{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,22]],"date-time":"2026-05-22T07:05:13Z","timestamp":1779433513241,"version":"3.53.1"},"reference-count":30,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,5,22]],"date-time":"2026-05-22T00:00:00Z","timestamp":1779408000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>Acquired angioedema due to C1 inhibitor deficiency (AAE-C1INH) is a rare bradykinin-mediated condition that may mimic hereditary angioedema (HAE). Management is largely extrapolated from HAE data. Therefore, retrospective observations in AAE-C1INH are particularly valuable for informing future approaches. This study aimed to evaluate the clinical characteristics, underlying conditions, and treatment outcomes of patients with AAE-C1INH.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We conducted a retrospective cohort study of adult patients diagnosed with AAE-C1INH, with a comprehensive review of demographic and clinical features.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Among 587 patients with recurrent angioedema, 1.7% had AAE-C1INH. Median onset age was 56.5 years (45.5\u201366.75), median follow-up was 60.5 months (23.25\u201366.5), and 20% were female. Clonal hematologic neoplasms were present in 60% of patients and monoclonal gammopathy of undetermined significance in 30%, with angioedema preceding the diagnosis of the underlying condition in 60% of cases. Long-term prophylaxis was required in 50% of patients. Antifibrinolytic agents showed limited efficacy, whereas attenuated androgens were associated with a marked reduction in attack frequency. Rituximab-based therapy effectively controlled angioedema, although relapse occurred during extended follow-up. Complete remission under Bruton\u2019s tyrosine kinase (BTK) inhibition was observed despite persistently low complement levels; however, concurrent withdrawal of renin\u2013angiotensin system blockers represents a potential confounder. Complement levels were observed to parallel treatment response in most patients, whereas this association was not observed in the patient receiving a BTK inhibitor.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>In this rare, well-characterized cohort with extended follow-up, angioedema frequently represented the earliest clinical manifestation of AAE-C1INH, preceding recognition of the underlying disorder. Antifibrinolytic prophylaxis showed limited benefit, whereas attenuated androgens were associated with reduced attack frequency. Furthermore, therapies targeting the underlying lymphoproliferative condition, including rituximab-based regimens and BTK inhibition, were associated with meaningful clinical benefit. These findings support an individualized, etiology-driven management approach and provide practical insights for clinicians managing this rare condition.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fimmu.2026.1836363","type":"journal-article","created":{"date-parts":[[2026,5,22]],"date-time":"2026-05-22T06:09:58Z","timestamp":1779430198000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Acquired angioedema due to C1 inhibitor deficiency: real-world clinical characteristics and treatment outcomes"],"prefix":"10.3389","volume":"17","author":[{"given":"\u0130lkim Deniz","family":"Toprak","sequence":"first","affiliation":[{"name":"Division of Immunology and Allergic Diseases, Department of Internal Medicine, Istanbul Faculty of Medicine, Istanbul Universitesi","place":["\u0130stanbul, T\u00fcrkiye"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Simge","family":"Erdem","sequence":"additional","affiliation":[{"name":"Division of Immunology and Allergic Diseases, Department of Internal Medicine, Istanbul Faculty of Medicine, Istanbul Universitesi","place":["\u0130stanbul, T\u00fcrkiye"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pelin","family":"Korkmaz","sequence":"additional","affiliation":[{"name":"Division of Immunology and Allergic Diseases, Department of Internal Medicine, Istanbul Faculty of Medicine, Istanbul Universitesi","place":["\u0130stanbul, T\u00fcrkiye"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Derya","family":"Unal","sequence":"additional","affiliation":[{"name":"Division of Immunology and