Autoimmune polyendocrinopathies (from English autoimmune polyglandular syndromes or APS) are a heterogeneous group of diseases characterized by a combination of multiple autoimmune manifestations that affect both the endocrine system and other organs. The clinical manifestations of these syndromes differ significantly, therefore, their classification solely on a phenotypic basis is often difficult, and sometimes even reductive.
Traditionally, there are four main types of autoimmune polyendocrinopathies:
- APS-1 or APECED: this is the only form with known genetic etiology, which is a monogenic disease with autosomal recessive inheritance, the main clinical signs of which are hypoparathyroidism, chronic mucocutaneous candidiasis and Addison's disease;
- APS-2, characterized by a combination of Addison's disease, autoimmune thyroiditis and / or type 1 diabetes mellitus;
- APS-3, corresponding to autoimmune thyroiditis and other manifestations of autoimmune etiology, with the exception of Addison's disease and hypoparathyroidism;
- APS-4, the diagnosis of which is based on the exclusion of the previous three forms. Other common manifestations include celiac disease, pernicious anemia, vitiligo, alopecia, autoimmune gastritis, and autoimmune hepatitis.
The etiopathogenesis of these diseases is still being studied from an endocrinological, immunological and genetic point of view. A great contribution to the understanding of these diseases was certainly made by the discovery of the AIRE gene, responsible for APS-1 or APECED. The mutation of this gene causes an alteration of the immune system's ability to discriminate between self and non-self, resulting in the development of multiple autoimmune manifestations. At the base of the other forms of polyendocrinopathies there is most likely a multifactorial etiology, in which both genetic factors not yet identified and environmental factors play an important role.