Urticaria and angioedema in children and adolescents: diagnostic challenge

Main Article Content

Luis Felipe Ensina
Larissa Silva Brandão
Herberto Chong Neto
Moshe Ben-Shoshan

Keywords

angioedema, children, diagnosis, urticaria

Abstract

Urticaria diagnosis may be challenging in children since it can be triggered or related to numerous conditions. In this paper, we reviewed the main aspects regarding the diagnosis of urticaria in the pediatric population. Acute urticaria is often due to viral infections. However, other culprits, including foods, insect stings, drugs, contrast media, vaccination, latex, and medical diseases, may account for acute patterns. Laboratory tests and confirmatory allergy tests should be individualized and guided by history. Chronic urticaria (CU) is defined when hives and/or angioedema last for more than 6 weeks. The most common type of chronic urticaria in children is chronic spontaneous urticaria (CSU). Chronic inducible urticaria (CindU) is less common but is important to diagnose in order to manage appropriately and reduce the risk of severe reactions. Inducible forms in children are often diagnosed with specific provocation tests similar to the tests used in adults. Given that chronic urticaria could rarely be a presentation of vasculitis, systemic-onset juvenile idiopathic arthritis, or auto-inflammatory syndromes, it is important to rule out these conditions. It is crucial to differentiate cases of chronic urticaria from mastocytosis and Bradykinin-mediated angioedema, given that treatment may differ. The management of chronic urticaria in children has improved over the last decade because of the development of both clear management guidelines and new effective drugs. It is crucial to increase awareness for appropriate diagnosis and new available treatment to improve the management of chronic urticaria in children.

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References

1. Talarico V, Marseglia GL, Lanari M, Esposito S, Masi S, De Filippo M, et al. Pediatric urticaria in the emergency department: Epidemiological characteristics and predictive factors for its persistence in children. Eur Ann Allergy Clin Immunol. 2021 Feb;53(02):80. 10.23822/EurAnnACI.1764-1489.148

2. Mazur M, Czarnobilska M, Czarnobilska E. Prevalence and potential risk factors of urticaria in the Polish population of children and adolescents. Adv Dermatol Allergol. 2020;37(5):785–9. 10.5114/ada.2020.100489

3. Zuberbier T, Abdul Latiff AH, Abuzakouk M, Aquilina S, Asero R, Baker D, et al. The International EAACI/GA2LEN/EuroGuiDerm/APAAACI Guideline for the definition, classification, diagnosis and management of urticaria. Allergy. 2022; 77(3):734-66. 10.1111/all.15090

4. Fricke J, Ávila G, Keller T, Weller K, Lau S, Maurer M, et al. Prevalence of chronic urticaria in children and adults across the globe: Systematic review with meta-analysis. Allergy Eur J Allergy Clin Immunol. 2020;75(2):423–32. 10.1111/all.14037

5. Jo YH, Yoo HW, Kim SH, Kim YM, Kim H-Y. Clinical characteristics and treatment response of chronic spontaneous urticaria according to age: A single-center Korean study. Asian Pac J Allergy Immunol. 2021. 10.12932/AP-050719-0594

6. Guo C, Saltoun C. Urticaria and angioedema. Allergy Asthma Proc. 2019;40(6):437–40. 10.2500/aap.2019.40.4266

7. Schaefer P. Acute and chronic urticaria: Evaluation and treatment. Am Fam Physician. 2017;95(11):717–24.

8. Minasi D, Manti S, Chiera F, Licari A, Marseglia GL. Acute urticaria in the infant. Pediatr Allergy Immunol. 2020;31(S26):49–51. 10.1111/pai.13350

9. Antia C, Baquerizo K, Korman A, Bernstein JA, Alikhan A. Urticaria: A comprehensive review: Epidemiology, diagnosis, and workup. J Am Acad Dermatol. 2018;79(4):599–614. 10.1016/j.jaad.2018.01.023

10. Sabroe RA. Acute urticaria. Immunol Allergy Clin North Am. 2014;34(1):11–21. 10.1016/j.iac.2013.07.010

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(5):1270–7.e66. 10.1016/j.jaci.2014.02.036

12. Kanani A, Betschel SD, Warrington R. Urticaria and angioedema. Allergy Asthma Clin Immunol. 2018;14(S2):1–13. 10.1186/s13223-018-0288-z

