Frequently Asked Questions
Hereditary angioedema or HAE, is technically a disease, “a condition … that impairs normal functioning and is typically manifested by distinguishing signs and symptoms (Merriam-Webster, 2011). The terms, disorder and condition, are often used interchangeably for disease, most likely because they do not have the negative connotations associated with them that the word, “disease”, has. Presumably, most people do not want to be labelled as having a “disease” and so condition or disorder are used instead.
Hereditary angioedema is caused by a genetic defect and, therefore, cure would involve use of genetic technology. At this time, there is no cure, but there is certainly treatment. In Canada, C1 esterase inhibitor replacement therapy is used, which involves replacing the protein whose absence or deficiency of is responsible for repeated swelling attacks (Bowen, 2010; Bowen et al., 2010). Other treatments, while not specific to hereditary angioedema, have been successful; these include attenuated androgens and antifibrinolytic agents (Agostoni et al., 2004; Bowen et al., 2010)
Hereditary angioedema is both a blood disorder and an immunologic disorder in that the deficient protein (C1 esterase inhibitor) is part of the blood and this protein regulates part of the immune system. The disorder involves the complement and contact systems of the immune response and the protein affected in hereditary angioedema is an inhibitor of these systems. C1 esterase inhibitor protein is an enzyme that is used by the body to shut down the immune response, which is responsible for the swelling (Agostoni et al., 2004; Ritchie, 2003). HAE patients can be followed by either immunologists or hematologists, but most tend to be referred to immunologists.
Hereditary angioedema attacks can range from mild to life threatening if they involve the airway. Swelling attacks involving the face, neck, tongue, and throat are considered serious and could potentially lead to a medical emergency (Bork & Ressel, 2003; Farkas, 2010) requiring a breathing tube to be placed down the throat or even directly into the trachea (or windpipe). Although not life threatening, severe abdominal pain can be debilitating and edema of the extremities can also be painful and disfiguring, causing the patient’s quality of life to be adversely affected (Zuraw, 2003).
An HAE attack occurs when the demand for C1 esterase inhibitor exceeds the amount of available functional C1 esterase in the body. C1 esterase is like a key that turns off the immune response (in the complement and contact systems). Therefore, deficiency in functional C1 esterase means that there will not be enough of this protein available to turn off this immune response, leading to increased bradykinin levels. Since bradykinin increases vascular permeability, fluid continues to leak into the surrounding tissues, causing the swelling or edema (Gower et al., 2011; Zuraw, 2003).People with hereditary angioedema need to be aware of factors that may trigger or increase the likelihood of an attack; these include stress, illness or infection, injury, pregnancy, menstruation, some drugs (eg. oral contraceptives; angiotensin-converting enzyme inhibitors), and dental procedures (Bowen et al., 2003).
There are three types of hereditary angioedema:
- Type I – Low C1 inhibitor protein level and function – most common type.
- Type II – Normal C1 inhibitor protein level, but abnormal function.
- HAE with Normal C1 inhibitor protein level and function – estrogen dependent.
Acquired angioedema (AAE) is also documented in the literature, but is not associated with family history. Drug-induced angioedema is another angioedema type found in the literature, associated with such drugs as angiotensin-converting enzyme inhibitors (Bowen et al., 2010).
The best treatment for you will be determined between you and your specialist.
The first step would be to see your family doctor and then be referred on to a specialist who deals with hereditary angioedema. Diagnostic tests include C4 and C1-INH (C1-inhibitor protein) levels (Bowen et al., 2010).
If you have lived with repeated swellings for any length of time, you may or may not have noticed symptoms that typically occur before an attack. These are varied between individuals and may even vary between different swelling attacks in the same individual. Dagen & Craig (2010) documented that “the most common identifiable prodromal symptoms include unusual fatigue, rash on arms or legs and muscle aches” (p. 3). The rash that occurs with HAE is erythema marginatum; it is not itchy and not raised (Gower et al., 2011). Tingling in the area that is about to swell is also another commonly noted prodrome (Frank, 2008; Gower et al., 2011). Headache, abdominal discomfort (Gibbs & Craig, 2007) and even irritability (Farkas et al., 2001 ) are other symptoms reported to signal the onset of an HAE attack.
These are questions that you should discuss with your doctor who specializes in the management of HAE. However, hereditary angioedema can impact considerably on quality of life. During an attack and for days subsequent to an attack, patients with hereditary angioedema may be unable to partake in their normal daily activities due to the pain, fatigue, and disfigurement associated with the edema. HAE attacks can considerably interfere with work or other activities that patients are involved with (Longhurst et al., 2010). There have been no studies found that document any relationship between diet and hereditary angioedema attacks.
Hereditary angieodema has been found to be exacerbated in many individuals in association with increased estrogen levels (Binkley & Davis III, 2003; Bouillet, 2010). Some individuals have been found to only have symptoms of edema during pregnancy, oral contraceptives, or estrogen-replacement therapy (Binkley & Davis III, 2003). Also well documented in the literature is the association between estrogen and angioedema attacks. Many people with hereditary angioedema are considered to be estrogen sensitive and therefore have increased attack frequency during pregnancy.The use of C1 esterase inhibitor replacement is indicated for treatment and prophylaxis of HAE attacks in pregnancy (Czaller et al., 2010; Hermans, 2007). Other treatments that are used to treat HAE are contraindicated in pregnancy due to either the risk for untoward effects on the fetus or the increased risk of blood clots in the mother (Gorman, 2008).
