Faculty Bibliography

At the 2017 annual meeting of the Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA), members received updates on several ongoing educational and research efforts. Among them were updates on GRAPPA's continued education efforts; GRAPPA's continued research efforts, including the Biomarker Project, a collaborative research effort to identify and study biomarkers of joint damage; treatment recommendations, including recommendations and core principles related to biosimilars; efforts to update GRAPPA's Website and to create a GRAPPA smart-phone application (app); and the Psoriasis and Psoriatic Arthritis Clinics Multicenter Advancement Network.

PURPOSE OF REVIEW: Diagnosis and treatment of psoriatic arthritis (PsA) can be challenging and require a multidisciplinary approach. This review provides an overview of combined dermatology-rheumatology clinics. RECENT FINDINGS: Combined dermatology-rheumatology clinics have emerged to optimize integrated care for patients with psoriasis and PsA. There are over 20 such clinics across the USA. These clinics facilitate multidisciplinary care for patients with psoriasis and PsA and have been found to improve outcomes and enhance both patient and physician satisfaction and knowledge. Challenges presented by these clinics include appropriate scheduling for both dermatologists and rheumatologists and proving the benefits of the clinics to obtain institutional support. Combined dermatology-rheumatology clinics are a novel model of care for patients with psoriasis and PsA. They improve outcomes, patient and physician satisfaction, and efficiency. As more of these clinics are established, we must further understand their impact on outcomes and care processes.

Optimal management of patients with both psoriasis and psoriatic arthritis (PsA) necessitates collaboration among dermatologists and rheumatologists. In this manuscript, we discuss challenges and opportunities for dual care models for patients with psoriasis and PsA and the results of a survey of combined clinics based in North America.

Anti-tumor necrosis factors (Anti-TNFs) are a class of biologic disease-modifying anti-rheumatic drugs indicated for the treatment of moderate-to-severe psoriatic arthritis (PsA). Refractory patients are commonly managed by switching from one anti-TNF to another. To assess the evidence on the effectiveness of anti-TNF cycling in PsA patients, a systematic review of the literature was conducted. MEDLINE- and Embase-indexed English-language publications were systematically searched from 1995 to 2015 for studies assessing real-world effectiveness outcomes of anti-TNF cycling in PsA patients. Of 1086 citations identified, 18 studies were included; most conducted in Europe. Six of seven studies testing between lines found significant differences in effectiveness between earlier and subsequent lines of anti-TNF therapy. First-line therapy yielded better results compared with second-line therapy, and significant differences were observed between second- and third-line anti-TNF treatments. In the only study with multivariate regression testing for predictors of response, Danish registry patients were less likely to respond (American College of Rheumatology 20 % or 50 % response) to a second anti-TNF course if safety, rather than lack of effect, caused them to switch (odds ratio [OR] 0.04; p = 0.003 and OR 0.05; p = 0.03, respectively). Effectiveness of anti-TNFs at second line and later is reported in a small number of real-world studies of PsA patients. Subsequent treatment lines may be associated with less response in some measures. More research is needed to quantify the effectiveness of sequential anti-TNF lines in this progressive population' and to compare these effects with responses to drugs with different mechanisms of action.

