Autoimmune diseases are heterogeneous, multifactorial disorders defined by a loss of immunological tolerance to self-antigens, resulting in chronic inflammation and tissue damage. Even though the immune system dysregulation most commonly elicits physical symptoms, neuropsychiatric manifestations are frequently observed in autoimmune diseases and are associated with increased morbidity, elevated mortality, and a marked decline in health-related quality of life. Although extensively characterized in systemic lupus erythematosus (SLE) due to its epidemiological relevance and diagnostic complexity, neuropsychiatric involvement holds clinical significance across a wider spectrum of rheumatologic disorders. The frequent co-occurrence of connective tissue disorders with mood and anxiety symptoms suggests shared etiological mechanisms. The early identification of neuropsychiatric manifestations in patients with chronic autoimmune diseases represents the cornerstone of clinical management, given the substantial impact these symptoms have on individuals already burdened by debilitating conditions. We reviewed the principal neuropsychiatric manifestations associated with selected systemic autoimmune diseases: the novelty of this research lies not only in its approach to autoimmune-related neuropsychiatric symptoms but also in the special emphasis placed on the immunopathogenic mechanisms potentially responsible for these manifestations and, more significantly, on therapeutic decision-making, including an evaluation of treatment strategies targeting immune dysregulation and their potential impact on the neuropsychiatric profile, to optimize clinical outcomes and ensure patients have a comprehensive cure.

Anaphylaxis is a severe systemic hypersensitivity reaction characterized by rapid onset, unpredictable clinical course, and potentially fatal outcomes. Although its diagnosis remains primarily clinical, the identification of biomarkers capable of improving risk stratification and understanding disease mechanisms remains an important unmet need. Among the mediators implicated in anaphylaxis, platelet-activating factor (PAF) has emerged as a key effector molecule involved in vascular permeability, bronchoconstriction, platelet activation, and cardiovascular dysfunction. The biological activity of PAF is tightly regulated by platelet-activating factor acetylhydrolase (PAF-AH), the enzyme responsible for its degradation, making the PAF–PAF-AH axis a potentially important determinant of reaction severity. OBJECTIVES: The present review summarizes current knowledge regarding the biology of PAF and PAF-AH and examines their role in the pathophysiology of anaphylaxis, with particular emphasis on Hymenoptera venom allergy (HVA). The therapeutic potential of targeting the PAF pathway is also discussed. Experimental and clinical evidence consistently suggests an association between increased PAF activity, reduced PAF-AH activity, and more severe anaphylactic reactions. However, methodological limitations, biological variability, and conflicting findings across studies currently limit the clinical applicability of these molecules as standalone biomarkers. Overall, the PAF–PAF-AH axis represents a biologically plausible link between molecular mechanisms and clinical severity in anaphylaxis. Further studies are required to standardize measurements, validate clinical utility, and define the role of this pathway as both a biomarker and therapeutic target; hence gaining insight into PAF’s role in various biological processes is critical.

Intravenous immunoglobulin (IVIg) is a pooled product containing polyclonal IgG collected from the plasma of thousands of healthy donors. Originally developed as a replacement therapy for patients with humoral immunodeficiencies, IVIg has since been widely adopted in the treatment of several autoimmune and inflammatory conditions, owing to its extensive immunomodulatory and anti-inflammatory effects. IVIg exerts a wide range of actions by influencing multiple components of both the innate and adaptive immune systems. These include modulation of Fcγ receptor expression and function, inhibition of complement activation, neutralization of autoantibodies, regulation of cytokine networks, control of pro-inflammatory monocytes, and regulation of multiple immune cells, also through epigenetic modulation. Pediatric Acute-Onset Neuropsychiatric Syndrome (PANS) represents one of the most complex conditions in pediatric neuropsychiatry, involving the basal ganglia and characterized by a broad range of abrupt-onset neuropsychiatric symptoms, irrespective of the underlying infectious trigger. Recent clinical and translational studies indicate that IVIg can attenuate neuropsychiatric symptoms and restore immune balance in children with PANS. Randomized trials have produced variable results. Converging clinical and mechanistic evidence supports the potential therapeutic value of IVIg in selected patients with moderate-to-severe or relapsing disease. In this overview, we examine current data on IVIg use in PANS, emphasizing its immunological rationale, emerging clinical benefits, and the need for biomarker-guided studies to better identify responders and optimize treatment outcomes.