autoimmune polyglandular syndrome; autoimmune polyendocrine syndrome

Classification

• autoimmune polyglandular syndrome-1 (APS-1)
• autoimmune polyglandular syndrome-2 (APS2)

Etiology

• checkpoint inhibitors can trigger APS-2

Epidemiology

• all ages
• APS-2 more common than APS-1
  • women predominate in APS-2

Pathology

• functional impairment of multiple endocrine glands due to loss of immune tolerance
• circulating autoantibodies
• lymphocytic infiltration of the affected tissues or organs, eventually leading to organ failure

Genetics

• APS-1
  • autosomal recessive
  • mutations in the autoimmune regulator gene AIRE
• APS-2
  • variants in DR3-DQ2 & DR4-DQ8 (variants that increase risk of type 1 diabetes
  • mutations in CTLA-4, PTPN22, BACH2, & CD25

Clinical manifestations

• insidious in onset
• APS-1 characterized by at least 2 of 3 during childhood
  • chronic mucocutaneous candidiasis
  • hypoparathyroidism
  • primary adrenal insufficiency (Addison' disease)
• other manifestations of APS-1
  • enamel hypoplasia
  • enteropathy with chronic diarrhea or constipation
  • primary ovarian insufficiency in ~60% of women before age 30 years
  • less frequent:
    • bilateral keratitis with photophobia
    • periodic fever with rash
    • autoimmune hepatitis
    • pneumonitis
    • nephritis
    • exocrine pancreatitis
    • functional asplenia
• APS-2 characterized by at least 2 of 3
  • type 1 diabetes
  • autoimmune thyroid disease
  • Addison's disease
• many patients with APS-2 develop other autoimmune conditions
  • celiac disease
  • alopecia
  • vitiligo
  • primary ovarian insufficiency
  • pernicious anemia
• patients are not susceptible to frequent infections []

Laboratory

• 21-hydroxylase Ab in serum - risk of adrenal insufficiency
• NALP5 autoantibody in serum - risk of hypoparathyroidism (no Loinc)

Management

• hormone-replacement therapy as needed
• treatment of complications
• patients with APS-1 are best followed by a multidisciplinary team led by an endocrinologist

More general terms

• autoimmune disease
• endocrine disease
• syndrome

More specific terms

• autoimmune polyendocrine syndrome type 3;
• autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED); autoimmune polyglandular syndrome type 1; Whitaker's syndrome
• Schmidt's syndrome; autoimmune polyglandular syndrome type 2