Appraisal of danazol prophylaxis for hereditary angioedema
Hereditary angioedema (HAE) is an autosomal dominant disease characterized by painful, recurrent attacks of inflammation affecting the hands, feet, face, abdomen, urogenital tract, and the larynx. The inflammation can be disfiguring, debilitating, quite painful, and, in the case of laryngeal attacks, life-threatening. Attacks are frequently the source of unnecessary exploratory abdominal procedures, extended hospital stays affecting a patient's ability to retain employment, and severe compromise of the patient's quality of life. HAE is estimated to affect 10,000 people in the US and is caused by deficient or dysfunctional C1-inhibitor, a naturally occurring molecule that is known to inhibit kallikrein, bradykinin, and other serine proteases in plasma. The treatment and management of HAE have been hampered by the dearth of safe and effective therapies. In the United States, there are currently no approved therapies for the treatment of acute HAE attacks. Although prophylactic HAE therapies do exist, they are often viewed as suboptimal due to moderate degrees of efficacy and the existence of adverse effects associated with therapy. Danazol, an attenuated androgen, is the most commonly prescribed prophylaxis treatment for HAE in the United States. Although it has demonstrated moderate efficacy in the prevention of HAE attacks, danazol's side-effect profile can be problematic because there is a correlation between frequency and severity of adverse events and dosage and duration of therapy.
Document Type: Review Article
Affiliations: Allergy Asthma and Immunology Section, Division Of Pulmonary, Allergy, and Critical Care, Penn State University, Hershey, Pennsylvania
Publication date: May 1, 2008
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