Allergic Diseases, Department of Internal Medicine, Istanbul Faculty of Medicine, Istanbul Universitesi","place":["\u0130stanbul, T\u00fcrkiye"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Osman Ozan","family":"Yegit","sequence":"additional","affiliation":[{"name":"Division of Immunology and Allergic Diseases, Department of Internal Medicine, Istanbul Faculty of Medicine, Istanbul Universitesi","place":["\u0130stanbul, T\u00fcrkiye"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Merve","family":"Hormet Igde","sequence":"additional","affiliation":[{"name":"Division of Immunology and Allergic Diseases, Department of Internal Medicine, Istanbul Faculty of Medicine, Istanbul Universitesi","place":["\u0130stanbul, T\u00fcrkiye"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"\u015eule","family":"\u00c7elik Kamac\u0131","sequence":"additional","affiliation":[{"name":"Division of Immunology and Allergic Diseases, Department of Internal Medicine, Istanbul Faculty of Medicine, Istanbul Universitesi","place":["\u0130stanbul, T\u00fcrkiye"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Okan","family":"\u00c7etin","sequence":"additional","affiliation":[{"name":"Division of Immunology and Allergic Diseases, Department of Internal Medicine, Istanbul Faculty of Medicine, Istanbul Universitesi","place":["\u0130stanbul, T\u00fcrkiye"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nida","family":"\u00d6ztop","sequence":"additional","affiliation":[{"name":"Division of Immunology and Allergic Diseases, TC Saglik Bakanligi Basaksehir Cam ve Sakura Sehir Hastanesi","place":["\u0130stanbul, T\u00fcrkiye"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Semra","family":"Demir","sequence":"additional","affiliation":[{"name":"Division of Immunology and Allergic Diseases, Department of Internal Medicine, Istanbul Faculty of Medicine, Istanbul Universitesi","place":["\u0130stanbul, T\u00fcrkiye"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Can","family":"T\u00fczer","sequence":"additional","affiliation":[{"name":"Division of Immunology and Allergic Diseases, TC Saglik Bakanligi Istanbul Sultan 2 Abdulhamid Han Egitim ve Arastirma Hastanesi","place":["\u0130stanbul, T\u00fcrkiye"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Metban","family":"Mastanzade","sequence":"additional","affiliation":[{"name":"Division of Immunology and Allergic Diseases, Department of Internal Medicine, Istanbul Faculty of Medicine, Istanbul Universitesi","place":["\u0130stanbul, T\u00fcrkiye"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tu\u011frul","family":"Elverdi","sequence":"additional","affiliation":[{"name":"Division of Hematology, Department of Internal Medicine, Istanbul Universitesi-Cerrahpasa Cerrahpasa Tip Fakultesi","place":["\u0130stanbul, T\u00fcrkiye"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mehmet Emin","family":"Sezgin","sequence":"additional","affiliation":[{"name":"Division of Immunology and Allergic Diseases, Department of Internal Medicine, Istanbul Faculty of Medicine, Istanbul Universitesi","place":["\u0130stanbul, T\u00fcrkiye"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sevgi","family":"Kalayo\u011flu Be\u015f\u0131\u015f\u0131k","sequence":"additional","affiliation":[{"name":"Division of Immunology and Allergic Diseases, Department of Internal Medicine, Istanbul Faculty of Medicine, Istanbul Universitesi","place":["\u0130stanbul, T\u00fcrkiye"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Asl\u0131","family":"Gelincik","sequence":"additional","affiliation":[{"name":"Division of Immunology and Allergic Diseases, Department of Internal Medicine, Istanbul Faculty of Medicine, Istanbul Universitesi","place":["\u0130stanbul, T\u00fcrkiye"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,5,22]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"398","DOI":"10.1016\/j.jaci.2024.03.024","article-title":"Definition, acronyms, nomenclature, and classification of angioedema (DANCE): AAAAI, ACAAI, ACARE, and APAAACI DANCE consensus","volume":"154","author":"Reshef","year":"2024","journal-title":"J Allergy Clin Immunol"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1186\/1710-1492-6-14","article-title":"Acquired