Hereditary Angioedema Workup

  • Author: Michael M Frank, MD; Chief Editor: Michael A Kaliner, MD   more...
 
Updated: Feb 8, 2012
 

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.

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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.

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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.[2, 12, 8] 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.[10] 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.

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Complement and Genetic Testing

The 3 types of HAE can be differentiated with complement testing and, in the case of type III, 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

Type III HAE 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[7, 15]
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Contributor Information and Disclosures
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, and Society for Pediatric Research

Disclosure: ViroPharma Consulting fee research; Shire Consulting fee Consulting; CSL Behring Consulting fee Consulting; Dyax Consulting fee Consulting

Coauthor(s)

Warren R Heymann, MD  Head, Division of Dermatology, Professor, Department of Internal Medicine, University of Medicine and Dentistry of New Jersey-New Jersey Medical School

Warren R Heymann, MD is a member of the following medical societies: American Academy of Dermatology, American Society of Dermatopathology, and Society for Investigative Dermatology

Disclosure: Nothing to disclose.

Amanda T Moon, MD  Resident Physician, Department of Dermatology, University of Rochester, Strong Memorial Hospital

Amanda T Moon, MD, is a member of the following medical societies: American Academy of Dermatology, American Medical Association, American Medical Student Association/Foundation, and Society for Pediatric Dermatology

Disclosure: Nothing to disclose.

Robert A Schwartz, MD, MPH  Professor and Head, Dermatology, Professor of Pathology, Pediatrics, Medicine, and Preventive Medicine and Community Health, University of Medicine and Dentistry of New Jersey-New Jersey Medical School

Robert A Schwartz, MD, MPH is a member of the following medical societies: Alpha Omega Alpha, American Academy of Dermatology, American College of Physicians, and Sigma Xi

Disclosure: Nothing to disclose.

Michael J Wells, MD  Associate Professor, Department of Dermatology, Texas Tech University Health Sciences Center, Paul L Foster School of Medicine

Michael J Wells, MD is a member of the following medical societies: Alpha Omega Alpha, American Academy of Dermatology, American Medical Association, and Texas Medical Association

Disclosure: Nothing to disclose.

Specialty Editor Board

Stephen Rosenfeld, MD  Professor Emeritus, Department of Medicine, Allergy, Immunology and Rheumatology Unit, University of Rochester School of Medicine and Dentistry

Stephen Rosenfeld, MD is a member of the following medical societies: American Academy of Allergy Asthma and Immunology, American Association of Immunologists, American Federation for Clinical Research, Clinical Immunology Society, and Medical Society of the State of New York

Disclosure: Nothing to disclose.

Francisco Talavera, PharmD, PhD  Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Medscape Salary Employment

Paul Krusinski, MD  Director of Dermatology, Fletcher Allen Health Care; Professor, Department of Internal Medicine, University of Vermont College of Medicine

Paul Krusinski, MD is a member of the following medical societies: American Academy of Dermatology, American College of Physicians, and Society for Investigative Dermatology

Disclosure: Nothing to disclose.

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

Disclosure: Nothing to disclose.

Chief Editor

Michael A Kaliner, MD  Clinical Professor of Medicine, George Washington University School of Medicine; Chief, Section of Allergy and Immunology, Washington Hospital Center; 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, and Association of American Physicians

Disclosure: Alcon Consulting fee Consulting; Teva Consulting fee Consulting; Meda Honoraria Speaking and teaching; Ista Consulting fee Consulting; sunovian Consulting fee Consulting; dey Honoraria Review panel membership

Additional Contributors

The authors and editors of Medscape Reference gratefully acknowledge the contributions of previous author Kathleen M Rossy, MD,to the development and writing of a source article.

References

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