Sharifinejad Niusha, Azizi Gholamreza, Rasouli Seyed Erfan, Chavoshzadeh Zahra, Mahdaviani Seyed Alireza, Tavakol Marzieh, Sadri Homa, Nabavi Mohammad, Ebrahimi Sareh Sadat, Shirkani Afshin, Vosughi Motlagh Ahmad, Momen Tooba, Sharafian Samin, Mesdaghi Mehrnaz, Eslami Narges, Delavari Samaneh, Bahrami Sasan, Yazdani Reza, Rezaei Nima, Abolhassani Hassan
Non-Communicable Diseases Research Center, Alborz University of Medical Sciences, Karaj 3149969415, Iran.
Research Center for Immunodeficiencies, Pediatrics Center of Excellence, Children's Medical Center, Tehran University of Medical Sciences, Tehran 1419733141, Iran.
Biology (Basel). 2023 Apr 24;12(5):644. doi: 10.3390/biology12050644.
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; = 0.022]. Consanguinity was more common among patients who developed skin disorders (81.4% vs. 65.2%, < 0.001). The overall skin infection rate and the type of dominant pathogens were significantly different among the IEI patients in different phenotypical classifications ( < 0.001). Atopic presentation, including urticaria, was highly prevalent among patients with congenital defects of phagocytes ( = 0.020). The frequency of eczema was also significantly higher among cases with both syndromic and non-syndromic combined immunodeficiency ( = 0.009). In contrast, autoimmune cutaneous manifestations, including alopecia and psoriasis, were most common in patients with immune dysregulation ( = 0.001) and defects in intrinsic or innate immunity ( = 0.031), respectively. The presence of autoimmune cutaneous complications significantly improved the survival rate of IEI patients ( = 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.
皮肤表现是免疫缺陷病（IEI）患者中最常见的症状之一。在大多数IEI患者中，这些皮肤表现往往是在疾病诊断之前最早出现的特征。我们研究了截至2022年11月伊朗IEI登记册中列出的521例可获得的单基因IEI患者。我们提取了每位患者的人口统计学信息、皮肤表现的详细临床病史以及免疫学评估结果。然后根据国际免疫学会联盟提供的表型分类对患者进行分类和比较。大多数患者被归类为综合征性联合免疫缺陷（25.1%）、非综合征性联合免疫缺陷（24.4%）、主要为抗体缺陷（20.7%）和免疫失调疾病（20.5%）。共有227例患者在中位（IQR）年龄2.0（0.5 - 5.2）岁时出现皮肤表现；其中共有66例（40.7%）患者最初表现为这些症状。有皮肤受累的患者在诊断时年龄普遍较大[5.0（1.6 - 8.0）岁 vs. 3.0（1.0 - 7.0）岁；P = 0.022]。近亲结婚在出现皮肤疾病的患者中更为常见（81.4% vs. 65.2%，P < 0.001）。不同表型分类的IEI患者中，总体皮肤感染率和主要病原体类型存在显著差异（P < 0.001）。特应性表现，包括荨麻疹，在吞噬细胞先天性缺陷患者中高度流行（P = 0.020）。在综合征性和非综合征性联合免疫缺陷病例中，湿疹的发生率也显著更高（P = 0.009）。相比之下，自身免疫性皮肤表现，包括脱发和银屑病，分别在免疫失调患者（P = 0.001）和固有或先天免疫缺陷患者（P = 0.031）中最为常见。自身免疫性皮肤并发症的存在显著提高了IEI患者的生存率（P = 0.21）。总之，在近44%的伊朗单基因IEI患者中观察到了皮肤表现。相当数量的有皮肤受累的患者将这些疾病作为疾病的首发表现，这在非综合征性联合免疫缺陷和吞噬细胞缺陷患者中尤为明显。IEI患者中被忽视的皮肤疾病可能会延迟诊断，诊断通常在出现皮肤相关问题后的3年内确定。皮肤疾病，尤其是自身免疫特征，可能表明IEI患者的预后较好。
