Search

Introduction: Hereditary angioedema (HAE) is a genetic disorder associated with recurrent episodes of angioedema in the absence of urticaria and pruritus. Hereditary angioedema is inherited in an autosomal dominant pattern and results in a quantitative deficiency (HAE type I) or dysfunction (HAE type II) of the C1-esterase inhibitor (C1-INH) protein. A very rare third type of HAE which is associated with normal quantitative and functional levels of C1-INH (HAE-nl-C1-INH) has been described.Case Report: A 54-year-old female with past medical history significant for HAE-nl-C1-INH presented to the emergency department (ED) for an acute attack of HAE and seizures. The patient arrived postictal after experiencing a total of three witnessed seizures, each lasting approximately 30 seconds. After the initial seizure was witnessed in the ED, the patient received 4200 Units of recombinant C1-INH intravenously. The patient’s mental status did not return to baseline, and she experienced two additional seizures. She was given a dose of the kallikrein inhibitor, ecallantide, as well as standard dosing of lorazepam and levetiracetam. The patient returned to her baseline and had no subsequent seizures while in the ED. Inpatient work-up included continuous video electroencephalography monitoring and magnetic resonance imaging of the brain, both of which were normal. The remainder of the inpatient course wasuncomplicated, and the patient was discharged home neurologically intact.Conclusion: We present a case of status epilepticus in a patient with HAE-nl-C1-INH. The focus of emergent medical management of status epilepticus includes airway protection, respiratory support, and administration of abortive and prophylactic antiepileptic drugs. The emergency medicine physician should also consider and treat possible underlying etiologies. The treatment of an acute attack of HAE should focus on replacing C1-INH and preventing the formation and limiting the action of bradykinin.

Background: Hereditary angioedema (HAE) is a rare, autosomal dominant disorder causing swelling attacks in various parts of the body, resulting in impacts on health-related quality of life (HRQoL). The symptoms of HAE and its impacts on HRQoL have been well-documented in adults; however, relatively little is known about the experiences of adolescents with HAE. The objective of this study was to use qualitative interviews to investigate how adolescents experience HAE symptoms and how HAE impacts their HRQoL. Methods: This was a non-interventional, qualitative study of adolescents with HAE. Participants were recruited via a patient advocacy organization and were eligible to take part in this study if they had a confirmed diagnosis of type I or type II HAE and were currently on prophylactic treatment to prevent HAE attacks. All participants completed a one-to-one, 60-minute, remote interview designed to elicit their experiences of HAE. Interview data were coded and analyzed using NVivo qualitative software. Results: Twelve adolescents took part in this study. HAE attacks were described as painful and uncomfortable. Attacks varied by trigger, frequency, severity, location, and duration. Participants described ways in which HAE impacted their daily lives, including impacts on physical, social, emotional, and cognitive functioning, in addition to sleep disturbance, school-related impacts, and a need to avoid attack triggers. Impacts on emotional and social functioning were particularly noteworthy, as participants reported having to miss or skip social events, and sometimes withdrawing socially. Since initiating prophylaxis, participants reported the frequency, severity, and duration of attacks had been reduced and their HAE-related impacts had been minimized. Participants were satisfied with their current prophylactic and acute treatments, and expressed a preference for treatments that were effective, convenient, self-administered, and had minimal side effects. Conclusion: Adolescents with HAE reported experiencing a range of symptoms that, when untreated, impacted their HRQoL in ways that are unique from adults. Further, participants reported that effective treatments (prophylactic and acute) inhibited symptoms and HRQoL impacts with minimal treatment burden. Findings from this study suggest that health care providers and clinical investigators should consider the unique HRQoL impacts experienced by adolescents when evaluating treatment benefit. [ABSTRACT FROM AUTHOR]

Background: Plasma-derived human C1-esterase inhibitor (C1-INH) concentrates are indicated for the treatment of acute episodes of hereditary angioedema. Intravenous C1-INH concentrate provides rapid relief to patients with acute hereditary angioedema symptoms. Objective: To develop a safe and efficient purification process for C1-INH from human plasma. Design: A combination of anion exchange and hydrophobic interaction chromatography was used to purify C1-INH from human plasma. Method: The cold insoluble fraction (cryoprecipitate) was separated via centrifugation; then, the cryoprecipitate-poor plasma was subjected to different separation techniques to purify C1-INH. First, separation was performed using diethylaminoethyl (DEAE) anion exchange chromatography to capture coagulation factors. Then, C1-INH was purified from the remaining plasma using quaternary amine (a strong anion exchanger) chromatography, followed by DEAE (a weak anion exchanger) chromatography. The final product was purified via hydrophobic interaction chromatography, followed by ultrafiltration to concentrate the purified C1-INH. This process is cost-effective because coagulation factors were captured before C1-INH purification and the waste fraction after the capture stage was diverted to Cohn fractionation to isolate other potential plasma products. Results: The final C1-INH preparation had a specific activity of >12 IU/mg protein, which is sufficient for its intended purpose. The purified preparation was characterized via sodium dodecyl sulfate–polyacrylamide gel electrophoresis, and coagulation factors were measured in the purified preparation. Furthermore, viral activity decreased via solvent detergent treatment and virus filtration. Conclusion: We successfully developed a purification process for C1-INH from human plasma. This process is easily adaptable and has been successfully scaled up to approximately 15-fold. It can be further scaled up for the large-scale production of C1-INH. [ABSTRACT FROM AUTHOR]

Angioedema can occur in the absence of urticaria and can be broadly divided into three main categories: mast cell-mediated (e.g., histamine), non-mast-cell-mediated (bradykinin-induced) and idiopathic angioedema. Non-mast-cell-mediated angioedema is largely driven by bradykinin. Bradykinin-induced angioedema can be hereditary, acquired or drug-induced, such as with angiotensin-converting enzyme (ACE) inhibitors. Although bradykinin-mediated angioedema can be self-limited, it can cause significant morbidity and laryngeal involvement may lead to fatal asphyxiation. The mainstays of management for angioedema are: (1) to avoid specific triggers (if possible and where known) and (2) treatment with medication (if indicated). For hereditary angioedema (HAE), there are specifically licensed treatments that can be used for the management of attacks, or for prophylaxis in order to prevent attacks. In this article, the authors will review the causes, diagnosis and management of angioedema. Key take-home messages: Angioedema can occur in the absence of urticaria, with ACE inhibitor-induced and idiopathic/spontaneous angioedema being the most common causes. ACE inhibitors should be discontinued in any individual who presents with angioedema without urticaria as this condition is associated with life-threatening upper airway angioedema. Idiopathic/spontaneous angioedema responds well to prophylactic antihistamines (which may be increased to fourfold the standard dosing); however, more advanced treatment, such as omalizumab, may be needed. In some acute situations, oral corticosteroids may be required. HAE and AAE are rare disorders also characterized by angioedema in the absence of urticaria; they result from a deficiency or dysfunction of the C1-INH (a plasma protease inhibitor that regulates several proinflammatory pathways) and can be associated with life-threatening upper airway swelling. The diagnosis of HAE and AAE should include the assessment of C4, C1q, and C1-INH function and antigenic levels. The management of HAE and AAE involves an approach to acute treatment, short-term and long-term prophylaxis that is evidence-based and follows current guideline recommendations. All patients suspected of having HAE or AAE should be referred to, and managed by, a specialist with expertise in these conditions. [ABSTRACT FROM AUTHOR]

