eMedicine Specialties > Pediatrics: General Medicine > Allergy & Immunology

Angioedema: Differential Diagnoses & Workup

Author: Shih-Wen Huang, MD, Medical Director of Allergy Service, Professor, Department of Pediatrics, Division of Immunology and Infectious Diseases, University of Florida College of Medicine
Contributor Information and Disclosures

Updated: Oct 21, 2009

Differential Diagnoses

Other Problems to Be Considered

Cellulitis: Usually, this is caused by gram-positive bacterial infection. Pain and fever are common.

Erysipelas: This is caused by group A beta streptococci. Tenderness, fever, and redness are common.

Lymphedema: Chronic thickening of tissues occurs in lymphedema, in contrast to the acute stretching of tissue observed in angioedema.

Systemic lupus erythematosus (SLE) or other collagen vascular disorders: The patient should have a history of systemic illness, indicating the presence of vasculitis. Laboratory findings reflect features of chronic inflammatory conditions.

Acute contact dermatitis: The patient has a history of contact with sensitizing agents. It is always accompanied by intense pruritus.

Idiopathic scrotal edema in children: The etiology is unknown, but swelling is limited to the scrotal area. Rarely, it causes systemic symptoms.

Rosenthal-Melkersson syndrome: Recurrent facial edema, recurrent peripheral facial nerve palsy, and remarkable fissuring of the tongue are characteristic.

Laryngeal swelling due to anaphylaxis: Patients most likely have a history of intense allergic diathesis. It could be caused by ingestion of food, drugs, insect sting, or latex allergy. Idiopathic anaphylaxis, which is rare in children, may occasionally cause difficulty in the differential diagnosis. Patients with hereditary angioedema (HAE) usually have a history of abdominal pain and unexplained diarrhea. Family history helps identify hereditary angioedema.

Surgical abdomen: Severe pain caused by hereditary angioedema can be difficult to distinguish from conditions leading to surgical abdomen. Conditions include intestinal obstruction and appendicitis. In addition, Crohn disease may cause chronic pain and diarrhea. History and physical examination should be helpful to distinguish those conditions with the aid of imaging studies.

Workup

Laboratory Studies

  • Plasma levels for the diagnosis of hereditary angioedema (HAE) include the following:
    • C4 level less than 14 mg/L (diagnostic)
    • C1q level greater than 77 mg/L
    • C1INH (antigenic) level less than 199 mg/L (diagnostic)
    • C1INH (functional) level less than 72% of the reference range (diagnostic)
  • The diagnostic workup for urticaria-related angioedema is the same for urticaria.
  • Perform immunoglobulin E (IgE) antibody skin test or radioallergosorbent test (RAST) if the history is suggestive of a rash caused by foods, drugs, insect venom, or latex.
  • Obtain a bacterial culture with sensitivity if the patient has a history of fever and sore throat.
  • Obtain a thyroid profile, antithyroid microsomal antibodies, and antithyroglobulin antibody if the patient has a strong family history of thyroid disorder or symptoms of hypothyroidism; this is more frequent in females. However, patients are often euthyroid.
  • Measure C1INH and C3 and C4 levels if the patient has a family history of angioedema.
  • Obtain stool for ova and parasites if the patient reports ingestion of poorly cooked meats or travel in unsanitary areas.
  • Perform antinuclear antibody testing and urinalysis with microscopic examination if the patient may have arthritis, photosensitivity, or other signs or symptoms of collagen vascular disease.
  • Obtain a CBC count with differential, C-reactive protein level, and erythrocyte sedimentation rate if the patient's history indicates underlying vasculitis or inflammatory diseases.
  • In laboratory findings, acquired angioedema (AAE) is characterized by low functional C1INH levels, low C4 levels, and C3 levels within the reference range. Concentration of C1q is often very low. 
  • The summary of complement profiles in different forms of angioedema is as follows:
    • HAE1: C1INH levels are low. C4 levels are almost always low and can be used as the first step of screening. C1, C3, and C1q levels are all within the reference range. These changes are seen in both hereditary and spontaneous mutation conditions. 
    • HAE2: C1INH levels may be normal or elevated but are dysfunctional. C1, C3, and C1q levels are within the reference range, but C4 levels are almost always low.
    • HAE3: The complement profile is normal.
    • AAE1: C1INH and C4 levels are low. C1q levels are usually, but not always, reduced.
    • AAE2: The findings are the same as in AAE1. Autoantibody testing may be appropriate.
    • Idiopathic angioedema: The complement profile is normal.
    • Nonhistaminergic angioedema (INAE): The complement profile is normal.
    • Allergic angioedema: The complement profile is normal.
    • ACE inhibitor–induced angioedema: The complement profile is normal.
  • Biomarkers were studied in 28 patients with C1INH deficiency during acute attacks and remission, in 35 patients without C1INH deficiencies during abdominal colic, and in 20 healthy subjects.8 During acute angioedema attacks, patients with C1INH deficiency had high prothrombin fragment (F1 + 2) and D-dimer levels, the measurement of which may have an important diagnostic value.