Background/Purpose: Psoriasis (PsO) is a chronic immune-mediated skin condition affecting ~3% of adults worldwide. Up to a third of PsO patients go on to develop psoriatic arthritis (PsA), a heterogeneous inflammatory arthritis characterized by concomitant bone erosion and osteoproliferation. Although multiple advances have been made in the pathogenesis and therapeutics of these disorders, it is currently not possible to predict which individuals will progress from PsO to PsA. The role of the microbiome as a potential trigger for autoimmunity and rheumatic disease has recently been implicated. The goal of this study was to characterize the cutaneous microbiota of patients with PsO and PsA (in both psoriatic plaques and unaffected skin) to determine if there are characteristic features related to disease phenotype. Methods: Skin swabs from subjects with PsO (n=29) and PsA (n=62) were collected from both psoriatic plaque lesions and contralateral unaffected skin. 16S rDNA was extracted per protocol (MoBio, USA) and amplicons targeting the hypervariable V4 region were sequenced using MiSeq (Illumina) to define the microbiota composition. The obtained 16S rRNA sequences were analyzed using the Quantitative Insights into Microbial Ecology (QIIME) pipeline. Taxonomic relative abundance was determined to compare their prevalence among different phenotypes using Kruskal-Wallis statistical analysis. Alpha diversity plots and weighted Unifrac analysis (beta diversity) of cutaneous bacterial communities were generated. False discovery rate analysis was applied to identify unique differentiating taxa. Results: Baseline characteristics were comparable in both groups. PsO samples had, on average, a similar number of operational taxonomic units as compared to PsA samples. Beta diversity plots did not demonstrate statistically distinct clustering of microbial communities between PsO and PsA subjects, PsO and PsA nonlesional skin, or PsO and PsA lesional skin. Staphylococcus and Corynebacterium were the most abundant genera across all samples. However, several genera were statistically more abundant in PsO compared to PsA lesions, including unclassified Bradyrhizobiaceae (p<0.0006), Rahnella (p<0.0006), unclassified Prevotellaceae (p<0.001), and Parvibaculum (p<0.002). Rothia was more abundant in PsA (p<0.02). Conclusion: Our results characterize, for the first time, the cutaneous microbial composition of individuals with PsO compared to those with PsA both in psoriatic lesions and unaffected skin. Although we did not find overall community differences among the various phenotypes, our preliminary observations point towards differences in specific genera, which are characteristically more abundant in PsO. Further in-depth analysis is required to better understand the significance of this dysbiotic process in PsA and whether it contributes to the pathogenesis of the psoriatic disease spectrum. Current efforts are devoted to incorporating healthy controls into our analysis, and analyzing the cutaneous microbiome (and metagenome) across multiple body sites, multiple visits, as well as pre- and post-immunosuppressive/biologic therapy

Background/Purpose: Previous studies have established the value of measuring complement activation products (C4d) bound to platelets (PC4d) for the diagnosis and monitoring of Systemic Lupus Erythematosus (SLE). Separately, Antiphospholipid (APL) antibodies have been associated with complement activation and PC4d expression. In this study, we sought to validate the performance characteristics of PC4d, stratified by the presence or absence of APL antibodies. Methods: This multi-centered validation cross sectional study (16 sites in the US) enrolled 402 SLE subjects fulfilling the 1982 American College of Rheumatology Criteria revised in 1997 (mean age 41 years; 91% female), 411 subjects with rheumatic and autoimmune diseases other than SLE (mean age 55, 86% female consisting of 181 rheumatoid arthritis, 90 primary fibromyalgia, 92 other rheumatic diseases, and 48 autoimmune thyroiditis or hepatitis) and 198 healthy volunteers (mean age 41 years; 66% female). PC4d densities were determined using flow cytometry (expressed as mean fluorescence intensity [MFI]). Positive PC4d consisted of PC4d levels greater than 20 net MFI. Anticardiolipin IgG, anti-Beta-2-glycoprotein 1 IgG, or anti-Phosphatidylserine/Prothrombin (PSPT) complex IgG antibodies were determined using ELISA (INOVA diagnostics, San Diego, CA). Presence of APL antibodies consisted of any of these antibodies above manufacturer cutoff. SLE Disease activity was assessed using the non-serological SLE Disease Activity Index SELENA modification (ns-SELENA-SLEDAI, without the complement and anti-dsDNA). Performance characteristics were established using sensitivity, specificity, and ROC Curve Area Under the Curve (AUC). Statistical evaluation was by t-test (for disease activity), by chi-squared test for equality of proportions (for sensitivities and specificities) and by the method of DeLong (for ROC Curve AUC). Results: PC4d was highly specific in distinguishing SLE from other rheumatic diseases (Table) and normals. Among SLE subjects, 47% (n=187) presented with at least one APL antibody as compared to 21% (n=86) of subjects with other diseases and 15% of normals. PC4d sensitivity for SLE was higher among APL positive subjects by comparison to APL negative subjects (p=0.003). Specificity was not significantly different between APL positive and negative subjects (p>0.372). ROC AUC was significantly higher among the APL positive compared to negative subjects (p=0.002). The incidence of APL antibodies among all PC4d positive subjects was 60% compared to 27% among PC4d negative subjects (p<0.001). SLE subjects presenting with positive PC4d had higher disease activity (4.1+/-0.5) than those presenting with negative PC4d (3.0+/-0.2) (p=0.03). Conclusion: We confirm that PC4d is highly specific for SLE, and is associated with disease activity. (Table Presented)