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Pediatric Angioedema

  • Pediatric Allergy and Immunology (W Dolen, Section Editor)
  • Published:
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Abstract

Purpose of Review

The aims of this study are to update the clinician on current understanding of angioedema as it presents in the pediatric population and to review proper diagnostic techniques and treatment modalities for various types of angioedema.

Recent Findings

Angioedema is still best classified by whether it is likely histaminergic or kinin-mediated. New guidelines have been published around the world to help diagnose and treat both forms (urticaria/angioedema and hereditary angioedema). The vast majority of the studies on treatment have been conducted in the adult population; however, there are data available in the pediatric population. In the realm of hereditary angioedema, there are multiple new therapies that have been studied in the pediatric population (down to 2 years in some studies) in recent years and offer the clinician options for treatment.

Summary

Angioedema (whether occurring with or without urticaria) is common in the pediatric population. The majority of the recent studies has been conducted in hereditary angioedema, and now, the clinician should have various options to treat all forms of angioedema. Many treatment options, especially for hereditary angioedema, are further being examined specifically in the pediatric population.

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References

Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance

  1. Zuraw BL. Urticaria and angioedema. In: Leung DYM, Szefler SJ, Bonilla FA, Akdis CA, Sampson HA, editors. Pediatric allergy: principles and practice. Oxford: Elsevier; 2016.

    Google Scholar 

  2. Furue M, Yamazaki S, Jimbow K, Tsuchida T, Amagai M, Tanaka T, et al. Prevalence of dermatological disorders in Japan: a nationwide, cross-sectional, seasonal, multicenter, hospital-based study. J Dermatol. 2011;38:310–20. doi:10.1111/j.1346-8138.2011.01209.

    Article  PubMed  Google Scholar 

  3. Madsen F, Attermann J, Linneberg A. Epidemiology of non-hereditary angioedema. Acta Derm Venereol. 2012;92:475–9. doi:10.2340/00015555-1389.

    Article  PubMed  Google Scholar 

  4. Dibbern DA Jr, Dreskin SC. Urticaria and angioedema: an overview. Immunol Allergy Clin N Am. 2004;24(v):141–62.

    Article  Google Scholar 

  5. Lumry WR. Overview of epidemiology, pathophysiology, and disease progression in hereditary angioedema. Am J Manag Care. 2013;19(7 Suppl):s103–10.

    PubMed  Google Scholar 

  6. Zuraw BL. The pathophysiology of hereditary angioedema. World Allergy Organ J. 2010;3(9 Suppl):S25–8. doi:10.1097/WOX.0b013e3181f3f21c.

    PubMed  PubMed Central  Google Scholar 

  7. Zingale LC, Beltrami L, Zanichelli A, Maggioni L, Pappalardo E, Cicardi B, et al. Angioedema without urticaria: a large clinical survey. CMAJ. 2006;175:1065–70.

    Article  PubMed  PubMed Central  Google Scholar 

  8. Karagol HI, Yilmaz O, Bakirtas A, Topal E, Demirsoy MS, Turktas I. Angioedema without urticaria in childhood. Pediatr Allergy Immunol. 2013;24:685–90. doi:10.1111/pai.12118.

    Article  Google Scholar 

  9. Kennedy JL, Stallings AP, Platts-Mills TA, Oliveira WM, Workman L, James HR, et al. Galactose-alpha-1,3-galactose and delayed anaphylaxis, angioedema, and urticaria in children. Pediatrics. 2013;131:e1545–52. doi:10.1542/peds.2012-2585.

    Article  PubMed  PubMed Central  Google Scholar 

  10. Kaplan AP. Clinical practice. Chronic urticaria and angioedema. N Engl J Med. 2002;346(3):175–9.

    Article  PubMed  Google Scholar 

  11. •• Bernstein JA, Lang DM, Khan DA, Craig T, Dreyfus D, Hsieh F, et al. The diagnosis and management of acute and chronic urticaria: 2014 update. J Allergy Clin Immunol. 2014;133:1270–7. doi:10.1016/j.jaci.2014.02.036. Update to guidelines that are essential, core knowledge for any practitioner caring for patients with chronic urticaria with our without angioedema.

