Service de médecine interne 2, CHU La Pitié-Salpêtrière, APHP, Université Paris 6, France; Service de réanimation médicale, CHU La Pitié-Salpêtrière, APHP, Université Paris 6, France.
Service de médecine interne, CH Bretagne Atlantique, Vannes, France.
Am J Med. 2017 Oct;130(10):1219.e19-1219.e27. doi: 10.1016/j.amjmed.2017.05.023. Epub 2017 Jun 9.
Monoclonal gammopathy-associated systemic capillary-leak syndrome, also known as Clarkson disease, is a rare condition characterized by recurrent life-threatening episodes of capillary hyperpermeability in the context of a monoclonal gammopathy. This study was conducted to better describe the clinical characteristics, natural history, and long-term outcome of monoclonal gammopathy-associated systemic capillary-leak syndrome.
We conducted a cohort analysis of all patients included in the European Clarkson disease (EurêClark) registry between January 1997 and March 2016. From diagnosis to last follow-up, studied outcomes (eg, the frequency and severity of attacks, death, and evolution toward multiple myeloma) and the type of preventive treatments administered were monitored every 6 months.
Sixty-nine patients (M/F sex ratio 1:1; mean ± SD age at disease onset 52 ± 12 years) were included in the study. All patients had monoclonal gammopathy of immunoglobulin G type, with kappa light chains in 47 (68%). Median (interquartile range) follow-up duration was 5.1 (2.5-9.7) years. Twenty-four patients (35%) died after 3.3 (0.9-8) years. Fifty-seven (86%) patients received at least one preventive treatment, including intravenous immunoglobulins (IVIg) n = 48 (73.8%), theophylline n = 22 (33.8%), terbutaline n = 22 (33.8%), and thalidomide n = 5 (7.7%). In the 65 patients with follow-up, 5- and 10-year survival rates were 78% (n = 35) and 69% (n = 17), respectively. Multivariate analysis found preventive treatment with IVIg (hazard ratio 0.27; 95% confidence interval, 0.10-0.70; P = .007) and terbutaline (hazard ratio 0.35; 95% confidence interval, 0.13-0.96; P = .041) to be independent predictors of mortality.
We describe the largest cohort to date of patients with well-defined monoclonal gammopathy-associated systemic capillary-leak syndrome. Preventive treatment with IVIg was the strongest factor associated with survival, suggesting the use of IVIg as the first line in prevention therapy.
单克隆丙种球蛋白相关性全身性毛细血管渗漏综合征，也称为克拉克森病，是一种罕见的疾病，其特征是在单克隆丙种球蛋白的背景下反复发作危及生命的毛细血管通透性增加。本研究旨在更好地描述单克隆丙种球蛋白相关性全身性毛细血管渗漏综合征的临床特征、自然史和长期结局。
我们对 1997 年 1 月至 2016 年 3 月期间纳入欧洲克拉克森病（EurêClark）登记处的所有患者进行了队列分析。从诊断到最后一次随访，监测研究结果（例如，发作的频率和严重程度、死亡和向多发性骨髓瘤的演变）和给予的预防治疗类型，每 6 个月监测一次。
本研究纳入了 69 例患者（男女比例为 1:1；疾病发病时的平均年龄±标准差为 52±12 岁）。所有患者均有免疫球蛋白 G 型单克隆丙种球蛋白，κ 轻链 47 例（68%）。中位（四分位距）随访时间为 5.1（2.5-9.7）年。24 例患者（35%）在 3.3（0.9-8）年后死亡。57 例（86%）患者接受了至少一种预防治疗，包括静脉注射免疫球蛋白（IVIg）n=48（73.8%）、茶碱 n=22（33.8%）、特布他林 n=22（33.8%）和沙利度胺 n=5（7.7%）。在有随访的 65 例患者中，5 年和 10 年生存率分别为 78%（n=35）和 69%（n=17）。多变量分析发现，IVIg（危险比 0.27；95%置信区间，0.10-0.70；P=0.007）和特布他林（危险比 0.35；95%置信区间，0.13-0.96；P=0.041）的预防治疗是死亡率的独立预测因素。
我们描述了迄今为止最大的一组明确的单克隆丙种球蛋白相关性全身性毛细血管渗漏综合征患者。IVIg 的预防治疗是与生存相关性最强的因素，提示将 IVIg 作为预防治疗的一线药物。
