This patient's presentation of facial swelling and laryngeal edema in the setting of prior episodic attacks and recent ACE-inhibitor use is consistent with a diagnosis of hereditary angioedema. Hereditary angioedema is caused by an autosomal dominant deficiency of C1 esterase inhibitor.
The lack of C1 esterase inhibitor leads to unchecked activation of C1, C2, and C4 complement components. In turn, bradykinin is the inflammatory mediator responsible for capillary leakage and resulting swelling (see illustration B). Symptoms may include swelling of the face, GI tract, extremities, and upper airways. Laryngeal edema is the most feared complication, with severe cases potentially requiring emergent intubation or a surgical airway. ACE-inhibitors should be avoided in these patients, as ACE-inhibitors lead to accumulation of bradykinin, which can precipitate attacks.
Pavletic discusses late angioedema caused by ACE inhibitors. 0.1-0.2% of patients initiated on an ACE-inhibitor are complicated by development of angioedema within 1 week of initiating treatment. Late-onset angioedema after ACE inhibitor therapy is a diagnosis that is commonly missed. African Americans are at increased risk of this complication. Management involves discontinuation of the causative agent and, for severe cases, epinephrine, diphenhydramine, steroids, and emergent cricothyroidotomy.
Duffey et al. review the management of hereditary angioedema, focusing on the medication ecallantide. Ecallantide is a reversible inhibitor of kallikrein indicated for acute hereditary angioedema attacks in patients over 12 years of age. It has demonstrated significant improvements in symptoms in comparison to placebo. Some reports have noted an increased risk of anaphylaxis with use of this medication.
Illustration A demonstrates an example of the progressive facial swelling (A to D) seen in hereditary angioedema. Illustration B shows the bradykinin pathway; note how the absence of C1 esterase inhibitor leads to unchecked activation of inflammatory mediators. Illustration C summarizes the different types of hereditary angioedema.
Answer 1: MHC class I deficiency results in bare lymphocyte syndrome, which presents with recurrent bacterial infections and decreased CD8+ T cell counts.
Answer 2: Chediak-Higashi syndrome is characterized by a defect in lysosomal storage proteins, leading to defective microtubule function that results in recurrent pyogenic infections, partial albinism, and peripheral neuropathy.
Answer 3: A lack of NADPH oxidase leads to chronic granulomatous disease and recurrent infections with catalase-positive organisms.
Answer 4: A defect in the Wiskott-Aldrich syndrome cytoskeletal glycoprotein leads to a partial B and T cell deficiency with symptoms including thrombotyopenic purpura, infections, and eczema.
Pavletic A. Late angioedema caused by ACE inhibitors underestimated. Am Fam Physician. 2002 Sep 15;66(6):956, 958.
PMID:12358222 (Link to Abstract)
Duffey H, Firszt R. Management of acute attacks of hereditary angioedema: role of ecallantide. J Blood Med. 2015 Apr 16;6:115-23. doi: 10.2147/JBM.S66825. eCollection 2015.
PMID:25931832 (Link to Abstract)