[CIS PIDD] Angioedema in CVID

[Riedl, Marc]

A couple of thoughts on these CVID/angioedema patients, as we see many individuals with each of these conditions at our center and a few with both.  I haven't been able to discern a causative link.  I think CVID patients are "allowed" to get other common medical conditions by chance.

 1.  Following the urticaria literature, it's clear that some idiopathic histamine-mediated angioedema requires high-dose daily antihistamines to achieve effects, I.e. Cetirizine 40 mg qd +/- hydroxizine 50-100 qhs.  We're commonly referred patients who are "unresponsive to antihistamines" and simply increasing the dose to these levels improves or suppresses their symptoms.
 2.  If a non-histamine mediated angioedema is strongly suspected, be aware that the C1INH functional assay done at the major commercial labs (LabCorp, Quest, etc.) is the Quidel assay which has been shown to have up at a 30% "false negative" rate, I.e. the functional C1INH level will be reported as normal when in fact it is low when assayed using the more sensitive and specific Chromogenic C1INH Functional assay.  To my knowledge, National Jewish Complement lab is the only lab in the country currently performing the Chromogenic assay.  It's worth considering this send-out test to definitively r/o C1INH deficiency, if in fact angioedema patients are truly refractory to high-dose antihistamines and corticosteroids.

Best,

Marc

Marc Riedl, M.D., M.S.
Associate Professor of Medicine
Section Head, Clinical Immunology and Allergy
UCLA - David Geffen School of Medicine
10833 Le Conte Ave, 37-131 CHS
Los Angeles, CA  90095-1680
Tel 310.206.4345  Fax 310.267.009


From: Yeşim Yılmaz Demirdağ <dryesimyilmaz at gmail.com<mailto:dryesimyilmaz at gmail.com>>
Reply-To: pagid listserve <pagid at list.clinimmsoc.org<mailto:pagid at list.clinimmsoc.org>>
To: pagid listserve <pagid at list.clinimmsoc.org<mailto:pagid at list.clinimmsoc.org>>
Subject: Re: [CIS PIDD] Angioedema in CVID

Hi Mike,
I am following a similar case:
He is a 22-year-old man with selective IgA deficiency and environmental allergies. He started having angioedema symptoms at age 19, he had peripheral and facial/lip/tongue swellings almost 2-3 times/wk. He was in the hospital almost every week. On several occasions he had urticarial lesions as well. Labs were all negative. Symptoms did not respond to therapeutic dose of H1 and H2 antihistamines, steroids, epi, Kalbitor (he had allergic reaction to Kalbitor after 3 rd treatment), and high dose IVIG. He had to quit his job and school and he was in the process of applying for disability.
Then 1.5 yr ago he started to take Allegra 180 bid, Zyrtec 10 bid, Zantac 300 mg bid, and Singulair 10 mg daily. And surprisingly he did not have any symptoms for about 6 months when he was on this combination. Moreover, his symptoms recur within 48 hours when we try to wean one of the H1 antihistamines and when we stop Singulair. He has not been in the hospital in the past 1.5 yr, he is back to work and school and doing great.
I cannot answer how this combination worked, but it worked. You may want to try this on your patient. Good luck,
Yesim

Yesim Yilmaz Demirdag, MD
Section of Allergy and Immunology
Department of Pediatrics
Morgantown, WV




On Sat, Jul 7, 2012 at 7:48 PM, Keller, Michael D <KellerMD at email.chop.edu<mailto:KellerMD at email.chop.edu>> wrote:
Dear colleagues:

We have a very mysterious case of a 16 year old with CVID and severe recurrent angioedema, detailed below.  We would be most grateful for any thoughts on possible diagnoses or treatments.

Best regards,

Mike Keller
Children's Hospital of Philadelphia

--------------------

The patient is a 16 yr old with CVID and recurrent facial angioedema episodes for the past 8 months.  These episodes occur irregularly, without clear trigger, with swelling of the lips and tongue and distressed breathing.  They have been associated with hives on the neck in some instances.

Three months after onset, he had a several angioedema flare requiring a 7 week hospitalization, including ICU admission and intubation.

Prior workup of the angioedema:
-Negative hereditary angioedema testing (normal C1 esterase inhibitor function, normal C3/C4)
-Normal thyroid screening
-Negative viral studies: Hep B (antigen), Hep C (serologic & pcr), EBV (pcr), HIV (Ag/Ab)
-Negative CIU index, negative ANCA, negative ANA, normal serum ACE
-Normal tryptase
-Normal SPEP
-Negative urine metanephrines
-Unremarkable PET scan to evaluate for occult infection / malignancy.

He does have multiple environmental and food allergies, but flares occur without any allergic triggers (including while inpatient and NPO during his most severe episode).  There are no obvious physical triggers for urticaria or angioedema, though in a few episodes, he has had a concurrent sinusitis.

With regard to therapies:
-flares seem to respond to epinephrine, but are steroid refractory
-antihistamines (allegra, zyrtec, doxepin) have failed to prevent episodes.  Diphenhydramine seems to have a minimal subjective impact.
-During more severe flares, other therapies have been tried without impact: FFP, xolair (x 2 doses), icatibant (which seemed to worsen swelling).
-Immunomodulatory (2g/kg) IVIG seemed to improve his most recent flare.

With regard to his CVID history, he was diagnosed at age 13 years, and has been maintained on IVIg since that time.   Aside from humoral deficiency, he has normal lymphocyte flow cytometry including present switched memory B-cells, and normal lymphocyte proliferation to PHA, ConA, and PWM.


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