The 17 α-alkylated androgens that can be used for treatment of HAE are danazol (Danacrine), stanozolol (Winstrol), oxandralone (Oxandrine) and methyltestosterone (Android). In patients with HAE, attenuated androgens can significantly reduce the frequency and severity of attacks; however, their use is limited by risk for untoward effects (virilization, abnormal liver function tests, change in libido, anxiety, etc.).21 There is also a risk for hepatotoxicity, including development of hepatic adenomas and hepatic carcinoma.
Antifibrinolytics also may have efficacy for HAE, but these agents have been associated with a variety of adverse effects, including nausea and diarrhea, postural hypotension, fatigue, enhanced thrombosis, retinal changes, and teratogenicity.8, 22, 23
In 2009, long-term prophylaxis with C1-INH concentrate was recommended for patients with HAE with frequent or disabling attacks, a history of laryngeal attacks, and poor quality of life. The 2007 International Consensus Algorithm for the Diagnosis, Therapy, and Management of HAE recommended long-term prophylaxis in patients with more than one monthly severe HAE attack, more than five days of disability per month, or any history of airway compromise.24, 25
The decision to prescribe long-term prophylaxis, and the dose/frequency of medication required, should be individualized based on clinical parameters, such as frequency and severity of attacks, and not on C1 INH or C4 levels.
It is well established that any trauma, including dental procedures or surgery, can precipitate HAE attacks. For this reason, short-term prophylactic treatment in HAE patients undergoing procedures is recommended. Ideally, avoiding endotracheal intubation is the best approach; however, if intubation cannot be avoided, then adequate prophylaxis should be administered.2
Attenuated androgens can be given up to seven days before a procedure, or C1 INH can be administered 24 hours in advance. If C1 INH is unavailable, FFP can be given six to 12 hours in advance in patients who are not symptomatic; in case of endotracheal intubation, either FFP or C1 INH should be administered immediately before.2
Several case reports in multiple specialty surgical patients (abdominal surgery, cardiopulmonary bypass, orthopedic surgery, etc.) have confirmed the successful use of C1 INH in the prevention of acute attacks with favorable outcomes.2
There is no need to follow C1 INH levels, as it has no clinical relevance.
Back to the Case
The patient was admitted to the ICU and received a total of eight units of FFP. He was transferred to our institution and was able to be extubated three days after initial presentation. Laboratory studies revealed C4 10mg/dL and C1 esterase inhibitor 10mg/dL (both low).
Danazol was resumed. However, within several months after discharge, Cinryze became available in the U.S. market and was eventually prescribed. The patient has not had further significant attacks requiring inpatient management.
Dr. Auron is an assistant professor of medicine and pediatrics at the Cleveland Clinic Lerner College of Medicine of Case Western Reserve University. Dr. Lang is co-director of the Asthma Center and director of the Allergy/Immunology Fellowship Training Program at the Cleveland Clinic.
- Bernstein, JA. Update on angioedema: evaluation, diagnosis, and treatment. Allergy Asthma Proc. 2011;32(6):408-412.
- Levy JH, Freiberger DJ, Roback J. Hereditary angioedema: current and emerging treatment options. Anesth Analg. 2010;110(5):1271-1280.
- Busse PJ. Angioedema: Differential diagnosis and treatment. Allergy Asthma Proc. 2011;32:Suppl 1:S3-S11.
- Khan DA. Hereditary angioedema: historical aspects, classification, pathophysiology, clinical presentation, and laboratory diagnosis. Allergy Asthma Proc. 2011;32(1):1-10.
- Bork K, Meng G, Staubach P, Hardt, J. Hereditary angioedema: new findings concerning symptoms, affected organs, and course. Am J Med. 2006;119(3):267-274.
- Zuraw BL, Christiansen SC. Pathogenesis and laboratory diagnosis of hereditary angioedema. Allergy Asthma Proc. 2009;30:487-492.
- Frazer-Abel A, Giclas PC. Update on laboratory tests for the diagnosis and differentiation of hereditary angioedema and acquired angioedema. Allergy Asthma Proc. 2011;32:Suppl 1:S17-S21.
- Banerjee A. Current treatment of hereditary angioedema: an update on clinical studies. Allergy Asthma Proc. 2010;31:398-406.
- Donaldson VH. Therapy of “the neurotic edema.” N Engl J Med. 1972;286(15):835-836.
- Riedl MA. Update on the acute treatment of hereditary angioedema. Allergy Asthma Proc. 2011;32:11-16.
- Zuraw BL, Busse PJ, White M, et al. Nanofiltered C1 inhibitor concentrate for treatment of hereditary angioedema. N Engl J Med. 2010;363:513-522.
- Cicardi M, Levy RJ, McNeil DL. Ecallantide for the treatment of acute attacks in hereditary angioedema. N Engl J Med. 2010;363:523-531.
- Caballero T, Farkas H, Bouillet L, et al. International consensus and practical guidelines on the gynecologic and obstetric management of female patients with hereditary angioedema caused by C1 inhibitor deficiency. J Allergy Clin Immunol. 2012;129(2):308-320.
- Cicardi M, Zanichelli A. Acquired angioedema. J Allergy Clin Immunol. 2010;6(1):14.
- Zanichelli A, Badini M, Nataloni I, Montano N, Cicardi M. Treatment of acquired angioedema with icatibant: a case report. Intern Emerg Med. 2011;6(3):279-280.
- Byrd JB, Adam A, Brown NJ. Angiotensin-converting enzyme inhibitor-associated angioedema. Immunol Allergy Clin North Am. 2006;26(4):725-737.
- Haymore BR, Yoon J, Mikita CP, Klote MM, DeZee KJ. Risk of angioedema with angiotensin receptor blockers in patients with prior angioedema associated with angiotensin-converting enzyme inhibitors: a meta-analysis. Ann Allergy Asthma Immunol. 2008;101(5):495-499.
- Beavers CJ, Dunn SP, Macaulay TE. The role of angiotensin receptor blockers in patients with angiotensin-converting enzyme inhibitor-induced angioedema. Ann Pharmacother. 2011;45(4):520-524.
- Nzeako UC. Diagnosis and management of angioedema with abdominal involvement: a gastroenterology perspective. World J Gastroenterol. 2010; 16(39):4913-4921.
- Banerji A, Sloane DE, Sheffer AL. Hereditary angioedema: a current state-of-the-art review, V: attenuated androgens for the treatment of hereditary angioedema. Ann Allergy Asthma Immunol. 2008;100(1) (Suppl 2):S19-22.
- Zuraw BL. Clinical practice. Hereditary angioedema. N Engl J Med. 2008; 359(10):1027-1036.
- Zuraw BL. Hereditary angioedema: a current state-of-the-art review, IV: short- and long-term treatment of hereditary angioedema: out with the old and in with the new? Ann Allergy Asthma Immunol. 2008;100(1) (Suppl 2):S13-S18.
- Bowen T, Cicardi M, Bork K, et al. Hereditary angioedema: a current state-of-the-art review, VII: Canadian Hungarian 2007 International Consensus Algorithm for the Diagnosis, Therapy, and Management of Hereditary Angioedema. Ann Allergy Asthma Immunol. 2008;100(1)(Suppl 2):S30-40.
- Craig T, Riedl M, Dykewicz M, et al. When is prophylaxis for hereditary angioedema necessary? Ann Allergy Asthma Immunol. 2009.102(5):366-372.
- Frank MM. Update on preventive therapy (prophylaxis) of hereditary angioedema. Allergy Asthma Proc. 2011;32(1):17-21.