[Long-term prophylactic therapy combined with on-demand therapy for the control of hereditary angioedema--Comment on the 2021 edition of the international WAO/EAACI guideline for the management of hereditary angioedema].

The 2021 edition of the international World Allergy Organization (WAO)/European Academy of Allergy and Clinical Immunology (EAACI) guideline for the management of hereditary angioedema (HAE) is mainly based on high-quality randomized controlled trials. It provides clinical classification for HAE and offers graded recommendations for on-demand therapy, short-term prophylactic therapy, and long-term prophylactic therapy. Additionally, it provides management strategies for people with different HAE types. This article focused on the interpretation of short-term, long-term prophylactic therapy and on-demand therapy for HAE, supplemented with the latest clinical evidence, aiming to provide references for the long-term management of HAE.

[Design and implementation of a transdisciplinary care model for patients with hereditary angioedema, in a Colombian health institution]. / Diseño e implementación de un modelo de atención transdisciplinaria para pacientes con angioedema hereditario, en una institución de salud colombiana.

OBJECTIVE: Describe the design and implementation of a transdisciplinary care model for patients with hereditary angioedema in Colombia. METHODS: Descriptive longitudinal observational study. 140 patients with hereditary angioedema were included in a transdisciplinary care model for one year. Seizure rates, hospitalizations, emergency room visits, quality of life, and pharmacological adherence were measured. RESULTS: The model was associated with reductions of 76% in seizures, 66% in hospitalizations, and 87% in emergency room visits. Pharmacological adherence increased 19% and was complete after four months. The quality of life increased significantly. CONCLUSIONS: Hereditary angioedema is an orphan disease that requires a comprehensive approach for effective care.

OBJETIVO: Describir el diseño e implementación de un modelo transdisciplinario de atención para pacientes con angioedema hereditario en Colombia. MÉTODOS: Estudio observacional longitudinal descriptivo. 140 pacientes con angioedema hereditario fueron incluidos en un modelo de atención transdisciplinario por un año. Se midieron tasas de crisis, hospitalizaciones, visitas a urgencias, calidad de vida y adherencia farmacológica. RESULTADOS: El modelo se asoció con reducciones del 76% en crisis, 66% en hospitalizaciones y 87% en visitas a urgencias. La adherencia farmacológica aumentó 19% y fue completa después de cuatro meses. La calidad de vida aumentó significativamente. CONCLUSIÓN: El angioedema hereditario es una enfermedad solitaria que requiere un abordaje integral para la atención eficaz.

Uncovering the true burden of hereditary angioedema due to C1-inhibitor deficiency: A focus on the Asia-Pacific region.

Hereditary angioedema (HAE) due to C1-inhibitor deficiency or dysfunction is a rare genetic disorder that causes recurrent episodes of swelling in various parts of the body. Treatment goals of HAE aim to "normalize" life for all patients; however, lack of diagnostic facilities and limited access to effective treatment options in developing nations cause delays in diagnosis and place a significant burden on patients. In this review, we aim to highlight the burden of disease caused by C1-inhibitor HAE across the Asia-Pacific region, considering its epidemiology, morbidity and mortality, and socioeconomic and psychological impact. We also review the availability of guideline-recommended diagnostic facilities and treatments, and how patients are currently managed. Data were collected from published literature and HAE experts in the region, who provided information regarding diagnosis and management in their countries. Current practice was reviewed against international guidelines, as well as local guidelines/consensus used in Australia, Japan, and China. Suggestions are provided for improving the time to diagnosis in the region, increasing access to guideline-recommended treatments, and providing support to reduce the burden on patients and caregivers. There is an urgent need to improve HAE services and provide access to life-saving treatment in developing countries, and efforts should be made to increase awareness of guideline recommendations in high-income economies that do not currently provide long-term prophylactic treatments.

[Hereditary angioedema due to C1-inhibitor deficiency, a national disease management programme]. / Hereditäres Angioödem durch C1-Inhibitor-Mangel, eine nationale Versorgungsleitlinie.

Hereditary angioedema (HAE) is a rare, painful, disabling and potentially fatal disease, where early diagnosis and effective treatment are critical. These Austrian guidelines for the diagnosis and management of HAE provide instructions and advice on the state of the art management of HAE in Austria in contrast to global guidelines, where the situation of all countries worldwide must be taken into account. Our goal is to help Austrian physicians to consider HAE as a differential diagnosis with corresponding symptoms, to make rational decisions for the diagnosis and management of HAE with C1-inhibitor deficiency (type 1 or type 2). The guidelines provide information on common and important clinical symptoms, diagnostic methods, treatment modalities, available HAE-specific medications in Austria and last but not least to motivate physicians to refer patients to HAE centers for confirmation of the diagnosis and adequate treatment decisions.

