Arquivos de Asma, Alergia e Imunologia
https://aaai-asbai.org.br/article/doi/10.5935/2526-5393.20170020
Arquivos de Asma, Alergia e Imunologia
Artigo Especial

Guia prático de atualização em dermatite atópica - Parte II: abordagem terapêutica. Posicionamento conjunto da Associação Brasileira de Alergia e Imunologia e da Sociedade Brasileira de Pediatria

Updated practical guide on atopic dermatitis - Part II: treatment approach. Joint position paper of the Brazilian Association of Allergy and Immunology and the Brazilian Society of Pediatrics

Vânia O. Carvalho; Dirceu Solé; Adriana A. Antunes; Ana E. Kiszewski Bau; Fábio C. Kuschnir; Márcia C. Mallozi; Jandrei R. Markus; Maria G. Nascimento e Silva; Mário C. Pires; Marice E. El Achkar Mello; Nelson A. Rosário Filho; Emanuel S. Cavalcanti Sarinho; Herberto J. Chong-Neto; Luciana R. Silva; Norma P. M. Rubini

Downloads: 0
Views: 26

Resumo

Nas últimas décadas o conhecimento sobre a etiopatogenia da dermatite atópica (DA) avançou muito. Além da identificação dos principais agentes desencadeantes e/ou agravantes envolvidos na expressão clínica da DA, verificou-se ser a integridade da barreira cutânea um dos pontos fundamentais para a manutenção da homeostase da pele. Assim, no tratamento do paciente com DA, além da evitação dos agentes desencadeantes e/ou irritantes, o uso de hidratantes é parte fundamental, e acredita-se que tenha ação preventiva de surtos agudos. Além disso, a aquisição de agentes anti-inflamatórios de uso tópico tem permitido o controle de pacientes com formas leves a moderadas da DA. Embora tenham uso mais restrito, os agentes imunossupressores sistêmicos também têm sido empregados no tratamento de pacientes com DA grave ou refratária aos procedimentos habituais. Comenta-se também a imunoterapia alérgeno-específica como tratamento adjuvante da DA para alguns pacientes, sobretudo alérgicos aos ácaros e com manifestações respiratórias associadas. A aquisição de novos agentes, os imunobiológicos, também são apresentados à luz das evidências científicas e clínicas atuais. O presente guia prático de atualização em dermatite atópica – abordagem terapêutica teve por objetivo rever os esquemas de tratamento disponíveis e empregados no acompanhamento de pacientes com DA, além de apresentar terapêuticas futuras, como os agentes imunobiológicos que em breve estarão à disposição para o tratamento de formas mais graves e/ou refratárias da DA.

Palavras-chave

Dermatite atópica, hidratação da pele, corticosteroides tópicos, inibidores da calcineurina, ciclosporina, imunobiológico, imunoterapia.

Abstract

Over the last few decades, knowledge of the etiopathogenesis of atopic dermatitis (AD) advanced greatly. The main triggering and/or aggravating factors involved in the clinical expression of AD have been identified, and cutaneous barrier integrity has been found to be key for the maintenance of skin homeostasis. Thus, when treating patients with AD, in addition to avoiding triggering and/ or irritating agents, recommending the use of skin moisturizers is paramount – and believed to have a preventive action against acute outbreaks. Moreover, topical anti-inflammatory agents have allowed AD control in patients with mild to moderate forms of the disease. Although more restricted, systemic immunosuppressive agents have also been used in the treatment of patients with severe or refractory AD. Specific allergen immunotherapy is presented as a possible adjunctive treatment for AD in some patients, especially those allergic to mites and presenting associated respiratory manifestations. Finally, the use of new immunobiological agents is discussed in the light of the scientific and clinical evidence currently available. The objectives of this updated practical guide on atopic dermatitis – treatment approach were to review the treatment regimens available and used in the follow-up of patients with AD and to present new therapies (e.g., immunobiological agents) that will soon be available for the treatment of more severe and/ or refractory forms of AD.

Keywords

Atopic dermatitis, skin moisturizing, topical corticosteroids, calcineurin inhibitors, cyclosporine, immunobiological agents, immunotherapy.

Referências

1. Paller AS, Mancini AJ, Hurwitz S. Clinical Pediatric Dermatology: a textbook of skin disorders of childhood and adolescence. 5ª ed. Nova Iorque: Elsevier; 2016. p. 640.

2. Mengeaud V, Phulpin C, Bacquey A, Boralevi F, Schmitt AM, Taieb A. An innovative oat-based sterile emollient cream in the maintenance therapy of childhood atopic dermatitis. Pediatr Dermatol. 2015;32:208-15.

3. Rubel D, Thirumoorthy T, Soebaryo RW, Wenq SC, Gabriel TM, Villafuerte LL, et al. Consensus guidelines for the manegement of atopic dermatitis: an Asia-Pacific perspective. J Dermatol. 2013;40:160-71.

