Frequently Asked Questions2022-02-21T16:18:53+01:00

FREQUENTLY ASKED QUESTIONS

On this page you can find the answers to most of your HAE related questions, provided as a FAQ (frequently asked questions). If your question is not answered please fill in the box on the right hand side and send us your question.

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What is Hereditary Angioedema (HAE)?2022-01-20T13:40:22+01:00

Hereditary Angioedema (HAE) is a rare genetic disorder characterized by recurrent, painful episodes of swelling of the skin or mucous membranes. This results in swelling of various body parts, including the hands, feet, face, abdomen (gastrointestinal tract), and throat (airway).

Swelling attacks affecting the larynx or tongue are particularly dangerous and can cause death by suffocation (choking) if untreated.

Hereditary Angioedema (HAE) is a rare genetic disorder characterized by recurrent, painful episodes of swelling of the skin or mucous membranes. [Bork 2021] This results in swelling of various body parts, including the hands, feet, face, abdomen (gastrointestinal tract), and throat (airway). [Bork 2021]

Swelling attacks affecting the larynx or tongue are particularly dangerous and can cause death by suffocation (choking) if untreated.

Bork 2021: Bork K, Anderson JT, Caballero T et al. Assessment and management of disease burden and quality of life in patients with hereditary angioedema: a consensus report. Allergy Asthma Clin Immunol. 2021 Apr 19;17(1):40. doi: 10.1186/s13223-021-00537-2. PMID: 33875020; PMCID: PMC8056543.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8056543/ [Free full text]

How many people are affected by HAE?2022-01-18T11:36:24+01:00

Exact figures regarding the frequency that HAE occurs (incidence) are not available. It is estimated that about 1 in 10,000 to 1 in 50,000 people are affected worldwide.

Exact figures regarding the frequency that HAE occurs (incidence) are not available. It is estimated that about 1 in 10,000 to 1 in 50,000 people are affected worldwide. [Agostoni 2004][ [Bowen 2008]

Agostoni 2004: Agostoni A, Aygören-Pürsün E, Binkley KE et al. Hereditary and acquired angioedema: problems and progress: proceedings of the third C1 esterase inhibitor deficiency workshop and beyond. J Allergy Clin Immunol. 2004 Sep;114(3 Suppl):S51-131. doi: 10.1016/j.jaci.2004.06.047. PMID: 15356535; PMCID: PMC7119155.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7119155/ [Free full text]

Bowen 2008: Bowen T, Cicardi M, Bork K, et al. Hereditary angiodema: a current state-of-the-art review, VII: Canadian Hungarian 2007 International Consensus Algorithm for the Diagnosis, Therapy, and Management of Hereditary Angioedema. Ann Allergy Asthma Immunol. 2008 Jan;100(1 Suppl 2):S30-40. doi: 10.1016/s1081-1206(10)60584-4. PMID: 18220150.
https://pubmed.ncbi.nlm.nih.gov/18220150/ [Abstract]

At what age do HAE attacks start?2022-03-04T11:24:41+01:00

The age of HAE onset varies. Most people with HAE first experience symptoms in childhood.

Studies suggest that:

  • 50% of people with HAE first experience an attack before age 10
  • Most people have experienced their first attack before 18 years of age
  • Around 10% of people with HAE report initial symptoms between age 18-25
  • HAE attacks have been reported in children as early as one (1) year of age

HAE attacks are generally infrequent in young children, and symptoms are usually mild. The frequency and severity of HAE attacks typically increase during puberty and adolescence.

Without treatment, people with HAE continue to experience attacks throughout their lives.

HAE can be successfully managed with effective preventative (prophylaxis) and on-demand (acute) treatment. When people with HAE can access modern therapies to manage their HAE, their quality of life improves.

>> Read more about how HAE can be treated

The age of HAE onset varies. Most people with HAE first experience symptoms in childhood. [Zuraw 2010]

Studies suggest that:

  • 50% of people with HAE first experience an attack before age 10 [Zuraw 2010]
  • Most people have experienced their first attack before 18 years of age [Banerji 2015]
  • Around 10% of people with HAE report initial symptoms between age 18-25 [Banerji 2015]
  • HAE attacks have been reported in children as early as one (1) year of age [Zuraw 2010]

HAE attacks are generally infrequent in young children, and symptoms are usually mild. [MacGinnitie 2014] The frequency and severity of HAE attacks typically increase during puberty and adolescence. [MacGinnitie 2014]

Without treatment, people with HAE continue to experience attacks throughout their lives.

HAE can be successfully managed with effective preventative (prophylaxis) and on-demand (acute) treatment. When people with HAE can access modern therapies to manage their HAE, their quality of life improves. [Castaldo 2020]

Zuraw 2010: Zuraw BL. The pathophysiology of hereditary angioedema. World Allergy Organ J. 2010 Sep;3(9 Suppl):S25-8. doi: 10.1097/WOX.0b013e3181f3f21c. PMID: 23282866; PMCID: PMC3666152.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3666152/ [Free full text]

Banerji 2015: Banerji A, Busse P, Christiansen SC et al. Current state of hereditary angioedema management: a patient survey. Allergy Asthma Proc. 2015 May-Jun;36(3):213-7. doi: 10.2500/aap.2015.36.3824. PMID: 25976438; PMCID: PMC4405601.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4405601/ [Free full text]

MacGinnitie 2014: MacGinnitie AJ. Pediatric hereditary angioedema. Pediatr Allergy Immunol. 2014 Aug;25(5):420-7. doi: 10.1111/pai.12168. Epub 2013 Dec 9. PMID: 24313851; PMCID: PMC4282351.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4282351/ [Free full text]

Castaldo 2020: Castaldo AJ, Jervelund C, Corcoran D et al. Assessing the cost and quality-of-life impact of on-demand-only medications for adults with hereditary angioedema. Allergy Asthma Proc. 2021 Mar 13;42(2):108-117. doi: 10.2500/aap.2021.42.200127. Epub 2021 Feb 13. PMID: 33581742; PMCID: PMC8133018.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8133018/ [Free full text]

What are the symptoms of HAE?2022-01-20T13:38:12+01:00

People with HAE experience recurrent, painful episodes of swelling of the skin or mucous membranes. This results in swelling of various body parts, including the hands, feet, face, abdomen (gastrointestinal tract), and throat (airway).

Although skin swelling is almost never associated with itching, people with HAE report a “tightness” sensation at the site where the swelling occurs, which can be unpleasant. Facial swelling can be disfiguring.

Swelling in the abdomen (intestinal wall) can result in excruciating abdominal pain, nausea, vomiting, and/or diarrhea. These symptoms are distinguishing features of HAE with C1-inhibitor deficiency as recurrent severe abdominal pain is rarely seen in allergic (histaminergic) angioedema.

Swelling in the throat is the most dangerous aspect of HAE because the airway can be closed and, without treatment, can cause death by choking (suffocation).

People with HAE experience recurrent, painful episodes of swelling of the skin or mucous membranes. [Bork 2021] This results in swelling of various body parts, including the hands, feet, face, abdomen (gastrointestinal tract), and throat (airway). [Bork 2021]

Although skin swelling is almost never associated with itching, [Agostoni 2004] people with HAE report a “tightness” sensation at the site where the swelling occurs, which can be unpleasant. [Agostoni 2004] Facial swelling can be disfiguring.

Swelling in the abdomen (intestinal wall) can result in excruciating abdominal pain, nausea, vomiting, and/or diarrhea. [Agostoni 2004] These symptoms are distinguishing features of HAE with C1-inhibitor deficiency as recurrent severe abdominal pain is rarely seen in allergic (histaminergic) angioedema. [Mumneh 2021]

Swelling in the throat is the most dangerous aspect of HAE because the airway can be closed and, without treatment, can cause death by choking (suffocation).

Bork 2021: Bork K, Anderson JT, Caballero T et al. Assessment and management of disease burden and quality of life in patients with hereditary angioedema: a consensus report. Allergy Asthma Clin Immunol. 2021 Apr 19;17(1):40. doi: 10.1186/s13223-021-00537-2. PMID: 33875020; PMCID: PMC8056543.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8056543/ [Free full text]

Agostoni 2004: Agostoni A, Aygören-Pürsün E, Binkley KE et al. Hereditary and acquired angioedema: problems and progress: proceedings of the third C1 esterase inhibitor deficiency workshop and beyond. J Allergy Clin Immunol. 2004 Sep;114(3 Suppl):S51-131. doi: 10.1016/j.jaci.2004.06.047. PMID: 15356535; PMCID: PMC7119155.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7119155/ [Free full text]

Mumneh N, Tick M, Borum M. Angioedema with severe acute abdominal pain: Think of hereditary angioedema. Clin Res Hepatol Gastroenterol. 2021 Jul;45(4):101702. doi: 10.1016/j.clinre.2021.101702. Epub 2021 Apr 14. PMID: 33864899.
https://www.sciencedirect.com/science/article/pii/S2210740121000814 [Free full text]

How often do swelling attacks of HAE occur?2022-01-18T11:46:47+01:00

The frequency of HAE attacks is highly variable between people. It may vary in the same individual during different stages of their life. Women seem to be more severely affected than men and have more frequent attacks than men. Without effective treatment, people with HAE experience attacks on average every two (2) weeks, with a frequency ranging from rarely to every three (3) days.

People with HAE experience attacks of swelling that affect various body parts. Swelling attacks occur most commonly in the skin (for example, hands, feet, face), abdomen (gastrointestinal tract), and throat (airway). Swelling in the throat is the most dangerous aspect of HAE because the airway can be closed and cause death by choking (suffocation).

Without treatment, HAE attack symptoms worsen over the first 12-36 hours and then subside; it can take between two to five (2-5) days for an attack to subside completely. Some people experience HAE attacks that last over a week.

