Neutropenia in primary immunodeficiency

Abstract

Purpose of review Neutropenia is a feature of several primary immunodeficiency diseases (PIDDs). Because of the diverse pathophysiologies of the PIDDs and the rarity of each disorder, data are often lacking, leading to the necessity of empiric treatment. Recent developments in the understanding of neutropenia in several of the PIDDs make a review of the data timely. Recent findings The category of severe congenital neutropenia continues to expand. Mutations in G6PC3 have been identified as the cause of neutropenia in a minority of previously molecularly undefined cases. Recent advances have broadened our understanding of the pathophysiology and the clinical expression of this disorder. A possible function of the C16orf57 gene has been hypothesized that may explain the clinical overlap between Clerucuzio-type poikiloderma with neutropenia and other marrow diseases. Plerixafor has been shown to be a potentially useful treatment in the warts, hypogammaglobulinemia, infection, and myelokathexis syndrome. Investigations of patients with adenosine deaminase deficient severe combined immunodeficiency have identified neutropenia, and particularly susceptibility to myelotoxins, as a feature of this disorder. Granulocyte-colony stimulating factor is the treatment of choice for neutropenia in PIDD, whereas hematopoietic cell transplantation is the only curative option. Summary The number of PIDDs associated with neutropenia has increased, as has our understanding of the range of phenotypes. Additional data and hypotheses have been generated helping to explain the diversity of presentations of neutropenia in PIDDs.

A novel phenotype variant of severe congenital neutropenia caused by G6PC3 deficiency

“…ANC recovery, absence of immature PMN in the peripheral blood and clinical improvement in our patient after G‐CSF treatment, indicate that granulocytes leaving the bone marrow were mature and functionally competent. Finally, the therapeutic response to G‐CSF in our patient is in agreement with the current use of G‐CSF as the treatment of choice for SCN4 syndrome 10.…”

Practice parameter for the diagnosis and management of primary immunodeficiency

“…Infections in neutropenic patients are generally associated with fever and malaise. 497,498 Pharyngitis with lymphadenopathy is common; pneumonia, mastoiditis, and cellulitis also occur. Periodontitis can accompany oral ulceration and gingivitis; vaginal and rectal mucosal ulcers are also seen.…”

Vaccine-associated varicella and rubella infections in severe combined immunodeficiency with isolated CD4 lymphocytopenia and mutations in IL 7 R detected by tandem whole exome sequencing and chromosomal microarray

“…Hypergammaglobulinaemia was also reported in another child with IL-7Rα-deficient SCID and maternal engraftment [36]. Neutropenia, not commonly associated with IL-7Rα-deficient SCID, was the most prominent abnormality identified in this patient prior to presentation with severe infection [36,37]. It is plausible that IL-7 may play a role in myelopoiesis, as IL-7 stimulation of T cells induces production of granulocyte-macrophage colony-stimulating factor (GM-CSF) [38].…”