Evaluation Of Non Infectious Presentation of Inborn Errors Of Immunity

Overview

Inborn errors of immunity (IEI) are a wide number of conditions featured by impaired immune response, and their classification is in a continuous update, with the discovery of new clinical entities . Historically, the warning signs to identify children at risk of IEI have been defined according to the susceptibility to multiple or severe infectious diseases. High recurrence of infections, severe infections with need for hospitalization, use of intravenous antibiotics, and delayed resolution (and recently, infections by unusual pathogens or restricted pathogen susceptibility) are universally recognized as "red flags" for IEI . Recent advances in the clinical comprehension of IEI,. the immune dysregulation observed in patients with IEI is clinically expressed with autoimmunity, atopy, and lymphoproliferation, and these manifestations represent the first sign of the disease in about 10% of the patients .

Inborn errors of immunity (IEI) are a wide number of conditions featured by impaired immune response, and their classification is in a continuous update, with the discovery of new clinical entities (1). Historically, the warning signs to identify children at risk of IEI have been defined according to the susceptibility to multiple or severe infectious diseases. High recurrence of infections, severe infections with need for hospitalization, use of intravenous antibiotics, and delayed resolution (and recently, infections by unusual pathogens or restricted pathogen susceptibility) are universally recognized as "red flags" for IEI . Recent advances in the clinical comprehension of IEI, together with the expansion of their genetic background and the formulation of specific genotype-phenotype correlations, allowed the better characterization of the non-infectious manifestations of IEI Specifically, the immune dysregulation observed in patients with IEI is clinically expressed with autoimmunity, atopy, and lymphoproliferation, and these manifestations represent the first sign of the disease in about 10% of the patients. Additionally, new diseases with predominant immune dysregulation phenotype in absence of a significant increase of infections have been identified, leading to an extension of the paradigm of immunodeficiency During the diagnostic work-up, patients with non-infectious onset of IEI are frequently addressed to different specialists, including hematologists, endocrinologists, rheumatologists, and allergologists, often resulting in a delayed diagnosis. In this paper, we provide a brief review on the non-infectious manifestations of IEI potentially evidenced at disease onset, focusing on the specific items to be considered for the different clinical specialists