Hyper-IgE syndrome

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Hyper IgE syndrome (HIES) is a heterogeneous group of disorders characterized by recurrent staphylococcal infections, unusual eczema-like skin rashes, severe lung infections that result in pneumatoceles (balloon-like lesions that may be filled with air or pus or scar tissue) and very high concentrations of serum IgE. Some patients have an autosomal dominant form of the disease; these patients have problems with their bones including recurrent fractures and scoliosis. Many patients with autosomal dominant hyper IgE syndrome fail to lose their baby teeth and have two sets of teeth simultaneously.

Synonyms
Also known as Job-Buckley syndrome, Job syndrome, and Buckley syndrome.

History
HIES was first described by Davis et al in 1966 in two girls with red hair, chronic dermatitis, and recurrent staphylococcal abscesses and pneumonias. They named the disease after the biblical character Job, whose body was covered with boils by Satan. In 1972, Buckley et al described two boys with similar symptoms as well as coarse facies, eosinophilia, and elevated serum IgE levels. These two syndromes are thought to be the same and are under the broad category of HIES.

Pathophysiology
Abnormal neutrophil chemotaxis due to decreased production of interferon gamma is thought to cause the disease. But both autosomal dominant and recessive inheritance have been described. The disease was linked to mutations in the STAT3 gene after cytokine profiles indicated alterations in the STAT3 pathway.

Laboratory studies
Elevated IgE is the hallmark of HIES, usually > 10 times normal. However, patients younger than 6 months of age may have very low to non-detectable IgE levels. Eosinophilia is also a common finding with greater than 90% of patients having eosinophil elevations greater than two standard deviations above the normal mean.

Clinical characteristics
HIES often appears early in life with recurrent staphylococcal and candidal infections, pneumonias, and eczematoid skin. Characteristic facial, dental, and skeletal abnormalities have also been described. Patients with HIES have either delay of or failure in shedding of primary teeth. The characteristic facial features are usually set by age 16. These include facial asymmetry, a prominent forehead, deep-set eyes, a broad nasal bridge, a wide, fleshy nasal tip, and mild prognathism. Additionally, facial skin was rough with prominent pores. Finally, some patients have scoliosis, as well as bones that fracture easily.

Treatment
Most patients with hyper IgE syndrome are treated with chronic antibiotics to help protect them from staphylococcal infections. Good skin care is also important in patients with hyper IgE syndrome. High-dose intravenous gamma-globulin has also been suggested for the treatment of severe eczema in patients with HIES and atopic dermatitis.