People with HAE experience a significant disease burden and reduced quality of life. Due to pain and other debilitating symptoms of attacks, HAE can impact an individual’s ability to carry out daily activities like attending work or school or participating in leisure or social activities. People with HAE experience higher levels of depression and anxiety due to the unpredictable nature of attacks, the potential for suffocation from a throat attack, and the possibility of passing the disease on to future generations.

The frequency of HAE attacks is highly variable between people. [Bork 2021] It may vary in the same individual during different stages of their life. [Agostoni 2004] Women seem to be more severely affected than men and have more frequent attacks than men. [Bork 2006] Without effective treatment, people with HAE experience attacks on average every two (2) weeks, with a frequency ranging from rarely to every three (3) days. [Bork 2021]

People with HAE experience attacks of swelling that affect various body parts. Swelling attacks occur most commonly in the skin (for example, hands, feet, face), abdomen (gastrointestinal tract), and throat (airway). [Cicardi 2012] [Bork 2021] Swelling in the throat is the most dangerous aspect of HAE because the airway can be closed and cause death by choking (suffocation).

Without treatment, HAE attack symptoms worsen over the first 12-36 hours and then subside; [Bork 2021] it can take between two to five (2-5) days for an attack to subside completely. [Bork 2021] Some people experience HAE attacks that last over a week. [Bork 2006]

People with HAE experience a significant disease burden and reduced quality of life. [Bork 2021] Due to pain and other debilitating symptoms of attacks, HAE can impact an individual’s ability to carry out daily activities like attending work or school or participating in leisure or social activities. [Bork 2021] People with HAE experience higher levels of depression and anxiety due to the unpredictable nature of attacks, the potential for suffocation from a throat attack, and the possibility of passing the disease on to future generations. [Bork 2021]

Bork 2021: Bork K, Anderson JT, Caballero T et al. Assessment and management of disease burden and quality of life in patients with hereditary angioedema: a consensus report. Allergy Asthma Clin Immunol. 2021 Apr 19;17(1):40. doi: 10.1186/s13223-021-00537-2. PMID: 33875020; PMCID: PMC8056543.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8056543/ [Free full text]

Agostoni 2004: Agostoni A, Aygören-Pürsün E, Binkley KE et al. Hereditary and acquired angioedema: problems and progress: proceedings of the third C1 esterase inhibitor deficiency workshop and beyond. J Allergy Clin Immunol. 2004 Sep;114(3 Suppl):S51-131. doi: 10.1016/j.jaci.2004.06.047. PMID: 15356535; PMCID: PMC7119155.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7119155/ [Free full text]

Bork 2006: Bork K, Meng G, Staubach P, Hardt J. Hereditary angioedema: new findings concerning symptoms, affected organs, and course. Am J Med 2006; 119: 267-74.
https://www.amjmed.com/article/S0002-9343(05)01081-8/fulltext [Free full text]

Cicardi 2012: Cicardi M, Bork K, Caballero T et al; HAWK (Hereditary Angioedema International Working Group). Evidence-based recommendations for the therapeutic management of angioedema owing to hereditary C1 inhibitor deficiency: consensus report of an International Working Group. Allergy. 2012 Feb;67(2):147-57. doi: 10.1111/j.1398-9995.2011.02751.x. Epub 2011 Nov 30. PMID: 22126399.
https://onlinelibrary.wiley.com/doi/full/10.1111/j.1398-9995.2011.02751.x [Free full text]

How long does an HAE swelling attack last?2022-01-18T11:44:50+01:00

Without treatment, HAE attack symptoms worsen over the first 12-36 hours and then subside; it can take between two to five (2-5) days for an attack to subside completely. Some people experience HAE attacks that last over a week.

Although HAE episodes are self-limiting, the unpredictable nature of attacks places considerable strain on the person living with HAE, often restricting the ability to lead a normal life and reducing the quality of life.

Because a typical attack lasts several days before it subsides, without treatment, people with HAE may be debilitated by symptoms for 100 days or more than three (3) months a year. The death rate for untreated people with HAE with airway angioedema is estimated to be around 30%.

Without treatment, HAE attack symptoms worsen over the first 12-36 hours and then subside; [Bork 2021] it can take between two to five (2-5) days for an attack to subside completely. [Bork 2021] Some people experience HAE attacks that last over a week. [Bork 2006]

Although HAE episodes are self-limiting, the unpredictable nature of attacks places considerable strain on the person living with HAE, often restricting the ability to lead a normal life and reducing the quality of life. [Bork 2021]

Because a typical attack lasts several days before it subsides, without treatment, people with HAE may be debilitated by symptoms for 100 days or more than three (3) months a year. [Cicardi 1996] The death rate for untreated people with HAE with airway angioedema is estimated to be around 30%. [Frank 1976] [Cicardi 1996] [Bork 2012]

Bork 2021: Bork K, Anderson JT, Caballero T et al. Assessment and management of disease burden and quality of life in patients with hereditary angioedema: a consensus report. Allergy Asthma Clin Immunol. 2021 Apr 19;17(1):40. doi: 10.1186/s13223-021-00537-2. PMID: 33875020; PMCID: PMC8056543.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8056543/ [Free full text]

Bork 2006: Bork K, Meng G, Staubach P, Hardt J. Hereditary angioedema: new findings concerning symptoms, affected organs, and course. Am J Med. 2006 Mar;119(3):267-74. doi: 10.1016/j.amjmed.2005.09.064. PMID: 16490473.
https://www.amjmed.com/article/S0002-9343(05)01081-8/fulltext [Free full text]

Cicardi 1996: Cicardi M, Agostoni A. Hereditary angioedema. N Engl J Med. 1996 Jun 20;334(25):1666-7. doi: 10.1056/NEJM199606203342510. PMID: 8628365.
https://pubmed.ncbi.nlm.nih.gov/8628365/ [Paywall for full text link]

Frank 1976: Frank MM, Gelfand JA, Atkinson JP. Hereditary angioedema: the clinical syndrome and its management. Ann Intern Med. 1976 May;84(5):580-93. doi: 10.7326/0003-4819-84-5-580. PMID: 1275365.
https://www.acpjournals.org/doi/pdf/10.7326/0003-4819-84-5-580 [Paywall for full text]

Bork 2012: Bork K, Hardt J, Witzke G. Fatal laryngeal attacks and mortality in hereditary angioedema due to C1-INH deficiency. J Allergy Clin Immunol. 2012 Sep;130(3):692-7. doi: 10.1016/j.jaci.2012.05.055. Epub 2012 Jul 28. PMID: 22841766.
https://www.jacionline.org/article/S0091-6749(12)01008-1/fulltext [Free full text]

Why can certain swelling attacks of HAE be life-threatening?2022-01-18T11:47:51+01:00

HAE attacks are painful and debilitating, they have a negative effect on the quality of life, and in the case of a throat attack, they can be life-threatening because the airway can be closed and cause death by choking (suffocation).

Because a typical attack lasts several days before it subsides, without treatment, people with HAE may be debilitated by symptoms for 100 days or more than three (3) months a year. The death rate for untreated people with HAE with airway angioedema is estimated to be around 30%.

HAE attacks are painful and debilitating, they have a negative effect on the quality of life, and in the case of a throat attack, they can be life-threatening [Bork 2021] because the airway can be closed and cause death by choking (suffocation).

Because a typical attack lasts several days before it subsides, without treatment, people with HAE may be debilitated by symptoms for 100 days or more than three (3) months a year. [Cicardi 1996] The death rate for untreated people with HAE with airway angioedema is estimated to be around 30%. [Frank 1976] [Cicardi 1996] [Bork 2012]

Cicardi 1996: Cicardi M, Agostoni A. Hereditary angioedema. N Engl J Med. 1996 Jun 20;334(25):1666-7. doi: 10.1056/NEJM199606203342510. PMID: 8628365.
https://pubmed.ncbi.nlm.nih.gov/8628365/ [Paywall for full text link]

Frank 1976: Frank MM, Gelfand JA, Atkinson JP. Hereditary angioedema: the clinical syndrome and its management. Ann Intern Med. 1976 May;84(5):580-93. doi: 10.7326/0003-4819-84-5-580. PMID: 1275365.
https://www.acpjournals.org/doi/pdf/10.7326/0003-4819-84-5-580 [Paywall for full text]

Bork 2012: Bork K, Hardt J, Witzke G. Fatal laryngeal attacks and mortality in hereditary angioedema due to C1-INH deficiency. J Allergy Clin Immunol. 2012 Sep;130(3):692-7. doi: 10.1016/j.jaci.2012.05.055. Epub 2012 Jul 28. PMID: 22841766.
https://www.jacionline.org/article/S0091-6749(12)01008-1/fulltext [Free full text]

What causes HAE?2022-02-21T15:57:08+01:00

You cannot ‘catch’ HAE – it is usually inherited from a parent.

Most people with HAE have a defect in the gene that controls an important protein called C1-inhibitor that is found in plasma – the fluid part of blood. Because of this genetic defect, the C1-inhibitor in people with HAE does not do its job, which is to control complex biological interactions that occur in plasma. Left uncontrolled, these interactions produce a substance called bradykinin that causes swelling by allowing plasma fluids to leak into the soft tissue of various body parts.

You cannot ‘catch’ HAE – it is usually inherited from a parent.

