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Psoriasis: HELP
Articles by Kevin D. Cooper
Based on 17 articles published since 2010
(Why 17 articles?)
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Between 2010 and 2020, K. Cooper wrote the following 17 articles about Psoriasis.
 
+ Citations + Abstracts
1 Review From the Medical Board of the National Psoriasis Foundation: Treatment targets for plaque psoriasis. 2017

Armstrong, April W / Siegel, Michael P / Bagel, Jerry / Boh, Erin E / Buell, Megan / Cooper, Kevin D / Callis Duffin, Kristina / Eichenfield, Lawrence F / Garg, Amit / Gelfand, Joel M / Gottlieb, Alice B / Koo, John Y M / Korman, Neil J / Krueger, Gerald G / Lebwohl, Mark G / Leonardi, Craig L / Mandelin, Arthur M / Menter, M Alan / Merola, Joseph F / Pariser, David M / Prussick, Ronald B / Ryan, Caitriona / Shah, Kara N / Weinberg, Jeffrey M / Williams, MaryJane O U / Wu, Jashin J / Yamauchi, Paul S / Van Voorhees, Abby S. ·Keck School of Medicine, University of Southern California, Los Angeles, California. Electronic address: aprilarmstrong@post.harvard.edu. · National Psoriasis Foundation, Portland, Oregon. · Windsor Dermatology, East Windsor, New Jersey; University Medical Center of Princeton at Plainsboro, Plainsboro, New Jersey. · Tulane University School of Medicine, New Orleans, Louisiana. · University Hospitals Case Medical Center, Cleveland, Ohio. · University of Utah School of Medicine, Salt Lake City, Utah. · University of California, San Diego School of Medicine, La Jolla, California. · Northwell Health and Hofstra North Shore University Hospital, Long Island Jewish Medical Center School of Medicine, Manhasset, New York. · University of Pennsylvania, Philadelphia, Pennsylvania. · Tufts University School of Medicine, Boston, Massachusetts. · University of California San Francisco Medical Center, San Francisco, California. · Icahn School of Medicine at Mount Sinai, New York, New York. · St Louis University Medical School, St Louis, Missouri. · Northwestern University Feinberg School of Medicine, Chicago, Illinois. · Baylor University Medical Center and Texas A&M Health Science Center, Dallas, Texas. · Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts. · Eastern Virginia Medical School, Norfolk, Virginia; Virginia Clinical Research Inc, Norfolk, Virginia. · George Washington University, Washington, District of Columbia. · Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio. · Keck School of Medicine, University of Southern California, Los Angeles, California. · Kaiser Permanente Los Angeles Medical Center, Los Angeles, California. · Division of Dermatology, David Geffen School of Medicine at University of California Los Angeles, Los Angeles, California. · Eastern Virginia Medical School, Norfolk, Virginia. ·J Am Acad Dermatol · Pubmed #27908543.

ABSTRACT: BACKGROUND: An urgent need exists in the United States to establish treatment goals in psoriasis. OBJECTIVE: We aim to establish defined treatment targets toward which clinicians and patients with psoriasis can strive to inform treatment decisions, reduce disease burden, and improve outcomes in practice. METHODS: The National Psoriasis Foundation conducted a consensus-building study among psoriasis experts using the Delphi method. The process consisted of: (1) literature review, (2) pre-Delphi question selection and input from general dermatologists and patients, and (3) 4 Delphi rounds. RESULTS: A total of 25 psoriasis experts participated in the Delphi process. The most preferred instrument was body surface area (BSA). The most preferred time for evaluating patient response after starting new therapies was at 3 months. The acceptable response at 3 months postinitiation was either BSA 3% or less or BSA improvement 75% or more from baseline. The target response at 3 months postinitiation was BSA 1% or less. During the maintenance period, evaluation every 6 months was most preferred. The target response at every 6 months maintenance evaluation is BSA 1% or less. LIMITATIONS: Although BSA is feasible in practice, it does not encompass health-related quality of life, costs, and risks of side effects. CONCLUSION: With defined treatment targets, clinicians and patients can regularly evaluate treatment responses and perform benefit-risk assessments of therapeutic options individualized to the patient.

2 Review Phototherapy-related ophthalmologic disorders. 2015

DePry, Jennifer / Brescoll, Jennifer / Szczotka-Flynn, Loretta / Rambhatla, Pranita / Lim, Henry W / Cooper, Kevin. ·Department of Dermatology University Hospitals Case Medical Center and Case Western Reserve University School of Medicine, Cleveland, OH. Electronic address: Jennifer.depry@uhhospitals.org. · Wayne State University School of Medicine, Detroit, MI. · Department of Ophthalmology & Visual Sciences Case Western Reserve University School of Medicine; University Hospitals Eye Institute, University Hospitals Case Medical Center, Cleveland, OH. · Department of Dermatology, Henry Ford Hospital, Detroit, MI. · Department of Dermatology University Hospitals Case Medical Center and Case Western Reserve University School of Medicine, Cleveland, OH; Louis Stokes VA Medical Center, Cleveland, OH. ·Clin Dermatol · Pubmed #25704945.

