Is there a need for clinical guidelines in the United States for the diagnosis of hereditary angioedema and the screening of family members of affected patients?
BACKGROUND
Hereditary angioedema (HAE) is an autosomal dominant disorder characterized by a deficiency of C1 esterase inhibitor (C1 INH) protein or function. Guidelines do not exist regarding diagnostic criteria or routine testing of family members of patients with HAE. Laboratory data for diagnosis include complement factor 4 level; C1 INH antigenic protein level, which is reduced in approximately 85% of patients with HAE; and C1 INH functional assay, which is considered an unreliable test in the United States secondary to inconsistent standardization of assays.


OBJECTIVE
To assess the shortcomings of diagnosing HAE and to determine whether family members of patients with HAE are being adequately screened.


METHODS
The top physician prescribers of danazol in the United States were screened via an Internet questionnaire focusing on the diagnosis and current management of HAE. To assess the patient perspective on HAE, affected individuals in the United States, the United Kingdom, France, Germany, and The Netherlands participated in the Web-based International Survey of Patient Experience of Hereditary Angioedema.


RESULTS
All 80 physicians who completed the survey were allergist or immunologists with a mean of 7 patients with C1 INH deficiency in their practices. Almost 84% of physician respondents used C1 INH level and function for diagnosis, and 63.8% used complement factor 4 levels. A total of 313 patients with HAE completed the survey. Respondents noted that only 48% of immediate family members and 26% of extended family members had been tested.


CONCLUSIONS
Guidelines could potentially alleviate delays in diagnosis and incorrect diagnoses and could lead to adequate screening of family members.
Lunn
Michael L
ML
Division of Pulmonary, Allergy, and Critical Care Medicine, Penn State Milton S. Hershey Medical Center, Hershey, Pennsylvania 17033, USA. mlunn@hmc.psu.edu
Santos
Carah B
CB
Craig
Timothy J
TJ
D054179:Angioedemas, Hereditary / Q000175:diagnosis* / Q000517:prevention & control; D050718:Complement C1 Inhibitor Protein / Q000032:analysis; D003181:Complement C4 / Q000032:analysis; D003613:Danazol / Q000627:therapeutic use; D003937:Diagnosis, Differential; D005060:Europe; D006801:Humans; D017410:Practice Guidelines as Topic / Q000592:standards*; D011795:Surveys and Questionnaires; D014481:United States
D050718:Complement C1 Inhibitor Protein; D003181:Complement C4; D003613:Danazol