Most people with HAE have a defect in the gene that controls an important protein called C1-inhibitor that is found in plasma – the fluid part of blood. Because of this genetic defect, the C1-inhibitor in people with HAE does not do its job, which is to control complex biological interactions that occur in plasma. Left uncontrolled, these interactions produce a substance called bradykinin that causes swelling by allowing plasma fluids to leak into the soft tissue of various body parts. [Zuraw 2008]

Zuraw 2008: Zuraw BL. Clinical practice. Hereditary angioedema. N Engl J Med. 2008 Sep 4;359(10):1027-36. doi: 10.1056/NEJMcp0803977. PMID: 18768946.

https://pubmed.ncbi.nlm.nih.gov/18768946/  [Paywall for full text]

What triggers an HAE attack?2022-02-21T15:03:00+01:00

Most HAE attacks occur spontaneously with no apparent reason or trigger. However, in some cases, a cause can be identified, e.g.:

  • Infections, minor injuries, and mechanical stimuli such as pressure can induce an attack.
  • Dental procedures or surgery to remove the tonsils are particularly critical, as they can cause swelling in the airway or throat (larynx).
  • Emotional and mental stress can also trigger an attack.
  • Hormonal factors are another known cause of HAE attacks. For example, the frequency of episodes can be higher in women taking oral contraceptives containing estrogen, products for menopausal complaints, or who have their menstruation.
  • People with HAE have also described other triggers such as exposure to cold, routine activities that can cause mechanical trauma such as gardening and prolonged sitting or standing.

A class of blood pressure-lowering drugs known as angiotensin-converting enzyme (ACE) inhibitors is known to increase the frequency and severity of HAE attacks. As a result, they are often contraindicated in HAE patients. HAE patients should avoid taking this type of medication.

Most HAE attacks occur spontaneously with no apparent reason or trigger. However, in some cases, a cause can be identified, e.g.:

  • Infections, minor injuries, and mechanical stimuli such as pressure can induce an attack. [Agostoni 2004] [Bygum 2019]
  • Dental procedures or surgery to remove the tonsils are particularly critical, as they can cause swelling in the airway or throat (larynx). [Agostoni 2004] [Busse 2020] [Bygum 2019]
  • Emotional and mental stress can also trigger an attack. [Agostoni 2004] [Busse 2020] [Bygum 2019]
  • Hormonal factors are another known cause of HAE attacks. For example, the frequency of episodes can be higher in women taking oral contraceptives containing estrogen, products for menopausal complaints, or who have their menstruation. [Agostoni 2004] [Busse 2020]
  • People with HAE have also described other triggers such as exposure to cold, routine activities that can cause mechanical trauma such as gardening and prolonged sitting or standing. [Agostoni 2004] [Bygum 2019]

A class of blood pressure-lowering drugs known as angiotensin-converting enzyme (ACE) inhibitors is known to increase the frequency and severity of HAE attacks. [Agostoni 2004] As a result, they are often contraindicated in HAE patients. [BNF 2021] HAE patients should avoid taking this type of medication.

Agostoni 2004: Agostoni A, Aygören-Pürsün E, Binkley KE et al. Hereditary and acquired angioedema: problems and progress: proceedings of the third C1 esterase inhibitor deficiency workshop and beyond. J Allergy Clin Immunol. 2004 Sep;114(3 Suppl):S51-131. doi: 10.1016/j.jaci.2004.06.047. PMID: 15356535; PMCID: PMC7119155.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7119155/ [Free full text]

Bygum 2019: Bygum A. Hereditary Angio-Oedema for Dermatologists. Dermatology. 2019;235(4):263-275. doi: 10.1159/000500196. Epub 2019 Jun 5. PMID: 31167185.
https://www.karger.com/Article/Fulltext/500196 [Free full text]

Busse 2020: Busse PJ, Christiansen SC, Riedl MA et al. US HAEA Medical Advisory Board 2020 Guidelines for the Management of Hereditary Angioedema. J Allergy Clin Immunol Pract. 2021 Jan;9(1):132-150.e3. doi: 10.1016/j.jaip.2020.08.046. Epub 2020 Sep 6. PMID: 32898710.
https://www.jaci-inpractice.org/article/S2213-2198(20)30878-3/fulltext [Free full text]

BNF 2021: British National Formulary, November 2021
https://bnf.nice.org.uk/drug-class/angiotensin-converting-enzyme-inhibitors.html Accessed January 2022 [Free full text]

How can you tell if the airway or throat (larynx) is starting to swell?2022-02-21T15:03:52+01:00

As with any HAE attack, an airway or throat swelling can happen spontaneously. Triggers for airway or throat swelling include dental procedures or surgery to remove the tonsils.

The signs of throat swelling include voice changes such as a deeper voice, hoarseness, or losing your voice. Many people with HAE also experience a feeling of a lump or tightness of the throat and difficulty swallowing.

Around half (50%) of people with HAE will experience one throat or airway swelling in their lifetime. The death rate for untreated people with HAE with airway angioedema is estimated to be around 30%.

It is important to recognize that throat swelling is an emergency that always requires immediate medical attention at the first sign of symptoms, even if effective HAE medication is given at home.

As with any HAE attack, an airway or throat swelling can happen spontaneously. Triggers for airway or throat swelling include dental procedures or surgery to remove the tonsils. [Agostoni 2004]

The signs of throat swelling include voice changes such as a deeper voice, hoarseness, or losing your voice. [Bork 2006] Many people with HAE also experience a feeling of a lump or tightness of the throat and difficulty swallowing. [Bork 2006]

Around half (50%) of people with HAE will experience one throat or airway swelling in their lifetime. [Agostoni 2004] The death rate for untreated people with HAE with airway angioedema is estimated to be around 30%. [Frank 1976] [Cicardi 1996] [Bork 2012]

It is important to recognize that throat swelling is an emergency that always requires immediate medical attention at the first sign of symptoms, even if effective HAE medication is given at home.

Agostoni 2004: Agostoni A, Aygören-Pürsün E, Binkley KE et al. Hereditary and acquired angioedema: problems and progress: proceedings of the third C1 esterase inhibitor deficiency workshop and beyond. J Allergy Clin Immunol. 2004 Sep;114(3 Suppl):S51-131. doi: 10.1016/j.jaci.2004.06.047. PMID: 15356535; PMCID: PMC7119155.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7119155/ [Free full text]

Bork 2006: Bork K, Meng G, Staubach P, Hardt J. Hereditary angioedema: new findings concerning symptoms, affected organs, and course. Am J Med. 2006 Mar;119(3):267-74. doi: 10.1016/j.amjmed.2005.09.064. PMID: 16490473.
https://www.amjmed.com/article/S0002-9343(05)01081-8/fulltext [Free full text]

Frank 1976: Frank MM, Gelfand JA, Atkinson JP. Hereditary angioedema: the clinical syndrome and its management. Ann Intern Med. 1976 May;84(5):580-93. doi: 10.7326/0003-4819-84-5-580. PMID: 1275365.
https://www.acpjournals.org/doi/pdf/10.7326/0003-4819-84-5-580 [Paywall for full text]

Cicardi 1996: Cicardi M, Agostoni A. Hereditary angioedema. N Engl J Med. 1996 Jun 20;334(25):1666-7. doi: 10.1056/NEJM199606203342510. PMID: 8628365.
https://pubmed.ncbi.nlm.nih.gov/8628365/ [Paywall for full text link]

Bork 2012: Bork K, Hardt J, Witzke G. Fatal laryngeal attacks and mortality in hereditary angioedema due to C1-INH deficiency. J Allergy Clin Immunol. 2012 Sep;130(3):692-7. doi: 10.1016/j.jaci.2012.05.055. Epub 2012 Jul 28. PMID: 22841766.
https://www.jacionline.org/article/S0091-6749(12)01008-1/fulltext [Free full text]

How is HAE diagnosed?2022-02-21T15:33:28+01:00

Most cases of angioedema or swelling are not HAE or C1-inhibitory deficiency.

Laboratory analysis of blood samples, or genetic samples, is required to establish a diagnosis of HAE. There are three specific blood tests used to confirm hereditary angioedema Type I or Type II:

  • C1-inhibitor quantitative (antigenic)
  • C1-inhibitor functional
  • C4

For people with HAE with normal C1-inhibitor, the C1-inhibitor levels and function are normal. Researchers have discovered that in some instances, HAE with normal C1-inhibitor is associated with mutations in factor XII (F12), plasminogen (PLG), angiopoietin (ANGPT1), kininogen (KNG1), or myoferlin (MYOF) genes. However, in many cases, the genetic cause of HAE with normal C1-inhibitor is unknown. Some commercial laboratories can test for Factor XII mutations, but there are no routine laboratory tests to confirm a diagnosis of HAE with normal C-1 inhibitor.

In general, a diagnosis of HAE should be suspected when a patient presents with a history of recurrent swelling. Additional signs and symptoms that support a diagnosis of HAE include:

  • a family history that includes swelling attacks or cases of HAE
  • the onset of symptoms in childhood
  • recurrent and painful abdominal symptoms
  • swelling of the throat or airway
  • the swelling doesn’t respond to treatment with antihistamines, glucocorticoids, or epinephrine
  • signs or symptoms that indicate a swelling attack will happen (prodromes)
  • the absence of wheals (urticaria or a rash) when the swelling occurs

Most cases of angioedema or swelling are not HAE or C1-inhibitory deficiency.

