Autoimmune polyglandular syndrome
Autoimmune Polyglandular Syndrome (APS), also known as polyglandular autoimmune syndrome or polyglandular failure syndrome, refers to a group of autoimmune disorders characterized by the failure of multiple endocrine glands. APS is classified into two main types: type 1 and type 2. Type 1 is associated with genetic defects in the AIRE gene, leading to a range of symptoms including chronic mucocutaneous candidiasis, adrenal insufficiency, and hypoparathyroidism, typically manifesting in early life. Type 2 can present later and often involves a combination of Addison's disease, thyroid autoimmune diseases, and type 1 diabetes, among other conditions.
The prevalence of APS varies significantly by ethnicity and geography, with certain populations, such as Iranian Jews and Sardinians, showing higher rates of occurrence. While the exact mechanisms of APS are not fully understood, it is believed that genetic susceptibility and environmental triggers play essential roles in its development. Although APS cannot be cured, effective management through hormone replacement therapy and treatment of associated infections can enable individuals to lead normal lives. Understanding APS requires a comprehensive approach, considering both the autoimmune processes and the diverse presentations of the syndrome.
Autoimmune polyglandular syndrome
ALSO KNOWN AS: APS; polyglandular autoimmune syndrome (PGA); polyglandular failure syndrome
DEFINITION The term “autoimmune polyglandular syndrome” (APS), sometimes called polyglandular autoimmune syndrome (PGA), is best described as a set of multiple endocrine system failures or insufficiencies. It also is known as polyglandular failure syndrome, and there are two further major classifications, denoted as type 1 and type 2. APS is an autoimmune disease that destroys endocrine gland tissues, shows multiple ectodermal disorders, and is responsible for a chronic case of mucocutaneous candidiasis, which is the medical term for a yeast infection. The genetic mode of transmission is autosomal recessive inheritance.
Risk Factors
The incidence of APS depends greatly on location and ethnicity. The disease is rare, with an APS-1 prevalence of 1 in 100,00 and 1 in 20,000 for types 2 to 4. There is an increased occurrence of APS-1 among specific populations, with Iranian Jews being the highest risk group at about 1 in 9,000. Sardinians have a ratio of 1 in 14,400, and the Finns have a ratio of 1 in 25,000. Research has shown that it does affect both sexes, but with a slight female preponderance in APS-2.
Etiology and Genetics
Research on APS began as early as the mid-nineteenth century, when Thomas Addison first started classifying the pathology behind adrenocortical failure with pernicious anemia. Since that time, the combined research of endocrinologists and immunologists has helped further explain both the pathophysiology and pathogenesis of APS. APS-1 is caused by an autosomal recessive gene inheritance, with the short arm of chromosome 21 near markers D21s49 and D21s171 on band 21p22.3 being the genetic locus. Mutations in the autoimmune regulator (AIRE) gene are to blame, due to the mutated encoding of the AIRE protein, which then acts as a transcription factor. The stop-codon mutation R257X has been shown to be responsible for 83 percent of Finnish APS-1 cases, while R139X mutations are commonly found among Sardinians and Y85C mutations among Iranian Jews with the condition, as reported by Peterson and Husebye. APS-2 is associated with multiple genes, including HLA genes on chromosome 6, CTLA-4 on chromosome 2, PTPN22, and NALP1, but may or may not be related to AIRE mutations.
Although the exact mechanisms remain rather poorly understood, a pathway has been postulated. First, a patient must have a predisposed genetic susceptibility and then must be exposed to some type of autoimmune trigger. This trigger could be an environmental one or even an intrinsic factor. Next, this trigger imitates the structure of a body’s self-antigen. At this point, the self-antigen reproduces in an organ, and organ-specific antibodies are replicated. Autoimmune activity increases in that organ to the extent that there is notable glandular destruction. This infection, if left untreated, can continue to spread until excessive organ damage has occurred because of autoimmune activity and the organ is filled with chronic inflammatory infiltrate, which is composed primarily of lymphocytes.
Symptoms
In order for a diagnosis of APS-1 to be given, at least two out of the following three symptoms must be present: chronic mucocutaneous candidiasis (CMC), autoimmune adrenal gland insufficiency, or chronic hypoparathyroidism. Other diseases that have been observed when APS-1 is present are vitiligo, alopecia, hypogonadism, chronic hepatitis, malabsorption, keratoconjunctivitis, autoimmune Addison’s disease (AAD), and chronic atrophic gastritis. CMC is the first symptom to become visible and usually attacks the skin, but it has also been known to spread to the mouth, esophagus, vagina, nails, and intestines. The second overall symptom to appear is the endocrine disease hypoparathyreosis.
Screening and Diagnosis
Most of the symptoms for APS-1 become evident in the first twenty years of life, APS-2 in adulthood (though earlier or later onset is possible). Most cases of APS-2 involve the combination of Addison’s disease with Hashimoto’s thyroiditis, (a thyroid autoimmune disease), while the fewest diagnosed APS-2 cases are a combination of Addison’s disease, mellitus type 1, and Graves’ disease (a type of autoimmune hyperthyroidism). In order to classify a patient with APS-2, there must be an occurrence of both AAD in combination with diabetes mellitus type 1 and/or thyroid autoimmune diseases. Other diseases that occur along with those three are celiac disease, pernicious anemia, and myasthenia gravis. There is also an APS type 3, which occurs when autoimmune thyroiditis is present without any form of autoimmune adrenalitis. The other diseases that can display symptoms are alopecia, Sjogren’s syndrome, pernicious anemia, and diabetes mellitus type 1.
Treatment and Therapy
Treatment options vary depending on type, but since all cases are chronic, lifelong diseases, there is no cure. APS-1 requires hormone replacement therapy, as a result of the use of ketoconazol (an antifungal medication) to combat the CMC. Ketoconazol inhibits the production of testosterone and cortisol, which can have a major impact on the function of the adrenal gland of patients who already exhibit a lower-than-average pituitary-adrenal reserve. Chronic hepatitis can be treated with immunosuppressive therapy by using medications such as prednisone or azathioprine. Other treatment options are available, but all depend on the combination of ailments and their symptoms.
Prevention and Outcomes
Although APS cannot be cured, patients can continue to live a normal life if the infections caused by APS can be controlled. This control can best be achieved if the hormone deficiencies are corrected, or by treating the yeast infections, or treating diabetes through the use of insulin.
Bibliography
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