Skin and Connective Tissue Diseases Commons^™

The Global Burden Of Scabies: A Cross-Sectional Analysis From The Global Burden Of Disease Study 2015., Chante Karimkhani, Danny V Colombara, Aaron M Drucker, Scott A Norton, Roderick Hay, Daniel Engelman, Andrew Steer, Margot Whitfeld, Mohsen Naghavi, Robert P Dellavalle

Daniel T. Engelman MD

Background

Numerous population-based studies have documented high prevalence of scabies in overcrowded settings, particularly among children and in tropical regions. We provide an estimate of the global burden of scabies using data from the Global Burden of Disease (GBD) Study 2015.

Methods

We identified scabies epidemiological data sources from an extensive literature search and hospital insurance data and analysed data sources with a Bayesian meta-regression modelling tool, DisMod-MR 2·1, to yield prevalence estimates. We combined prevalence estimates with a disability weight, measuring disfigurement, itch, and pain caused by scabies, to produce years lived with disability (YLDs). With an assumed zero …

Suppression Of Systemic Autoimmunity By The Innate Immune Adaptor Sting, Shrutie Sharma, Allison M. Campbell, Jennie Chan, Stefan A. Schattgen, Gregory M. Orlowski, Ribhu Nayar, Annie H. Huyler, Kerstin Nundel, Chandra Mohan, Leslie J. Berg, Mark J. Shlomchik, Ann Marshak-Rothstein, Katherine A. Fitzgerald

Katherine A. Fitzgerald

Cytosolic DNA-sensing pathways that signal via Stimulator of interferon genes (STING) mediate immunity to pathogens and also promote autoimmune pathology in DNaseII- and DNaseIII-deficient mice. In contrast, we report here that STING potently suppresses inflammation in a model of systemic lupus erythematosus (SLE). Lymphoid hypertrophy, autoantibody production, serum cytokine levels, and other indicators of immune activation were markedly increased in STING-deficient autoimmune-prone mice compared with STING-sufficient littermates. As a result, STING-deficient autoimmune-prone mice had significantly shorter lifespans than controls. Importantly, Toll-like receptor (TLR)-dependent systemic inflammation during 2,6,10,14-tetramethylpentadecane (TMPD)-mediated peritonitis was similarly aggravated in STING-deficient mice. Mechanistically, STING-deficient macrophages failed to …

Fungal Infections From Human And Animal Contact, Dennis J. Baumgardner

Dennis J. Baumgardner, MD

Fungal infections in humans resulting from human or animal contact are relatively uncommon, but they include a significant proportion of dermatophyte infections. Some of the most commonly encountered diseases of the integument are dermatomycoses. Human or animal contact may be the source of all types of tinea infections, occasional candidal infections, and some other types of superficial or deep fungal infections. This narrative review focuses on the epidemiology, clinical features, diagnosis and treatment of anthropophilic dermatophyte infections primarily found in North America. Other human-acquired and zoonotic fungal infections also are discussed in brief.

Toward The Global Control Of Human Scabies: Introducing The International Alliance For The Control Of Scabies, Daniel Engelman, Karen Kiang, Olivier Chosidow, James Mccarthy, Claire Fuller, Patrick Lammie, Roderick Hay, Andrew Steer

Daniel T. Engelman MD

Scabies, the human skin disease caused by infestation by the mite Sarcoptes scabiei var. hominis, causes considerable morbidity and mortality through direct effects and as a result of secondary bacterial infection. Scabies is a truly neglected disease, largely absent from the global health agenda, and its huge burden of disease is largely underappreciated. We contend that coordinated, global efforts to control this ubiquitous pathogenic mite are both important and achievable.

Stinging Nettle: The Bad, The Good, The Unknown, Dennis J. Baumgardner

Dennis J. Baumgardner, MD

Stinging nettle (Urtica dioica) is native to most of the United States. It has a characteristic description and distribution in the environment. Physical contact with numerous tiny needlelike hairs present on leaves and stems of this plant may result in a contact urticarial dermatitis due to chemical and mechanical irritation triggered by skin penetration of the hairs. The manifestations are self-limited in humans and may be treated by washing the skin, topical preparations and oral antihistamines. Explanation of the natural history of these encounters to the patient is helpful in reducing the sometimes significant anxiety. Preparations and extracts of stinging …

Golimumab In Patients With Active Rheumatoid Arthritis After Treatment With Tumor Necrosis Factor Inverted Question Mark Inhibitors: Findings With Up To Five Years Of Treatment In The Multicenter, Randomized, Double-Blind, Placebo-Controlled, Phase 3 Go-After Study, Josef S. Smolen, Jonathan Kay, Mittie Doyle, Robert Landewe, Eric L. Matteson, Norman Gaylis, Jurgen Wollenhaupt, Frederick T. Murphy, Stephen Xu, Yiying Zhou, Elizabeth C. Hsia

