Pistachio Allergy: Integrating Molecular Diagnostics and Clinical Phenotypes

Background: Pistachio allergy is an increasingly recognized form of tree nut allergy and is strongly associated with cashew allergy due to pronounced molecular cross-reactivity. Despite its relatively low prevalence in the general population, pistachio allergy may result in severe systemic reactions and represents a significant diagnostic challenge, particularly in polysensitized patients. Objective: This narrative review aims to critically evaluate current diagnostic approaches to pistachio allergy, with a focus on molecular allergen components, mechanisms of cross-reactivity, clinical phenotypes, and the added value of advanced diagnostic tools for risk stratification. Methods: A narrative synthesis of the literature was conducted, integrating data from population-based studies, clinical cohorts, component-resolved diagnostics, basophil activation testing, and oral food challenge studies. Emphasis was placed on the diagnostic performance and clinical utility of extract-based versus molecular and functional assays. Results: Pistachio allergy is predominantly associated with sensitization to seed storage proteins, including 2S albumins, 7S vicilins, and 11S legumins, which share high sequence and structural homology with corresponding cashew allergens. This molecular relationship underlies frequent co-sensitization and clinical co-reactivity. Conventional extract-based tests show limited specificity, whereas component-resolved diagnostics and functional assays improve diagnostic precision, facilitate phenotype-based risk stratification, and may reduce the need for oral food challenges in selected patients. Conclusions: Accurate diagnosis of pistachio allergy requires an integrated approach combining clinical history with molecular and functional diagnostics. Incorporation of component-resolved diagnostics and basophil activation testing into diagnostic algorithms allows improved differentiation between asymptomatic sensitization and clinically relevant allergy, supporting individualized patient management and safer clinical decision-making.