Polyglandular autoimmunsyndrome type 2E31.0

Rare, polyglandular autoimmune syndrome of the adult with adrenal insufficiency, thyroid autoimmune disease and/or diabetes mellitus.

In contrast to PolyglandularAutoimmune Syndrome Type 1 (see Chronic Mucocutaneous Candidiasis), the juvenile form,

polyglandular autoimmune syndrome type 2, the adult form (also called Schmidt syndrome).

no recognizable genetic defect is present. Pathophysiologically, it is a pure autoimmune disease, the pathogenesis of which, however, has not yet been clarified. A positive family history with metabolic disorders as well as the HLA constellation: HLA-B8-DR3, are indications of this constellation of symptoms (Betterle C et al. 2004).

The prevalence in Europe is 1.4-2/100,000.

The etiology is almost always autoimmunogenic. Risk factors for the development of autoimmunity include:

genetic factors (genetic factors include AIRE gene mutation causing type 1).

Evidence of:HLA-B8-DR3

Triggering environmental factors (viral infections? nutritional factors?).

While type 1 of the polyglandular autoimmune syndrome already occurs in childhood (juvenile form) and is inherited monogenetically (see below Chronic mucocutaneous candidiasis), type 2 is a familial syndrome of adult age (adult form).

The syndrome is characterized by the following constellation of symptoms:

• primary adrenocortical insufficiency
• autoimmune thyreopathy
• diabetes mellitus type 1

Inconstantly, the following symptoms are observed: celiac disease, pernicious anemia, vitiligo, alopecia areata; myasthenia gravis, primary hypogonadism (Singh G et al. 2021).

Depending on the organ manifestation, symptoms are often non-specific and variable. Observed are: fatigue and Addison-typical distributed hyper- and at the same time hypopigmentation of the skin, depigemtnations(vitiligo), or also (more rarely) eruptive pigment naevi (Sünkel S et al. 2001).

Laboratory chemistry tests are recommended depending on the symptoms.

A family history is essential to clarify differential diagnoses.

Approximately 10% of PAS-2 patients with adrenal insufficiency have first-degree relatives with adrenal insufficiency.

Approximately 10% of patients with PAS-2 and DM type 1 have first-degree relatives with the same disease, and autoimmune thyroiditis is even more common.

Antibody detections that can prove autoimmunogenesis even before the onset of full symptoms may be detectable against 21-hydroxylase (Addison's disease), GAD-65 and IA2 (DM1), TSH receptor and thyroperoxidase (autoimmune thyroiditis) .

At least 2 of the typical diseases must be present

Detection of autoantibodies

The therapy consists mainly of consistent hormone replacement therapy as well as symptom-oriented therapy of occurring complications.

1. Betterle C et al (2004) Autoimmune polyglandular syndrome type 2: the tip of an iceberg? Clin Exp Immunol 137:225-233.
2. Kahaly GJ et al (2018) Polyglandular autoimmune syndromes. J Endocrinol Invest 41:91-98.
3. Singh G et al (2021) Polyglandular autoimmune syndrome type II In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing PMID: 30252248.
4. Sünkel S et al. (2001)Pigmentary proliferation in Schmidt syndrome (polyglandular autoimmune syndrome type II) Der Hautarzt 52: 974-976.