Case report of a young child with disseminated histoplasmosis and review of hyper immunoglobulin e syndrome (HIES)

Type 1 hyper IgE syndrome (HIES) is an autosomal dominant disorder due to defects in signal transducer and activator of transcription 3 (STAT3) signaling [1,2]. HIES was first described in 1966 and called Job's syndrome for the clinical manifestation of recurrent staphylococcal abscesses [3]. The association with elevated IgE levels was discovered in 1972 and was referred to as Buckley syndrome [4] which was found to be the same condition as Job's syndrome. The genetic mutation of HIES was discovered in 2007. Minegishi et al. and Holland et al. reported heterozygous dominant-negative mutations in STAT3 in the DNA-binding and SH2 domains [5,6]. STAT3 plays an important signaling role in Th17 differentiation.Type 1 HIES is characterized by immunologic and non-immunologic findings. These manifestations are accompanied by elevated IgE levels and reduced IL-17 producing CD3+CD4+ T cells. Immunologic findings include newborn rash, recurrent sinopulmonary infections, recurrent skin infections, recurrent cyst-forming pneumonias, eczema, mucocutaneous fungal disease, eosinophilia and elevated IgE. Non-immunologic findings include characteristic face, retained primary teeth, multiple fractures, scoliosis, hyperextensibility, Chiari I malformations and craniosynostosis.Diagnosis in young children can be challenging as symptoms accumulate over time along with confounding clinical dilemmas. A clinical HIES scoring system by the National Institutes of Health (NIH) was developed in 1999 [1]. A more recent scoring system with fewer but more pathogonomonic clinical findings was reported in 2010 [2]. These scoring systems can be used as tools to assess the likelihood of HIES diagnosis.Also reported are autosomal recessive forms of HIES, i.e. defects in dedicator of cytokinesis 8 protein (DOCK8) and tyrosine kinase 2 (TYK2). These forms are less common, mostly described in consanguineous communities and have several different clinical distinctions.This patient with wiry hair and squar