Abstract Introduction Acquired angioedema (AAE) due to C1-esterase inhibitor (C1-INH) deficiency is a rare, potentially fatal disorder caused by increased bradykinin activity leading to vascular permeability and submucosal edema. Unlike hereditary angioedema, AAE typically presents later in life, lacks a family history, and is frequently associated with underlying B-cell lymphoproliferative disorders or autoimmune diseases. Among these, splenic marginal zone lymphoma (MZL) is disproportionately represented, highlighting a paraneoplastic link between complement consumption and tumor activity. Because bradykinin-mediated angioedema does not respond to epinephrine, corticosteroids, or antihistamines, recognition and disease-specific management are crucial to avoid airway compromise. Case Description A 65-year-old woman with newly diagnosed splenic MZL presented with her third episode of sudden tongue swelling now accompanied by progressive dysarthria, drooling, and respiratory distress. In the emergency department, she was administered 1g intravenous (IV) Tranexamic acid, 20 mg IV Famotidine, 50 mg IV Diphenhydramine, and 125 mg IV Methylprednisolone without improvement. Worsening edema necessitated emergent endotracheal intubation for impending airway obstruction.In the intensive care unit, she was treated with intravenous corticosteroids, diphenhydramine, famotidine, and received two units of fresh frozen plasma. Complement studies revealed a low C1q level (2 mg/dL), and markedly reduced C1 esterase inhibitor assay ( 7%), confirming acquired C1-INH deficiency. C4 level was also depressed, and autoimmune serologies were negative. Following stabilization, she self-extubated without rebound swelling and was discharged with hematology follow-up for ongoing lymphoma-directed therapy and referral to Allergy-Immunology. Discussion This case underscores a rare but clinically significant manifestation of AAE in the setting of splenic MZL. Adult-onset, recurrent, non-pruritic angioedema unresponsive to conventional histaminergic therapies should prompt evaluation for bradykinin-mediated etiologies. Diagnostic confirmation relies on complement testing, specifically, low C1q and C1-INH levels with normal C1-INH gene sequence, distinguishing AAE from hereditary forms. Acute management centers on airway protection and targeted therapy such as plasma-derived or recombinant C1-INH, icatibant (a bradykinin B2-receptor antagonist), or ecallantide (a kallikrein inhibitor), when available. FFP remains a pragmatic option in resource-limited settings. Long-term control depends on treating the underlying lymphoproliferative disorder, which can normalize complement levels and prevent recurrence.Heightened clinical awareness of AAE in patients with unexplained angioedema and concurrent B-cell malignancies can prevent morbidity and mortality through timely diagnosis and multidisciplinary management. This abstract is funded by: none
Barodi et al. (Fri,) studied this question.