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International Journal of Molecular... Mar 2019Research on psoriasis pathogenesis has largely increased knowledge on skin biology in general. In the past 15 years, breakthroughs in the understanding of the... (Review)
Review
Research on psoriasis pathogenesis has largely increased knowledge on skin biology in general. In the past 15 years, breakthroughs in the understanding of the pathogenesis of psoriasis have been translated into targeted and highly effective therapies providing fundamental insights into the pathogenesis of chronic inflammatory diseases with a dominant IL-23/Th17 axis. This review discusses the mechanisms involved in the initiation and development of the disease, as well as the therapeutic options that have arisen from the dissection of the inflammatory psoriatic pathways. Our discussion begins by addressing the inflammatory pathways and key cell types initiating and perpetuating psoriatic inflammation. Next, we describe the role of genetics, associated epigenetic mechanisms, and the interaction of the skin flora in the pathophysiology of psoriasis. Finally, we include a comprehensive review of well-established widely available therapies and novel targeted drugs.
Topics: Animals; Chronic Disease; Diagnosis, Differential; Disease Susceptibility; Humans; Psoriasis; Skin; Symptom Assessment
PubMed: 30909615
DOI: 10.3390/ijms20061475 -
Journal of the American Academy of... Jan 2022Itch pathogenesis is broadly characterized into histaminergic and nonhistaminergic pathways and transmitted via 2 main receptor families: G protein-coupled receptors and... (Review)
Review
Itch pathogenesis is broadly characterized into histaminergic and nonhistaminergic pathways and transmitted via 2 main receptor families: G protein-coupled receptors and transient receptor potential channels. In the skin, itch is primarily transmitted by unmyelinated type C and thinly myelinated type Aδ nerve fibers. Crosstalk between the immune and neural systems modulates itch transmission at the skin, spinal cord, and brain. Among the many known pruritogens, Th2 cytokines, such as interleukin-4, interleukin-13, interleukin-31, and thymic stromal lymphopoietin, are particularly important mediators that signal through shared Janus kinase pathways, representing novel targets for novel itch therapeutics. Emerging evidence has also revealed that the opioidergic system is a potent modulator of itch transmission, with increased μ-opioid activity and decreased κ-opioid activity contributing to itch pathogenesis. Optimal management of itch requires that treatment approaches be tailored to specific etiologic itch subtypes. When the etiology is unknown and patients are given a diagnosis of chronic pruritus of unknown origin, treatment should be guided by the presence of Th2 polarization, often reflected by increased blood eosinophils. In the second article of this 2-part series, we outline our current understanding of itch pathogenesis and discuss available and emerging treatments for itch.
Topics: Analgesics, Opioid; Humans; Pruritus; Skin
PubMed: 34648873
DOI: 10.1016/j.jaad.2021.07.078 -
International Journal of Molecular... Mar 2023Psoriatic arthritis (PsA), a heterogeneous chronic inflammatory immune-mediated disease characterized by musculoskeletal inflammation (arthritis, enthesitis,... (Review)
Review
Psoriatic arthritis (PsA), a heterogeneous chronic inflammatory immune-mediated disease characterized by musculoskeletal inflammation (arthritis, enthesitis, spondylitis, and dactylitis), generally occurs in patients with psoriasis. PsA is also associated with uveitis and inflammatory bowel disease (Crohn's disease and ulcerative colitis). To capture these manifestations as well as the associated comorbidities, and to recognize their underlining common pathogenesis, the name of psoriatic disease was coined. The pathogenesis of PsA is complex and multifaceted, with an interplay of genetic predisposition, triggering environmental factors, and activation of the innate and adaptive immune system, although autoinflammation has also been implicated. Research has identified several immune-inflammatory pathways defined by cytokines (IL-23/IL-17, TNF), leading to the development of efficacious therapeutic targets. However, heterogeneous responses to these drugs occur in different patients and in the different tissues involved, resulting in a challenge to the global management of the disease. Therefore, more translational research is necessary in order to identify new targets and improve current disease outcomes. Hopefully, this may become a reality through the integration of different omics technologies that allow better understanding of the relevant cellular and molecular players of the different tissues and manifestations of the disease. In this narrative review, we aim to provide an updated overview of the pathophysiology, including the latest findings from multiomics studies, and to describe current targeted therapies.
