Hereditary Angioedema (HAE)

Hereditary angioedema (HAE) is a rare genetic disease. The most common cause of HAE is C1-inhibitor (C1-INH) deficiency due to a mutation in the SERPING1 gene. The disease is characterized by self-limiting edema involving the face, extremities, gastrointestinal tract, genitals, and upper airway, without the presence of urticaria. Patients experiencing attacks involving the upper airway are at risk of asphyxiation. Timely and accurate diagnosis and the accessibility of on-demand treatment determine the mortality rate associated with HAE.^1,2 

Hereditary angioedema, though rare, can have detrimental complications. Asphyxiation can develop from laryngeal edema. Abdominal attacks might result in unneeded surgeries, delayed diagnoses, and narcotic dependence due to excruciating pain. Cutaneous attacks can cause disfigurement and disability, reducing quality of life. People with early-onset HAE have a worse prognosis than patients who experience attacks later in life. The mortality rate was reported to be 20% to 30% before effective medications were developed. With the optimum usage of prophylactic therapy, the prognosis for patients with HAE has improved. Appropriate androgen use decreases both short-term and long-term disease consequences. The introduction of kinin pathway inhibitors and C1-inhibitor concentrate can also significantly improve treatment in affected individuals.³ Severe attacks represent the greatest burden for patients with HAE, as they can cause a person to leave work and/or society as well as have major economic and social impacts on their family.⁴ 

Studies on Life Expectancy in Hereditary Angioedema

A German study that comprised 728 patients with HAE from 182 families reported 214 overall deaths. The mean age of patients who died from an HAE attack was 40.6 years. The study showed that accurate diagnosis significantly decreased the occurrence of laryngeal edema. However, asphyxiation continued to be a frequent cause of mortality, even in patients who had been diagnosed.⁵

A review study of death certificates in the United States from 1999 to 2010 revealed that HAE was a contributing factor or the underlying cause of mortality in 600 people, with 270 of these fatalities being specifically linked to the disease.⁶ 

According to an Italian study, life expectancy in patients with HAE did not differ considerably from that of the general population. They reported fewer cases of asphyxiation compared to previous studies. Patients have had access to plasma-derived C1-inhibitor protein since 1985. The study concluded that asphyxiation was not the main cause of death in patients with HAE when on-demand therapy was available and used appropriately.² 

Another study intended to analyze global laryngeal edema-related mortality in patients with HAE and their families over time and report the epidemiological and clinical findings related to this event. The analyzed HAE studies included 3292 patients and 411 deaths due to asphyxia secondary to laryngeal edema. There were 103 deaths of close relatives that were documented to be secondary to the same cause. On average, 1 death from laryngeal edema occurred in every 20 patients. Eight studies mentioned deaths of relatives. One relative died for every 7.4 patients in these investigations. Three studies reported proportions of deaths due to laryngeal edema of 32.7%, 44.4%, and 56%, respectively. The high frequency of these results indicates that deaths continue to occur and that HAE management needs improvement.⁷ 

References

1. Cafasso J. Living with hereditary angioedema (HAE). Medical News Today. August 30, 2021. Accessed June 30, 2022.
2. Perego F, Gidaro A, Zanichelli A, et al; ITACA (ITAlian network for C1 inhibitor Angioedema). Life expectancy in Italian patients with hereditary angioedema due to C1-inhibitor deficiency. J Allergy Clin Immunol Pract. 2020;8(5):1772-1774. doi:10.1016/j.jaip.2020.01.007
3. Frank MM. Hereditary angioedema: prognosis. Medscape. Updated August 30, 2018. Accessed June 30, 2022.
4. Lumry WR. Hereditary angioedema: the economics of treatment of an orphan disease. Front Med (Lausanne). 2018;5:22. doi:10.3389/fmed.2018.00022
5. Bork K, Hardt J, Witzke G. Fatal laryngeal attacks and mortality in hereditary angioedema due to C1-INH deficiency. J Allergy Clin Immunol. 2012;130(3):692-697. doi:10.1016/j.jaci.2012.05.055
6. Kim SJ, Brooks JC, Sheikh J, Kaplan MS, Goldberg BJ. Angioedema deaths in the United States, 1979-2010. Ann Allergy Asthma Immunol. 2014;113(6):630-634. doi:10.1016/j.anai.2014.09.003
7. Minafra FG, Gonçalves TR, Alves TM, Pinto JA. The mortality from hereditary angioedema worldwide: a review of the real-world data literature. Clin Rev Allergy Immunol. 2022;62(1):232-239. doi:10.1007/s12016-021-08897-8

Reviewed by Kyle Habet, MD, on 6/30/2022.

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Harshi Dhingra, MD

Harshi Dhingra is a licensed medical doctor with specialization in Pathology. She is currently employed as faculty in a medical school with a tertiary care hospital and research center in India. Dr. Dhingra has over a decade of experience in diagnostic, clinical, research, and teaching work, and has written several publications and citations in indexed peer reviewed journals. She holds medical degrees for MBBS and an MD in Pathology.