Angioedema Is an Uncommon but Serious Condition

Angioedema is a localized swelling of the tissues underneath the skin.

This condition was first described by German physician Heinrich Quincke in 1882 after he observed its occurrence on a patient’s uvula. Although this is a rather rare presentation of the condition, angioedema does mainly affect similar areas with loose connective tissues, such as the bowel wall, extremities, eyelids, genitalia, larynx, lips, mouth, and throat. The occurrence in soft tissues is a unique characteristic of angioedema, as other forms of edema occur in different areas of the body, depending on the underlying condition. Angioedema is also unique from other forms of edema in that can be associated with signs of an allergic reaction and is asymmetrically distributed, non-gravitational or position dependent, and self-limiting.¹

There are 2 main clinical forms of angioedema distinguished by the type of vasoactive mediators involved. These substances increase vascular permeability, leading to the leakage of intravascular fluid into the surrounding interstitial space. The more common form is mast cell—mediated angioedema. Because of mast cell involvement, it is often accompanied by signs of an allergic reaction, such as flushing, pruritus, and urticaria. In severe cases, it can even lead to anaphylactic shock and bronchospasm. Some allergens that can trigger this form of angioedema include animal dander, food, pollen, venom, and drugs, such as aspirin, non-steroidal anti-inflammatory drugs, opiates, and radiopaque contrast agents.²

The second, less common, form is bradykinin-mediated angioedema. Although mast cell-mediated angioedema can occur within minutes to hours after allergen exposure, the onset of this form occurs within hours to days. Additionally, it presents in isolation without the accompanied signs and symptoms of an allergic reaction. The relationship between the trigger and the onset of symptoms is not readily apparent. For instance, patients taking angiotensin-converting enzyme inhibitors, which increase the levels of bradykinin, can experience angioedema within a week of starting the medication or after years of being on it.² Other forms of bradykinin-mediated angioedema include acquired and inherited C1 inhibitor deficiency, a condition that also results in an increased level of bradykinin. Triggers that can precipitate the onset include cold exposure, food, pregnancy, viral illness, and mild trauma from procedures, such as dental work and piercings.²

Treatment options for angioedema include anti-itch drugs, such as antihistamines, which reduce allergy symptoms, itching, and swelling. Most of these products are available over the counter. Another treatment option is anti-inflammatory drugs, such as corticosteroids. An example of this class of medication would be prednisone, which helps reduce itching, redness, and swelling. Also, drugs that suppress the immune system may be prescribed if antihistamines and corticosteroids are not effective.

There are also treatment options for hereditary angioedema (HAE), which is characterized as recurrent episodes of severe swelling. These treatment options are FDA-approved to prevent and treat HAE attacks. They include C1-inhibitors, such as Berinert and Cinryze, as well as B2 bradykinin receptor antagonists, such as Firazyr (icatibant). Haegarda is a self-administered C1-esterase inhibitor that can also help HAE attacks. Kalbitor (ecallantide) is an FDA-approved Kallikrein inhibitor for patients age 12 years and older, as is Takhzyro (ianadelumab-flyo). Orladeyo (berotralstat) is approved to prevent attacks in individuals age 12 years and older. Ruconest, is another option that is a plasma-free recombinant C1-inhibitor to treat HAE attacks.³

In addition, there are home and lifestyle remedies for those with mild angiodema or hives. These include avoiding triggers, such as food, insect stings, medication, and pollen. In addition, patients can use OTC anti-allergy medications, such as Benadryl, Claritin, and Zyrtec. Applying cold compresses to itchy skin and ease discomfort and limit scratching. Taking a cool bath with baking soda or oatmeal powder to relieve itching is also a potential short-term solution. Avoiding sun exposure and wearing loose, smooth-textured cotton clothing can also relieve discomfort.⁴

Saro Arakelians, PharmD, is vice president of pharmacy operations at a pharmacy in the Los Angeles, California, area. Ngoctran Tran is a PharmD candidate at the University of Southern California School of Pharmacy in Los Angeles.

References

• Nedelea I, Deleanu D. Isolated angiodema: an overview of clinical features and etiology. Exp Ther Med. 2019;17(2):1068—1072. doi:10.3892/etm.2018.6982
• Delves PJ. Angioedema. Merck Professional Manual. Updated October 2020. Accessed January 1, 2021. https://www.merckmanuals.com/professional/immunology-allergic-disorders/allergic,-autoimmune,-and-other-hypersensitivity-disorders/angioedema#v6516288
• US Hereditary Angioedema Association. FDA approved treatments. Accessed January 1, 2021. https://www.haea.org/pages/p/ApprovedTreatments
• Mayo Clinic. Hives and angioedema. Accessed January 4, 2021. https://www.mayoclinic.org/diseases-conditions/hives-and-angioedema/diagnosis-treatment/drc-20354914