13. Pier J, Bingemann TA. Urticaria, angioedema, and anaphylaxis. Pediatr Rev. 2020;41(6):283–90. 10.1542/pir.2019-0056

14. Abuelgasim E, Dona ACM, Sondh RS, Harky A. Management of urticaria in COVID-19 patients: A systematic review. Dermatol Ther. 2021;34(1):e14328. 10.1111/dth.14328

15. Algaadi SA. Urticaria and COVID-19: A review. Dermatol Ther. 2020;33(6). 10.1111/dth.14290

16. Cetinkaya PG, Soyer O, Esenboga S, Sahiner UM, Teksam O, Sekerel BE. Predictive factors for progression to chronicity or recurrence after the first attack of acute urticaria in preschool-age children. Allergol Immunopathol (Madr). 2019;47(5):484–90. 10.1016/j.aller.2018.12.010

17. Magen E, Zueva E, Mishal J, Schlesinger M. The clinical and laboratory characteristics of acute spontaneous urticaria and its progression to chronic spontaneous urticaria. Allergy Asthma Proc. 2016 Sep 1;37(5):394–9. 10.2500/aap.2016.37.3971

18. Techasatian L, Phungoen P, Chaiyarit J, Uppala R. Etiological and predictive factors of pediatric urticaria in an emergency context. BMC Pediatr. 2021 Dec 19;21(1):92. 10.1186/s12887-021-02553-y

19. Santa C, Valente CL, Mesquita M, Lopes J, Cardoso I, Rodrigues J, et al. Acute urticaria in children: From pediatric emergency department to allergology consultation at a central hospital. Eur Ann Allergy Clin Immunol. 2021 Apr;online first. 10.23822/EurAnnACI.1764-1489.204

20. Imbalzano E, Casciaro M, Quartuccio S, Minciullo PL, Cascio A, Calapai G, et al. Association between urticaria and virus infections: A systematic review. Allergy Asthma Proc. 2016 Jan 3;37(1):18–22. 10.2500/aap.2016.37.3915

21. Caffarelli C, Duse M, Martelli A, Calvani M, Cardinale F, Chiappini E, et al. Urticaria in childhood. Acta Biomed. 2020;91(11-S):e2020013.

22. Le NK, Brooks JP. Acute urticaria as the initial presentation of COVID-19 in a pediatric patient. JAAD Case Rep. 2021 May;11:137–8. 10.1016/j.jdcr.2021.03.001

23. Marques-Mejías MA, Tomás-Pérez M, Vilà-Nadal G, Quirce S. Acute urticaria in the pediatric emergency department. Ann Allergy Asthma Immunol. 2020 Apr;124(4):396–7. 10.1016/j.anai.2020.01.007

24. Aydoğan M, Topal E, Uysal P, Acar HC, Cavkaytar O, Hızlı Demirkale Z, et al. Proven food-induced acute urticaria and predictive factors for definitive diagnosis in childhood. Int Arch Allergy Immunol. 2021;182(7):607–14. 10.1159/000513267

25. Ebisawa M, Ito K, Fujisawa T, Ebisawa M, Ito K, Fujisawa T, et al. Japanese guidelines for food allergy 2020. Allergol Int. 2020 Jul;69(3):370–86. 10.1016/j.alit.2020.03.004

26. Muraro A, Werfel T, Hoffmann-Sommergruber K, Roberts G, Beyer K, Bindslev-Jensen C, et al. EAACI food allergy and anaphylaxis guidelines: Diagnosis and management of food allergy. Allergy. 2014 Aug;69(8):1008–25. 10.1111/all.12429

27. Valluzzi RL, Fierro V, Arasi S, Mennini M, Pecora V, Fiocchi A. Allergy to food additives. Curr Opin Allergy Clin Immunol. 2019 Jun;19(3):256–62. 10.1097/ACI.0000000000000528

28. Andreozzi L, Giannetti A, Cipriani F, Caffarelli C, Mastrorilli C, Ricci G. Hypersensitivity reactions to food and drug additives: Problem or myth? Acta Biomed. 2019;90(3-S):80–90.

