Pediatric Angioedema Treatment & Management

  • Author: Shih-Wen Huang, MD; Chief Editor: Harumi Jyonouchi, MD   more...
 
Updated: Jan 6, 2012
 

Approach Considerations

Farkas advised that management of hereditary angioedema (HAE) in pediatric patients differs in many respects, is different from the management of adults. He recommends prompt control of edematous attacks, short-term prophylaxis, and intermittent therapy as the primary means for the management of pediatric HAE.

Currently, antifibrinolytics, attenuated androgens, and C1INH replacement therapy are used for the treatment of children with HAE. Antifibrinolytics are recommended for long-term prophylaxis because of their favorable safety profiles, but efficacy may be lacking. Attenuated androgens administered in the lowest effective dose are another option. C1INH replacement therapy is also effective and safe for children. Regular monitoring and follow-up of patients is highly recommended.[7]

For other discussions on angioedema, see the overview topics Acquired Angioedema and Hereditary Angioedema.

Next

Preventive Measures

Ideally, episodes of swelling should be prevented with long-term or short-term prophylaxis. Once an angioedema episode occurs, mediators that increase vascular permeability have already been released, and intervention measures can only (possibly) reduce the severity or duration of the attack. Therefore, treatment is aimed at preventing attacks.

Successful pharmacologic approaches have included prevention of the activation of kinin-releasing enzymes or increasing the blood level of normal C1INH. Androgens and antifibrinolytic agents are frequently used to achieve this goal. C1INH concentrate (Cinryze) for prophylaxis, especially before surgery, has been used.[13]

Previous
Next

Treatment of Acute Angioedema

Minor episodes of subepithelial swelling need no treatment, but the patient with edema of the face and neck should be closely observed for spread of edema and signs of airway involvement. When hoarseness or other signs of a compromised airway occur, an otolaryngologist should be consulted for possible tracheostomy. This procedure is usually not needed but is sometimes a life-saving measure.

Berinert is a freeze-dried C1 esterase inhibitor derived from human plasma.[14] This agent was approved in the United States for treatment of acute abdominal attacks and facial swelling in adolescents and adults in September 2009. Berinert was also approved for acute treatment of laryngeal HAE in January 2012. Its long half-life may provide an extended a period of protection, even after the symptoms of an attack have subsided.[15] The safety and effectiveness in children aged 12 years or younger has not been established.

In December 2009, ecallantide (Kalbitor) was approved by the Food and Drug Administration (FDA) for treating acute HAE attacks. During attacks, unregulated plasma kallikrein activity results in excessive bradykinin generation, resulting in swelling, inflammation, and pain. Ecallantide is a potent, selective, reversible inhibitor of plasma kallikrein, thereby reducing the conversion of kininogen to bradykinin.

Cicardi et al observed significantly better outcome scores in patients treated for acute attacks of angioedema with ecallantide compared with placebo.[16] This was a double-blind, placebo-controlled trial in 71 patients.

Another treatment that may be beneficial is an oropharyngeal spray of a 1:1000 dilution of racemic epinephrine (0.2-0.3 mL). However, one study indicated that fewer than 27% of patients with HAE considered that the epinephrine injection was effective during acute attack.[10]

Icatibant (Firazyr), a selective bradykinin B2 receptor antagonist, was approved by the US Food and Drug Administration for treatment of acute attacks HAE in adults. Approval was based on 3 double-blind, randomized, controlled clinical trials known as For Angioedema Subcutaneous Treatment (FAST) 1, 2, and 3.[17, 18]

Cautious sedation with antihistamines may be beneficial. These patients may be frightened when airway symptoms or difficulty in swallowing occurs, especially if they have witnessed affected relatives die during such episodes.

When an episode of abdominal colic occurs, symptomatic treatment with narcotics may be required to relieve pain. These patients may become addicted.

When a major loss of fluid from the vascular compartment occurs, replacement with physiologic intravenous fluid may aid in recovery. The degree of hemoconcentration may boost hematocrit (Hct) or leukocyte counts.