Jonathan Kay

Introduction: The aim of this study was to assess long-term golimumab therapy in rheumatoid arthritis (RA) patients who discontinued previous tumor necrosis factor- inverted question mark (TNF)-inhibitor(s). Methods:Patients enrolled into this multicenter, randomized, double-blind, placebo-controlled study of active RA ( inverted question mark4 tender, inverted question mark4 swollen joints) received placebo (Group 1) or golimumab 50 mg (Group 2) or 100 mg (Group 3) injections every 4 weeks. Patients in Groups 1 and 2 with inadequate response at week 16 escaped to golimumab 50 and 100 mg, respectively. At week 24, Group 1 patients crossed-over to golimumab 50 mg, Group …

Golimumab 3-Year Safety Update: An Analysis Of Pooled Data From The Long-Term Extensions Of Randomised, Double-Blind, Placebo-Controlled Trials Conducted In Patients With Rheumatoid Arthritis, Psoriatic Arthritis Or Ankylosing Spondylitis, Jonathan Kay, Roy Fleischmann, Edward Keystone, Elizabeth C. Hsia, Benjamin Hsu, Michael Mack, Neil Goldstein, Jurgen Braun, Arthur Kavanaugh

Jonathan Kay

OBJECTIVE: To assess pooled golimumab safety up to year 3 of rheumatoid arthritis (RA), psoriatic arthritis (PsA) and ankylosing spondylitis (AS) trials. METHODS: Golimumab 50 and 100 mg, administered subcutaneously (SC) every 4 weeks (q4wk), were assessed in patients with active RA (methotrexate-naive, methotrexate-experienced and anti-TNF (tumour necrosis factor)-experienced), PsA or AS, despite conventional therapy. Placebo control continued up to week (wk) 24 (wk 52, methotrexate-naive), with early escape at wk 16 (wk 28, methotrexate-naive); subsequently, all patients received golimumab 50 or 100 mg q4wk. After the blinded controlled period, golimumab doses could be adjusted per investigator discretion. Pooled safety …

Sarilumab For The Treatment Of Ankylosing Spondylitis: Results Of A Phase Ii, Randomised, Double-Blind, Placebo-Controlled Study (Align), Joachim Sieper, Jurgen Braun, Jonathan Kay, Salvatore Badalamenti, Allen R. Radin, Lixia Jiao, Stefano Fiore, Tanya Momtahen, George D. Yancopoulos, Neil Stahl, Robert D. Inman

Jonathan Kay

OBJECTIVES: The ALIGN study (NCT01061723) evaluated the efficacy and safety of sarilumab, the first fully human monoclonal antibody against interleukin-6 receptor-alpha (IL-6Ralpha), in patients with ankylosing spondylitis (AS). METHODS: Patients with active AS despite conventional treatment were randomised to placebo, or one of five subcutaneous dose regimens of sarilumab (100, 150 or 200 mg every other week, or 100 or 150 mg every week), for 12 weeks. The primary efficacy end point was the percentage of patients achieving the Axial SpondyloArthritis international Society (ASAS) 20 response criteria at week 12. Secondary endpoints included ASAS40 response, ASAS partial remission, AS Disease …

Detection Of Igg4-Specific Autoantibodies In Rheumatoid Arthritis Serum Samples, Azra Borogovac, Youmna Lahoud, Janice Weaver, Sheldon M. Cooper, Mercedes Rincon, Jonathan Kay, Ellen M. Gravallese

Ellen M. Gravallese

Background: Rheumatoid arthritis (RA) is a chronic multi-system autoimmune disease characterized by inflammatory synovitis. Autoantibodies such as rheumatoid factor (RF) and anti-citrullinated protein antibodies (ACPA) have been implicated in the pathogenesis of RA, and are currently important criteria for diagnosis within the 2010 American College of Rheumatology (ACR)/European League Against Rheumatism (EULAR) classification criteria.1 Yet, many patients diagnosed with RA do not have measurable circulating ACPA or RF which may result in delayed diagnosis and treatment. After IgG1, IgG4 is the second most predominant isotype among ACPA and RF; however it is not detected in currently available diagnostic assays. Recent …

Detection Of Igg4-Specific Autoantibodies In Rheumatoid Arthritis Serum Samples, Azra Borogovac, Youmna Lahoud, Janice Weaver, Sheldon M. Cooper, Mercedes Rincon, Jonathan Kay, Ellen M. Gravallese