Background: Hereditary angioedema with normal C1-inhibitor (HAE-nC1-INH) is a rare genetic disease. The symptoms can resemble other forms of hereditary angioedema (HAE), but the specific laboratory values are inconspicuous. The knowledge about treatment strategies in HAE-nC1-INH remains insufficient; most of the drugs are only licensed and approved for other types of HAE. Methods: An analysis of all patients with HAE-nC1-INH was carried out in a certified angioedema treatment center in southern Germany. Only patients with a confirmed HAE-nC1-INH mutation were included. The impact of disease was monitored with validated questionnaires. Results: Eighteen patients were included: two families with a factor XII mutation and seven families with a plasminogen mutation. All individuals received icatibant for on-demand therapy—efficient treatment response was reported. Three patients were severely affected, and prophylaxis was initiated with lanadelumab. According to the questionnaires, the clinical course and symptoms improved significantly under this prophylactic regime. Conclusion: This is one of the first descriptions of the clinical outcomes as a response to prophylactic treatment with lanadelumab in HAE-nC1-INH patients with a known mutation. The therapeutic management of HAE-1 and HAE-2 should also be the basis of HAE-nC1-INH, including prophylaxis. [ABSTRACT FROM AUTHOR]

Introduction: Hereditary angioedema (HAE) is a rare genetic disease characterized by submucosal and subcutaneous edema with high morbidity and possibility of mortality. This study presents the sociodemographic characteristics of a large Brazilian family with HAE. Methods: Descriptive cross-sectional study with patients from two family branches coming from the same city and HAE diagnosis was carried out. Clinical, laboratory, and treatment data of patients have been collected. Genetic testing was performed on some individuals. Correlation tests and comparisons between variables were applied using IBM SPSS Statistics® 2.0 program. Results: We provide a detailed characterization of two families affected by HAE due to C1-INH deficiency, residing in a small town in southern Brazil. These families harbor an identified mutation in the SERPING1 gene (c.1104del, p.Asp369ThrfsTer2). The mean age at HAE diagnosis was 16.7 (±14.0) years, with the mean onset of symptoms at 6.0 (±6.1) years of age. A correlation was observed between patients' current age and age at HAE diagnosis, with older patients being diagnosed later than younger individuals (p < 0.0001). On average, there were 16.8 emergency visits in the past year (±24.8), and 53.5% of patients reported at least one lifetime hospitalization. Notably, treatment modalities often diverged from consensus recommendations regarding optimal prophylaxis and management of HAE attacks. Conclusions: This study describes one of the largest known families with HAE in Brazil and highlights the significant impact of unfavorable social conditions on disease control. [ABSTRACT FROM AUTHOR]

The article discusses the efficacy of garadacimab in preventing hereditary angioedema (HAE) attacks, with protection starting as early as Week 1 after the first administration. The study shows that garadacimab significantly reduces the monthly number of attacks compared to a placebo, with a high percentage of patients remaining attack-free throughout the study. The data support garadacimab as a long-term prophylactic therapy for HAE, providing early and durable protection against attacks, in line with the latest guidelines for HAE treatment. [Extracted from the article]

Urticaria and angioedema are common in children who present to the Emergency Department. Given the broad range of possible diagnoses and the lack of immediate results from specialised tests in an acute setting, diagnosis depends largely on a thorough clinical history and careful physical examination. These patients may also present with life-threatening airway compromise or anaphylaxis, requiring immediate intervention and pharmacological treatment. Fortunately, in most cases, acute urticaria in children -- though distressing to parents -- is typically triggered by an infection and requires symptomatic treatment and reassurance. On the other hand, the cause of chronic urticaria often remains unknown. Angioedema may occur on its own and can be hereditary. In such cases, antihistamines and systemic corticosteroids are ineffective and treatment with fresh frozen plasma or newer on-demand therapies is recommended. If uncertain about the diagnosis, choice of special investigations or treatment, emergency physicians should promptly consult a specialist to ensure optimal management and follow-up care. [ABSTRACT FROM AUTHOR]

Hereditary angioedema (HAE) due to C1-inhibitor deficiency is a rare, debilitating, genetic disorder characterized by recurrent, unpredictable, attacks of edema. The clinical symptoms of HAE arise from excess bradykinin generation due to dysregulation of the plasma kallikrein-kinin system (KKS). A quantitative systems pharmacology (QSP) model that mechanistically describes the KKS and its role in HAE pathophysiology was developed based on HAE attacks being triggered by autoactivation of factor XII (FXII) to activated FXII (FXIIa), resulting in kallikrein production from prekallikrein. A base pharmacodynamic model was constructed and parameterized from literature data and ex vivo assays measuring inhibition of kallikrein activity in plasma of HAE patients or healthy volunteers who received lanadelumab. HAE attacks were simulated using a virtual patient population, with attacks recorded when systemic bradykinin levels exceeded 20 pM. The model was validated by comparing the simulations to observations from lanadelumab and plasma-derived C1-inhibitor clinical trials. The model was then applied to analyze the impact of nonadherence to a daily oral preventive therapy; simulations showed a correlation between the number of missed doses per month and reduced drug effectiveness. The impact of reducing lanadelumab dosing frequency from 300 mg every 2 weeks (Q2W) to every 4 weeks (Q4W) was also examined and showed that while attack rates with Q4W dosing were substantially reduced, the extent of reduction was greater with Q2W dosing. Overall, the QSP model showed good agreement with clinical data and could be used for hypothesis testing and outcome predictions. [ABSTRACT FROM AUTHOR]

Bradykinin-mediated angioedema can broadly be categorised into hereditary angioedema (HAE) and acquired angioedema (AAE). Both HAE and AAE are grossly under-recognised in the country largely because of lack of awareness. Type 1 and 2 HAE is caused by pathogenic variants in the SERPING1 gene that codes for C1-inhibitor protein. Deficiency of C1-inhibitor protein leads to recurrent swelling episodes involving hands, feet, eyes, lips, tongue and genitalia. These episodes are typically not associated with itching or urticaria. Involvement of the larynx leads to a potentially life-threatening episode of choking and, in the past, the mortality because of laryngeal edema used to be as high as 30%. AAE is usually associated with lymphoreticular malignancies; predominantly B cell lymphomas and systemic lupus erythematosus. Angioedema often precedes the diagnosis of primary illness. The clinical features of both AAE and HAE are similar. However, AAE should be suspected in patients with onset of disease in older age. Management of HAE is broadly categorised into three types: on-demand therapy and short-term and long-term prophylaxis (LTP). Patients with AAE also need management of the underlying disease with immunosuppressants. This review focuses on clinical manifestations, diagnostic evaluation, and clinical mimics of HAE and AAE from the perspective of a rheumatologist. The review also briefly discusses the management principles of HAE and AAE. [ABSTRACT FROM AUTHOR]

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. Highlights: One 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. [ABSTRACT FROM AUTHOR]

