Lahuna Constance, Defendi Federica, Bouillet Laurence, Boccon-Gibod Isabelle, Mekinian Arsene, Coppo Paul, Adamski Henri, Amarger Stephanie, Armengol Guillaume, Aubineau Magali, Bibes Beatrice, Blanchard-Delaunay Claire, Blaison Gilles, Brihaye Benoit, Cathebras Pascal, Caubet Olivier, Demoreuil Claire, Desblache Julien, Durupt Francois, Gayet Stephane, Gondran Guillaume, Hadjadj Jerome, Kalmi Galith, Kanny Gisele, Lacoste Marion, Launay David, Ly Kim Heang, McAvoy Chloé, Martin Ludovic, Ollivier Yann, Pelletier Fabien, Robbins Aylsa, Roos-Weil Damien, Fain Olivier, Gobert Delphine
Sorbonne Université, service de médecine interne, AP-HP, Hôpital Saint Antoine, Paris, France.
Immunology Laboratory, University Hospital, Grenoble, France.
J Allergy Clin Immunol Pract. 2024 Dec;12(12):3283-3291. doi: 10.1016/j.jaip.2024.09.016. Epub 2024 Sep 30.
No specific description of monoclonal gammopathies of undetermined significance (MGUS)-associated angioedema due to acquired C1 inhibitor deficiency (AAE-C1-INH) has been reported yet.
To describe the biological and clinical characteristics, evolution, and response to treatment of MGUS-associated AAE-C1-INH.
We conducted a French national retrospective observational study on MGUS-associated acquired angioedema spanning a 30-year period.
Forty-one patients with MGUS-associated AAE-C1-INH at diagnosis were included; 68% displayed anti-C1-INH antibodies. The monoclonal component was an IgM in 24 patients, IgG in 11, and IgA in 6 patients. The mean age at first angioedema attack was 63 years (standard deviation [SD] = 13 years) and at diagnosis 66 years (SD = 11 years). A total of 88% patients benefited from acute attack treatments, and 77% from long-term prophylaxis, either danazol, tranexamic acid, or lanadelumab. Median follow-up was 7 years, during which 14 patients (33%) evolved into well-defined malignant hemopathies. Fifty percent of patients were given a hematological treatment, either rituximab alone, indicated by recurrent attacks of angioedema in patients with AAE-C1-INH with anti-C1-INH antibodies, or validated combinations of chemotherapies, indicated by evolution into a lymphoma in 7 patients and a myeloma in 3 patients. Fifteen patients (35%) were in clinical complete remission of angioedema at last visit, of whom 60% had an undetectable serum monoclonal immunoglobulin.
Complete remission of AAE-C1-INH is correlated to complete remission of the underlying hematological malignancy, as defined by an undetectable serum monoclonal immunoglobulin. In our MGUS-associated acquired angioedema cohort, we recorded an incidence of evolution into hematological malignancy of 4% per patient-year. It is therefore crucial to conduct full hematological workup during follow-up at an annual rate, and earlier if AAE relapses or if acute attack frequency increases.
尚未有关于意义未明的单克隆丙种球蛋白病（MGUS）相关的获得性C1抑制剂缺乏所致血管性水肿（AAE-C1-INH）的具体描述。
描述MGUS相关的AAE-C1-INH的生物学和临床特征、病情演变及治疗反应。
我们开展了一项为期30年的关于MGUS相关获得性血管性水肿的法国全国性回顾性观察研究。
纳入41例诊断为MGUS相关AAE-C1-INH的患者；68%的患者出现抗C1-INH抗体。单克隆成分在24例患者中为IgM，11例中为IgG，6例中为IgA。首次血管性水肿发作的平均年龄为63岁（标准差[SD]=13岁），诊断时为66岁（SD=11岁）。共有88%的患者从急性发作治疗中获益，77%的患者从长期预防治疗中获益，预防治疗药物为达那唑、氨甲环酸或拉那度单抗。中位随访时间为7年，在此期间14例患者（33%）进展为明确的恶性血液病。50%的患者接受了血液学治疗，对于有抗C1-INH抗体的AAE-C1-INH患者，若血管性水肿反复发作则单独使用利妥昔单抗，对于7例进展为淋巴瘤、3例进展为骨髓瘤的患者则采用经验证的联合化疗方案。15例患者（35%）在最后一次就诊时血管性水肿达到临床完全缓解，其中60%的患者血清单克隆免疫球蛋白检测不到。
AAE-C1-INH的完全缓解与潜在血液系统恶性肿瘤的完全缓解相关，完全缓解定义为血清单克隆免疫球蛋白检测不到。在我们的MGUS相关获得性血管性水肿队列中，我们记录到进展为血液系统恶性肿瘤的发生率为每年每位患者4%。因此，在随访期间每年进行全面的血液学检查至关重要，若AAE复发或急性发作频率增加则应更早进行检查。
