Hyper IgE in the Allergy Clinic- when is it Primary Immunodeficiency?

The 2017 International Union of Immunological Societies (IUIS) classification recognises 3 Hyper-IgE Syndromes (HIES), including the prototypic Job's syndrome (autosomal dominant STAT3-loss of function) and autosomal recessive PGM3 and SPINK5 syndromes. Early diagnosis of PID can direct life-saving or transformational interventions, however remains challenging owing to the rarity of these conditions. This can result in diagnostic delay and worsen prognosis. Within increasing access to 'clinical-exome' testing, clinicians need to be aware of the implication and rationale for genetic testing, including the benefits and limitations of current therapies. Extreme elevation of serum IgE have been associated with a growing number of PID syndromes including the novel CARD11 and ZNF341 deficiencies. Variable elevations in IgE are associated with defects in innate, humoral, cellular, and combined immunodeficiency syndromes. Barrier compromise can closely phenocopy these conditions. The aim of this article is to update readers on recent developments at this important interface between allergy and immunodeficiency, highlighting key clinical scenarios which should draw attention to possible immunodeficiency associated with extreme elevation of IgE, and outline initial laboratory assessment and management. This article is protected by copyright. All rights reserved.