Hyper-IgE syndrome: case reports

Abstract

Hyper-IgE syndromes (HIES) are rare primary immunodeficiency disorders characterised by markedly elevated serum immunoglobulin E (IgE) levels, recurrent cutaneous and respiratory infections, and variable multisystem involvement. They arise from mutations in genes central to immune signalling pathways, most notably STAT3 in autosomal dominant HIES (AD-HIES) and DOCK8 in autosomal recessive HIES (AR-HIES). The first case, an 11-month-old boy with recurrent staphylococcal skin infections, sepsis, eosinophilia and an IgE level of 9,867 IU/ml, was found on whole-exome sequencing to have a heterozygous STAT3 mutation, confirming AD-HIES. The second case, a 2-year-old boy with severe atopic dermatitis, recurrent wheezing, repeated pneumonias and an IgE level exceeding 100,000 IU/ml, was diagnosed with AR-HIES due to a homozygous DOCK8 mutation. These cases highlight the distinct clinical patterns of the two forms: AD-HIES commonly presents with non-immunologic features such as skeletal and dental anomalies, whereas AR-HIES is associated with severe viral infections, profound IgE elevation and higher mortality. Early recognition through clinical suspicion and genetic confirmation is essential, as management requires multidisciplinary care, prophylactic antimicrobial strategies and, in severe DOCK8 deficiency, consideration of haematopoietic stem-cell transplantation.