    Article  PubMed  Google Scholar 

  12. Stevens W, Buchheit K, Cahill KN. Aspirin-exacerbated diseases: advances in asthma with nasal polyposis, urticaria, angioedema, and anaphylaxis. Curr Allergy Asthma Rep. 2015;15(12):69. doi:10.1007/s11882-015-0569-2.

    Article  PubMed  Google Scholar 

  13. Capriles-Behrens E, Caplin J, Sanchez-Borges M. NSAID facial angioedema in a selected pediatric atopic population. J Investig Allergol Clin Immunol. 2000;10:277–9.

    CAS  PubMed  Google Scholar 

  14. Sanchez-Borges M, Capriles-Behrens E, Caballero-Fonseca F. Hypersensitivity to non-steroidal anti-inflammatory drugs in childhood. Pediatr Allergy Immunol. 2004;15:376–80.

    Article  PubMed  Google Scholar 

  15. Bork K, Meng G, Staubach P, Hardt J. Hereditary angioedema: new findings concerning symptoms, affected organs, and course. Am J Med. 2006;119:267–74.

    Article  PubMed  Google Scholar 

  16. Christiansen SC, Davis DK, Castaldo AJ, Zuraw BL. Pediatric hereditary angioedema: onset, diagnostic delay, and disease severity. Clin Pediatr (Phila). 2016;55(10):935–42. doi:10.1177/0009922815616886.

    Article  Google Scholar 

  17. Farkas H, Csuka D, Zotter Z, et al. Treatment of attacks with plasma-derived C1-inhibitor concentrate in pediatric hereditary angioedema patients. J Allergy Clin Immunol. 2013;131:909–11. doi:10.1016/j.jaci.2012.08.036.

    Article  CAS  PubMed  Google Scholar 

  18. Nanda MK, Elenburg S, Bernstein JA, Assa'ad AH. Clinical features of pediatric hereditary angioedema. J Allergy Clin Immunol Pract. 2015;3:392–5. doi:10.1016/j.jaip.2014.11.012.

    Article  PubMed  Google Scholar 

  19. Bennett G, Craig T. Hereditary angioedema with a focus on the child. Allergy Asthma Proc. 2015;36:70–3. doi:10.2500/aap.2015.36.3806.

    Article  PubMed  Google Scholar 

  20. Prematta MJ, Bewtra AK, Levy RJ, Wasserman RL, Jacobson KW, Machnig T, et al. Per-attack reporting of prodromal symptoms concurrent with C1-inhibitor treatment of hereditary angioedema attacks. Adv Ther. 2012;10:913–22. doi:10.1007/s12325-012-0053-5.

    Article  Google Scholar 

  21. Yucelten D, Kus S. Chicken-wire erythema, but not urticaria, as the presenting sign of hereditary angioedema. Eur J Dermatol. 2006;16:197–8.

    PubMed  Google Scholar 

  22. Martinez-Saguer I, Farkas H. Erythema marginatum as an early symptom of hereditary angioedema: case report of 2 newborns. Pediatrics. 2016;137:2015–411. doi:10.1542/peds.2015-2411.

    Article  Google Scholar 

  23. Zuraw BL, Bork K, Binkley KE, Banerji A, Christiansen SC, Castaldo A, et al. Hereditary angioedema with normal C1 inhibitor function: consensus of an international expert panel. Allergy Asthma Proc. 2012;33(Suppl. 1):S145–56. doi:10.2500/aap.2012.33.3627.

    Article  CAS  PubMed  Google Scholar 

  24. Wahn V, Aberer W, Eberel W, Faßhauer M, Kühne T, Kurnik K, et al. Hereditary angioedema (HAE) in children and adolescents—a consensus on therapeutic strategies. Eur J Pediatr. 2012;171:1339–48. doi:10.1007/s00431-012-1726-4.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Wu MA, Castelli R. The Janus faces of acquired angioedema: C1-inhibitor deficiency, lymphoproliferation and autoimmunity. Clin Chem Lab Med. 2016;54:207–14. doi:10.1515/cclm-2015-0195. doi: 10.1515/cclm-2015-0195.

