Q:

1/16/2013
I am seeing a 17 year old male for recurrent episodes of angioedema. He has had recurrent episodes of facial and lip swelling without any clear triggers (foods, medications, exercise, insect stings, etc). There is no family history of angioedema. He has been on twice daily fexofenadine with some decrease in the frequency of his angioedema flares. Laboratory evaluation for hereditary angioedema on multiple occasions has demonstrated a low C1 INH level on multiple occasions (non-functional), with normal C4 (both during and in between episodes), normal C1 INH functional level, and normal C1q. Do you think that the low C1 INH level by itself without a low C4 indicates hereditary angioedema. His C1 INH level ranges between 18-19 with our lab normal being between 21-39. I know that there are some cases of hereditary angioedema with normal C4. Thank you for your assistance and I look forward to your response.

A:

Thank you for your inquiry.

You are correct in that hereditary angioedema can exist with a normal C4 level. However, all cases of which I am aware have normal levels only during asymptomatic periods. C4 levels are depressed during an episode (1). The fact that your patient has a normal C4 during both symptomatic and asymptomatic periods strongly mitigates against a pathogenesis related to a defective function of C1 inhibitor. Coupled with this of course is the lack of family history and the normal functional level of C1 inhibitor. If taken as a whole, these findings point toward idiopathic angioedema.

I add parenthetically that even if his episodes are idiopathic, he may still respond with drugs usually reserved for treatment of C1 esterase inhibitor deficiency syndromes as noted on several previous entries to our Ask the Expert website. The most recent of these was entitled “Recalcitrant angioedema; potential treatment with icatibant” which was posted on 11/20/2012. You can access this entry by going to our website and typing “angioedema” into the search box.

I would also, in answering your inquiry, call your attention to a recent reference which provides a new nosology for angioedema based upon a consensus of an expert panel convened by the Hereditary Angioedema Society. This article will also help put your patient into perspective (2).

Thank you again for your inquiry and we hope this response is helpful to you.

References:
1. Frank J Eidelman. Hereditary angioedema: New therapeutic options for a potentially deadly disorder. BMC Blood Disorders 2010; 10:3.
2. Zuraw BL, Bork K, E Binkley K, Banerji A,Christiansen SC, Castaldo A, Kaplan A, Riedl M, Kirkpatrick C, Magerl M, Drouet C, Cacardi M. Hereditary angioedema with normal C1 inhibitor function: Consensus of an international expert panel. Allergy Asthma Proc 2012 (Dec 13).

Sincerely,
Phil Lieberman, M.D.

AAAAI - American Academy of Allergy Asthma & Immunology