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 characterized by recurrent Staph aureus chest infections, characteristic coarse facial appearance and dental problems with eczema-like pruritic dermatitis.
There are as least two types of HIES 2:
- autosomal dominant (STAT3 deficiency)
- more common
- caused by a mutation in STAT3 gene
- autosomal recessive
- etiology unknown
- maybe be associated with DOCK8 deficiency and phosphoglucomutase 3 (PGM3) deficiency
This article is concerned with the more common autosomal dominant HIES.
First sign of disease is pustules and eczematoid rashes in the face and scalp. Skeletal manifestations include scoliosis, minimal trauma fractures due to osteoporosis, and hyperextensibility of the joints. Failure of exfoliation of primary teeth. After delayed shedding of primary teeth or extraction, the normal secondary teeth will emerge. Facial changes such as facial asymmetry, broad nose, and deep-set eyes with a prominent forehead, facial skin thickening with prominent pores occur during adolescence.
The most characteristic features are recurrent Staphylococcal cold abscesses and recurrent relatively silent pulmonary infections 2.
Recurrent chest infections in childhood with Staph aureus usually are less symptomatic than in immunologically normal children hence in most cases, delayed treatment results in severe damage to the lung parenchyma. Besides, even after adequate treatment of the acute infection, healing process in these patients causes severe parenchymal injury, bronchiectasis, scarring, and large pneumatocele formation. After initial injuries, lungs become susceptible to the secondary indolent infections with Pseudomonas and Aspergillus infections which are difficult to treat and they usually worsen the parenchymal and bronchial damage.
History and etymology
HIES was first described by Davis et al in 1966, who referenced the biblical Job who was "smote in sore boils" 2.
- 1. Jończyk-Potoczna K, Szczawińska-Popłonyk A, Warzywoda M et-al. Hyper Ig E syndrome (Job syndrome, HIES) - radiological images of pulmonary complications on the basis of three cases. Pol J Radiol. 2012;77 (2): 69-72. Free text at pubmed - Pubmed citation
- 2. Freeman AF, Holland SM. The hyper-IgE syndromes. Immunol Allergy Clin North Am. 2008;28 (2): 277-91, viii. doi:10.1016/j.iac.2008.01.005 - Free text at pubmed - Pubmed citation
- 3. García-Peña P, Boixadera H, Barber I et-al. Thoracic findings of systemic diseases at high-resolution CT in children. Radiographics. 2011;31 (2): 465-82. doi:10.1148/rg.312095160 - Pubmed citation