Long Term Longitudinal Follow up of AD-HIES Cohort: Impact of Early Diagnosis and Enrolment to IPINet Centres on Natural History of Job Syndrome

Abstract

The Job Syndrome or Autosomal Dominant Hyper Immunoglobulin E Syndrome (AD-HIES, LOF-STAT3 gene) is a very rare inborn error of immunity disorder with multi-organ involvement and long-life post-infective damages. Longitudinal registries are of main importance to improve knowledge on natural history and management of these rare disorders. This study aims to describe the natural history of 30 Italian patients recorded in the IPINet registry with AD-HIES, with a cumulative observational-time of 721.1 patient-years. Age at disease onset was < 12 months in the 66.7% of patients, but the mean time of diagnostic delay was 13.7 years. At diagnosis skin involvement was present in 93.3% of patients (eczema 80.8%, abscess 66.7%). At the follow up eczema was still present in 63.3% and abscess in 56.7%. Respiratory complications such as bronchiectasis and pneumatoceles were present at diagnosis in the 46.7% and 43.3% respectively. Antimicrobial prophylaxis resulted in decrease of pneumonia from 76.7–46.7%. Antifungal prophylaxis decreased mucocutaneous candidiasis occurrence from 70–56.7%. In the course of SARS-CoV-2 pandemic, seven patients developed COVID-19. Survival analyses showed that 27 out of 30 patients are still alive, while three patients died at age of 28, 39 and 46 as consequence of lungs bleeding, lymphoma and sepsis, respectively. Our study shows that many severe complications can affect AD-HIES patients. Analysis of a cumulative follow-up of 278.7 patient-years has shown that early diagnosis, adequate management at expertise centres for primary immunodeficiency, prophylactic antibiotic and antifungal therapy improve outcome and can positively influence patients’ life expectancy.