angioedema","volume":"6","author":"Cicardi","year":"2010","journal-title":"Allergy Asthma Clin Immunol"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaip.2016.12.032","article-title":"Diagnosis, course, and management of angioedema in patients with acquired C1-inhibitor deficiency","volume":"5","author":"Zanichelli","year":"2017","journal-title":"J Allergy Clin Immunology: In Pract"},{"key":"B4","doi-asserted-by":"publisher","first-page":"100627","DOI":"10.1111\/all.15214","article-title":"The international WAO\/EAACI guideline for the management of hereditary angioedema\u2013the 2021 revision and update","volume":"15","author":"Maurer","year":"2022","journal-title":"World Allergy Organ J"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1111\/all.13686","article-title":"Long\u2010term effects upon rituximab treatment of acquired angioedema due to C1\u2010inhibitor deficiency","volume":"74","author":"Levi","year":"2019","journal-title":"Allergy"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1007\/s10875-012-9691-2","article-title":"Acquired C1-inhibitor deficiency: 7 patients treated with rituximab","volume":"32","author":"Branellec","year":"2012","journal-title":"J ClinImmunol"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1016\/j.clim.2021.108819","article-title":"Where we are with acquired angioedema due to C1 inhibitor deficiency: a systematic literature review","volume":"230","author":"Shi","year":"2021","journal-title":"Clin Immunol"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaip.2024.09.016","article-title":"Angioedema due to acquired C1-inhibitor deficiency associated with monoclonal gammopathies of undetermined significance characteristics of a French national cohort","volume":"12","author":"Lahuna","year":"2024","journal-title":"J Allergy Clin Immunology: In Pract"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1097\/md.0000000000004363","article-title":"A nationwide study of acquired C1-inhibitor deficiency in France: characteristics and treatment responses in 92 patients","volume":"95","author":"Gobert","year":"2016","journal-title":"Medicine"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaip.2023.10.017","article-title":"Efficacy and safety of rituximab-based treatments in angioedema with acquired C1-inhibitor deficiency","volume":"12","author":"Kalmi","year":"2024","journal-title":"J Allergy Clin Immunology: In Pract"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.1056\/nejmoa0906393","article-title":"Icatibant, a new bradykinin-receptor antagonist, in hereditary angioedema","volume":"363","author":"Cicardi","year":"2010","journal-title":"N Engl J Med"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.1159\/000521646","article-title":"Acquired angioedema due to C1-inhibitor deficiency: a challenging condition","volume":"183","author":"Valle","year":"2022","journal-title":"Int Arch Allergy Immunol"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.3238\/arztebl.2017.0489","article-title":"Acquired angioedema due to C1-inhibitor deficiency (AAE-C1-INH)\u2014a bicenter retrospective study on diagnosis, course, and therapy","volume":"11","author":"Trainotti","year":"2023","journal-title":"J Allergy Clin Immunology: In Pract"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.1093\/cei\/uxae121","article-title":"A multi-centre UK-based survey on angioedema secondary to acquired C1 inhibitor deficiency","volume":"219","author":"Morsi","year":"2025","journal-title":"Clin Exp Immunol"},{"key":"B15","doi-asserted-by":"publisher","first-page":"65","DOI":"10.1186\/s13023-019-1043-3","article-title":"Angioedema due to acquired C1-inhibitor deficiency: spectrum and treatment with C1-inhibitor concentrate","volume":"14","author":"Bork","year":"2019","journal-title":"Orphanet J Rare Dis"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaip.2024.12.027","article-title":"Angioedema due to acquired C1-inhibitor deficiency without hematological condition: a multicenter French cohort study of 34 patients","volume":"13","author":"Stammler","year":"2025","journal-title":"J Allergy Clin Immunology: In Pract"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaip.2021.11.018","article-title":"Angioedema due to acquired deficiency of C1-inhibitor: a cohort