Prevalence and severity of psoriasis is associated with impaired vascular health [Meeting Abstract]
Access to Injectable Biologic Medications by Medicare Beneficiaries: Geographic Distribution of U.S. Dermatologist Prescribers
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.
Perturbations of the gut fungal and bacterial microbiome with biologic therapy in spondyloarthritis [Meeting Abstract]
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
Vascular endothelial and inflammatory differences in psoriasis and psoriatic arthritis patients [Meeting Abstract]
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
Inflammasome signaling and impaired vascular health in psoriasis [Meeting Abstract]
Early Recognition and Treatment Heralds Optimal Outcomes: the Benefits of Combined Rheumatology-Dermatology Clinics and Integrative Care of Psoriasis and Psoriatic Arthritis Patients
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.
Prevalence of Depression and Attention Deficit Hyperactivity Disorder in Female Patients at a Combined Psoriasis-Psoriatic Arthritis Center [Meeting Abstract]
Cutaneous microbiota features distinguish psoriasis from psoriatic arthritis [Meeting Abstract]
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
IgA vasculitis (Henoch-Schonlein purpura)
We report the first case of direct immunoflourescence-proven immunoglobulin A (IgA) vasculitis associated with influenza infection in an adult patient. IgA vasculitis, which was previously known as Henoch-Schonlein purpura, is the most common systemic vasculitis in children but rarely occurs in adults. Disease onset often occurs after upper respiratory tract infections that are caused by adenovirus or enterovirus. The American College of Rheumatology defines IgA vasculitis by the presence of any two of the following four criteria: age = 20 years at disease onset, palpable purpura, acute abdominal pain, and a biopsy specimen that shows granulocytes in the walls of small arterioles or venules. Purpura, abdominal pain, and arthralgia comprise the classic triad. Renal involvement may be severe, especially in adults. Treatment is most often supportive but glucocorticoids and/or immunosuppressive agents are recommended in severe or refractory cases.
Vesicular erythema migrans: an atypical and easily misdiagnosed form of Lyme disease
Erythema migrans is the initial sign in the majority of patients infected with Borrelia, the genus of spirochetes that causes Lyme disease. Early identification and treatment decrease the risk of progression to later stages of disease. Although a "bull's eye" appearance owing to lesional clearing is considered classic for erythema migrans, this feature is surprisingly often lacking among patients in the United States. Furthermore, cutaneous Lyme disease can exhibit a wide range of morphologic variability in a minority of patients. Herein, we describe the case of a patient with Lyme disease in which the presence of atypical vesicular features, in conjunction with the initial absence of clearing, resulted in multiple misdiagnoses and delayed treatment. We also review the literature on the epidemiology and management of erythema migrans for cases in which the diagnosis may pose a challenge.