Hereditary Angioedema

Hereditary angioedema (HAE) is an autosomal dominant genetic disease characterized by recurrent attacks of localized subcutaneous and mucosal swelling.1,2

Angioedema attacks most commonly affect the face, extremities, abdomen and urogenital area and are often painful and debilitating.1,2

Less commonly, they can occur in the laryngeal area causing airway obstruction and potentially becoming life-threatening.2

Hereditary Angioedema illustration

Epidemiology

HAE is a rare condition with an estimated prevalence of 1 in 50,000, though exact prevalence may vary due to misdiagnosis and geographical region.1,2,3 Symptoms are unpredictable and can manifest at any age, but typically appear during childhood (5 to 11 years), worsen during puberty (particularly among females), and persist throughout life.2,4,5,6,7 

Pathophysiology

HAE is an autosomal dominant disorder resulting from a deficiency of C1 inhibitor (C1-INH), which is a naturally occurring protein that inhibits plasma kallikrein, a key mediator of inflammation.1,8,9,10,11 C1-INH deficiency results in uncontrolled kallikrein activity, leading to increased generation of the vasoactive peptide bradykinin and associated symptoms of pain and swelling.8,9,10,11,12 

The disease is marked by its genetic variability – more than 510 different mutations of the C1-INH gene (SERPING1) have been identified.13 However, it is generally classified into 3 types according to the underlying cause and levels of C1-INH:
 

  • Type I (~85% of cases) is associated with low plasma levels of the C1-INH protein2,14,15
  • Type II (~15% of cases) is associated with a dysfunctional C1-INH protein despite normal plasma levels2,14,15
  • HAE with normal C1-inhibitor levels (formerly type III, estrogen-dependent) is very rare and is associated with normal C1-INH levels and function but has been linked to a number of other mutations2,14,15

Diagnosis

Due to its rarity and symptom overlap with other conditions, HAE is frequently under-recognized leading to delayed diagnosis.4,7,16,17 Historically, the rate of mortality has been higher in undiagnosed HAE patients due to lack of awareness of potential fatal laryngeal attacks and inadequate treatment.18 The two most common forms of HAE (types I/II) should be suspected when a patient presents with a history of recurrent angioedema attacks and further substantiated by:19 

  • Positive family history (may be absent in 25% of cases)
  • Onset of symptoms in childhood/adolescence
  • Recurrent and painful abdominal symptoms
  • Occurrence of upper airway edema
  • Failure to respond to antihistamines, glucocorticoids, or epinephrine
  • Presence of prodromal signs/symptoms before swellings
  • Absence of urticaria (wheals/hives)

To confirm diagnosis, patients should be assessed for blood levels of C1-INH protein, C4 and C1-INH function.19

Navigating HAE

The condition is associated with a substantial and multifaceted burden of illness affecting various aspects of a patient's quality of life (e.g., emotional state, career and education progression, and the decision to have children).2,7,20,21,22,23,24 Types I/II are indistinguishable in their clinical presentation, having identical symptoms characterized by edema attacks that can vary in location, frequency, duration, and severity.1,25,26 Swelling and other symptoms gradually worsen over 12 to 36 hours, intensifying in a relentless manner, sometimes spreading to other sites, and then resolving over 2 to 5 days.7,14,27

A variety of possible triggers for attacks have been proposed, most commonly mechanical trauma, mental stress, and airway infection.2,4,28 Nevertheless, many attacks occur without an obvious trigger, particularly in children, highlighting the need for individualized treatment plans.2,4,19

Medication Resources

Cinryze®

[C1 Esterase Inhibitor (Human)]

Firazyr®

(icatibant injection)

Kalbitor®

(ecallantide)

Takhzyro®

(lanadelumab-flyo)

Upcoming & Past Conferences in Allergy & Immunology

  • Upcoming

  • Past

Association of Pulmonary Advanced Practice Providers (APAPP), 2024

June 20 - 22, 2024 | Link to Event

The Association of Pulmonary Advanced Practice Providers (APAPP) is the first association to focus solely on advanced practice providers (APPs) working in the realm of pulmonary medicine. Join over 200 nurse practitioners and physician associates for in-depth reviews and discussions highlighting the latest developments and current concepts in pulmonary, critical care, and sleep medicine.

