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At a glance

A genetic immunologic disorder characterized by recurrent skin (eczema-like) and severe lung infections, mainly caused by Staphylococcus aureus, multiple fractures, eczematous dermatitis, coarse facies, and elevated immunoglobulin(Ig)E. The presence of pneumatoceles in association with the skin lesions is a characteristic of this medical condition. In the recent years, other features have been described with this condition and include vascular abnormalities, including coronary aneurysm without atherosclerosis, focal cerebral hyperintensities, and Chiari Type I malformations. Mortality is usually associated to recurrent lung infections in adulthood period.

Synonyms

Hyper IgE Syndrome; Hyperimmunoglobulin E Syndrome; HIE Syndrome; Hyperimmunoglobulin E-Recurrent Infection Syndrome; Job Buckley Syndrome; Buckley Syndrome.

History

The Hyperimmunoglobulin E Syndrome (HIES; Hyper IgE Syndrome) was first described by S. Davis et al in 1966 in two girls with red hair, chronic dermatitis, and recurrent staphylococcal abscesses and pneumonias. This medical condition was named after the biblical figure Job whose body was covered with boils by Satan. In 1972, R. 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. In 2007, Freeman et al, reported important clinical variants symptoms to the disease.

Incidence

Undetermined; no sex or racial prevalence. The age of onset of the disease has been reported in a retrospective study at puberty, ie, 12 years of age.

Genetic inheritance

Autosomal recessive trait with variable penetrance. In 2007, autosomal dominant mutations in signal transducer and activator of transcription-3 (STAT3) gene were identified as the molecular cause of this disease.

Pathophysiology

Affected patients have an inadequate inflammatory response as a consequence of decreased chemotactic responses by neutrophils. Additionally, there is an imbalance between T-helper Type 1 (Th1) cell production of interferon-gamma, which is low, and T-helper Type 2 (Th2) cell production of interleukin-4, which is high. In more recent years, the presence of mutations in the family of signal transducer and activator of transcription (STAT3) gene was identified in almost all cases of clinically verified HIES. STAT3 is one of seven human STAT proteins that are critical second messengers for many cytokine, hormone, and growth factor receptors. Whether these cytokine abnormalities could be consistent with increased IgE production, there is no correlation between IgE and interleukin-4 levels. These cytokine disorders cannot explain the high incidences of bone fractures, skeletal disorders, and facial features of the syndrome.

Diagnosis

Based on clinical symptoms (immunodeficiency syndrome characterized by recurrent bacterial [staphylococcal] infections and elevated IgE levels) and immunoglobulin assays.

Clinical aspects

Patients look generally well with red hair, fair skin; they have reddish-brown eyes, coarse ...

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