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Hyperimmunoglobulinemia E syndrome in Infant/Neonate
Other Resources UpToDate PubMed

Hyperimmunoglobulinemia E syndrome in Infant/Neonate

Contributors: Nnenna Agim MD, Susan Burgin MD
Other Resources UpToDate PubMed

Synopsis

Hyperimmunoglobulinemia E syndrome (hyper-IgE syndrome) represents a group of multisystem immunodeficiency disorders characterized by atopic dermatitis, recurrent cutaneous and systemic (usually pulmonary) infections, and variably high levels of IgE. Signal transducer and activator of transcription-3 (STAT3) mutations are associated with the classic form termed Job syndrome. However, mutations in IL6R, ERBB21P, CARD11, DOCK8, PGM3, and ZNF431 can cause a similar clinical phenotype. Facial dysmorphism and skeletal, dental, and connective tissue anomalies are additional findings. Autosomal dominant and autosomal recessive forms occur, and the underlying genotypes also confer unique clinical variation. For example, patients with DOCK8 mutations have a high susceptibility to severe mucocutaneous viral infections, mucocutaneous candidiasis, and squamous cell carcinoma (SCC). Patients with PGM3 deficiency have neurologic abnormalities and may present with leukocytoclastic vasculitis (LCV) in addition to viral and candidal infections. Patients with ZNF431 mutations phenotypically resemble autosomal dominant hyper-IgE syndrome.

The "cold abscesses" in autosomal dominant hyper-IgE syndrome (Job syndrome) occur due to impaired IL-6 transduction and PGE2 release in the brain. This is not a usual feature in DOCK8 deficiency, where low IgM levels may be identified.

Patients with CARD11 mutations resemble those with DOCK8 mutations; however, incidence of viral infections and malignancy is lower and severe cases of molluscum contagiosum occur. Autoimmune colitis, primary ovarian failure, T-cell lymphoma, and lichen planus have been associated with the CARD11 mutations.

Pathogens associated with the infections include Staphylococcus aureus, most frequently, followed by Haemophilus influenzae, Streptococcus pyogenes, Escherichia coli, Pseudomonas, and Candida albicans. There is impaired chemotaxis in neutrophils, and retention of primary dentition may occur due to STAT-3's influence on IL-11, a necessary factor for dental exfoliation.

There is a National Institutes of Health (NIH) scoring system to assist in making this diagnosis. Scores greater than 40 on this scale indicate a high probability of the diagnosis.

Codes

ICD10CM:
D82.4 – Hyperimmunoglobulin E [IgE] syndrome

SNOMEDCT:
50926003 – Hyperimmunoglobulin E syndrome

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Last Reviewed:06/29/2022
Last Updated:07/07/2022
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Hyperimmunoglobulinemia E syndrome in Infant/Neonate
A medical illustration showing key findings of Hyperimmunoglobulinemia E syndrome (Cutaneous) : Axilla, Diaper area, Face, IgE elevated, Scalp, Recurring episodes
Clinical image of Hyperimmunoglobulinemia E syndrome - imageId=2367277. Click to open in gallery.  caption: 'A weeping and crusted plaque on the scalp.'
A weeping and crusted plaque on the scalp.
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