Q:

1/29/2013
I would like your help in the management of a 68 yr old Syrian lady with a history recurrent angioedema for the last 5 years with multiple admissions to the hospital in Syria for angioedema symptoms of the face, extremities and abdomen. She was treated with steroids and H1 and H2 blockers, but as they lacked the ability to do any tests to investigate this further no further work-up was initiated. The family lives here and due to their concern, she came to her family here for further evaluation. She has never had any urticaria associated with the angioedema. The daughter states hat she has not responded to steroids and antihistamines while in hospital and her symptoms would eventually resolve. Tests done here include C4, CH50, C1q and C1 esterase inhibitor (functional and quantitative) all of which were normal. I wish to know how to proceed in treating her since she has not improved on the traditional antihistamines and steroid combinations. She is equipped with an epipen but I am not sure how useful this will be, if it is bradykinin-mediated. I have read anecdotally that Dapsone is benign used as are some treatments for HAE. Thank you for helping me in the management of this lady.

A:

Thank you for your inquiry.

The problem with your patient, recalcitrant angioedema, is one that has been dealt with many times on our website. Unfortunately, there is no definitive management strategy. However, the most common tactics applied for management of a patient with recalcitrant angioedema and normal complement levels is to employ alternative therapies.

Over the last several years, anti-kinin therapy has been used successfully in a number of cases with no evidence of complement abnormalities, but a clinical course significant with kinin-mediated disease. The terminology recent employed to refer to these patients is “non-histaminergic angioedema.” Not all such cases respond to anti-kinin therapy, but I would choose it as the first choice in your patient. Several references (1-4) have dealt with this issue. I think the most helpful one would be Reference Number 1 from the Annals of Allergy, Asthma, and Immunology. In this instance, icatibant was employed, and that would be my first choice in your patient.

You mentioned dapsone, and this is another potential alternative therapy. The best discussion of such alternative therapies can be found in Reference Numbers 5 and 6. These two articles discuss alternative therapies for recalcitrant chronic urticaria, but the same drugs can be employed for angioedema. The use of one of these agents, which includes dapsone, would be a second choice if icatibant did not work, or you could not obtain this drug.

In addition to dapsone, there are a number of other agents that have been used successfully. Probably cyclosporin/tacrolimus has been most commonly reported in the literature, but mycophenolate mofetil has also been a successfully employed alternative drug.

I know of no other prospective therapy except for the agents noted above.

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

References:
1. Annals of Allergy, Asthma, and Immunology 2012; 108(6):460-461.

2. Cougno M, et al. Bradykinin and the pathophysiology of angioedema. International Immunopharmacology 2003 (March); 3(3):311-317.

3. Franzen D, et al. Idiopathic non-histaminergic angioedema-oedema after routine extubation successfully treated with fresh frozen plasma. Anaesthesia 2006; 61(7):698-701.

4. Bouillet L, et al. Non-histaminic angioedema management: diagnostic and therapeutic interest of tranexamic acid. Rev Med Interne 2004 (December); 25(12):924-926

5. Morgan and Kahn. Therapeutic alternatives for chronic urticaria, an evidence-based review, Part 1. Annals of Allergy, Asthma and Immunology, Volume 100 (Number 5), pages 403-412, May 2008.

6. Morgan and Kahn. Therapeutic alternatives for chronic urticaria, an evidence-based review, Part 2. Annals of Allergy, Asthma and Immunology, Volume 100 (Number 6), pages 517-526, 2008.

Sincerely,
Phil Lieberman, M.D.

AAAAI - American Academy of Allergy Asthma & Immunology