Review: A Contemporary, Multifaced Insight into Psoriasis Pathogenesis.

Psoriasis is a chronic recurrent inflammatory autoimmune pathology with a significant genetic component and several interferences of immunological cells and their cytokines. The complex orchestration of psoriasis pathogenesis is related to the synergic effect of immune cells, polygenic alterations, autoantigens, and several other external factors. The major act of the IL-23/IL-17 axis, strongly influencing the inflammatory pattern established during the disease activity, is visible as a continuous perpetuation of the pro-inflammatory response and keratinocyte activation and proliferation, leading to the development of psoriatic lesions. Genome-wide association studies (GWASs) offer a better view of psoriasis pathogenic pathways, with approximately one-third of psoriasis's genetic impact on psoriasis development associated with the MHC region, with genetic loci located on chromosome 6. The most eloquent genetic factor of psoriasis, PSORS1, was identified in the MHC I site. Among the several factors involved in its complex etiology, dysbiosis, due to genetic or external stimulus, induces a burst of pro-inflammatory consequences; both the cutaneous and gut microbiome get involved in the psoriasis pathogenic process. Cutting-edge research studies and comprehensive insights into psoriasis pathogenesis, fostering novel genetic, epigenetic, and immunological factors, have generated a spectacular improvement over the past decades, securing the path toward a specific and targeted immunotherapeutic approach and delayed progression to inflammatory arthritis. This review aimed to offer insight into various domains that underline the pathogenesis of psoriasis and how they influence disease development and evolution. The pathogenesis mechanism of psoriasis is multifaceted and involves an interplay of cellular and humoral immunity, which affects susceptible microbiota and the genetic background. An in-depth understanding of the role of pathogenic factors forms the basis for developing novel and individualized therapeutic targets that can improve disease management.

Dickkopf-Related Protein 1 (DKK-1) as a Possible Link between Bone Erosions and Increased Carotid Intima-Media Thickness in Psoriatic Arthritis: An Ultrasound Study.

Psoriatic arthritis (PsA) is a heterogenous systemic inflammatory disorder that affects peripheral joints and skin, but also causes inflammation at entheseal sites, digits (dactylitis) and the axial skeleton. Despite considerable advances, our understanding of the pathogenesis and management of PsA is hampered by its complex clinical expression. We enrolled patients who met the ClASsification for Psoriatic Arthritis (CASPAR) criteria for PsA (n = 17), and healthy controls (n = 13). The lipid profile, C-reactive protein (CRP) and Dickkopf-related protein 1 (DKK-1) circulating levels were measured for all subjects. For the patients with PsA, (1) the erosive character of the articular disease was assessed by a musculoskeletal ultrasound and (2) the cardiovascular risk was evaluated using the Systematic Coronary Risk Evaluation (SCORE) chart and the ultrasound measurement of the carotid intima-media thickness. A higher titer of serum DKK-1 was associated with the presence of erosions (p < 0.005) and the cIMT correlated with DKK-1 levels in patients with PsA (r = 0.6356, p = 0.0061). Additionally, we observed a positive correlation between increased cIMT and CRP (r = 0.5186, p = 0.0329). Our results suggest that DKK-1 could be used as an early biomarker for the erosive character of the articular disease and for the assessment of the cardiovascular risk in PsA patients.

MMP-13, VEGF, and Disease Activity in a Cohort of Rheumatoid Arthritis Patients.

Identifying certain serum biomarkers associated with the degree of rheumatoid arthritis (RA) activity can provide us with a more accurate view of the evolution, prognosis, and future quality of life for these patients. Our aim was to analyze the presence and clinical use of matrix metalloproteinase-13 (MMP-13), along with vascular endothelial growth factor (VEGF) and well-known cytokines such as tumor necrosis factor-alpha (TNF-α) and interleukin 6 (IL-6) for patients with RA. We also wanted to identify the possible correlations between MMP-13 and these serological markers, as well as their relationship with disease activity indices, quality of life, and ultrasonographic evaluation. For this purpose, we analyzed serum samples of 34 RA patients and 12 controls. In order to assess serum concentrations for MMP-13, VEGF, TNF-α, and IL-6, we used the enzyme-linked immunosorbent assay (ELISA) technique. Our results concluded that higher levels of MMP-13, VEGF, TNF-α, and IL-6 were present in the serum of RA patients compared to controls, with statistical significance. We furthermore identified moderately positive correlations between VEGF, MMP-13, and disease activity indices, as well as with the ultrasound findings. We also observed that VEGF had the best accuracy (97.80%), for differentiating patients with moderate disease activity. According to the data obtained in our study, that although MMP-13, TNF-α and C-reactive protein (CRP) have the same sensitivity (55.56%), MMP-13 has a better specificity (86.67%) in the diagnosis of patients with DAS28(4v) CRP values corresponding to moderate disease activity. Thus, MMP-13 can be used as a biomarker that can differentiate patients with moderate or low disease activity. VEGF and MMP-13 can be used as additional parameters, along with TNF-α and IL-6, that can provide the clinician a better picture of the inflammatory process, disease activity, and structural damage in patients with RA. Our data can certainly constitute a start point for future research and extended studies with multicenter involvement, to support the selection of individualized and accurate therapeutic management strategies for our patients.

Entheseal involvement in a group of psoriatic arthritis patients: An ultrasonographic study.

Psoriatic arthritis (PsA) is an inflammatory potentially destructive disease that requires early diagnosis and therapeutic approach. Its main pathogenic event and the condition's hallmark is considered to be enthesitis. Clinical examination of the enthesis can be a challenge in the clinical practice; thus, ultrasonography (US) has emerged as an indispensable imaging tool for evaluating both structural and inflammatory changes of this structure. In the present study, we aimed to analyze the type and frequency of entheseal involvement in PsA patients by US examination, performing a retrospective study on 41 patients diagnosed with PsA. Ultrasonographically confirmed enthesitis, identified according to Outcome Measures in Rheumatology group (OMERACT, initially Outcome Measures in Rheumatoid Arthritis Clinical Trials) definitions, was present in 26 of the included patients, Achilles enthesis being the most common site involved. The prevalence of tendon structure abnormalities and the presence of entesophytes underlines the importance of chronic inflammation on entheseal sites. US examination has proven to be a reliable imaging method, with significant and continuous improvement, which is clearly a requisite part for current understanding and diagnosis of enthesitis and more than this, for the patient follow-up algorithm.