Immunodeficiencies: non-infectious manifestations

Classical immunodeficiencies are mainly characterized by infectious conditions. In recent years, manifestations related to allergy, inflammation, autoimmunity, lymphoproliferation, and malignancies related to this group of diseases have been described. The text intends to make an update on the non-infectious manifestations of the primary defects of the immune system.

Searches were carried out in the PubMed database for review articles published in the last five years, in English, French, or Spanish, using the terms "allergy," "inflammation," "autoimmunity," "lymphoproliferation," "cancer," AND "immunodeficiency" or "primary immunodeficiency" or "inborn errors of immunity" NOT "HIV".

Non-infectious manifestations characterize the primary defects in which there is dysregulation of the immune system. The most common manifestations of autoimmunity in this group of diseases are autoimmune cytopenias. Exacerbated inflammatory processes, benign lymphoproliferation, and propensity to malignancy of the lymphoreticular system are related to several diseases in this group. Severe manifestations of atopy or food allergy characterize some immunodeficiencies. Disorders of inborn immunity of the autoinflammatory type are characterized by an aseptic inflammatory process in the absence of autoimmunity, with fever and recurrent manifestations in different organs.

Not only infectious conditions should raise the suspicion of immunodeficiencies, but also manifestations of allergy, inflammation, autoimmunity, lymphoproliferation, or cancer, especially if they are recurrent, associated to each other, affecting young patients, or in severe and/or difficult to treat conditions.