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Due to the similarity between the pathomechanism of SARS-CoV-2 infections and hereditary angioedema due to C1-inhibitor deficiency (C1-INH-HAE), a possibility emerged that C1-INH-HAE may worsen the course of the infection, or that the infection may influence the severity of angioedema (HAE) attacks in C1-INH-HAE patients. Our study aimed to evaluate the effects of the COVID-19 pandemic on the quality of life (QoL) of Hungarian C1-INH-HAE patients, and to survey the acute course of the infection, post COVID symptoms (PCS), vaccination coverage and the side effects of vaccines in this patient population. 93 patients completed our questionnaire between 1st July 2021 and 31st October 2021. In this same period and between March 2019 and March 2020, 63 patients completed the angioedema quality of life questionnaire (AE-QoL). Out of those patients infected with SARS-CoV-2 in the examined period (18/93 patients; 19%), 5% required hospitalization, 28% experienced HAE attacks in the acute phase of the infection, and 44% experienced PCS. A total number of 142 doses of vaccines were administered to the patients. Serious vaccine reactions did not occur in any case, 4 (5%) out of the 73 vaccinated patients experienced HAE attacks. No significant difference (p = 0.59) was found in the median of the AE-QoL total score, or in the number of HAE attacks prior and during the pandemic. Based on our study, HAE patients did not experience more serious SARS-CoV-2 infection, and it did not aggravate the course of HAE either. Changes in the QoL were not significant, and vaccines were safe in HAE patients.

Background Bradykinin-mediated angioedema (Bk-AE) can be life-threatening and requires specific targeted therapies. Knowledge of its epidemiology may help optimize its management. Methods We systematically searched the medical literature to identify abstracts of interest indexed between 1948 and March, 2016. We used published national survey data on the proportion of the population treated with angiotensin-converting enzyme inhibitors (ACEI) to derive estimates of the population prevalence of ACEI-AE in the USA, Germany and France. For hereditary angioedema (C1-INH-HAE) and C1-inhibitor related acquired angioedema (C1-INH-AAE), publications had to contain original epidemiologic data collection within a defined geographical area. Hereditary angioedema with normal C1-INH was not included in the analysis due to lack of clearly defined criteria. Results We identified 4 relevant publications on the prevalence of ACEI-AE, 6 on the prevalence of C1-INH-HAE, and 1 on the prevalence of C1-INH-AAE. The 1st year cumulative incidence of ACEI-AE was estimated to vary between 0.12 (population-based analyses) and 0.30 (meta-analyses of clinical trials) per 100 patient-years. The population prevalence of ACEI-AE was modeled to vary between 7 and 26 in 100,000. The prevalence of C1-INH-HAE was estimated to vary between 1.1 and 1.6 per 100,000. The prevalence of C1-INH-AAE was estimated to be 0.15 per 100,000 in one epidemiological investigation of AAE in Denmark. Conclusions Epidemiological evidence on Bk-AE is limited to North America and Europe. ACEI-AE is more common than C1-INH-HAE (~ 10:1), which is more common than C1-INH-AAE (~ 10:1). More studies are needed to comprehensively assess the epidemiological burden of Bk-AE.

Background This systematic study aims to assess the global epidemiologic, economic, and humanistic burden of illness associated with all types of hereditary angioedema. Methods A systematic search for articles reporting the epidemiologic, economic, and humanistic burden associated with patients with HAE was conducted using English and Chinese literature databases from the inception to May 23, 2022. The selected studies were assessed for their quality and risk of bias. The study was conducted in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses and registered with the International Prospective Register of Systematic Reviews (PROSPERO; CRD42022352377). Results In total, 65 articles that met the search inclusion criteria reported 10,310 patients with HAE, of whom 5861 were female patients. Altogether, 4312 patients (81%) and 479 patients (9%) had type 1 and type 2 HAE, respectively, whereas 422 patients (8%) had HAE-normal C1-INH. The overall prevalence of all types of HAE was between 0.13 and 1.6 cases per 100,000. The mean or median delay from the first onset of a symptom of HAE to confirmed diagnosis ranged from 3.9 to 26 years. The estimated risk of death from asphyxiation was 8.6% for patients with HAE. Hospitalization, medication, unnecessary surgeries, doctor visits, specialist services, and nursing costs are direct expenses that contribute to the growing economic burden. The indirect cost accounted mostly due to missing work ($3402/year) and loss of productivity ($5750/year). Furthermore, impairment of QoL as reported by patient-reported outcomes was observed. QoL measures identified depression, anxiety, and stress to be the most common symptoms for adult patients and children. Conclusion This study highlights the importance of early diagnosis and the need for improving awareness among health care professionals to reduce the burden of HAE on patients and society.