29. Nettis E, Colanardi MC, Ferrannini A, Tursi A. Suspected tartrazine-induced acute urticaria/angioedema is only rarely reproducible by oral rechallenge. Clin Exp Allergy. 2003 Dec;33(12):1725–9. 10.1111/j.1365-2222.2003.01825.x

30. Jares EJ, Sánchez-Borges M, Cardona-Villa R, Ensina LF, Arias-Cruz A, Gómez M, et al. Multinational experience with hypersensitivity drug reactions in Latin America. Ann Allergy Asthma Immunol. 2014 Sep;113(3):282–9. 10.1016/j.anai.2014.06.019

31. Ensina LF, Aranda CS, de Lacerda AE, Camelo-Nunes I, Solé D, Martins AM, et al. Laronidase hypersensitivity and desensitization in type I mucopolysaccharidosis: A case report. Pediatr Allergy Immunol. 2014 Aug;25(5):498–9. 10.1111/pai.12209

32. Ensina LF, de Lacerda AE, de Andrade DM, Machado L, Camelo-Nunes I, Solé D. Drug-induced anaphylaxis in children: Nonsteroidal anti-inflammatory drugs and drug provocation test. J Allergy Clin Immunol Pract. 2014 Nov;2(6):825. 10.1016/j.jaip.2014.08.016

33. Demoly P, Adkinson NF, Brockow K, Castells M, Chiriac AM, Greenberger PA, et al. International Consensus on drug allergy. Allergy. 2014 Apr;69(4):420–37. 10.1111/all.12350

34. Doña I, Pérez-Sánchez N, Eguiluz-Gracia I, Muñoz-Cano R, Bartra J, Torres MJ, et al. Progress in understanding hypersensitivity reactions to nonsteroidal anti-inflammatory drugs. Allergy. 2020 Mar 28;75(3):561–75. 10.1111/all.14032

35. Mayorga C, Fernandez TD, Montañez MI, Moreno E, Torres MJ. Recent developments and highlights in drug hypersensitivity. Allergy. 2019 Dec 23;74(12):2368–81. 10.1111/all.14061

36. Akcal O, Ozen S, Taskirdi I, Haci IA, Kanik ET, Karkiner CS, et al. The use of in vivo and in vitro tests in children with beta lactam allergy. Allergol Immunopathol (Madr). 2020 Nov;48(6):633–9. 10.1016/j.aller.2020.03.013

37. Cardona V, Ansotegui IJ, Ebisawa M, El-Gamal Y, Fernandez Rivas M, Fineman S, et al. World allergy organization anaphylaxis guidance 2020. World Allergy Organ J. 2020;13(10):100472. 10.1016/j.waojou.2020.100472

38. Simons FER, Ardusso LRF, Bilò MB, El-Gamal YM, Ledford DK, Ring J, et al. World Allergy Organization guidelines for the assessment and management of anaphylaxis. World Allergy Organ J. 2011;4(2):13–37. 10.1097/WOX.0b013e318211496c

39. Schuch A, Brockow K. Mastocytosis and anaphylaxis. Immunol Allergy Clin North Am. 2017 Feb;37(1):153–64. 10.1016/j.iac.2016.08.017

40. Worm M, Francuzik W, Renaudin J-M., Bilo MB, Cardona V, Scherer Hofmeier K, et al. Factors increasing the risk for a severe reaction in anaphylaxis: An analysis of data from the European Anaphylaxis Registry. Allergy. 2018 Jun 8;73(6):1322–30. 10.1111/all.13380

41. Muñoz-Cano R, Pascal M, Araujo G, Goikoetxea MJ, Valero AL, Picado C, et al. Mechanisms, cofactors, and augmenting factors involved in anaphylaxis. Front Immunol. 2017 Sep 26;8:1193. 10.3389/fimmu.2017.01193

42. Netchiporouk E, Sasseville D, Moreau L, Habel Y, Rahme E, Ben-Shoshan M. Evaluating comorbidities, natural history, and predictors of early resolution in a cohort of children with chronic urticaria. JAMA Dermatol. 2017;153(12):1236–42. 10.1001/jamadermatol.2017.3182

43. Kozel MMA, Mekkes JR, Bossuyt PMM, Bos JD. Natural course of physical and chronic urticaria and angioedema in 220 patients. J Am Acad Dermatol. 2001 Sep;45(3):387–91. 10.1067/mjd.2001.116217

44. Miles LM, Gabrielli S, Le M, Netchiporouk E, Baum S, Greenberger S, et al. Clinical characteristics, management, and natural history of chronic inducible urticaria in a pediatric cohort. Int Arch Allergy Immunol. 2021;182(8):757–64. 10.1159/000514757

