Ichthyoses are genetically determined cornification disorders of the epidermis characterized by the presence of different degrees of scaling, hyperkeratosis, and erythroderma often associated with palmoplantar keratoderma. Different classifications of these diseases have been proposed, often based upon the involved genes and/or the clinical presentation. The clinical features of these diseases present some overlap of phenotypes among distinct genetic entities, depending mainly on the penetrance of mutations. In this study, using a clinical, genetic, and molecular approach, we analyzed a family with two affected members who had clinical and histological features resembling erythrokeratodermia variabilis (EKV) or a type of erythrodermic hyperkeratosis with palmoplantar keratoderma. Despite of the clinical presentation, we demonstrated that the affected patients were genetically double heterozygous for two different mutations in the ABCA12 gene, known to be responsible for harlequin ichthyosis. To explain the mild phenotype of our patients, we performed a molecular characterization of the skin. In the upper layers of the epidermis, the results showed a patchy presence of the glucosyl-ceramides (GlcCer), which is the lipid transported by ABCA12, fundamental in contributing to skin impermeability. Indeed, the two mutations detected do not completely abolish ABCA12 activity, indicating that the mild phenotype is due to a partial loss of function of the enzyme, thus giving rise to an intermediate phenotype resembling EKVP, due to a partial depletion of GlcCer deposition.

Kidney transplantation is currently the treatment of choice for patients with end-stage kidney diseases. Although significant advancements in kidney transplantation have been achieved over the past decades, the host’s immune response remains the primary challenge, often leading to potential graft rejection. Effective management of the immune response is essential to ensure the long-term success of kidney transplantation. To address this issue, immunosuppressives have been developed and are now fully integrated into the clinical management of transplant recipients. However, the considerable inter- and intra-patient variability in pharmacokinetics (PK) and pharmacodynamics (PD) of these drugs represents the primary cause of graft rejection. This variability is primarily attributed to the polymorphic nature (genetic heterogeneity) of genes encoding xenobiotic-metabolizing enzymes, transport proteins, and, in some cases, drug targets. These genetic differences can influence drug metabolism and distribution, leading to either toxicity or reduced efficacy. The main objective of the present review is to report an historical overview of the pharmacogenetics of immunosuppressants, shedding light on the most recent findings and also suggesting how relevant is the research and investment in developing validated NGS-based commercial panels for pharmacogenetic profiling in kidney transplant recipients. These advancements will enable the implementation of precision medicine, optimizing immunosuppressive therapies to improve graft survival and kidney transplanted patient outcomes.

Background/Objectives: Alopecia areata is an autoimmune condition characterized by rapid hair loss in the scalp, eyebrows, and eyelashes, for which treatments are limited. Baricitinib, an oral inhibitor of Janus kinases 1 and 2, has been recently approved to treat alopecia areata. Methods: A total of 23 patients affected by severe alopecia areata (SALT > 50) for more than 6 months were enrolled, including 14 with AU, 3 with AT, and 6 with ophiasis, and all of whom were treated with baricitinib for a minimum of 52 weeks. Clinical and trichoscopic assessments were performed at each visit, and the impact on quality of life, anxiety, and depression was evaluated using the Skindex-16 and the Hospital Anxiety and Depression Scale (HADS), respectively. Results: A total of 23 patients were enrolled, with a mean age of 44.62 years and a mean SALT of 83.66. The mean value of the SALT score decreased to 51.23 at 6 months and 42.41 after one year. Psychological well-being and quality of life also improved, as demonstrated by the decrease in Skindex-16 and HADS scores. Trichoscopic signs showed a decrease in yellow dots and black dots and an increase in vellus hairs and hair regrowth. Adverse events during the treatment period were reported in 18.75% patients. No drop-outs were registered. Conclusions: Data on the effectiveness and safety of baricitinib are promising and support the use of this drug in severe forms of AA, also in the early stages. We also suggest performing trichoscopy in response to therapy.

SARS-CoV-2 severe acute respiratory syndrome has rapidly spread worldwide since 2019. All scientific and technological forces have concentrated towards the formulation of vaccines to contain the disease. In less than one year (December 2020) a first messenger RNA vaccine (Comirnaty, BioNTech/Pfizer) was authorized. However, the research community has wondered about possible side effects on the immune system, given the vaccines administration in phase 4. This study aims to evaluate the mRNA vaccine impact on the development of possible positive autoantibody profile in healthcare workers without any previous underlying pathology, after first, second and booster dose of Pfizer vaccine, by determining: circulating immune complexes concentrations (CIC); anti-myeloperoxidase (MPO) and anti-proteinase 3 (PR3) autoantibodies, the presence of antinuclear antibodies (ANA) and subsequent second level tests (extractable nuclear antigen (ENA) screen, double-strand DNA, extractable nuclear antigen (ANA) profile). The subjects were divided according to anti-SARS-CoV-2 IgG RBD antibodies increasing concentrations in: Group I < 10 BAU/ml (N = 114); Group II > 1000 BAU/ml (N = 112); Group III > 2500 BAU/ml (N = 78). Our data show no autoreactive response changes over time in healthy subjects after vaccination. In fact, evaluation of ANA, CIC, anti-MPO, anti-PR3 and the detection of specific autoantigens, did not display significant variations. The results suggest the exclusion of a correlation between the administration of the vaccine and the possible onset of autoimmune disorders. Nevertheless, further investigations will be needed to test for any long-term side effects on an ever-growing population.

Background/Objectives: Risk stratification of patients presenting to the emergency department (ED) with suspected infection is essential. Soluble urokinase plasminogen activator receptor (suPAR) has emerged as a promising biomarker of immune activation and outcome prediction, but its role in febrile ED patients remains to be fully defined. The aim of this study was to evaluate the prognostic value of suPAR and its potential clinical application in the ED. Methods: A single-center retrospective study including 125 patients was performed. Plasma suPAR levels were measured together with C-reactive protein (CRP) and procalcitonin (PCT), and their association with 28-day mortality using Cox regression and ROC curve analyses was assessed. Results: SuPAR was independently associated with the risk of 28-day mortality, showing a very high negative predictive value. Higher suPAR levels were associated with an increased risk of death. Conclusions: SuPAR may represent a valuable tool to support early patient assessment and risk stratification in the ED, potentially improving resource utilization and patient prioritization.