Allergic Manifestations of Inborn Errors of Immunity

Allergic disorders are increasingly recognized in patients with inborn errors of immunity (IEI), with predominance of bronchial asthma and atopic dermatitis. On the other hand, urticaria is more rarely described in patients with IEI, in most of the cases in patients with autoinflammatory disorders. Distinguishing classical allergic disorders from IEI is very important since the onset of allergic manifestations can lead to a significant diagnostic delay. Atopic phenotypes have been observed in several IEI, such as Omenn syndrome, hyper-IgE syndromes, Wiskott-Aldrich syndrome, IPEX and related disorders, STAT6 mutations, and CBM-opathies due to mutations in CARD, BCL10, and MALT1. Clinical red flags including autoimmunity, infections, lymphoproliferation, malignancy, growth failure, connective tissue abnormalities, high IgE levels, eosinophilia, family history or consanguinity, and early age at onset associated with atopic phenotypes should arise the suspicion for considering IEI. Indeed, only the early suspicion of an immune defect may lead to carry out immunological and genetic investigations to make a timely and correct diagnosis. Therefore, early diagnosis with the knowledge of the genetic/functional defect could allow to adopt targeted or semi-targeted therapies as well as to improve the quality and the expectancy of life of IEI patients.