Psoriasis is a chronic inflammatory skin disease, the immunologic model of which has been profoundly revised following recent advances in the understanding of its pathophysiology. In the current model, a crosstalk between keratinocytes, neutrophils, mast cells, T cells, and dendritic cells is thought to create inflammatory and pro-proliferative circuits mediated by chemokines and cytokines. Various triggers, including recently identified autoantigens, Toll-like receptor agonists, chemerin, and thymic stromal lymphopoietin may activate the pathogenic cascade resulting in enhanced production of pro-inflammatory and proliferation-inducing mediators such as interleukin (IL)-17, tumor necrosis factor (TNF)-α, IL-23, IL-22, interferon (IFN)-α, and IFN-γ by immune cells. Among these key cytokines lie therapeutic targets for currently approved antipsoriatic therapies. This review aims to provide a comprehensive overview on the immune-mediated mechanisms characterizing the current pathogenic model of psoriasis.

Background Drug survival analysis of biologic agents in psoriasis is of extreme importance, as it allows not only the evaluation of objective clinical outcomes (such as effectiveness and safety) but also of factors that are associated with patients' adherence to treatment. The aim of this study was to evaluate and compare the drug survival of the most recent biologic agents approved for the treatment of moderate-to-severe psoriasis-ustekinumab, secukinumab, ixekizumab, brodalumab, guselkumab, and risankizumab-and to identify clinical predictors that can influence the drug survival of these drugs. Methods This retrospective multicentric cohort study from 16 dermatology centers in Portugal,

Background: Toxic epidermal necrolysis (TEN) is a rare, life-threatening condition caused by certain medications. Keratinocytes affected by TEN have been found to undergo apoptosis mediated by Fas-FasL interactions. Treatment with intravenous immunoglobulin (IVIG) has been proposed to inhibit this interaction.Objective: To demonstrate the effectiveness of IVIG therapy in reducing mortality in patients with TEN.Design: A retrospective analysis of 16 consecutive patients with TEN who were treated with IVIG. The SCORTEN system, a validated predictor of TEN mortality, was used to analyze the data of these patients. Using SCORTEN, we compared the predicted mortality of our patient population with observed mortality.Setting: Dermatology inpatient unit at a universityaffiliated hospital.Intervention: All 16 patients received IVIG treatment daily for 4 days. Fifteen patients received 1 g/kg per day and 1 patient received 0.4 g/kg per day.Main Outcome Measures: For each patient, causes of TEN and other medical problems were documented prior to IVIG therapy, as were the 7 independent SCORTEN risk factors.Results: One patient died. Based on the SCORTEN system, 5.81 patients were expected to die. These mortality rates were compared using the standardized mortality ratio (SMR) analysis ([⌺ observed deaths/⌺ expected deaths] ϫ 100) to determine the efficacy of this treatment, which showed that patients with TEN treated with IVIG were 83% less likely to die than those not treated with IVIG (SMR = 0.17; 95% confidence interval, 0.0-0.96). Conclusion:Based on comparison of our observed mortality rate with the SCORTEN-predicted mortality rate, treatment with IVIG significantly decreased mortality in patients with TEN.

Background: Even after the description of papuloerythroderma of Ofuji (PEO) in 1984, little is known about this clinical entity. Objective:To report on 2 new cases of PEO and review of the worldwide literature on this topic. Methods: Article citations were searched on several biomedical search engines (PubMed, EMBASE, SCOPUS, Google Scholar). Papers were retrieved either online or in print. Results: A grand total of 170 PEO cases were identified. Most patients were older than 55 years and of Asian or white descent, with an overall male/female ratio of 4.0. Itch and the deck-chair sign were observed in all patients. Peripheral eosinophilia, lymphocytopenia and increased serum IgE were common findings. Histopathology mostly showed aspecific inflammation, while 17 showed histological features of cutaneous T-cell lymphoma (CTCL). Atopy, malignancies, infections and drugs were rarely linked to PEO. Conclusion: PEO represents a rather monomorphous entity both clinically and, with the remarkable exception of CTCL, also histologically. Nonetheless, no causative factor could be identified in the vast majority of cases. An etiological classification and diagnostic criteria are proposed in the attempt to contribute framing this puzzling clinical entity.

Kaposi’s sarcoma (KS) herpesvirus (KSHV) causes KS, an angiogenic AIDS-associated spindle-cell neoplasm, by activating host oncogenic signaling cascades through autocrine and paracrine mechanisms. Tyrosine kinase receptor (RTK) proteomic arrays, identified PDGF receptor-alpha (PDGFRA) as the predominantly-activated RTK in KSHV-induced mouse KS-tumors. We show that: 1) KSHV lytic replication and the vGPCR can activate PDGFRA through upregulation of its ligands PDGFA/B, which increase c-myc, VEGF and KSHV gene expression in infected cells 2) KSHV infected spindle cells of most AIDS-KS lesions display robust phospho-PDGFRA staining 3) blocking PDGFRA-signaling with N-acetyl-cysteine, RTK-inhibitors Imatinib and Sunitinib, or dominant-negative PDGFRA inhibits tumorigenesis 4) PDGFRA D842V activating-mutation confers resistance to Imatinib in mouse-KS tumorigenesis. Our data show that KSHV usurps sarcomagenic PDGFRA signaling to drive KS. This and the fact that PDGFRA drives non-viral sarcomas highlights the importance for KSHV-induced ligand-mediated activation of PDGFRA in KS sarcomagenesis and shows that this oncogenic axis could be successfully blocked to impede KS tumor growth.