Neutrophil Disorders

Diagnosis

Indications for Testing

  • Recurrent bacterial infections in the early neonatal period

Laboratory Testing

  • Initial testing – CBC, immunoglobulin evaluation; other testing based on clinical presentation
    • If severe neutropenia is present, consider evaluation for neutropenic disorders
  • Hyper IgE syndrome (Job syndrome)
    • Immunoglobulin testing
      • IgE levels – elevated, usually ≥200 IU/mL
      • All other levels – normal
    • Chemotaxis studies show that 80% of polynuclear neutrophils may have movement defects
    • Candida-specific IgE may be elevated
    • Molecular assay for mutations in STAT3 gene (available on a research basis)
  • Chédiak-Higashi
    • CBC with differential testing
      • Peripheral smear demonstrates large cytoplasmic myeloperoxidase-containing granules in the neutrophils and monocytes
      • Defective chemotaxis and slow intracellular killing of bacteria

Differential Diagnosis

  • Bone marrow aplasia
  • Drug-induced neutropenia
  • Antibody-mediated neutropenia
  • Hypersplenism
  • Viral bone marrow suppression
  • Neutropenic disorders of early childhood

Clinical Background

Neutrophil disorders are rare disorders associated with significant morbidity and mortality.

Epidemiology

  • Incidence – each individual disorder is rare
  • Age – usually discovered <1 year
  • Sex – M:F, equal, except for X-linked disorders

Classification

Specific Diseases

  • Hyper IgE syndrome (Job syndrome)
    • Inheritance – dominant mutations in STAT3 gene
    • Clinical presentation
      • Recurrent boils
      • Coarse facies
      • Impaired resorption of primary teeth
      • Recurrent mucocutaneous candida infections
      • Pneumonias, often with pneumatoceles
      • Recurrent bone fractures
      • Poor inflammatory responses
      • Increased risk of non-Hodgkin lymphoma
  • Chédiak-Higashi
    • Inheritance – autosomal recessive
    • Clinical presentation
      • Partial albinism
      • Severe infections – particularly with encapsulated organisms
      • Defective platelets with bleeding tendency (easy bruising, mucosal bleeding)

Indications for Laboratory Testing

  • Tests generally appear in the order most useful for common clinical situations
  • Click on number for test-specific information in the ARUP Laboratory Test Directory
Test Name and Number Recommended Use Limitations Follow Up
CBC with Platelet Count and Automated Differential 0040003
Method: Automated Cell Count/Differential

Identify the presence of neutropenia

   
Neutrophil-Associated Antibodies 0055506
Method: Qualitative Flow Cytometry

Rule out autoimmune neutropenia

 

May need to repeat complete blood count

Immunoglobulin E 0050345
Method: Quantitative ImmunoCAP® Fluorescent Enzyme Immunoassay

Rule out other syndromes, eg, hyper IgM, Bruton agammaglobulinemia

Test components include IgA, IgG, and IgM

   
Immunoglobulins (IgA, IgG, IgM), Quantitative 0050630
Method: Quantitative Nephelometry

Rule out immunoglobulin disorder

   
Myeloperoxidase Stain 0049030
Method: Cytochemical Stain

Use along with other clinical findings to diagnose chronic granulomatous disease 

   
Additional Tests Available
 
Click the plus sign to expand the table of additional tests.
Test Name and NumberComments
Lymphocyte Subset Panel 4 - T-Cell Subsets Percent and Absolute, Whole Blood 0095950
Method: Quantitative Flow Cytometry

Exclude reticular dysgenesis in infants