[Diagnostic approach to suspected inborn errors of immunity]

Inborn errors of immunity (IEI) are currently categorized into 10 groups, encompassing 559 distinct disorders according to the latest classification, and this number is expected to continue growing. While the classic manifestations prompting diagnosis often relate to immunodeficiency, such as opportunistic, recurrent, or severe infections, non-infectious phenotypes frequently serve as the initial diagnostic clue. These include immune dysregulation-associated conditions, such as autoimmune enteropathy and other autoimmune diseases, as well as lymphoproliferative disorders and malignancies. This review aims to facilitate the clinical recognition of IEI based on both immunodeficiency and these atypical signs by outlining the characteristic manifestations across different IEI categories and the typical age at definitive diagnosis. It also overviews cases in which a malignancy prompts the diagnosis of IEI. By highlighting the clinical significance of non-infectious phenotypes, this review aims to guide clinicians in pursuing the necessary investigations for a definitive diagnosis and determining appropriate treatment strategies.