Stammler Romain, Defendi Federica, Aubineau Magali, Bibes Beatrice, Boccon-Gibod Isabelle, Bouillet Laurence, Crabol Yoann, Dalmas Marie Caroline, de Moreuil Claire, Delluc Aurelien, Dingremont Claire, Du-Thanh Aurelie, Hadjadj Jerome, Jeandel Pierre-Yves, Kalmi Galith, Lacoste Marion, Martin Ludovic, Avoy Chloé Mc, Blanchard-Delaunay Claire, Taquet Marie Caroline, Fain Olivier, Gobert Delphine
Service de Médecine Interne, Hôpital Saint Antoine, AP-HP, Sorbonne Université, Paris, France.
Immunology Department, Grenoble University Hospital, Grenoble, France.
J Allergy Clin Immunol Pract. 2025 Mar;13(3):542-550.e2. doi: 10.1016/j.jaip.2024.12.027. Epub 2025 Jan 3.
Angioedema (AE) due to acquired C1-inhibitor deficiency (AAE-C1-INH) is a rare disease associating recurrent edema of the mucosa and skin. Several underlying diseases have been reported, mainly lymphoproliferative diseases and monoclonal gammopathy. However, 15% to 20% of patients never exhibit such a hematological condition.
To analyze specific features of patients with AAE-C1-INH without a hematological condition.
This is a multicenter, retrospective cohort study of patients with AAE-C1-INH without a hematological condition included from January 1999 to May 2024 in the French national CREAK (Centre de reference des angioedèmes à kinine) registry. The clinical and biological characteristics of patients were detailed and then compared with those of patients with AAE-C1-INH associated with lymphoid hemopathies or monoclonal gammopathy.
Thirty-four patients were included. All patients displayed a functional C1-INH below 50% of the reference value, 26 (76%) also had a decreased C1-INH antigen level, and 26 (76%) displayed anti-C1-INH antibodies. After a median follow-up of 65 months, 4 (12%) patients were in spontaneous complete remission of AE; 15 (44%) were in complete response under long-term prophylactic treatment. Compared with 75 patients with lymphoma-associated AAE-C1-INH, patients with AAE-C1-INH without a hematological condition displayed a higher incidence of anti-C1-INH antibodies and received more frequently symptomatic or prophylactic treatment with a lower remission rate at last follow-up. Clinical and biological features of patients with AAE-C1-INH without a hematological condition were similar to those of 30 patients with monoclonal gammopathy-associated AAE-C1-INH.
AAE-C1-INH without a hematological condition displays a different clinical and biological presentation from lymphoma-associated AAE-C1-INH. No autoimmune disease was identified. Unlike rituximab, long-term prophylaxis seems to prevent AE attacks among these patients.
获得性C1抑制物缺乏所致血管性水肿（AAE-C1-INH）是一种罕见疾病，伴有黏膜和皮肤反复水肿。已有多种潜在疾病被报道，主要是淋巴增殖性疾病和单克隆丙种球蛋白病。然而，15%至20%的患者从未出现此类血液学状况。
分析无血液学状况的AAE-C1-INH患者的特定特征。
这是一项多中心回顾性队列研究，纳入了1999年1月至2024年5月法国国家CREAK（激肽性血管性水肿参考中心）登记处中无血液学状况的AAE-C1-INH患者。详细记录患者的临床和生物学特征，然后与伴有淋巴造血系统疾病或单克隆丙种球蛋白病的AAE-C1-INH患者进行比较。
共纳入34例患者。所有患者的功能性C1-INH均低于参考值的50%，26例（76%）患者的C1-INH抗原水平也降低，26例（76%）患者出现抗C1-INH抗体。中位随访65个月后，4例（12%）患者的血管性水肿自发完全缓解；15例（44%）患者在长期预防性治疗下完全缓解。与75例淋巴瘤相关的AAE-C1-INH患者相比，无血液学状况的AAE-C1-INH患者抗C1-INH抗体的发生率更高，接受对症或预防性治疗的频率更高，末次随访时缓解率较低，但无血液学状况的AAE-C1-INH患者的临床和生物学特征与30例单克隆丙种球蛋白病相关的AAE-C1-INH患者相似。
无血液学状况的AAE-C1-INH与淋巴瘤相关的AAE-C1-INH在临床和生物学表现上有所不同。未发现自身免疫性疾病。与利妥昔单抗不同，长期预防似乎可预防这些患者的血管性水肿发作。