45. Sahiner UM, Civelek E, Tuncer A, Yavuz ST, Karabulut E, Sackesen C, et al. Chronic urticaria: Etiology and natural course in children. Int Arch Allergy Immunol. 2011;156(2):224–30. 10.1159/000322349

46. Gregoriou S, Rigopoulos D, Katsambas A, Katsarou A, Papaioannou D, Gkouvi A, et al. Etiologic aspects and prognostic factors of patients with chronic urticaria: Nonrandomized, prospective, descriptive study. J Cutan Med Surg. 2009 Jul 1;13(4):198–203. 10.2310/7750.2008.08035

47. Kulthanan K, Jiamton S, Thumpimukvatana N, Pinkaew S. Chronic idiopathic urticaria: Prevalence and clinical course. J Dermatol. 2007 Apr 4;34(5):294–301. 10.1111/j.1346-8138.2007.00276.x

48. Magerl M, Altrichter S, Borzova E, Giménez-Arnau A, Grattan CEH, Lawlor F, et al. The definition, diagnostic testing, and management of chronic inducible urticarias—The EAACI/GA 2 LEN/EDF/UNEV consensus recommendations 2016 update and revision. Allergy. 2016 Jun;71(6):780–802. 10.1111/all.12884

49. Arik Yilmaz E, Karaatmaca B, Sackesen C, Sahiner UM, Cavkaytar O, Sekerel BE, et al. Parasitic infections in children with chronic spontaneous urticaria. Int Arch Allergy Immunol. 2016;171(2):130–5. 10.1159/000450953

50. Kolkhir P, Balakirski G, Merk HF, Olisova O, Maurer M. Chronic spontaneous urticaria and internal parasites—A systematic review. Allergy. 2016 Mar;71(3):308–22. 10.1111/all.12818

51. Cavkaytar O, Arik Yilmaz E, Buyuktiryaki B, Sekerel BE, Sackesen C, Soyer OU. Challenge-proven aspirin hypersensitivity in children with chronic spontaneous urticaria. Allergy. 2015 Feb;70(2):153–60. 10.1111/all.12539

52. Mehr S, Allen R, Boros C, Adib N, Kakakios A, Turner PJ, et al. Cryopyrin-associated periodic syndrome in Australian children and adults: Epidemiological, clinical and treatment characteristics. J Paediatr Child Health. 2016 Sep;52(9):889–95. 10.1111/jpc.13270

53. Kolkhir P, Pogorelov D, Olisova O, Maurer M. Comorbidity and pathogenic links of chronic spontaneous urticaria and systemic lupus erythematosus—A systematic review. Clin Exp Allergy. 2016 Feb;46(2):275–87. 10.1111/cea.12673

54. Sprinzl B, Greiner G, Uyanik G, Arock M, Haferlach T, Sperr WR, et al. Genetic regulation of tryptase production and clinical impact: Hereditary alpha tryptasemia, mastocytosis and beyond. Int J Mol Sci. 2021 Feb 28;22(5):2458. 10.3390/ijms22052458

55. Wahn V, Aberer W, Aygören-Pürsün E, Bork K, Eberl W, Faßhauer M, et al. Hereditary angioedema in children and adolescents—A consensus update on therapeutic strategies for German-speaking countries (Atanaskovic-Markovic M, editor). Pediatr Allergy Immunol. 2020 Nov 16;31(8):974–89. 10.1111/pai.13309

56. Ben-Shoshan M, Grattan CE. Management of pediatric urticaria with review of the literature on chronic spontaneous urticaria in children. J Allergy Clin Immunol Pract. 2018;6(4):1152–61. 10.1016/j.jaip.2018.02.015

57. Caffarelli C, Cuomo B, Cardinale F, Barberi S, Dascola C, Agostinis F, et al. Aetiological factors associated with chronic urticaria in children: A systematic review. Acta Derm Venereol. 2013;93(3):268–72. 10.2340/00015555-1511

58. Vezir S, Kaya F, Vezir E, Karaosmanoğlu N, Adiloğlu AK. Evaluation of intestinal parasites in patients with chronic spontaneous urticaria in a territory hospital in Turkey. J Infect Dev Ctries. 2019 Oct 31;13(10):927–32. 10.3855/jidc.11552

59. Kocatürk E, Salman A, Cherrez-Ojeda I, Criado PR, Peter J, Comert-Ozer E, et al. The global impact of the COVID-19 pandemic on the management and course of chronic urticaria. Allergy. 2021 Mar 29;76(3):816–30.

