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Severity of Hereditary Angioedema, Prevalence, and Diagnostic Considerations
Jonathan A. Bernstein, MD
Economic Burden Limiting Proper Healthcare Delivery, Management, and Improvement of Patient Outcomes
William J. Cardarelli, PharmD
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Severity of Hereditary Angioedema, Prevalence, and Diagnostic Considerations

Jonathan A. Bernstein, MD
Another physician survey conducted by Lunn and colleagues found that patients with HAE in the United States visited an average of 4.4 physicians before receiving a diagnosis of HAE; 65% of patients initially received a misdiagnosis; and the average time to diagnosis was 8.3 years. Also, just 63.8% of physicians used C4 levels to aid in their diagnosis.34 Similarly, a patient-based survey in the United States found that although one-third of patients received a diagnosis of HAE within 1 year of their initial attack, another one-third experienced a delay to diagnosis of more than 10 years.21 Patients with abdominal symptoms associated with HAE are especially likely to be susceptible to the consequences of misdiagnosis and to undergo unnecessary surgical procedures, such as an appendectomy or exploratory diagnostic procedure.35,36

Zanichelli and colleagues found that 44.3% of patients with HAE reported receiving 1 or more prior misdiagnoses, with the most common misdiagnoses being allergic angioedema and appendicitis. It is important to note that patients who had a history of prior misdiagnosis experienced a median delay of 13.3 years to achieve a correct diagnosis versus 1.7 years to diagnosis for patients who did not experience a previous misdiagnosis.37 

Therefore, in patients with HAE, achieving the correct diagnosis early in the course of symptoms is critical to optimize patient outcomes. Most cases of HAE are still undiagnosed for several years after the initial attack, leading to significant morbidity, frequent emergency department visits, and potential mortality. Improved healthcare provider awareness and understanding of the condition and its differential diagnosis will assist in improving outcomes in patients with HAE.

Conclusions

Hereditary angioedema is a lifelong disorder that is often misdiagnosed or unrecognized when patients initially present with symptoms of angioedema. It is critical to understand the framework for the diagnosis of HAE, including a deficiency in functional C1-INH, and to recognize the variability in frequency and severity of attacks that may occur among patients. Early and accurate diagnosis will assist in developing an individual plan to effectively manage, treat, and prevent future attacks. 

Author affiliation: Professor of Clinical Medicine, University of Cincinnati College of Medicine, Department of Internal Medicine; Division of Immunology, Allergy Section, Cincinnati, OH.
Funding source: This activity is supported by educational grants from CSL Behring and Shire.
Author disclosure: Dr Bernstein has the following relevant financial relationships with commercial interests to disclose: GRANT/RESEARCH SUPPORT: BioCryst, CSL Behring, Genentech, Novartis, Pharming, Shire. CONSULTANT: AstraZeneca, BioCryst, CSL Behring, Merck, Sanofi, Shire. SPEAKERS BUREAU: AstraZeneca, CSL Behring, Pharming, Shire.
Authorship information: Concept and design; critical revision of the manuscript for important intellectual content; drafting of the manuscript; supervision.
Address correspondence to: jonathan.bernstein@uc.edu.
Dr Bernstein gratefully acknowledges Mona Shah, PharmD, for her contributions to the development of this article.
 
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