Lo Schiavo Ada, Ruocco Eleonora, Gambardella Alessio, O'Leary Ryan E, Gee Sarah
Department of Dermatology, Second University of Naples, via Sergio Pansini, 5, 80131 Naples, Italy.
Department of Dermatology, Second University of Naples, via Sergio Pansini, 5, 80131 Naples, Italy.
Clin Dermatol. 2014 Sep-Oct;32(5):646-53. doi: 10.1016/j.clindermatol.2014.04.012.
Granulomatous disorders are chronic cell-mediated immune responses histologically characterized by collections of macrophages, epithelioid cells, and multinucleated giant cells. This disease spectrum often has an infectious origin, but sometimes neither an infective agent nor an inciting antigenic stimulus can be identified. The skin may be a preferential target for these disorders, especially in the areas that have been damaged by various forms of skin injury (eg, herpetic infections, trauma, thermal or solar burns, vaccinations, tattoos). These damaged skin sites frame the new concept of an immunocompromised cutaneous district (ICD), which defines a skin area with acquired immune dysregulation that can pave the way for the local onset of opportunistic disorders, such as infections, tumors, and granulomatous disorders. Sarcoidosis, granuloma annulare (GA), and forms of granulomatous vasculitis, such as Churg-Strauss syndrome (CSS) and Wegener's granulomatosis (WG), are the most common granulomatous disorders that occur in an ICD and may share common pathogenic mechanisms. Recent studies have found clinical and pathologic overlapping features across noninfectious granulomas. Although no unifying etiology exists, the development of granulomatous processes in the ICD has often been reported and the literature contains various hypotheses to explain it: (1) overactive immune response in a previously injured region with or without loss of immune tolerance; (2) overall reduced immune response; (3) retention of an exogeneous antigen or foreign body; (4) altered neural signaling; and (5) a combination of all the aforementioned processes. T helper cells, T regulatory cells, and macrophages, as well as a number of antigenic proteins, have been identified as potential contributing factors. In addition, a genetic predisposition and an intact systemic immune system are both instrumental for the persistence of local granuloma formation in the ICD.
肉芽肿性疾病是慢性细胞介导的免疫反应，在组织学上的特征是巨噬细胞、上皮样细胞和多核巨细胞的聚集。这类疾病谱通常起源于感染，但有时既找不到感染因子，也无法确定激发抗原刺激。皮肤可能是这些疾病的优先靶器官，尤其是在受到各种形式皮肤损伤（如疱疹感染、创伤、热烧伤或日光烧伤、疫苗接种、纹身）的部位。这些受损的皮肤部位构成了免疫受损皮肤区域（ICD）的新概念，它定义了一个获得性免疫失调的皮肤区域，这可能为机会性疾病（如感染、肿瘤和肉芽肿性疾病）的局部发生铺平道路。结节病、环状肉芽肿（GA）以及肉芽肿性血管炎的一些形式，如变应性肉芽肿血管炎（CSS）和韦格纳肉芽肿（WG），是在ICD中发生的最常见的肉芽肿性疾病，可能具有共同的致病机制。最近的研究发现非感染性肉芽肿存在临床和病理重叠特征。虽然不存在统一的病因，但ICD中肉芽肿形成过程的发生屡有报道，文献中有各种假说来解释这一现象：（1）先前受损区域的免疫反应过度活跃，有无免疫耐受丧失；（2）整体免疫反应降低；（3）外源性抗原或异物的存留；（4）神经信号改变；（5）上述所有过程的组合。辅助性T细胞、调节性T细胞和巨噬细胞以及一些抗原蛋白已被确定为潜在的促成因素。此外，遗传易感性和完整的全身免疫系统对于ICD中局部肉芽肿形成的持续存在都至关重要。
