Hereditary Angioedema Workup

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