Autoimmune polyglandular syndromes (APS) Flashcards
Autoimmune polyglandular syndromes are a heterogenous group of disorders of 2 or more autoimmune endocrine gland failures with non-endocrine autoimmune disease.
There are 2+1 forms of APS:
1. Type 1 APS
2. Type 2 APS
3. Recently described Type 3 APS (not in PACES)
APS type 1 is also known as autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED)
It is a monogenic autosomal recessive mutation of AIRE (autoimmune regulator) gene on chromosome 21q22
(AIRE protein mediates expression of peripheral tissue antigens to eliminate self-reactive T cells)
It typically occurs in childhood ages 3–5 years
Incidence < 1:100,000
Diagnosis is a triad (2 out of 4 required)
1. Candidiasis mucocutaneous (chronic) - skin, nails, mucous membrane (70-80%)
2. Hypoparathyroidism (and hypocalcaemia) (80-85%)
3. Addison’s disease (adrenal insufficiency) (60-70%)
4. Ectodermal dystrophy (dental enamel hypoplasia, nail dystrophy, keratopathy)
Other autoimmune endocrinopathies:
1. Type 1 diabetes mellitus
2. Hypogonadism (and premature ovarian failure)
3. Autoimmune thyroid disease
Non-endocrine autoimmune components:
1. Asplenia or hyposplenism
2. Vitiligo
3. Alopecia areata
4. Autoimmune gastritis
5. Pernicious anaemia
6. Autoimmune hepatitis
7. Coeliac disease
8. Sjogren’s syndrome
9. Rheumatoid arthritis
10. Myasthenia gravis
APS type 2
- Schmidt’s syndrome: Addison + Hashimoto
- Carpenter’s syndrome: Addison + type 1 DM
It is polygenic and associated with HLA-DR3 and HLA-DR4, as well as CTLA4, PTPN22 and other genes in immune regulation
It occurs in adulthood, peaking 3rd-4th decade.
More common in females
10% of affected patients have a family member with at least one autoimmune disease.
Diagnosis:
1. Compulsory - Addison’s disease
2. Autoimmune thyroid disease (Hashimoto’s or Graves)
3. Type 1 diabetes mellitus
Other autoimmune endocrinopathies:
1. Hypoparathyroidism
2. Hypopituitarism
3. Primary hypogonadism
Non-endocrine autoimmune components:
1. Coeliac disease
2. Vitiligo
3. Alopecia areata
4. Pernicious anaemia
5. Sjogren’s syndrome
6. RA, SLE
7. Myasthenia gravis
Investigations for various autoimmune diseases
Patients with APS type 2 may suddenly develop profound hypoglycaemia or poorly controlled hyperglycaemia
Think hypothyroidism or hyperthyroidism
Think adrenal insufficiency
Treatment of APS may be challenging
Levothyroxine treatment in hypothyroidism may precipitate adrenal crisis in concomitant Addison
- Thyroid hormone increases metabolic clearance rate of cortisol
Mucocutaneous candidiasis can be treated with PO fluconazole 100-200mg OM for 7-14 days
Additional fluconazole 100mg 3x/week for suppressive therapy
Alternative: itraconazole, posaconazole for refractory disease