Copyright of Chinese Journal of Dermatovenereology is the property of Xi'an Jiaotong University Periodicals Center and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Long-term prophylaxis (LTP) has been shown to reduce the frequency of hereditary angioedema (HAE) attacks; however, attacks occurring in patients receiving LTP have not been well characterized. The objective of this systematic review was to evaluate the proportion of type I/II HAE (HAE-C1INH) patients who experience attacks while receiving LTP, the characteristics of these attacks, and associated on-demand therapy use. A systematic search was conducted in PubMed to identify studies reporting LTP use with plasma-derived C1 inhibitor (pdC1INH), lanadelumab, berotralstat, androgens, or antifibrinolytics in patients with HAE-C1INH. Forty-five primary studies met the inclusion criteria. In phase 3 trials, attack-free rates were 40% for subcutaneous pdC1INH 60 IU/kg twice weekly at 16 weeks, and 44% for lanadelumab 300 mg every second week at 6 months (77% during steady-state [days 70–182]); there was no difference in attack-free rate for berotralstat 150 mg versus placebo at 24 weeks. Phase 3 studies reported a lower average attack severity with subcutaneous and intravenous pdC1INH versus placebo. With lanadelumab and berotralstat, the prophylactic treatment effect was more pronounced in peripheral attacks than in abdominal and laryngeal attacks. Laryngeal attacks accounted for 2%-7% of all attacks in observational and interventional studies, regardless of the LTP agent received. On-demand therapy was used in 49%-94% of attacks occurring in the presence of LTP. In conclusion, patients receiving LTP experienced attacks in all anatomic locations, including the larynx. Most attacks were treated with on-demand therapy, although outcomes were not reported. Access to on-demand therapy remains essential for all people with HAE-C1INH. [ABSTRACT FROM AUTHOR]

Objective To report a family with hereditary angioedema (HAE) and to conduct their genetic mutation analysis. Methods Clinical data of the HAE family were collected, and DNA was extracted from the peripheral blood of the family members. The exon coding region of serine protease inhibitor G1(SERPING1) gene of the proband and family members was directly sequenced by Sanger sequencing technology. Results The family had a total of 16 people for three consecutive generations, with 9 patients suffering from HAE. All the 9 patients showed repeated erythema, edema and pruritus of the whole-body skin, among which 3 patients died of acute attack. Genetic sequencing was conducted in all 13 individuals. A heterozygous mutation in SERPING1 gene c.1396C>G (p.Arg466Gly) was detected in all the 6 HAE patients, while no gene mutation was found in the 7 healthy person. Conclusion The heterozygous mutation of c.1396C>G in the SERPING1 gene might be the cause of hereditary angioedema in this family. [ABSTRACT FROM AUTHOR]

Hereditary angioedema (HAE) with normal C1 inhibitor (C1-INH) (HAE-nC1-INH) is a rare disease that presents with laryngeal edema due to oral surgical procedures. Familial Mediterranean fever (FMF) is a disorder commonly characterized by an autosomal recessive inflammatory process, and manifests in the oral cavity and facial structures. A 50-year-old woman with HAE-nC1-INH and FMF was referred to our department for bone augmentation in the right maxillary molar region. We performed lateral window sinus augmentation under the backup support of an anesthesiologist. A hematologist used intravenous Berinert® and oral Orladeyo® to prevent perioperative angioedema attacks. The postoperative course was uneventful. Regarding surgical intervention in patients with HAE, interdepartmental cooperation is crucial to prevent angioedema attacks and prepare for life-threatening complications. Oral hygiene and occlusion should be considered in the dental implant treatment of patients with FMF. Every oral and maxillofacial surgeon and dental practitioner should familiarize themselves with HAE and FMF. [ABSTRACT FROM AUTHOR]

Introduction: In patients with Hereditary Angioedema (HAE) related to primary C1 inhibitor deficiency (C1INH), the defective clearance of immune complexes and apoptotic materials along with impairment of normal humoral response potentially leads to autoimmunity. Few studies report evidence on autoimmune diseases in C1INH-HAE, but no large population studies focus on rare connective tissue diseases (RCTDs). We aim at evaluating for the first time prevalence and distribution of RCTDs - Systemic Lupus Erytematosus (SLE), primary Sjogren Syndrome (SjS), primary antiphospholipid syndrome (APS), Systemic Sclerosis (SSc), and mixed connective tissue diseases (MCTD) in a large Italian cohort of C1INH-HAE patients. Methods: A multicenter observational study includes C1INH-HAE patients from ITACA Centers throughout Italy (time frame Sept 2023-March 2024). Inclusion criteria are i. a defined diagnosis of type I or type II C1INH-HAE; ii. age =15 years (puberty already occurred); iii. enrollment in the ITACA Registry. The diagnosis of SLE, primary SjS, primary APS, SSc, and MCTD are made in accordance with international classification criteria. Results: Data are collected from a total of 855 C1INH-HAE patients referring to 15 ITACA Centers. Patients with concomitant RCTDs were 18/855 (2.1%) with F:M ratio 3.5 and a prevalent type I C1INH-HAE diagnosis (87.2%). A diagnosis of SLE results in 44.5% of cases (n=8) while the remaining diagnoses are primary SjS (22.2%, n=4), primary APS (16.6%, n=3), SSc (11.2%, n=2), and a single case of MCTD (5.5%). The female gender is prevalent in all the RCTDs. Patients on long term prophylaxis (LTP) are significantly prevalent in RCTDs group than in the whole C1INH-HAE population (p<0.01). Conclusions: A relevant prevalence of RCTDs is documented in C1INH-HAE patients, mainly SLE. Patients with RCTDs are on LTP in a significant proportion supporting the idea of a bidirectional link between C1INH-HAE and autoimmunity. [ABSTRACT FROM AUTHOR]

Background and Objectives: Hereditary angioedema (HAE) is characterized by unpredictable skin and mucosal angioedema attacks. We aimed to find the frequency of sexual-activity-triggered attacks (STAs) and understand how the sexual life of HAE with C1-inhibitor deficiency (HAE-C1INH) patients is affected. Materials and Methods: Adult HAE-C1INH patients were included in this cross-sectional study, which started in March 2020. Demographic information, marriage properties, gender-specific sexual life characteristics, and the HAE-specific histories of the patients were collected. The Hospital Anxiety and Depression Scale (HADS) and the Turkish version of the New Sexual Satisfaction Scale (NSSS) were applied to all participants. Results: Among 42 symptomatic HAE patients, 33 (78.57%) had genital attacks and 17 (42.5%) had STAs. Ten (58.8%) had genital pain, tenderness, or swelling, and five (29.4%) had isolated abdominal and groin pain. Eight (47.1%) patients with STAs experienced a HAE attack during their first time engaging in sexual intercourse. Anxiety/depression scales, NSSS scores, and distribution of other HAE attack localizations were similar in patients with and without STAs, and no gender differences were observed. Compared to the patients without STAs, the ratio of patients who stated that their sexual lives were negatively affected and that they lost their sexual desire was higher in patients with STAs. Conclusions: Genital or abdominal attacks triggered by sexual activity may be more common than thought. Sexual activity should also be questioned for evaluating attack triggers. There is a possibility of triggering an attack with the first and ongoing sexual intercourse, and patients should be informed to keep their attack treatment medications ready in advance. [ABSTRACT FROM AUTHOR]

