Kolivras Athanassios, Meiers Isabelle, Sass Ursula, Thompson Curtis T
Department of Dermatology and Dermatopathology, Saint-Pierre, Brugmann and Queen Fabiola Children's University Hospitals, Université Libre de Bruxelles, 1000 Brussels, Belgium.
Department of Pathology, Laboratoire Luc Olivier, 5380 Fernelmont, Belgium.
Dermatopathology (Basel). 2021 Jun 8;8(2):202-220. doi: 10.3390/dermatopathology8020026.
Autoinflammation is defined by aberrant, antigen-independent activation of the innate immune signaling pathways. This leads to increased, pro-inflammatory cytokine expression and subsequent inflammation. In contrast, autoimmune and allergic diseases are antigen-directed immune responses from activation of the adaptive immune system. The innate and adaptive immune signaling pathways are closely interconnected. The group of 'complex multigenic diseases' are a result of mutual dysregulation of both the autoinflammatory and autoimmune physiologic components. In contrast, monogenic autoinflammatory syndromes (MAIS) result from single mutations and are exclusively autoinflammatory in their pathogenesis. Studying the clinical and histopathological findings for the various MAIS explains the phenotypical correlates of their specific mutations. This review aims to group the histopathologic clues for autoinflammation into three recognizable patterns. The presence of these histologic patterns in a pediatric patient with recurrent fevers and systemic inflammation should raise suspicion of an autoinflammatory component in MAIS, or, more frequently, in a complex multigenic disease. The three major histopathological patterns seen in autoinflammation are as follows: (i) the 'neutrophilic' pattern, seen in urticarial neutrophilic dermatosis, pustular psoriasis, aseptic neutrophilic folliculitis, and Sweet's syndrome; (ii) the 'vasculitic' pattern seen in small vessel-vasculitis (including hypersensitivity/leukocytoclastic vasculitis, thrombosing microangiopathy and lymphocytic vasculitis), and intermediate-sized vessel vasculitis, mimicking polyarteritis nodosa; and (iii) the 'granulomatous' pattern. Beyond these three patterns, there are additional histopathologic clues, which are detailed below. It is important for a dermatopathologist to recognize the patterns of autoinflammation, so that a diagnosis of MAIS or complex multigenic diseases may be obtained. Finally, careful histopathologic analyses could contribute to a better understanding of the various clinical manifestations of autoinflammation.
自身炎症反应是由先天免疫信号通路的异常、抗原非依赖性激活所定义的。这会导致促炎细胞因子表达增加以及随后的炎症反应。相比之下，自身免疫性疾病和过敏性疾病是适应性免疫系统激活后针对抗原的免疫反应。先天免疫和适应性免疫信号通路紧密相连。“复杂多基因疾病”是自身炎症反应和自身免疫生理成分相互失调的结果。相反，单基因自身炎症综合征（MAIS）由单一突变引起，其发病机制完全是自身炎症性的。研究各种MAIS的临床和组织病理学发现可以解释其特定突变的表型相关性。本综述旨在将自身炎症反应的组织病理学线索分为三种可识别的模式。在患有反复发热和全身炎症的儿科患者中出现这些组织学模式，应引起对MAIS中自身炎症成分的怀疑，或者更常见的是，对复杂多基因疾病中自身炎症成分的怀疑。自身炎症反应中可见的三种主要组织病理学模式如下：（i）“中性粒细胞”模式，见于荨麻疹性中性粒细胞性皮肤病、脓疱型银屑病、无菌性中性粒细胞性毛囊炎和Sweet综合征；（ii）“血管炎”模式，见于小血管血管炎（包括超敏性/白细胞破碎性血管炎、血栓性微血管病和淋巴细胞性血管炎）以及类似结节性多动脉炎的中等大小血管血管炎；（iii）“肉芽肿”模式。除了这三种模式外，还有其他组织病理学线索，如下详述。皮肤病理学家认识自身炎症反应的模式很重要，这样才能做出MAIS或复杂多基因疾病的诊断。最后，仔细的组织病理学分析有助于更好地理解自身炎症反应的各种临床表现。