    CAS  PubMed  Google Scholar 

  26. Bukhari E, Safdar O, Shalaby M, AlSharif SM, Alsufiany K, Kari JA. Potentially lethal ACE-inhibitor-induced angioedema in a child. Clin Case Rep. 2015;3(6):427–30. doi:10.1002/ccr3.265.

    Article  PubMed  PubMed Central  Google Scholar 

  27. Quintana EC, Attia MW. Angiotensin-converting enzyme inhibitor angioedema in a pediatric patient: a case report and discussion. Pediatr Emerg Care. 2001;17:438–40.

    Article  CAS  PubMed  Google Scholar 

  28. Krishnamurthy A, Naguwa SM, Gershwin ME. Pediatric angioedema. Clin Rev Allergy Immunol. 2008;34:250–9. doi:10.1007/s12016-007-8037-y.

    Article  PubMed  Google Scholar 

  29. Feldman MF, Khan DA, Brown ES, Bernstein JA. Factitious angioedema: a mimic of refractory "angioedema". J Allergy Clin Immunol Pract. 2014;2(6):795–7. doi:10.1016/j.jaip.2014.08.010.

    Article  PubMed  Google Scholar 

  30. Zuberbier T, Aberer W, Asero R, et al. The EAACI/GA(2)LEN/EDF/WAO Guideline for the definition, classification, diagnosis, and management of urticaria: the 2013 revision and update. Allergy. 2014;69:868–87. doi:10.1111/all.12313.

    Article  CAS  PubMed  Google Scholar 

  31. • Lang DM, Aberer W, Bernstein JA, Chng HH, Grumach AS, Hide M, et al. International consensus on hereditary and acquired angioedema. Ann Allergy Asthma Immunol. 2012;109:395–402. doi:10.1016/j.anai.2012.10.008. International Consensus panel on both HAE and acquired angioedema that aids in presentation, diagnosis and treatment.

    Article  PubMed  Google Scholar 

  32. • Frank MM, Zuraw B, Banerji A, Bernstein JA, Craig T, Busse P, et al. Management of children with hereditary angioedema due to C1 inhibitor deficiency. Pediatrics. 2016;138(5). doi:10.1542/peds.2016-0575. A nice expert consensus panel specifically examining HAE treatment in the pediatric population.

  33. Pedrosa M, Phillips-Angles E, López-Lera A, López-Trascasa M, Caballero T. Complement study versus CINH gene testing for the diagnosis of type I hereditary angioedema in children. J Clin Immunol. 2016;36(1):16–8. doi:10.1007/s10875-015-0222-9.

    Article  PubMed  Google Scholar 

  34. • Sharma M, Bennett C, Cohen SN, Carter B. H1-antihistamines for chronic spontaneous urticaria. Cochrane Database Syst Rev. 2014;(11):CD006137. doi:10.1002/14651858.CD006137.pub2. An exhaustive Cochrane review of the use of antihistamines in urticaria/angioedema.

  35. Doshi DR, Weinberger MM. Experience with cyclosporine in children with chronic idiopathic urticaria. Pediatr Dermatol. 2009;26:409–413. 104. doi:10.1111/j.1525-1470.2009.00869.x.

    Article  PubMed  Google Scholar 

  36. • Maurer M, Rosen K, Hsieh HJ, Saini S, Grattan C, Gimenez-Arnau A, et al. Omalizumab for the treatment of chronic idiopathic or spontaneous urticaria. N Engl J Med. 2013;368:924–35. doi:10.1056/NEJMoa1215372. The seminal paper showing efficacy of omalizumab for chronic urticaria/angioedema.

    Article  CAS  PubMed  Google Scholar 

  37. Kaplan A, Ledford D, Ashby M, Canvin J, Zazzali JL, Conner E, et al. Omalizumab in patients with symptomatic chronic idiopathic/ spontaneous urticaria despite standard combination therapy. J Allergy Clin Immunol. 2013;132:101–9. doi:10.1016/j.jaci.2013.05.013.

