Autoimmune Polyendocrinopathy Candidiasis Ectodermal Dystrophy (APECED) is a rare, monogenic disease caused by mutations in the Autoimmune Regulator (AIRE) gene, resulting in loss of central and peripheral immune self-tolerance. It is clinically defined by the presence of two of the classic triad; chronic mucocutaneous candidiasis (CMC), hypoparathyroidism and adrenal insufficiency, or one of these in a sibling of an APECED patient (1). We present two patients with markedly differing presentations of APECED at age 2years and 4years, who have both been successfully managed with the immunomodulatory agent Sirolimus. It was commenced in one patient due to critical illness with brainstem encephalitis, and in the other due to growth failure and rapidly progressive onset of autoimmune endocrinopathies. Their markedly differing features and clinical courses illustrate the heterogenous nature of APECED and the inadequacy of the current diagnostic criteria. By broadening the criteria to include some of the more common features outside of the classic triad, the median age at diagnosis can be brought forward and significant morbidity and mortality associated with life threatening endocrine crises can be mitigated(2).
Whilst Sirolimus has been widely used as an immunoregulatory agent in many conditions (eg.transplant medicine), it has not been recognised as a preferred agent in APECED(3). Both patients have exhibited significant improvement in symptom control, well-being and stability of their clinical course within months of commencement of therapy. As yet, neither of our cases have experienced adverse side effects from the Sirolimus, likely in part by aiming for trough levels well below that used in other autoimmune conditions.
We propose that the diagnostic criteria for APECED should be broadened so as to avoid diagnostic delay, and that Sirolimus should be considered early in the disease course to achieve clinical stability, optimise wellbeing, and potentially modulate the rate and character of disease progression.