Abstract Background Hereditary angioedema (HAE) is a rare autosomal dominant genetic disease characterized by recurrent edema and a potentially fatal risk. Despite its severity, there is a notable lack of effective methods for predicting and preventing HAE attacks. This study aims to thoroughly investigate the underlying pathological mechanisms of HAE and identify potential biomarkers that could aid in its prediction and prevention. Results In our investigation, we have discovered a novel pathogenic variant of the SERPING1 gene, specifically c.708T > G, in a Han family affected by HAE. Our observations indicate that this variant leads to an increase in the accumulation of C1-INH within the endoplasmic reticulum (ER), resulting in the upregulation of GRP75 protein expression. This cascade of events resulted in Ca2+ overload, disruption of mitochondrial structure and function, and eventually triggered apoptosis. Using siRNA to knock down GRP75 mitigates cellular calcium overload and mitochondrial damage induced by the SERPING1 mutation. Conclusion Based on our findings, we propose that the detection of intracellular Ca2+ concentration could serve as a valuable biomarker for predicting acute attacks of HAE in patients. This discovery holds significant implications for the development of more targeted and effective strategies in the management of HAE.

Abstract Background Hereditary angioedema with normal C1-inhibitor function (HAE nC1-INH) and idiopathic angioedema of unknown etiology (AE-UNK) are rare conditions that cause recurrent subcutaneous and submucosal swelling. The characteristics and clinical outcomes of patients with these conditions in Canada have not been studied. Methods The aim of this study was to extract real-world evidence from the electronic health records of patients with HAE nC1-INH or AE-UNK who were managed in selected practices of Canadian HAE-treating specialist physicians between 01-Jan-2012 and 01-Jan-2022, to examine case numbers, treatment, clinical outcomes, and healthcare utilization. Results Of 60 patients (37 with HAE nC1-INH, 23 with AE-UNK), median (range) age at symptom onset was 21.5 (5.0–57.0) and 23.0 (10.0–54.0) years, respectively. Time to diagnosis from onset of symptoms was 7.0 (0.0–43.0) and 2.0 (− 10.0 to 50.0) years. Significant differences were observed in terms of the predominant triggers for angioedema attacks between patients with HAE nC1-INH and AE-UNK: stress (65% vs. 26%, p = 0.007) and estrogen therapy (35% vs. 9%, p = 0.031). Before diagnosis, most patients received antihistamines (50% of HAE nC1-INH and 61% of AE-UNK patients). Post-diagnosis, 73% and 74% of HAE nC1-INH and AE-UNK patients received long-term prophylaxis (LTP), with the most common LTP treatments being subcutaneous pdC1-INH (43% of HAE nC1-INH patients and 39% of AE-UNK patients) and tranexamic acid (41% of HAE nC1-INH patients and 35% of AE-UNK patients). Of patients with HAE nC1-INH, and patients with AE-UNK, 22% and 13%, respectively, were taking more than one LTP treatment concurrently. Before HAE treatment initiation, significantly fewer patients with AE-UNK compared to patients with HAE nC1-INH had angioedema attacks affecting their extremities (13% vs. 38%, p = 0.045) and GI system (22% vs. 57%, p = 0.015). In the three months following treatment initiation, patients with AE-UNK experienced significantly fewer angioedema attacks compared to patients with HAE nC1-INH (median 2.0 attacks [0.0–48.0] vs. 6.0 attacks [0.0–60.0], p = 0.044). Additionally, fewer patients with AE-UNK compared to HAE nC1-INH experienced attacks affecting their GI system (26% vs. 57%, p = 0.032). Attack duration and frequency significantly decreased for patients with HAE nC1-INH from a median of 1.00 day (range: 0.00–7.00) to 0.29 day (range: 0.02–4.00; p = 0.001) and from 10.50 attacks (range: 0.00–90.00) to 6.00 attacks (range: 0.00–60.00; p = 0.004) in the three months following HAE treatment initiation. Conclusions Using Canadian real-world evidence, these data demonstrate differing clinical trajectories between patients with HAE nC1-INH and AE-UNK, including diagnostic delays, varied attack characteristics, treatment responses and healthcare utilization. Despite treatment response, many patients still experienced frequent angioedema attacks. These results suggest an unmet need for treatment guidelines and therapies specifically for patients with HAE nC1-INH and AE-UNK and better understanding of the pathophysiology accounting for the reported differences between the two.

Abstract Background Hereditary Angioedema (HAE) due to C1-inhibitor deficiency (C1INH) is a rare condition, clinically characterised by recurrent swelling. The unpredictability of attacks affects the patients’ quality of life (QoL). HAE patients and their families have vast unmet physical, psychological, and social needs. A human-centred design (HCD) approach to describing the needs of different user types is to utilise personas, a data-driven narrative tool for communicating user archetypes that capture the individuals’ attitudes, goals, and behaviours. The aim of this study was to create and analyse personas based on HAE patients’ and their caregivers’ interviews. Semi-structured interviews were conducted through anthropological conversations with patients, patient-caregivers (double role of patient and caregiver), and non-affected caregivers. Qualitative and quantitative insights from analyses formed the basis to create personas. Results We enrolled 17 subjects: 15 patients (6 of them were patient-caregivers) and 2 non-affected caregivers. The mean age of participants was 50.3 ± 14.4 years. Eight patients were on treatment with prophylactic therapy. The mean percentage score of Angioedema Quality of Life (AE-QoL) for HAE patients was 19.8 ± 12.0. Six personas were identified describing the participants’ personal history, disease management, and needs: four personas referred to patients, one to patient-caregivers, and one non-affected caregiver personas were identified. Across patient personas, the most expressed needs were psychological support and better awareness amongst healthcare professionals. Caregivers, on their side, desired better information about the disease, including the latest therapies, and higher awareness within the community. Conclusion A Human Centred Innovative Approach Based on Persona extends beyond the physical symptoms to encompass the psychological and social aspects of the individual's well-being also including the family in the evaluation.

The article "Berotralstat for hereditary angioedema with C1 inhibitor deficiency: a practical guide for clinicians" discusses the use of berotralstat as a treatment option for hereditary angioedema due to C1 inhibitor deficiency. Berotralstat is an oral medication that inhibits plasma kallikrein and has been shown to reduce swelling attacks in patients. The article provides information on the drug's pharmacology, clinical efficacy, side effects, drug interactions, and guidance on transitioning patients to berotralstat from other long-term prophylaxis treatments. It emphasizes the importance of individualized care and monitoring for optimal patient outcomes. [Extracted from the article]