    Article  CAS  PubMed  Google Scholar 

  38. Neverman L, Weinberger M. Treatment of chronic urticaria in children with antihistamines and cyclosporine. J Allergy Clin Immunol Pract. 2014;2:434–8. doi:10.1016/j.jaip.2014.04.011.

    Article  PubMed  Google Scholar 

  39. Zuraw BL, Banerji A, Bernstein JA, Busse PJ, Christiansen SC, Davis-Lorton M, et al. US Hereditary Angioedema Association Medical Advisory Board 2013 recommendations for the management of hereditary angioedema due to C1 inhibitor deficiency. J Allergy Clin Immunol Pract. 2013;1:458–67. doi:10.1016/j.jaip.2013.07.002.

    Article  PubMed  Google Scholar 

  40. Cicardi M, Bork K, Caballero T, Craig T, Li HH, Longhurst H, et al. Evidence-based recommendations for the therapeutic management of angioedema owing to hereditary C1 inhibitor deficiency: consensus report of an International Working Group. Allergy. 2012;67:147–57. doi:10.1111/j.1398-9995.2011.02751.x.

    Article  CAS  PubMed  Google Scholar 

  41. Craig T, Pursun EA, Bork K, Bowen T, Boysen H, Farkas H, et al. WAO guideline for the management of hereditary angioedema. World Allergy Organ J. 2012;5:182–99. doi:10.1097/WOX.0b013e318279affa.

    Article  PubMed  PubMed Central  Google Scholar 

  42. Craig TJ, Schneider LC, MacGinnitie AJ. Plasma-derived C1-INH for managing hereditary angioedema in pediatric patients: a systematic review. Pediatr Allergy Immunol. 2015;26:537–44. doi:10.1111/pai.12425.

    Article  PubMed  Google Scholar 

  43. Farkas H, Jakab L, Temesszentandrási G, Visy B, Harmat G, Füst G, et al. Hereditary angioedema: a decade of human C1-inhibitor concentrate therapy. J Allergy Clin Immunol. 2007;120(4):941–7.

    Article  CAS  PubMed  Google Scholar 

  44. Craig TJ, Levy RJ, Wasserman RL, Bewtra AK, Hurewitz D, Obtułowicz K, et al. Efficacy of human C1 esterase inhibitor concentrate compared with placebo in acute hereditary angioedema attacks. J Allergy Clin Immunol. 2009;124(4):801–8. doi:10.1016/j.jaci.2009.07.017.

    Article  CAS  PubMed  Google Scholar 

  45. Craig TJ, Bewtra AK, Bahna SL, Hurewitz D, Schneider LC, Levy RJ, et al. C1 esterase inhibitor concentrate in 1085 hereditary angioedema attacks: final results of the I.M.P.A.C.T.2 study. Allergy. 2011;66(12):1604–11. doi:10.1111/j.1398-9995.2011.02702.x.

    Article  CAS  PubMed  Google Scholar 

  46. Kreuz W, Rusicke E, Martinez-Saguer I, Aygören-Pürsün E, Heller C, Klingebiel T. Home therapy with intravenous human C1-inhibitor in children and adolescents with hereditary angioedema. Transfusion. 2012;52(1):100–7. doi:10.1111/j.1537-2995.2011.03240.x.

    Article  CAS  PubMed  Google Scholar 

  47. Schneider L, Hurewitz D, Wasserman R, Obtulowicz K, Machnig T, Moldovan D, et al. C1-INH concentrate for treatment of acute hereditary angioedema: a pediatric cohort from the I.M.P.A.C.T. Studies. Pediatr Allergy Immunol. 2013;24:54–60. doi:10.1111/pai.12024.

    Article  PubMed  Google Scholar 

  48. Lumry W, Soteres D, Gower R, Jacobson KW, Li HH, Chen H, et al. Safety and efficacy of C1 esterase inhibitor for acute attacks in children with hereditary angioedema. Pediatr Allergy Immunol. 2015;26:674–80. doi:10.1111/pai.12444.

