Abstract
BackgroundHereditary angioedema with normal C1 inhibitor (HAE-nC1 INH) is a rare, underappreciated condition characterized by recurrent subcutaneous angioedema. The underlying pathophysiology and diagnostic criteria continues to evolve. There is a significant overlap between HAE-nC1 INH and idiopathic nonhistaminergic angioedema, ultimately this may be found to be the same condition. Characterization of cohorts suspected to have either of these conditions is warranted to help refine diagnosis, pathophysiology, and treatment response.MethodsA retrospective chart review of 418 patients diagnosed with angioedema was conducted. The following inclusion criteria was used: lack of response to antihistamines, steroids, and epinephrine; normal C4, C1 inhibitor (C1 INH) level and function; lack of urticaria or pruritus; occurrence without offending drugs; and positive family history. Enzyme immunoassays for C1 INH function were performed at the Mayo Clinic. Charts meeting these criteria were reviewed for frequency and type of episodes as well as use and response to therapies.Results6 patients met the above criteria. 3 of these completed genetic testing, none were found to have factor XII abnormalities. None had angiopoietin 1 or plasminogen gene sequencing. 5 of 6 patients were successfully treated with C1 INH or tranexamic acid for acute treatment of attacks (4 with C1 INH and 1 with tranexamic acid). 4 patients have used Icatibant with good response (typically under 40 min for near full recovery); of these, 3 required Icatibant as acute treatment after other therapies (C1 inhibitor and tranexamic acid) were ineffective. There were 9 patients who otherwise met criteria, but due to a lack of family history were classified as having idiopathic non-histaminergic angioedema.ConclusionsThis retrospective chart review found 6 HAE-nC1 INH patients in Manitoba. 1 responded to tranexamic acid and not C1 INH, 4 typically responded to C1 INH, and 1 responded exclusively to Icatibant. All patients—4 total—who used Icatibant responded; of these 4 patients, 3 required Icatibant after other therapies had failed.
Highlights
Hereditary angioedema with normal C1 inhibitor (HAE-nC1 hereditary angioedema with normal C1 inhibitor (INH)) is a rare, underappreciated condition characterized by recurrent subcutaneous angioedema
Hereditary angioedema with normal C1 inhibitor (HAE-nC1 INH) is a rare, underappreciated condition characterized by recurrent angioedema and can be life threatening if it involves the upper airway
Genetic testing was confined to factor XII and was only performed in 3 patients due to limited availability in our current healthcare system. 4 of 6 patients have used Icatibant and all demonstrated a response. 3 patients responded to Icatibant when other treatments (C1 inhibitor and tranexamic acid) were ineffective
Summary
Hereditary angioedema with normal C1 inhibitor (HAE-nC1 INH) is a rare, underappreciated condition characterized by recurrent subcutaneous angioedema. Hereditary angioedema with normal C1 inhibitor (HAE-nC1 INH) is a rare, underappreciated condition characterized by recurrent angioedema and can be life threatening if it involves the upper airway. Family history is extremely useful when making the diagnosis, the rate of de novo mutations in HAE-nC1 INH is unknown; as a reference, 25% of patients with HAE types I and II have de novo mutations, i.e. no family history [3]. Genetic testing is only useful when positive, as only 20–25% of HAE-nC1 INH patients have a FXII mutation [1]. As pathogenic mutations continue to be discovered, genome sequencing may play an increasing role in the diagnosis of HAE-nC1 INH. There is significant overlap between HAE-nC1 INH and idiopathic nonhistaminergic angioedema: these may be found to be the same condition
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