60. Muntean IA, Pintea I, Bocsan IC, Dobrican CT, Deleanu D. COVID-19 disease leading to chronic spontaneous urticaria exacerbation: A Romanian retrospective study. Healthcare. 2021 Sep 1;9(9):1144. 10.3390/healthcare9091144

61. Napolitano M, Megna M, Costa C, Balato N, Patruno C. Chronic inducible urticarias in children. J Allergy Clin Immunol Pract. 2018 Jul;6(4):1391–3. 10.1016/j.jaip.2017.12.021

62. Yee CSK, El Khoury K, Albuhairi S, Broyles A, Schneider L, Rachid R. Acquired cold-induced urticaria in pediatric patients: A 22-year experience in a tertiary care center (1996–2017). J Allergy Clin Immunol Pract. 2019 Mar;7(3):1024–31.e3. 10.1016/j.jaip.2018.10.025

63. Liccioli G, Nappi L, Mori F, Barni S, Giovannini M, Sarti L, et al. Dermatographism and urticaria in a pediatric population (Atanaskovic-Markovic M, editor). Pediatr Allergy Immunol. 2020 Apr 23;31(3):318–20. 10.1111/pai.13209

64. Schmetzer O, Lakin E, Topal FA, Preusse P, Freier D, Church MK, et al. IL-24 is a common and specific autoantigen of IgE in patients with chronic spontaneous urticaria. J Allergy Clin Immunol. 2018;142(3):876–82. 10.1016/j.jaci.2017.10.035

65. Grattan C. Autoimmune chronic spontaneous urticaria. J Allergy Clin Immunol. 2018 Mar;141(3):1165–6. 10.1016/j.jaci.2017.09.014

66. Chang J, Cattelan L, Ben-Shoshan M, Le M, Netchiporouk E. Management of pediatric chronic spontaneous urticaria: A review of current evidence and guidelines. J Asthma Allergy. 2021 Mar;14:187–99. 10.2147/JAA.S249765

67. Kolkhir P, Borzova E, Grattan C, Asero R, Pogorelov D, Maurer M. Autoimmune comorbidity in chronic spontaneous urticaria: A systematic review. Autoimmun Rev. 2017 Dec;16(12):1196–208. 10.1016/j.autrev.2017.10.003

68. Altrich ML, Halsey JF, Altman LC. Comparison of the in vivo autologous skin test with in vitro diagnostic tests for diagnosis of chronic autoimmune urticaria. Allergy Asthma Proc. 2009 Jan 1;30(1):28–34. 10.2500/aap.2009.30.3185

69. Azkur D, Civelek E, Toyran M, Mısırlıoğlu ED, Erkoçoğlu M, Kaya A, et al. Clinical and etiologic evaluation of the children with chronic urticaria. Allergy Asthma Proc. 2016 Nov 1;37(6):450–7. 10.2500/aap.2016.37.4010

70. Netchiporouk E, Moreau L, Rahme E, Maurer M, Lejtenyi D, Ben-Shoshan M. Positive CD63 basophil activation tests are common in children with chronic spontaneous urticaria and linked to high disease activity. Int Arch Allergy Immunol. 2016;171(2):81–8. 10.1159/000451084

71. Davis MDP, van der Hilst JCH. Mimickers of urticaria: Urticarial vasculitis and autoinflammatory diseases. J Allergy Clin Immunol Pract. 2018;6(4):1162–70. 10.1016/j.jaip.2018.05.006

72. Hernández-Ostiz S, Prieto-Torres L, Xirotagaros G, Noguera-Morel L, Hernández-Martín TA. Autoinflammatory diseases in pediatric dermatology—Part 1: Urticaria-like syndromes, pustular syndromes, and mucocutaneous ulceration syndromes. Actas Dermosifiliogr. 2017;108(7):609–19. 10.1016/j.ad.2016.12.021

73. Kuemmerle-Deschner JB, Ozen S, Tyrrell PN, Kone-Paut I, Goldbach-Mansky R, Lachmann H, et al. Diagnostic criteria for cryopyrin-associated periodic syndrome (CAPS). Ann Rheum Dis. 2017;76(6):942–7. 10.1136/annrheumdis-2016-209686

74. Booshehri LM, Hoffman HM. CAPS and NLRP3. J Clin Immunol. 2019;39(3):277–86. 10.1007/s10875-019-00638-z

75. Gattorno M, Hofer M, Federici S, Vanoni F, Bovis F, Aksentijevich I, et al. Classification criteria for autoinflammatory recurrent fevers. Ann Rheum Dis. 2019;78(8):1025–32. 10.1136/annrheumdis-2019-215048

