Hyperimmunoglobulin IgE syndrome

Hyperimmunoglobulin E (hyper IgE) syndrome (HIES), also known as Job syndrome, consists of a heterogeneous group of complex hereditary combined B- and T-cell immune deficiency diseases characterised by recurrent Staphylococcus aureus chest infections, characteristic coarse facial appearance and dental problems with an eczema-like pruritic dermatitis. 

Terminology

There are at least two types of hyper IgE syndrome ²:

• autosomal dominant (STAT3 deficiency)
  • more common
  • caused by a mutation in STAT3 gene
• autosomal recessive
  • aetiology unknown
  • maybe be associated with DOCK8 deficiency and phosphoglucomutase 3 (PGM3) deficiency

This article is concerned with the more common autosomal dominant hyper IgE syndrome (HIES), also known as STAT3 deficiency.

Clinical presentation

The first sign of the disease is pustules and eczematoid rashes of the face and scalp.

• skeletal manifestations
  • scoliosis
  • minimal trauma fractures due to osteoporosis
  • hyperextensibility of the joints
  • delayed exfoliation of primary teeth, then normal permanent dentition
• facial changes
  • facial asymmetry
  • broad nose
  • deep-set eyes with a prominent forehead
  • facial skin thickening with prominent pores occurs during adolescence

The most characteristic features are recurrent Staphylococcal cold abscesses and recurrent relatively silent pneumonias ².

Radiographic features

In hyper IgE syndrome recurrent chest infections in childhood with Staphylococcus aureus are usually less symptomatic than in immunocompetent children. Hence in most cases, delayed treatment results in severe damage to the lung parenchyma. Besides, even after adequate treatment of the acute infection, the healing process causes severe parenchymal injury, bronchiectasis, scarring, and large pneumatocele formation.

After several pulmonary infections, the lungs become more susceptible to secondary indolent infections with Pseudomonas and Aspergillus which are difficult to treat, with usual worsening of the parenchymal and bronchial damage, resulting in a vicious circle of lung infections and injury.

History and etymology

Hyper IgE syndrome was first described by American paediatrician Starkey D Davis et al in 1966, who referenced the biblical Job who was "smote in sore boils" ^2,4.