Imaging Studies

  • Ultrasonography of the GI tract may help differentiate between hereditary angioedema and conditions of surgical abdomen.
  • In hereditary angioedema, ascites and edema of the intestinal walls are present in more than 80% of patients during acute attacks.

More on Angioedema

Overview: Angioedema
Differential Diagnoses & Workup: Angioedema
Treatment & Medication: Angioedema
Follow-up: Angioedema
Multimedia: Angioedema
References
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References

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  3. Visy B, Fust G, Varga L, et al. Sex hormones in hereditary angioneurotic oedema. Clin Endocrinol (Oxf). Apr 2004;60(4):508-15. [Medline].

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  28. Martinez-Saguer, Rusicke E, Aygoren-Pursun, et al. Clinical manifestation and therapy in children with HAE: A prospective follow-up. J Allergy Clin Immunol. 2004;114 (3):S107-108.

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Further Reading

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Keywords

HANE disease, hereditary angioedema, HAE, hereditary angioneurotic edema, angioedema, urticaria, subcutaneous swelling, generalized urticaria, C1 inhibitor, C1INH, HAE type 1, HAE1, HAE type 2, HAE2, HAE type 3, HAE3, AAE type 1, AAE1, AAE type 2, AAE2, acquired angioedema, C1INH deficiency, angioneurotic edema, nonhistaminergic angioedema, INAE, idiopathic angioedema, allergic angioedema, lymphoid, urticaria-associated angioedema

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Contributor Information and Disclosures

Author

Shih-Wen Huang, MD, Medical Director of Allergy Service, Professor, Department of Pediatrics, Division of Immunology and Infectious Diseases, University of Florida College of Medicine
Shih-Wen Huang, MD is a member of the following medical societies: American Academy of Allergy Asthma and Immunology
Disclosure: Nothing to disclose.

Medical Editor

C Lucy Park, MD, Head, Division of Allergy, Immunology, and Pulmonology, Associate Professor, Department of Pediatrics, University of Illinois at Chicago
C Lucy Park, MD is a member of the following medical societies: American Academy of Allergy Asthma and Immunology, American Medical Association, Chicago Medical Society, Clinical Immunology Society, and Illinois State Medical Society
Disclosure: Nothing to disclose.

Pharmacy Editor

Mary L Windle, PharmD, Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy, Pharmacy Editor, eMedicine
Disclosure: Pfizer Inc Stock Investment from financial planner; Avanir Pharma Stock Investment from financial planner ; WebMD Salary and stock Employment and investment from financial planner

Managing Editor

John Wilson Georgitis, MD, Consulting Staff, Lafayette Allergy Services
John Wilson Georgitis, MD is a member of the following medical societies: American Academy of Allergy Asthma and Immunology, American Academy of Pediatrics, American Association for the Advancement of Science, American College of Chest Physicians, American Lung Association, American Medical Writers Association, and American Thoracic Society
Disclosure: Nothing to disclose.

CME Editor

David Pallares, MD, Clinical Assistant Professor, Department of Pediatrics, Division of Allergy and Immunology, University of Louisville
David Pallares, MD is a member of the following medical societies: American Academy of Allergy Asthma and Immunology
Disclosure: Nothing to disclose.

Chief Editor

Harumi Jyonouchi, MD, Associate Professor, Division of Pulmonary Allergy/Immunology and Infectious Diseases, Department of Pediatrics, UMDNJ-New Jersey Medical School
Harumi Jyonouchi, MD is a member of the following medical societies: American Academy of Allergy Asthma and Immunology, American Academy of Pediatrics, American Association of Immunologists, American Medical Association, Clinical Immunology Society, New York Academy of Sciences, Society for Experimental Biology and Medicine, Society for Mucosal Immunology, and Society for Pediatric Research
Disclosure: Nothing to disclose.

 
 
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