D3.407 - Angioedema: cause or consequence?

Acquired angioedema (AAE) is a rare, non-genetic disorder characterized by recurrent subcutaneous or submucosal swelling, commonly caused by acquired C1-inhibitor (C1-INH) deficiency. It may occur as a paraneoplastic manifestation of B-cell lymphoproliferative disorders, such as non-Hodgkin lymphoma (NHL). Clinical onset typically occurs after the age of 40 and in the absence of a family history. Treating the underlying malignancy is crucial to achieve symptom resolution and biochemical normalization.

We report a case of a 60-year-old (yo) woman, 40 pack-year smoker, with pulmonary emphysema, chronic sciatic pain with regular NSAID use and NHL at 55 yo, treated for 5 months with rituximab, fludarabine and cyclophosphamide. At 58 yo she was referred to an Immunoallergology outpatient clinic due to a three-month history of recurrent, asymmetrical face edema that initially would resolve spontaneously. It occurred once monthly and was non-pitting, non-pruritic, painless, not associated with urticaria or NSAIDs intake, trauma, stress or therapy with ACE inhibitors, estrogen or gliptins. Similar symptoms had occurred prior to the diagnosis of NHL and had resolved following oncological treatment. She denied B symptoms or family history of recurrent angioedema. Blood analysis showed low C4, C1-INH and C1q levels, with normal functional C1-INH. Hemogram, liver and renal function tests were normal, serum and urine immunofixation showed no monoclonal component. A diagnosis of AAE was assumed, and prophylactic C1-INH concentrate was recommended prior to invasive procedures. Over the following months, weekly angioedema episodes prompted the initiation of crisis treatment with aminocaproic acid with a good response. Additionally, she experienced astheny and 10% weight loss within one month. Clinical recurrence of NHL was assumed, and second line therapy with venetoclax and rituximab was started, leading to complete resolution of the angioedema episodes and biochemical normalization of C4, C1-INH and C1q levels within six months.

In conclusion, the resolution of AAE symptoms and normalization of biochemical markers depend fundamentally on the effective treatment of the underlying condition. This case highlights the importance of rigorous hematological evaluation in patients presenting with late-onset angioedema and acquired C1-INH deficiency with no family history. Written informed consent for publication of the clinical details was obtained from the patient.