Autoimmune Polyglandular Syndromes
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Autoimmune polyglandular syndromes are combinations of organ-specific autoimmune endocrine diseases that occur together in one patient or family. Type 1, caused by AIRE gene mutations, presents in childhood with chronic mucocutaneous candidiasis, hypoparathyroidism and Addison disease, while type 2 presents in adults with Addison disease together with thyroid autoimmunity or type 1 diabetes.
What you must remember
- APS type 1: autosomal recessive, caused by mutations in the AIRE gene, with onset in childhood.
- Classic components: chronic mucocutaneous candidiasis, hypoparathyroidism and Addison disease, with two of the three usually needed for diagnosis.
- Other APS type 1 features: hypothyroidism, hypogonadism, type 1 diabetes, alopecia, vitiligo, pernicious anaemia, chronic hepatitis and dental enamel hypoplasia.
- APS type 2: Schmidt syndrome, with Addison disease in adults plus autoimmune thyroid disease, type 1 diabetes or both.
- HLA association: APS type 2 is linked to HLA-DR3 and HLA-DR4, while APS type 1 is a monogenic AIRE disorder.
- Addison disease: a core component of both syndromes, so adrenal autoantibodies and cortisol assessment are essential.
- Other autoimmune links: coeliac disease, pernicious anaemia, vitiligo, alopecia areata and myasthenia gravis.
- Management: each endocrine deficiency is replaced for life, and chronic candidiasis is treated with antifungal therapy.
Comparing APS type 1 and type 2
The two syndromes share Addison disease but differ in genetics, age of onset and components. The table sets out the features that examiners use to separate them. Both are uncommon, but a single component often leads the clinician to search for the others.
| Feature | APS type 1 | APS type 2 |
|---|---|---|
| Genetics | AIRE mutation, autosomal recessive | Polygenic, with HLA-DR3 and DR4 association |
| Typical onset | Childhood | Usually adults |
| Core components | Candidiasis, hypoparathyroidism, Addison disease | Addison disease with thyroid disease or type 1 diabetes |
| Characteristic extras | Alopecia, vitiligo, enamel hypoplasia | Coeliac disease, vitiligo, alopecia |
| Key tests | AIRE sequencing and organ autoantibodies | Adrenal and thyroid antibodies, HLA typing |
Chronic candidiasis or hypoparathyroidism in a child points strongly to type 1, while Addison disease with thyroid or diabetic disease in an adult points to type 2. Screening relatives is useful in both syndromes, especially when a family history is known. Each affected organ should be checked during follow-up, because new components can appear years after the first diagnosis.
Where the exam tries to catch you
Examiners test the core triad, the age split and the genetic basis of each syndrome.
- Trap: Calling every Addison disease with thyroid disease APS type 1. Correct: Type 2 is the adult syndrome with Addison disease plus thyroid or diabetes, and candidiasis points to type 1.
- Trap: Treating recurrent oral candidiasis as an isolated infection in a child. Correct: Chronic candidiasis is a component of APS type 1, so look for hypoparathyroidism and Addison disease.
- Trap: Assuming all polyglandular autoimmunity has the same genetic basis. Correct: APS type 1 is a monogenic AIRE disorder, whereas APS type 2 is polygenic with HLA association.
Frequently asked questions
Which gene is mutated in APS type 1?
The AIRE gene is mutated in autoimmune polyglandular syndrome type 1, also called APECED. AIRE controls central tolerance in the thymus, and the inheritance pattern is autosomal recessive.
What are the classic components of APS type 1?
Chronic mucocutaneous candidiasis, hypoparathyroidism and Addison disease form the classic components of APS type 1. Diagnosis usually needs two of these three, and features such as alopecia, vitiligo and enamel hypoplasia support it.
Which features define APS type 2?
APS type 2, or Schmidt syndrome, combines Addison disease with autoimmune thyroid disease or type 1 diabetes, usually in adults. It is associated with HLA-DR3 and HLA-DR4, and coeliac disease or vitiligo may coexist.
Why is APS type 2 a concern in patients with Addison disease?
Addison disease in APS type 2 may coexist with thyroid autoimmunity or type 1 diabetes, so each should be screened for. Adrenal and thyroid autoantibodies help identify patients at risk, and missing an associated disease can lead to serious complications.