The US Hereditary Angioedema Association Scientific Registry: hereditary angioedema demographics, disease severity, and comorbidities.

BACKGROUND: Hereditary angioedema (HAE) and idiopathic nonhistaminergic angioedema (INHA) are ultra-rare diseases whose natural histories and comorbidities are incompletely understood. OBJECTIVE: To develop a national patient-centric registry to address these deficiencies in our knowledge and improve our ability to assess the real-world impact of therapeutic interventions. METHODS: Data from members of the US HAE Association were collected into an online registry between 2009 and April 7, 2021. Cohorts were categorized by reported physician diagnosis. Patient reported data were collected using a series of questionnaires. Demographic, natural history, and family history outcomes of the HAE due to C1 inhibitor deficiency (HAE-C1INH) participants were compared with those of the combined HAE with normal C1 inhibitor (HAE-nl-C1INH) plus INHA group. The prevalence of comorbid conditions in the HAE-C1INH group was compared with the general US population. RESULTS: A total of 485 HAE-C1INH, 26 HAE-nl-C1INH, and 70 INHA participants were included in the analysis. Delay to diagnosis was shorter in HAE-C1INH (5 vs 11 years), but both had decreasing delays over time. Differences in attack frequency and location were found between the groups. Morbidity surrogates including emergency department visits, hospitalizations, unnecessary abdominal surgeries, and intubations were strikingly high as was mortality with 36.9% of HAE-C1INH and 15.4% of HAE-nl-C1INH participants reporting family members who died from a HAE attack. Females with HAE-C1INH had a significant increase in the prevalence of depression, sleep disorders, kidney disease, anemia, and hepatitis. Cardiovascular comorbidities were significantly reduced in the HAE-C1INH group. CONCLUSION: The US HAEA Scientific Registry provides a mechanism to enhance our knowledge of HAE and INHA.

Consequences of Insurance Coverage Delays and Denials for Patients With Hereditary Angioedema.

BACKGROUND: Hereditary angioedema (HAE) is a rare and potentially fatal genetic disease associated with recurrent and unpredictable episodes of angioedema. Although modern therapies have dramatically increased quality of life, insurance changes, delays, and denials are becoming more common. OBJECTIVE: To examine the impact of insurance delays and denials on patient health and well-being. METHODS: A total of 20 patients with HAE (type 1 and 2) who recently experienced insurance delays or denials completed an online survey, and 19 participated in a follow-up focus group. The survey and focus group addressed the impact of insurance challenges on the use of health care services, work/school attendance, and anxiety. Three independent reviewers coded each focus group transcript using a thematic saturation approach. RESULTS: A total of 70% of participants reported an increased frequency of angioedema attacks resulting from insurance delays or denials. More than 50% missed work/school days because of increased attacks, and 90% reported greater anxiety. Twenty-five percent of respondents reported more urgent care or emergency department visits. In focus groups, participants identified specific ways that losing access to medication had a negative impact on their health, family, and work/school life. Insufficient notification of health insurance policy changes and the time and effort required to regain access to medications compounded patients' frustration and anxiety. CONCLUSION: Insurance delays and denials have significant impacts on individuals with HAE including (1) increased urgent care and emergency department visits, (2) missed work/school days, (3) higher levels of anxiety, and (4) a negative impact on family life.

[Diagnosis and treatment procedures and health management for patients with hereditary angioedema].

As a recognized rare and highly fatal disease, hereditary angioedema (HAE) is difficult to diagnose and characterized by recurrent edema involving the head, limbs, genitals and larynx, etc. Diagnosis of HAE is not difficult. However, low incidence and lack of clinical characteristics lead to difficulty of doctors on timely diagnosis and correct intervention for HAE patients. Therefore, it is crucial to improve the awareness of this disease and prevent its recurrence. for HAE patients. In view of absent cognition of doctors and the general public on HAE, patients often suffer from sudden death or become disabled due to laryngeal edema which cannot be treated in time. Thus, based on the Internet mobile terminal platform, the team set up an all-day rapid emergency response system which is provided for HAE patients by setting up "one-click help". The aim is to offer optimization on overall management of HAE and designed the intelligent follow-up management to provide timely assistance and specialized suggestion for patients with acute attacks.

Hereditary Angioedema.

Hereditary angioedema (HAE) is a rare autosomal dominant genetic disorder that usual results from a decreased level of functional C1-INH and clinically manifests with intermittent attacks of swelling of the subcutaneous tissue or submucosal layers of the respiratory or gastrointestinal tracts. Laboratory studies and radiographic imaging have limited roles in evaluation of patients with acute attacks of HAE except when the diagnosis is uncertain and other processes must be ruled out. Treatment begins with assessment of the airway to determine the need for immediate intervention. Emergency physicians should understand the pathophysiology of HAE to help guide management decisions.