Laboratory analysis of blood samples, or genetic samples, is required to establish a diagnosis of HAE. There are three specific blood tests used to confirm hereditary angioedema Type I or Type II [Maurer 2018]:

  • C1-inhibitor quantitative (antigenic)
  • C1-inhibitor functional
  • C4

For people with HAE with normal C1-inhibitor, the C1-inhibitor levels and function are normal. Researchers have discovered that in some instances, HAE with normal C1-inhibitor is associated with mutations in factor XII (F12), plasminogen (PLG), angiopoietin (ANGPT1), kininogen (KNG1), or myoferlin (MYOF) genes. However, in many cases, the genetic cause of HAE with normal C1-inhibitor is unknown. [Bork 2021] Some commercial laboratories can test for Factor XII mutations, but there are no routine laboratory tests to confirm a diagnosis of HAE with normal C-1 inhibitor. [Magerl 2017]

In general, a diagnosis of HAE should be suspected when a patient presents with a history of recurrent swelling. [Maurer 2022] Additional signs and symptoms that support a diagnosis of HAE include [Maurer 2022]:

  • a family history that includes swelling attacks or cases of HAE
  • the onset of symptoms in childhood
  • recurrent and painful abdominal symptoms
  • swelling of the throat or airway
  • the swelling doesn’t respond to treatment with antihistamines, glucocorticoids, or epinephrine
  • signs or symptoms that indicate a swelling attack will happen (prodromes)
  • the absence of wheals (urticaria or a rash) when the swelling occurs

Maurer 2022: Maurer M, Magerl M, Betschel S et al. The international WAO/EAACI guideline for the management of hereditary angioedema-The 2021 revision and update. Allergy. 2022 Jan 10. doi: 10.1111/all.15214. Epub ahead of print. PMID: 35006617.
https://onlinelibrary.wiley.com/doi/10.1111/all.15214 [Free full text]

Bork 2021: Bork K, Anderson JT, Caballero T et al. Assessment and management of disease burden and quality of life in patients with hereditary angioedema: a consensus report. Allergy Asthma Clin Immunol. 2021 Apr 19;17(1):40. doi: 10.1186/s13223-021-00537-2. PMID: 33875020; PMCID: PMC8056543.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8056543/ [Free full text]

Magerl 2017: Magerl M et al. Hereditary Angioedema with Normal C1 Inhibitor: Update on Evaluation and Treatment. Immunol Allergy Clin North Am. 2017 Aug;37(3):571-584. doi: 10.1016/j.iac.2017.04.004. PMID: 28687110.
https://pubmed.ncbi.nlm.nih.gov/28687110/ [Abstract]

What does HAE mean for a pregnancy and vice versa?2022-02-21T15:35:20+01:00

Women with HAE can have children as HAE does not impair fertility.

Pregnancy can, however, impact the frequency and severity of HAE attacks. As a result, some women may experience more frequent and/or severe HAE attacks. In contrast, others may experience fewer or no HAE attacks while pregnant.

During pregnancy and breastfeeding, treatment with anabolic androgens (or steroids) or tranexamic acid is not recommended.

Most women with HAE experience a healthy delivery of their baby, just like those within the general population. HAE attacks are rare at the time of delivery. There is some indication of an increase in attack frequency in the post-partum period.

As HAE is an inherited condition, each baby born to a parent with HAE has a 50% possibility of inheriting HAE. If you want to get pregnant or are pregnant, your doctor will follow you closely to discuss appropriate management of your HAE with you.

Women with HAE can have children as HAE does not impair fertility. [Banerji 2016]

Pregnancy can, however, impact the frequency and severity of HAE attacks. As a result, some women may experience more frequent and/or severe HAE attacks. In contrast, others may experience fewer or no HAE attacks while pregnant. [Agostoni 2004] [Maurer 2022]

During pregnancy and breastfeeding, treatment with anabolic androgens (or steroids) or tranexamic acid is not recommended. [Busse 2020]

Most women with HAE experience a healthy delivery of their baby, just like those within the general population. HAE attacks are rare at the time of delivery. [Maurer 2022] There is some indication of an increase in attack frequency in the post-partum period. [Banerji 2016]

As HAE is an inherited condition, each baby born to a parent with HAE has a 50% possibility of inheriting HAE. [Agostoni 2004] [Zuraw 2010] If you want to get pregnant or are pregnant, your doctor will follow you closely to discuss appropriate management of your HAE with you.

Banerji 2016: Banerji A, Riedl M. Managing the female patient with hereditary angioedema. Womens Health (Lond). 2016 Jun;12(3):351-61. doi: 10.2217/whe.16.6. Epub 2016 Mar 15. PMID: 26978558; PMCID: PMC5384520.
https://journals.sagepub.com/doi/full/10.2217/whe.16.6 [Free full text]

Agostoni 2004: Agostoni A, Aygören-Pürsün E, Binkley KE et al. Hereditary and acquired angioedema: problems and progress: proceedings of the third C1 esterase inhibitor deficiency workshop and beyond. J Allergy Clin Immunol. 2004 Sep;114(3 Suppl):S51-131. doi: 10.1016/j.jaci.2004.06.047. PMID: 15356535; PMCID: PMC7119155.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7119155/ [Free full text]

Maurer 2022: Maurer M, Magerl M, Betschel S et al. The international WAO/EAACI guideline for the management of hereditary angioedema-The 2021 revision and update. Allergy. 2022 Jan 10. doi: 10.1111/all.15214. Epub ahead of print. PMID: 35006617.
https://onlinelibrary.wiley.com/doi/10.1111/all.15214 [Free full text]

Busse 2020: Busse PJ, Christiansen SC, Riedl MA et al. US HAEA Medical Advisory Board 2020 Guidelines for the Management of Hereditary Angioedema. J Allergy Clin Immunol Pract. 2021 Jan;9(1):132-150.e3. doi: 10.1016/j.jaip.2020.08.046. Epub 2020 Sep 6. PMID: 32898710.
https://www.jaci-inpractice.org/article/S2213-2198(20)30878-3/fulltext [Free full text]

Zuraw 2010: Zuraw BL. The pathophysiology of hereditary angioedema. World Allergy Organ J. 2010 Sep;3(9 Suppl):S25-8. doi: 10.1097/WOX.0b013e3181f3f21c. PMID: 23282866; PMCID: PMC3666152.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3666152/ [Free full text]

Why does it often take more than 8 years to diagnose HAE?2022-01-18T11:52:37+01:00

HAE is a rare and relatively unknown disease, and many doctors aren’t familiar with HAE symptoms. The symptoms are also similar to those of other common illnesses. [Zuraw 2008] This often leads to a wrong diagnosis and consequently the wrong treatment.

Symptoms of HAE that can often be misdiagnosed as an allergic reaction include:

  • Abdominal swelling and pain
  • Face and throat swelling
  • Swelling in general

As a result, it can take more than 8 years [Lumry 2020] to recognize and then diagnose HAE. A simple blood test can confirm an HAE diagnosis.

While the symptoms can often be mistaken for an allergic reaction, HAE attacks do not respond to common allergy treatments, including antihistamines, corticosteroids, or epinephrine.

HAE is a rare and relatively unknown disease, and many doctors aren’t familiar with HAE symptoms. [Bygum 2019] The symptoms are also similar to those of other common illnesses. [Zuraw 2008] This often leads to a wrong diagnosis and consequently the wrong treatment.

Symptoms of HAE that can often be misdiagnosed as an allergic reaction include: [Zuraw 2008]

  • Abdominal swelling and pain
  • Face and throat swelling
  • Swelling in general

As a result, it can take more than 8 years [Lumry 2020] to recognize and then diagnose HAE. A simple blood test can confirm an HAE diagnosis.

While the symptoms can often be mistaken for an allergic reaction, [Zuraw 2008] HAE attacks do not respond to common allergy treatments, including antihistamines, corticosteroids, or epinephrine. [Zuraw 2008] [Agostoni 2004]

Bygum 2019: Bygum A. Hereditary Angio-Oedema for Dermatologists. Dermatology. 2019;235(4):263-275. doi: 10.1159/000500196. Epub 2019 Jun 5. PMID: 31167185.
https://www.karger.com/Article/Fulltext/500196 [Free full text]

Zuraw 2008: Zuraw BL. Clinical practice. Hereditary angioedema. N Engl J Med. 2008 Sep 4;359(10):1027-36. doi: 10.1056/NEJMcp0803977. PMID: 18768946.
https://pubmed.ncbi.nlm.nih.gov/18768946/  [Paywall for full text]

Lumry 2020: Lumry WR, Settipane RA. Hereditary angioedema: Epidemiology and burden of disease. Allergy Asthma Proc. 2020 Nov 1;41(Suppl 1):S08-S13. doi: 10.2500/aap.2020.41.200050. PMID: 33109318.
https://pubmed.ncbi.nlm.nih.gov/33109318/ [Abstract]

Agostoni 2004: Agostoni A, Aygören-Pürsün E, Binkley KE et al. Hereditary and acquired angioedema: problems and progress: proceedings of the third C1 esterase inhibitor deficiency workshop and beyond. J Allergy Clin Immunol. 2004 Sep;114(3 Suppl):S51-131. doi: 10.1016/j.jaci.2004.06.047. PMID: 15356535; PMCID: PMC7119155.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7119155/ [Free full text]

How does HAE affect people’s lives?2022-01-18T12:13:34+01:00

The frequency of HAE attacks is highly variable between people. It may vary in the same individual during different stages of their life.

People with HAE experience a significant disease burden and reduced quality of life. Due to pain and other debilitating symptoms of attacks, HAE can impact an individual’s ability to carry out daily activities like attending work or school or participating in leisure or social activities.

People with HAE experience higher levels of depression and anxiety due to the unpredictable nature of attacks, the potential for choking (suffocation) from a throat attack, and the possibility of passing the disease on to future generations.

HAE can be successfully managed with effective preventative (prophylaxis) and on-demand (acute) treatment. When people with HAE can access modern therapies to manage their HAE, their quality of life improves.