ABSTRACT: Phototherapy is an effective treatment option for a variety of dermatologic disorders, and the list of indications for its use continues to grow with advances in technology and our understanding of disease processes. Commonly used types of phototherapy include PUVA, broadband UVB, narrowband UVB, photodynamic therapy, and intense pulsed light therapy. Each therapeutic modality can have adverse acute and chronic effects on periocular and ocular structures, including the conjunctiva, cornea, crystalline lens, and retina. There are many types of protective eyewear options available, including goggles and contact lenses that can be used to prevent damage to ocular structures during phototherapy, particularly if eyelid closure is incomplete.

3 Clinical Trial Does imiquimod pretreatment optimize 308-nm excimer laser (UVB) therapy in psoriasis patients? 2017

Tacastacas, Joselin D / Oyetakin-White, Patricia / Soler, David C / Young, Andrew / Groft, Sarah / Honda, Kord / Cooper, Kevin D / McCormick, Thomas S. ·Department of Dermatology, Case Western Reserve University, University Hospitals Cleveland Medical Center, Cleveland, OH, USA. ·Photodermatol Photoimmunol Photomed · Pubmed #28168735.

ABSTRACT: BACKGROUND/PURPOSE: Psoriasis continues to be a debilitating skin disease affecting 1-3% of the United States population. Although the effectiveness of several current biologic therapies have described this pathology as a IL-23, TNF-a and Th17-mediated disease, less invasive approaches are still in use and in need of refinement. One of these is the usage of narrow band-UVB (NB-UVB) therapy to deplete specifically intra-epidermal CD3+, CD4+ and CD8+ cells to clear psoriatic plaques. AIMS/OBJECTIVES: In order to improve NB-UVB therapy, we sought to determine whether skin pre-treatment with the TLR7 agonist imiquimod (IMQ) would help increase the efficiency of the former at resolving psoriatic plaques. MATERIALS AND METHODS: Eucerin RESULTS: Our results suggests that although IMQ seemed to activate the type I interferon pathway as previously described, its concomitant usage with NB-UVB for clearing psoriatic skin was ineffective. Although upregulation of genes MxA, GRAMD1A and DMXL2 suggested that IMQ treatment did induce skin changes in psoriasis patients, more optimal dosing of IMQ and NB-UVB might be necessary to achieve desired treatment responses. CONCLUSION: The observation that psoriasis involvement was not aggravated by usage of topical IMQ was encouraging. Additional observational studies might be necessary to further tailor the combination of IMQ with NB-UVB therapy to reliably improve the psoriatic pathology.

4 Clinical Trial Single administration of lesion-limited high-dose (TURBO) ultraviolet B using the excimer laser: clinical clearing in association with apoptosis of epidermal and dermal T cell subsets in psoriasis. 2012

Kagen, Mark / Cao, Lauren Y / Oyetakin-White, Patricia / Tacastacas, Joselin D / Yan, Chunlin / McCormick, Thomas S / Cooper, Kevin D. ·Department of Dermatology, University Hospitals Case Medical Center, Cleveland, OH 44106-5028, USA. ·Photodermatol Photoimmunol Photomed · Pubmed #23126290.

ABSTRACT: BACKGROUND/PURPOSE: Development of effective therapy for psoriasis is confounded by numerous factors contributing to disease pathogenesis, including pathogenic immunocytes which appear to drive epidermal keratinocyte hyperproliferation. Our objective was to study clinical and biomarker effects of a single dose of TURBO laser UVB (308 nm) applied directly to psoriatic plaques. METHODS: Eighteen patients with chronic plaque psoriasis received a single dose of 10 minimal erythema dose (MED) UVB and were followed for 8 weeks. Keratome and punch biopsies were assessed for T cell depletion and apoptosis following a single 308-nm dose of UVB. RESULTS: Patients demonstrated clinical improvement as indicated by decreased global Psoriasis Area and Severity Index scores and reduced numbers of pathogenic memory/effector T cells infiltrating lesional epidermis and dermis. Consistent with apoptosis induction, caspase activation increased in lesional T cells after treatment. CONCLUSION: We conclude that a single 10 MED dose of TURBO UVB is effective at reducing the severity and extent of psoriatic lesions. We hypothesize that the reason a single treatment is sufficient to clear a psoriatic plaque is that the 10 MED dose is able to deliver sufficient photons to a microanatomic area of the lesion where susceptible pathogenic T cell mechanisms are operative.

5 Clinical Trial Positive treatment effects of ustekinumab in psoriasis: analysis of lesional and systemic parameters. 2010

Reddy, Manjula / Torres, Gisela / McCormick, Thomas / Marano, Colleen / Cooper, Kevin / Yeilding, Newman / Wang, Yuhua / Pendley, Charles / Prabhakar, Uma / Wong, Jackson / Davis, Cuc / Xu, Stephen / Brodmerkel, Carrie. ·Department of Oncology Biomarkers, Ortho Biotech, Unit of Centocor R&D, Malvern, PA, USA. ·J Dermatol · Pubmed #20536646.

