Leukocyte adhesion disorders (LAD) are a primary immune deficiency affecting phagocytic blood cells.

Epidemiology

• Incidence - <1/1,000,000
• Age - usually identified in infancy or early childhood

Inheritance 

• Heterogeneous mutations in the CD18 leukocyte integrin gene
• At least 3 defects known (LAD-I, LAD-II, LAD-III)
• Autosomal recessive inheritance

Pathophysiology

• Blood neutrophils are the first line of defense against bacterial and fungal infection
• Initial neutrophil adherence is weak but becomes strong with the aid of beta integrin interactions
• LAD involve defects in integrin expression leading to defective adhesion of neutrophils
  • Which then leads to increased susceptibility to bacterial and fungal infections
• LAD I - integrin expression defect; LAD II - selectin defect; LAD III - defect in integrin activation

Clinical Presentation

• LAD I - characterized by delayed separation of the umbilical cord, recurrent soft tissue infections, chronic periodontitis, marked leukocytosis
• LAD II - same features as LAD I, but also growth and mental retardation abnormalities and no delay in separation of umbilical cord
• LAD III - same features as LAD I and severe bleeding tendency

Treatment

• Early intervention for periodontal disease
• Preventive antibiotics for infection
• Allogeneic bone marrow transplant for severe disease

Diagnosis

• Laboratory testing
  • CBC reveals leukocytosis with neutrophilia (even in the absence of infection but exaggerated during infection)
  • Flow cytometric analysis
    • CD11b and CD18 expression on leukocytes
      • No expression - 75% die in infancy
      • 1-10% - 33% survive to age 40 years
      • >10% - mild deficiency which may not be recognized until late teen years

Differential Diagnosis

• Neutropenic syndromes
• Agranulocytosis
• IRAK-4 deficiency
• Job syndrome
• Chronic granulomatous disease