Autoimmune Polyendocrinopathy Candidiasis Ectodermal Dystrophy (APECED): Epidemiology, Pathogenesis, Clinical...

Autoimmune Polyendocrinopathy Candidiasis Ectodermal Dystrophy (APECED), or Autoimmune Polyendocrine Syndrome Type 1 (APS-1), is recognized as a rare monogenic disease with an underlying etiology of biallelic mutations in the AIRE gene. Defective AIRE protein disrupts central and peripheral immune tolerance, resulting in widespread immune dysregulation. The disease is characterized by substantial phenotypic heterogeneity, with manifestations that may develop progressively throughout life.

This review integrates current evidence from published APECED-related articles addressing epidemiology, genetic background, immunopathogenesis, clinical manifestations, diagnostic approaches, and management strategies.

These patients present with a spectrum of clinical manifestations, including chronic mucocutaneous candidiasis, autoimmune endocrinopathies, hypoparathyroidism, primary adrenal insufficiency (Addison's disease), pneumonitis, enteropathy, ectodermal dystrophy, and increased susceptibility to severe infections. The onset, severity, and combination of these manifestations vary considerably among affected individuals, reflecting the clinical heterogeneity of the disease. Diagnosing APECED remains challenging, as many patients do not initially present with the classical triad. Moreover, additional endocrine and non-endocrine manifestations may develop progressively during the disease course, contributing to diagnostic delay and increasing the complexity of clinical management.

This review highlights the broad clinical heterogeneity of APECED and discusses recent advances in diagnosis, multidisciplinary management, and emerging targeted therapeutic strategies while emphasizing the need for further clinical validation. Improved recognition of atypical and nonclassical manifestations, together with advances in genetic and immunological evaluation, may facilitate earlier diagnosis and more individualized management.

Early diagnosis and continuous multidisciplinary follow-up are essential to optimize clinical outcomes and quality of life in patients with APECED.