ABSTRACT: Ustekinumab, a human anti-interleukin (IL)-12/IL-23p40 monoclonal antibody has demonstrated significant efficacy in patients with moderate-to-severe psoriasis. Skin lesion biopsies, cell surface markers on peripheral blood lymphocytes, and ex vivo T-helper (Th)1/Th2 cytokine responses from peripheral blood mononuclear cells (PBMC) from patients receiving ustekinumab 45 or 90 mg, or placebo were evaluated at baseline and week 12. Inflammatory serum protein levels were measured at baseline, week 2 and week 12. At week 12, median epidermal thickness decreased from 312.1 to 132.7 microm, and median levels of cellular proliferation (Ki67) and T-cell infiltration (CD3) decreased by 84.3% and 70.7%, respectively, in the combined ustekinumab group (all P < or = 0.002). Serum levels of tumor necrosis factor (TNF)-alpha, C-C motif ligand 27 (CCL27) and other inflammatory cytokines remained unchanged. Minimal variation in the percentage of T cells expressing cutaneous lymphocyte antigen (CLA) was observed following ustekinumab treatment, with no significant variation in the percentage of cells expressing CD45RA, CD45RO, CD25, human leukocyte antigen-DR (HLA-DR), and C-X-C motif receptor 3 (CXCR3). No apparent effect on the magnitude of Th1/Th2 responses to external stimuli in PBMC was observed following placebo or ustekinumab treatment. Ustekinumab improves histological psoriasis measures, with minimal impact on the systemic immune system.

6 Article Psoriasis and Psoriatic Arthritis Cardiovascular Disease Endotypes Identified by Red Blood Cell Distribution Width and Mean Platelet Volume. 2020

Conic, Rosalynn Rz / Damiani, Giovanni / Schrom, Kory P / Ramser, Amy E / Zheng, Chunlei / Xu, Rong / McCormick, Thomas S / Cooper, Kevin D. ·Department of Dermatology, Case Western Reserve University, Cleveland, OH 44106, USA. · Department of Dermatology, University Hospitals, Cleveland Medical Center, Cleveland, OH 44106, USA. · Clinical Dermatology, IRCCS Istituto Ortopedico Galeazzi, 20161 Milan, Italy. · Department of Biomedical, Surgical and Dental Sciences, University of Milan, 20161 Milan, Italy. · Department of Population and Quantitative Health Sciences, Case Western Reserve University, 44106 Cleveland, OH, USA. · Department of Dermatology, Veteran's Administration Medical Center, Cleveland, OH 44106, USA. ·J Clin Med · Pubmed #31936662.

ABSTRACT: In a subset of psoriasis (PsO) and psoriatic arthritis (PsA) patients, the skin and/or joint lesions appear to generate biologically significant systemic inflammation. Red cell distribution width (RDW) and mean platelet volume (MPV) are readily available clinical tests that reflect responses of the bone marrow and/or plasma thrombogenicity (e.g., inflammation), and can be markers for major adverse cardiac events (MACE). We aimed to evaluate if RDW and MPV may be employed as inexpensive, routinely obtained biomarkers in predicting myocardial infarction (MI), atrial fibrillation (AF), and chronic heart failure (CHF) in psoriatic and psoriatic arthritis patients. The study was divided into two parts: (a) case control study employing big data (Explorys) to assess MPV and RDW in psoriasis, psoriatic arthritis and control cohorts; (b) a clinical observational study to validate the predictive value of RDW and to evaluate RDW response to anti-psoriatic therapies. We used Explorys, an aggregate electronic database, to identify psoriatic patients with available MPV and RDW data and compared them to gender and age matched controls. The incidence of myocardial infarction (MI), atrial fibrillation (AF), and chronic heart failure (CHF) was highest among patients with both elevated RDW and MPV, followed by patients with high RDW and normal MPV. RDW elevation among PsA patients was associated with an increased risk of MI, AF, and CHF. In a local clinical cohort, high RDWs were concentrated in a subset of patients who also had elevated circulating resistin levels. Among a small subset of participants who were treated with various systemic and biologic therapies, and observed over a year, and in whom RDW was elevated at baseline, a sustained response to therapy was associated with a decrease in RDW. RDW and MPV, tests commonly contained within routine complete blood count (CBC), may be a cost-effective manner to identify PsO and PsA patients at increased risk of MACE.

7 Article Phenotypical analysis of ectoenzymes CD39/CD73 and adenosine receptor 2A in CD4 2018

Han, Ling / Sugiyama, Hideaki / Zhang, Qi / Yan, Kexiang / Fang, Xu / McCormick, Thomas S / Cooper, Kevin D / Huang, Qiong. ·Department of Dermatology, Huashan Hospital, Shanghai, China. · Department of Dermatology, Case Western Reserve University, Cleveland, Ohio, USA. · Department of Dermatology, Seirei Yokohama General Hospital, Yokohama, Japan. · The Murdough Family Center for Psoriasis, University Hospital Case Medical Center, Cleveland, Ohio, USA. ·Australas J Dermatol · Pubmed #28295154.

