Hereditary and acquired angioedema

Abstract

Hereditary angioedema (HAE) is an autosomal dominant disorder defined by a deficiency of functional C1 esterase inhibitor (C1-INH). Acquired angioedema is due to either consumption (type 1) or inactivation (type 2) of CI-INH. Both HAE and acquired angioedema can be life-threatening. Of the three types of HAE, type 1 is most common, occurring in approximately 85% of patients and characterized by decreased production of C1-INH, which results in reduced functional activity to 5‐40% of normal. Type 2 occurs in 15% of cases; C1-INH is detectable in normal or elevated quantities but is dysfunctional. Also, HAE with normal CI-INH (previously called type 3 HAE) is rare and characterized by normal complement studies. Specific genetic mutations have been linked to factor XII, angiopoietin-1, and plasminogen gene. Patients with unknown mutations are classified as unknown. The screening test for types 1 and 2 is complement component C4, which is low to absent at times of angioedema and during quiescent periods. A useful test to differentiate HAE from acquired angioedema is C1q protein, which is normal in HAE and low in acquired angioedema. The management of HAE has been transformed with the advent of disease-specific therapies. On-demand therapy options include plasma and recombinant C1-INH for intravenous infusion; ecallantide, an inhibitor of kallikrein; and icatibant, a bradykinin β2 receptor antagonist, both administered subcutaneously. For long-term prophylaxis, intravenous or subcutaneous C1-INH enzyme replacement and lanadelumab, a monoclonal antibody against kallikrein that is administered subcutaneously, are effective agents.

Novel SERPING1 gene mutations and clinical experience of type 1 hereditary angioedema from North India

“…These include mutations in angiopoietin 1 gene (HAE‐ANGPT1), plasminogen gene (HAE‐PLG), and Kininogen‐1 gene 8,22–25 . Acquired angioedema (AAE‐C1‐INH) has mostly been reported in association with drugs, autoimmune diseases, and B‐cell lymphoproliferative disorders 26 . Patients with AAE have older age at onset (4th or 5th decades of life).…”

Acute Presentation of Undiagnosed Hereditary Angioedema of the Larynx: Averting Death

“…The primary differential diagnosis to be excluded is AAE, which can be secondary to hematologic malignancy (9). Patients who present at an advanced age need to be investigated to rule out AAE (9,10). The presence of B-symptoms, clinical examination, peripheral blood morphology, and immunoglobulin levels may be useful on a case to case basis (10).…”

Between two storms, vasoactive peptides or bradykinin underlie severity of COVID‐19?

“…This was timely recognized by several groups of investigators early during the pandemic (Roche & Roche, 2020; van de Veerdonk et al, 2020) and most recently was confirmed by a preliminary gene expression analysis study focusing on detailed evaluation of the RAS members, bradykinin and associated systems in samples from COVID‐19 and control patients (Garvin et al, 2020). This is a critical development, because bradykinin is a potent inflammatory mediator that has been associated with a number of pathophysiological conditions including angioedema (Patel & Pongracic, 2019), vasculitis (Karpman & Kahn, 2009), asthma (Ricciardolo et al, 2018), autoimmunity (Dutra, 2017), acute brain injury and neuroinflammation (Albert‐Weissenberger et al, 2013).…”