A Case Report of Hereditary Angioedema: Challenges in Diagnosis and Management.

Hereditary angioedema (HAE) is a rare autosomal dominant genetic disorder which causes bradykinin mediated angioedema. Although it can be life threatening, HAE may be underdiagnosed due to a lack of awareness of the disease and limited access to laboratory testing. Here, we report a case of HAE which was diagnosed only after the patient was referred for COVID-19 vaccination even though he had been experiencing recurrent angioedema for the past 30 years.

Hereditary Angioedema: A Disease Often Misdiagnosed and Mistreated.

Hereditary angioedema is a rare autosomal dominant condition characterized by episodes of swelling of the upper airway, intestines, and skin. The disorder is characterized by deficiency in C1 esterase inhibitor (C1-INH) or a decrease in functional C1-INH. Treatment options include on demand therapy (treatment of acute attacks), long-term prophylaxis, and short-term prophylaxis. Corticosteroids, epinephrine, and antihistamines are not effective for this form of angioedema. The high mortality in patients undiagnosed underscores a need for broader physician awareness to identify these patients and initiate therapy.

Hereditary Angioedema: Diagnosis, Clinical Implications, and Pathophysiology.

Hereditary angioedema (HAE) is an autosomal dominant disorder caused by a mutation in the C1 esterase inhibitor gene. HAE affects 1/50,000 people worldwide. Three main types of HAE exist: type I, type II, and type III. Type I is characterized by a deficiency in C1-INH. C1-INH is important in the coagulation complement, contact systems, and fibrinolysis. Most HAE cases are type I. Type I and II HAE result from a mutation in the SERPING1 gene, which encodes C1-INH. Formally known as type III HAE is typically an estrogen-dependent or hereditary angioedema with normal C1-INH activity. Current guidelines now recommend subdividing hereditary angioedema with normal C1 esterase inhibitor gene (HAE-nl-C1-INH formerly known as HAE type III) based on underlying mutations such as in kininogen-1 (HAE-KNG1), plasminogen gene (PLG-HAE), myoferlin gene mutation (MYOF-HAE), heparan sulfate-glucosamine 3-sulfotransferase 6 (HS3ST6), mutation in Hageman factor (factor XII), and in angiopoietin-1 (HAE-ANGPT-1). The clinical presentation of HAE varies between patients, but it usually presents with nonpitting angioedema and occasionally abdominal pain. Young children are typically asymptomatic. Those affected by HAE usually present with symptoms in their early 20s. Symptoms can arise as a result of stress, infection, or trauma. Laboratory testing shows abnormal levels of C1-INH and high levels of bradykinin. C4 and D-dimer levels can also be monitored if an acute HAE attack is suspected. Acute treatment of HAE can include IV infusions of C1-INH, receptor antagonists, and kallikrein inhibitors. Short- and long-term prophylaxis can also be administered to patients with HAE. First-line therapies for long-term prophylaxis also include IV infusion of C1-INH. This review aims to thoroughly understand HAE, its clinical presentation, and how to treat it.

Hereditary Angioedema During Pregnancy: Considerations in Management.

In recent years, hereditary angioedema (HAE) management has substantially advanced but also become more complex with additional therapeutic options. Pregnancy significantly influences the clinical symptoms of HAE in many women because of estrogen effects or other physiologic factors, and also introduces important safety concerns related to HAE medications. Management of HAE during pregnancy requires clinicians to be familiar with the potential clinical course, triggers, and recommended treatment strategies to provide guidance and optimal medical management to women and families affected by the condition. This review provides an overview of data, considerations, and recommendations related to HAE and pregnancy.

Epidemiology, Management, and Treatment Access of Hereditary Angioedema in the Asia Pacific Region: Outcomes From an International Survey.

BACKGROUND: Hereditary angioedema (HAE) is a rare genetic disease with significant morbidity and mortality for which early diagnosis and effective therapy are critical. Many Asia Pacific (AP) countries still lack access to diagnostic tests and evidence-based therapies. Epidemiologic data from the AP is needed to formulate regional guidelines to improve standards of care for HAE. OBJECTIVE: To investigate the estimated minimal prevalence, needs, and potential interventions for the diagnosis and management of HAE in the AP. METHODS: A structured questionnaire was distributed to representative experts from member societies of the Asia Pacific Association of Allergy, Asthma and Clinical Immunology. Patient profiles and the presence of diagnostic facilities or tests, regional and national HAE guidelines, and patient support groups were reported and compared. RESULTS: Completed questionnaires were received from 14 representatives of 12 member countries and territories, representing 46% of the world population. Overall minimal prevalence of HAE in the AP region was 0.02/100,000 population, with significant heterogeneity across different centers. Only one-half and one-third had registered on-demand and prophylactic medications, respectively. Few had patient support groups (58%) or regional guidelines (33%), and their existence was associated with the availability of HAE-specific medications. Availability of C1-inhibitor level testing was associated with a lower age at HAE diagnosis (P = .017). CONCLUSIONS: Hereditary angioedema in the AP differs from that in Western countries. Hereditary angioedema-specific medications were registered in only a minority of countries and territories, but those with patient support groups or regional guidelines were more likely to have better access. Asia Pacific-specific consensus and guidelines are lacking and urgently needed.

