Snapshot A 23-year-old woman with past medical history of multiple allergies leading to facial swelling presents with marked difficulty breathing, abdominal pain, and swelling of the face and neck. On physical exam, her extremities are also noted to be markedly swollen (picture). She is immediately sedated for intubation to maintain patency of airway. Chart review reveals newly-started ACE-inhibitor. She is given epinephrine, fluids, and fresh frozen plasma. Introduction Disorder of complement, causing angioedema Genetics autosomal dominant Pathogenesis C1 esterase inhibitor deficiency C1 esterase inhibitor inhibits kallikrein-kinin pathway remember kallikrein activates bradykinin bradykinin ↑ vasodilation ↑ permeability ↑ pain ACE-inhibitors are contraindicated ACE inactivates bradykinin ACE-inhibitors allows ongoing bradykinin, causing angioedema Epidemiology attacks begin during childhood Risk factors family history of angioedema family history of those contraindicated with ACE-inhibitors autoimmune conditions Presentation Symptoms/physical exam recurrent episodes of angioedema without urticaria as opposed to anaphylaxis, which typically has urticarial angioedema of the face, oropharynx, extremities, or abdomen angioedema of GI tract severe abdominal pain GI upset worst at 24 hours resolves over 48-72 hours often preceded by prodrome fatigue flu-like symptoms not responsive to epinephrine (epi-pen) or antihistamines Evaluation Best initial test ↓ C4 and C2 levels if C4 are normal, C1 inhibitor deficiency is unlikely To confirm diagnosis if ↓ C4 ↓ C1 inhibitor antigenic levels ↓ C1 inhibitor functional levels Differential Diagnosis Anaphylaxis Allergic angioedema Facial cellulitis SVC syndrome Treatment Anaphylaxis presents very similarly to angioedema and often cannot be differentiated immediately in an emergency room setting therefore, patients are often initially treated with medications for anaphylaxis given urgent, life-threatening nature of anaphylaxis epinephrine fluid replacement anti-histamines Assess airway, even after administering treatment intubate if necessary As soon as possible, especially if epinephrine and anti-histamines are not effective, administer medications for hereditary angioedema plasma-derived C1 inhibitor recombinant human C1 inhibitor fresh frozen plasma if above are not available Prognosis, Prevention, and Complications Prognosis mortaliy >30% in those with laryngeal angioedema angioedema is unpredictable Complications small bowel obstruction compartment syndrome death by asphyxiation