ABSTRACT: BACKGROUND: CD39 and CD73 are two novel cell surface markers of CD25 METHODS: Peripheral blood mononuclear cells (PMBC) were prepared from patients with three different types of psoriasis (psoriasis vulgaris, pustular psoriasis and erythrodermic psoriasis). CD4 RESULTS: The expression of single CD73 CONCLUSIONS: The differences in the expression of CD39

8 Article Combining mechanism-based prediction with patient-based profiling for psoriasis metabolomics biomarker discovery. 2017

Wang, QuanQiu / McCormick, Thomas S / Ward, Nicole L / Cooper, Kevin D / Conic, Ruzica / Xu, Rong. ·ThinTek, LLC, Palo Alto, CA, USA. · Department of Dermatology, School of Medicine, Case Western Reserve University, Cleveland, OH, USA. · Department of Epidemiology and Biostatistics, Institute of Computational Biology, School of Medicine, Case Western Reserve University, Cleveland, OH, USA. ·AMIA Annu Symp Proc · Pubmed #29854244.

ABSTRACT: Psoriasis is a chronic, debilitating skin condition that affects approximately 125 million individuals worldwide. The cause of psoriasis appears multifactorial, and no unified mitigating signal or single antigenic target has been identified to date. Metabolomic studies hold great potential for explaining disease mechanism, facilitating early diagnosis, and identifying potential therapeutic areas. Here, we present an integrated disease metabolomic biomarker discovery strategy that combines mechanism-based biomarker discovery with clinical sample-based metabolomic profiling. We applied this strategy in identifying and understanding metabolite biomarkers for psoriasis. The key innovation of our strategy is a novel mechanism-based metabolite prediction system, mmPredict, which assimilates vast amounts of existing knowledge of diseases and metabolites. mmPredict first constructed a psoriasis-specific mouse mutational phenotype profile. It then constructed phenotype profiles for a total of 259,170 chemicals/metabolites using known chemical genetics and human metabolomic data. Metabolites were then prioritized based on the phenotypic similarities between disease- and metabolites. We evaluated mmPredict using 150 metabolites identified using our in-house metabolome profiling study of psoriasis patient samples. mmPredict found 96 of the 150 metabolites and ranked them highly (recall: 0.64, mean ranking: 8.73%, median ranking: 2.33%, p-value: 4.75E-44). These results show that mmPredict is consistent with, as well as a complement to, traditional human metabolomic profiling studies. We then developed a strategy to combine outputs from both systems and found that the oxidative product of linoleic acid, 13(S)-hydroxy-9Z,11E-octadecadienoic acid (13- HODE), ranked highly by both mmPredict and our in-house experiments. Our integrated analysis indicates that 13- HODE may be a mechanistic link between psoriasis and cardiovascular comorbidities associated with psoriasis. In summary, we developed an integrated metabolomic prediction system that combines both human metabolomic studies and mechanism-based prediction and demonstrated its application in the skin disease psoriasis. Our system is highly general and can be applied to other diseases when patient-based metabolomic profiling data becomes more increasingly available. Data is publicly available at: http://nlp. CASE: edu/public/data/mmPredict_PSO.

9 Article Feasibility of carotid artery PET/MRI in psoriasis patients. 2016

Rajiah, Prabhakar / Hojjati, Mojgan / Lu, Ziang / Kosaraju, Vijaya / Partovi, Sasan / O'Donnell, James K / Longenecker, Christopher / McComsey, Grace A / Golden, Jackelyn B / Muakkassa, Fuad / Santilli, Scott / McCormick, Thomas S / Cooper, Kevin D / Korman, Neil J. ·Department of Radiology, University Hospital Cleveland Case Medical Center, Case Western Reserve University School of MedicineCleveland, Ohio, United States; Department of Radiology, Cardiothoracic Imaging, UT Southwestern Medical CenterDallas, Texas, United States. · Department of Radiology, University Hospital Cleveland Case Medical Center, Case Western Reserve University School of Medicine Cleveland, Ohio, United States. · Department of Cardiology, University Hospital Cleveland Case Medical Center, Case Western Reserve University School of Medicine Cleveland, Ohio, United States. · Department of Pediatrics and Medicine, University Hospital Cleveland Case Medical Center, Case Western Reserve University School of Medicine Cleveland, Ohio, United States. · Department of Dermatology, University Hospital Cleveland Case Medical Center, Case Western Reserve University School of Medicine Cleveland, Ohio, United States. ·Am J Nucl Med Mol Imaging · Pubmed #27648374.

