[CIS PIDD] Angioedema in CVID

[Keller, Michael D]

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

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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.