The frequency of HAE attacks is highly variable between people. [Bork 2021] It may vary in the same individual during different stages of their life. [Agostoni 2004]

People with HAE experience a significant disease burden and reduced quality of life. [Bork 2021] Due to pain and other debilitating symptoms of attacks, HAE can impact an individual’s ability to carry out daily activities like attending work or school or participating in leisure or social activities. [Bork 2021]

People with HAE experience higher levels of depression and anxiety due to the unpredictable nature of attacks, the potential for choking (suffocation) from a throat attack, and the possibility of passing the disease on to future generations. [Bork 2021]

HAE can be successfully managed with effective preventative (prophylaxis) and on-demand (acute) treatment. When people with HAE can access modern therapies to manage their HAE, their quality of life improves. [Castaldo 2020]

Bork 2021: Bork K, Anderson JT, Caballero T et al. Assessment and management of disease burden and quality of life in patients with hereditary angioedema: a consensus report. Allergy Asthma Clin Immunol. 2021 Apr 19;17(1):40. doi: 10.1186/s13223-021-00537-2. PMID: 33875020; PMCID: PMC8056543.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8056543/ [Free full text]

Agostoni 2004: Agostoni A, Aygören-Pürsün E, Binkley KE et al. Hereditary and acquired angioedema: problems and progress: proceedings of the third C1 esterase inhibitor deficiency workshop and beyond. J Allergy Clin Immunol. 2004 Sep;114(3 Suppl):S51-131. doi: 10.1016/j.jaci.2004.06.047. PMID: 15356535; PMCID: PMC7119155.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7119155/ [Free full text]

Castaldo 2020: Castaldo AJ, Jervelund C, Corcoran D et al. Assessing the cost and quality-of-life impact of on-demand‐only medications for adults with hereditary angioedema. Allergy Asthma Proc. 2021 Mar 13;42(2):108-117. doi: 10.2500/aap.2021.42.200127. Epub 2021 Feb 13. PMID: 33581742; PMCID: PMC8133018.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8133018/ [Free full text]

What are the types of HAE?2022-02-21T14:58:07+01:00

HAE with C1-inhibitor deficiency is classified into Type I and Type II. There are also people who experience symptoms that are similar to those of Type I and II, but blood tests reveal normal levels and function of C1-inhibitor.

Type I is the most common (approx. 85% of people with HAE) and is characterized by low quantitative levels of C1-inhibitor.

Type II affects approx. 15% of people with HAE. Lab tests show normal or elevated levels of C1-inhibitor, but the protein does not function properly.

HAE is hereditary because the genetic defect that causes HAE is passed on in families: A child has a 50% possibility of inheriting HAE if one of the parents has it. However, the absence of family history does not rule out an HAE diagnosis. Up to 25% of HAE cases result from a spontaneous mutation of the C1-Inhibitor gene at conception.

There are also people who experience symptoms that are similar to Type I and II, but blood tests reveal normal levels and function of C1-Inhibitor. This rarer type of HAE is known as HAE with normal C1-inhibitor. Researchers have discovered that in some instances, HAE with normal C1-inhibitor is associated with mutations in factor XII (F12), plasminogen (PLG), angiopoietin (ANGPT1), kininogen (KNG1), or myoferlin (MYOF) genes. However, in many cases, the genetic cause of HAE with normal C1-INH is unknown. Some commercial laboratories can test for Factor XII mutations, but there are no routine laboratory tests to confirm a diagnosis of HAE with normal C-1 inhibitor.

HAE with C1-inhibitor deficiency is classified into Type I and Type II. There are also people who experience symptoms that are similar to those of Type I and II, but blood tests reveal normal levels and function of C1-Inhibitor. [Zuraw 2008]

Type I is the most common (approx. 85% of people with HAE) and is characterized by low quantitative levels of C1-inhibitor. [Zuraw 2008]

Type II affects approx. 15% of people with HAE. Lab tests show normal or elevated levels of C1-inhibitor, but the protein does not function properly. [Zuraw 2008]

HAE is hereditary because the genetic defect that causes HAE is passed on in families: A child has a 50% possibility of inheriting HAE if one of the parents has it. [Agostoni 2004] [Zuraw 2010] However, the absence of family history does not rule out an HAE diagnosis. [Zuraw 2010] [Maurer 2022] Up to 25% of HAE cases result from a spontaneous mutation of the C1-Inhibitor gene at conception. [Maurer 2022]

There are also people who experience symptoms that are similar to Type I and II, but blood tests reveal normal levels and function of C1-Inhibitor. This rarer type of HAE is known as HAE with normal C1-inhibitor. [Zuraw 2008] Researchers have discovered that in some instances, HAE with normal C1-inhibitor is associated with mutations in factor XII (F12), plasminogen (PLG), angiopoietin (ANGPT1), kininogen (KNG1), or myoferlin (MYOF) genes. However, in many cases, the genetic cause of HAE with normal C1-INH is unknown. [Bork 2021] Some commercial laboratories can test for Factor XII mutations, but there are no routine laboratory tests to confirm a diagnosis of HAE with normal C-1 inhibitor. [Magerl 2017]

Zuraw 2008: Zuraw BL. Clinical practice. Hereditary angioedema. N Engl J Med. 2008 Sep 4;359(10):1027-36. doi: 10.1056/NEJMcp0803977. PMID: 18768946.
https://pubmed.ncbi.nlm.nih.gov/18768946/  [Paywall for full text]

Agostoni 2004: Agostoni A, Aygören-Pürsün E, Binkley KE et al. Hereditary and acquired angioedema: problems and progress: proceedings of the third C1 esterase inhibitor deficiency workshop and beyond. J Allergy Clin Immunol. 2004 Sep;114(3 Suppl):S51-131. doi: 10.1016/j.jaci.2004.06.047. PMID: 15356535; PMCID: PMC7119155.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7119155/ [Free full text]

Zuraw 2010: Zuraw BL. The pathophysiology of hereditary angioedema. World Allergy Organ J. 2010 Sep;3(9 Suppl):S25-8. doi: 10.1097/WOX.0b013e3181f3f21c. PMID: 23282866; PMCID: PMC3666152.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3666152/ [Free full text]

Maurer 2022: Maurer M, Magerl M, Betschel S et al. The international WAO/EAACI guideline for the management of hereditary angioedema-The 2021 revision and update. Allergy. 2022 Jan 10. doi: 10.1111/all.15214. Epub ahead of print. PMID: 35006617.
https://onlinelibrary.wiley.com/doi/10.1111/all.15214 [Free full text]

Bork 2021: Bork K, Anderson JT, Caballero T et al. Assessment and management of disease burden and quality of life in patients with hereditary angioedema: a consensus report. Allergy Asthma Clin Immunol. 2021 Apr 19;17(1):40. doi: 10.1186/s13223-021-00537-2. PMID: 33875020; PMCID: PMC8056543.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8056543/ [Free full text]

Magerl 2017: Magerl M et al. Hereditary Angioedema with Normal C1 Inhibitor: Update on Evaluation and Treatment. Immunol Allergy Clin North Am. 2017 Aug;37(3):571-584. doi: 10.1016/j.iac.2017.04.004. PMID: 28687110.
https://pubmed.ncbi.nlm.nih.gov/28687110/ [Abstract]

What treatment strategies are available for HAE?2022-02-21T15:53:00+01:00

There are effective treatments that help reduce the frequency and severity of swellings and relieve symptoms. Sadly, and similar to many other diseases, there is no cure for HAE.

The goals of HAE treatment are to achieve complete control of the disease and to normalize patients’ lives. Research is ongoing to develop more and more effective medications for HAE. With the effective modern medication available today for HAE, some people with HAE report that they can live life effectively free from swellings.

Current HAE treatment strategies focus on medications to [Maurer 2022]:

  • Provide rapid relief during attacks (on-demand or acute treatment)
  • Prevent symptoms in people with HAE who experience a high frequency of attacks (long-term prophylaxis)
  • Prevent symptoms in people with HAE who undergo dental or surgical procedures, which may trigger an attack (preprocedural or short-term prophylaxis).

All people with HAE should work with their physician to develop an individualized HAE management plan which includes a treatment action plan.

While the symptoms can often be mistaken for an allergic reaction, HAE attacks do not respond to common allergy treatments, including antihistamines, corticosteroids, or epinephrine.

About medicine classes and names

Medicines with certain similarities can be grouped into drug classes. The similarities could be due to the chemical structure of the medicine, their mode of action, or that they are used to treat the same disease.

Every medicine has an approved generic name. This is the name of the active ingredient in that particular medicine. As several companies may make the same generic medicine, each company will give their product a brand or trade name.

An example of this is the painkiller, ibuprofen. The drug class that ibuprofen belongs to is called non-steroidal anti-inflammatory drugs. The generic name is ibuprofen, and several companies make it with brand names such as Advil®, Neurofen®, Motrin®, Ibumetin®, Dolgit®.

We will refer to drug classes and generic names when discussing specific medicines for HAE.

There are effective treatments that help reduce the frequency and severity of swellings and relieve symptoms. Sadly, and similar to many other diseases, there is no cure for HAE.

The goals of HAE treatment are to achieve complete control of the disease and to normalize patients’ lives. Research is ongoing to develop more and more effective medications for HAE. With the effective modern medication available today for HAE, some people with HAE report that they can live life effectively free from swellings.

Current HAE treatment strategies focus on medications to [Maurer 2022]:

  • Provide rapid relief during attacks (on-demand or acute treatment)
  • Prevent symptoms in people with HAE who experience a high frequency of attacks (long-term prophylaxis)
  • Prevent symptoms in people with HAE who undergo dental or surgical procedures, which may trigger an attack (preprocedural or short-term prophylaxis).

All people with HAE should work with their physician to develop an individualized HAE management plan which includes a treatment action plan.

While the symptoms can often be mistaken for an allergic reaction, [Zuraw 2008] HAE attacks do not respond to common allergy treatments, including antihistamines, corticosteroids, or epinephrine. [Zuraw 2008] [Agostoni 2004]

About medicine classes and names

Medicines with certain similarities can be grouped into drug classes. The similarities could be due to the chemical structure of the medicine, their mode of action, or that they are used to treat the same disease. [Drugs.com 2022]

Every medicine has an approved generic name. This is the name of the active ingredient in that particular medicine. As several companies may make the same generic medicine, each company will give their product a brand or trade name. [Patient.info 2022]

An example of this is the painkiller, ibuprofen. The drug class that ibuprofen belongs to is called non-steroidal anti-inflammatory drugs. The generic name is ibuprofen, and several companies make it with brand names such as Advil®, Neurofen®, Motrin®, Ibumetin®, Dolgit®.