Hereditary angioedema (HAE) is a rare, potentially life-threatening disorder characterised by recurrent episodes of localised oedema caused by bradykinin overproduction. Accurate epidemiological data are essential for optimising diagnosis and treatment, particularly in underrepresented regions such as the Baltic states. This study aimed to examine the prevalence, clinical characteristics, genetic variants, and treatment accessibility for patients with HAE in the Baltic states of Estonia, Latvia, and Lithuania. This retrospective study included HAE patients diagnosed according to the WAO/EAACI 2021 criteria between 2004 and 2024. Demographic, clinical, and genetic data were collected and evaluated. Descriptive statistical analysis was performed using Jamovi (version 2.3). A total of 78 patients were identified in Estonia (n=30), Latvia (n=12) and Lithuania (n=36) from 2004 till 2024. In Lithuania, 7 patients had died and 3 were lost to follow-up, resulting in 26 patients remaining under active observation. While the total number of HAE cases identified across the three countries was reported, detailed clinical data and analyses were limited to the 68 patients who were alive and actively followed at the time of data collection. Estonia exhibited the highest point prevalence (2.19 per 100, 000), while Latvia had the lowest (0.65). The median diagnostic delay was longest in Latvia (24 years) and shortest in Estonia (9.5 years). gene pathogenic variants predominated. Estonia had the broadest availability of treatments, whereas Latvia had restricted access to modern therapies. Considerable variation exists in HAE prevalence, diagnosis, and treatment across the Baltic states. Estonia exemplifies best practices, while Latvia remains underserved. Regional collaboration and standardised care protocols are urgently needed.

Hereditary angioedema due to C1 inhibitor deficiency (C1-INH-HAE) is a rare and life-threatening condition characterized by recurrent localized edema. We conducted a systematic screening of SERPING1 defects in a cohort of 207 Czech patients from 85 families with C1-INH-HAE. Our workflow involved a combined strategy of sequencing extended to UTR and deep intronic regions, advanced in silico prediction tools, and mRNA-based functional assays. This approach allowed us to detect a causal variant in all families except one and to identify a total of 56 different variants, including 5 novel variants that are likely to be causal. We further investigated the functional impact of two splicing variants, namely c.550 + 3A > C and c.686-7C > G using minigene assays and RT-PCR mRNA analysis. Notably, our cohort showed a considerably higher proportion of detected splicing variants compared to other central European populations and the LOVD database. Moreover, our findings revealed a significant association between HAE type 1 missense variants and a delayed HAE onset when compared to null variants. We also observed a significant correlation between the presence of the SERPING1 variant c.-21 T > C in the trans position to causal variants and the frequency of attacks per year, disease onset, as well as Clinical severity score. Overall, our study provides new insights into the genetic landscape of C1-INH-HAE in the Czech population, including the identification of novel variants and a better understanding of genotype–phenotype correlations. Our findings also highlight the importance of comprehensive screening strategies and functional analyses in improving the C1-INH-HAE diagnosis and management.

Hereditary angioedema (HAE) is a rare genetic disorder characterized by recurrent episodes of skin and mucosal edema. The main treatment goal is to enable a “normal life” for all patients. However, due to high costs, there are limited options for the management of HAE in most developing and low-income countries. As a result, most of the recommended first-line treatments are not available. In this review, we attempt to highlight the disparities in health-care resources for the management of patients with HAE amongst different countries. Data was collected from HAE experts in countries who provide tabulated information regarding management and availability of HAE treatments in their countries. We reviewed the two most recent international HAE guidelines. Using India, the world’s second most populous country, as a paradigm for HAE management in lower-income countries, we reviewed the evidence for second-line and non-recommended practices reported by HAE experts. Results suggest significant inequities in provision of HAE services and treatments. HAE patients in low-income countries do not have access to life-saving acute drugs or recently developed highly effective prophylactic medications. Most low-income countries do not have specialized HAE services or diagnostic facilities, resulting in consequent long delays in diagnosis. Suggestions for optimizing the use of limited resources as a basis for future discussion and reaching a global consensus are provided. There is an urgent need to improve HAE services, diagnostics and treatments currently available to lower-income countries. We recommend that all HAE stakeholders support the need for global equity and access to these essential measures.

Introduction Hereditary angioedema due to C1-inhibitor deficiency (C1-INH-HAE type I) or dysfunction (C1-INH-HAE type II) is a rare disease characterized by recurrent episodes of edema with an estimated frequency of 1:50,000 in the global population without racial or gender differences. In this study we present the results of a nationwide survey of C1-INH-HAE patients referring to 17 Italian centers, the Italian network for C1-INH-HAE, ITACA. Methods Italian patients diagnosed with C1-INH-HAE from 1973 to 2013 were included in the study. Diagnosis of C1-INH-HAE was based on family and/or personal history of recurrent angioedema without urticaria and on antigenic and/or functional C1-INH deficiency. Results 983 patients (53% female) from 376 unrelated families were included in this survey. Since 1973, 63 (6%) patients diagnosed with C1-INH-HAE died and data from 3 patients were missing when analysis was performed. Accordingly, the minimum prevalence of HAE in Italy in 2013 is 920:59,394,000 inhabitants, equivalent to 1:64,935. Compared to the general population, patients are less represented in the early and late decades of life: men start reducing after the 5 th decade and women after the 6 th . Median age of patients is 45 (IQ 28-57), median age at diagnosis is 26 years (IQ 13-41). C1-INH-HAE type 1 are 87%, with median age at diagnosis of 25 (13-40); type 2 are 13% with median age at diagnosis of 31 (IQ 16-49). Functional C1INH is ≤50% in 99% of patients. Antigen C1INH is ≤50% in 99% of type 1. C4 is ≤50% in 96% of patients. The chance of having C1-INH-HAE with C4 plasma levels >50% is < 0.05. Conclusion This nationwide survey of C1-INH-HAE provides for Italy a prevalence of 1:64,935. C1-INH-HAE patients listed in our database have a shorter life expectancy than the general population. An increased awareness of the disease is needed to reduce this discrepancy. Measurement of C4 antigen can exclude diagnosis of C1-INH-HAE with an accuracy > 95%. This parameter should be therefore considered for initial screening in differential diagnosis of angioedema.

