RESUMEN
Cutaneous immune-related adverse events are frequently associated with immune checkpoint inhibitors (ICIs) administration in cancer patients. In fact, these monoclonal antibodies bind the cytotoxic T-lymphocyte antigen-4 and programmed cell death-1/ligand 1 leading to a non-specific activation of the immune system against both tumoral cells and self-antigens. The skin is the most frequently affected organ system appearing involved especially by inflammatory manifestations such as maculopapular, lichenoid, psoriatic, and eczematous eruptions. Although less common, ICI-induced autoimmune blistering diseases have also been reported, with an estimated overall incidence of less than 5%. Bullous pemphigoid-like eruption is the predominant phenotype, while lichen planus pemphigoides, pemphigus vulgaris, and mucous membrane pemphigoid have been described anecdotally. Overall, they have a wide range of clinical presentations and often overlap with each other leading to a delayed diagnosis. Achieving adequate control of skin toxicity in these cases often requires immunosuppressive systemic therapies and/or interruption of ICI treatment, presenting a therapeutic challenge in the context of cancer management. In this study, we present a case series from Italy based on a multicenter, retrospective, observational study, which included 45 patients treated with ICIs who developed ICI-induced bullous pemphigoid. In addition, we performed a comprehensive review to identify the cases reported in the literature on ICI-induced autoimmune bullous diseases. Several theories seeking their underlying pathogenesis have been reported and this work aims to better understand what is known so far on this issue.
RESUMEN
BACKGROUND: Atopic dermatitis is a disease characterized by a chronic inflammatory process in the skin, but its link to miRNA 155 is less known. The aim of the study was to evaluate the expression of microRNA155, and T helper type 17 cells and Treg cells in children with atopic dermatitis. METHODS: The study population consisted of: children seen for atopic dermatitis at the outpatient ambulatory of Dermatology at the Children Hospital Regina Margherita, Torino, Italy (N.=23); healthy control subjects (N.=23). Blood samples were taken during routine control analysis and the expression of miRNA 155 and the production of FOXP3 and RORγ was determined using PCR real time. RESULTS: The analysis of miR-155 shows that the over-expression of miR-155 is statistically significant (P=0.0040) in the group of patients with atopic dermatitis compared to the healthy control group. Analysis of mRNAs of FOXP3 and RORγ shows a FOXP3 mRNA expression statistically higher in the group of patients (P=0.0057). The Th17 / Treg ratio is significantly smaller in patients with atopic dermatitis (P=0.0012). Also the ratio miR-155/Th17/Treg is larger in the group of patients with atopic dermatitis (P=0.0002). CONCLUSIONS: Our results suggest that increased miR-155 and FOXP3 and RORγ responses may provide a link to immune dysregulation associated with atopic dermatitis. Although a point-by-point correlation between miR-155 and the ratio Th17/Treg is not demonstrated, our findings shows that these two elements do not appear to be completely unrelated to each other.