4. Catherine Mack Correa M, Nebus J. Management of patients with atopic dermatitis: the role of emollient therapy. Dermatol Res Pract. 2012;2012:836931.

5. Draelos ZD. Modern moisturizer myths, misconceptions, and truths. Cutis. 2013;91:308-14.

6. Flynn TC, Petros J, Clark RE, Viehman GE. Dry skin and moisturizers. Clin Dermatol. 2001;19:387-92.

7. Eichenfield LF, Tom WL, Berger TG, Krol A, Paller AS, Schwarzenberger K, et al. Guidelines of care for the management of atopic dermatitis: Section 2. Management and treatment of atopic dermatitis with topical therapies. J Am Acad Dermatol. 2014;71:116‑32.

8. Ring J, Alomar A, Bieber T, Deleuran M, Fink-Wagner A, Gelmetti C, et al. Guidelines for treatment of atopic eczema (atopic dermatitis) part I. J Eur Acad Dermatol Venereol. 2012;26(8):1045-60.

9. Wollenberg A, Oranje A, Deleuran M, Simon D, Szalai Z, Kunz B, et al. ETFAD/EADV Eczema task force 2015 position paper on diagnosis and treatment of atopic dermatitis in adult and paediatric patients. J Eur Acad Dermatol Venereol. 2016;30(5):729-47.

10. Oliveira ZNP, Schvarstman BGS, Maluf PT. Pediatria Instituto Criança Hospital das Clínicas-Dermatologia Pediátrica. 1ªed. Barueri, SP: Editora Manole; 2009. p. 480.

11. Devillers AC, Oranje AP. Wet-wrap treatment in children with atopic dermatitis: a practical guideline. Pediatr Dermatol. 2012;29:24-7.

12. Aubert-Wastiaux H, Moret L, Le Rhun A, Fontenoy AM, Nguyen JM, Leux C, et al. Topical corticosteroid phobia in atopic dermatitis: a study of its nature, origins and frequency. Br J Dermatol. 2011;165(4):808‑14.

13. Siegfried EC, Jaworski JC, Kaiser JD, Hebert AA. Systematic review of published trials: long-term safety of topical corticosteroids and topical calcineurin inhibitors in pediatric patients with atopic dermatitis. BMC pediatrics. 2016;16:75.

14. Fukuie T, Hirakawa S, Narita M, Nomura I, Matsumoto K, Tokura Y, et al. Potential preventive effects of proactive therapy on sensitization in moderate to severe childhood atopic dermatitis: A randomized, investigator-blinded, controlled study. J Dermatol. 2016;43(11):1283‑92.

15. Ng SY, Begum S, Chong SY. Does Order of Application of Emollient and Topical Corticosteroids Make a Difference in the Severity of Atopic Eczema in Children? Pediatr Dermatol. 2016;33(2):160-4.

16. Sigurgeirsson B, Boznanski A, Todd G, Vertruyen A, Schuttelaar ML, Zhu X, et al. Safety and efficacy of pimecrolimus in atopic dermatitis: a 5-year randomized trial. Pediatrics. 2015;135(4):597-606.

17. Hanifin JM, Ling MR, Langley R, Breneman D, Rafal E. Tacrolimus ointment for the treatment of atopic dermatitis in adult patients: part I, efficacy. J Am Acad Dermatol. 2001;44(1 Suppl):S28-38.

18. Luger T, Boguniewicz M, Carr W, Cork M, Deleuran M, Eichenfield L, et al. Pimecrolimus in atopic dermatitis: consensus on safety and the need to allow use in infants. Pediatr Allergy Immunol. 2015;26(4):306-15.

19. Chia BK, Tey HL. Systematic review on the efficacy, safety, and costeffectiveness of topical calcineurin inhibitors in atopic dermatitis. Dermatitis. 2015;26(3):122-32.

20. Cury Martins J, Martins C, Aoki V, Gois AF, Ishii HA, da Silva EM. Topical tacrolimus for atopic dermatitis. Cochrane database.2015(7):Cd009864.

21. Ministério da Saúde. Dermatologia na Atenção Básica de Saúde / Cadernos de Atenção Básica Nº 9 / Série A - Normas de Manuais Técnicos; n° 174.

22. Ständer S, Weisshaar E, Mettang T, Szepietowski JC, Carstens E, Ikoma A, et al. Clinical classification of itch: a position paper of the International Forum for the Study of Itch. Acta Derm Venereol. 2007;87:291‑4.

23. Kini SP, DeLong LK, Veledar E, McKenzie-Brown AM, Schaufele M, Chen SC. The impact of pruritus on quality of life: the skin equivalent of pain. Arch Dermatol. 2011;147:1153-6.

