Case study showcases difficulty with angioedema diagnosis

Woman has endured more than a decade of facial swelling attacks

Marisa Wexler, MS avatar

by Marisa Wexler, MS |

Share this article:

Share article via email
In this case study illustration, doctors hold a giant magnifying glass in front of a patient who has red spots on his face and neck.

A woman still doesn’t have a definitive answer as to the underlying cause of her angioedema after more than a decade of recurrent facial swelling, underscoring the difficulties in diagnosing the condition.

“This case report demonstrates the challenge of the differential diagnosis of angioedema without wheals,” the researchers wrote in “Angioedema with normal complement studies: What do we know?,” which was published in The Journal of Allergy and Clinical Immunology: In Practice.

Angioedema is the medical term for swelling in the deeper layers of the skin. There are several types of angioedema, depending on its underlying cause or causes.

The researchers here described the case of a 65-year-old woman of Italian heritage who’d worked as a cook but retired in 2006 after she started having episodes of facial swelling.

The swelling was initially assumed to be an allergic reaction to a cholesterol-lowering medication she’d recently started, but the episodes continued even after she stopped taking it and her swelling didn’t ease in response to allergy medicines. She also didn’t have a rash or wheals accompanying the swelling, which is commonly seen with allergy-related angioedema.

Recommended Reading
A magnifying glass highlights one of many ticked boxes on a survey form.

Diagnosis of HAE delayed a median of 20 years in Latvia: Study

Trouble diagnosing angioedema

The woman reported having facial swelling eight to 10 times a year, generally lasting for several days, but never interfering with her breathing. She also reported swelling in her legs and feet once or twice a month.

The woman had a history of other medical issues, including high blood pressure, diabetes, and depression. She was receiving treatment for these issues, including with some medications that can cause swelling as side effects. While her clinicians were unable to rule out the possibility that her swelling might be a medication side effect, changing treatments didn’t notably affect the swelling episodes.

The researchers said her clinical picture suggested she had some form of angioedema that was driven by the excessive production of the signaling molecule bradykinin. Increased bradykinin signaling drives swelling attacks in hereditary angioedema (HAE).

Most cases of HAE are caused by mutations that disrupt the activity of C1-inhibitor, a protein that normally blocks the activity of other proteins that promote bradykinin’s production. However, tests of C1-inhibitor activity were normal.

Rarer forms of HAE caused by mutations in different genes also have been reported. But genetic testing failed to identify any known HAE-causing mutations in this woman.

Relatives in Italy said one of the patient’s uncles once had swelling episodes, suggesting a possible family history. However, details about his condition weren’t available, so nothing could be definitively concluded.

The woman started treatment with tranexamic acid and, while she’s still having swelling attacks, the treatment lowered their severity. She was instructed to seek immediate medical attention if she ever has a swelling attack that impairs her ability to breathe and she’s been given a letter that details the history of her condition in case of an emergency.

The researchers described this as “a complicated case with many implications underscoring the importance of a comprehensive personal and family history, a careful medication history, and the reported effectiveness of previously trialed medications.”