76. Gusdorf L, Lipsker D. Neutrophilic urticarial dermatosis: A review. Ann Dermatol Venereol. 2018;145(12):735–40. 10.1016/j.annder.2018.06.010

77. Gusdorf L, Lipsker D. Schnitzler syndrome: A review. Curr Rheumatol Rep. 2017;19(8):1–6. 10.1007/s11926-017-0673-5

78. Gusdorf L, Asli B, Barbarot S, Néel A, Masseau A, Puéchal X, et al. Schnitzler syndrome: Validation and applicability of diagnostic criteria in real-life patients. Allergy Eur J Allergy Clin Immunol. 2017;72(2):177–82. 10.1111/all.13035

79. Weiler CR. Mast cell activation syndrome: Tools for diagnosis and differential diagnosis. J Allergy Clin Immunol Pract. 2020;8(2):498–506. 10.1016/j.jaip.2019.08.022

80. Brockow K. Epidemiology, prognosis, and risk factors in mastocytosis. Immunol Allergy Clin North Am. 2014 May;34(2):283–95. 10.1016/j.iac.2014.01.003

81. Ben-Amitai D, Metzker A, Cohen HA. Pediatric cutaneous mastocytosis: A review of 180 patients. ISR Med Assoc J. 2005 May;7(5):320–2.

82. Le M, Miedzybrodzki B, Olynych T, Chapdelaine H, Ben-Shoshan M. Natural history and treatment of cutaneous and systemic mastocytosis. Postgrad Med. 2017 Nov 17;129(8):896–901. 10.1080/00325481.2017.1364124

83. Tamay Z, Ozceker D. Current approach to cutaneous mastocytosis in childhood. Türk Pediatr Arşivi. 2016 Aug 29;51(3):123–7. 10.5152/TurkPediatriArs.2016.2418

84. Hartmann K, Escribano L, Grattan C, Brockow K, Carter MC, Alvarez-Twose I, et al. Cutaneous manifestations in patients with mastocytosis: Consensus report of the European Competence Network on Mastocytosis; the American Academy of Allergy, Asthma & Immunology; and the European Academy of Allergology and Clinical Immunology. J Allergy Clin Immunol. 2016 Jan;137(1):35–45. 10.1016/j.jaci.2015.08.034

85. Lange M, Nedoszytko B, Górska A, Zawrocki A, Sobjanek M, Kozlowski D. Mastocytosis in children and adults: Clinical disease heterogeneity. Arch Med Sci. 2012 Jul 4;8(3):533–41. 10.5114/aoms.2012.29534

86. Horny H-P, Sotlar K, Valent P. Mastocytosis: State of the art. Pathobiology. 2007;74(2):121–32. 10.1159/000101711

87. Theoharides TC, Valent P, Akin C. Mast cells, mastocytosis, and related disorders. N Engl J Med. 2015;373(2):163–72. 10.1056/NEJMra1409760

88. Bonadonna P, Zanotti R, Müller U. Mastocytosis and insect venom allergy. Curr Opin Allergy Clin Immunol. 2010;10(4):347–53. 10.1097/ACI.0b013e32833b280c

89. Afrin LB, Self S, Menk J, Lazarchick J. Characterization of mast cell activation syndrome. Am J Med Sci. 2017 Mar;353(3):207–15. 10.1016/j.amjms.2016.12.013

90. Valent P, Akin C, Arock M, Brockow K, Butterfield JH, Carter MC, et al. Definitions, criteria and global classification of mast cell disorders with special reference to mast cell activation syndromes: A consensus proposal. Int Arch Allergy Immunol. 2012;157(3):215–25. 10.1159/000328760

91. Kolkhir P, André F, Church MK, Maurer M, Metz M. Potential blood biomarkers in chronic spontaneous urticaria. Clin Exp Allergy. 2017;47(1):19–36. 10.1111/cea.12870

92. Karaman S, Turedi B. Neutrophil-lymphocyte ratio: A possible marker of remission in children with chronic spontaneous urticaria. Allergol Immunopathol (Madr). 2020 May;48(3):290–4. 10.1016/j.aller.2019.11.007