24. Pires MC, Santos RNR. Dermatites e Eczemas. In: Sittart JAS & Pires MC, Dermatologia na prática médica. São Paulo: Ed. Roca;

2007. p. 31-62.

25. Pires MC, Cestari S. In: Dermatite atópica. Rio de Janeiro: Ed. Diagraphic; 2005. p. 111‑8.

26. Kido-Nakahara M, Furue M, Ulzii D, Nakahara T. Itch and atopic dermatitis. Immunol Allergy Clin N Am. 2017;37(1):113‑22.

27. Han L, Dong X. Itch mechanisms and circuits. Annu Rev Biophys. 2014;43:331-55.

28. Dhand A, Aminoff MJ. The neurology of itch. Brain. 2014;137(Pt 2):313-22.

29. Mollanazar NK, Smith PK, Yosipovitch G. Mediators of chronic pruritus in atopic dermatitis: getting the itch out? Clin Rev Allergy Immunol 2015. Clin Rev Allergy Immunol. 2016;51(3):263‑92.

30. Tominaga M, Takamori K. Itch and nerve fibers with special reference to atopic dermatitis: therapeutic implications. J Dermatol. 2014;41:205‑12.

31. Lambert J. Pruritus in female patients. Biomed Res Int. 2014;2014:541967.

32. Metz M, Wahn U, Gieler U, Stock P, Schmitt J, Blume-Peytavi U. Chronic pruritus associated with dermatologic disease in infancy and childhood: update from an interdisciplinary group of dermatologists and pediatricians. Pediatric Allergy Immunol. 2013;24(6):527-39.

33. Sittart JAS, Pires MC. Pruridos e prurigos. In: Sittart & Pires. Dermatologia na prática médica. São Paulo: Ed. Roca; 2007. p. 93‑100.

34. Rhoades RB, Leifer KN, Cohan R, Wittig HJ. Suppression of histamine-induced pruritus by three antihistamine drugs. J Allergy Clin Immunol. 1975;55:180‑5.

35. Arnold AJ, Simpson JG, Jones HE, Ahmed AR. Suppression of histamine-induced pruritus by hydroxyzine and various neuroleptics. J Am Acad Dermatol. 1979;1:509-12.

36. O’Donoghue M, Tharp MD. Antihistamine and their role as antipruritics. Dermal Ther. 2005;18:333-40.

37. Leyva-Castillo JM, Hener P, Michea P, Karasuyama H, Chan S, Soumelis V, et al. Skin thymic stromal lymphopoietin initiates Th2 responses through an orchestrated immune cascade. Nat Commun. 2013;4:2847.

38. Aktar MK, Kido-Nakahara M, Furue M, Nakahara T. Mutual upregulation of endothelin-1 and IL-25 in atopic dermatitis. Allergy. 2015;70:846‑54.

39. Mochizuki H, Kakigi R. Itch and brain. J Dermatol. 2015;42:761‑7.

40. Mochizuki H, Papoiu ADP, Yosipovitch G. Brain processing of itch and scratching. In: Carstens E, Akiyama T (ed). Itch: mechanisms and treatment. Boca Raton (FL): CRC Press; 2014. p. 391‑407.

41. Lio PA. Efficacy of a moisturizing foam in Skin Barrier regeneration and itch relief in subjects prone do atopic dermatitis. J Drugs Dermatol. 2016;1;15(11):s77-s80.

42. Mahtani R, Parekh N, Mangat I, Bhalerao S. Alleviating the itch-scratch cycle in atopic dermatitis. Psychosomatics. 2005;46(4):373‑4.

43. Kraft M, Worm M. Dupilumab in the treatment of moderate-to-severe atopic dermatitis. Expert Rev Clin Immunol. 2017;13(4):301‑10.

44. Paller AS, Tom WL, Lebwohl MG, Blumenthal RL, Boguniewicz M, Call RS, et al. Efficacy and safety of crisaborole ointment, a novel, nonsteroidal phosphodiesterase 4 (PDE4) inhibitor for the topical treatment of atopic dermatitis (AD) in children and adults. J Am Acad Dermatol. 2016;75(3):494-503.

45. Sun D, Ong PY. Infectious Complications in Atopic Dermatitis. Immunol Allergy Clin N Am. 2017;37(1):75-93.

46. Paller A, Mancini AJ, Hurwitz S. Hurwitz clinical pediatric dermatology. 4th ed. Edinburgh; New York: Elsevier Saunders; 2011.

47. Sugarman JL, Hersh AL, Okamura T, Howard R, Frieden IJ. A retrospective review of streptococcal infections in pediatric atopic dermatitis. Pediatr Dermatol. 2011;28(3):230‑4.

