A multi-centre UK-based survey on angioedema secondary to acquired C1 inhibitor deficiency

Acquired angioedema due to C1-inhibitor deficiency (AAE-C1-INH) is very rare compared to its prototype, hereditary angioedema. An updated characterisation of the AAE-C1-INH cohort in UK is required to inform management. To describe the disease burden of AAE-C1-INH, long-term prophylaxis (LTP) and the clinical, immunochemical and treatment profiles of AAE-associated diseases in UK. Retrospective data on 117 AAE-C1-INH patients were collected using a national survey proforma across 25/34 Adult Clinical Immunology and Allergy centres in UK. Other European cohorts were compared. Median age at AAE-C1-INH diagnosis was 65 years with 3.4% of patients diagnosed below 40 years. The median delay in diagnosis was one year. Antifibrinolytics and attenuated androgens showed comparable efficacy as LTP 88.9% and 89.5%, respectively. A haematological disorder was identified in 83.8% AAE-C1-INH patients compared to 3.4% autoimmune diseases. The predominant haematological disorders were splenic marginal zone lymphoma (SZL) 34% followed by MGUS 16%. The severity of angioedema did not depend on the associated disease. Anti-C1INH-autoantibodies testing was limited at 23.1%. Rituximab monotherapy was effective in treating 9/9 SZL and 1/2 MGUS-associated AAE-C1-INH. Rituximab efficacy was independent of anti-C1INH-autoantibodies detection with response in 3/3 seronegative and 4/4 seropositive patients. The diagnosis of AAE-C1-INH should not be overlooked below the age of 40 years. The choice of oral LTP should be informed by propensity to side-effects. B-cell depletion could be considered in treating monoclonal B cell disorder-associated-AAE-C1-INH in the absence of haematological indications. Further studies are required to address the clinical utility of anti-C1INH-autoantibodies.