From the Guidelines
APECED syndrome must be excluded by testing for the typical mutations in the AIRE gene in patients with autoimmune hepatitis and multiple endocrine disorders. This recommendation is based on the evidence from the study published in Hepatology in 2010 1, which highlights the importance of considering APECED syndrome in the differential diagnosis of patients with autoimmune hepatitis and multiple endocrine disorders. The study provides a diagnostic approach to autoimmune hepatitis, including the use of serological tests to assist in the diagnosis, and emphasizes the need to exclude other conditions that can cause chronic hepatitis.
Key Features of APECED Syndrome
- Chronic mucocutaneous candidiasis
- Hypoparathyroidism
- Adrenal insufficiency (Addison's disease)
- Other autoimmune conditions may develop over time
Diagnosis and Management
- Testing for typical mutations in the AIRE gene to exclude APECED syndrome
- Lifelong monitoring and treatment by an endocrinologist
- Management of specific symptoms, including:
- Antifungal medications like fluconazole for candidiasis
- Calcium and vitamin D supplements for hypoparathyroidism
- Hormone replacement therapy (hydrocortisone and fludrocortisone) for adrenal insufficiency
The importance of considering APECED syndrome in the differential diagnosis of patients with autoimmune hepatitis and multiple endocrine disorders is also supported by a study published in the Journal of Internal Medicine in 2014 1, which provides a consensus statement on the diagnosis, treatment, and follow-up of patients with primary adrenal insufficiency. This study highlights the need for a comprehensive approach to the diagnosis and management of patients with autoimmune polyendocrine syndromes, including APECED syndrome.
From the Research
Definition and Causes of APECED
- APECED, also known as autoimmune polyglandular syndrome type-1 (APS-1), is a rare monogenic autoimmune disease caused by loss-of-function mutations in the autoimmune regulator (AIRE) gene 2.
- The AIRE deficiency impairs immune tolerance in the thymus, resulting in the peripheral escape of self-reactive T lymphocytes and the generation of several cytokine- and tissue antigen-targeted autoantibodies 2.
- APECED is a rare autosomal recessive disease, caused by mutations of a single gene named autoimmune regulator gene (AIRE) which results in a failure of T cell tolerance within the thymus 3.
Clinical Manifestations of APECED
- The classic triad of characteristic clinical manifestations of APECED consists of chronic mucocutaneous candidiasis (CMC), hypoparathyroidism, and primary adrenal insufficiency (Addison's disease) 2, 3.
- In addition to the classic triad, APECED patients develop several non-endocrine autoimmune manifestations with variable frequencies 2.
- Other autoimmune conditions may be associated with APECED, such as hypothyroidism, hypogonadism, insulin-dependent diabetes mellitus, chronic active hepatitis, pernicious anemia, vitiligo, alopecia, biliary cirrhosis, and ectodermal dysplasia 4.
- American APECED patients develop a diverse syndrome, with dramatic enrichment in organ-specific nonendocrine manifestations starting early in life, compared with European patients 5.
Diagnosis and Diagnostic Criteria of APECED
- Developing any two of the classic triad manifestations establishes the diagnosis of APECED 5.
- The diagnosis of APECED can be challenging due to the variability of its clinical expression, and a considerable delay often occurs between the appearance of symptoms and the diagnosis 3.
- The current diagnostic criteria for APECED may need to be updated, as some patients present with atypical features or isolated major clinical APECED features 4.
- Incorporation of new manifestations into American diagnostic criteria would accelerate diagnosis by approximately 4 years and potentially prevent life-threatening endocrine complications 5.