Neutrophil Disorders

Neutrophil Disorders

Immunodeficiency Evaluation for Chronic Infections in Infants and Children Testing Algorithm

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 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
- Malignant infiltration of bone marrow (eg, neuroblastoma)
- Leukemia (ALL)

Tests generally appear in the order most useful for common clinical situations

Test name: CBC with Platelet Count & Automated Differential

ARUP #: 0040003

Methodology: Automated Cell Count with Flow Cell Differential

Use:

Identify the presence of neutropenia

Test name: Lymphocyte Antigen & Mitogen Proliferation Panel

ARUP #: 0096056

Methodology: Cell Culture

Use:

Antigens tested are phytohemagglutinin, concanavalin A, pokeweed mitogen, Candida antigen, and tetanus

Rule out hyper IgE syndrome

Test name: Neutrophil-Associated Antibodies

ARUP #: 0055506

Methodology: Qualitative Flow Cytometry

Use:

Rule out autoimmune neutropenia

Follow-up:

May need to repeat complete blood count

Test name: Lymphocyte Subset Panel 7 - Congenital Immunodeficiencies

ARUP #: 0095899

Methodology: Quantitative Flow Cytometry

Use:

Exclude reticular dysgenesis in infants

Test name: Immunoglobulin E

ARUP #: 0050345

Methodology: Quantitative Electrochemiluminescent Immunoassay

Use:

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

Test components include IgA, IgG, and IgM

Test name: Immunoglobulins, Quantitative

ARUP #: 0050630

Methodology: Quantitative Nephelometry

Use:

Rule out immunoglobulin disorder

Test name: Myeloperoxidase Stain

ARUP #: 0049030

Methodology: Cytochemical Stain

Use:

Use along with other clinical findings to diagnose chronic granulomatous disease

Additional Tests Available

Test name: Lymphocyte Subset Panel 4 - T-Cell Subsets Percent and Absolute, Whole Blood

ARUP #: 0095950

Methodology: Quantitative Flow Cytometry

Comments:

Exclude reticular dysgenesis in infants

General

ARUP Institute for Clinical and Experimental Pathology®

Medical Reviewers

Comprehensive Review: April 2011
Last Update: April 2011

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