Infections in Inborn Errors of Immunity with Combined Immune Deficiency: A Review

Abstract

Enhanced susceptibility to microbes, often resulting in severe, intractable and frequent infections due to usually innocuous organisms at uncommon sites, is the most striking feature in individuals with an inborn error of immunity. In this narrative review, based on the International Union of Immunological Societies’ 2022 (IUIS 2022) Update on phenotypic classification of human inborn errors of immunity, the focus is on commonly encountered Combined Immunodeficiency Disorders (CIDs) with susceptibility to infections. Combined immune deficiency disorders are usually commensurate with survival beyond infancy unlike Severe Combined Immune Deficiency (SCID) and are often associated with clinical features of a syndromic nature. Defective humoral and cellular immune responses result in susceptibility to a broad range of microbial infections. Although disease onset is usually in early childhood, mild defects may present in late childhood or even in adulthood. A precise diagnosis is imperative not only for determining management strategies, but also for providing accurate genetic counseling, including prenatal diagnosis, and also in deciding empiric treatment of infections upfront before investigation reports are available.

Severe Combined Immunodeficiency—Classification, Microbiology Association and Treatment

“…Recurrent sinopulmonary infections are characteristic of primary immunodeficiencies such as SCID, and can result in severe complications including lung abscess, empyema, and pneumatocele. The bacterial causes of pneumonia include Staphylococcus aureus , Pseudomonas spp., Mycobacterium bovis , and other atypical mycobacteria [ 66 ]. Clinical imaging provides an important diagnostic clue in acute pulmonary infections in children with primary immunodeficiencies, as they often lack a thymic shadow [ 67 ].…”

Recurrent or unusual infections in children – when to worry about inborn errors of immunity

“…There are different susceptibilities to infection depending on the immunological defect; therefore, the pattern of infection may provide clues to the underlying immunological diagnosis. 1 We are increasingly recognising a wider phenotype of IEI. Extra-immune manifestations and associations are being reported regularly, with immune dysregulation and predisposition to malignancy now recognised as features of IEI.…”