Inborn errors of immunity with atopic phenotypes: A practical guide for allergists

Abstract

Inborn errors of immunity (IEI) are a heterogeneous group of disorders, mainly resulting from mutations in genes associated with immunoregulation and immune host defense. These disorders are characterized by different combinations of recurrent infections, autoimmunity, inflammatory manifestations, lymphoproliferation, and malignancy. Interestingly, it has been increasingly observed that common allergic symptoms also can represent the expression of an underlying immunodeficiency and/or immune dysregulation. Very high IgE levels, peripheral or organ-specific hypereosinophilia, usually combined with a variety of atopic symptoms, may sometimes be the epiphenomenon of a monogenic disease. Therefore, allergists should be aware that severe and/or therapy-resistant atopic disorders might be the main clinical phenotype of some IEI. This could pave the way to target therapies, leading to better quality of life and improved survival in affected patients.

Keywords: Allergy; Atopic phenotypes; Atopy; Inborn errors of immunity; Primary immunodeficiency.

Fig. 1

Proposal for a diagnostic algorithm for the identification of IEI with atopic phenotypes

Fig. 2

Upper eyelid abscess in a patient with STAT3-HIES

Fig. 3

Severe eczema in a patient with DOCK8 deficiency

Fig. 4

Severe eczema, petechiae and purpura in a patient with Wiskott-Aldrich syndrome

Fig. 5

Cutaneous rash associated with macrophage activation syndrome (MAS) in a patient with ARPC1B deficiency (adapted from Brigida et al.