Abstract & Commentary

Identifying Children with Primary Immunodeficiency Diseases

By Hal B. Jenson, MD, FAAP, Dean, Western Michigan University School of Medicine, Kalamazoo, MI, is Associate Editor for Infectious Disease Alert.

Dr. Jenson reports no financial relationship to this field of study.

Synopsis: The three strongest identifiers of primary immunodeficiency were a family history of immunodeficiency disease, use of intravenous antibiotics for sepsis (neutrophil deficiencies), and failure to thrive (T lymphocyte deficiencies).

Source: Subbarayan A, Colarusso G, Hughes SM, et al. Clinical features that identify children with primary immunodeficiency diseases. Pediatrics 2011;127:810-816.

A retrospective study was conducted of 563 children who presented over the last decade to two pediatric immunodeficiency centers in the United Kingdom. The study included 133 children for whom detailed investigations failed to identify immunodeficiency, and 430 children diagnosed with primary immunodeficiency disease (74 with neutrophil or monocytic immuno-deficiency, 92 with B lymphocyte immuno-deficiency, 22 with complement immunodeficiency, and 242 with T lymphocyte immunodeficiency). As is typical, T lymphocyte deficiencies presented at a median of 1 month of age, neutrophil immunodeficiencies presented in early infancy, and B lymphocyte and complement immunodeficiencies presented in late infancy and early childhood.

The strongest identifiers of primary immuno-deficiency diseases were a family history of physician-diagnosed immunodeficiency disease (present in 34% of children with primary immunodeficiency and 4% without), use of IV antibiotics for sepsis (an indicator of neutrophil immunodeficiencies), and failure to thrive (an indicator for T lymphocyte immunodeficiencies). These three signs identified 96% of patients with neutrophil and complement deficiencies, and 89% of T lymphocyte immuno-deficiencies. Family history was the only warning identifier for children with B lymphocyte immunodeficiencies.


The incidence of primary immunodeficiency diseases in the United Kingdom and United States is approximately 1 per 10,000 and 20,000, respectively. This study found that these three sentinel indicators were the most important in identifying children with primary immunodeficiencies.

The National Primary Immunodeficiency Resource Center in the United States and the Primary Immunodeficiency Association in the United Kingdom promote the use of 10 warning signs of primary immunodeficiency. These criteria were developed by the Jeffery Model Foundation based on expert opinion with little or no population-based data to support their general use. The results of this study indicate that a simplified set of three screening criteria are able to correctly identify 96% of patients with neutrophil and complement deficiencies, and 89% of T lymphocyte immunodeficiencies.

Physicians managing children with recurrent, unusual, or severe infections should always inquire about a family history of primary immunodeficiency as well as a history of unexpected deaths among relatives during early childhood. Neutrophil immunodeficiency should always be considered in children requiring IV antibiotics for sepsis; screening tests include a complete blood count and differential count, and a neutrophil oxidative burst test. T lymphocyte immunodeficiency should always be considered in infants with failure to thrive; screening tests include a complete blood count and differential count, and lymphocyte subsets. Increased awareness of these three warning indicators among physicians is likely of more benefit than increased awareness of the 10 warning signs among parents.