Granulocytes

1

What are the signs and symptoms suggestive of a defect in neutrophil number or function?

The skin and mucous membranes are the first line of defense against infection. Once these barriers are broken, the white blood cells (WBCs), specifically neutrophils, come into play. When neutrophil counts are low or defective, the most common sites of infection are the skin and mucous membranes. Common presentations include cellulitis, superficial or deep abscesses, furunculosis, pneumonia, and septicemia. Also common are gingivitis, aphthous ulcers, perirectal inflammation, and otitis media. Recurrent respiratory infections, such as pneumonia or sinusitis, also raise suspicion of a WBC disorder. With profound neutropenia (< 200 cells/μL), patients may present with high fevers and no obvious focus of infection. The usual inflammatory signs may be absent because the neutrophils normally release cytokines to mediate an inflammatory response. Infants with frequent infections should be evaluated for an underlying problem in the neutrophils or other branches of the immune system.

2

What are the common pathogens noted in patients with neutrophil disorders?

Common infections arise from skin and gut flora. Patients with additional underlying immune defects (such as lymphocytes) or those who are neutropenic secondary to chemotherapy are also at risk for viral, fungal, and parasitic pathogens because of a more global immunodeficiency. Individuals with chronic granulomatous disease (CGD) are unable to mount a respiratory burst to destroy organisms. Common infections include Staphylococcus aureus, but there are also unusual pathogens, such as Burkholderia cepacia, Serratia marcescens, Candida species, and Aspergillus fumigatus.

3

What are normal values for white blood cells and neutrophil counts?

WBC and neutrophil counts vary with age and race. Newborns have high WBC counts of 10,000 to 30,000 cells/μL with predominantly neutrophils. These numbers drop sharply after the first few days of life. An infant’s WBC count after the first month is slightly higher than older children and adults (6,000–17,000 cells/μL), and the differential is predominantly lymphocytes, 60% to 70%, with 20% to 30% neutrophils. The toddler and preschool-aged child have approximately equal numbers of lymphocytes and neutrophils. The older child and adolescent have predominantly neutrophils with WBC counts similar to adults (5,000–11,000 cells/μL).

Neutropenia is defined as an absolute neutrophil count (ANC) less than 1,000 cells/μL for infants less than 1 year of age and 1,500 cells/μL for individuals greater than 1 year of age. The ANC is calculated by multiplying the total WBC count by the percentage of neutrophils plus bands. People of African or Caribbean ancestry have 200 to 600 neutrophils/μL fewer compared with Caucasians.

The severity and duration of neutropenia correlate with risk of infections. Neutropenia is graded according to ANC as follows:

• Mild neutropenia: ANC 1,000 to 1,500 cells/μL

• Moderate neutropenia: ANC 500 to 1,000 cells/μL

• Severe neutropenia: ANC less than 500 cells/μL

4

What are the clinical features of alloimmune and autoimmune neutropenia?

Neonatal alloimmune neutropenia is analogous to Rh hemolytic disease in that maternal antibodies directed against paternal antigens expressed on the surface of the neonate’s neutrophils cross the placenta and mediate immune destruction. The mother lacks the fetal WBC antigens that are inherited from the father. The most common antigens are NA1 and NA2, which are isotypes of the Fcγ receptor IIIB (FcγRIIIB). The infants may be quite ill with infections secondary to profound neutropenia, or they may be asymptomatic. Omphalitis, skin infections, pneumonia, sepsis, and meningitis are the most common infections. The diagnosis of alloimmune neutropenia is established by detecting antineutrophil antibodies in the mother that react with paternal cells.

Autoimmune neutropenia of childhood is generally a benign disorder. Affected individuals are often found incidentally with a routine blood count or when diagnosed with a minor infection. Despite ANCs of less than 500 cells/μL, 80% to 90% of patients do not have severe infectious complications. The total WBC count is normal. Some patients exhibit increased numbers of monocytes and eosinophils. The median age at diagnosis is 8 months with a range of 3 to 30 months. Other signs of autoimmune disease are absent. The disease is self-limited, often resolving by 4 years of age. Granulocyte colony-stimulating factor (G-CSF) can be used for those patients with severe infections.

Autoimmune neutropenia in adolescents and adults may be associated with systemic disease, such as systemic lupus erythematosus (SLE), rheumatoid arthritis, common variable immunodeficiency, hyper immunoglobulin M (IgM) syndrome, and immunoglobulin A (IgA) deficiency.