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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
Interactions
disease interactions
Specific
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
General
autoimmune disease
endocrine disease
syndrome
References
- Husebye ES, Anderson MS, Kampe O.
Autoimmune Polyendocrine Syndromes.
N Engl J Med 2018; 378:1132-1141. March 22, 2018
PMID: 29562162
http://www.nejm.org/doi/full/10.1056/NEJMra1713301
- NEJM Knowledge+ Allergy/Immunology