ABSTRACT: We report our initial experience of performing integrated PET/MR imaging of the carotid arteries in psoriatic patients. Eleven patients with psoriasis and ten controls underwent carotid PET/MRI. Following injection of the FDG tracer, 3d T1w gradient echo sequence (atMR) was obtained for attenuation correction of PET data. High resolution images of carotid artery were then obtained, including pre-and post-contrast T1-w, T2-w and proton-density images as well as TOF images followed by PET imaging of the torso. From the fused axial PET/MRI, the arterial wall SUVmax and TBRmax was quantified in each slice. MRI images were also evaluated for vessel wall volume, plaque and internal composition. SUVmax and TBRmax were respectively, 1.72 ± 0.38 & 1.17 ± 0.27 in L- CCA, 1.75 ± 0.39 & 1.24 ± 0.19 in R-CCA, 1.59 ± 0.24 & 1.08 ± 0.14 in L-ICA and 1.62 ± 0.27 & 1.15 ± 0.17 in R-ICA in psoriatic patients and 1.74 ± 0.22 & 1.28 ± 0.44 in L- CCA, 1.74 ± 0.33 & 1.07 ± 0.28 in R-CCA, 1.78 ± 0.32 & 1.29 ± 0.39 in L-ICA and 1.60 ± 0.29 & 0.98 ± 0.25 in R-ICA in the controls. No discrete plaques were identified in any of the vessel segments in MRI. PET/MRI is feasible in evaluation of carotid arteries in psoriatic patients.

10 Article Visualization of atherosclerosis as detected by coronary artery calcium and carotid intima-media thickness reveals significant atherosclerosis in a cross-sectional study of psoriasis patients in a tertiary care center. 2016

Santilli, S / Kast, D R / Grozdev, I / Cao, L / Feig, R L / Golden, J B / Debanne, S M / Gilkeson, R C / Orringer, C E / McCormick, T S / Ward, N L / Cooper, K D / Korman, N J. ·Department of Dermatology, University Hospitals Case Medical Center, 11000 Euclid Ave, Cleveland, OH, 44106, USA. · The Murdough Family Center for Psoriasis, Cleveland, USA. · Department of Pathology, Case Western Reserve University, Cleveland, USA. · Center For Clinical Investigation, Case Western Reserve University, Cleveland, USA. · Department of Epidemiology and Biostatistics, Case Western Reserve University, Cleveland, USA. · University of Miami, Miller School of Medicine, Miami, FL, 33125, USA. · Department of Dermatology, University Hospitals Case Medical Center, 11000 Euclid Ave, Cleveland, OH, 44106, USA. tsm4@case.edu. · The Murdough Family Center for Psoriasis, Cleveland, USA. tsm4@case.edu. · Louis Stokes VA Medical Center, Cleveland, OH, USA. ·J Transl Med · Pubmed #27448600.

ABSTRACT: BACKGROUND: Psoriasis is a chronic inflammatory disease of the skin and joints that may also have systemic inflammatory effects, including the development of cardiovascular disease (CVD). Multiple epidemiologic studies have demonstrated increased rates of CVD in psoriasis patients, although a causal link has not been established. A growing body of evidence suggests that sub-clinical systemic inflammation may develop in psoriasis patients, even from a young age. We aimed to evaluate the prevalence of atherosclerosis and identify specific clinical risk factors associated with early vascular inflammation. METHODS: We conducted a cross-sectional study of a tertiary care cohort of psoriasis patients using coronary artery calcium (CAC) score and carotid intima-media thickness (CIMT) to detect atherosclerosis, along with high sensitivity C-reactive protein (hsCRP) to measure inflammation. Psoriasis patients and controls were recruited from our tertiary care dermatology clinic. Presence of atherosclerosis was defined using validated numeric values within CAC and CIMT imaging. Descriptive data comparing groups was analyzed using Welch's t test and Pearson Chi square tests. Logistic regression was used to analyze clinical factors associated with atherosclerosis, and linear regression to evaluate the relationship between psoriasis and hsCRP. RESULTS: 296 patients were enrolled, with 283 (207 psoriatic and 76 controls) having all data for the hsCRP and atherosclerosis analysis. Atherosclerosis was found in 67.6 % of psoriasis subjects versus 52.6 % of controls; Psoriasis patients were found to have a 2.67-fold higher odds of having atherosclerosis compared to controls [95 % CI (1.2, 5.92); p = 0.016], after adjusting for age, gender, race, BMI, smoking, HDL and hsCRP. In addition, a non-significant trend was found between HsCRP and psoriasis severity, as measured by PASI, PGA, or BSA, again after adjusting for confounders. CONCLUSIONS: A tertiary care cohort of psoriasis patients have a high prevalence of early atherosclerosis, increased hsCRP, and psoriasis remains a risk factor for the presence of atherosclerosis even after adjustment of key confounding clinical factors. Psoriasis may contribute to an accelerated systemic inflammatory cascade resulting in increased risk of CVD and CV events.

