Chronic hand eczema (CHE) is a common inflammatory skin condition that significantly impacts the quality of life. From work-related disabilities to social embarrassment, pain, and financial costs, the burden on society is substantial. Managing this condition presents challenges such as long-term treatment, poor patient compliance, therapy side effects, and economic feasibility. As a result, significant efforts have been made in this field in recent years. Specifically, the broader understanding of CHE pathogenesis has led to the development of new drugs, both topical and systemic. The aim of this narrative review is to summarize the current available data on hand eczema pathophysiology and explore the resulting developments in drugs for its treatment. A comprehensive search on PubMed and the other main scientific databases was conducted using keywords related to CHE and its pathogenesis. The most relevant pathways targeted by therapies include the JAK-STAT cascade, IL-4, and IL-13 axis, phosphodiesterase 4 enzyme, and chemo-attractant cytokines. In the near future, physicians will have a plethora of therapeutic alternatives. Consequently, they should be well-trained not only in how to use these alternatives but also how to combine these treatments to address the ongoing challenges related to efficacy, tolerability, and safety.

In recent years, the incidence of metabolic syndrome (MS) has increased due to lifestyle-related factors in developed countries. MS represents a group of conditions that increase the risk of diabetes, cardiovascular diseases, and other severe health problems. Low-grade chronic inflammation is now considered one of the key aspects of MS and could be defined as a new cardiovascular risk factor. Indeed, an increase in visceral adipose tissue, typical of obesity, contributes to the development of an inflammatory state, which, in turn, induces the production of several proinflammatory cytokines responsible for insulin resistance. Psoriasis is a chronic relapsing inflammatory skin disease and is characterized by the increased release of pro-inflammatory cytokines, which can contribute to different pathological conditions within the spectrum of MS. A link between metabolic disorders and Psoriasis has emerged from evidence indicating that weight loss obtained through healthy diets and exercise was able to improve the clinical course and therapeutic response of Psoriasis in patients with obesity or overweight patients and even prevent its occurrence. A key factor in this balance is the gut microbiota; it is an extremely dynamic system, and this makes its manipulation through diet possible via probiotic, prebiotic, and symbiotic compounds. Given this, the gut microbiota represents an additional therapeutic target that can improve metabolism in different clinical conditions.

Psoriasis and obesity, while distinct, are inter-related inflammatory conditions. Adipose tissue (AT)-derived mediators could be pathogenically active in triggering and/or amplifying psoriatic skin inflammation and, vice versa, skin inflammation could drive increased adiposity that triggers the development of several chronic conditions. Gaining insight into their intricate relationship could be essential for effective management and treatment. The aim of this study was to determine (i) the pathogenic role of psoriasis-signature cytokines in contributing to AT metabolism and (ii) the role of AT-derived mediators in triggering and/or amplifying skin inflammation. For this reason, firstly, whole AT was treated with IL-17 and TNF-α, alone or in combination, to investigate their effects on the expression and production of adipokines and inflammatory factors. IL-17 and TNF-α were able to induce an additive or synergistic effect on AT-derived mediators. In order to assess the effects on the skin of inflamed AT by psoriasis-signature cytokines, ex vivo skin organ culture was performed and an increase in several inflammatory mediators was observed. These findings confirm that psoriasis and obesity amplify each other’s inflammatory processes and understanding this mutual exacerbation could lead to more effective therapeutic strategies that address both skin inflammation and AT metabolism.

In late December 2019, SARS-CoV-2 was identified as the cause of a new pneumonia (COVID-19), leading to a global pandemic declared by the WHO on 11 March 2020, with significant human, economic, and social costs. Although most COVID-19 cases are asymptomatic or mild, 14% progress to severe disease, and 5% develop critical illness with complications such as interstitial pneumonia, acute respiratory distress syndrome (ARDS), and multiple organ dysfunction syndrome (MODS). SARS-CoV-2 primarily targets the respiratory system but can affect multiple organs due to the widespread presence of angiotensin-converting enzyme 2 (ACE2) receptors, which the virus uses to enter cells. This broad distribution of ACE2 receptors means that SARS-CoV-2 infection can lead to cardiovascular, gastrointestinal, renal, hepatic, central nervous system, and ocular damage. The virus triggers the innate and adaptive immune systems, resulting in a massive cytokine release, known as a “cytokine storm”, which is linked to tissue damage and poor outcomes in severe lung disease. Interleukin-6 (IL-6) is particularly important in this cytokine release, with elevated levels serving as a marker of severe COVID-19. IL-6 is a multifunctional cytokine with both anti-inflammatory and pro-inflammatory properties, acting through two main pathways: classical signalling and trans-signalling. Classical signalling involves IL-6 binding to its membrane-bound receptor IL-6R and then to the gp130 protein, while trans-signalling occurs when IL-6 binds to the soluble form of IL-6R (sIL-6R) and then to membrane-bound gp130 on cells that do not express IL-6R. The soluble form of gp130 (sgp130) can inhibit IL-6 trans-signalling by binding to sIL-6R, thereby preventing it from interacting with membrane-bound gp130. Given the central role of IL-6 in COVID-19 inflammation and its association with severe disease, we aimed to analyse the behaviour of IL-6 and its soluble receptor complex during different waves of the pandemic. This analysis could help determine whether IL-6 levels can serve as prognostic markers of disease severity.