We will refer to drug classes and generic names when discussing specific medicines for HAE.

Maurer 2022: Maurer M, Magerl M, Betschel S et al. The international WAO/EAACI guideline for the management of hereditary angioedema-The 2021 revision and update. Allergy. 2022 Jan 10. doi: 10.1111/all.15214. Epub ahead of print. PMID: 35006617.
https://onlinelibrary.wiley.com/doi/10.1111/all.15214 [Free full text]

Zuraw 2008: Zuraw BL. Clinical practice. Hereditary angioedema. N Engl J Med. 2008 Sep 4;359(10):1027-36. doi: 10.1056/NEJMcp0803977. PMID: 18768946.
https://pubmed.ncbi.nlm.nih.gov/18768946/  [Paywall for full text]

Agostoni 2004: Agostoni A, Aygören-Pürsün E, Binkley KE et al. Hereditary and acquired angioedema: problems and progress: proceedings of the third C1 esterase inhibitor deficiency workshop and beyond. J Allergy Clin Immunol. 2004 Sep;114(3 Suppl):S51-131. doi: 10.1016/j.jaci.2004.06.047. PMID: 15356535; PMCID: PMC7119155.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7119155/ [Free full text]

Drugs.com 2022: Drug classes.
https://www.drugs.com/drug-classes.html Accessed January 2022. [Free full text]

Patient.info 2022: What are generic and brand names?
https://patient.info/treatment-medication/medicines-to-keep-at-home/generic-vs-brand-name-medicines Accessed January 2022. [Free full text]

What is long-term prophylaxis? What options are available?2022-02-21T16:10:11+01:00

Long-term prophylaxis (LTP) is where a person with HAE uses regular medication to prevent swelling attacks from occurring. LTP reduces the number of swelling attacks a person with HAE experiences and, some modern LTP medications mean that people with HAE no longer experience swellings.

HAE (Type I and II) therapies for LTP vary from country to country as specific treatments are not licensed in all countries.

This treatment strategy should be tailored to the individual and considered for all people with HAE taking into account the frequency and severity of attacks, the individual’s quality of life, the availability of healthcare resources, and failure to achieve adequate control with on-demand or acute treatments.

As swelling attacks can still happen even if LTP is used, all people with HAE using LTP should also have on-demand or acute medication available.

In recent years, additional medications for HAE LTP have been approved by medicine regulators. The types of specific HAE medication available and recommended for LTP include:

  • C1-inhibitor concentrate
    • products made from blood plasma (pdC1-inhibitor concentrate)
  • Plasma kallikrein inhibitor
    • lanadelumab
    • berotralstat

Where these medications are not available, attenuated androgens can be used for LTP.  They have been shown to reduce the number of swelling attacks. However, they have many side effects, contraindications, and drug interactions. Antifibrinolytics such as tranexamic acid can also be used for LTP when attenuated androgens are contraindicated. Antifibrinolytics are not formally recommended due to a lack of evidence of their effectiveness, but the Guideline experts noted that some people with HAE may find them helpful. Their side effects are usually minor.

FOR CHILDREN

The types of specific HAE medication available and recommended for LTP in children and adolescents generally mirror those available for adults. Where pdC1-inhibitor concentrate is unavailable, antifibrinolytics such as tranexamic acid can be used for LTP. Due to their better safety profile, LTP with antifibrinolytics is preferred over androgens in children. However, there is a lack of data to support its use.

Long-term prophylaxis (LTP) is where a person with HAE uses regular medication to prevent swelling attacks from occurring. [Maurer 2022] LTP reduces the number of swelling attacks a person with HAE experiences and, some modern LTP medications mean that people with HAE no longer experience swellings. [Maurer 2022]

HAE (Type I and II) therapies for LTP vary from country to country as specific treatments are not licensed in all countries.

This treatment strategy should be tailored to the individual and considered for all people with HAE taking into account the frequency and severity of attacks, the individual’s quality of life, the availability of healthcare resources, and failure to achieve adequate control with on-demand or acute treatments. [Maurer 2022]

As swelling attacks can still happen even if LTP is used, all people with HAE using LTP should also have on-demand or acute medication available. [Maurer 2022]

In recent years, additional medications for HAE LTP have been approved by medicine regulators. The types of specific HAE medication available and recommended for LTP include [Maurer 2022]:

  • C1-inhibitor concentrate
    • products made from blood plasma (pdC1-inhibitor concentrate)
  • Plasma kallikrein inhibitor
    • lanadelumab
    • berotralstat

Where these medications are not available, attenuated androgens can be used for LTP.  They have been shown to reduce the number of swelling attacks. However, they have many side effects, contraindications, and drug interactions. [Maurer 2022] Antifibrinolytics are not recommended for LTP due to a lack of evidence of their effectiveness, but the Guideline experts noted that some people with HAE may find them helpful. Their side effects are usually minor. [Maurer 2022]

FOR CHILDREN

The types of specific HAE medication available and recommended for LTP in children and adolescents generally mirror those available for adults. [Maurer 2022] Where pdC1-inhibitor concentrate is unavailable, antifibrinolytics such as tranexamic acid can be used for LTP. Due to their better safety profile, LTP with antifibrinolytics is preferred over androgens in children. However, there is a lack of data to support its use. [Maurer 2022]

Maurer 2022: Maurer M, Magerl M, Betschel S et al. The international WAO/EAACI guideline for the management of hereditary angioedema-The 2021 revision and update. Allergy. 2022 Jan 10. doi: 10.1111/all.15214. Epub ahead of print. PMID: 35006617.
https://onlinelibrary.wiley.com/doi/10.1111/all.15214 [Free full text]

What is short-term prophylaxis? What options are available?2022-02-21T16:12:37+01:00

Short-term prophylaxis is usually performed before surgical procedures or dental treatment. Dental procedures or surgery to remove the tonsils are potentially critical triggers as they can cause swelling in the throat or airway (larynx).

Where is it available, the use of intravenous plasma-derived (pd) C1-inhibitor concentrate is considered the short-term prophylaxis treatment of choice. It is administered as close as possible to the start of the procedure. Recombinant C1-inhibitor concentrate can be considered if intravenous pdC1-inhibitor is not available. Where neither intravenous C1-inhibitor concentrate is available:

  • Fresh frozen plasma (FFP) may be used.
  • Attenuated androgens can also be considered as an alternative. For scheduled pre-procedure prophylaxis, androgens are used for 5 days before and 2-3 days post-event.

There is always the potential that a breakthrough attack can occur, so on-demand treatment needs to be available during the procedure.

FOR CHILDREN

Similar to adults, where pdC1-inhibitor concentrate is available, it is considered the short-term prophylaxis of choice. A short course of attenuated androgens can be used as an alternative when C1-inhibitor concentrate is unavailable. There is always the potential that a breakthrough attack can occur, so on-demand treatment should be available during the procedure.

Short-term prophylaxis is usually performed before surgical procedures or dental treatment. Dental procedures or surgery to remove the tonsils are potentially critical triggers as they can cause swelling in the throat or airway (larynx). [Agostoni 2004]

Where is it available, the use of intravenous plasma-derived (pd) C1-inhibitor concentrate is considered the short-term prophylaxis treatment of choice. [Maurer 2022] It is administered as close as possible to the start of the procedure. Recombinant C1-inhibitor concentrate can be considered if intravenous pdC1-inhibitor is not available. Where neither intravenous C1-inhibitor concentrate is available:

  • Fresh frozen plasma (FFP) may be used. [Maurer 2022]
  • Attenuated androgens can also be considered as an alternative. For scheduled pre-procedure prophylaxis, androgens are used for 5 days before and 2-3 days post-event. [Maurer 2022]

There is always the potential that a breakthrough attack can occur, so on-demand treatment needs to be available during the procedure. [Maurer 2022]

FOR CHILDREN

Similar to adults, where pdC1-inhibitor concentrate is available, it is considered the short-term prophylaxis of choice. [Maurer 2022] A short course of attenuated androgens can be used as an alternative when C1-inhibitor concentrate is unavailable. [Maurer 2022] There is always the potential that a breakthrough attack can occur, so on-demand treatment should be available during the procedure. [Maurer 2022]

Agostoni 2004: Agostoni A, Aygören-Pürsün E, Binkley KE et al. Hereditary and acquired angioedema: problems and progress: proceedings of the third C1 esterase inhibitor deficiency workshop and beyond. J Allergy Clin Immunol. 2004 Sep;114(3 Suppl):S51-131. doi: 10.1016/j.jaci.2004.06.047. PMID: 15356535; PMCID: PMC7119155.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7119155/ [Free full text]

Maurer 2022: Maurer M, Magerl M, Betschel S et al. The international WAO/EAACI guideline for the management of hereditary angioedema-The 2021 revision and update. Allergy. 2022 Jan 10. doi: 10.1111/all.15214. Epub ahead of print. PMID: 35006617.
https://onlinelibrary.wiley.com/doi/10.1111/all.15214 [Free full text]

What does it mean that HAE is a hereditary disease?2022-02-21T14:59:26+01:00

HAE is hereditary because the genetic defect that causes HAE is passed on in families: A child has a 50% possibility of inheriting HAE if one of the parents has it. However, the absence of family history does not rule out an HAE diagnosis. Up to 25% of HAE cases result from a spontaneous mutation of the C1-Inhibitor gene at conception.

HAE is an autosomal dominant disease, which means one copy of the defective gene in each cell is sufficient to cause the disorder.

