Polyglandular autoimmune syndromesE31.0

Group of rare autoimmunological endocrinopathies characterized by immunological destruction and thus by insufficiency of endocrine organs. Depending on the organ manifestation, different clinical clinical pictures result.

In the "autoimmunological endocrinopathies" 4 types of disease can be distinguished from each other:

• APS type 1: Autoimmunologic polyglandular syndrome type 1 (syn: Chronic mucocutaneous candidiasis; juvenile form, called Schmidt syndrome or APECED ); autosomal recessive inheritance.
• APS type 2: autoimmunologic polyglandular syndrome type 2 (adult form, Carpenter syndrome; APS).

• APS type 3: is defined by autoimmunologic thyroid disease and another autoimmune disease, excluding Addison's disease (Betterle C et al. 2014).

• APS type 4: is usually a diagnosis of exclusion. It includes 2 or more organ-specific autoimmune diseases that cannot be classified as APS types 1 to 3. Described are different combinations of: autoimmunological hypophysitis, vitiligo, primary immune thrombocytopenia, autoimmune gastritis or pernicious anemia.

• Related syndromes /e.g. XPID

Type 1 shows different prevalences in different ethnic groups (high prevalence among Iranian Jews and among Finns). In most European countries only sporadic occurrence.

Type 2 is much more common with 15-45 /1.0 million inhabitants.

Type 1: Mutations in the autoimmune regulatory gene (AIRE - the AIRE gene - chromosome 21q22.3) are detected.

Type 1: Childhood (APECED = Autoimmune Polyendocrinopathy-Candidiasis-Ectodermal Dystrophy Syndrome)

Type 2: Adulthood (3rd decade of life)

APS type 1: Autoimmunologic polyglandular syndrome type 1 is characterized by:

• Hypoparathyroidism (87%), chronic muco-cutaneous candidiasis (mostly before the age of 5), ectodermal dysplasias (dystrophy of the nails, gingival hyploasias, hypotrichosis, keratopathies) and adrenocortical insufficiency - Addison's disease - (69%). In addition, Hashimoto's thyroiditis, Graves' disease and ovarian insufficiency are less common.
• Other symptoms:
  • Malabsorption syndrome (24% of APECED patients; steatorrhea, watery diarrhea).
  • Autoimmune hepatitis (10-20% of APECED patients). This can be asymptomatic and self-limiting, but can also be fulminant.
  • Diabetes mellitus (about 18% of APECED patients).
  • Hypogonadismue is found in 60%of female and in 14% of male APECED patients.

APS type 2: Autoimmunologic polyglandular syndrome type 2 (APS-2) occurs in families. The syndrome affects women>men (1.6 - 3x more often). First manifestation usually in adulthood.

The following predominant symptoms are found in type 2:

• Addison's disease
• Diabetes mellitus type 1
• Hashimoto thyroiditis
• Other symptoms include:
  • Alopecia areata
  • Vitiligo
  • Diabetes insipidus
  • celiac disease
  • primary hypogonadism
  • pernicious anemia
  • myasthenia gravis
  • Frequently, other organ-specific atoimmune diseases exist.
• APS type 3: Autoimmune polyglandular syndrome type 3 consists of a rare association of autoimmune thyreopathy, diabetes mellitus type 1, autoimmune nephritis, ITP, SLE, myasthenia gravis, and other autoimmuneopathies. Dermatologically, lichen planus and autoimmune bullous diseases have been described.
• APS type 4: Autoimmunologic polyglandular syndrome type 4 is a diagnosis of exclusion that includes 2 or > 2 organ-specific autoimmune diseases that cannot be classified as types 1 to 3. These include XPID syndrome and POEMS syndrome, among others.

Situational internal gfls also dermatological treatment according to the individual diseases. Regarding mucocutaneous candidosis see there.

1. Betterle C et al (2014) A rare combination of type 3 autoimmune polyendocrine syndrome (APS-3) or multiple autoimmune syndrome (MAS-3). Auto immune highlights 5: 27-31.

2. De Bellis A et al. (2014) Rituximab-induced remission of autoimmune hypophysitis and primary immune thrombocytopenia in a patient with autoimmune polyendocrine syndrome type 4
   .Expert Rev Endocrinol Metab 9:313-317.

3. Iijima T et al(2018) Concurrent variant type 3 autoimmune polyglandular syndrome and pulmonary arterial hypertension in a Japanese woman. Endocr J 65:493-498.

4. Kahaly GJ et al (2018) Polyglandular autoimmune syndromes.
   J Endocrinol Invest 41:91-98.

5. Vita R et al (2017) Autoimmune Syndromes Type 3, Particularly in Those Who Require Thyroxine Treatment. Front Endocrinol (Lausanne)8:212.

6. Vogel A et al (2002) Autoimmune Polyglandular Syndromes. Aspects of pathogenesis, prognosis and therapy. Dt Medical Journal 99: 1428-1439