hyperimmunoglobulin E (Job's syndrome)

Epidemiology

rare

Pathology

• associated with primary immunodeficiency
• phagocyte dysfunction
  • reduced chemotaxis (some patients)
• reduced suppressor T-cell activity
  • skewed T helper 1 (Th1) cell/Th2 cell ratio
• involvement of chemokines

Genetics

• most cases are sporadic
• autosomal dominant & autosomal recessive forms
• associated with defects in STAT3

Clinical manifestations

• chronic eczematoid or pruritic dermatitis
• recurrent staphylococcal abscesses
• sporadic & autosomal dominant
  • generally part of a multisystem disorder including
    • abnormalities of soft tissue, skeleton, & dentition
  • recurrent pneumonias with Staphylococcus aureus
    • bronchopleural fistulas
    • cyst formation
    • bronchiectasis
    • pneumatoceles
  • scoliosis
• autosomal recessive
  • severe molluscum contagiosum & other viral infections
  • may develop severe neurological complications
  • lack skeletal or dental involvement
  • do not develop lung cysts
• other variants
  • restrictive lung disease
  • sinusitis
  • mucocutaneous candidiasis
  • atopy
  • coarse facies

Laboratory

• high serum levels of IgE & IgD
  • serum IgE > 2000 IU/mL
  • high serum anti S. aureus IgE
• normal serum levels of IgA, IgG & IgM
  • low or absent serum & salivary anti S. aureus IgA
• sputum
  • gram stain & culture
    • Staphylococcus aureus
    • Streptococcus pneumoniae
    • gram negative bacilli
  • fungal stains & culture
    • Candida albicans
    • Aspergillus species
• complete blood count
  • mild eosinophilia

Differential diagnosis

• allergic pulmonary aspergillosis
  • asthma, eosinophilia, elevated serum IgE, bronchiectasis
• hyper IgE recurrent infection syndrome autosomal recessive

Management

• prevention & management of infections
  • sustained systemic antibiotics & antifungals
• topical therapy for eczema
• drainage of abscesses
• anti-staphylococcal antibiotic prophylaxis may be useful
• interferons, immunoglobulin supplementation, & low-dose cyclosporine A of suggested benefit in selected patients, but generally not indicated

More general terms

• mixed cellular & humoral immune dysfunction
• phagocytic disorder
• syndrome

Additional terms

• IgE in serum
• immunoglobulin-E (IgE)