93. Dilek F, Ozceker D, Ozkaya E, Tamay Z, Yazici M, Kesgin S, et al. Plasma levels of matrix metalloproteinase-9 in children with chronic spontaneous urticaria. Allergy Asthma Immunol Res. 2016;8(6):522. 10.4168/aair.2016.8.6.522

94. Akelma AZ, Mete E, Cizmeci MN, Kanburoglu MK, Malli DD, Bozkaya D. The role of mean platelet volume as an inflammatory marker in children with chronic spontaneous urticaria. Allergol Immunopathol (Madr). 2015 Jan;43(1):10–3. 10.1016/j.aller.2013.06.002

95. Bas M, Adams V, Suvorava T, Niehues T, Hoffmann TK, Kojda G. Nonallergic angioedema: Role of bradykinin. Allergy. 2007 Aug;62(8):842–56. 10.1111/j.1398-9995.2007.01427.x

96. MacGinnitie AJ. Pediatric hereditary angioedema. Pediatr Allergy Immunol. 2014 Aug 9;25(5):420–7. 10.1111/pai.12168

97. Giavina-Bianchi P, Arruda LK, Aun MV, Campos RA, Chong-Neto HJ, Constantino-Silva RN, et al. Diretrizes brasileiras para o diagnóstico e tratamento do angioedema hereditário—2017. Arq Asma Alerg e Imunol. 2017;1(1):23-48. 10.5935/2526-5393.20170005

98. Campos R de A, Valle SOR, Toledo EC. Hereditary angioedema: a disease seldom diagnosed by pediatricians. J Pediatr (Rio J). 2021 Mar;97:S10–6. 10.1016/j.jped.2020.10.011

99. Pagnier A. L’angioedème héréditaire en pédiatrie: enjeux diagnostique et thérapeutique. Presse Med. 2015 Jan;44(1):89–95. 10.1016/j.lpm.2014.07.018

100. Otani IM, Banerji A. Acquired C1 inhibitor deficiency. Immunol Allergy Clin North Am. 2017 Aug;37(3):497–511. 10.1016/j.iac.2017.03.002

101. Araújo-Simões J, Boanova AGP, Constantino-Silva RN, Fragnan NTML, Pinto JA, Minafra FG, et al. The challenges in the follow-up and treatment of Brazilian children with hereditary angioedema. Int Arch Allergy Immunol. 2021;182(7):585–91. 10.1159/000512944

102. Read N, Lim E, Tarzi MD, Hildick-Smith P, Burns S, Fidler KJ. Paediatric hereditary angioedema: A survey of UK service provision and patient experience. Clin Exp Immunol. 2014 Dec;178(3):483–8. 10.1111/cei.12433

103. Bork K, Hardt J, Witzke G. Fatal laryngeal attacks and mortality in hereditary angioedema due to C1-INH deficiency. J Allergy Clin Immunol. 2012 Sep;130(3):692–7. 10.1016/j.jaci.2012.05.055

104. Ghazanfar MN, Kibsgaard L, Thomsen SF, Vestergaard C. Risk of comorbidities in patients diagnosed with chronic urticaria: A nationwide registry study. World Allergy Organ J. 2020 Jan;13(1):100097. 10.1016/j.waojou.2019.100097

105. Andrade Coelho Dias G, Cunha Coelho F, Filippo P, Lacerda Pedrazzi D, Nogueira Arraes AC, Perello MI, et al. Clinical experience of a chronic urticaria referral university center. Eur Ann Allergy Clin Immunol. 2020 May;52(03):74. 10.23822/EurAnnACI.1764-1489.103

106. Cornillier H, Giraudeau B, Munck S, Hacard F, Jonville-Bera A-P, D’Acremont G, et al. Chronic spontaneous urticaria in children—A systematic review on interventions and comorbidities. Pediatr Allergy Immunol. 2018 May;29(3):303–10. 10.1111/pai.12870

107. Lewis-Jones MS, Finlay AY. The Children’s Dermatology Life Quality Index (CDLQI): Initial validation and practical use. Br J Dermatol. 2010 Sep 6;132(6):942–9. 10.1111/j.1365-2133.1995.tb16953.x

108. Daudén E, Sánchez-Perez J, Prieto M, Roset M. Validación de la versión española de la escala de intensidad del picor (Cuestionario Itch Severity Scale, ISS). Estudio PSEDA. Actas Dermosifiliogr. 2011 Sep 102(7):527–36. 10.1016/j.ad.2011.03.011