Men and women are equally likely to have HAE.

If you have been diagnosed with HAE and are concerned that other family members may have it, you may wish to make an appointment to speak to your HAE doctor to talk through your concerns. This way, you will have further background information and can feel more prepared before speaking to your family.

HAE is hereditary because the genetic defect that causes HAE is passed on in families: A child has a 50% possibility of inheriting HAE if one of the parents has it. [Agostoni 2004] [Zuraw 2010] However, the absence of family history does not rule out an HAE diagnosis. [Zuraw 2010] [Maurer 2022] Up to 25% of HAE cases result from a spontaneous mutation of the C1-Inhibitor gene at conception. [Maurer 2022]

HAE is an autosomal dominant disease [Zuraw 2010], which means one copy of the defective gene in each cell is sufficient to cause the disorder.

Men and women are equally likely to have HAE. [Nzeako 2001] [Zuraw 2008]

If you have been diagnosed with HAE and are concerned that other family members may have it, you may wish to make an appointment to speak to your HAE doctor to talk through your concerns. This way, you will have further background information and can feel more prepared before speaking to your family.

Agostoni 2004: Agostoni A, Aygören-Pürsün E, Binkley KE et al. Hereditary and acquired angioedema: problems and progress: proceedings of the third C1 esterase inhibitor deficiency workshop and beyond. J Allergy Clin Immunol. 2004 Sep;114(3 Suppl):S51-131. doi: 10.1016/j.jaci.2004.06.047. PMID: 15356535; PMCID: PMC7119155.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7119155/ [Free full text]

Zuraw 2010: Zuraw BL. The pathophysiology of hereditary angioedema. World Allergy Organ J. 2010 Sep;3(9 Suppl):S25-8. doi: 10.1097/WOX.0b013e3181f3f21c. PMID: 23282866; PMCID: PMC3666152.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3666152/ [Free full text]

Maurer 2022: Maurer M, Magerl M, Betschel S et al. The international WAO/EAACI guideline for the management of hereditary angioedema-The 2021 revision and update. Allergy. 2022 Jan 10. doi: 10.1111/all.15214. Epub ahead of print. PMID: 35006617.
https://onlinelibrary.wiley.com/doi/10.1111/all.15214 [Free full text]

Nzeako 2001: Nzeako UC, Frigas E, Tremaine WJ. Hereditary angioedema: a broad review for clinicians. Arch Intern Med. 2001 Nov 12;161(20):2417-29. doi: 10.1001/archinte.161.20.2417. PMID: 11700154.
https://jamanetwork.com/journals/jamainternalmedicine/fullarticle/649449 {Free full text}

Zuraw 2008: Zuraw BL. Clinical practice. Hereditary angioedema. N Engl J Med. 2008 Sep 4;359(10):1027-36. doi: 10.1056/NEJMcp0803977. PMID: 18768946.
https://pubmed.ncbi.nlm.nih.gov/18768946/  [Full text link – paywall]

Who is more likely to have HAE?2022-02-21T15:00:37+01:00

HAE is usually inherited from a parent. You cannot ‘catch’ HAE.

Men and women are equally likely to have HAE.

The age of HAE onset varies considerably from early childhood to teenage years. Most people with HAE experience an increased frequency of attacks during puberty.

HAE is hereditary because the genetic defect that causes HAE is passed on in families: A child has a 50% possibility of inheriting HAE if one of the parents has it. However, the absence of family history does not rule out an HAE diagnosis. Up to 25% of HAE cases result from a spontaneous mutation of the C1-Inhibitor gene at conception.

HAE is usually inherited from a parent. You cannot ‘catch’ HAE.

Men and women are equally likely to have HAE. [Nzeako 2001] [Zuraw 2008]

The age of HAE onset varies considerably from early childhood to teenage years. [Agostoni 2004] Most people with HAE experience an increased frequency of attacks during puberty. [Zuraw 2010]

HAE is hereditary because the genetic defect that causes HAE is passed on in families: A child has a 50% possibility of inheriting HAE if one of the parents has it. [Agostoni 2004] [Zuraw 2010] However, the absence of family history does not rule out an HAE diagnosis. [Zuraw 2010] [Maurer 2022] Up to 25% of HAE cases result from a spontaneous mutation of the C1-Inhibitor gene at conception. [Maurer 2022]

Nzeako 2001: Nzeako UC, Frigas E, Tremaine WJ. Hereditary angioedema: a broad review for clinicians. Arch Intern Med. 2001 Nov 12;161(20):2417-29. doi: 10.1001/archinte.161.20.2417. PMID: 11700154.
https://jamanetwork.com/journals/jamainternalmedicine/fullarticle/649449 {Free full text}

Zuraw 2008: Zuraw BL. Clinical practice. Hereditary angioedema. N Engl J Med. 2008 Sep 4;359(10):1027-36. doi: 10.1056/NEJMcp0803977. PMID: 18768946.
https://pubmed.ncbi.nlm.nih.gov/18768946/  [Full text link – paywall]

Agostoni 2004: Agostoni A, Aygören-Pürsün E, Binkley KE et al. Hereditary and acquired angioedema: problems and progress: proceedings of the third C1 esterase inhibitor deficiency workshop and beyond. J Allergy Clin Immunol. 2004 Sep;114(3 Suppl):S51-131. doi: 10.1016/j.jaci.2004.06.047. PMID: 15356535; PMCID: PMC7119155.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7119155/ [Free full text]

Zuraw 2010: Zuraw BL. The pathophysiology of hereditary angioedema. World Allergy Organ J. 2010 Sep;3(9 Suppl):S25-8. doi: 10.1097/WOX.0b013e3181f3f21c. PMID: 23282866; PMCID: PMC3666152.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3666152/ [Free full text]

Maurer 2022: Maurer M, Magerl M, Betschel S et al. The international WAO/EAACI guideline for the management of hereditary angioedema-The 2021 revision and update. Allergy. 2022 Jan 10. doi: 10.1111/all.15214. Epub ahead of print. PMID: 35006617.
https://onlinelibrary.wiley.com/doi/10.1111/all.15214 [Free full text]

Swelling is a common symptom of HAE and allergy, so why can’t you treat HAE with allergy medicines?2022-01-18T12:19:29+01:00

Although both HAE and allergy symptoms include swelling, they have different causes. Swelling from allergy is caused by histamine.

HAE swelling is caused by excessive levels of bradykinin in the blood. As a result, HAE attacks do not respond to common allergy treatments, including antihistamines, corticosteroids, or epinephrine.

Current HAE treatment options focus on providing rapid relief during swelling attacks (acute or on-demand therapy) or preventing attacks from occurring (prophylaxis therapy).

Although both HAE and allergy symptoms include swelling, [Zuraw 2008] they have different causes. Swelling from allergy is caused by histamine. [White 1990]

HAE swelling is caused by excessive levels of bradykinin in the blood. [Caccia 2014] As a result, HAE attacks do not respond to common allergy treatments, including antihistamines, corticosteroids, or epinephrine. [Zuraw 2008] [Agostoni 2004]

Current HAE treatment options focus on providing rapid relief during swelling attacks (acute or on-demand therapy) or preventing attacks from occurring (prophylaxis therapy).

Zuraw 2008: Zuraw BL. Clinical practice. Hereditary angioedema. N Engl J Med. 2008 Sep 4;359(10):1027-36. doi: 10.1056/NEJMcp0803977. PMID: 18768946.
https://pubmed.ncbi.nlm.nih.gov/18768946/  [Paywall for full text]

White 1990: White MV. The role of histamine in allergic diseases. J Allergy Clin Immunol. 1990 Oct;86(4 Pt 2):599-605. doi: 10.1016/s0091-6749(05)80223-4. PMID: 1699987.
https://pubmed.ncbi.nlm.nih.gov/1699987/ [Free full text]

Caccia 2014: Caccia S, Suffritti C, Cicardi M. Pathophysiology of Hereditary Angioedema. Pediatr Allergy Immunol Pulmonol. 2014;27(4):159-163. doi:10.1089/ped.2014.0425
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4268578/ [Free full text}

Agostoni 2004: Agostoni A, Aygören-Pürsün E, Binkley KE et al. Hereditary and acquired angioedema: problems and progress: proceedings of the third C1 esterase inhibitor deficiency workshop and beyond. J Allergy Clin Immunol. 2004 Sep;114(3 Suppl):S51-131. doi: 10.1016/j.jaci.2004.06.047. PMID: 15356535; PMCID: PMC7119155.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7119155/ [Free full text]

Why is early diagnosis of HAE important?2022-01-18T13:41:23+01:00

Early diagnosis and treatment of HAE is important as HAE attacks are painful and debilitating, they have a negative effect on the quality of life, and in the case of a throat attack, they can be life-threatening:

  • People with HAE experience recurrent, painful episodes of swelling in various body parts, including the hands, feet, face, abdomen (gastrointestinal tract), and throat (airway).
  • Swelling in the abdomen (intestinal wall) can result in excruciating abdominal pain, nausea, vomiting, and/or diarrhea.
  • Swelling in the throat is the most dangerous aspect of HAE because the airway can be closed and cause death by choking (suffocation).

Once an individual is diagnosed, experts recommend that all immediate family members (parents, siblings and children) are tested for HAE. Testing for HAE is possible within the first year of life however, some physicians recommend that you wait until a baby is at least one (1) year old before testing. This is due to highly variable C1 antigenic and C4 levels in the first year of life.

These symptoms can often be mistaken for an allergic reaction, but HAE attacks do not respond to common allergy treatments, including antihistamines, corticosteroids, or epinephrine.

Because a typical attack lasts several days before it subsides, without treatment, people with HAE may be debilitated by symptoms for 100 days or more than three (3) months a year. The death rate for untreated people with HAE with airway angioedema is estimated to be around 30%.

