Modulation of Toll-like receptors in psoriatic patients during therapy with adalimumab

Toll-like receptors (TLRs) are a key part of the innate immune system that detect pathogen-associated molecular patterns (PAMPs) of microorganisms and their stimulation results in the activation of signaling pathways leading to the modulation of inflammatory and immune responses. Since psoriasis is a complex, inflammatory and immune skin disease, characterized by an abnormal immune response and increased proliferation of keratinocytes, with an increased production of proinflammatory cytokines, TLRs could play an important role in the pathogenesis of the disease. We propose to assess the modulation of TLR expression on psoriatic skin of patients treated with Adalimumab and systemic conventional therapies. We therefore recruited fifteen patients: ten were treated with adalimumab and five with systemic conventional therapies; their clinical conditions were analyzed by PASI index and skin biopsies were evaluated for TLR1 and TLR2 expression by immunohistochemistry assays. Our data suggest adalimumab is not only able to improve the clinical condition of psoriatic patients, but also to modulate TLR1 and TLR2 expression involved in psoriasis, as in healthy skin. Adalimumab is a most promising biological drug able to orchestrate immune and inflammatory responses in psoriatic lesions, recovering TLR expression on basal keratinocytes and improving clinical conditions of psoriatic patients, with no evident side effects

Chemerin expression marks early psoriatic skin lesions and correlates with plasmacytoid dendritic cell recruitment

Psoriasis is a type I interferon-driven T cell–mediated disease characterized by the recruitment of plasmacytoid dendritic cells (pDC) into the skin. The molecules involved in pDC accumulation in psoriasis lesions are unknown. Chemerin is the only inflammatory chemotactic factor that is directly active on human blood pDC in vitro. The aim of this study was to evaluate the role of the chemerin/ChemR23 axis in the recruitment of pDC in psoriasis skin. Prepsoriatic skin adjacent to active lesions and early lesions were characterized by a strong expression of chemerin in the dermis and by the presence of CD15+ neutrophils and CD123+/BDCA-2+/ChemR23+ pDC. Conversely, skin from chronic plaques showed low chemerin expression, segregation of neutrophils to epidermal microabscesses, and few pDC in the dermis. Chemerin expression was localized mainly in fibroblasts, mast cells, and endothelial cells. Fibroblasts cultured from skin of psoriatic lesions expressed higher levels of chemerin messenger RNA and protein than fibroblasts from uninvolved psoriatic skin or healthy donors and promoted pDC migration in vitro in a chemerin-dependent manner. Therefore, chemerin expression specifically marks the early phases of evolving skin psoriatic lesions and is temporally strictly associated with pDC. These results support a role for the chemerin/ChemR23 axis in the early phases of psoriasis development

Extracellular serine empowers epidermal proliferation and psoriasis-like symptoms

The contribution of nutrient availability to control epidermal cell proliferation, inflammation, and hyperproliferative diseases remains unknown. Here, we studied extracellular serine and serine/glycine metabolism using human keratinocytes, human skin biopsies, and a mouse model of psoriasis-like disease. We focused on a metabolic enzyme, serine hydroxymethyltransferase (SHMT), that converts serine into glycine and tetrahydrofolate-bound one‑carbon units to support cell growth. We found that keratinocytes are both serine and glycine auxotrophs. Metabolomic profiling and hypoxanthine supplementation indicated that SHMT silencing/inhibition reduced cell growth through purine depletion, leading to nucleotide loss. In addition, topical application of an SHMT inhibitor suppressed both keratinocyte proliferation and inflammation in the imiquimod model and resulted in a decrease in psoriasis-associated gene expression. In conclusion, our study highlights SHMT2 activity and serine/glycine availability as an important metabolic hub controlling both keratinocyte proliferation and inflammatory cell expansion in psoriasis and holds promise for additional approaches to treat skin diseases

The integrated care pathway for melanoma: the Istituto Dermopatico dell'Immacolata experience in Rome

Introduction: The Integrated Care Pathway (ICP) represents a multidisciplinary outline of anticipated care, placed in an appropriate timeframe, to support patients with specific conditions or symptoms. The aim of this paper is to define the ICP for patients with melanoma referring to the "Istituto Dermopatico dell'Immacolata-IRCCS di Roma e Villa Paola" ("Center"). Methods and results: A multidisciplinary group (oncologists, dermatologists, surgeons, pathologists etc.) was defined as well as a facilitator to act as a link between all experts. The first step of ICP development was a review of current practice for patients with melanoma referring to the Center. This first step had the scope to define the multidisciplinary process map (a "picture" of the care plan) for patients with melanoma. The process map defined: i) the activities performed during delivery of care to the patients, ii) the responsibilities for these activities and iii) potential problem areas or opportunities for improvements. The process map formed the basis of the final ICP document. Conclusion: The adoption of melanoma ICP will allow the multidisciplinary group to ensure that clinical guidelines and available evidence are incorporated into everyday practice. (Oncology, HTA & Market Access

Granuloma inframammary adultorum, a case report

Granuloma inframammary adultorum represents a variant of erosive papulonodular dermatosis; we report a case of a patient with bilateral erosive plaques and nodules predominantly located under the breast

Granuloma inframammary adultorum, a case report

Granuloma inframammary adultorum represents a variant of erosive papulonodular dermatosis; we report a case of a patient with bilateral erosive plaques and nodules predominantly located under the breast

Adherence to the Mediterranean diet model and psoriatic disease (skin, joint and metabolic expression of psoriasis)

Psoriasis is a chronic disease, characterized by systemic inflammation with skin, joint and metabolic involvement. The most common tools to evaluate the severity of each disease is respectively the Psoriasis Area Severity Index (PASI) and the Disease Activity Index for Psoriatic Arthritis (DAPSA). The association between psoriasis and obesity and the role of visceral fat in producing an inflammatory state have been demonstrated. The Mediterranean Diet (MD) has been recommended as a model of healthy diet on the basis of scientific evidence and considered as an adjuvant therapy for all patients affected by chronic inflammatory diseases. Our study evaluated the association between adherence to MD (assessed with the Predimed questionnaire) and psoriatic disease severity. 80 patients (40 with psoriasis and 40 with psoriatic arthritis) were evaluated for disease severity (PASI, DAPSA) and were assessed for Metabolic Syndrome according to the International Diabetes Federation (IDF) definition. To evaluate adherence to the MD, each patient was administered the Predimed questionnaire which includes 14 questions. Our study shows a correlation between low adherence to MD and a high expression of psoriasis, considering cutaneous, joint symptoms and the metabolic profile

The holistic approach to psoriasis patients with comorbidities: the role of investigational drugs

Introduction: Psoriasis is a high-burden syndrome characterized by cutaneous and extracutaneous manifestations that profoundly reduce patients' quality of life. The presence of concomitant comorbidities often represents a limit to the most appropriate psoriasis treatment that will be overcome by the development of drugs effective for diseases with common pathogenetic pathways. Areas covered: The current review summarizes the latest findings on investigational drugs for psoriasis and their role on potentially concomitant diseases that share similar pathogenetic pathways. Expert opinion: The development of novel drugs that target key-molecules in the pathogenesis of several diseases, including psoriasis, will impact on the reduction of polypharmacy and drug interaction with increased patients' compliance to treatment, wellbeing and quality of life. Certainly, the efficacy and safety profile of each novel agent must be defined and evaluated in real-life, since the performance may vary according to comorbidities and their severity. Anyway, future is now, and research must continue in this direction