Previous
Next

Treatment Strategies for Hereditary Angioedema

C1INH concentrate administration is preferred for acute treatment of HAE1 and HAE2 and has recently received US Food and Drug Administration (FDA) approval in the United States.[19] Androgens such as danazol and oxandrolone are used for possible prevention of episodes. Hypotension accompanied by abdominal symptoms may require fluid replacement therapy. The combination of meperidine (Demerol) and prochlorperazine (Compazine) suppositories (and possibly dicyclomine to relieve abdominal pain and vomiting) is useful.

Trials by Birjmohun et al documented the effects of short-term and long-term danazol treatment on healthy volunteers and patients with HAE (10 females and 7 males).[20] Short-term danazol treatment in healthy volunteers was associated with a reduction in high-density lipoprotein cholesterol levels without a significant effect on endothelial function or coagulation parameters.

In contrast, patients with HAE treated for more than 2 years with danazol had increased activation of coagulation. However, no significant difference in high-density lipoprotein cholesterol levels or carotid intima-media thickness (CIMT) was noted when compared with matched healthy controls.

Previous
Next

Treatment Strategies for Acquired Angioedema

Diagnosis and treatment of underlying lymphoproliferative disease often eliminates the root ppressivcause of type 1 acquired angioedema (AAE1). Antifibrinolytics, such as tranexamic acid and epsilon-aminocaproic acid, may be administered for possible prevention of episodes. Androgen may be helpful. A case report of treatment of acquired angioedema with icatibant was recently reported in a single patient.[21]

A potentially life-threatening laryngeal edema in a patient with AAE that was nonresponsive to standard therapy with plasma-derived C1INH was successfully relieved with subcutaneous injection of icatibant within 2 hours and a complete recovery was achieved within 12 hours. Potential exists for using the same therapy on an outpatient basis in such patients.

For type 2 acquired angioedema, antifibrinolytics, such as tranexamic acid and epsilon-aminocaproic acid, may be administered for possible prevention of episodes. Immunosue therapy may be successful.

Previous
Next

Treatment Strategies for Other Forms of Angioedema

Idiopathic angioedema

Antihistamines are primarily used. Dehydroepiandrosterone 1-thyroxine is used for thyroid dysfunction. Prednisone therapy may be considered.

Nonhistaminergic angioedema

Consider antifibrinolytics such as tranexamic acid and epsilon-aminocaproic acid for patients with nonhistaminergic angioedema.

Allergic angioedema

Avoid the substance that causes the allergic reaction. Antihistamines and adrenaline (epinephrine, possibly given by auto-injector [EpiPen]) are used in case of emergency.

ACE inhibitor–induced angioedema

In patients who develop angioedema after being placed on ACE inhibitor therapy, the medication is either suspended or changed.

Previous
Next

Activity

Patients with HAE should be told that an acute attack could lead to a potentially fatal outcome. Direct patients as follows:

  • No contact sports are allowed
  • If surgery or dental procedures are necessary, the patient should be evaluated for prophylactic management
  • The patient should wear a MedicAlert bracelet or carry an identification card at all times
Previous
Next

Consultations

Consultation with an otolaryngologist for possible tracheostomy may be necessary in cases with severe laryngeal edema.

Consultation with allergists for workup to differentiate between hereditary angioedema and other similar conditions and initiation of proper prophylaxis for patients is appropriate.

Abdominal ultrasonography by a radiologist may be useful in acute attack.

Patients with acquired C1INH deficiency often have malignancy, especially lymphoproliferative disorder. Management of the underlying disorder should be a priority.

Previous
Next

Pregnancy and Delivery

Pregnancy and delivery are always a medical concern for patients with HAE. In one study, a woman treated during the last 8 weeks of pregnancy showed no side effects, but her female newborn had transient signs of virilization.[22] Thus, danazol, even when it is administered at low doses and late in pregnancy (ie, after sexual differentiation of the fetus) can still interfere with normal female external genital phenotype. A careful evaluation appears to be appropriate when attenuated androgens are proposed for pregnant women with HAE.