Current HAE treatment options focus on providing rapid relief during swelling attacks (acute therapy) or preventing attacks from occurring (prophylaxis therapy).

Early diagnosis and treatment of HAE is important as HAE attacks are painful and debilitating, they have a negative effect on the quality of life, and in the case of a throat attack, they can be life-threatening: [Bork 2021]

  • People with HAE experience recurrent, painful episodes of swelling in various body parts, including the hands, feet, face, abdomen (gastrointestinal tract), and throat (airway). [Bork 2021]
  • Swelling in the abdomen (intestinal wall) can result in excruciating abdominal pain, nausea, vomiting, and/or diarrhea. [Agostoni 2004]
  • Swelling in the throat is the most dangerous aspect of HAE because the airway can be closed and cause death by choking (suffocation).

Once an individual is diagnosed, experts recommend that all immediate family members (parents, siblings and children) are tested for HAE. [Busse 2020] Testing for HAE is possible within the first year of life however, some physicians recommend that you wait until a baby is at least one (1) year old before testing. This is due to highly variable C1 antigenic and C4 levels in the first year of life. [Busse 2020]

These symptoms can often be mistaken for an allergic reaction, [Zuraw 2008] but HAE attacks do not respond to common allergy treatments, including antihistamines, corticosteroids, or epinephrine. [Zuraw 2008] [Agostoni 2004]

Because a typical attack lasts several days before it subsides, without treatment, people with HAE may be debilitated by symptoms for 100 days or more than three (3) months a year. [Cicardi 1996] The death rate for untreated people with HAE with airway angioedema is estimated to be around 30%. [Frank 1976] [Cicardi 1996] [Bork 2012]

Current HAE treatment options focus on providing rapid relief during swelling attacks (acute therapy) or preventing attacks from occurring (prophylaxis therapy).

Bork 2021: Bork K, Anderson JT, Caballero T et al. Assessment and management of disease burden and quality of life in patients with hereditary angioedema: a consensus report. Allergy Asthma Clin Immunol. 2021 Apr 19;17(1):40. doi: 10.1186/s13223-021-00537-2. PMID: 33875020; PMCID: PMC8056543.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8056543/ [Free full text]

Agostoni 2004: Agostoni A, Aygören-Pürsün E, Binkley KE et al. Hereditary and acquired angioedema: problems and progress: proceedings of the third C1 esterase inhibitor deficiency workshop and beyond. J Allergy Clin Immunol. 2004 Sep;114(3 Suppl):S51-131. doi: 10.1016/j.jaci.2004.06.047. PMID: 15356535; PMCID: PMC7119155.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7119155/ [Free full text]

Busse 2020: Busse PJ, Christiansen SC, Riedl MA et al. US HAEA Medical Advisory Board 2020 Guidelines for the Management of Hereditary Angioedema. J Allergy Clin Immunol Pract. 2021 Jan;9(1):132-150.e3. doi: 10.1016/j.jaip.2020.08.046. Epub 2020 Sep 6. PMID: 32898710.
https://www.jaci-inpractice.org/article/S2213-2198(20)30878-3/fulltext [Free full text]

Zuraw 2008: Zuraw BL. Clinical practice. Hereditary angioedema. N Engl J Med. 2008 Sep 4;359(10):1027-36. doi: 10.1056/NEJMcp0803977. PMID: 18768946.
https://pubmed.ncbi.nlm.nih.gov/18768946/  [Paywall for full text]

Cicardi 1996: Cicardi M, Agostoni A. Hereditary angioedema. N Engl J Med. 1996 Jun 20;334(25):1666-7. doi: 10.1056/NEJM199606203342510. PMID: 8628365.
https://pubmed.ncbi.nlm.nih.gov/8628365/ [Paywall for full text link]

Frank 1976: Frank MM, Gelfand JA, Atkinson JP. Hereditary angioedema: the clinical syndrome and its management. Ann Intern Med. 1976 May;84(5):580-93. doi: 10.7326/0003-4819-84-5-580. PMID: 1275365.
https://www.acpjournals.org/doi/pdf/10.7326/0003-4819-84-5-580 [Paywall for full text]

Bork 2012: Bork K, Hardt J, Witzke G. Fatal laryngeal attacks and mortality in hereditary angioedema due to C1-INH deficiency. J Allergy Clin Immunol. 2012 Sep;130(3):692-7. doi: 10.1016/j.jaci.2012.05.055. Epub 2012 Jul 28. PMID: 22841766.
https://www.jacionline.org/article/S0091-6749(12)01008-1/fulltext [Free full text]

What is on-demand or acute treatment? What options are available?2022-02-21T16:05:25+01:00

On-demand or acute treatment is used to stop the progression of the swelling and to relieve the symptoms. Rapid use of on-demand or acute treatment is especially important where the swelling in is the throat or airway. If the throat attack is left untreated, it can lead to death by choking (suffocation).

HAE (Type I and II) therapies for on-demand or acute treatment vary from country to country as specific treatments are not licensed in all countries.

The types of specific HAE medication available and recommended for on-demand or acute treatment include:

  • Intravenous C1-inhibitor concentrate
    • Products made from blood plasma (pdC1-inhibitor concentrate)
    • Products that are not made from blood plasma (recombinant or rhC1-inhibitor concentrate).
  • Plasma kallikrein inhibitor
    • ecallantide
  • Bradykinin-receptor antagonist
    • icatibant

In countries where HAE-specific on-demand or acute treatments are not available, physicians are limited to non-HAE-specific medications or even just pain killers.

The International WAO/EAACI Guideline for the Management of Hereditary Angioedema makes the following recommendations for acute or on-demand treatment for HAE:

  • Early treatment with intravenous C1-inhibitor concentrate, ecallantide, or icatibant provides a better response than late treatment, often resulting in a shorter time to complete symptom relief and a shorter duration of the swelling overall.
  • HAE attacks should be treated as early as possible. Early treatment can be achieved with self-administration. All C1-inhibitor concentrates and icatibant are licensed for self-administration although approved product uses vary around the world.
  • If C1-inhibitor concentrates, ecallantide, or icatibant are not available then solvent-detergent treated plasma (SDP) should be used.
  • If SDP is not available then fresh frozen plasma (FFP) should be used to treat attacks, where a safe supply is available.

The experts who developed the Guideline advise against using antifibrinolytics (e.g., tranexamic acid) or androgens (e.g., danazol) as on-demand treatments for HAE attacks. Studies show no, or very small, effects when used in this way.

FOR CHILDREN

The types of specific HAE medication available and recommended for on-demand or acute treatment for children or adolescents include:

  • C1-inhibitor concentrate
    • Products made from blood plasma (pdC1-inhibitor concentrate)
    • Products that are not made from blood plasma (recombinant or rhC1-inhibitor concentrate).
  • Bradykinin-receptor antagonist
    • icatibant

Where these modern medications are not available, solvent-detergent treated plasma (SDP) is preferred to fresh frozen plasma (FFP), but both can be considered.

On-demand or acute treatment is used to stop the progression of the swelling and to relieve the symptoms. [Maurer 2022] Rapid use of on-demand or acute treatment is especially important where the swelling in is the throat or airway. [Maurer 2022] If the throat attack is left untreated, it can lead to death by choking (suffocation).

HAE (Type I and II) therapies for on-demand or acute treatment vary from country to country as specific treatments are not licensed in all countries.

The types of specific HAE medication available and recommended for on-demand or acute treatment include [Maurer 2022]:

  • Intravenous C1-inhibitor concentrate
    • Products made from blood plasma (pdC1-inhibitor concentrate)
    • Products that are not made from blood plasma (recombinant or rhC1-inhibitor concentrate).
  • Plasma kallikrein inhibitor
    • ecallantide
  • Bradykinin-receptor antagonist
    • icatibant

In countries where HAE-specific on-demand or acute treatments are not available, physicians are limited to non-HAE-specific medications or even just pain killers.

The International WAO/EAACI Guideline for the Management of Hereditary Angioedema makes the following recommendations for acute or on-demand treatment for HAE [Maurer 2022]:

  • Early treatment with intravenous C1-inhibitor concentrate, ecallantide, or icatibant provides a better response than late treatment, often resulting in a shorter time to complete symptom relief and a shorter duration of the swelling overall.
  • HAE attacks should be treated as early as possible. Early treatment can be achieved with self-administration. All C1-inhibitor concentrates and icatibant are licensed for self- administration although approved product uses vary around the world.
  • If C1-inhibitor concentrates, ecallantide, or icatibant are not available then solvent-detergent treated plasma (SDP) should be used.
  • If SDP is not available then fresh frozen plasma (FFP) should be used to treat attacks, where a safe supply is available.

The experts who developed the Guideline advise against using antifibrinolytics (e.g., tranexamic acid) or androgens (e.g., danazol) as on-demand treatments for HAE attacks. Studies show no, or very small, effects when used in this way.

FOR CHILDREN

The types of specific HAE medication available and recommended for on-demand or acute treatment for children or adolescents include [Maurer 2022]:

  • C1-inhibitor concentrate
    • Products made from blood plasma (pdC1-inhibitor concentrate)
    • Products that are not made from blood plasma (recombinant or rhC1-inhibitor concentrate).
  • Bradykinin-receptor antagonist
    • icatibant

Where these modern medications are not available, solvent-detergent treated plasma (SDP) is preferred to fresh frozen plasma (FFP), but both can be considered. [Maurer 2022]

Maurer 2022: Maurer M, Magerl M, Betschel S et al. The international WAO/EAACI guideline for the management of hereditary angioedema-The 2021 revision and update. Allergy. 2022 Jan 10. doi: 10.1111/all.15214. Epub ahead of print. PMID: 35006617.
https://onlinelibrary.wiley.com/doi/10.1111/all.15214 [Free full text]

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