Approach Considerations

Patients with hereditary angioedema (HAE) usually have normal results on most routine laboratory tests. An increased erythrocyte sedimentation rate or eosinophilia is not usually found. If either is present, the clinician should consider a coexisting or different diagnosis.

During attacks, patients can demonstrate hemoconcentration or prerenal azotemia, both of which reflect intravascular volume loss. The white blood cell count is usually not increased during attacks, although a leukocytosis may occur with gastrointestinal episodes.

The most reliable and cost-effective screening test for HAE is a serum C4 level.^{[13, 19, 21]}The C4 concentration is almost always decreased during attacks and is usually low between attacks. If the C4 level is in the normal range but suspicion for angioedema is high, the test should be repeated.^[1]The concentrations of C3 and C1q are normal in patients with HAE, regardless of the clinical status of their disease.

During attacks, the total serum hemolytic complement (CH50) is typically decreased, but it returns to normal with recovery. Because a deficiency in any of several components of complement can cause a decrease in CH50, a decreased value is not a particularly helpful finding (ie, low positive predictive value). Keep in mind that patients can have antigenically present but nonfunctional C1 inhibitor (C1-INH). Therefore, functional tests may be useful. Unfortunately, functional testing has a high error rate.

Complement and Genetic Testing

The 3 types of HAE can be differentiated with complement testing and, in the case of HAE with normal C1 inhibitor levels, genetic testing.

Type I HAE is characterized by the following:

C1-INH level is low
C4 and C2 levels are low
C1q level is normal

Type II HAE is characterized by the following:

C1-INH level is normal or elevated but dysfunctional
C4 and C2 levels are low
C1q level is normal

HAE with normal C1 inhibitor levels is characterized by the following:

C1-INH level is normal
C1-INH functional assay is normal
C4 level may be normal
Factor XII mutation may be present^{[5, 6]}

Imaging Studies

During attacks of gastrointestinal edema, abdominal radiographs may demonstrate features of ileus in HAE patients. Abdominal ultrasonography or computed tomography may show edematous thickening of the intestinal wall, a fluid layer around the bowel, and large amounts of free peritoneal fluid. Chest radiographs may demonstrate pleural effusions.

Histologic Findings

Very few histologic studies have been performed. Histologically, the angioedema of HAE is indistinguishable from other types of angioedema. Typically, perivascular mononuclear cell infiltrate and dermal edema similar to that seen with chronic urticaria or angioedema of other types are observed. Edema is found in the reticular dermis or subcutaneous or submucosal edema, without infiltrating inflammatory cells. Vasodilation may be present.

Treatment & Management

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Author

Michael M Frank, MD Samuel L Katz Professor of Pediatrics, Professor of Medicine and Immunology, Duke University School of Medicine, Duke University Medical Center

Michael M Frank, MD is a member of the following medical societies: American Academy of Pediatrics, American Pediatric Society, American Society for Clinical Investigation, Association of American Physicians, Society for Pediatric Research

Disclosure: Received consulting fee from Shire for consulting; Received honoraria from Robert Michael Educationsl Institute for speaking and teaching; Received consulting fee from BioCryst for consulting.

Chief Editor

Michael A Kaliner, MD Clinical Professor of Medicine, George Washington University School of Medicine; Medical Director, Institute for Asthma and Allergy

Michael A Kaliner, MD is a member of the following medical societies: American Academy of Allergy Asthma and Immunology, American Association of Immunologists, American College of Allergy, Asthma and Immunology, American Society for Clinical Investigation, American Thoracic Society, Association of American Physicians

Disclosure: Nothing to disclose.

Acknowledgements

Dirk M Elston, MD Director, Ackerman Academy of Dermatopathology, New York

Dirk M Elston, MD is a member of the following medical societies: American Academy of Dermatology