Hereditary Angioedema (HAE)

Hereditary angioedema (HAE) is characterized by repeated attacks of nonpitting, nonpruritic swelling that is not accompanied by urticarial plaques. The condition is caused by a lack or reduced function of C1 esterase inhibitor (C1-inh). Type 1 HAE, the most common form, is caused by a lack of C1-inh and is characterized by low serum C1-inh levels. The function of C1-inh is diminished in type 2 HAE, whereas type 3 HAE has normal C1-inh serum levels and C1-inh function. Episodes of HAE can involve the larynx, face, extremities, gastrointestinal tract, and urogenital area, among other sites.¹ 

Gastrointestinal Complications 

The gastrointestinal tract is one of the most common sites involved in HAE. Due to difficulties in linking gastrointestinal symptoms to HAE, diagnosis is sometimes delayed, and unneeded surgical operations may be performed. The most common signs and symptoms of intestinal edema include nausea, vomiting, diarrhea, and abdominal pain. The symptoms of HAE in the gastrointestinal system, which are produced by visceral edema, can also cause complications like intestinal obstruction.^2,3  

Attacks of HAE can affect the entire gastrointestinal tract. Dysphagia, laryngeal edema, and tongue swelling can all be symptoms of oropharyngeal and esophageal involvement. Abdominal pain, distension, vomiting, ascites, and diarrhea are all symptoms of stomach and small intestinal involvement. Increased levels of liver enzymes, exudative ascites, and reversible parenchymal alterations are all findings associated with liver involvement. Pancreatic edema can result in partial duct occlusion, which can lead to repeated attacks of pancreatitis. Constipation is a typical symptom of colonic involvement, with some cases causing intussusception as well. Fatal complications such as circulatory collapse may occur due to a combination of vasodilation, fluid loss from emesis and diarrhea, and fluid extravasation from bowel wall edema and ascites. This can lead to considerable hypovolemia and hemoconcentration.² 

Cutaneous Complications 

Extravasation of plasma into the deep layers of the skin or mucous membranes causes HAE symptoms and complications. Skin edema is a type of edema that is nonpitting and has ill-defined borders. It usually affects the face, extremities, and genitals. The lips, eyelids, and tongue are the most commonly affected areas of the face. Genital edema is most commonly caused by trauma during intercourse, parturition, or even horseback riding.^2-4 Angioedema of the gastrointestinal system normally lasts for 12 to 24 hours, while cutaneous angioedema may persist over several days.³ 

Respiratory Complications

Some of the most severe signs of HAE occur when edema develops in the respiratory system. Edema of the larynx, nose, and sinuses can cause respiratory tract impairment and mortality from suffocation. Since the edema occurring in acute episodes often develops at or above the larynx, tracheostomy can be a lifesaver in these situations. Due to upper airway blockage, HAE mortality can reach up to 30% to 40% if it goes undetected. Even in people who have been diagnosed with HAE, waiting too long to seek adequate medical attention has often culminated in asphyxiation. Asphyxia can affect patients of any age, with cases reported from the age of 4 weeks to 78 years of age.³ 

Other Complications 

Two case reports have indicated migraine-like and transient ischemic attack symptoms during acute HAE attacks.^5,6 Seizures and hemiparesis have also been reported in the literature.^7-9 Local cerebral edema and subsequent cerebral hypoperfusion, which occur during acute HAE episodes, are thought to be the sources of these symptoms.^7-9

Headaches, transient neurologic impairments, urethral and bladder swelling and spasms, joint swelling, chest tightness and pain, and renal colic have all been reported in HAE attacks.²

References

1. Gelincik A, Demir S. Hereditary angioedema. In: Kartal SP, Kutlubay Z, eds. A Comprehensive Review of Urticaria and Angioedema. London, UK: IntechOpen; 2017;chap 11. May 31, 2017. Accessed June 20, 2022.
2. Patel N, Suarez LD, Kapur S, Bielory L. Hereditary angioedema and gastrointestinal complications: an extensive review of the literature. Case Reports Immunol. 2015;2015:925861. doi:10.1155/2015/925861
3. Nzeako UC, Frigas E, Tremaine WJ. Hereditary angioedema: a broad review for clinicians. Arch Intern Med. 2001;161(20):2417-2429. doi:10.1001/archinte.161.20.2417
4. Banerji A, Riedl M. Managing the female patient with hereditary angioedema. Womens Health (Lond). 2016;12(3):351-361. doi:10.2217/whe.16.6
5. Krause KH, Rentrop U, Mehregan U. [Cerebral manifestations in angioneurotic edema (author’s transl)]. J Neurol Sci. 1979;42(3):429-435. German. doi:10.1016/0022-510x(79)90175-8
6. Brettle RP, Dunmow RE, Milne LA, Yap PL. Angioneurotic oedema in the elderly. Scott Med J. 1982;27(4):309-311. doi:10.1177/003693308202700409
7. Frank MM, Gelfand JA, Atkinson JP. Hereditary angioedema: the clinical syndrome and its management. Ann Intern Med. 1976;84(5):580-593. doi:10.7326/0003-4819-84-5-580
8. Thorvaldsson SE, Sedlack RE, Gleich GJ, Ruddy SJ. Angioneurotic edema and deficiency of C′1 esterase inhibitor in a 61-year-old woman. Ann Intern Med. 1969;71(2):353-357. doi:10.7326/0003-4819-71-2-353
9. Landerman NS. Hereditary angioneurotic edema: I. case reports and review of the literature. J Allergy. 1962;33(4):316-329. doi:10.1016/0021-8707(62)90031-x

Reviewed by Hasan Avcu, MD, on 6/26/2022.

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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.