Hereditary angioedema with C1 inhibitor (C1-INH) deficit: the strength of recognition (51 cases)

Abstract

Hereditary angioedema (HAE) is a rare autosomal dominant disease due to C1 esterase inhibitor deficiency (C1-INH). The disease is characterized by subcutaneous and submucosal edema in the absence of urticaria due to the accumulation of bradykinin. This descriptive study aimed to evaluate the clinical characteristics of patients with a confirmed diagnosis of HAE referred to our Outpatient Clinic between December 2009 and November 2017. Fifty-one patients (38 F, 13 M) with a mean age of 32 years (range: 7–70 y) were included. Family history of HAE was reported in 70% (36/51) of the cases; 33/46 patients became symptomatic by 18 years of age. The median time between onset of symptoms and diagnosis was 13 years (3 mo–50 y). The most frequent triggering factors for attacks were stress (74.4%), trauma (56.4%), and hormonal variations (56%). The main symptoms were subcutaneous edema in 93.5% (43/46) of patients, gastrointestinal symptoms in 84.8% (39/46), and obstruction in the upper airways in 34.8% (16/46). Hospitalization occurred in 65.2%, of whom 13.3% had to be transferred to the Intensive Care Unit. Prophylactic treatment was instituted in 87% (40/46) of patients, and 56.5% (26/46) required additional treatment to control attacks. Owing to our data collection over a period of 8 years, a significant number of patients were identified by this HAE reference center. Despite early recognition and prophylactic treatment, a high percentage of patients were hospitalized. HAE is still diagnosed late, reinforcing the need for more reference centers specialized in diagnosis and educational projects for health professionals.

Identification of the factor XII contact activation site enables sensitive coagulation diagnostics

“…FXII-HAE arises by a variant of FXII whereby Thr309 is substituted with a lysine or arginine (FXII-Lys/Arg309; 49 , 50 ). FXII Lys/Arg309 variants exhibit defective glycosylation which leads to a FXII structure that is more readily activated in the presence of a surface 51 , 52 . Recently N-glycosylation at Asn230 was identified 53 , offering an explanation for the low apparent molecular mass of FXII_∆KR mutant lacking that specific site.…”

First Census of Patients with Hereditary Angioedema in the Canary Islands

“…This could be explained by the protective role of male hormones, as it was observed in other HAE patient study series [45]. Indeed, the high predominance of affected women may also be related to hormones, being the estrogens one of the main triggers of attacks in HAE [46,47]. However, we found that symptomatic females started to develop their symptoms sometime after the puberty period on average (25.4 ± 12.8 years), the period when most women affected by HAE debuts with symptoms.…”

The prevalence of hereditary angioedema in a Chinese cohort with decreased complement 4 levels

“…It is worth noting that consumption of C4 happens even when patients do not have exposure to angioedema attacks. 8 Approximately 95% of HAE-C1INH patients show a reduced C4 level during remission and virtually 100% during an attack. 13 As HAE is a rare disease and the symptoms in the involved organ (for example, gastrointestinal tract) may resemble those of more common diseases (such as irritable bowel syndrome, small bowel obstruction, pancreatitis, or appendicitis), many patients with HAE may be underdiagnosed or misdiagnosed.…”

“…In most epidemiological reports, type 1 and type 2 HAE, characterized by deficiency in C1–INH quantity and/or quality, account for the majority of the patients. 8 , 9 One study involving 137 Chinese HAE patients with C1–INH deficiency showed that type 1 HAE accounts for the majority (98.73%) of HAE patients and a minority (1.27%) of Chinese patients developed type 2 HAE. 10 Several SERPING1 gene mutations have been reported in Chinese HAE-C1INH patients.…”