study in Spain and a comparison with other series","volume":"10","author":"Baeza","year":"2022","journal-title":"J Allergy Clin Immunology: In Pract"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.1159\/000512933","article-title":"Acquired angioedema with C1 inhibitor deficiency: occurrence, clinical features, and management: a nationwide retrospective study in the Czech Republic patients","volume":"182","author":"Sobotkova","year":"2021","journal-title":"Int Arch Allergy Immunol"},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.1111\/cei.13667","article-title":"Acquired angioedema in B cell lymphoproliferative disease: a retrospective case series","volume":"206","author":"Wonnaparhown","year":"2021","journal-title":"Clin Exp Immunol"},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.1159\/000351452","article-title":"Acquired angioedema-occurrence, clinical features and associated disorders in a Danish nationwide patient cohort","volume":"162","author":"Bygum","year":"2013","journal-title":"Int Arch Allergy Immunol"},{"key":"B21","doi-asserted-by":"crossref","DOI":"10.2500\/aap.2022.43.220043","article-title":"Longitudinal experience with treatment of acquired angioedema using tranexamic acid","volume-title":"Allergy & Asthma Proceedings","author":"Kesh","year":"2022"},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.1016\/j.heliyon.2022.e11292","article-title":"Long term follow-up of complement parameters to improve the management of acquired angioedema due to C1-inhibitor deficiency","volume":"8","author":"Polai","year":"2022","journal-title":"Heliyon"},{"key":"B23","article-title":"Acquired angioedema: a new target for rituximab","volume":"89","author":"Ziakas","year":"2004","journal-title":"Haematologica"},{"key":"B24","doi-asserted-by":"publisher","DOI":"10.1016\/j.amjmed.2005.09.018","article-title":"Rituximab-induced elimination of acquired angioedema due to C1-inhibitor deficiency","volume":"119","author":"Levi","year":"2006","journal-title":"Am J Med"},{"key":"B25","doi-asserted-by":"publisher","DOI":"10.1200\/jco.2011.38.9957","article-title":"Acquired angioedema and marginal zone lymphoma","volume":"30","author":"Lam","year":"2012","journal-title":"J Clin Oncol"},{"key":"B26","doi-asserted-by":"publisher","DOI":"10.2340\/00015555-1157","article-title":"Acquired angioedema responding to rituximab","volume":"91","author":"Hassan","year":"2011","journal-title":"Acta Dermato-Venereologica"},{"key":"B27","doi-asserted-by":"publisher","DOI":"10.2147\/jaa.s68548","article-title":"Rituximab therapy in a patient with low grade B-cell lymphoproliferative disease and concomitant acquired angioedema","volume":"7","author":"Kaur","year":"2014","journal-title":"J Asthma Allergy"},{"key":"B28","article-title":"Successful rituximab B lymphocyte depletion therapy for angioedema due to acquired C1 inhibitor protein deficiency: association with reduced C1 inhibitor protein autoantibody titers","volume":"16","author":"Dreyfus","year":"2014","journal-title":"Israel Med Assoc Journal: IMAJ"},{"key":"B29","first-page":"349","article-title":"Acquired C1 esterase inhibitor deficiency in a marginal zone lymphoma patient treated with rituximab","volume":"20","author":"Ates","year":"2015","journal-title":"J BU ON: Off J Balkan Union Oncol"},{"key":"B30","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaip.2020.08.052","article-title":"The importance of complement testing in acquired angioedema related to angiotensin-converting enzyme inhibitors","volume":"9","author":"Balla","year":"2021","journal-title":"J Allergy Clin Immunology: In Pract"}],"container-title":["Frontiers in Immunology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2026.1836363\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,5,22]],"date-time":"2026-05-22T06:09:59Z","timestamp":1779430199000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2026.1836363\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,5,22]]},"references-count":30,"alternative-id":["10.3389\/fimmu.2026.1836363"],"URL":"https:\/\/doi.org\/10.3389\/fimmu.2026.1836363","relation":{},"ISSN":["1664-3224"],"issn-type":[{"value":"1664-3224","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,5,22]]},"article-number":"1836363"}}