Recurrent Angioedema: Occurrence, Features, and Concomitant Diseases in an Italian Single-Center Study

Abstract

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.

Evaluation of retinal microvascular perfusion in hereditary angioedema: a case-control study

“…As a remark, no significant correlations between OCT-A parameters and complement components levels occurred. Anyway, our data cannot exclude definitely the potential correlations between complement levels and retinal microvasculature because HAE patients have not been evaluated during an acute attack and both prophylactic and on-demand treatment likely affect circulating complement levels as well as the disease course [2]. Accordingly, no significant correlations occurred between OCT-A findings and number or severity of attacks in our cohort.…”

“…We enrolled 20 type I HAE patients referring to our tertiary center for HAE ("Policlinico Tor Vergata", Rome, Italy) during a 3-month period (May-July 2018). Inclusion criteria were: 1) diagnosis of type I HAE [1,2]; 2) age ≥ 18/≤ 75 years old; 3) intraocular pressure (IOP) < 21 mmHg; 4) best-corrected visual acuity (BCVA) ≥ 0.5 LogMAR; 5) spherical equivalent refractive error between − 6.0/+ 4.0 diopters; 6) open anterior chamber angle on slit-lamp examination [11,12]. Exclusion criteria were: 1) established primary ocular diseases; 2) systemic disorders including hypertension and/or treatments that may affect retinal function; 3) pregnancy or lactation; 4) neoplasia [11,12].…”

“…At the enrollment, clinical records of 20 patients were registered from all HAE patients including family history, HAE disease duration, sites and severity of attacks, time interval between the last attack and the visit, concomitant disorders, on-demand and prophylactic HAE treatment. From each patient, laboratory assays were performed on the same day of the ophthalmological examination at the laboratory of the "Policlinico Tor Vergata" (Rome, Italy) and included measurements of serum C3, C4, antigenic and functional C1INH, and C1q levels (see Additional file 1) [2,13]. Systolic and diastolic blood pressure was measured, and the derived mean arterial blood pressure (MABP) was assessed from all the subjects in the study [14,15].…”

“…Hereditary angioedema (HAE) due to C1 esterase inhibitor protein (C1INH) deficiency (type I HAE) is a rare disorder that is characterized by widely variable and potentially fatal attacks of subcutaneous and submucosal edema [1,2]. Evidence supports that the contact activation resulting in the increase of vascular permeability during HAE attack is both a systemic and a local process at the affected tissues [3].…”

Recent Advances in Clinical Allergy and Immunology

“…Recent research has provided evidence that there is a heterogeneity of pathogenesis and phenotypes that allows a classification of subgroups, the establishment of diagnostic algorithms, and also has implications for treatment [72]. The characterization of patients with recurrent AE without urticaria reveals distinct subgroups based on clinical data and complement screening [73]. In order to diagnose and correctly treat hereditary AE (HAE) to avoid fatalities, an “ABC” for the warning signs of HAE has been developed: A = AE, B = bradykinin, C = C1 inhibitor, D = distress factors, E = epinephrine unresponsive, F = family history, and G = glottis/gastrointestinal edema (Table 1) [74].…”