Autoimmune versus Non-autoimmune Cutaneous Features in Monogenic Patients with Inborn Errors of Immunity
Niusha Sharifinejad,
Gholamreza Azizi,
Seyed Erfan Rasouli,
Zahra Chavoshzadeh,
Seyed Alireza Mahdaviani,
Marzieh Tavakol,
Homa Sadri,
Mohammad Nabavi,
Sareh Sadat Ebrahimi,
Afshin Shirkani,
Ahmad Vosughi Motlagh,
Tooba Momen,
Samin Sharafian,
Mehrnaz Mesdaghi,
Narges Eslami,
Samaneh Delavari,
Sasan Bahrami,
Reza Yazdani,
Nima Rezaei,
Hassan Abolhassani
Affiliations
Niusha Sharifinejad
Non-Communicable Diseases Research Center, Alborz University of Medical Sciences, Karaj 3149969415, Iran
Gholamreza Azizi
Non-Communicable Diseases Research Center, Alborz University of Medical Sciences, Karaj 3149969415, Iran
Seyed Erfan Rasouli
Non-Communicable Diseases Research Center, Alborz University of Medical Sciences, Karaj 3149969415, Iran
Zahra Chavoshzadeh
Pediatric Infections Research Center, Mofid Children’s Hospital, Shahid Beheshti University of Medical Sciences, Tehran 1985717443, Iran
Seyed Alireza Mahdaviani
Pediatric Respiratory Diseases Research Center, National Research Institute of Tuberculosis and Lung Diseases, Shahid Beheshti University of Medical Sciences, Tehran 1985717443, Iran
Marzieh Tavakol
Non-Communicable Diseases Research Center, Alborz University of Medical Sciences, Karaj 3149969415, Iran
Homa Sadri
Non-Communicable Diseases Research Center, Alborz University of Medical Sciences, Karaj 3149969415, Iran
Mohammad Nabavi
Department of Allergy and Clinical Immunology, Rasool e Akram Hospital, Iran University of Medical Sciences, Tehran 1449614535, Iran
Sareh Sadat Ebrahimi
Department of Immunology and Allergy, Kerman University of Medical Sciences, Kerman 7619833477, Iran
Afshin Shirkani
Allergy and Clinical Immunology Department, School of Medicine, Bushehr University of Medical Science, Moallem St., Bushehr 7514763448, Iran
Ahmad Vosughi Motlagh
Department of Pediatrics, North Khorasan University of Medical Sciences, Bojnurd 7487794149, Iran
Tooba Momen
Department of Asthma, Allergy and Clinical Immunology, Child Growth and Development Research Center, Research Institute of Primordial Prevention of Non-Communicable Disease, Isfahan University of Medical Sciences, Isfahan 8174673461, Iran
Samin Sharafian
Pediatric Infections Research Center, Mofid Children’s Hospital, Shahid Beheshti University of Medical Sciences, Tehran 1985717443, Iran
Mehrnaz Mesdaghi
Pediatric Infections Research Center, Mofid Children’s Hospital, Shahid Beheshti University of Medical Sciences, Tehran 1985717443, Iran
Narges Eslami
Pediatric Infections Research Center, Mofid Children’s Hospital, Shahid Beheshti University of Medical Sciences, Tehran 1985717443, Iran
Samaneh Delavari
Research Center for Immunodeficiencies, Pediatrics Center of Excellence, Children’s Medical Center, Tehran University of Medical Sciences, Tehran 1419733141, Iran
Sasan Bahrami
Department of Digital Media, Westphal College of Media Arts and Design, Drexel University, Philadelphia, PA 19104, USA
Reza Yazdani
Research Center for Immunodeficiencies, Pediatrics Center of Excellence, Children’s Medical Center, Tehran University of Medical Sciences, Tehran 1419733141, Iran
Nima Rezaei
Research Center for Immunodeficiencies, Pediatrics Center of Excellence, Children’s Medical Center, Tehran University of Medical Sciences, Tehran 1419733141, Iran
Hassan Abolhassani
Research Center for Immunodeficiencies, Pediatrics Center of Excellence, Children’s Medical Center, Tehran University of Medical Sciences, Tehran 1419733141, Iran
Cutaneous manifestations are one of the most common presentations among patients with inborn errors of immunity (IEI). These skin manifestations are often among the first presenting features in the majority of patients preceding the IEI diagnosis. We studied 521 available monogenic patients with IEI listed in the Iranian IEI registry up to November 2022. We extracted each patient’s demographic information, detailed clinical history of cutaneous manifestations, and immunologic evaluations. The patients were then categorized and compared based on their phenotypical classifications provided by the International Union of Immunological Societies. Most patients were categorized into syndromic combined immunodeficiency (25.1%), non-syndromic combined immunodeficiency (24.4%), predominantly antibody deficiency (20.7%), and diseases of immune dysregulation (20.5%). In total, 227 patients developed skin manifestations at a median (IQR) age of 2.0 (0.5–5.2) years; a total of 66 (40.7%) of these patients initially presented with these manifestations. Patients with cutaneous involvement were generally older at the time of diagnosis [5.0 (1.6–8.0) vs. 3.0 (1.0–7.0) years; p = 0.022]. Consanguinity was more common among patients who developed skin disorders (81.4% vs. 65.2%, p p p = 0.020). The frequency of eczema was also significantly higher among cases with both syndromic and non-syndromic combined immunodeficiency (p = 0.009). In contrast, autoimmune cutaneous manifestations, including alopecia and psoriasis, were most common in patients with immune dysregulation (p = 0.001) and defects in intrinsic or innate immunity (p = 0.031), respectively. The presence of autoimmune cutaneous complications significantly improved the survival rate of IEI patients (p = 0.21). In conclusion, cutaneous manifestations were observed in nearly 44% of Iranian patients with monogenic IEI. A considerable number of patients with cutaneous involvements developed these disorders as their first manifestation of the disease, which was particularly noticeable in patients with non-syndromic combined immunodeficiency and phagocytic defects. The neglected skin disorders in IEI patients might delay diagnosis, which is generally established within a 3-year interval from the development of skin-related problems. Cutaneous disorders, especially autoimmune features, might indicate a mild prognosis in IEI patients.