Jonathan Kay

Background: Rheumatoid arthritis (RA) is a chronic multi-system autoimmune disease characterized by inflammatory synovitis. Autoantibodies such as rheumatoid factor (RF) and anti-citrullinated protein antibodies (ACPA) have been implicated in the pathogenesis of RA, and are currently important criteria for diagnosis within the 2010 American College of Rheumatology (ACR)/European League Against Rheumatism (EULAR) classification criteria.1 Yet, many patients diagnosed with RA do not have measurable circulating ACPA or RF which may result in delayed diagnosis and treatment. After IgG1, IgG4 is the second most predominant isotype among ACPA and RF; however it is not detected in currently available diagnostic assays. Recent …

Osteopontin: A Bridge Between Bone And The Immune System, Ellen M. Gravallese

Ellen M. Gravallese

The molecular mechanisms underlying the putative role of osteopontin in the chronic inflammatory disease rheumatoid arthritis are unclear. A study in a murine model of arthritis now demonstrates that a specific antibody directed against the exposed osteopontin epitope SLAYGLR is capable of preventing inflammatory cell infiltration in arthritic joints.

The Role Played By Cell-Substrate Interactions In The Pathogenesis Of Osteoclast-Mediated Peri-Implant Osteolysis, Zhenxin Shen, Tania N. Crotti, Kevin P. Mchugh, Kenichiro Matsuzaki, Ellen M. Gravallese, Benjamin E. Bierbaum, Steven R. Goldring

Ellen M. Gravallese

Prosthetic wear debris-induced peri-implant osteolysis is a major cause of aseptic loosening after total joint replacement. In this condition, wear particles released from the implant components induce a granulomatous inflammatory reaction at the interface between implant and adjacent bone, leading to progressive bone resorption and loss of fixation. The present study was undertaken to characterize definitively the phenotype of osteoclast-like cells associated with regions of peri-implant focal bone resorption and to compare the phenotypic features of these cells with those of mononucleated and multinucleated cells associated with polyethylene wear particles. Peri-implant tissues were obtained from patients undergoing hip revision surgery …

The Role Of Tnf-Receptor Family Members And Other Traf-Dependent Receptors In Bone Resorption, Ellen M. Gravallese, Deborah L. Galson, Steven R. Goldring, Philip E. Auron

Ellen M. Gravallese

The contribution of osteoclasts to the process of bone loss in inflammatory arthritis has recently been demonstrated. Studies in osteoclast biology have led to the identification of factors responsible for the differentiation and activation of osteoclasts, the most important of which is the receptor activator of NF-kappa B ligand/osteoclast differentiation factor (RANKL/ODF), a tumor necrosis factor (TNF)-like protein. The RANKL/ODF receptor, receptor activator of NF-kappa B (RANK), is a TNF-receptor family member present on both osteoclast precursors and mature osteoclasts. Like other TNF-family receptors and the IL-1 receptor, RANK mediates its signal transduction via TNF receptor-associated factor (TRAF) proteins, suggesting …

Critical Roles For Interleukin 1 And Tumor Necrosis Factor Alpha In Antibody-Induced Arthritis, Hong Ji, Allison Pettit, Koichiro Ohmura, Adriana Ortiz-Lopez, Veronique Duchatelle, Claude Degott, Ellen M. Gravallese, Diane Mathis, Christophe Benoist

Ellen M. Gravallese

In spontaneous inflammatory arthritis of K/BxN T cell receptor transgenic mice, the effector phase of the disease is provoked by binding of immunoglobulins (Igs) to joint surfaces. Inflammatory cytokines are known to be involved in human inflammatory arthritis, in particular rheumatoid arthritis, although, overall, the pathogenetic mechanisms of the human affliction remain unclear. To explore the analogy between the K/BxN model and human patients, we assessed the role and relative importance of inflammatory cytokines in K/BxN joint inflammation by transferring arthritogenic serum into a panel of genetically deficient recipients. Interleukin (IL)-1 proved absolutely necessary. Tumor necrosis factor (TNF)-alpha was also …

Mechanisms Of Bone Loss In Inflammatory Arthritis: Diagnosis And Therapeutic Implications, Steven R. Goldring, Ellen M. Gravallese

Ellen M. Gravallese

Rheumatoid arthritis represents an excellent model in which to gain insights into the local and systemic effects of joint inflammation on skeletal tissues. Three forms of bone disease have been described in rheumatoid arthritis. These include: focal bone loss affecting the immediate subchondral bone and bone at the joint margins; periarticular osteopenia adjacent to inflamed joints; and generalized osteoporosis involving the axial and appendicular skeleton. Although these three forms of bone loss have several features in common, careful histomorphometric and histopathological analysis of bone tissues from different skeletal sites, as well as the use of urinary and serum biochemical markers …