Peripheral Nerve Society (PNS), 2024

June 22 - 25, 2024 | Link to Event

The largest peripheral nerve meeting globally, offering the latest international research across specialties in peripheral neuropathy.

American Association of Nurse Practitioners (AANP), 2024

June 25 - 30, 2024 | Link to Event

A national conference offering exclusive continuing education, legislative policy updates, hands-on workshops, lively exhibitors, and networking opportunities for the nurse practitioner community.

Neuromuscular Study Group (NMSG), 2024

September 20 - 22, 2024 | Link to Event

Annual conference aiming to advance knowledge about the cause(s), pathogenesis, epidemiology, and clinical manifestations of muscle disease and related neuromuscular disorders and to develop and implement strategies to examine promising therapeutic interventions.

American College of Chest Physicians (CHEST), 2024

October 6 - 9, 2024 | Link to Event

Annual meeting offering the most up-to-date education in pulmonary, sleep, and critical care medicine through simulation sessions and original research presentations with clinical relevance to practitioners.

Academy of Managed Care Pharmacy Nexus (AMCP Nexus), 2024

October 14 - 17, 2024 | Link to Event

Annual event with more than 2,500 members and non-members of the AMCP to engage on the latest innovations and most intentional networking in managed care pharmacy.

American Association of Neuromuscular & Electrodiagnostic Medicine (AANEM), 2024

October 15 - 18, 2024 | Link to Event

Annual meeting dedicated to the advancement of neuromuscular, musculoskeletal, and electrodiagnostic  medicine.

The European Society for Immunodeficiencies (ESID), 2024

October 16 - 19, 2024 | Link to Event

Biennial meeting that covers the latest discoveries in basic and clinical science covering our expanding field, bringing together internationally renowned scientists and clinicians to present and discuss major developments in diagnosis, clinical management, genetics, and immunobiology of inborn errors of immunity.

Immunoglobulin National Society (IgNS), 2024

October 17 - 20, 2024 | Link to Event

National conference of IgNS bringing together professionals and practitioners from all disciplines and clinical specialties to advance Ig therapy practice, while providing networking and comprehensive education opportunities.

American College of Allergy, Asthma & Immunology (ACAAI), 2024

October 24 - 28, 2024 | Link to Event

Global meeting featuring thought leaders from around the world focused on advancing patient care in allergy and immunology.

European Academy of Allergy & Clinical Immunology (EAACI), 2024

May 31 - June 3, 2024

The flagship meeting of the EAACI and the world’s largest congress specializing in the field of allergy and clinical immunology.

Eastern Allergy Conference (EAC), 2024

May 30 - June 2, 2024

Regional annual conference discussing the most current information from top experts in allergy, asthma, and immunology.

American Thoracic Society (ATS), 2024

May 17 - 22, 2024

International conference showcasing the latest advances in pulmonary disease, critical illness, and sleep disorders for scientists and clinicians at all stages of their careers.

Professional Society for Health Economics and Outcomes Research (ISPOR), 2024

May 5 - 8, 2024

Leading global conference discussing how to establish, incentivize, and share value sustainable for health systems, patients, and technology developers.

Clinical Immunology Society (CIS), 2024

May 1 - 4, 2024

Annual meeting with the goal of providing a stimulating forum with presentations and discussions on the latest advances in clinical immunology, including primary immunodeficiencies and immune dysregulatory diseases.

Academy of Managed Care Pharmacy (AMCP), 2024

April 15 - 18, 2024

Large assembly of pharmacy and healthcare professionals dedicated to the issues of managed care pharmacy, offering immersive education sessions and keynote presentations.