11 Article Increased, but Functionally Impaired, CD14(+) HLA-DR(-/low) Myeloid-Derived Suppressor Cells in Psoriasis: A Mechanism of Dysregulated T Cells. 2016

Soler, David C / Young, Andrew B / Fiessinger, Lori / Galimberti, Fabrizio / Debanne, Sara / Groft, Sarah / McCormick, Thomas S / Cooper, Kevin D. ·Department of Dermatology, Case Western Reserve University, Cleveland, Ohio, USA. · Department of Epidemiology and Biostatistics, Case Western Reserve University, Cleveland, Ohio, USA. · Department of Dermatology, Case Western Reserve University, Cleveland, Ohio, USA; The Murdough Family Center for Psoriasis, Cleveland, Ohio, USA. · Department of Dermatology, Case Western Reserve University, Cleveland, Ohio, USA; The Murdough Family Center for Psoriasis, Cleveland, Ohio, USA; University Hospitals Case Medical Center and VA Medical Center, Cleveland, Ohio, USA. Electronic address: kdc@case.edu. ·J Invest Dermatol · Pubmed #26807516.

ABSTRACT: The clinical extent of psoriasis pathology is regulated in part by defects in immune networks, including a defect in the suppressive actions of regulatory T cells. Recently, CD14(+) HLA-DR(-/low) monocytic myeloid-derived suppressor cells (Mo-MDSCs) have been shown to suppress T-cell activation as one of their suppressive mechanisms. However, little is known about the role of Mo-MDSCs and their functional relationship to T-cell suppression in relation to human chronic immune-mediated inflammatory diseases, including psoriasis. Despite psoriasis being a hyperinflammatory condition, Mo-MDSCs were elevated in psoriatic patient peripheral blood mononuclear cells compared to nonpsoriatic healthy controls (2.6% vs. 0.9%, P < 0.002). Freshly isolated psoriatic Mo-MDSCs directly suppressed CD8 T-cell proliferation less efficiently than healthy control Mo-MDSCs. In addition, psoriatic Mo-MDSCs expressed reduced surface expression of programmed cell death protein 1 compared to healthy controls. Additional in vitro assays also demonstrated that psoriatic and control Mo-MDSCs both induce regulatory T-cell conversion from naïve T effector cells, but, importantly, the regulatory T cells induced by psoriatic Mo-MDSCs displayed decreased suppressive functionality. These results suggest that aberrations in psoriatic Mo-MDSCs prevent proper suppression of effector T-cell expansion and hamper the immune system's ability to correctly self-regulate.

12 Article Chronic Psoriatic Skin Inflammation Leads to Increased Monocyte Adhesion and Aggregation. 2015

Golden, Jackelyn B / Groft, Sarah G / Squeri, Michael V / Debanne, Sara M / Ward, Nicole L / McCormick, Thomas S / Cooper, Kevin D. ·Department of Dermatology, Case Western Reserve University, Cleveland, OH 44106; Department of Pathology, Case Western Reserve University, Cleveland, OH 44106; · Department of Dermatology, Case Western Reserve University, Cleveland, OH 44106; · Department of Epidemiology and Biostatistics, Case Western Reserve University, Cleveland, OH 44106; · Department of Dermatology, Case Western Reserve University, Cleveland, OH 44106; Murdough Family Center for Psoriasis, Cleveland, OH 44106; University Hospitals Case Medical Center, Cleveland, OH 44106; and. · Department of Dermatology, Case Western Reserve University, Cleveland, OH 44106; Department of Pathology, Case Western Reserve University, Cleveland, OH 44106; Murdough Family Center for Psoriasis, Cleveland, OH 44106; University Hospitals Case Medical Center, Cleveland, OH 44106; and Veterans Affairs Medical Center, Cleveland, OH 44106 kdc@case.edu. ·J Immunol · Pubmed #26223654.

ABSTRACT: Psoriasis patients exhibit an increased risk of death by cardiovascular disease (CVD) and have elevated levels of circulating intermediate (CD14(++)CD16(+)) monocytes. This elevation could represent evidence of monocyte dysfunction in psoriasis patients at risk for CVD, as increases in circulating CD14(++)CD16(+) monocytes are predictive of myocardial infarction and death. An elevation in the CD14(++)CD16(+) cell population has been previously reported in patients with psoriatic disease, which has been confirmed in the cohort of our human psoriasis patients. CD16 expression was induced in CD14(++)CD16(-) classical monocytes following plastic adhesion, which also elicited enhanced β2 but not β1 integrin surface expression, suggesting increased adhesive capacity. Indeed, we found that psoriasis patients have increased monocyte aggregation among circulating PBMCs, which is recapitulated in the KC-Tie2 murine model of psoriasis. Visualization of human monocyte aggregates using imaging cytometry revealed that classical (CD14(++)CD16(-)) monocytes are the predominant cell type participating in these aggregate pairs. Many of these pairs also included CD16(+) monocytes, which could account for apparent elevations of intermediate monocytes. Additionally, intermediate monocytes and monocyte aggregates were the predominant cell type to adhere to TNF-α- and IL-17A-stimulated dermal endothelium. Ingenuity Pathway Analysis demonstrated that monocyte aggregates have a distinct transcriptional profile from singlet monocytes and monocytes following plastic adhesion, suggesting that circulating monocyte responses to aggregation are not fully accounted for by homotypic adhesion, and that further factors influence their functionality.

