time, the effects of two biologic therapies on human intestinal fungal and bacterial microbiota composition. Treatment with biologics, particularly IL-17i, leads to a gut microbial dysbiosis characterized by significant changes in abundance of C. albicans and Clostridia in a subgroup of SpA patients. This is in line with the known increased risk of candidiasis seen with IL-17i, and may at least partially explain the potential link between IL-17 blockade, intestinal dysbiosis, and the subclinical and clinical gut inflammation observed in some patients treated with these molecules. Further studies to understand the downstream effects of these perturbations may allow for the development of precision medicine approaches in PsA and SpA