Pediatric Angioedema Workup
- Author: Shih-Wen Huang, MD; Chief Editor: Harumi Jyonouchi, MD more...
The diagnostic workup for urticaria-related angioedema is the same for urticaria. Perform an 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 C1 inhibitor (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 complete blood cell count (CBC) with differential, C-reactive protein level, and erythrocyte sedimentation rate if the patient's history indicates underlying vasculitis or inflammatory diseases.
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.
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 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.
Prothrombin fragment (F1 + 2) and D-dimer levels may have an important diagnostic value. A study 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 found high levels of these biomarkers during acute angioedema attacks in patients with C1INH deficiency.
Ultrasonography of the GI tract may help differentiate between HAE 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.
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. 2004 Sep. 114(3 Suppl):S51-131. [Medline].
Patel NN, Patel DN. Hereditary angioedema with normal C1 inhibitor. Am J Med. 2008 Nov. 121(11):949-51. [Medline].
Visy B, Fust G, Varga L, et al. Sex hormones in hereditary angioneurotic oedema. Clin Endocrinol (Oxf). 2004 Apr. 60(4):508-15. [Medline].
Cichon S, Martin L, Hennies HC, Muller F, Van Driessche K, Karpushova A. Increased activity of coagulation factor XII (Hageman factor) causes hereditary angioedema type III. Am J Hum Genet. 2006 Dec. 79(6):1098-104. [Medline].
Prieto A, Tornero P, Rubio M, Fernandez-Cruz E, Rodriguez-Sainz C. Missense mutation Thr309Lys in the coagulation factor XII gene in a Spanish family with hereditary angioedema type III. Allergy. 2009 Feb. 64(2):284-6. [Medline].
Duan QL, Binkley K, Rouleau GA. Genetic analysis of Factor XII and bradykinin catabolic enzymes in a family with estrogen-dependent inherited angioedema. J Allergy Clin Immunol. 2009 Jan 27. [Medline].
Farkas H. Pediatric hereditary angioedema due to C1-inhibitor deficiency. Allergy Asthma Clin Immunol. 2010 Jul 28. 6(1):18. [Medline]. [Full Text].
[Guideline] Bowen T, Cicardi M, Farkas H, Bork K, Longhurst HJ, Zuraw B, et al. 2010 International consensus algorithm for the diagnosis, therapy and management of hereditary angioedema. Allergy Asthma Clin Immunol. 2010 Jul 28. 6(1):24. [Medline]. [Full Text].
Bork K. Diagnosis and treatment of hereditary angioedema with normal C1 inhibitor. Allergy Asthma Clin Immunol. 2010 Jul 28. 6(1):15. [Medline]. [Full Text].
Kumar A, Khamkar K, Gopal H. Serum sickness and severe angioedema following rituximab therapy in RA. Int J Rheum Dis. 2012 Feb. 15(1):e6-7. [Medline].
Toklu Y, Sarac O, Berk S, Simsek S. Angioedema after intravitreal bevacizumab injection. Cutan Ocul Toxicol. 2012 Mar. 31(1):85-6. [Medline].
Tukenmez Demirci G, Kivanc Altunay I, Atis G, Kucukunal A. Allergic contact dermatitis mimicking angioedema due to paraphenylendiamine hypersensitivity: a case report. Cutan Ocul Toxicol. 2012 Sep. 31(3):250-2. [Medline].
Studdiford JS, Conniff KM, Trayes KP, Tully AS. Bedbug infestation. Am Fam Physician. 2012 Oct 1. 86(7):653-8. [Medline].
Miller DG, Sweis RT, Toerne TS. Penile angioedema developing after 3 years of ACEI therapy. J Emerg Med. 2012 Aug. 43(2):273-5. [Medline].
Hu XH, Gong XY, Hu P. Transient small bowel angioedema due to intravenous iodinated contrast media. World J Gastroenterol. 2012 Mar 7. 18(9):999-1002. [Medline]. [Full Text].
Huang SW. Results of an on-line survey of patients with hereditary angioedema. Allergy Asthma Proc. 2004 Mar-Apr. 25(2):127-31. [Medline].
Perricone C, Agmon-Levin N, Shoenfeld N, de Carolis C, Guarino MD, Gigliucci G, et al. Evidence of impaired sense of smell in hereditary angioedema. Allergy. 2010 Jul 22. [Medline].