13 Article Psoriasis and cardiovascular risk factors: increased serum myeloperoxidase and corresponding immunocellular overexpression by Cd11b(+) CD68(+) macrophages in skin lesions. 2013

Cao, Lauren Y / Soler, David C / Debanne, Sarah M / Grozdev, Ivan / Rodriguez, Myriam E / Feig, Rivka L / Carman, Teresa L / Gilkeson, Robert C / Orringer, Carl E / Kern, Elizabeth F / McCormick, Thomas S / Cooper, Kevin D / Korman, Neil J. ·Murdough Family Center for Psoriasis, Department of Dermatology, University Hospitals Case Medical Center Cleveland, OH, USA ; Case Western Reserve University School of Medicine Cleveland, OH, USA. · Case Western Reserve University Division of Biostatistics Cleveland, OH, USA. · Murdough Family Center for Psoriasis, Department of Dermatology, University Hospitals Case Medical Center Cleveland, OH, USA. · Case Western Reserve University School of Medicine Cleveland, OH, USA ; Department of Vascular Medicine, University Hospitals Case Medical Center Cleveland, OH, USA. · Case Western Reserve University School of Medicine Cleveland, OH, USA ; Department of Radiology, University Hospitals Case Medical Center Cleveland, OH, USA. · Case Western Reserve University School of Medicine Cleveland, OH, USA ; Department of Cardiology, University Hospitals Case Medical Center Cleveland, OH, USA. · Case Western Reserve University School of Medicine Cleveland, OH, USA ; Department of Nephrology, University Hospitals Case Medical Center Cleveland, OH, USA. · Murdough Family Center for Psoriasis, Department of Dermatology, University Hospitals Case Medical Center Cleveland, OH, USA ; Case Western Reserve University School of Medicine Cleveland, OH, USA ; Department of Dermatology, Veterans Affairs Medical Center Cleveland, OH, USA. ·Am J Transl Res · Pubmed #24349618.

ABSTRACT: BACKGROUND: Recent studies report independent associations between psoriasis, cardiovascular (CV) events and risk factors. Blood Myeloperoxidase (MPO) from activated myeloid cells is associated with CV risk mainly through lipid oxidation, induction of endothelial dysfunction and release of IL-12 from macrophages. OBJECTIVES: To elucidate associations between psoriasis and conventional CV risk factors. METHODS: We performed a cross-sectional study of 100 psoriasis patients and 53 controls, group matched on age, gender and body mass index, to assess levels of MPO in serum, as well as immunohistochemical staining from psoriasis skin lesions, psoriasis uninvolved skin, and normal skin. RESULTS: Although the groups did not differ on waist circumference, glucose, cholesterol, triglycerides, creatinine or personal history of CV events, psoriasis patients had significantly higher waist-to-hip ratios, blood pressures, proportion of current smokers, and lower high density lipoprotein level than controls. Serum MPO level was elevated 2.5 fold (P<0.001) in psoriasis patients, even after adjusting for the CV risk factors on which the groups differed. MPO did correlate with coronary artery calcification, carotid plaque, carotid intima media thickness and flow mediated dilation, but did not correlate with psoriasis severity. However, MPO was highly expressed in lesional psoriatic skin and colocalized predominantly with CD45(+) CD11b(+) leukocytes. CD11b(+) cell density correlated with circulation MPO levels. CONCLUSION: Lesional skin CD11b(+) leukocytes activated to generate MPO may contribute to serum levels of MPO. Lesional CD11b(+) cell activity may be an alternative measure of disease burden to PASI that underlies the MPO biomarker for systemic inflammation related to Cardiovascular Disease.

14 Article Psoriasis patients exhibit impairment of the high potency CCR5(+) T regulatory cell subset. 2013

Soler, David C / Sugiyama, Hideaki / Young, Andrew B / Massari, Jessica V / McCormick, Thomas S / Cooper, Kevin D. ·Department of Dermatology, Case Western Reserve University, Cleveland, OH 44106, USA; The Murdough Family Center for Psoriasis, University Hospitals Case Medical Center, Cleveland, OH 44106, USA. ·Clin Immunol · Pubmed #23954573.

ABSTRACT: CCR5 expression on CD4(+)CD25(high)Foxp3(+) regulatory T cells (Tregs) has been reported to be crucial for limiting Th1 inflammation associated with autoimmunity and bacterial infections. We inquired whether abnormalities in chemokine receptors expressed on Tregs might be involved in the psoriatic pathogenesis. Indeed, the proportion of CCR5(+) Treg was 58.8% in healthy individuals (n=9), whereas only half as many CCR5(+) Treg cells were found in psoriatic individuals (29.1%, n=8, p<0.01). The flow-enriched control CCR5(+) Tregs consistently exceeded the suppressive capacity of unsorted Tregs in autologous MLR assays (n=5, p<0.05) showing that CCR5(+) Treg subset is a high potency regulatory T cell population. Interestingly, psoriatic CCR5(+) Treg cells exhibited significantly less migratory capacity toward CCR5 ligands MIP-1β and RANTES in vitro compared to CCR5(+) Treg controls (n=3, p<0.05). Our data demonstrate that psoriatic CCR5(+) Tregs cells are numerically-, functionally- and chemotactically-deficient compared to controls and may pose a triple impairment on the ability of psoriatic Tregs to restrain inflammation.

