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Background: 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., Objective: To describe the biological and clinical characteristics, evolution, and response to treatment of MGUS-associated AAE-C1-INH., Materials and Methods: We conducted a French national retrospective observational study on MGUS-associated acquired angioedema spanning a 30-year period., Results: 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., Conclusions: 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., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: The systemic capillary leak syndrome (SCLS), also known as Clarkson disease, is a very rare condition characterized by recurrent life-threatening episodes of vascular hyperpermeability in the presence of a monoclonal gammopathy. Extended intravenous immunoglobulin (IVIG) treatment is associated with fewer recurrences and improved survival, but the optimal treatment dosage and duration remain unknown., Objective: We aim to evaluate the safety of IVIG tapering and withdrawal in patients with SCLS., Methods: We conducted a retrospective multicenter study including all adult patients with monoclonal gammopathy-associated SCLS from the EurêClark registry who received at least 1 course of IVIG. The primary end point was overall survival according to IVIG withdrawal., Results: Fifty-nine patients of mean ± SD age 51 ± 13 years were included. Overall cumulative probabilities of 2-, 5-, 10- and 15-year survival were 100%, 85%, 72%, 44%, respectively. The IVIG was withdrawn at least once in 18 patients (31%; W+ group) and never in 41 patients (69%; W- group). Cumulative probabilities of 10-year survival in W+ versus W- groups were 50% and 83% (log rank test, P = .02), respectively. Relapse rate and the median number of relapses in the W+ versus the W- groups were 72% versus 58% (P = 0.3) and 2.5 (0.3-4) versus 1 (0-2) (P = .03), respectively. The IVIG tapering was not statistically associated with increased person-year incidence of attacks using a mixed linear model., Conclusions: The IVIG withdrawal was associated with increased mortality and higher rate of recurrence in SCLS patients. The IVIG tapering might be cautiously considered in stable SCLS patients., (Copyright © 2022 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)