Takhzyro® (lanadelumab-flyo)

  • Comparison of Real-World Healthcare Resource Utilization and Costs Among Patients With Hereditary Angioedema on Lanadelumab or Berotralstat Long-Term Prophylaxis

American Academy of Neurology (AAN), 2024

April 13 - 18, 2024

Annual meeting in neurology promoting high quality patient-centric care in a variety of topics and specialties through various learning formats.

HyQvia® (Human Immune Globulin 10% with Recombinant Human Hyaluronidase)

  • Facilitated subcutaneous immunoglobulin 10% for CIDP: interim results from a long-term safety and tolerability study
  • Infusion-related Costs for HyQvia Compared to Hizentra in Chronic Inflammatory Demyelinating Polyradiculoneuropathy
  • Patient-reported outcomes with hyaluronidase-facilitated subcutaneous immunoglobulin 10% maintenance therapy for chronic inflammatory demyelinating polyradiculoneuropathy

National Home Infusion Association (NHIA), 2024

March 23 - 27, 2024

Annual conference ideal for infusion professionals or those seeking opportunities in the industry to come together and explore the latest trends in offering home-based services.

Hereditary Angioedema International (HAEi), 2024

March 15 - 17, 2024

Every second year HAEi gathers HAE patients, caregivers, healthcare professionals, and industry representatives with a sole focus of sharing experience and knowledge on HAE topics.

Annual Meeting American Academy of Allergy Asthma and Immunology (AAAAI), 2024

February 23 - 26, 2024

Premier global educational event for allergists and immunologists, with thousands of attendees each year, discussing allergies, asthma, and immune deficiency disorders.

  • Patient-Reported Outcomes Among Patients With Hereditary Angioedema Within Underrepresented Racial or Ethnic Groups

Takhzyro® (lanadelumab-flyo)

  • Real-World Treatment Outcomes in Patients With Hereditary Angioedema Receiving Lanadelumab or Other Long-Term Prophylaxis
  • Understanding the Impact of Long-Term Prophylaxis Switches for Patients With Hereditary Angioedema
  • Real-World Treatment Outcomes of Lanadelumab in the Prevention of Hereditary Angioedema Attacks: An Interim Analysis of a Polish Prospective, Multicenter, Observational Study (CHOPIN)
  • Real-World Treatment Patterns and Characteristics of Patients With Hereditary Angioedema Treated With Lanadelumab: Results From a US Retrospective Chart Review Study
  • Long-Term Effectiveness and Safety of Lanadelumab in Patients With Hereditary Angioedema From the United States and Canada: Final Data From the EMPOWER Study
  • Burden of Illness in Adult Patients With Controlled and Poorly Controlled Hereditary Angioedema: Findings From a Multinational Survey
  • Burden of Illness in Female and Male Adult Patients With Hereditary Angioedema: Findings From a Multinational Survey and the HELP OLE Study
  • Lanadelumab Effectiveness and Safety in Adolescent Patients With Hereditary Angioedema Aged 12 to <18 Years: Pooled Results From the Real-World ENABLE and EMPOWER Studies

Western Society of Allergy, Asthma and Immunology (WSAAI), 2024

February 4 - 8, 2024

Annual scientific session uniting allergists, immunologists, nurses, and physician assistants aimed at maintaining the highest standard of practice in allergy care.

  • Understanding Social Determinants of Health and Outcomes in Patients With Hereditary Angioedema in the United States
  • Quality of Life Among Patients With Hereditary Angioedema Within Underrepresented Racial or Ethnic Groups

Takhzyro® (lanadelumab-flyo)

  • Real-World Quality of Life in Patients With HAE Receiving Lanadelumab or Other Long-Term Prophylaxis

American College of Allergy, Asthma & Immunology (ACAAI), 2023

November 9 - 13, 2023

Global meeting featuring thought leaders from around the world focused on advancing patient care in allergy and immunology.

