Hereditary Angioedema

Not actual patients.

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

  1. Lumry WR. Am J Manag Care 2013;19(Suppl 7):S111-S118.
  2. Lumry WR. Am J Manag Care 2013;19(Suppl 7):S103-S110.
  3. Aygören-Pürsün E, Mageri M, Maetzel A, et al. Orphanet J Rare Dis. 2018;13(1):73.
  4. Farkas H, Martinez-Saguer I, Bork K, et al. Allergy 2017;72(2):300-313.
  5. Christiansen SC, Davis DK, Castaldo AJ, et al. Clin Pediatr. 2016;55(10):935-942.
  6. Schöffl C, Wiednig M, Koch L, et al. J Dtsch Dermatol Ges. 2019;17(4):416-423.
  7. Banerji A. Ann Allergy Asthma Immunol. 2013;111(5):329-336.
  8. Reshef A, Kidon M, Leibovich I. Clinic Rev Allerg Immunol. 2016;51(2):121-139.
  9. Kaplan AP and Joseph K. Ann Allergy Asthma Immunol. 2010;104(3):193-204.
  10. Zuraw BL, Christiansen SC. Clinic Rev Allerg Immunol. 2016;51(2):216-229.
  11. Hofman ZL, Relan A, Zeerleder S, et al. J Allergy Clin Immunol. 2016;138(2):359-366.
  12. Lumry WR, Li HH, Levy RJ, et al. Ann Allergy Asthma Immunol. 2011;107(6):529-537.
  13. Liu S, Xu Y, Liu Y, et al. Eur J Dermatol. 2019;29(1):14-20.
  14. Zuraw BL. N Engl J Med. 2008;359(10):1027-1036.
  15. Zuraw BL. J Allergy Clin Immunol. 2018;141(3):884-885.
  16. Zanichelli A, Longhurst HJ, Maurer M, et al. Ann Allergy Asthma Immunol. 2016;117(4):394-398.
  17. Longhurst HJ and Bork K. Br J Hosp Med. 2019;80(7):391-398.
  18. Bork K, Hardt J, Witzke G. J Allergy Clin Immunol. 2012;130(3):692-697.
  19. Maurer M, Mageri M, Ansotegui I, et al. Allergy. 2018;73(8):1575-1596.
  20. Aygören-Pürsün E, Bygum A, Beusterien K, et al. Orphanet J Rare Dis. 2014;9:99.
  21. Lumry WR, Castaldo AJ, Vernon MK, et al. Allergy Asthma Proc. 2010;31(5):407-414.
  22. Savarese L, Bova M, De Falco R, et al. Orphanet J Rare Dis. 2018;13(1):115.
  23. Caballero T, Aygoren-Pursun E, Bygum A, et al. Allergy Asthma Proc. 2014;35(1):47-53.
  24. Tunçel K, Gokmen NM, Demir E, et al. Int J Psychiatry Med. 2019 [Epub ahead of print].
  25. Nzeako UC, Frigas E, Tremaine WJ. Arch Intern Med. 2001;161(20):2417-2429.
  26. Farkas H. Allergy Asthma Clin Immunol. 2010;6(1):18.
  27. MacGinnitie AJ. Pediatr Allergy Immunol. 2014;25(5):420-427.
  28. Steiner UC, Kolliker L, Weber-Chrysochoou C, et al. Orphanet J Rare Dis. 2018;13(1):90.

Medication Resources

Cinryze®

[C1 Esterase Inhibitor (Human)]

Firazyr®

(icatibant injection)

Kalbitor®

(ecallantide)

Takhzyro®

(lanadelumab-flyo)

Upcoming & Past Conferences in Allergy & Immunology

  • Upcoming

  • Past

Western Society of Allergy, Asthma and Immunology (WSAAI), 2025

February 9 - 13, 2025 | Link to Event

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

Annual Meeting American Academy of Allergy Asthma and Immunology (AAAAI), 2025

February 28 - March 3, 2025 | Link to Event

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

American Academy of Neurology (AAN), 2025

April 5 - 9, 2025 | Link to Event

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

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

October 24 - 28, 2024

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

Immunoglobulin National Society (IgNS), 2024

October 17 - 20, 2024

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.

The European Society for Immunodeficiencies (ESID), 2024

October 16 - 19, 2024

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.

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

October 15 - 18, 2024

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

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

October 14 - 17, 2024

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 College of Chest Physicians (CHEST), 2024

October 6 - 9, 2024

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.

Neuromuscular Study Group (NMSG), 2024

September 20 - 22, 2024

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.

  • A Quantitative Study on the Patient Journey and Experience in Patients with CIDP and MMN
  • Plasma Proteomics and Autoantibody Screening: a Tool for Patient Stratification and Monitoring CIDP Treatment Responses

Consortium of Independent Immunology Clinics (CIIC), 2024

September 13 - 14, 2024

Semi-annual conference of key opinion leaders in the Allergy, Asthma, and Immunology space.

Takhzyro® (lanadelumab-flyo)

  • Understanding Treatment Switching Patterns and Continuation Rates for Patients With Hereditary Angioedema Receiving Lanadelumab: Analysis of Real-World Data

Bradykinin Symposium

September 5 - 6, 2024

International experts in the field of bradykinin discuss the genetic, molecular, and cellular drivers of angioedema.

  • Comorbid Conditions in Patients With Hereditary Angioedema: Icatibant Outcome Survey

American Association of Nurse Practitioners (AANP), 2024

June 25 - 30, 2024

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

Peripheral Nerve Society (PNS), 2024

June 22 - 25, 2024

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

  • A Quantitative Study on The Patient Journey and Experience in Patients with CIDP and MMN

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

  • Hyaluronidase-Facilitated Subcutaneous Immunoglobulin 10% For Chronic Inflammatory Demyelinating Polyradiculoneuropathy: Final Results from a Long-Term Safety and Tolerability Study

Association of Pulmonary Advanced Practice Providers (APAPP), 2024

June 20 - 22, 2024

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.

  • Overcoming Racial and Ethnic Biases in The Diagnosis of Patients with Alpha-1 Antitrypsin Deficiency in The United States Using a Machine-Learning Model

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

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.

Consider Hereditary Angioedema in the Differential Diagnosis for Unexplained Recurring Abdominal Pain 

Learn about the delayed and misdiagnosis of Hereditary Angioedema (HAE) in patients presenting with abdominal symptoms.

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.