15 Article Chronic skin-specific inflammation promotes vascular inflammation and thrombosis. 2012

Wang, Yunmei / Gao, Huiyun / Loyd, Candace M / Fu, Wen / Diaconu, Doina / Liu, Shijian / Cooper, Kevin D / McCormick, Thomas S / Simon, Daniel I / Ward, Nicole L. ·Department of Medicine, Division of Cardiovascular Medicine, Case Western Reserve University, Cleveland, Ohio 44106, USA. ·J Invest Dermatol · Pubmed #22572815.

ABSTRACT: Patients with psoriasis have systemic and vascular inflammation and are at increased risk for myocardial infarction, stroke, and cardiovascular death. However, the underlying mechanism(s) mediating the link between psoriasis and vascular disease is incompletely defined. This study sought to determine whether chronic skin-specific inflammation has the capacity to promote vascular inflammation and thrombosis. Using the KC-Tie2 doxycycline-repressible (Dox-off) murine model of psoriasiform skin disease, spontaneous aortic root inflammation was observed in 33% of KC-Tie2 compared with 0% of control mice by 12 months of age (P=0.04) and was characterized by the accumulation of macrophages, T lymphocytes, and B lymphocytes, as well as by reduced collagen content and increased elastin breaks. Importantly, aortic inflammation was preceded by increases in serum tumor necrosis factor-α, IL-17A, vascular endothelial growth factor, IL-12, monocyte chemotactic protein-1, and S100A8/A9, as well as splenic and circulating CD11b(+)Ly-6C(hi) pro-inflammatory monocytes. Doxycycline treatment of old mice with severe skin disease eliminated skin inflammation and the presence of aortic root lesion in 1-year-old KC-Tie2 animals. Given the bidirectional link between inflammation and thrombosis, arterial thrombosis was assessed in KC-Tie2 and control mice; mean time to occlusive thrombus formation was shortened by 64% (P=0.002) in KC-Tie2 animals; and doxycycline treatment returned thrombosis clotting times to that of control mice (P=0.69). These findings demonstrate that sustained skin-specific inflammation promotes aortic root inflammation and thrombosis and suggest that aggressive treatment of skin inflammation may attenuate pro-inflammatory and pro-thrombotic pathways that produce cardiovascular disease in psoriasis patients.

16 Article Physical and mental impact of psoriasis severity as measured by the compact Short Form-12 Health Survey (SF-12) quality of life tool. 2012

Grozdev, Ivan / Kast, Douglas / Cao, Lauren / Carlson, Diana / Pujari, Prasad / Schmotzer, Brian / Babineau, Denise / Kern, Elizabeth / McCormick, Thomas / Cooper, Kevin D / Korman, Neil J. ·Department of Dermatology, Murdough Family Center for Psoriasis, University Hospitals Case Medical Center, Case Western Reserve University Cleveland, Cleveland, Ohio 44106, USA. ·J Invest Dermatol · Pubmed #22205305.

ABSTRACT: The Short Form-12 Health Survey (SF-12) is used to assess the patient's quality of life (QoL) using the physical component score (PCS) and the mental component score (MCS). The purpose of this study was to determine whether the SF-12 PCS and MCS are associated with psoriasis severity and to compare QoL between Murdough Family Center for Psoriasis (MFCP) patients and patients with other major chronic diseases included in the National Survey of Functional Health Status data. We used data from 429 adult patients enrolled in MFCP. Psoriasis Area Severity Index (PASI) was used to assess psoriasis severity at the time of completion of the SF-12 questionnaire. Other variables included age, sex, body mass index, psoriatic arthritis, psychiatric disorders, and comorbidities. Linear regression models were used to estimate effect sizes ± 95% confidence intervals. For every 10-point increase in PASI, there was a 1.1 ± 1.3 unit decrease in MCS (P=0.100) and a 2.4 ± 1.3 unit decrease in PCS (P<0.001). Psoriasis severity was associated with PCS and MCS after adjusting for variables, although the strength of the relationship was attenuated in some models. Psoriasis severity is associated with decreased QoL. SF-12 may be a useful tool for assessing QoL among psoriasis patients.

17 Unspecified Acute pustular eruption following a Jarisch-Herxheimer reaction in the treatment of syphilis. 2018

Giesey, Rachel L / Delost, Gregory R / Sharma, Timmie R / Cooper, Kevin D. ·Ohio University Heritage College of Osteopathic Medicine, Athens, Ohio. · Department of Dermatology, University Hospitals Cleveland Medical Center, Cleveland, Ohio. ·JAAD Case Rep · Pubmed #29687066.

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