Recurrent Fevers for the Pediatric Immunologist: It's Not All Immunodeficiency

Autoinflammatory diseases are disorders of the innate immune system, characterized by systemic inflammation independent of infection and autoreactive antibodies or antigen-specific T cells. Similar to immunodeficiencies, these immune dysregulatory diseases have unique presentations, genetics, and available therapies. Given the presentation of fevers, rashes, and mucosal symptoms in many of the disorders, the allergist/immunologist is the appropriate medical home for these patients: to appropriately rule out immunodeficiencies, evaluate for allergic disease, and diagnose and treat recurrent fever disorders. However, many practicing physicians are unfamiliar with the clinical presentation, diagnosis, and treatment of autoinflammatory disorders. This review will focus on understanding the signs and symptoms of classic autoinflammatory disorders, introduce newly described monogenic and polygenic disorders, and address the approach to the patient with recurrent fevers to distinguish autoinflammation from immunodeficiency and autoimmunity.