The autoimmune polyglandular syndromes (APS) are characterized by variable combinations
of autoimmune endocrine diseases, such as Addison disease, hypoparathyroidism, and
type 1 diabetes (T1D). Three types of APS have been distinguished (Table 1). These include the rare type 1 (APS1, OMIM 240,300), the more common type 2 (Schmidt's
complex, 269,200) and type 3 APS [
1
,
2
]. APS1 also is known as autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy
(APECED). Patients who have APS1 usually present with at least two of these diseases:
Addison disease, hypoparathyroidism, and chronic mucocutaneous candidiasis. In patients
who have APS1, Addison disease predominantly begins in childhood or early adulthood.
It is associated frequently with chronic active hepatitis, malabsorption, juvenile-onset
pernicious anemia, alopecia, and primary hypogonadism. T1D or autoimmune thyroid disease
are infrequent. Patients who have APS2 present with Addison disease and autoimmune
thyroid disease or T1D, but do not have hypoparathyroidism or candidiasis. APS2 is
not confined to one age group or sex; it is predominant in middle-aged women. The
autoimmune disorders that occur with APS1, such as chronic active hepatitis, are rare
in APS2, except for a low frequency of gonadal failure. Addison disease probably has
a different genetic basis in APS1 than in APS2. The third type of APS, APS3, is represented
by patients who have autoimmune thyroid disease and one or more other autoimmune disorders
but do not have Addison disease. This article focuses on the mutation analysis in
patients who have APS1 and the functional analyses of the autoimmune regulator (AIRE)
protein.
Table 1Component diseases and their frequencies in autoimmune polyglandular syndromes
| Component diseases | APS1 | APS2 | APS3 |
|---|---|---|---|
| Endocrine components | |||
| Hypoparathyroidism | 80% | 0% | 0% |
| Addison disease | 70% (early) | 100% (late) | 0% |
| Hypothyroidism | 5% | 70% | 70% |
| Hyperthyroidism | 0% | ++ | ∀ |
| Insulin-dependent diabetes mellitus | 2–5% | 52% | ∀ |
| Ovarian failure | 60% | 4% | 0% |
| Testicular failure | 14% | 2% | 0% |
| Pernicious anemia | 15% (early) | 1% (late) | ++ |
| Hypopituitarism | ∀ | + | − |
| Nonendocrine components | |||
| Mucocutaneous candidiasis | 82–100% | 0% | 0% |
| Alopecia | 26% | 1% | ∀ |
| Vitiligo | 10% | 5% | >10% |
| Chronic active hepatitis | 11% | 0% | 0% |
| Keratopathy | 35% | 0% | 0% |
| Squamous cell carcinoma, septicemia | ++ | + | − |
| Intestinal malabsorption | 18% | 0% | 0% |
| Enamel hypoplasia | 77% | 0% | 0% |
| IgA deficiency | 10% | − | − |
| Genetics | Recessive, AIRE | ? | ? |
| HLA association | None | DR, DQ | ? |
The exact frequencies for some component diseases are unknown but are estimated based
on our clinical observation: ++ very common, + common, ∀ occasional presence, − absence.
Abbreviations: DR, HLA-DR; DQ, HLA-DQ.
Data from Neufeld M, Maclaren N, Blizzard R. Autoimmune polyglandular syndromes. Pediatr Ann
1980;9(4):154–62 and Ahonen P, Myllarniemi S, Sipila I, Perheentupa J. Clinical variation
of autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED) in a series
of 68 patients. N Engl J Med 1990;322(26):1829–36.
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