1 Infectious Disease Service and Critical Care Division, Memorial Hospital of Rhode Island and the Alpert Medical School of Brown University, Providence, USA.
2 Department of History and Classical Studies, McGill University, Montreal, Canada.
Innate Immun. 2018 Nov;24(8):466-479. doi: 10.1177/1753425918808008.
Ninety years ago, Gregory Shwartzman first reported an unusual discovery following the intradermal injection of sterile culture filtrates from principally Gram-negative strains from bacteria into normal rabbits. If this priming dose was followed in 24 h by a second intravenous challenge (the provocative dose) from same culture filtrate, dermal necrosis at the first injection site would regularly occur. This peculiar, but highly reproducible, event fascinated the microbiologists, hematologists, and immunologists of the time, who set out to determine the mechanisms that underlie the pathogenesis of this reaction. The speed of this reaction seemed to rule out an adaptive, humoral, immune response as its cause. Histopathologic material from within the necrotic center revealed fibrinoid, thrombo-hemorrhagic necrosis within small arterioles and capillaries in the micro-circulation. These pathologic features bore a striking resemblance to a more generalized coagulopathic phenomenon following two repeated endotoxin injections described 4 yr earlier by Sanarelli. This reaction came to be known as the generalized Shwartzman phenomenon, while the dermal reaction was named the localized or dermal Shwartzman reaction. A third category was later added, called the single organ or mono-visceral form of the Shwartzman phenomenon. The occasional occurrence of typical pathological features of the generalized Shwartzman reaction limited to a single organ is notable in many well-known clinical events (e.g., hyper-acute kidney transplant rejection, fulminant hepatic necrosis, or adrenal apoplexy in Waterhouse-Fredrickson syndrome). We will briefly review the history and the significant insights gained from understanding this phenomenon regarding the circuitry and control mechanisms responsible for disseminated intravascular coagulation, the vasculopathy and the immunopathy of sepsis.
九十年前，格雷戈里·施瓦茨曼（Gregory Shwartzman）首次报道了一项不同寻常的发现，即在将主要为革兰氏阴性菌的无菌培养滤液经皮内注射入正常兔子体内后。如果 24 小时后用相同培养滤液进行第二次静脉挑战（激发剂量），则第一次注射部位会经常出现皮肤坏死。这种奇特但高度可重复的现象引起了当时的微生物学家、血液学家和免疫学家的兴趣，他们开始确定这种反应发病机制的基础。这种反应的速度似乎排除了适应性、体液、免疫反应作为其原因。坏死中心的组织病理学材料显示小动脉和微循环中的毛细血管内有纤维蛋白样、血栓性出血性坏死。这些病理特征与 Sanarelli 四年前描述的两次重复内毒素注射后更广泛的凝血障碍现象非常相似。这种反应被称为全身性施瓦茨曼现象，而皮肤反应则被称为局部或皮肤施瓦茨曼反应。后来又添加了第三个类别，称为施瓦茨曼现象的单一器官或单器官形式。在许多著名的临床事件中，偶尔会出现全身性施瓦茨曼反应的典型病理特征仅限于单个器官，这一点值得注意（例如，超急性肾移植排斥反应、暴发性肝坏死或 Waterhouse-Fredrickson 综合征中的肾上腺中风）。我们将简要回顾这一现象的历史和从理解这一现象中获得的重要见解，这些见解涉及负责弥散性血管内凝血、败血症的血管病和免疫病的电路和控制机制。