Background Methods Results Conclusion Hereditary angioedema (HAE) is a chronic, unpredictable disease. Long‐term prophylactic treatments that offer durable efficacy, safety, and convenience are required to assist patients in achieving complete disease control, per international guidelines. We report an interim analysis of an ongoing phase 3 (VANGUARD) open‐label extension (OLE) study evaluating the long‐term safety and efficacy of garadacimab for HAE prophylaxis.Adults and adolescents aged ≥12 years with HAE previously participating in phase 2 and pivotal phase 3 (VANGUARD) studies were rolled over to an OLE, alongside newly enrolled patients. Patients received garadacimab 200 mg subcutaneously, once monthly for ≥12 months. The primary endpoint was treatment‐emergent adverse events (TEAEs) in patients with C1 inhibitor deficiency/dysfunction.At data cut‐off (February 13, 2023; N = 161), median (interquartile range) exposure was 13.8 months (11.9–16.3). For the primary endpoint, 133/159 patients experienced ≥1 TEAE (524 events), equivalent to 0.23 events/administration and 2.84 events/patient‐year. Garadacimab‐related TEAEs (13% of patients, 52 events) were most commonly injection‐site reactions (ISRs). No deaths occurred. One patient discontinued treatment due to garadacimab‐related moderate ISR. Most TEAEs were mild/moderate; three events were serious (COVID‐19, two events; abdominal HAE attack, one event) and not garadacimab related. No abnormal bleeding, thromboembolic, severe hypersensitivity, or anaphylactic events were observed. Mean HAE attack rate decreased by 95% from the run‐in period; 60% of patients were attack‐free. Almost all patients (93%) rated their response to garadacimab as “good” or “excellent.”Garadacimab has a favorable safety profile suitable for long‐term use and provides durable protection against HAE attacks. [ABSTRACT FROM AUTHOR]

\nIntroduction: Hereditary angioedema (HAE) is a rare genetic disorder caused by deficiency or dysfunction of C1-esterase inhibitor that is characterized by recurrent episodes of bradykinin-mediated edema. Lanadelumab has been the only available first-line therapy for long-term prophylaxis (LTP) of HAE in China since its approval in 2020. The present study aimed to investigate the clinical efficacy and safety of lanadelumab for LTP in Chinese patients. Methods: A retrospective clinical data were collected for the 6 patients and used to examine the frequency of attack symptoms, disease-related loss of work days, and quality of life before and after LTP with lanadelumab. Health-related quality of life was assessed using the Dermatology Life Quality Index (DLQI) and the Angioedema Quality of Life Questionnaire (AE-QoL). Results: Lanadelumab led to reductions of 97.8% and 98.5% in the attack rate and treated attack rate, respectively. All patients exhibited significant improvements in AE-QoL and DLQI scores (100% reduction rates) during the early treatment period (4 weeks and 2 weeks, respectively) and in missed work days/year (98.9% reduction rate). The efficacy of lanadelumab remained stable during COVID-19 vaccination and infection. No serious/severe treatment-emergent adverse events occurred during lanadelumab treatment. Conclusion: This study is the first report that demonstrates the clinical efficacy of lanadelumab and safety of LTP in HAE patients from Chinese mainland. A reasonable dosage plan can ensure a quick and long-lasting protective role of lanadelumab against HAE attacks, during COVID-19 pandemic period. Hereditary angioedema (HAE) is a rare genetic disease characterized by recurring episodes of painful swelling of the subcutaneous and submucosal tissue, and its pathogenesis is due to the deficiency or dysfunction C1-esterase inhibitors. HAE attacks can affect many areas of the body, but most frequently involve the extremities, gastrointestinal tract, genitals, face, and upper airway. Swelling of the larynx can occur, with potentially fatal consequences owing to asphyxiation. Since 2020, China has had the only first-line treatment drug that can prevent HAE attacks – lanadelumab. Our study evaluated the efficacy and safety of lanadelumab by observing the 6 patients in China mainland who were the first to use it. Our research showed that lanadelumab can prevent the attack of HAE, greatly improve the quality of life of patients, and has good safety. A reasonable dosage plan can ensure stable therapeutic effects of lanadelumab. In addition, the efficacy of lanadelumab remained stable during COVID-19 vaccination and infection. [ABSTRACT FROM AUTHOR]

Hereditary angioedema (HAE) is a rare and potentially life-threatening genetic disorder, constituting approximately 2% of all clinical cases of angioedema, with a global prevalence estimated between 1 in 50,000 and 1 in 150,000 individuals. The condition affects individuals of all genders and ethnic backgrounds without significant variation. HAE is classified into three types. Type I HAE, which accounts for 85% of cases, is characterized by a deficiency of the C1 esterase inhibitor (C1-INH) gene. Type II HAE, making up 15% of cases, involves a dysfunctional C1-INH. Type III HAE, which represents about 5% to 10% of cases, is often estrogen-dependent and although several mutations have been identified, it typically involves normal C1-INH activity. Despite the differences in C1-INH functionality, all three types of HAE manifest with similar clinical symptoms. HAE leads to recurrent episodes of non-pruritic angioedema, which occurs in the absence of urticaria. Breakthroughs in understanding HAE pathophysiology have revolutionized treatment, leading to the development of highly targeted therapies for both acute management and long-term prevention. Meanwhile, cutting-edge advancements in omics technologies are unlocking new possibilities for biomarker discovery, paving the way for more precise diagnoses and personalized treatment strategies that could significantly enhance patient outcomes. This review will delve into the intricate pathophysiology, diverse clinical presentations, and diagnostic challenges of HAE while exploring emerging biomarkers and innovative approaches to therapeutic management and prevention strategies. Additionally, it will underscore the vital importance of screening family members of affected individuals, even when symptoms are not present. [ABSTRACT FROM AUTHOR]

Hereditary angioedema is a rare, genetic disorder characterized by painful, debilitating and potentially life-threatening angioedema attacks in subcutaneous and submucosal tissue. While usually unpredictable, attacks can be provoked by a variety of triggers including physical injury and certain medication and are often preceded by prodromal symptoms. Hereditary angioedema has a profound influence on the patients' lives. The fundamental cause of hereditary angioedema in almost all patients is a mutation in the SERPING1 gene leading to a deficiency in C1-inhibitor. Subsequently, the contact activation cascade and kallikrein-kinin pathway are insufficiently inhibited, resulting in excessive bradykinin production triggering vascular leakage. While C1-inhibitor is an important regulator of the intrinsic coagulation pathway, fibrinolytic system and complement cascade, patients do not have an increased risk of coagulopathy, autoimmune conditions or immunodeficiency disorders. Hereditary angioedema is diagnosed based on C1-inhibitor level and function. Genetic analysis is only required in rare cases where hereditary angioedema with normal C1-inhibitor is found. In recent years, new, highly specific therapies have greatly improved disease control and angioedema-related quality of life. This article reviews the clinical picture of hereditary angioedema, the underlying pathophysiology, diagnostic process and currently available as well as investigational therapeutic options. [ABSTRACT FROM AUTHOR]

