Neutrophil Dysfunction

Clinical Background

Numerous disorders may cause neutropenia, which is defined as an absolute reduction in the number of circulating neutrophils.

Epidemiology

Incidence - each individual disorder is rare except for autoimmune disorders
Age - most often discovered before 1 year old
Gender - no gender preference except for X-linked disorders

Classification

Congenital
- Cyclic hematopoiesis (cyclic neutropenia)
- Severe chronic neutropenia
- Familial benign neutropenia
- Myelokathexis
Immune-mediated
- Autoimmune neutropenia of infancy (ANI)
- Immune-mediated neutropenia in the neonate
Complex syndromes
- Chronic granulomatous disease
- Primary immunodeficiencies (X-linked hyper IgM syndrome, hyper IgE syndrome)
- Chédiak-Higashi syndrome
- Shwachman-Diamond syndrome
- Cartilage hair hypoplasia (onychotrichodysplasia)
- Metabolic disorders - glycogen storage disease
- Reticular dysgenesis
- Fanconi anemia

Specific Diseases

Cyclical neutropenia
- Genetics - autosomal dominant
- Clinical presentation - recurring fever, mucosal ulcers and occasional life-threatening infections
Severe chronic neutropenia (Kostmann syndrome)
- Genetics
  - Autosomal dominant, autosomal recessive, sporadic
- Clinical presentation
  - Early onset of severe neutropenia and life-threatening infections
    - Cellulitis, omphalitis, stomatitis, sepsis, meningitis
    - Common organisms include S. aureus, E. coli and Pseudomonas spp
  - Late developing myelodysplastic syndrome and acute myelogenous leukemia
Autoimmune neutropenia of infancy (ANI)
- Clinical presentation
  - Later onset of mild to severe infections (8-10 months old)
    - Pyoderma, URIs, otitis media
Immune-mediated neutropenia in the neonate
- Clinical Presentation
  - Similar to ANI
Hyper IgE syndrome (Jobs syndrome)
- Clinical Presentation
  - Recurrent boils
  - Coarse facies
  - Impaired resorption of primary teeth
  - Recurrent mucocutaneous candida infections
Chédiak-Higashi
- Genetics - autosomal recessive
- Clinical Presentation
  - Partial albinism
  - Severe infections - particularly with encapsulated organisms
  - Defective platelets
Shwachman-Diamond syndrome
- Genetics - autosomal recessive
- Clinical Presentation
  - Pancreatic insufficiency, neutropenia, chronic eczema and metaphyseal dysostosis
Onychotrichodysplasia
- Genetics - autosomal recessive
- Clinical Presentation
  - Hypoplastic nails
  - Neutropenia
  - Sparse hair
Glycogen storage disease type 1b (GSD 1b)
- Clinical Presentation (identical to von Gierke type [GSD 1a])
  - Hypoglycemia, hyperlipidemia and lactic acidosis
  - Hepatomegaly
  - Recurrent infections - oral and perianal abscesses
Reticular dysgenesis
- Clinical Presentation
  - Lymphoid and thymic hypoplasia with severe combined immune deficiency
  - Overwhelming infections in the first two weeks of life