Dipartimento di Fisiopatologia Medico-Chirurgica e dei Trapianti, Università degli Studi di Milano, Milan, Italy.
Unità Operativa di Dermatologia, IRCCS Fondazione Ca' Granda, Ospedale Maggiore Policlinico, Milan, Italy.
Clin Rev Allergy Immunol. 2018 Feb;54(1):114-130. doi: 10.1007/s12016-017-8621-8.
Neutrophilic dermatoses are a group of conditions characterized by the accumulation of neutrophils in the skin and clinically presenting with polymorphic cutaneous lesions, including pustules, bullae, abscesses, papules, nodules, plaques and ulcers. In these disorders, the possible involvement of almost any organ system has lead to coin the term 'neutrophilic diseases'. Neutrophilic diseases have close clinicopathological similarities with the autoinflammatory diseases, which present with recurrent episodes of inflammation in the affected organs in the absence of infection, allergy and frank autoimmunity. Neutrophilic diseases may be subdivided into three main groups: (1) deep or hypodermal forms whose paradigm is pyoderma gangrenosum, (2) plaque-type or dermal forms whose prototype is Sweet's syndrome and (3) superficial or epidermal forms among which amicrobial pustulosis of the folds may be considered the model. A forth subset of epidermal/dermal/hypodermal forms has been recently added to the classification of neutrophilic diseases due to the emerging role of the syndromic pyoderma gangrenosum variants, whose pathogenesis has shown a relevant autoinflammatory component. An increasing body of evidence supports the role of pro-inflammatory cytokines like interleukin (IL)-1-beta, IL-17 and tumour necrosis factor (TNF)-alpha in the pathophysiology of neutrophilic diseases similarly to classic monogenic autoinflammatory diseases, suggesting common physiopathological mechanisms. Moreover, mutations of several genes involved in autoinflammatory diseases are likely to play a role in the pathogenesis of neutrophilic diseases, giving rise to regarding them as a spectrum of polygenic autoinflammatory conditions. In this review, we focus on clinical aspects, histopathological features and pathophysiological mechanisms of the paradigmatic forms of neutrophilic diseases, including pyoderma gangrenosum, Sweet's syndrome, amicrobial pustulosis of the folds and the main syndromic presentations of pyoderma gangrenosum. A simple approach for diagnosis and management of these disorders has also been provided.
中性粒细胞皮肤病是一组以中性粒细胞在皮肤中积累为特征的疾病，临床上表现为多形性皮肤损伤，包括脓疱、大疱、脓肿、丘疹、结节、斑块和溃疡。在这些疾病中，几乎任何器官系统都可能受累，因此被称为“中性粒细胞疾病”。中性粒细胞疾病与自身炎症性疾病具有密切的临床病理相似性，后者在没有感染、过敏和明显自身免疫的情况下，表现为受累器官反复发生炎症。中性粒细胞疾病可分为三大类：（1）深部或皮下形式，其范例是坏疽性脓皮病；（2）斑块型或真皮形式，其原型是Sweet 综合征；（3）浅表或表皮形式，其中皱褶部位的非微生物性脓疱病可被视为模型。由于综合征性坏疽性脓皮病变异型的新兴作用，最近在中性粒细胞疾病的分类中增加了第四组表皮/真皮/皮下形式，其发病机制显示出相关的自身炎症成分。越来越多的证据支持促炎细胞因子（如白细胞介素 (IL)-1β、IL-17 和肿瘤坏死因子 (TNF)-α）在中性粒细胞疾病的病理生理学中的作用与经典的单基因自身炎症性疾病相似，提示存在共同的生理病理机制。此外，参与自身炎症性疾病的几个基因的突变可能在中性粒细胞疾病的发病机制中发挥作用，使它们成为多基因自身炎症性疾病的一个谱系。在这篇综述中，我们重点关注中性粒细胞疾病的典范形式，包括坏疽性脓皮病、Sweet 综合征、皱褶部位的非微生物性脓疱病和坏疽性脓皮病的主要综合征表现，包括临床方面、组织病理学特征和病理生理学机制。还提供了这些疾病的诊断和管理的简单方法。
