A Case Of Hereditary Angioedema

A 34-year-old female establishes care in your clinic. Her medical history consists of intermittent abdominal pain and episodes of angioedema in the past with unclear etiology. She has received multiple laparoscopic procedures that were unrevealing. During the initial interview, she relates several past episodes of lip and tongue swelling, for which she has not sought medical assistance. She has tried diphenhydramine without significant improvement. The swelling episodes resolve without intervention after 3–4 days.
Which of the following laboratory tests would be most helpful in establishing the diagnosis in this
patient?

A) ANA.
B) C3 complement level.
C) C4 complement level.
D) Complete blood count (CBC).
E) SS-A and SS-B.

Answer And Discussion

The correct answer is “C.” ( C4 complement level.)

This patient’s presentation should raise concern for hereditary angioedema (HAE), or C1-esterase inhibitor deficiency. This entity is clinically characterized by recurrent episodes of angioedema involving any part of the body. Thus, it can present with laryngeal angioedema (the major
cause of death) or recurrent abdominal pain (generally with a normal white count and “always” without peritoneal signs). Urticaria is not a feature of this disorder.
HAE is caused by a C1-esterase inhibitor deficiency, which allows an over exuberant activation of the complement cascade. For this reason, patients with C1- esterase inhibitor deficiency have chronically low levels of C2 and C4. They may have normal levels of C1-esterase inhibitor but have a nonfunctional allele. Thus, “C” is the right answer and C4 levels should be low if the patient has C1-esterase inhibitor deficiency. Of course, you will also check a C1- esterase inhibitor level keeping in mind that the nonfunctional allele may give a false negative test (e.g., the presence of a nonfunctional C1-esterase inhibitor).

While awaiting the test results, you discuss HAE with your patient. In order to minimize future attacks of angioedema, you recommend which of the following?

A) Avoidance of estrogen containing medications.
B) Avoidance of ACE inhibitors.
C) Testing and treatment of Helicobacter pylori.
D) All of the above.

Discussion
The correct answer is “D.”

Education is the cornerstone of treatment of HAE. Patients need to know what triggers to avoid and how to identify symptoms early. Most attacks are precipitated by trauma (often head and upper airway trauma), medical procedures (dental and oral surgery in particular), emotional stress, infections, menstruation, or the use of medications, especially oral contraceptives and ACE
inhibitors. Interestingly, H. pylori infection has been associated with HAE, and H. pylori eradication reduces the frequency of angioedema attacks.

Your patient is ultimately diagnosed with HAE. In this particular patient, which medication would
be most helpful in preventing future episodes?

A) Emergency epinephrine.
B) Oral diphenhydramine.
C) Fresh frozen plasma (FFP).
D) Androgens (e.g., danazol)
E) No prophylactic treatment is available.

Discussion
The correct answer is “D.” Emergency epinephrine and antihistamines have not generally been effective, as HAE is not allergic in nature. Prophylactic treatment in the form of attenuated androgens (danazol) is available. Attenuated androgens appear to work by up-regulating the synthetic capability of hepatic cells that make C1-esterase inhibitor, thus raising the C4 level and reducing the number and severity of acute exacerbations.

Treatment of acute episodes of HAE includes FFP that contains C1-esterase inhibitor, the C1-esterase
inhibitor replacement protein products, and bradykinin/kallikrein inhibitors (ecallantide and icatibant). Additionally, these three options could be used as prophylactic treatment in short-term
situations, such as prior to surgery in a high-risk patient. However, FFP would not be a long-term
preventive measure, so “C” is incorrect.

Make sure patients with HAE receive the hepatitis B vaccination series as they may require blood products for acute treatment of angioedema.