Topics: Humans; Arthritis, Psoriatic; Comorbidity; Cytokines; Psoriasis
PubMed: 36902329
DOI: 10.3390/ijms24054901 -
Minerva Ginecologica Oct 2017Endometriosis is a chronic, inflammatory, condition of high incidence and serious reproductive and general health consequences. Understanding the pathogenesis of... (Review)
Review
Endometriosis is a chronic, inflammatory, condition of high incidence and serious reproductive and general health consequences. Understanding the pathogenesis of endometriosis is crucial for proper diagnostic and ordering the most effective treatment. Even though there is a large body of data regarding this pathology our understanding of the pathogenesis of this disease remains incomplete. The aim of this review is to summarize contemporary data regarding pathogenesis of endometriosis. Current data regarding endometrial origin, metaplastic and Mullerian embryonic rests theory will be reviewed here. Also genetic, epigenetic, environmental factors and immunological dysfunction role in endometriosis will be summarized. To conclude, a lot of effort must be put to integrate the abundant data from genetic, epigenetic and immunological studies to propose one coherent theory for the pathogenesis of endometriosis.
Topics: Endometriosis; Epigenesis, Genetic; Female; Humans; Mullerian Ducts; Risk Factors
PubMed: 28271702
DOI: 10.23736/S0026-4784.17.04048-5 -
Journal of Immunology Research 2019Inflammatory bowel disease (IBD) is a chronic and life-threating inflammatory disease of gastroenteric tissue characterized by episodes of intestinal inflammation. The... (Review)
Review
Inflammatory bowel disease (IBD) is a chronic and life-threating inflammatory disease of gastroenteric tissue characterized by episodes of intestinal inflammation. The pathogenesis of IBD is complex. Recent studies have greatly improved our knowledge of the pathophysiology of IBD, leading to great advances in the treatment as well as diagnosis of IBD. In this review, we have systemically reviewed the pathogenesis of IBD and highlighted recent advances in host genetic factors, gut microbiota, and environmental factors and, especially, in abnormal innate and adaptive immune responses and their interactions, which may hold the keys to identify novel predictive or prognostic biomarkers and develop new therapies.
Topics: Animals; Disease Susceptibility; Environment; Gastrointestinal Microbiome; Genetic Predisposition to Disease; Humans; Inflammatory Bowel Diseases
PubMed: 31886308
DOI: 10.1155/2019/7247238 -
Frontiers in Immunology 2021Immunoglobin A (IgA) vasculitis (IgAV), formerly called the Henoch-Schönlein purpura (HSP), is a small vessel vasculitis, characterized by IgA1-dominant immune... (Review)
Review
Immunoglobin A (IgA) vasculitis (IgAV), formerly called the Henoch-Schönlein purpura (HSP), is a small vessel vasculitis, characterized by IgA1-dominant immune deposition at diseased vessel walls. IgAV is the most common form of vasculitis in children; typical symptoms include palpable purpura, arthritis or arthralgia, abdominal pain, and hematuria or proteinuria. Galactose-deficient IgA1 is detected in the tissues of the kidney and skin in patients with IgAV; it forms immune complexes leading to subsequent immune reactions and injuries. This report provides the recent advances in the understanding of environmental factors, genetics, abnormal innate and acquired immunity, and the role of galactose-deficient IgA1 immunocomplexes in the pathogenesis of IgAV.
Topics: Animals; Environment; Humans; IgA Vasculitis
PubMed: 34858429
DOI: 10.3389/fimmu.2021.771619 -
Chinese Medical Journal Feb 2020Etiology of adolescent idiopathic scoliosis (AIS), a complicated three-dimensional spinal deformity with early-onset, receives continuous attention but remains unclear.... (Review)
Review
Etiology of adolescent idiopathic scoliosis (AIS), a complicated three-dimensional spinal deformity with early-onset, receives continuous attention but remains unclear. To gain an insight into AIS pathogenesis, this review searched PubMed database up to June 2019, using key words or medical subject headings terms including "adolescent idiopathic scoliosis," "scoliosis," "pathogenesis," "etiology," "genetics," "mesenchymal stem cells," and their combinations, summarized existing literatures and categorized the theories or hypothesis into nine aspects. These aspects include bone marrow mesenchymal stem cell studies, genetic studies, tissue analysis, spine biomechanics measurements, neurologic analysis, hormone studies, biochemical analysis, environmental factor analysis, and lifestyle explorations. These categories could be a guidance for further etiology or treatment researches to gain inspiration.