Nakachi S, Inokuma S. Eleven cases of angioedema with eosinophilia treated in a single hospital in Japan. Allergol Int. 2012 Jun. 61(2):259-63. [Medline].
Cugno M, Zanichelli A, Bellatorre AG, Griffini S, Cicardi M. Plasma biomarkers of acute attacks in patients with angioedema due to C1-inhibitor deficiency. Allergy. 2009 Feb. 64(2):254-7. [Medline].
Kusuma A, Relan A, Knulst AC, et al. Clinical impact of peripheral attacks in hereditary angioedema patients. Am J Med. 2012 Sep. 125(9):937.e17-24. [Medline].
Jung M, Rice L. "Surgical" abdomen in a patient with chronic lymphocytic leukemia: a case of acquired angioedema. J Gastrointest Surg. 2011 Dec. 15(12):2262-6. [Medline]. [Full Text].
Sánchez-Borges M, Asero R, Ansotegui IJ, et al. Diagnosis and Treatment of Urticaria and Angioedema: A Worldwide Perspective. World Allergy Organ J. 2012 Nov. 5(11):125-147. [Medline].
Jaiganesh T, Hughan C, Webster A, Bethune C. Hereditary angioedema: a survey of UK emergency departments and recommendations for management. Eur J Emerg Med. 2012 Aug. 19(4):271-4. [Medline].
Epstein TG, Bernstein JA. Current and emerging management options for hereditary angioedema in the US. Drugs. 2008. 68(18):2561-73. [Medline].
Reshef A, Leibovich I, Goren A. Hereditary angioedema: new hopes for an orphan disease. Isr Med Assoc J. 2008 Dec. 10(12):850-5. [Medline].
Bernstein JA, Ritchie B, Levy RJ, Wasserman RL, Bewtra AK, Hurewitz DS, et al. Population pharmacokinetics of plasma-derived C1 esterase inhibitor concentrate used to treat acute hereditary angioedema attacks. Ann Allergy Asthma Immunol. 2010 Aug. 105(2):149-54. [Medline].
Riedl MA, Bernstein JA, Li H, et al. Recombinant human C1-esterase inhibitor relieves symptoms of hereditary angioedema attacks: phase 3, randomized, placebo-controlled trial. Ann Allergy Asthma Immunol. 2014 Feb. 112(2):163-169.e1. [Medline].
Cicardi M et al. Ecallantide for the treatment of acute attacks in hereditary angioedema. N Engl J Med. Aug 2010. 363:523-31.
Cicardi M, Banerji A, Bracho F, Malbrán A, Rosenkranz B, Riedl M, et al. Icatibant, a new bradykinin-receptor antagonist, in hereditary angioedema. N Engl J Med. 2010 Aug 5. 363(6):532-41. [Medline]. [Full Text].
Lumry WR, et al. Results from FAST-3: A phase III randomized, double-blind, placebo-controlled, multicenter study of subcutaneous icatibant in patients with acute hereditary angioedema (HAE) attacks. American Academy of Allergy, Asthma, & Immunology Meeting. March 22, 2011; Abstract L2.
Zuraw BL et al. Nanofiltered C1 inhibitor concentrate for treatment of hereditary angioedema. N Engl J Med. Aug 2010. 363:513-22.
Birjmohun RS, Kees Hovingh G, Stroes ES, et al. Effects of short-term and long-term danazol treatment on lipoproteins, coagulation, and progression of atherosclerosis: two clinical trials in healthy volunteers and patients with hereditary angioedema. Clin Ther. 2008 Dec. 30(12):2314-23. [Medline].
Zanichelli A, Badini M, Nataloni I, Montano N, Cicardi M. Treatment of acquired angioedema with icatibant: a case report. Intern Emerg Med. 2010 Aug 3. [Medline].
Herrmann G, Schneider L, Krieg T. Efficacy of danazol treatment in a patient with the new variant of hereditary angio-oedema (HAE III). Br J Dermatol. 2004 Jan. 150(1):157-8. [Medline].
[Guideline] Grattan CE, Humphreys F. Guidelines for evaluation and management of urticaria in adults and children. Br J Dermatol. 2007 Dec. 157(6):1116-23. [Medline].
Morgan BP. Hereditary angioedema--therapies old and new. N Engl J Med. 2010 Aug 5. 363(6):581-3. [Medline].