eMedicine Specialties > Allergy and Immunology > Complement-Related Abnormalities

Hereditary Angioedema: Differential Diagnoses & Workup

Author: Michael M Frank, MD, Distinguished Professor, Departments of Pediatrics and Medicine, Professor, Pediatric Allergy and Immunology Division, Duke University School of Medicine
Contributor Information and Disclosures

Updated: Oct 26, 2009

Differential Diagnoses

Other Problems to Be Considered

Acquired angioedema, allergic angioedema

Usually, the swelling is not confused with the swelling of rheumatic disease. Occasionally, when the swelling surrounds a joint and movement of the joint becomes difficult, the difference between hereditary angioedema (HAE) and rheumatic disease becomes more difficult to distinguish.

Workup

Laboratory Studies

  • The results of most routine laboratory tests performed on patients with hereditary angioedema (HAE) are usually normal. Patients typically do not have increased erythrocyte sedimentation rates or eosinophilia. 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.
  • The screening tests for HAE are serum C4 and C1-INH levels.2,3,1 The C4 concentration is almost always decreased during attacks and is usually low between attacks. 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-INH. Therefore, functional tests may be useful. Unfortunately, functional testing has a high error rate.

Imaging Studies

  • Imaging studies are usually unrevealing, but mechanical bowel obstruction is occasionally observed during attacks of gastrointestinal edema. Ultrasonographic examination of the abdomen of a patient with gastrointestinal edema may show edema within the intestinal wall but may be unrevealing.

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.

More on Hereditary Angioedema

Overview: Hereditary Angioedema
Differential Diagnoses & Workup: Hereditary Angioedema
Treatment & Medication: Hereditary Angioedema
Follow-up: Hereditary Angioedema
References
[ CLOSE WINDOW ]

References

  1. Zuraw BL. Clinical practice. Hereditary angioedema. N Engl J Med. Sep 4 2008;359(10):1027-36. [Medline].

  2. Frank MM, Gelfand JA, Atkinson JP. Hereditary angioedema: the clinical syndrome and its management. Ann Intern Med. May 1976;84(5):580-93. [Medline].

  3. Rosen FS, Alper CA, Pensky J, et al. Genetically determined heterogeneity of the C1 esterase inhibitor in patients with hereditary angioneurotic edema. J Clin Invest. Oct 1971;50(10):2143-9. [Medline].

  4. Bork K, Barnstedt SE, Koch P, Traupe H. Hereditary angioedema with normal C1-inhibitor activity in women. Lancet. Jul 15 2000;356(9225):213-7. [Medline].

  5. Nielsen EW, Gran JT, Straume B, et al. Hereditary angio-oedema: new clinical observations and autoimmune screening, complement and kallikrein-kinin analyses. J Intern Med. Feb 1996;239(2):119-30. [Medline].

  6. US Food and Drug Administration (FDA). FDA Approves Berinert to Treat Abdominal Attacks, Facial Swelling Associated With Hereditary Angioedema. FDA Web site. Available at http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm186257.htm. Accessed October 23, 2009.

  7. Agostoni A, Aygoren-Pursun E, Binkley KE, et al. Hereditary and acquired angioedema: problems and progress: proceedings of the third C1 esterase inhibitor deficiency workshop and beyond. J Allergy Clin Immunol. Sep 2004;114(3 Suppl):S51-131. [Medline].

  8. Bork K, Witzke G. Long-term prophylaxis with C1-inhibitor (C1 INH) concentrate in patients with recurrent angioedema caused by hereditary and acquired C1-inhibitor deficiency. J Allergy Clin Immunol. Mar 1989;83(3):677-82. [Medline].

  9. Cicardi M, Bergamaschini L, Cugno M, et al. Long-term treatment of hereditary angioedema with attenuated androgens: a survey of a 13-year experience. J Allergy Clin Immunol. Apr 1991;87(4):768-73. [Medline].

  10. Gelfand JA, Sherins RJ, Alling DW, Frank MM. Treatment of hereditary angioedema with danazol. Reversal of clinical and biochemical abnormalities. N Engl J Med. Dec 23 1976;295(26):1444-8. [Medline].

  11. Sheffer AL, Fearon DT, Austen KF. Clinical and biochemical effects of stanozolol therapy for hereditary angioedema. J Allergy Clin Immunol. Sep 1981;68(3):181-7. [Medline].

  12. Gadek JE, Hosea SW, Gelfand JA, et al. Replacement therapy in hereditary angioedema: successful treatment of acute episodes of angioedema with partly purified C1 inhibitor. N Engl J Med. Mar 6 1980;302(10):542-6. [Medline].

  13. Waytes AT, Rosen FS, Frank MM. Treatment of hereditary angioedema with a vapor-heated C1 inhibitor concentrate. N Engl J Med. Jun 20 1996;334(25):1630-4. [Medline].

[ CLOSE WINDOW ]

Further Reading

[ CLOSE WINDOW ]

Keywords

hereditary angioedema, C1 inhibitor deficiency, C1 esterase inhibitor deficiency, HAE, oedema, complement deficiency induced angioedema, angioneurotic edema, acquired angioedema, AAE, complement component 1 inhibitor deficiency, laryngeal edema, Quincke's disease

[ CLOSE WINDOW ]

Contributor Information and Disclosures

Author

Michael M Frank, MD, Distinguished Professor, Departments of Pediatrics and Medicine, Professor, Pediatric Allergy and Immunology Division, Duke University School of Medicine
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: Lev Pharma Grant/research funds research; CSL Behring Grant/research funds research; DYAX Consulting fee Review panel membership; Jerini Consulting fee Consulting

Medical Editor

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: Elan Ownership interest None; Invitrogen Ownership interest None; Merck Ownership interest None; Pfizer Ownership interest None; Medco Health Ownership interest None; Millipore Ownership interest None

Pharmacy Editor

Francisco Talavera, PharmD, PhD, Senior Pharmacy Editor, eMedicine
Disclosure: eMedicine Salary Employment

Managing Editor

Samuel R Marney, Jr, MD, Director, Associate Professor, Department of Internal Medicine, Division of Allergy and Immunology, Vanderbilt University School of Medicine
Samuel R Marney, Jr, MD is a member of the following medical societies: American Academy of Allergy Asthma and Immunology, American College of Allergy, Asthma and Immunology, American College of Physicians, and Tennessee Medical Association
Disclosure: Nothing to disclose.

CME Editor

Timothy D Rice, MD, Associate Professor, Departments of Internal Medicine and Pediatrics and Adolescent Medicine, Saint Louis University School of Medicine
Timothy D Rice, MD is a member of the following medical societies: American Academy of Pediatrics and American College of Physicians
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: Abbott Consulting fee Consulting; Alcon Consulting fee Consulting; Glaxo Consulting fee Consulting; Greer Consulting fee Consulting; Sanofi Consulting fee Consulting; Schering Consulting fee Consulting; Teva  Consulting; Meda Honoraria Speaking and teaching

 
 
HONcode

We subscribe to the
HONcode principles of the
Health On the Net Foundation

All material on this website is protected by copyright, Copyright© 1994- by Medscape.
This website also contains material copyrighted by 3rd parties.

DISCLAIMER: The content of this Website is not influenced by sponsors. The site is designed primarily for use by qualified physicians and other medical professionals. The information contained herein should NOT be used as a substitute for the advice of an appropriately qualified and licensed physician or other health care provider. The information provided here is for educational and informational purposes only. In no way should it be considered as offering medical advice. Please check with a physician if you suspect you are ill.