The hyperimmunoglobulin E syndrome - clinical manifestation diversity in primary immune deficiency

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.

Cutaneous Manifestations of Primary Immunodeficiency Diseases in Libyan Children

“…It was apredominant feature in HIES, it was of early onset in infancy, atypical and different from eczema in normal individuals in that it is chronic, extensive and refractory to treatment with tendency to become 2ry infected and to flare up with systemic infections [13].…”

Important differences in the diagnostic spectrum of primary immunodeficiency in adults versus children

“…Short stature, skeletal dysplasia and limb dwarfism (due to mutations in the RNF168, MCM4, ACTB, ACP5, STAT5B, FILS, SMARCAL1, RMPR and BLM genes), hyperextensive joint (in STAT3 hyper IgE syndrome), dystrophy (in the CANDLE syndrome) and chondrodysplasia (in the Shwachman-Diamond syndrome [SDS]) in PID children may be observed by pediatric orthopedists or rheumatologists [50][51][52][53].…”

“…STAT3 patients with hyper IgE syndrome may develop aneurysms that may be incidentally visualized by brain imaging [50].…”

“…Odontologists who encounter children suffering from a delay in the shedding of primary teeth (STAT3 deficiency) or dental enamel hypoplasia (autoimmune polyendocrinopathy with candidiasis and ectodermal dystrophy or APECED) should be aware about the possibility of PID [50,76].…”

The 10 warning signs

“…In the neonatal period, generalized erythroderma should raise the possibility of Omenn syndrome [11 && ]. Eczema in association with recurrent cutaneous viral infections or abscesses may trigger a referral to evaluate for DOCK8 deficiency [10] or autosomaldominant hyper-IgE syndrome (AD-HIES) [22], respectively, whereas the presence of petechiae or a history of bleeding may prompt assessment of platelet number and volume for suspected WiskottAldrich syndrome. In a patient with cystic acne, an associated sterile arthritis, pyoderma gangrenosum or pathergy may herald the pyogenic arthritis, pyoderma gangrenosum and acne syndrome [23].…”