Neutrophil Disorders

Diagnostic Algorithm

  Immunodeficiency Evaluation for Chronic Infections in Infants and Children Testing Algorithm

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

• Chronic granulomatous disease
• Leukocyte adhesion deficiency
• Hyper IgE syndrome
• Chédiak-Higashi

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)

Diagnosis

Indications for Testing

• Recurrent bacterial infections in the early neonatal period

Laboratory Testing

• Initial testing – CBC, immunoglobulins for most disorders; 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
  • Malignant infiltration of bone marrow (eg, neuroblastoma)
  • Leukemia

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

Click the plus sign to expand the table of additional tests.

Test Name and Number	Comments
Lymphocyte Subset Panel 4 - T-Cell Subsets Percent & Absolute, Whole Blood 0095950 Method: Flow Cytometry	Exclude reticular dysgenesis in infants