Infections and demanding endocrine care contribute to increased mortality in patients with APECED

Abstract

Objective: Autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED) has variable clinical course. Overall mortality is increased but reasons for this remain larg ely unknown. Our objective was to assess the causes of death and factors contributing to increased mortality. Design: A follow-up study of the Finnish APECED cohort in 1970-2019. Methods: In 33 deceased patients with APECED, causes of death and clini cal course preceding the death were analyzed using national registry data, death certificates, autopsy report s, and patient records. Results: Most common causes leading to death were infections (24%), ora l and esophageal malignancies (15%; median age at death 36.7 years; median survival 1.5 years), and diseas es of the circulatory system (18%). Adrenal crisis was an independent cause of death in two patients. In addition, in four patients, the adrenal crisis was a complicating factor during a fatal infection. Other APECED manifestations le ading to death were hypoparathyroidism, diabetes, and hepatitis. Other causes of death included accidents (12%), alco hol-related causes, and amyotrophic lateral sclerosis. Challenges in overall, and especially in the endocrine, care co ntributed to deaths related to carcinomas and adrenal crisis. Age at death and year of death correlated ( r = 0.345, P = 0.045), suggesting improved longevity. Conclusions: Infections, malignancies, and diseases of the circulatory syst em are the most common primary causes of death in patients with APECED. Adrenal crisis is an independent cause of death but more often a contributing factor in fatal infections. Despite the high overall mortality and the demanding care, our results suggest improved patient survival in recent years 2021 European Society of Endocrinology Printed in Great Britain.