Hereditary Angioedema Caused By C1-Esterase Inhibitor Deficiency: A Literature-Based Analysis and Clinical Commentary on Prophylaxis Treatment Strategies

Abstract

Hereditary angioedema (HAE) caused by C1-esterase inhibitor deficiency is an autosomal-dominant disease resulting from a mutation in the C1-inhibitor gene. HAE is characterized by recurrent attacks of intense, massive, localized subcutaneous edema involving the extremities, genitalia, face, or trunk, or submucosal edema of upper airway or bowels. These symptoms may be disabling, have a dramatic impact on quality of life, and can be life-threatening when affecting the upper airways. Because the manifestations and severity of HAE are highly variable and unpredictable, patients need individualized care to reduce the burden of HAE on daily life. Although effective therapy for the treatment of HAE attacks has been available in many countries for more than 30 years, until recently, there were no agents approved in the United States to treat HAE acutely. Therefore, prophylactic therapy is an integral part of HAE treatment in the United States and for selected patients worldwide. Routine long-term prophylaxis with either attenuated androgens or C1-esterase inhibitor has been shown to reduce the frequency and severity of HAE attacks. Therapy with attenuated androgens, a mainstay of treatment in the past, has been marked by concern about potential adverse effects. C1-esterase inhibitor works directly on the complement and contact plasma cascades to reduce bradykinin release, which is the primary pathologic mechanism in HAE. Different approaches to long-term prophylactic therapy can be used to successfully manage HAE when tailored to meet the needs of the individual patient.

Orolingual angioedema after alteplase therapy of acute ischaemic stroke: incidence and risk of prior angiotensin‐converting enzyme inhibitor use

“…The incidence of rt‐PA‐related OA may also be associated with various genetic or ethnic predispositions. Genetic polymorphism which causes C1‐esterase deficiency leads to bradykinin overproduction . This genetic cofactor may increase the susceptibility of rt‐PA‐related OA.…”

Human Plasma-Derived, Nanofiltered, C1-Inhibitor Concentrate (Cinryze®), a Novel Therapeutic Alternative for the Management of Hereditary Angioedema Resulting from C1-Inhibitor Deficiency

“…The second step is the introduction of pharmacotherapy. The goal of prophylactic treatment is either to decrease the number and severity of angioedema attacks (longterm prophylaxis) or to reduce the likelihood of swelling in a patient undergoing a stress or procedure likely to precipitate an attack (short-term prophylaxis) [14, 24]. …”

Hereditary Angioedema Post-liver Transplant

“…HAE is a rare autosomal dominant inherited disorder affecting 1:70,000 in the general population (2). It is classically due to mutations in SERPING1 which results in C1‐esterase inhibitor (C1‐INH) deficiency (3), although other genetic defects have been described. The disease is heterogeneous in presentation, ranging from abdominal pain to fatal upper airway obstruction (2).…”