Long term longitudinal follow-up of an AD-HIES cohort: the impact of early diagnosis and enrollment to IPINet centers on the natural history of Job’s syndrome

Allergy, Asthma & Clinical Immunology

卷:19

Research

Lucia Pacillo¹  Caterina Cancrini¹  Andrea Finocchi¹  Maria Carrabba²  Giovanna Fabio²  Cinzia Milito³  Isabella Quinti³  Bianca Laura Cinicola⁴  Rosa Maria Dellepiane⁵  Lucia Augusta Baselli⁵  Maria Cristina Pietrogrande⁶  Davide Montin⁷  Fausto Cossu⁸  Giuliana Giardino⁹  Claudio Pignata⁹  Emilia Cirillo⁹  Francesca Conti¹⁰  Andrea Pession¹⁰  Annarosa Soresina¹¹  Laura Dotta¹¹  Manuela Cortesi¹¹  Raffaele Badolato¹¹  Rita Consolini¹² 

[1] Academic Department of Pediatrics (DPUO), Immune and Infectious Diseases Division, Research Unit of Primary Immunodeficiencies, IRCCS, Bambino Gesù Children’s Hospital, Rome, Italy;Chair of Pediatrics, Department of Systems Medicine, University of Rome ‘‘Tor Vergata’’, Rome, Italy;

[2] Department of Internal Medicine, Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, Milan, Italy;

[3] Department of Molecular Medicine, “Sapienza” University of Roma, Rome, Italy;

[4] Department of Molecular Medicine, “Sapienza” University of Roma, Rome, Italy;Department of Maternal Infantile and Urological Sciences, “Sapienza” University of Rome, Rome, Italy;

[5] Department of Pediatrics, Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, Milan, Italy;

[6] Department of Pediatrics, Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, Milan, Italy;Università Degli Studi of Milan, Milan, Italy;

[7] Division of Pediatric Immunology and Rheumatology, Department of Public Health and Pediatrics, “Regina Margherita” Children Hospital, University of Turin, Turin, Italy;

[8] Pediatric Clinic, Antonio Cao Hospital, Cagliari, Italy;

[9] Pediatric Section, Department of Translational Medical Science, Federico II University, Naples, Italy;

[10] Pediatric Unit, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy;

[11] Pediatrics Clinic and Institute for Molecular Medicine A. Nocivelli, Department of Clinical and Experimental Sciences, University of Brescia and ASST-Spedali Civili di Brescia, Brescia, Italy;

[12] Section of Pediatrics Immunology and Rheumatology, Department of Pediatrics, University of Pisa, Pisa, Italy;

关键词: AD-HIES;    Job’s syndrome;    Immunodeficiency;    Inborn errors of immunity;    STAT3;    Pneumatocele;    Staphylococcal infections;    Mucocutaneous candidiasis;    COVID-19;   

DOI  :  10.1186/s13223-023-00776-5

 received in 2022-06-30, accepted in 2023-02-20,  发布年份 2023

来源: Springer

【 摘 要 】

Job’s syndrome, or autosomal dominant hyperimmunoglobulin E syndrome (AD-HIES, STAT3-Dominant Negative), is a rare inborn error of immunity (IEI) with multi-organ involvement and long-life post-infective damage. Longitudinal registries are of primary importance in improving our knowledge of the natural history and management of these rare disorders. This study aimed to describe the natural history of 30 Italian patients with AD-HIES recorded in the Italian network for primary immunodeficiency (IPINet) registry. This study shows the incidence of manifestations present at the time of diagnosis versus those that arose during follow up at a referral center for IEI. The mean time of diagnostic delay was 13.7 years, while the age of disease onset was < 12 months in 66.7% of patients. Respiratory complications, namely bronchiectasis and pneumatoceles, were present at diagnosis in 46.7% and 43.3% of patients, respectively. Antimicrobial prophylaxis resulted in a decrease in the incidence of pneumonia from 76.7% to 46.7%. At the time of diagnosis, skin involvement was present in 93.3% of the patients, including eczema (80.8%) and abscesses (66.7%). At the time of follow-up, under therapy, the prevalence of complications decreased: eczema and skin abscesses reduced to 63.3% and 56.7%, respectively. Antifungal prophylaxis decreased the incidence of mucocutaneous candidiasis from 70% to 56.7%. During the SARS-CoV-2 pandemic, seven patients developed COVID-19. Survival analyses showed that 27 out of 30 patients survived, while three patients died at ages of 28, 39, and 46 years as a consequence of lung bleeding, lymphoma, and sepsis, respectively. Analysis of a cumulative follow-up period of 278.7 patient-years showed that early diagnosis, adequate management at expertise centers for IEI, prophylactic antibiotics, and antifungal therapy improve outcomes and can positively influence the life expectancy of patients.

【 授权许可】

CC BY   
© The Author(s) 2023

【 图 表 】

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