Q:

1/25/2013
I have a 45yo female patient that I am suspicious has HAE with normal C1 INH function. She has had several episodes of angioedema of her face and larynx about 2x per year for the past 3 years, and abdominal episodes of severe abdominal pain with distention for approximately 24 hours 3x per year as well. NO urticaria. Recently admitted in the ICU for laryngeal angioedema that required 4 doses of epinephrine. Normal TSH, negative Anti-IgE receptor antibodies, negative thyroid antiboides, normal c4 and normal c1 INH. She takes Claritin daily and now is on combination H1/H2/leukotriene antagonists. Not clear if she is nonresponsive to antihistamines and steroids since episodes only a few times per year. How do I assess her for the factor 12 mutation? Has there been any success in getting firazyr approved in these patients? Thanks for your insight!

A:

Thank you for your inquiry.

Your inquiry is topical in that it coincides with a landmark article recently published in Allergy and Asthma Proceedings dealing with the issues highlighted by your patient. This article should be available to you online free of charge. The full reference is:

Hereditary angioedema with normal C1 inhibitor function: consensus of an international expert panel. Allergy and Asthma Proceedings 2012 (November/December) (Supplement 3); 33(6). The lead author of this publication was Dr. Bruce Zuraw.

Dr. Zuraw is an internationally known expert in angioedema, and I am going to ask him to respond to your inquiry. As soon as we receive his response, we will forward it to you.

Thank you again for your inquiry.

Sincerely,
Phil Lieberman, M.D.

We have received a response from Dr. Bruce Zuraw regarding your Ask the Expert inquiry. Thank you again for your inquiry and we hope this response is helpful to you.

Sincerely,
Phil Lieberman, M.D.

Response from Dr. Bruce Zuraw:
I would agree that HAE with normal C1INH is a possibility in this patient.

Some further diagnostic questions would be:

- does she have a family history of angioedema? It is important to keep in mind that HAE with normal C1INH has low penetrance and can appear to skip generations, esp in men

- I presume that she did not respond to epi based on the fact that she required 4 doses; but it would be good to state that if true

- you say that her C1INH was normal, but is that antigenic or functional? If functional, was it the Quidel assay or the chromogenic assay? To exclude a diagnosis of type II HAE, it is best to make sure that you measure the C1INH function using the chromogenic assay, which is available from National Jewish complement lab

- the standard factor XII mutational assay is also available from National Jewish complement lab

If you do establish a diagnosis of HAE with normal C1INH, most insurance plans will approve a trial of icatibant. It is important, however, to closely monitor the efficacy of icatibant as the cost is very high and you don't want patients self-injecting repeatedly if the value is questionable.

Another good therapeutic option (prophylactically) is to put her on a strong progesterone, which is reported to work in the large majority of these patients.

Finally, if you cannot make a clear diagnosis of HAE with normal C1INH (or even if you do), you might consider a trial of epsilon aminocaproic acid or tranexemic acid.

Regards,
Bruce Zuraw

AAAAI - American Academy of Allergy Asthma & Immunology