CCL20 in Psoriasis: A Potential Biomarker of Disease Severity, Inflammation, and Impaired Vascular Health
BACKGROUND:Psoriasis is associated with increased cardiovascular risk that is not captured by traditional pro-inflammatory biomarkers. OBJECTIVE:To investigate the relationship between psoriasis area and severity index (PASI), circulating pro-inflammatory biomarkers, and vascular health in psoriasis. METHODS:In psoriasis and age, sex-matched controls, 273 proteins were analyzed utilizing the OLINK platform, while vascular endothelial inflammation and health was measured via direct transcriptomic analysis of brachial vein endothelial cells. RESULTS:= 48.18, p<0.001) in predicting vascular endothelial inflammation. LIMITATIONS/CONCLUSIONS:Our study was observational and does not allow for causal inference in the relationship between CCL20 and cardiovascular risk. CONCLUSION/CONCLUSIONS:We demonstrate that CCL20 expression has a strong association with vascular endothelial inflammation, reflects systemic inflammation, and may serve as a potential biomarker of impaired vascular health in psoriasis.
Covid-19 in Immune-Mediated Inflammatory Diseases - Case Series from New York [Letter]
IL-17 Inhibition in Spondyloarthritis Associates with Subclinical Gut Microbiome Perturbations and a Distinctive IL-25-Driven Intestinal Inflammation
OBJECTIVE:To characterize the ecological effects of biologic therapies on the gut bacterial and fungal microbiome of psoriatic arthritis (PsA)/spondyloarthritis (SpA) patients. METHODS:Fecal samples from PsA/SpA patients pre- and post-treatment with tumor necrosis factor inhibitors (TNFi; n=15) or an anti-interleukin (IL)-17A monoclonal antibody inhibitor (IL-17i; n=14) underwent sequencing (16S, ITS and shotgun metagenomics) and computational microbiome analysis. Fecal levels of fatty acid metabolites and cytokines/proteins implicated in PsA/SpA pathogenesis or intestinal inflammation were correlated with sequence data. Additionally, ileal biopsies obtained from SpA patients who developed clinically overt Crohn's disease (CD) after treatment with IL-17i (n=5) were analyzed for expression of IL-23/Th-17 related cytokines, IL-25/IL-17E-producing cells and type-2 innate lymphoid cells (ILC2s). RESULTS:There were significant shifts in abundance of specific taxa after treatment with IL-17i compared to TNFi, particularly Clostridiales (p=0.016) and Candida albicans (p=0.041). These subclinical alterations correlated with changes in bacterial community co-occurrence, metabolic pathways, IL-23/Th17-related cytokines and various fatty acids. Ileal biopsies showed that clinically overt CD was associated with expansion of IL-25/IL-17E-producing tuft cells and ILC2s (p<0.05) compared to pre-IL-17i treatment levels. CONCLUSION/CONCLUSIONS:In a subgroup of SpA patients, the initiation of IL-17A blockade correlated with features of subclinical gut inflammation and intestinal dysbiosis of certain bacterial and fungal taxa, most notably C. albicans. Further, IL-17i-related CD was associated with overexpression of IL-25/IL-17E-producing tuft cells and ILC2s. These results may help to explain the potential link between inhibition of a specific IL-17 pathway and the (sub)clinical gut inflammation observed in SpA.
Activated Platelets Induce Endothelial Cell Inflammatory Response in Psoriasis Via COX-1 (Cyclooxygenase-2)
OBJECTIVE:=0.02). CONCLUSIONS:In patients with psoriasis, platelets are activated and induce endothelial cell inflammation. Low-dose aspirin improved endothelial cell health in psoriasis via platelet COX-1 inhibition. These data demonstrate a previously unappreciated role of platelets in psoriasis and endothelial cell inflammation, which suggests that aspirin may be effective in improving vascular health in patients with psoriasis. Registration: URL: http://www.clinicaltrials.gov. Unique identifier: NCT03228017.
Patient health-seeking behavior on WeChat: Social media and dermatology [Case Report]
A case of porphyria cutanea tarda in the setting of hepatitis C infection and tobacco usage
Porphyria cutanea tarda (PCT) is the most common type of porphyria, presenting in middle-aged patients with a photodistributed vesiculobullous eruption, milia, and scars. Porphyria cutanea tarda occurs in relation to inhibition of uroporphyrinogen decarboxylase, a key enzyme in the heme biosynthesis pathway. A number of genetic and acquired factors increase susceptibility to PCT by reducing uroporphyrinogen decarboxylase activity. A handful of other vesiculobullous conditions may mimic PCT both clinically and histologically; therefore, both skin biopsy and laboratory evaluation are helpful in confirming the diagnosis. We report a case of PCT in the setting of cigarette usage and untreated hepatitis C infection.
The paradoxical effect of depression on psoriatic arthritis outcomes in a combined psoriasis-psoriatic arthritis center [Meeting Abstract]
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
Assessing risk of PSA progression: Results from a combined psoriasis-psa center cohort [Meeting Abstract]
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 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
Validated Patient-Reported Outcome Measurements for Psoriasis may not Reflect Patients' Current Preferences
Inflammasome Signaling and Impaired Vascular Health in Psoriasis
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=1Ã—10-7) including upregulation of CASP5 and interleukin ( IL) -1Î². Proteomic panels revealed IL-6 as a top differentially expressed cytokine in psoriasis with pathway analysis highlighting IL-1Î²( Z score 3.7; P=1.02Ã—10-23) as an upstream activator of the observed upregulated proteins. Direct profiling of harvested brachial vein endothelial cells demonstrated inflammatory transcript (eg, IL-1Î², 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-1Î². 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.