Endocrine Disorders and Genital Infections Impair Gynecological Health in APECED (APS-1).

Viivi Saari,Saila Laakso,Aila Tiitinen,Elina Holopainen,Outi Mäkitie

doi:10.3389/fendo.2021.784195

Abstract

ObjectiveIn autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED) defects in the autoimmune regulator gene lead to impaired immunotolerance. We explored the effects of immunodeficiency and endocrinopathies on gynecologic health in patients with APECED.DesignCross-sectional cohort study combined with longitudinal follow-up data.MethodsWe carried out a gynecologic evaluation, pelvic ultrasound, and laboratory and microbiologic assessment in 19 women with APECED. Retrospective data were collected from previous study visits and hospital records.ResultsThe study subjects’ median age was 42.6 years (range, 16.7-65.5). Sixteen patients (84%) had premature ovarian insufficiency, diagnosed at the median age of 16.5 years; 75% of them used currently either combined contraception or hormonal replacement therapy. In 76% of women, the morphology and size of the uterus were determined normal for age, menopausal status, and current hormonal therapy. Fifteen patients (79%) had primary adrenal insufficiency; three of them used dehydroepiandrosterone substitution. All androgen concentrations were under the detection limit in 11 patients (58%). Genital infections were detected in nine patients (47%); most of them were asymptomatic. Gynecologic C. albicans infection was detected in four patients (21%); one of the strains was resistant to azoles. Five patients (26%) had human papillomavirus infection, three of which were high-risk subtypes. Cervical cell atypia was detected in one patient. No correlation between genital infections and anti-cytokine autoantibodies was found.ConclusionsOvarian and adrenal insufficiencies manifested with very low androgen levels in over half of the patients. Asymptomatic genital infections, but not cervical cell atypia, were common in female patients with APECED.

Highlights

Autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED), called autoimmune polyendocrine syndrome type I (APS-I), is a rare disorder arising from mutations in the autoimmune regulator (AIRE) gene [1]
The classic triad of APECED is characterized by hypoparathyroidism (HP), primary adrenocortical insufficiency (PAI), and chronic mucocutaneous candidiasis (CMC)
Studies in APECED have found oral CMC to correlate with circulating antibodies against Th17 related cytokines IL-22 and IL-17F [7, 8]

Summary

Introduction

Autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED), called autoimmune polyendocrine syndrome type I (APS-I), is a rare disorder arising from mutations in the autoimmune regulator (AIRE) gene [1]. Studies in APECED have found oral CMC to correlate with circulating antibodies against Th17 related cytokines IL-22 and IL-17F [7, 8] These anti-cytokine autoantibodies are common in patients with APECED even before any clinical disease manifestations develop [5, 9, 10]. Oral CMC can predispose to oral squamous cell carcinoma [11], but it is unknown if CMC may predispose to cell atypia on other mucosal surfaces, such as genital mucosa. It is not known whether patients with APECED have increased risk for other gynecologic infections including human papillomavirus (HPV) infections and for cervical neoplasms

Methods

Results

Conclusion