Anesthetic management of a patient with acquired angioedema submitted to broncofibroscopy: a case report.

Acquired angioedema with C1 inhibitor deficiency (AAE-C1INH) is a very rare condition of bradykinin-mediated angioedema. One of its major complications is potentially life-threatening, laryngeal edema. We report a 53-year-old woman with AAE-C1INH proposed for an elective broncofibroscopy. The direct stimulation caused by broncofibroscopy poses a high risk of angioedema, thus presenting an anesthetic challenge. Due to the risk of death, it is essential to adopt preventive measures. Short-term prophylaxis was performed, and the acute treatment was readily available. A well-structured multidisciplinary periprocedural plan makes it possible to safely approach the airway, in a remote area of the hospital.

Anesthetic management of a patient with acquired angioedema submitted to broncofibroscopy: a case report

Abstract Acquired angioedema with C1 inhibitor deficiency (AAE-C1INH) is a very rare condition of bradykinin-mediated angioedema. One of its major complications is potentially life-threatening, laryngeal edema. We report a 53-year-old woman with AAE-C1INH proposed for an elective broncofibroscopy. The direct stimulation caused by broncofibroscopy poses a high risk of angioedema, thus presenting an anesthetic challenge. Due to the risk of death, it is essential to adopt preventive measures. Short-term prophylaxis was performed, and the acute treatment was readily available. A well-structured multidisciplinary periprocedural plan makes it possible to safely approach the airway, in a remote area of the hospital.

CRISPR infusion eases symptoms in genetic disease.

Some patients no longer need drugs to prevent swelling.

Isolated angioedema: A review of classification and update on management.

OBJECTIVE: To review the various types of angioedema including diagnosis and treatment. DATA SOURCES: PubMed search of articles in the English language of various types of angioedema. STUDY SELECTIONS: Articles on the subject matter were selected and reviewed. RESULTS: Herein, a case-based approach is presented for discussing the major types of angioedema, including the following: hereditary angioedema types I and II and normal complement, acquired angioedema, angiotensin-converting enzyme-induced angioedema, and histaminergic and nonhistaminergic angioedema. Emerging treatments of hereditary angioedema including targets of prekallikrein, DNA vector technology replacing C1-INH protein, and CRIPSR technology targeting prekallikrein among many others are explored. In addition, other causes and mimickers of angioedema are briefly reviewed. Finally, a novel algorithm is proposed to help guide the treating physician through the workup and management of patients with suspected idiopathic angioedema unresponsive to conventional therapy with antihistamines. CONCLUSION: Over the years, many strides have been made in both understanding the pathophysiology of various types of angioedema and expansion of treatment options. It is important for clinicians to be aware of current and emerging treatment options. We provide a novel practical algorithm to guide clinicians in challenging cases of idiopathic angioedema refractory to antihistamines.

Shared decision-making in the management of hereditary angioedema: An analysis of patient and physician perspectives.

Background: Hereditary angioedema (HAE) is a rare genetic disorder characterized by recurrent, localized episodes of edema. Current treatment guidelines highlight the importance of shared decision-making (SDM) during implementation of HAE management plans. Objective: To determine what constitutes a successful SDM approach in HAE management. Method: Qualitative telephone interviews, which lasted ∼1 hour, were conducted with four HAE physicians and four patients from the APeX-S trial. The physicians were asked to describe the structure and/or content of typical HAE prophylaxis consultations and factors to consider when selecting medications for long-term treatment. Insights from these interviews were used to develop an SDM process diagram. The patients were interviewed to assess how closely the diagram fit their perspectives on the HAE consultation and their involvement in decisions that concerned their care. Interview transcripts were assessed by the interviewer to determine the degree of SDM involvement in each consultation by using qualitative criteria from the literature. Results: Two physicians followed a high-SDM format, and one physician used a "blended" approach. The fourth physician followed a standard (low SDM) format. A successful SDM approach was found to require pre-visit planning, a commitment on behalf of the physician to use SDM methods to learn more about the patient, and empowerment of the patient to reflect on and vocalize his or her preferences and/or needs. Patients engaged in SDM were more likely to proactively request a treatment switch. Conclusion: The adoption of validated HAE-specific treatment decision aids, as well as measures to change the mindsets of patients and physicians, may facilitate successful implementation of SDM in HAE.Clinical Trial Registration: The APeX-S trial was registered with clinicaltrials.gov (NCT03472040).