  • Healthcare Experiences Prior to Hereditary Angioedema Diagnosis in Underrepresented Racial/Ethnic Groups in the United States
  • Perspectives of Medical Care Among Patients With Hereditary Angioedema Within Underrepresented Racial or Ethnic Groups

Takhzyro® (lanadelumab-flyo)

  • Real-World Outcomes in Patients With HAE Receiving Lanadelumab Long-Term Prophylaxis for 3 Years or Longer
  • Real-World Quality of Life in Patients With HAE Receiving Lanadelumab or Other Long-Term Prophylaxis

Academy of Managed Care Pharmacy Nexus (AMCP Nexus), 2023

October 16 - 19, 2023

Annual event with more than 2,500 members and non-members of the AMCP to engage on the latest innovations and most intentional networking in managed care pharmacy.

  • Healthcare Resource Use Among Individuals With Chronic Obstructive Pulmonary Disease With and Without Alpha-1 Antitrypsin Deficiency in a United States Medicare Advantage Population
  • Characteristics, Healthcare Resource Utilization, and Costs Among Patients With Multifocal Motor Neuropathy: a United States Claims Database Cohort Study

Takhzyro® (lanadelumab-flyo)

  • A Cost Model Comparing Long-Term Prophylaxis Options for Hereditary Angioedema: Lanadelumab and Berotralstat
  • Characteristics of Patients With Hereditary Angioedema on Long-Term Prophylaxis With Lanadelumab Who Did and Did Not Down-Titrate Lanadelumab During 18 Months of Treatment Persistence

ID Week, 2023

October 11 - 15, 2023

The joint annual meeting of leading global societies dedicated to infectious disease research and advances.

American College of Chest Physicians (CHEST), 2023

October 8 - 11, 2023

Annual meeting offering the most up-to-date education in pulmonary, sleep, and critical care medicine through simulation sessions and original research presentations with clinical relevance to practitioners.

Immunoglobulin National Society (IgNS), 2023

October 5 - 8, 2023

National conference of IgNS bringing together professionals and practitioners from all disciplines and clinical specialties to advance Ig therapy practice, while providing networking and comprehensive education opportunities.

Aspen Allergy Conference (AAC), 2023

July 30 - August 3, 2023

Annual conference that invites state-of-the-art speakers from around the world to discuss basic science and clinical topics on allergy, asthma, and immunology.

European Academy of Allergy & Clinical Immunology (EAACI), 2023

June 9 - 11, 2023

The flagship meeting of the EAACI and the world’s largest congress specializing in the field of allergy and clinical immunology.

Takhzyro® (lanadelumab-flyo)

  • Clinical Outcomes and Quality of Life in Patients With HAE Receiving Lanadelumab Long-Term Prophylaxis: Interim Analysis of 3-Year Real-World Data

American Society of Clinical Oncology (ASCO), 2023

June 2 - 6, 2023

Annual meeting providing a forum for oncology professionals, patient advocates, and industry representatives to learn about and discuss the important issues in cancer care across a variety of disease sites, treatment approaches, and disciplines.

Videos

 

Watch videos focused on Hereditary Angioedema (HAE).

HAE Mechanism of Disease

Learn about Hereditary Angioedema (HAE), including the prevalence of the three types of HAE and their causes.

Additional Resources

 

Find materials to help foster a deeper understanding of Hereditary Angioedema (HAE).

Hereditary Angioedema Disease Awareness Fact Sheet

An overview of HAE epidemiology, pathophysiology, signs and symptoms, diagnosis, and burden of disease.

Hereditary Angioedema Diagnosis Fact Sheet

An overview of HAE misdiagnosis, causes of angioedema, types of HAE, and diagnosing/testing for HAE.

Hereditary Angioedema nC1-INH Fact Sheet

An overview of HAE with nC1-INH including prevalence, pathophysiology, diagnosis, and subtypes.

Hereditary Angioedema in Pediatric Patients Fact Sheet

An overview of HAE in pediatric patients including diagnosis, clinical presentation, and disease burden.