Clinical Disease Activity And Acute Phase Reactant Levels Are Discordant Among Patients With Active Rheumatoid Arthritis: Acute Phase Reactant Levels Contribute Separately To Predicting Outcome At One Year, Jonathan Kay, Olga Morgacheva, Susan P. Messing, Joel M. Kremer, Jeffrey D. Greenberg, George W. Reed, Ellen M. Gravallese, Daniel E. Furst

Jonathan Kay

INTRODUCTION: Clinical trials of new treatments for rheumatoid arthritis (RA) typically require subjects to have an elevated acute phase reactant (APR), in addition to tender and swollen joints. However, despite the elevation of individual components of the Clinical Disease Activity Index (CDAI) (tender and swollen joint counts and patient and physician global assessment), some patients with active RA may have normal erythrocyte sedimentation rate (ESR) and/or C-reactive protein (CRP) levels and thus fail to meet entry criteria for clinical trials. We assessed the relationship between CDAI and APRs in the Consortium of Rheumatology Researchers of North America (CORRONA) registry by …

Regulated Splicing Of The Alpha6 Integrin Cytoplasmic Domain Determines The Fate Of Breast Cancer Stem Cells, Hira Lal Goel, Tatiana Gritsko, Bryan Pursell, Cheng Chang, Leonard D. Shultz, Dale L. Greiner, Jens Henrik Norum, Rune Toftgard, Leslie M. Shaw, Arthur M. Mercurio

Arthur M. Mercurio

Although the alpha6beta1 integrin has been implicated in the function of breast and other cancer stem cells (CSCs), little is known about its regulation and relationship to mechanisms involved in the genesis of CSCs. We report that a CD44(high)/CD24(low) population, enriched for CSCs, is comprised of distinct epithelial and mesenchymal populations that differ in expression of the two alpha6 cytoplasmic domain splice variants: alpha6A and alpha6B. alpha6Bbeta1 expression defines the mesenchymal population and is necessary for CSC function, a function that cannot be executed by alpha6A integrins. The generation of alpha6Bbeta1 is tightly controlled and occurs as a consequence of …

Expression And Function Of Hypoxia Inducible Factor-1 Alpha In Human Melanoma Under Non-Hypoxic Conditions, Caroline N. Mills, Sandeep S. Joshi, Richard M. Niles

Richard M. Niles

Background Hypoxia inducible factor-1 alpha (HIF-1α) protein is rapidly degraded under normoxic conditions. When oxygen tensions fall HIF-1α protein stabilizes and transactivates genes involved in adaptation to hypoxic conditions. We have examined the normoxic expression of HIF-1α RNA and protein in normal human melanocytes and a series of human melanoma cell lines isolated from radial growth phase (RGP), vertical growth phase (VGP) and metastatic (MET) melanomas. Results HIF-1α mRNA and protein was increased in RGP vs melanocytes, VGP vs RGP and MET vs VGP melanoma cell lines. We also detected expression of a HIF-1α mRNA splice variant that lacks part …

Volume Measures Using A Digital Image Analysis System Are Reliable In Diabetic Foot Ulcers, Sue Gardner, Rita Frantz, Stephen Hillis, Thomas Blodgett, Lorraine Femino, Shannon Lehman

Thomas Blodgett

Reliable measures of wound size are critical to wound healing research and clinical management. Measurement of full-thickness wounds is increasingly being done using digital images and photogrammetric software, such as VeVMD (Vista Medical, Winnipeg, Manitoba, Canada), to estimate wound volume. The reliability of VeVMD in determining wound volume is unknown. The present study sought to examine the reliability of wound volume measurements obtained using VeVMD.

Análise Da Produção Bibliográfica Sobre Qualidade De Vida De Portadores De Feridas Crônicas / Bibliographical Analysis On Quality Of Life Of Patients With Chronic Wounds, Everton Alves, Edilson De Albuquerque

Everton Fernando Alves

O estudo teve como objeto analisar algumas características da produção bibliográfica sobre a Qualidade de Vida (QV) de portadores de Feridas Crônicas (FC) no Brasil entre 2000 e 2009. Para tanto, realizou-se uma revisão sistemática da literatura através da busca de estudos indexados nas bases de dados da BIREME. Os materiais encontrados e utilizados foram sete artigos, uma dissertação e uma tese. Destes, a maioria dos artigos se concentrou no ano de 2001 e 2006, correspondendo a 50% das publicações levantadas. Os resultados demonstraram que apenas uma publicação, ou seja, (16,6%) dos dados, foi encontrada na Revista Ciencia y Enfermería …

John Contracts Skin Disease At Spa, Donna M. Hughes Dr., Melanie Shapiro Esq

Donna M. Hughes