Abstract:

Type 1 autoimmune polyglandular syndrome (APS-1), also referred to as autoimmune polyendocrinopathy–candidiasis–ectodermal dystrophy (APECED), is an uncommon monogenic disorder presenting with immune-mediated destruction of a variety of endocrine and non-endocrine organs. It was first characterised clinically in the early 20th century and subsequently associated with mutations in the autoimmune regulator (AIRE) gene, which defined its genetic and immunological aetiology. On initial presentation, APS-1 presents most frequently in childhood with chronic mucocutaneous candidiasis, followed by hypoparathyroidism and primary adrenal insufficiency; however, the combination of symptoms varies widely. This article addresses the long journey in which this infection has been known from early clinical characters to molecular diagnosis and describes the unique aspects of its natural history, immunopathogenesis, and chronic phase complications. Knowledge of the time course of diagnostics and the wide range in clinical presentation are very important for early diagnosis, full treatment and a better prognosis. Type 1 autoimune polyglandular syndrome (APS-1) or autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy is an 103 rare genetic disease mainly characterized by immune-mediated destruction of different endocrine organs and chronic mucocutaneous candidiasis. Its diagnostic definition has evolved from a mere clinical recognition of the symptom clusters to molecular identification and characterization of mutations in the autoimmune regulator (AIRE) gene. This article reviews the history of diagnostic methods and emphasizes the unique clinical course of the disease. Particular attention is given to initial presentation of the disease, immunological signs and genetic diagnoses and long-term systemic aspects. Onset is usually in childhood with candidiasis followed by hypoparathyroidism and then adrenal insufficiency, although there is high variability and organ presentation. Immunogenetics and autoantibody profiling have progressed in early diagnosis and risk stratification. Notwithstanding these advances, delayed detection is still common that is related to the rarity and variations in presentation. Awareness of the historical progression of diagnostic approaches and the intricate clinical course is a key to timely treatment, to prevent life-threatening complications and to enhance patient’s outcomes.