When to consider an inborn error of immunity: clues for physicians

Abstract

The term inborn errors of immunity (IEIs) refers to the rapidly expanding group of genetic disorders causing dysregulation of the immune system. With improved genetic testing in recent years, the number of defined IEIs and their range of phenotypic presentations has grown vastly, with more than 550 IEIs now described. IEIs cause diverse clinical manifestations, including infection, autoimmunity, lymphoproliferation, allergy and malignancy, with initial manifestations often appearing long before the diagnosis of an IEI is made. Furthermore, IEIs are increasingly diagnosed in adulthood, and a family history of disease is not always apparent. Physicians in all specialties are likely to encounter patients with IEIs, often before a formal diagnosis of an IEI is made or immunology consultation sought. Early diagnosis of an IEI improves patient outcomes through access to specialist immunology services and the potential for more specific, targeted treatment options. All physicians, therefore, need an understanding of IEIs and presenting manifestations in order to identify these patients early. This review outlines common clinical presentations of IEIs in adulthood across different specialties, including guidelines regarding when an underlying IEI should be considered.