Topics: Adolescent; Biomechanical Phenomena; Bone Density; Cerebellum; Chromosome Aberrations; Epigenesis, Genetic; Humans; Melatonin; Scoliosis; Vestibular Nuclei
PubMed: 31972723
DOI: 10.1097/CM9.0000000000000652 -
World Journal of Gastroenterology Jan 2017Neutropenic colitis is a severe condition usually affecting immunocompromised patients. Its exact pathogenesis is not completely understood. The main elements in disease... (Review)
Review
Neutropenic colitis is a severe condition usually affecting immunocompromised patients. Its exact pathogenesis is not completely understood. The main elements in disease onset appear to be intestinal mucosal injury together with neutropenia and the weakened immune system of the afflicted patients. These initial conditions lead to intestinal edema, engorged vessels, and a disrupted mucosal surface, which becomes more vulnerable to bacterial intramural invasion. Chemotherapeutic agents can cause direct mucosal injury (mucositis) or can predispose to distension and necrosis, thereby altering intestinal motility. This article aims to review current concepts regarding neutropenic colitis' pathogenesis, diagnosis, and management.
Topics: Anti-Bacterial Agents; Antineoplastic Agents; Colectomy; Combined Modality Therapy; Enterocolitis, Neutropenic; Fluid Therapy; Humans; Leukocyte Transfusion; Lower Body Negative Pressure; Neoplasms; Neutropenia; Parenteral Nutrition; Typhlitis
PubMed: 28104979
DOI: 10.3748/wjg.v23.i1.42 -
Brain and Behavior Sep 2015Multiple sclerosis is an acquired demyelinating disease of the central nervous system. It is the second most common cause of disability in adults in United States after... (Review)
Review
BACKGROUND
Multiple sclerosis is an acquired demyelinating disease of the central nervous system. It is the second most common cause of disability in adults in United States after head trauma.
DISCUSSION
The etiology of MS is probably multifactorial, related to genetic, environmental, and several other factors. The pathogenesis is not fully understood but is believed to involve T-cell-mediated inflammation directed against myelin and other related proteins with a possible role for B cells. The McDonald criteria have been proposed and revised over the years to guide the diagnosis of MS and are based on clinical presentation and magnetic resonance imaging (MRI) of the brain and spinal cord to establish dissemination in time and space. The treatment of MS includes disease modification with immunomodulator drugs and symptom management to address the specific symptoms such as fatigue, spasticity, and pain.
CONCLUSION
An update on etiology, pathogenesis, diagnosis, and immunomodulatory treatment of MS is presented.
Topics: Brain; Diagnosis, Differential; Humans; Magnetic Resonance Imaging; Multiple Sclerosis; Spinal Cord
PubMed: 26445701
DOI: 10.1002/brb3.362 -
International Journal of Molecular... Jun 2021Melanoma develops from malignant transformations of the pigment-producing melanocytes. If located in the basal layer of the skin epidermis, melanoma is referred to as... (Review)
Review
Melanoma develops from malignant transformations of the pigment-producing melanocytes. If located in the basal layer of the skin epidermis, melanoma is referred to as cutaneous, which is more frequent. However, as melanocytes are be found in the eyes, ears, gastrointestinal tract, genitalia, urinary system, and meninges, cases of mucosal melanoma or other types (e.g., ocular) may occur. The incidence and morbidity of cutaneous melanoma (cM) are constantly increasing worldwide. Australia and New Zealand are world leaders in this regard with a morbidity rate of 54/100,000 and a mortality rate of 5.6/100,000 for 2015. The aim of this review is to consolidate and present the data related to the aetiology and pathogenesis of cutaneous melanoma, thus rendering them easier to understand. In this article we will discuss these problems and the possible impacts on treatment for this disease.
Topics: Animals; Genetic Predisposition to Disease; Humans; Melanoma; Risk Factors; Signal Transduction; Skin; Skin Neoplasms; Melanoma, Cutaneous Malignant
PubMed: 34203771
DOI: 10.3390/ijms22126395