Autoimmune polyglandular syndrome type 1

Author: Brian Wu, MD candidate, Keck School of Medicine, Los Angeles, USA. DermNet New Zealand Editor in Chief: Hon A/Prof Amanda Oakley, Dermatologist, Hamilton, New Zealand. December 2016.


Autoimmune polyglandular syndrome type 1
close
Synonyms:
APS1, Polyendocrinopathy-candidiasis–ectodermal dystrophy, Whitaker syndrome, Polyendocrine syndrome type 1, APECED, Candidiasis-hypoparathyroidism–Addison disease syndrome, Polyglandular autoimmune syndrome type 1, APS type 1, Autoimmune polyendocrine syndrome type 1, Blizzard syndrome, HAM syndrome, Juvenile familial endocrinopathy
Categories:
Autoimmune disorders
ICD-11 MMS:
5B00
SNOMED CT:
11244009

What is autoimmune polyglandular syndrome type 1?

Autoimmune polyglandular syndrome type 1 (APS1) is an autoimmune condition that results in insufficiencies of multiple endocrine glands. It is also known as autoimmune polyendocrine syndrome type 1, polyendocrinopathy-candidiasis–ectodermal dystrophy (APECED), Whitaker syndrome, and candidiasis-hypoparathyroidism–Addison disease syndrome, among its many other names.

APS1 was first described by Dr Thomas Addison in the 19th century.

Who gets autoimmune polyglandular syndrome type 1?

APS1 is inherited, with women and girls being slightly more likely than men and boys to develop the syndrome. It most often occurs in particular ethnic populations due to consanguinity or the clustering of descendants from a common family founder. It is most prevalent in:

  • Iranian Jews (1 in 9000)
  • Sardinians (1 in 14,400)
  • Finns (1 in 25,000).

APS1 is rare in other populations.

What causes autoimmune polyglandular syndrome type 1?

APS1 is caused by gene mutations in the autoimmune regulator gene, AIRE, on chromosome 21q22. It is inherited in an autosomal recessive pattern (two copies of an abnormal gene must be present in order for the syndrome to develop). These gene mutations lead to autoantibodies and cause chronic inflammatory cell infiltratesin the affected organs.

What are the clinical features of autoimmune polyglandular syndrome type 1?

Symptoms most often appear in children aged 3–5 years, most cases of APS1 have appeared by early adolescence, and all cases by the time an individual is in their early 30s.

APS1 is based on three main clinical features:

  1. Mucocutaneous candidiasis affecting skin and mucous membranes
  2. Hypoparathyroidism, resulting in numbness and tingling in the face and limbs, muscle cramps and aches, weakness and fatigue due to low levels of circulating calcium
  3. Addison disease, an insufficiency of the adrenal glands, presenting with changes in skin pigmentation, loss of appetite and weight loss, fatigue, low blood pressure and fatigue.

While less common, other possible features of this syndrome can include:

    • Hypogonadotropic hypogonadism
    • Pernicious anaemia
    • Chronic active hepatitis
    • Asplenia
    • Keratoconjunctivitis
    • Interstitial nephritis
    • Diabetes mellitus type 1
    • Cholelithiasis
    • Alopecia areata
    • Malabsorption
    • Vitiligo.
Skin signs of APS type 1

How is autoimmune polyglandular syndrome type 1 diagnosed?

If an individual presents with evidence of more than one endocrine deficiency, further testing can be done to confirm autoimmune polyglandular syndrome type 1 (APS1), including:

  • A serum autoimmune screen
  • End-organ function tests.

Additional possible blood tests can include testing of testosterone, oestradiol, follicle-stimulating hormone (FSH), luteinising hormone (LH), prolactin, adrenocorticotropic hormone (ACTH), plasma renin activity, electrolyte levels, and a complete blood count.

Skin swabs and scrapings may also be taken to detect Candida albicans.

How is autoimmune polyglandular syndrome type 1 treated?

The treatment of APS1 will depend upon its specific features.

What is the outcome for autoimmune polyglandular syndrome type 1?

The prognosis for APS1 is variable. Survival rates have improved greatly since the 1970s.

Contribute to Dermnet

Did you find this page useful? We want to continue to deliver accurate dermatological information to health professionals and their patients — for free. Funding goes towards creating articles for DermNet, supporting researchers, and improving dermatological knowledge around the world.

Donate now with credit card or Paypal

 

Related information

 

References

On DermNet NZ

Other websites

Books about skin diseases

See the DermNet NZ bookstore.