Abstract
The hyper-IgE syndromes are rare, complex primary immunodeficiencies characterized by clinical manifestation diversity, by particular susceptibility to staphylococcal and mycotic infections as well as by a heterogeneous genetic origin. Two distinct entities - the classical hyper-IgE syndrome which is inherited in an autosomal dominant pattern and the autosomal recessive hyper-IgE syndrome have been recognized. The autosomal dominant hyper-IgE syndrome is associated with a cluster of facial, dental, skeletal, and connective tissue abnormalities which are not observable in the recessive type. In the majority of affected patients with autosomal dominant hyper-IgE syndrome a mutation in the signal transducer and the activator of the transcription 3 gene has been identified, leading to an impaired Th17 cells differentiation and to a downregulation of an antimicrobial response. A mutation in the dedicator of the cytokinesis 8 gene has been identified as the cause of many cases with autosomal recessive hyper-IgE syndrome and, in one patient, a mutation in tyrosine kinase 2 gene has been demonstrated. In this paper, the authors provide a review of the clinical manifestations in the hyper-IgE syndromes with particular emphasis on the diversity of their phenotypic expression and present current diagnostic guidelines for these diseases.
Highlights
The hyper-IgE syndrome (HIES) was first described in 1966 by Davis, Wedgwood and Schaller [1]; the authors perceived the similarity of severe dermatitis associated with “cold” abscesses with the disease attributed to the prophet Job and designated it “Job’s Syndrome”
Recent studies have demonstrated that hypomorphic mutations in the signal transducer and the activator of transcription 3 (STAT3) gene result in the classical multisystemic, autosomal dominant form of HIES, associated with facial, dental, skeletal, and connective tissue abnormalities [14,15,16]
In the report by Freeman et al [78] coronary artery tortuosity or dilation occurred in 70%, with aneurysms present in 37% of STAT3 mutated HIES patients, suggesting that STAT3 may play an integral role in vascular remodeling
Summary
The hyper-IgE syndrome (HIES) was first described in 1966 by Davis, Wedgwood and Schaller [1]; the authors perceived the similarity of severe dermatitis associated with “cold” abscesses with the disease attributed to the prophet Job and designated it “Job’s Syndrome”. Autosomal dominant HIES The clinical triad of symptoms found generally in 75% of all cases of AD-HIES and in 85% of patients over 8 years old includes: 1) recurrent staphylococcal abscesses, 2) recurrent airway infections, 3) increased concentration of immunoglobulin E in serum [7]. It has been stressed in the literature that neonatal rash is typically the first clinical manifestation of the hyper-IgE syndrome [20,21]. A review on the vascular features of both autosomal dominant, sporadic
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