Hereditary angioedema (HAE) types 1/2 are rare genetic disorders leading to C1 inhibitor (C1INH) deficiency/dysfunction. Guidelines recommend long-term prophylaxis (LTP) to prevent HAE attacks. Subcutaneous (SC) C1INH replacement therapy is approved for LTP in patients with HAE (age indication varies between countries). There is little real-world data on the outcomes of patients who switch to C1INH SC in Europe, particularly those who switch from C1INH IV. This retrospective patient chart analysis captured real-world evidence of the effectiveness of C1INH SC LTP in patients with HAE in Germany (n=69) and Spain (n=37). The primary endpoint was change in annualized attack rate (AAR) in patients who used C1INH IV LTP during a 6-month baseline period and switched to C1INH SC LTP for ≥6 months. Switching to C1INH SC LTP from C1INH IV LTP was associated with a 73.2% reduction in AAR (n=48; P<0.001) compared to baseline. Emergency Room (ER) visits and rescue medication use were also significantly reduced after switching to C1INH SC LTP from C1INH IV LTP. A similar reduction in AAR (68.9%), ER visits (49.8%), and rescue medication use (61.9%) was observed in the overall population (n=105), regardless of treatment at baseline. Similar changes from baseline were seen in patients from Germany and Spain.

Hereditary angioedema (HAE) is a rare genetic disorder. The pattern of HAE is different in children as compared to adults. There is limited literature from developing countries where all first-line treatments are either unavailable or not easily accessible. Data of children with HAE were retrieved from medical records of patients registered in the Pediatric Immunodeficiency Clinic at our institute. Of the 206 patients with HAE, 61 were diagnosed before the age of 18 years. Male: female ratio was 1.1:1. Median age at onset of symptoms and diagnosis were 6.2 years (range 1–17 years) and 10.7 years (range 1.5–18 years) respectively. Median delay in diagnosis was 4.9 years (range 0–16 years). The commonest presentation was facial swelling (51/61) followed by swelling of extremities (47/61). Laryngeal edema and abdominal symptoms were reported in 28/61 and 31/61 patients respectively. Abdominal attacks were found to be less common in children as compared to adults. Most patients in our cohort received fresh-frozen plasma (n = 5/61) as on-demand therapy. Long-term prophylaxis included attenuated androgens (n = 25/61) and tranexamic acid (n = 23/61). Median duration of follow-up was 2242 patient months. One patient died on follow-up in this cohort. This is the largest single-centre cohort of pediatric HAE from resource-constrained settings. Facial attacks were more common, and there were significant delays in diagnosis when the age of onset of symptoms was younger. Gastrointestinal symptoms were less common in children than adults.HighlightsOne of the largest single-centre cohorts of pediatric HAE and the only one from resource-constrained settings.There were significant delays in diagnosis when the age of onset of symptoms was younger.Abdominal attacks were found to be less common in children as compared to adults.

Background and Objectives: Hereditary angioedema (HAE) represents a specific form of life-threatening inborn errors of immunity. Current guidelines recommend regular assessment of the disease burden, disease control and quality of life. This study describes the profile of HAE patients in Slovakia, disease control, quality of life, states of anxiety and depression, and socioeconomic situation. Materials and Methods: We used a set of standardized questionnaires—AE-QoL, AECT, HADS and Socioeconomic Status Questionnaire, and a non-standardized questionnaire—to describe the characteristics of the population. Results: We collected data on 56.44% (57 out of 101) of HAE adult patients registered in Slovakia. Moderate to severe HAE was present in 61.40% of patients; 73.68% were on long-term prophylactic treatment; and 19.30% received rescue treatment due to an acute HAE attack during the last 4 weeks. Most patients achieved lower AE-QoL scores, indicating a good quality of life. The AECT score indicated well-controlled disease in 91.23% of patients. Anxiety and/or depression scores were higher than normal in 17.54% of patients. Patients with HAE earned less than the average population, but most of them were economically active with relatively low rates of presenteeism and absenteeism. Only a minority of patients used social system benefits. Patients were exclusively cared for by relatives. Conclusions: The QoL scores achieved in all three standardized questionnaires indicate a good quality of life of HAE patients in Slovakia, which is associated with a high and specialized standard of care. Anxiety and/or depression were present in 17.54% of patients. Direct patients costs and social care costs are low, but there is an indirect socioeconomic burden on patients and their families.