Idiopathic non-histaminergic acquired angioedema (InH-AAE) is a rare disease, with unknown etiology and pathogenesis, characterized by recurrent clinical manifestations and resistance to antihistamines and corticosteroids. We aim to evaluate clinical features and potential markers of disease in an Italian cohort of patients with InH-AAE. We enrolled 26 patients diagnosed with InH-AAE. Information about clinical features, treatments, routine laboratory investigations, immunological and genetic tests were collected. We assessed plasma levels of complement components, angiogenic and lymphangiogenic mediators, proinflammatory cytokines and chemokines, and activity of phospholipases A2. Finally, patients underwent nailfold videocapillaroscopy (NVC); both quantitative and qualitative capillaroscopic parameters were analyzed. Plasma levels of VEGFs were similar in healthy controls and in InH-AAE patients. ANGPT1 was decreased in InH-AAE patients compared to controls while ANGPT2 was similar to controls. Interestingly, the ANGPT2/ANGPT1 ratio (an index of vascular permeability) was increased in InH-AAE patients compared to controls. sPLA2 activity, elevated in patients with C1-INH-HAE, showed differences also when measured in InH-AAE patients. TNF-α concentration was higher in InH-AAE patients than in healthy controls, conversely, the levels of CXCL8, and IL-6 were similar in both groups. At the NVC, the capillary loops mainly appeared short and tortuous in InH-AAE patients. InH-AAE represents a diagnostic challenge. Due to the potential life-threatening character of this condition, a prompt identification of the potentially bradykinin-mediated forms is crucial. A better comprehension of the mechanism involved in InH-AAE would also lead to the development of new therapeutic approaches to improve life quality of patients affected by this disabling disease. [ABSTRACT FROM AUTHOR]

Introduction: The widespread use of the internet has made health information more accessible. However, it has also increased problems such as health anxiety and cyberchondria. Aim: This study aimed to assess cyberchondria levels in allergy and immunology clinic patients and examine the relationship between cyberchondria and health anxiety. Material and methods: This study was conducted on patients diagnosed with allergic disorders, chronic urticaria, hereditary angioedema (HAE), and primary immunodeficiency (PID). Cyberchondria severity was assessed using the Cyberchondria Severity Scale (CSS-12), while health anxiety was evaluated using the Short Health Anxiety Inventory (SHAI). Results: A total of 550 patients were included in the study, with 71% of the participants being female. The highest CSS-12 scores were observed in the HAE group (33.5 ±8.8), followed by the PID group (28.4 ±8.6). The allergic disorders group had the lowest level of cyberchondria severity (27.7 ±8.5). According to SHAI scores, PID and HAE groups had the highest values. A significant positive relationship was found between cyberchondria and health anxiety (r(548) = 0.416, p < 0.001). Conclusions: An increase in cyberchondria raises health anxiety and disease burden among allergy and immunology patients. Therefore, physicians should take this into account when treating these patients. [ABSTRACT FROM AUTHOR]

Background: Hereditary angioedema with normal C1-inhibitor function (HAE nC1-INH) and idiopathic angioedema of unknown etiology (AE-UNK) are rare conditions that cause recurrent subcutaneous and submucosal swelling. The characteristics and clinical outcomes of patients with these conditions in Canada have not been studied. Methods: The aim of this study was to extract real-world evidence from the electronic health records of patients with HAE nC1-INH or AE-UNK who were managed in selected practices of Canadian HAE-treating specialist physicians between 01-Jan-2012 and 01-Jan-2022, to examine case numbers, treatment, clinical outcomes, and healthcare utilization. Results: Of 60 patients (37 with HAE nC1-INH, 23 with AE-UNK), median (range) age at symptom onset was 21.5 (5.0–57.0) and 23.0 (10.0–54.0) years, respectively. Time to diagnosis from onset of symptoms was 7.0 (0.0–43.0) and 2.0 (− 10.0 to 50.0) years. Significant differences were observed in terms of the predominant triggers for angioedema attacks between patients with HAE nC1-INH and AE-UNK: stress (65% vs. 26%, p = 0.007) and estrogen therapy (35% vs. 9%, p = 0.031). Before diagnosis, most patients received antihistamines (50% of HAE nC1-INH and 61% of AE-UNK patients). Post-diagnosis, 73% and 74% of HAE nC1-INH and AE-UNK patients received long-term prophylaxis (LTP), with the most common LTP treatments being subcutaneous pdC1-INH (43% of HAE nC1-INH patients and 39% of AE-UNK patients) and tranexamic acid (41% of HAE nC1-INH patients and 35% of AE-UNK patients). Of patients with HAE nC1-INH, and patients with AE-UNK, 22% and 13%, respectively, were taking more than one LTP treatment concurrently. Before HAE treatment initiation, significantly fewer patients with AE-UNK compared to patients with HAE nC1-INH had angioedema attacks affecting their extremities (13% vs. 38%, p = 0.045) and GI system (22% vs. 57%, p = 0.015). In the three months following treatment initiation, patients with AE-UNK experienced significantly fewer angioedema attacks compared to patients with HAE nC1-INH (median 2.0 attacks [0.0–48.0] vs. 6.0 attacks [0.0–60.0], p = 0.044). Additionally, fewer patients with AE-UNK compared to HAE nC1-INH experienced attacks affecting their GI system (26% vs. 57%, p = 0.032). Attack duration and frequency significantly decreased for patients with HAE nC1-INH from a median of 1.00 day (range: 0.00–7.00) to 0.29 day (range: 0.02–4.00; p = 0.001) and from 10.50 attacks (range: 0.00–90.00) to 6.00 attacks (range: 0.00–60.00; p = 0.004) in the three months following HAE treatment initiation. Conclusions: Using Canadian real-world evidence, these data demonstrate differing clinical trajectories between patients with HAE nC1-INH and AE-UNK, including diagnostic delays, varied attack characteristics, treatment responses and healthcare utilization. Despite treatment response, many patients still experienced frequent angioedema attacks. These results suggest an unmet need for treatment guidelines and therapies specifically for patients with HAE nC1-INH and AE-UNK and better understanding of the pathophysiology accounting for the reported differences between the two. [ABSTRACT FROM AUTHOR]

Background: Hereditary angioedema (HAE) is a rare autosomal dominant genetic disease characterized by recurrent edema and a potentially fatal risk. Despite its severity, there is a notable lack of effective methods for predicting and preventing HAE attacks. This study aims to thoroughly investigate the underlying pathological mechanisms of HAE and identify potential biomarkers that could aid in its prediction and prevention. Results: In our investigation, we have discovered a novel pathogenic variant of the SERPING1 gene, specifically c.708T > G, in a Han family affected by HAE. Our observations indicate that this variant leads to an increase in the accumulation of C1-INH within the endoplasmic reticulum (ER), resulting in the upregulation of GRP75 protein expression. This cascade of events resulted in Ca2+ overload, disruption of mitochondrial structure and function, and eventually triggered apoptosis. Using siRNA to knock down GRP75 mitigates cellular calcium overload and mitochondrial damage induced by the SERPING1 mutation. Conclusion: Based on our findings, we propose that the detection of intracellular Ca2+ concentration could serve as a valuable biomarker for predicting acute attacks of HAE in patients. This discovery holds significant implications for the development of more targeted and effective strategies in the management of HAE. [ABSTRACT FROM AUTHOR]

