Mechanisms of Inflammation in Neutrophil-Mediated Skin Diseases

Abstract

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.

Are the cutaneous manifestations during or due to SARS-CoV-2 infection/COVID-19 frequent or not? Revision of possible pathophysiologic mechanisms

“…Inadequate negative or positive regulation of innate immune receptors, may lead to signals that stimulate nucleic acid and subsequent protein transcription, which can occur as monogenic genetic disorders, with gain in function (GOF) or loss of function (LOF). These are known as type I interferonopathies or other autoinflammatory diseases [76][77][78][79][80][81].…”

Lessons from dermatology about inflammatory responses in Covid‐19

“…CAPS are a group of rare inherited inflammatory disorders associated with dominant mutations in the cryopyrin‐coding gene NLRP3 (nucleotide‐binding domain, leucine‐rich repeat containing gene family, pyrin domain‐containing protein 3) on chromosome 1q44 which is also known as CIAS1, PYPAF1 or NALP3. Currently, more than 90 mutations involving NLRP3 and associated with CAPS phenotypes have been reported 57 …”

Pyoderma gangrenosum: From historical perspectives to emerging investigations

“…Still, no triggers have been identified. 24,47,48 The first study to demonstrate IL-8 overexpression in tissue was performed by Oka et al 49 51 performed a study using human skin biopsies of PG which showed that abundant expression of matrix metalloproteinase (MMP) 9, MMP-10, and TNF-α, and lack of epithelial MMP-1 and MMP-26 characterised PG. This marked the first multipatient molecular-level study of PG.…”