Medical Mystery of the Week

Because of the COVID19 pandemic, you are practicing medicine by telemedicine. Your patient, a 45-year-old woman, presented to the emergency room with acute onset abdominal pain, nausea, and emesis of non-bloody clear fluid. She also noted simultaneous swelling of her hands.

You are provided with an x-ray of her abdomen taken after the ingestion of gastrograffin and a picture of her hands (see below).

What is your diagnosis, what test(s) would you order to confirm your suspicions, and what treatment, if any, would you recommend?

DIAGNOSIS: Acute episode of hereditary angioedema (HEA).

HEA is due to deficient levels of C1-inhibitor (C1INH) as a result of inherited or acquired mutations in the Serping-1 gene. Often in the setting of vascular trauma, such as might occur during a surgical or dental procedure, C1INH deficiency causes acute episodes of angioedema intitiated by activation of the classical pathway of complement and by binding of bradykinin to endothelial cell B2 receptors. The former reduces blood levels of complement components C1 and C4, the latter leads to activation of prekallekrein and factor XII → kallekrein and factor X!Ia → angioedema. As demonstrated in the present case, the angioedema can involve the gastrointestinal tract and present with acute onset abdominal pain and x-ray evidence of mucosal edema. The clinical clue to the diagnosis in the presented case is the concurrent edema of the hands. Angioedema caused by ACE inhibitors is also due to activation of the kallekrein system.

Treatment of acute episodes of HEA consists of the administration of fresh frozen plasma or, if available, recombinmant C1INH. Long term management is difficult, particularly in pediatric patients (the onset of HAE is often in this age group). Newer investigative therapies include kallekrein inhibitors and concentrates of human recominant C1INH that can be administered subcutaneously.