    Article  PubMed  Google Scholar 

  49. Lumry W, Manning ME, Hurewitz DS, Davis-Lorton M, Fitts D, Kalfus IN, et al. Nanofiltered C1-esterase inhibitor for the acute management and prevention of hereditary angioedema attacks due to C1-inhibitor deficiency in children. J Pediatr. 2013;162:1017–1022, e1–2. doi:10.1016/j.jpeds.2012.11.030.

    Article  CAS  PubMed  Google Scholar 

  50. • Longhurst H, Cicardi M, Craig T, Bork K, Grattan C, Baker J, et al. Prevention of hereditary angioedema attacks with a subcutaneous C1 inhibitor. N Engl J Med. 2017;376(12):1131. doi:10.1056/NEJMoa1613627. The first subcutaneous C1 inhibitor to be approved.

    Article  CAS  PubMed  Google Scholar 

  51. Baker JW, Reshef A, Moldovan D, Harper JR, Relan A, Riedl MA. Recombinant human C1-esterase inhibitor to treat acute hereditary angioedema attacks in adolescents. J Allergy Clin Immunol Pract. 2017; doi:10.1016/j.jaip.2016.11.005.

  52. Riedl MA, Bernstein JA, Li H, Reshef A, Lumry W, Moldovan D, et al. Recombinant human C1-esterase inhibitor relieves symptoms of hereditary angioedema attacks: phase 3, randomized, placebo-controlled trial. Ann Allergy Asthma Immunol. 2014;112:163–169.e1. doi:10.1016/j.anai.2013.12.004.

    Article  CAS  PubMed  Google Scholar 

  53. Farkas H, Reshef A, Aberer W, Caballero T, McCarthy L, Hao J, et al. Treatment effect and safety of Icatibant in pediatric patients with hereditary angioedema. J Allergy Clin Immunol Pract. 2017; doi:10.1016/j.jaip.2017.04.010.

  54. Cicardi M, Levy RJ, McNeil DL, Li HH, Sheffer AL, Campion M, et al. Ecallantide for the treatment of acute attacks in hereditary angioedema. N Engl J Med. 2010;363:523–31. doi:10.1056/NEJMoa0905079.

    Article  CAS  PubMed  Google Scholar 

  55. MacGinnitie AJ, Davis-Lorton M, Stolz LE, Tachdjian R. Use of ecallantide in pediatric hereditary angioedema. Pediatrics. 2013;132(2):e490–7. doi:10.1542/peds.2013-0646.

    Article  PubMed  Google Scholar 

  56. Aygören-Pürsün E, Magerl M, Graff J, Martinez-Saguer I, Kreuz W, Longhurst H, et al. Prophylaxis of hereditary angioedema attacks: a randomized trial of oral plasma kallikrein inhibition with avoralstat. J Allergy Clin Immunol. 2016;138(3):934. doi:10.1016/j.jaci.2016.03.043.

    Article  PubMed  Google Scholar 

  57. Banerji A, Busse P, Shennak M, Lumry W, Davis-Lorton M, Wedner HJ, et al. Inhibiting plasma Kallikrein for hereditary angioedema prophylaxis. N Engl J Med. 2017;376(8):717. doi:10.1056/NEJMoa1605767.

    Article  CAS  PubMed  Google Scholar 

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Authors and Affiliations

  1. Department of Internal Medicine, Division of Rheumatology, The University of Tennessee Health Science Center, 51 North Dunlap, Suite 400, Memphis, TN, 38105, USA

    Debendra Pattanaik

  2. Department of Pediatrics, Division of Allergy & Immunology, The University of Tennessee Health Science Center, 51 North Dunlap, Suite 400, Memphis, TN, 38105, USA

    Jay Adam Lieberman

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  1. Debendra Pattanaik
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Correspondence to Jay Adam Lieberman.

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This article is part of the Topical Collection on Pediatric Allergy and Immunology

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Pattanaik, D., Lieberman, J.A. Pediatric Angioedema. Curr Allergy Asthma Rep 17, 60 (2017). https://doi.org/10.1007/s11882-017-0729-7

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