Patients With APECED Have Increased Early Mortality Due to Endocrine Causes, Malignancies and infections

Abstract

Context Autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED) is an autoimmune endocrinopathy with severe and unpredictable course. The impact of APECED on mortality has not been determined. Objective To assess overall and cause-specific mortality of patients with APECED. Design and Setting A follow-up study of Finnish patients with APECED from 1971 to 2018. Causes and dates of death were collected from Finnish registries. Patients Ninety-one patients with APECED. Main Outcome Measure Overall and cause-specific standardized mortality ratios (SMRs) determined by comparing the observed numbers of death and those expected on the basis of respective population death rates in Finland. Results The overall disease mortality was significantly increased (29 deaths, SMR 11; 95% confidence interval [CI] 7.2-16; P < 0.001). The relative risk (SMR) was highest in the youngest age groups but the absolute excess risk was similar (about 10 per 10 000 person-years) in all age categories. The highest SMRs were seen for endocrine and metabolic diseases (SMR 570; 95% CI, 270-1000; P < 0.001) and for oral and esophageal malignancies (SMR 170; 95% CI, 68-360; P < 0.001). Mortality was also increased for infections, diseases of digestive system, alcohol-related deaths, and for accidents. Due to the small number of cases we were unable to evaluate whether mortality was affected by disease severity. Conclusions Patients with APECED have significantly increased mortality in all age groups. Highest SMRs are found for causes that are directly related to APECED but also for infections. Increased alcohol- and accident-related deaths may be influenced by psychosocial factors.

Pubertal development and premature ovarian insufficiency in patients with APECED

“…We and other have previously shown high mortality in patients with APECED (12,13). Causes of death in our patients were in line with a recent study reporting increased mortality among the Finnish patients with APECED (23).…”

Anti-CD45RC antibody immunotherapy prevents and treats experimental autoimmune polyendocrinopathy–candidiasis–ectodermal dystrophy syndrome

“…The long-term use of immunosuppressive drugs increases the risk of developing complications, such as cancer and/or infection ( 2 , 14 ), a serious concern for APECED patients, who are already prone to chronic mucosal Candida infection ( 15 ). The life expectancy of APECED patients is reduced and has not increased in recent decades ( 16 ). Thus, identification of targeted therapeutic interventions is needed to improve the morbidity and mortality associated with this syndrome.…”

A COVID-19 pneumonia case report of autoimmune polyendocrine syndrome type 1 in Lombardy, Italy: letter to the editor

“…Our case might not be considered a paradigmatic example of PAI; at variance with other forms of autoimmune Addison disease, patients with APS-1 have primary immunodeficiency, which explains the T-cell deficiency-related chronic mucocutaneous candidiasis. This feature has relevant clinical consequences; in fact, a recent prospective study showed that the Finnish APS-1 cohort had an increased mortality from infections (standardized mortality ratio 36; 95% CI 6.4-110) in comparison to the general population [5].…”