Idiopathic Angioedema: Difficult Cases and Uncommon Findings
Saturday, March 5, 2016
South Exhibit Hall H (Convention Center)
Laura E. Noonan, MSN, FNP-C, Oral Alpan, M.D., Denise Loizou, RN, Ozlem Goker-Alpan, M.D.

Idiopathic angioedema is a poorly defined disorder.  We present two cases of steroid and antihistamine non-responsive angioedema whose workup showed genetic variations outside the immune and complement pathways that may be potential triggers for their symptoms.


Whole exome sequencing (WES) performed by Gene Dx.


The first case is a 17 year old female who presented with recurrent swelling of her face, hands, and feet, headaches, and severe abdominal pain.  She has normal C1 esterase inhibitor level and function.  Symptoms are not relieved by antihistamines or steroids.  The patient has moderate relief with use of C1 esterase inhibitor.  WES identified compound heterozygosity for p.E172K and p.G216R variants of the TIE-1 gene.  This has been found in a murine model to cause vascular leakage.

The second case is a 20 year old female with a history of recurrent swelling of her lips and tongue with normal C1 esterase inhibitor level and function.  She gets no relief with allergy or HAE treatments.  WES showed she is heterozygous for a variant of unknown significance of the PDE11A gene.  In vitro studies demonstrate that PDE11A is involved with cyclic AMP (cAMP) and cyclic GMP (cGMP) metabolism, and mutations lead to increased cGMP and cAMP levels in cell models.  We hypothesize that increased cAMP and cGMP levels may contribute to sustained vasodilation and enhancement of triggers leading to the severity of her symptoms. 


Genetic evaluation, such as WES, may provide insight for patients whose angioedema does not respond to conventional allergy or HAE treatments.