HAE presents in an autosomal dominant pattern, which means that only one parent needs to have HAE to pass it on to the children. By definition of autosomal dominance, there is a 50% chance that a child of a parent with HAE will be affected.
Finding a specialist who is familiar with HAE is important. Please refer to the list on the Canadian HAE Network (CHAEN)’s website . This is the website of the physician group our patient group partners with.
Agostoni, A., Aygoren-Pursun, E., Binkley, K. E., Blanch, A., Bork, K., Bouillet, L., et al. (2004). Hereditary and acquired angioedema: Problems and progress: Proceedings of the third C1 esterase inhibitor deficiency workshop and beyond. The Journal of Allergy and Clinical Immunology, 114(3), S51-S131.
Binkley, K. E., & Davis III, A. E. (2003). Estrogen-dependent inherited angioedema. Transfusion and Apheresis Science, 29, 215-219.
Bork, K., & Ressel, N. (2003). Sudden upper airway obstruction in patients with hereditary angioedema. Transfusion and Apheresis Science, 29, 235-238.
Bouillet, L. (2010). Hereditary angioedema in women. Allergy, Asthma & Clinical Immunology, 6(17). Retrieved October 13, 2011, from www.aacijournal.com/content/6/1/17
Bowen, T. (2010). Hereditary angioedema: beyond international consensus – circa December 2010 – The Canadian Society of Allergy and Immunology Dr. David McCourtie Lecture. Allergy, Asthma & Clinical Immunology, 7(1). Retrieved October 13, 2011, from www.aacijournal.com/content/7/1/1
Bowen, T., Cicardi, M., Farkas, H., Bork, K., Longhurst, H. J., Zuraw, B., et al. (2010). 2010 international consensus algorithm for the diagnosis, therapy and management of hereditary angioedema, Allergy, Asthma & Clinical Immunology, 6(24). Retrieved October 13, 2011, from www.aacijournal.com/content/6/1/24
Czaller, I., Visy, B., Csulka, D., Fust, G., Toth, F., & Farkas, H. (2010). The natural history of hereditary angioedema and the impact of treatment with human C1-inhibitor concentrate during pregnancy: a long-term survey. European Journal of Obstretics & Gynecology and Reproductive Biology, 152(1), 44-49.
Dagen, C., & Craig, T. J. (2011). Treatment of hereditary angioedema: items that need to be addressed in practice parameter. Allergy, Asthma & Clincial Immunology, 6(11). Retrieved October 13, 2011, from www.aacijournal.com/content/6/1/11
Farkas, H. (2010). Management of upper airway edema caused by hereditary angioedema. Allergy, Asthma & Clinical Immunology, 6(19). Retrieved October 13, 2011, from www.aacijournal.com/content/6/1/19
Farkas, H., Harmat, G., Fay, A., Fekete, B. Karadi, I., Visy, B., et al. (2001). Erythema marginatum preceding an acute oedematous attack of hereditary angioeneurotic oedema. Acta Derm Venereol, 81(5), 376-377.
Gibbs, J. G., & Craig, T. J. (2007). Prodromal symptoms before exacerbations of hereditary angioedema. Journal of Allergy and Clinical Immunology, 119(1), S278. Retrieved October 13, 2011, from download.journals.elsevierhealth.com/pdfs/journals/0091-6749/PIIS009167490802798X.pdf
Gorman, P. J. (2008). Hereditary angioedema and pregnancy: A successful outcome using C1 esterase inhibitor concentrate. Official Publication of the College of Family Physicians of Canada, 54(3), 365-366.
Gower, R. G., Busse, P. J., Aygoren-Pursun, E., Barakat, A. J., Caballero, T., Davis-Lorton, M., et al. (2011). Hereditary angioedema caused by C1-esterase inhibitor deficiency: A literature-based analysis and cliknical commentary on prophylaxis treatment strategies. World Allergy Organization Journal, 4(2), S9-S21. Retrieved June 24, 2015, from http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3666183/
Hermans, C. (2007). Successful management with C1-inhibitor concentrate of hereditary angioedema attacks during two successive pregnancies: a case report. Archives of Gynecology and Obstetrics, 276(3), 271-276.
Longhurst, H. J., Farkas, H., Craig, T., Aygoren-Pursun, E., Bethune, C., Bjorkander, J., et al. (2010). HAE international home therapy consensus document. Allergy, Asthma & Clinical Immunology, 6(22). Retrieved October 13, 2011, from www.aacijournal.com/content/6/1/22
Merriam-Webster (2011). Retrieved October 13, 2011 from www.merriam-webster.com/dictionary/disease
Ritchie, B. (2003). Protease inhibitors in the treatment of hereditary angioedema. Transfusion and Apheresis Science, 29, 259-267.
Zuraw, B. L. (2003). Diagnosis and management of hereditary angioedema: an American approach. Transfusion and Apheresis Science, 29, 239-245.