Recurrent angioedema: occurrence, features, and concomitant diseases in an Italian single-center study

Background: Angioedema (AE) is a potentially life-threatening condition with hereditary (HAE), acquired (AAE), or iatrogenic causes. A careful workup allows for the identification of the etiology of attacks and the appropriate management. In this cohort study, based on a clinical practice setting, we aimed at investigating clinical and laboratory findings concerning different features of patients with recurrent AE who were referred to a single, tertiary-level center for HAE. Methods: Clinical and laboratory data of patients fulfilling the criteria for C1-inhibitor-deficient HAE (C1-INH-HAE), C1-INH-AAE, angiotensin-converting enzyme inhibitor-related AE (ACEI-RA), and idiopathic AAE (I-AAE) were evaluated. Descriptive statistics were analyzed by means of the Mann-Whitney U test. The Fisher exact test was used for group comparisons. Results: Patients were diagnosed with type 1 HAE (n = 14), type 2 HAE (n = 1), C1-INH-AAE (n = 8), ACEI-RA (n = 16), or I-AAE (n = 26). We included only patients with concomitant autoimmune diseases from the I-AAE group (n = 8, aut-I-AAE). Age at disease onset and at diagnosis was younger in type 1 HAE than in all the other groups. The diagnostic delay was longer in type 1 HAE than in ACEI-RA. C4 and C1q levels were lower in C1-INH-AAE than in type 1 HAE, ACEI-RA, and aut-I-AAE. Both HAE and C1-INH-AAE showed lower C1-INH antigen and function compared to the other groups. Peripheral attacks were more frequent in type 1 HAE, while airway, abdominal, and oral attacks were prevalent in C1-INH-AAE. Conclusion: Investigating the clinical and laboratory features of recurrent AE without wheals represents a major topic for facilitating early diagnosis and improving treatment strategies for this heterogeneous and misdiagnosed condition