Objective Hereditary angioedema (HAE) is characterized by attacks of subcutaneous and mucosal edema. HAE usually affects the skin or mucosal tissues of the upper respiratory and gastrointestinal tract. Irritable bowel syndrome (IBS) is one of the diseases in which the abdominal symptoms of HAE may be confused. In this study, we aimed to clarify the role of IBS in clinical presentation and diagnostic delay in HAE. Material and Method 50 patients with HAE followed in our clinic between January 2013 and April 2023 were included in this study, and hospital records were retrospectively reviewed. Patients with HAE were divided into two groups, those with and without IBS, and evaluated according to Rome IV criteria for diagnosing IBS. Results The mean age of the study group was 40 ± 13 years, and 60% (n=30) were female. IBS was observed in 30% (n=15) of the patients, and 60% (n=9) had IBS before diagnosing HAE. The frequency of attacks and history of gastrointestinal tract medical/surgical history were more frequent in HAE patients with IBS (p<0.001, p=0.032, respectively). Abdominal symptoms before the diagnosis of HAE and persistent abdominal symptoms other than attacks after the diagnosis of HAE were more common in HAE patients with IBS (p<0.001, p<0.001, respectively). HAE patients with IBS had a more significant delay in diagnosing HAE (p=0.011). Conclusion Clinicians should keep HAE in mind in patients with suspected IBS or patients presenting with recurrent unexplained abdominal pain. [ABSTRACT FROM AUTHOR]

Background: Hereditary angioedema (HAE) is a rare genetic disorder characterized by unpredictable, debilitating episodes of submucosal and/or subcutaneous tissue swelling, which may be life‐threatening depending on anatomic location. The two primary management strategies for HAE are ready access to effective on‐demand treatment in all patients and the prevention of attacks (short‐term prophylaxis [STP] and long‐term prophylaxis [LTP]) in appropriate patients. All approved on‐demand and most LTP medications require subcutaneous or intravenous administration. Injection‐related challenges include trypanophobia (fear of needles), difficulty with self‐administration, injection‐site reactions (e.g., pain, erythema, bleeding, bruising), and anxiety—all contributing to poor compliance and administration delays. Oral HAE treatments may improve outcomes by reducing treatment barriers. Aim: To review oral therapies, approved or in development, for on‐demand treatment and/or prevention of HAE attacks. Materials and Methods: To provide a comprehensive review, data was obtained from publicly available resources through a targeted PubMed literature review and supplemented by information provided on company websites (search cutoff of May 31, 2024). Results: Berotralstat, an oral plasma kallikrein (PKa) inhibitor, is approved for LTP. Sebetralstat, another PKa inhibitor, is the investigational first oral on‐demand HAE treatment to complete a phase 3 trial. Deucrictibant, an oral bradykinin B2 receptor antagonist, has completed phase 2 trials for on‐demand therapy and LTP. Several other oral PKa inhibitors (ATN249, VE‐4666, and VE‐4062) are in early development for LTP. Conclusion: Substantial advances have been made in the development of oral treatments for HAE. These treatments have the potential to improve and optimize clinical outcomes, satisfaction, and quality of life among patients with HAE. [ABSTRACT FROM AUTHOR]

In the recent years, there was an important improvement in the understanding of the pathogenesis of hereditary angioedema (HAE). Notwithstanding, in a large portion of patients with unknown mutation (HAE-UNK) the genetic cause remains to be identified. To identify new genetic targets associated with HAE, a large Argentine family with HAE-UNK spanning 3 generations was studied. Whole exome sequencing was performed on affected family members to identify potential genetic variants associated with HAE-UNK. In silico analyses and experimental studies were applied to assess the role of the identified gene variant. A missense variant (p.D239N) in DAB2IP was identified. The variant occurred in the C2-domain, the region interacting with vascular endothelial growth factor receptor 2 (VEGFR2). It was found to be rare, and predicted to have a detrimental effect on the functionality of DAB2IP. Protein structure modeling predicted changes in the mutant p.D239N protein structure, impacting protein stability. The p.D239N variant affected the subcellular localization of VEGFR2. Cells transfected with the DAB2IP-239N transcript exhibited an intracellular distribution, and VEGFR2 remained associated with the cell membrane. The altered localization pattern indicated reduced colocalization of the mutant protein with VEGFR2, suggesting a diminished ability of VEGFR2 binding. The study identified a novel missense variant (p.D239N) in DAB2IP in a family with HAE-UNK and highlighted the role of dysregulated VEGF-mediated signaling in altered endothelial permeability. DAB2IP loss-of-function pathogenic variants lead to the impairment of the endothelial VEGF/VEGFR2 ligand system and represent a new pathophysiologic cause of HAE-UNK. [ABSTRACT FROM AUTHOR]

Background: Hereditary Angioedema (HAE) due to C1-inhibitor deficiency (C1INH) is a rare condition, clinically characterised by recurrent swelling. The unpredictability of attacks affects the patients' quality of life (QoL). HAE patients and their families have vast unmet physical, psychological, and social needs. A human-centred design (HCD) approach to describing the needs of different user types is to utilise personas, a data-driven narrative tool for communicating user archetypes that capture the individuals' attitudes, goals, and behaviours. The aim of this study was to create and analyse personas based on HAE patients' and their caregivers' interviews. Semi-structured interviews were conducted through anthropological conversations with patients, patient-caregivers (double role of patient and caregiver), and non-affected caregivers. Qualitative and quantitative insights from analyses formed the basis to create personas. Results: We enrolled 17 subjects: 15 patients (6 of them were patient-caregivers) and 2 non-affected caregivers. The mean age of participants was 50.3 ± 14.4 years. Eight patients were on treatment with prophylactic therapy. The mean percentage score of Angioedema Quality of Life (AE-QoL) for HAE patients was 19.8 ± 12.0. Six personas were identified describing the participants' personal history, disease management, and needs: four personas referred to patients, one to patient-caregivers, and one non-affected caregiver personas were identified. Across patient personas, the most expressed needs were psychological support and better awareness amongst healthcare professionals. Caregivers, on their side, desired better information about the disease, including the latest therapies, and higher awareness within the community. Conclusion: A Human Centred Innovative Approach Based on Persona extends beyond the physical symptoms to encompass the psychological and social aspects of the individual's well-being also including the family in the evaluation. [ABSTRACT FROM AUTHOR]

This article discusses a survey conducted among 208 hereditary angioedema (HAE) patients in the UK and Spain to investigate the prodromal symptoms, or early signs and symptoms, that precede HAE attacks. The majority of patients reported experiencing prodromes before swelling occurred, with the most common symptoms being tiredness/fatigue, pressure or tightness in the skin, and abdominal pressure. The actions taken by patients at the onset of prodromal symptoms differed between countries, with UK patients more likely to self-medicate and Spanish patients more likely to wait. The study suggests that early treatment may be associated with better outcomes, but there is variability in patient behavior regarding "early treatment." Clearer communication between healthcare providers and patients is important, and further research is needed to determine the predictive value of prodromes and their relationship to HAE attacks. [Extracted from the article]

Aim: To compare the efficacy and safety of lanadelumab versus other approved long-term prophylaxis (LTP) treatments in patients with pediatric hereditary angioedema (HAE) aged

Hereditary angioedema (HAE) is an inherited disorder causing attacks of subcutaneous tissue or mucosa swelling. The disease burden and attack frequencies vary significantly among patients. This is the first pilot study investigating small extracellular vesicles (sEV) as potential disease modulators in HAE.Plasma-derived sEVs from HAE patients and healthy donors (HD) were thoroughly characterized by Western blot, transmission electron microscopy, nanoparticle tracking and bead-based flow cytometry. The miRNA content of sEVs was examined by nCounter technology and used to predict sEV-based pathomechanisms in silico. All sEV readouts were analyzed regarding HAE-related changes and associations with clinical parameters and attack frequency.Total sEV protein levels were elevated in HAE patients compared to HD. In HAE patients, lower levels of sEVs carrying CD8, CD209, CD81, CD24 and CD44 were measured. sEV miRNA profiling revealed 84 HAE-exclusive and 30 significantly HAE-upregulated candidates. Core hubs of their predicted interaction networks were AGO2, VEGF, RGS5, MTA1, IFG1 and BAX. A set of 12 and 36 sEV miRNAs were restricted to patients with absent attacks or patients with present attacks during prophylactic therapy, respectively.sEVs, especially sEV miRNAs, could contribute to disease pathogenesis and differential attack frequencies. They emerged as disease modulators in HAE and require further study to reveal underlying mechanisms.

