Deroux Alban, Dumestre-Perard Chantal, Khalil-Mgharbel Abir, Maignan Maxime, Boccon-Gibod Isabelle, Fevre Marie-Cécile, Vilgrain Isabelle, Bouillet Laurence
Internal Medicine Department, Grenoble University Hospital, Grenoble, France.
Int Arch Allergy Immunol. 2016;170(2):108-114. doi: 10.1159/000446959. Epub 2016 Jul 30.
The aetiology of angio-oedema (AE) is difficult to determine; however, it is essential in emergency situations when two major contexts may be present: mast cell-mediated AE and bradykinin-mediated AE. Different forms of AE are currently distinguished based on clinical criteria (spontaneous duration of the attack, presence of concomitant or late-appearing superficial urticaria, history of atopy, and others), but specific biomarkers could improve patient management.
In this prospective study, potential biomarkers have been identified, and their statistical characteristics were examined.
Samples were taken on day 0 (D0) and D7 for 3 patient groups (n = 11 each): bradykinin-mediated AE [peripheral site of attack, ear, nose, throat (ENT), and abdominal involvement], mast cell-mediated AE, and non-bradykinin-mediated abdominal pain.
Assay of the potential biomarkers revealed no significant differences in C1 inhibitor and C4 levels. In contrast, D-dimer levels peaked during bradykinin-mediated AE attacks (median 2.2 mg/l at D0 vs. 0.52 mg/l at D7; p < 10-3) as well as during mast cell-mediated AE attacks (1.97 vs. 0.65 mg/l; p = 0.04) and were high in bradykinin-mediated AE compared to the control group (0.69 mg/l; p = 0.01). A threshold value of 0.62 mg/l was found to have a negative predictive value of 100% for bradykinin-mediated AE compared to other causes of abdominal pain (group 3). Circulating VE-cadherin levels were also increased during an attack (1,990 at D0 vs. 1,566 ng/ml at D7; p = 0.01), but could not distinguish between bradykinin-mediated and mast cell-mediated AE, like D-dimers.
Exploration of changes in fibrinolysis-related markers (particularly D-dimers) is thus promising for the diagnosis of AE attacks in difficult-to-diagnose abdominal forms, although it was not able to differentiate between bradykinin and mast cell-mediated AE.
血管性水肿（AE）的病因难以确定；然而，在两种主要情况可能存在的紧急情况下，这一点至关重要：肥大细胞介导的AE和缓激肽介导的AE。目前根据临床标准（发作的自发持续时间、是否伴有或迟发性浅表性荨麻疹、特应性病史等）区分不同形式的AE，但特定的生物标志物可以改善患者管理。
在这项前瞻性研究中，已确定潜在的生物标志物，并对其统计特征进行了检查。
在第0天（D0）和第7天对3组患者（每组n = 11）采集样本：缓激肽介导的AE [发作的外周部位、耳、鼻、喉（ENT）和腹部受累]、肥大细胞介导的AE和非缓激肽介导的腹痛。
对潜在生物标志物的检测显示，C1抑制剂和C4水平无显著差异。相比之下，D-二聚体水平在缓激肽介导的AE发作期间达到峰值（D0时中位数为2.2 mg/l，D7时为0.52 mg/l；p < 10-3）以及在肥大细胞介导的AE发作期间（1.97 vs. 0.65 mg/l；p = 0.04），并且与对照组（0.69 mg/l；p = 0.01）相比，缓激肽介导的AE中D-二聚体水平较高。发现阈值为0.62 mg/l时，与其他腹痛原因（第3组）相比，对缓激肽介导的AE具有100%的阴性预测价值。发作期间循环血管内皮钙黏蛋白水平也升高（D0时为1990，D7时为1566 ng/ml；p = 0.01），但与D-二聚体一样，无法区分缓激肽介导的AE和肥大细胞介导的AE。
因此，探索纤溶相关标志物（特别是D-二聚体）的变化对于诊断难以诊断的腹部形式的AE发作具有前景，尽管它无法区分缓激肽介导的AE和肥大细胞介导的AE。