For more information, see the Hereditary Angioedema Association.

Previous
Proceed to Medication
 
 
Contributor Information and Disclosures
Author

Shih-Wen Huang, MD  Professor Emeritus of Pulmonology and Allergy, Department of Pediatrics, 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.

Chief Editor

Harumi Jyonouchi, MD  Associate Professor, Division of Pulmonary, Allergy/Immunology, and Infectious Diseases, Department of Pediatrics, University of Medicine and Dentistry of New Jersey-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.

Additional Contributors

C Lucy Park MD, Head, Division of Allergy, Immunology, and Pulmonology, Associate Professor, Department of Pediatrics, University of Illinois at Chicago College of Medicine

C Lucy Park 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.

Mary L Windle, PharmD Adjunct Associate Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Nothing to disclose.

References
  1. 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].

  2. Patel NN, Patel DN. Hereditary angioedema with normal C1 inhibitor. Am J Med. Nov 2008;121(11):949-51. [Medline].

  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].

  4. 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. Dec 2006;79(6):1098-104. [Medline].

  5. 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. Feb 2009;64(2):284-6. [Medline].

  6. 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. Jan 27 2009;[Medline].

  7. Farkas H. Pediatric hereditary angioedema due to C1-inhibitor deficiency. Allergy Asthma Clin Immunol. Jul 28 2010;6(1):18. [Medline]. [Full Text].

  8. [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. Jul 28 2010;6(1):24. [Medline]. [Full Text].

  9. Bork K. Diagnosis and treatment of hereditary angioedema with normal C1 inhibitor. Allergy Asthma Clin Immunol. Jul 28 2010;6(1):15. [Medline]. [Full Text].

  10. Huang SW. Results of an on-line survey of patients with hereditary angioedema. Allergy Asthma Proc. Mar-Apr 2004;25(2):127-31. [Medline].

  11. 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. Jul 22 2010;[Medline].

  12. 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. Feb 2009;64(2):254-7. [Medline].

  13. Epstein TG, Bernstein JA. Current and emerging management options for hereditary angioedema in the US. Drugs. 2008;68(18):2561-73. [Medline].

  14. Reshef A, Leibovich I, Goren A. Hereditary angioedema: new hopes for an orphan disease. Isr Med Assoc J. Dec 2008;10(12):850-5. [Medline].

  15. 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. Aug 2010;105(2):149-54. [Medline].

  16. Cicardi M et al. Ecallantide for the treatment of acute attacks in hereditary angioedema. N Engl J Med. Aug 2010;363:523-31.

  17. 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. Aug 5 2010;363(6):532-41. [Medline]. [Full Text].

  18. 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.

  19. Zuraw BL et al. Nanofiltered C1 inhibitor concentrate for treatment of hereditary angioedema. N Engl J Med. Aug 2010;363:513-22.

  20. 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. Dec 2008;30(12):2314-23. [Medline].

  21. Zanichelli A, Badini M, Nataloni I, Montano N, Cicardi M. Treatment of acquired angioedema with icatibant: a case report. Intern Emerg Med. Aug 3 2010;[Medline].

  22. 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. Jan 2004;150(1):157-8. [Medline].

  23. [Guideline] Grattan CE, Humphreys F. Guidelines for evaluation and management of urticaria in adults and children. Br J Dermatol. Dec 2007;157(6):1116-23. [Medline].

  24. Morgan BP. Hereditary angioedema - therapies old and new (Editorial). N Engl J Med. Aug 2010;363:581-583.

Previous
Next
 
The mechanism of angioedema resulting from C1-esterase inhibitor deficiency.
Angioedema secondary to ACE inhibitors
 
 
 
All material on this website is protected by copyright, Copyright © 1994-2012 by WebMD LLC.
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.