Hereditary angioedema (HAE) is a rare genetic condition characterized by episodes of cutaneous or submucosal edema, most commonly affecting the skin, the abdomen, and the upper respiratory tract. The most common cause of HAE is either a deficiency (type 1) or dysfunction (type 2) of the C1-inhibitor, leading to the overproduction of bradykinin and activation of bradykinin B2 receptors. This increases vascular permeability and results in angioedema attacks. Anatomic, physiological, and hormonal changes during pregnancy can have an impact on the manifestations of the disease and therefore its treatment. Here, we describe the case of a 30-year-old woman who experienced a significant worsening in both the number and severity of angioedema attacks during pregnancy. The cesarean section was complicated by thrombosis of the ovarian vein and inferior vena cava.

Background: The impact of recurrent angioedema can be severely debilitating and remains difficult to quantify. Several standardized patient-reported outcome measures (PROMs), including the Angioedema Activity Score (AAS), Angioedema Quality of Life (AE-QoL) questionnaire, and Angioedema Control Test (AECT), have been developed and translated into different languages. However, these PROMs have yet to be validated in Chinese individuals, and their correlations in the Chinese population remain unknown. Objective: Our aim was to validate the Chinese versions of the AAS, AE-QoL questionnaire, and AECT and assess their intercorrelations. Methods: A prospective cohort of 118 Chinese patients with recurrent angioedema at the Angioedema and Urticaria Centre of Reference and Excellence in Hong Kong completed the traditional Chinese versions of the AAS, AE-QoL questionnaire, and AECT. We analyzed the reliability and validity of these PROMs and their correlations with each other as well as with generic PROMs. Results: The Chinese AAS, AE-QoL questionnaire, and AECT demonstrated excellent internal consistency (Cronbach α = 0.920, 0.976, and 0.832, respectively; McDonald ω = 0.972, 0.977, and 0.901, respectively). Confirmatory factor analysis for the AE-QoL questionnaire showed an acceptable fit with the 4-dimensional model (comparative fit index = 0.869; Tucker-Lewis index = 0.842). The AECT showed significant correlations with both the AAS and AE-QoL questionnaire (ρ = –0.750 and –0.456 respectively [both P < .05]). The AE-QoL questionnaire was moderately correlated with certain domains of generic PROMs such as the Work Productivity and Activity Impairment Questionnaire: General Health, version 2.0, and the Short Form 12-Item Health Survey, version 2 (all ρ < 0.60). Conclusion: The Chinese AE-QoL questionnaire, AAS, and AECT are valid and reliable tools for use with Chinese patients. More validated tools should be made available to improve patient care and research for all patients with angioedema globally.

Introduction: Hereditary angioedema (HAE) is a rare genetic disease characterized by recurrent, potentially life-threatening angioedema episodes. Despite its severity, including the risk of asphyxiation, HAE often remains underdiagnosed. The disease significantly impacts patient quality of life (QoL), leading to anxiety, depression, and avoidance behaviors due to the unpredictable nature of attacks. Understanding the perspectives of patients is crucial for identifying unmet needs in managing this complex condition. Objective: This study aimed to gather real-world insights from Brazilian patients with C1 inhibitor deficiency HAE to identify their unmet needs and assess their perceptions of the effectiveness of current care in preventing and treating HAE attacks. Methods: A cross-sectional study utilized a SurveyMonkey questionnaire distributed to HAE patients through ABRANGHE via email. Participants provided informed consent, and their responses were anonymous. The questionnaire, developed with input from experts and patients, covered aspects of HAE diagnosis, treatment experiences, and QoL assessments. Results: The survey included 178 HAE patients, predominantly female (81%), aged 30–50 years (58%), and college-educated (62%). The most common HAE defect was C1–INH deficiency (53%), followed by HAE-nC1INH (23%), with nearly a quarter unaware of their specific defect. Diagnosis delays were prevalent, with a significant number reporting 13–50 attacks annually (33%) and 15% experiencing more than 50 attacks per year. Laryngeal involvement was reported by 26% of respondents. Most patients (69%) attended regular follow-ups, with 72% on prophylactic treatment and 67% managing acute attacks. The most used acute treatment was Icatibant (49%), followed by pdC1INH (24%). However, confusion regarding medication use persisted, with 45% incorrectly believing that oral medications could effectively treat attacks. Key unmet needs identified included improved access to emergency rooms during attacks (73%), better availability of prophylactic treatment (69%), and enhanced access to specialized care (63%). Patients also emphasized the need for psychological support, increased awareness of HAE, and educational initiatives for patients and healthcare providers. Discussion: This study highlighted significant challenges in HAE management among Brazilian patients, particularly concerning delayed diagnosis, misconceptions about treatment, and inadequate access to specialized care and prophylactic treatments. The high frequency of emergency room visits underscores the difficulties in managing the disease. The substantial burden of HAE on QoL emphasizes the urgent need for improved physician education, streamlined diagnostic processes, and equitable access to effective medications and specialized care facilities. Addressing these gaps is crucial to better support HAE patients, improve diagnostic timeliness, enhance treatment efficacy, and ultimately enhance the overall quality of life for individuals living with HAE.

Hereditary angioedema (HAE) is a rare genetic condition characterized by episodes of cutaneous or submucosal edema, most commonly affecting the skin, the abdomen, and the upper respiratory tract. The most common cause of HAE is either a deficiency (type 1) or dysfunction (type 2) of the C1-inhibitor, leading to the overproduction of bradykinin and activation of bradykinin B2 receptors. This increases vascular permeability and results in angioedema attacks. Anatomic, physiological, and hormonal changes during pregnancy can have an impact on the manifestations of the disease and therefore its treatment. Here, we describe the case of a 30-year-old woman who experienced a significant worsening in both the number and severity of angioedema attacks during pregnancy. The cesarean section was complicated by thrombosis of the ovarian vein and inferior vena cava. [ABSTRACT FROM AUTHOR]

Hereditary angioedema (HAE) is an autosomal dominantly inherited disease caused by deficiency of C1 esterase inhibitor protein type 1 (about 85% of patients with HAE-C1-INH) or type 2 oedema (about 15% of patients with HAE-C1-INH) by C1 inhibitor dysfunction, with normal serum levels (HAE-2). Long-term treatment to prevent further attacks consists of continuous and regular administration of medications to reduce the number and severity of oedema attacks in HAE patients, thereby reducing the indirect burden of the disease. With the severe course of the disease, potentially life-threatening during flare-ups, it is expedient to implement long-term HAE attacks prophylaxis, which was very limited in Poland until September 2021.

Abstract 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.