The immunocompromised patient: primary immunodeficiencies

The genetic understanding of primary immunodeficiency diseases (PIDs) has rapidly advanced over the past 10 years; the number of known genetic causes now approaches 200. Most are very rare disorders that have increased our understanding of the crucial cellular pathways required for protection against infection by a wide variety of microbes. Although genetic disorders causing auto-inflammatory disease are often included under the PID umbrella, this review will focus on those associated with a susceptibility to infection. Most clinicians do not need a detailed knowledge of the different types of PID, but they should be aware of the possibility of PID in patients presenting with recurrent or persistent infection, and be in a position to refer patients to a regional specialized clinic. An understanding of which components of the immune system protect against different infections makes the diagnostic process more rewarding. Because many of the more severe PIDs present in infancy or childhood, paediatricians should have some special training in the area so that they know which patients require urgent referral to an expert centre. There have been some landmark recent advances in the management of severe PIDs, particularly in human bone marrow/stem cell transplantation and gene therapy where complete cures have been achieved.