Mechanisms of Inflammation in Neutrophil-Mediated Skin Diseases

Neutrophil-mediated skin diseases, originally named neutrophilic dermatoses (NDs), are a group of conditions due to an altered neutrophil recruitment and activation, characterized by polymorphic cutaneous manifestations with possible internal organ involvement. Although a number of diseases are included in this setting, the two prototypic forms are pyoderma gangrenosum (PG) and Sweet's syndrome (SS) which usually present with skin ulcers and plaque-type lesions, respectively. They have central features significantly overlapping with autoinflammatory conditions which manifest as repeated episodes of tissue inflammation. However, in contrast to appropriate inflammatory responses to insults or to autoimmune disease, there is an absence of identifiable pathogens, autoantibodies, or autoreactive lymphocytes. The recognition of monogenic autoinflammatory diseases which can present with NDs has led to study several genes involved in autoinflammation in NDs. Based on discovering of a number of mutations involving different autoinflammatory genes, neutrophil-mediated skin diseases are nowadays regarded as a spectrum of polygenic autoinflammatory conditions. Although disease mechanisms have not yet been completely elucidated, NDs are recognized as diseases involving dysfunctional cellular signaling mediated by pathways mainly related to inflammasome and IL-1 with the contributory role of IL-17 and other effector molecules. The precise elucidation of the above-mentioned pathologic mechanisms may pave the way to tailored treatments for patients with different neutrophil-mediated skin diseases

International league of associations for rheumatology recommendations for the management of psoriatic arthritis in resource-poor settings

Background Psoriatic arthritis (PsA) is a challenging heterogeneous disease. The European League Against Rheumatism (EULAR) and the Group for Research and Assessment of Psoriasis and PsA (GRAPPA) last published their respective recommendations for the management of PsA in 2015. However, these guidelines are primarily based on studies conducted in resource replete countries and may not be applicable in countries in the Americas (except Canada and USA) and Africa. We sought to adapt the existing recommendations for these regions under the auspices of the International League of Associations for Rheumatology (ILAR). Process The ADAPTE Collaboration (2009) process for guideline adaptation was followed to adapt the EULAR and GRAPPA PsA treatment recommendations for the Americas and Africa. The process was conducted in three recommended phases: set-up phase; adaptation phase (defining health questions, assessing source recommendations, drafting report), and finalization phase (external review, aftercare planning, and final production). Result ILAR recommendations have been derived principally by adapting the GRAPPA recommendations, additionally, EULAR recommendations where appropriate and supplemented by expert opinion and literature from these regions. A paucity of data relevant to resource-poor settings was found in PsA management literature. Conclusion The ILAR Treatment Recommendations for PsA intends to serve as reference for the management of PsA in the Americas and Africa. This paper illustrates the experience of an international working group in adapting existing recommendations to a resource-poor setting. It highlights the need to conduct research on the management of PsA in these regions as data are currently lacking

Pyoderma gangrenosum : proposed pathogenesis and current use of biologics with an emphasis on complement C5a inhibitor IFX-1

Introduction: Pyoderma gangrenosum (PG) is a rare neutrophilic dermatosis with no FDA-approved treatment. The complement pathway has received renewed attention because it is elevated in inflammatory cutaneous conditions such as hidradenitis suppurativa (HS) and psoriasis. IFX-1 is a complement C5a inhibitor which inhibits neutrophil activation, chemotaxis, and reduces inflammatory signaling and complement driven tissue damage in various diseases. Areas covered: The article discusses a proposed pathogenesis of PG, early clinical investigations of IFX-1 for the treatment of HS and PG, its potential as a treatment for PG, and those other biologics currently under investigation. Expert opinion: Further studies should explore how patients with PG and other neutrophilic conditions may respond to complement inhibitors such as IFX-1. C5a blockade led to a reduction in inflammatory tunnels in HS, and alteration in neutrophil migration and activation supports the role of this pathway in the development of PG. The main challenges to the approval of IFX-1 are the identification of the optimal dose, duration, and stage-dependent factors in cutaneous inflammatory disorders. Further studies are required; however, complement inhibitors such as IFX-1 could find a place in clinical practice in years to come for severe, resistant PG that does not respond to conventional therapies

Molecular characterization and antifungal susceptibility of Cryptococcus neoformans strains collected from a single institution in Lima, Peru

Mercedes Tello is supported by a scholarship for postgraduate studies in Cellular and Molecular Biology, from the Consejo Nacional de Ciencia y Tecnología (CONCYTEC-Perú). Ericson Gutierrez is supported by a scholarship for postgraduate studies in Demography and Population Health,from the Belgian Development Q6 Cooperation CTB-Perú (L11PER016)Consejo Nacional de Ciencia, Tecnología e Innovación Tecnológica - Concyte