Inborn errors of immunity with atopic phenotype: what we know so far

Inborn errors of immunity with atopic phenotypes (IEIwA) represent a growing and complex subset of monogenic disorders that manifest primarily through severe and multifaceted allergic symptoms. These conditions bridge the fields of immunodeficiency and atopy, posing significant diagnostic and therapeutic challenges.

A literature search was performed via the online database PubMed, including all publication years 2021-2024, with the objective of identifying the most recent advancements in the field of IEIwA. This review provides an updated synthesis of the immunogenetic mechanisms underlying IEIwA, categorizing them by pathophysiological pathways, including impaired T cell receptor signaling, cytokine dysregulation, T cell repertoire restrictions, regulatory T cell dysfunction, metabolic abnormalities, and skin barrier defects. Advances in genomic technologies, especially whole-exome/genome sequencing, have refined the classification and recognition of these disorders. Moreover, the review highlights red flags that may aid in differentiating monogenic IEIwA from multifactorial allergic conditions. Emerging targeted therapies, such as monoclonal antibodies and small molecules, offer new avenues for precision medicine, though curative treatments like hematopoietic stem cell transplantation remain essential for many conditions.

This review underscores the need for heightened awareness, early recognition, and tailored management strategies to improve outcomes in patients with IEIwA.