Hereditary Angioedema Differential Diagnoses

Updated: Aug 30, 2018
  • Author: Michael M Frank, MD; Chief Editor: Michael A Kaliner, MD  more...
  • Print

Diagnostic Considerations

Other types of angioedema without urticaria, referred to as acquired angioedema (AAE), can complicate the diagnostic evaluation of patients with possible hereditary angioedema (HAE). In some cases, AAE may represent a response to an allergen and is treated like urticaria. In other cases, the pathophysiology may be similar to HAE.

As with patients with HAE, those with this type of AAE have decreased C1 inhibitor (C1-INH) activity and experience the same spectrum of clinical disease. However, the 2 conditions differ in several respects. Acquired angioedema is due to (1) an autoantibody to the C1-INH that prevents its function, (2) marked utilization of the normal C1 inhibitor by high levels of antigen-antibody complexes, or (3) factors formed by lymphoid tumors that destroy C1-INH activity.

In general, patients with AAE have low levels of C1q. This distinguishes them from patients with HAE, who have normal levels of the protein.

Although HAE is a treatable disease, the agents used to treat more common forms of angioedema are not effective. Thus, the diagnosis of HAE should be considered when angioedema is not associated with urticaria or when cutaneous or laryngeal attacks do not respond to the usual therapy. Once the diagnosis has been made, efforts should be made to prevent attacks associated with dental and surgical procedures.

Usually, the swelling of HAE does not resemble that of rheumatic disease. Occasionally, when the swelling surrounds a joint and movement of the joint becomes difficult, the difference between HAE and rheumatic disease becomes more difficult to distinguish.

Other problems to be considered in the evaluation of patients with possible HAE are ACE inhibitor–induced angioedema, episodic angioedema with eosinophilia, and vibratory- or pressure-induced angioedema.

Differential Diagnoses