In late December 2019 a novel RNA beta-coronavirus was recognized as the causative agent of previously pneumonia cases of unknown origin. The virus was successively named Severe Acute Respiratory Syndrome CoronaVirus 2 (SARS-CoV-2) as well as the respiratory illness that it causes Coronavirus disease 19 (COVID-19) (1, 2). The global spread of SARS-CoV-2 and the thousands of deaths caused by COVID-19 led the World Health Organization (WHO) to declare a pandemic on 11 March 2020. To date, the world has paid a high toll in this pandemic in terms of human lives lost, economic repercussions and increased poverty. Indeed, even if most patients with COVID-19 are asymptomatic or experience mild self-limiting disease, 14% of them progress to severe disease and 5% to critical illness with complications, such as interstitial pneumonia, respiratory failure with acute respiratory distress syndrome (ARDS) and multiple organ dysfunction syndromes (MODS) (3). It is accepted that SARS-CoV-2 primarily affects the respiratory system, although other organs are also involved (4). The virus enters host cells by attaching its Spike like surface projections to the angiotensin-converting enzyme-2 (ACE2) receptor which is mainly expressed on alveolar epithelial cells and in nearly all human organs in varying degrees. Thus, although the central target of SARS-CoV-2 infection is the lung, the wide distribution of ACE2 receptors in other organs may lead to cardiovascular, gastrointestinal, kidney, liver, central nervous system and ocular damages that have to be closely monitored during the disease (5, 6). The virus then activates the innate and adaptive immune system resulting in a large number of cytokines release, known as “cytokine storm”, that is directly correlated with tissue injury and unfavourable prognosis of severe lung disease (7). In particular, interleukin (IL)-6 seems to plays an important role in driving this cytokine release so that its increased levels have been recognized as a hallmark inflammatory signature in sera of COVID-19 patients (8). IL-6 is a polyfunctional cytokine with both anti-inflammatory and pro-inflammatory properties which exerts its several functions through two main signal transduction pathways (9). In the classical signal transduction pathway, IL-6 binds to IL-6-trans membrane receptor (IL-6R) to form a complex that, then, binds to the trans membrane glycoprotein gp130, inducing its homo-dimerization and initiating intracellular signal transduction. This kind of signaling is limited to cells (hepatocytes, macrophages, neutrophils, T cells, etc.) that express IL-6R on their cell surface (10). Nevertheless, cells do not express IL- 6R, as stromal and epithelial cells, are able to still respond to IL-6 because the soluble form of the receptor (sIL-6R) binds to IL-6 in circle and then anchors to membrane gp130 receptor, initiating the trans-signaling pathway. For this reason, sIL-6R is able to increase the function of IL-6 and is considered the agonist form of its receptor. When the level of IL-6 increases, its effects are widely expressed because gp130 molecules are ubiquitous and, therefore, also present in cells without IL-6R in the membrane form. On the contrary, a soluble form of the glycoprotein 130 (sgp130) can complex with sIL-6R to prevent the sIL-6R from binding to the membrane-bound gp130. In this case sgp130 is able to decrease the function of IL-6 and is considered the antagonist form of IL-6 receptor system (11). Based on the central role of IL-6 in the inflammatory pathology of COVID-19 and the consistent association between elevated levels of the cytokine and severe disease outcomes found in the first phase of infection, we sought to analysis IL-6 and its soluble receptor complex behavior during the different waves of COVID-19 pandemic, in order to evaluate the possible differences which occur among them and to hypothesize if they might be used as prognostic markers of disease severity.

The aim of this study was to investigate the role of polyclonal free light chains (FLCs) of the immunoglobulins as markers of immune activation in the management of psoriatic patients on treatment with biologics. The overall study population included 30 patients affected by mild-to-severe psoriasis with either ongoing biological treatment or without any current systemic therapy and