Abstract
Autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED/APS-1) is a monogenic autoimmune disorder of impaired central tolerance classically diagnosed by the presence of 2 out of 3 classic triad manifestations: chronic mucocutaneous candidiasis, hypoparathyroidism, and adrenal insufficiency. However, many patients develop non-triad manifestations years earlier, delaying recognition and care. In 2016, we proposed expanded diagnostic criteria incorporating 3 early clinical manifestations — APECED rash, autoimmune enteritis, and enamel hypoplasia — based on observations in 35 North American patients. Here, we provide further support for the clinical utility of these expanded diagnostic criteria in independent cohorts of 57 American and 12 European patients enrolled in a prospective natural history study at the NIH. Across all cohorts, the expanded diagnostic criteria decreased the time to diagnosis by half relative to the classic diagnostic criteria. Patients exhibited an enrichment of early non-endocrine autoimmune manifestations, underscoring disease heterogeneity and the potential for developing organ-specific autoimmunity before endocrine failure. These findings demonstrate the clinical utility of the expanded APECED diagnostic criteria and support the notion that their adoption might enable earlier disease recognition and timely immunomodulatory therapy to improve long-term outcomes.
Authors
Elise M.N. Ferré, Joseph Pechacek, Monica M. Schmitt, Taura Webb, Heather Moorman, Thomas DiMaggio, Princess Barber, Vasielios Oikonomou, Stacey R. Rose, Peter D. Burbelo, Lindsey B. Rosen, Amy P. Hsu, Jennifer Stoddard, Shakuntala Rampertaap, Sergio D. Rosenzweig, Anjali Rai, Maria Teresa Magone, Chantal Cousineau-Krieger, Niki M. Moutsopoulos, Pamela J. Gardner, Heidi H. Kong, Leslie Castelo-Soccio, Ariane Soldatos, Katherine R. Calvo, Meryl Waldman, Behdad Afzali, Stefania Pittaluga, David Kleiner, Steven M. Holland, Kevin Fennelly, Jill Rothschild, Bryce A. Seifert, Magdalena Walkiewicz-Yvon, Theo Heller, Karen Winer, Michail S. Lionakis
Figure 2
Proposed screening of prospective APECED patients.
