Intestinal Dysfunction in APECED Syndrome Could Mimic IPEX Syndrome

Abstract

To the Editor: Classical diagnosis of autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED) syndrome depends on the appearance of 2 of its 3 major criteria: mucocutaneous candidiasis, autoimmune hypoparathyroidism, and adrenal failure. A variety of clinical components may be seen in the clinical picture, however, and they may occur before onset of the 3 major criteria, resulting in diagnostic delay (1). Intestinal dysfunction is one such component of APECED syndrome and is observed in 18% to 22% of patients with APECED syndrome. A variety of causes are attributed to this intestinal dysfunction, such as celiac disease, cystic fibrosis, pancreatic insufficiency, intestinal infections with candida albicans, and loss of enteroendocrine cells caused by autoimmune attack (2,3). Mutations of the forkhead box P3 (FoxP3) gene result in impaired function of regulatory T cells, which leads to immune dysregulation, polyendocrinopathy, enteropathy, and X-linked (IPEX) syndrome. In about one-third of patients, with clinical symptoms resembling IPEX syndrome, no mutation was found in the FoxP3 gene (4). So far, only 2 articles have been published about these IPEX-like patients. One of them suggested improvement of clinical symptoms with sirolimus usage in 2 IPEX and 5 IPEX-like patients (5). And a recently published article showed significant reduction in peripheral regulatory T cells in an impressive cohort of 28 IPEX-like patients (4). In that report, the authors declared exclusion of the Wiskott-Aldrich syndrome, Omenn syndrome, hyper-immunoglobulin E syndrome, and autoimmune lymphoproliferative syndrome, which were originally included in the differential diagnosis; however, APECED syndrome was not included in the differential diagnosis, despite its involvement in the same group of congenital diarrheal disorders as IPEX and IPEX-like syndromes, according to defects in the modulation of immune response (6). Additionally, a reduction in regulatory T cells in patients with APECED syndrome was previously discovered (7). Assessment of these patients for APECED syndrome could have occurred whether APECED syndrome was substantially part of the IPEX-like syndromes or not.