48. Ryan C, Shaw RE, Cockerell CJ, Hand S, Ghali FE. Novel sodium hypochlorite cleanser shows clinical response and excellent acceptability in the treatment of atopic dermatitis. Pediatr Dermatol. 2013;30(3):308‑15.

49. Huang JT, Abrams M, Tlougan B, Rademaker A, Paller AS, Frieden J. Treatment of Staphylococcus aureus colonization in atopic dermatitis decreases disease severity. Pediatrics. 2009;123(5):e808-14.

50. Fritz SA, Camins BC, Eisenstein KA, Fritz JM, Epplin EK, Burnhem CA, et al. Effectiveness of measures to eradicate Staphylococcus aureus carriage in patients with community-associated skin and softtissue infections: a randomized trial. Infect Control Hosp Epidemiol. 2011;32(9):872‑80.

51. Frisch S, Siegfried EC. The clinical spectrum and therapeutic challenge of eczema herpeticum. Pediatr Dermatol. 2011;28(1):46‑52.

52. Berger EM, Orlow SJ, Patel RR, Schaffer JV. Experience with molluscum contagiosum and associated inflammatory reactions in a pediatric dermatology practice: the bump that rashes. Arch Dermatol. 2012;148(11):1257-64.

53. Mathes EF, Oza V, Frieden IJ, Cordoro KM, Yagi S, Howard R, et al. “Eczema coxsackium” and unusual cutaneous findings in an enterovirus outbreak. Pediatrics. 2013;132(1):e149‑57.

54. Schneider L, Tilles S, Lio P, Schneider L, Tilles S, Lio P, et al. Atopic dermatitis: a practice parameter update 2012. J Allergy Clin Immunol. 2013;131:295-9.

55. Slavyanakaya TA, Derkach VV, Sepiashvili RI. Debates in allergy medicine: specific immunotherapy efficiency in children with atopic dermatitis. WAO Journal. 2016;9:15-25.

56. Gutgesell C, Heise S, Seubert S, Seubert A, Domhof S, Brunner E, et al. Atopic dermatitis, house-dust mite, and the placebo effect. Allergy. 2001;56:1226-7.

57. Holm L, Bengtsson A, van Hage-Hamsten M, Ohman S, Scheynius A. Effectiveness of occlusive bedding in the treatment of atopic dermatitis - a placebo-controlled trial of 12 months’ duration. Allergy. 2001;56:152-8.

58. Tan BB, Weald D, Strickland I, Friedmann PS. Double-blind controlled trial of effect of housedust-mite allergen avoidance on atopic dermatitis. Lancet. 1996;347:15-8.

59. Oosting AJ, de Bruin-Weller MS, Terreehorst I, Tempels-Pavlica Z, Aalberse RC, de Monchy JG, et al. Effect of mattress encasings on atopic dermatitis outcome measures in a double-blind, placebocontrolled study: the Dutch mite avoidance study. J Allergy Clin Immunol. 2002;110:500-6.

60. Rubini NPM, Wandalsen GF, Rizzo MCV, Aun MV, Chong HJ, Solé D. Guia prático sobre controle ambiental para pacientes com rinite alérgica. Arq Asma Alerg Imunol. 2017;1(1):7-22.

61. Skripak JM, Matsui EC, Mudd K, Wood RA. The natural history of IgE-mediated cow’s milk allergy. J Allergy Clin Immunol. 2007;120:1172-7.

62. Keet CA, Matsui EC, Dhillon G et al. The natural history of wheat allergy. Ann Allergy Asthma Immunol. 2009;102:410-5.

63. Savage JH, Matsui EC, Skripak JM, Wood RA. The natural history of egg allergy. J Allergy Clin Immunol. 2007;120:1413-7.

64. Savage JH, Kaeding AJ, Matsui EC, Wood RA. The natural history of soy allergy. J Allergy Clin Immunol. 2010;125:683-6.

65. Ministério da Saúde, Consultoria Jurídica/Advocacia Geral da União. Nota Técnica N° 285/2013, Brasília, agosto de 2013. Ciclosporina. Disponível em www.agu.gov.br/page/download/index/id/23707821. Acessado em 20 de fevereiro de 2017.

66. Roekevisch E, Spuls P I, Kuester D, Limpens J, Schmitt J. Efficacy and safety of systemic treatments for moderate-to-severe atopic dermatitis: A systematic review. J Allergy Clin Immunol 2014;133:429-38.

67. Simon D, Bieber T. Systemic therapy for atopic dermatites. Allergy 2014;69:46‑55.

68. Schmitt J, Schakel K, Fölster-Holst R, Bauer A, Oertel R, Augustin M, Aberer W, et al. Prednisolone vs. ciclosporin for severe adult eczema. An investigator-initiated double-blind placebo-controlled multicentre trial. Br J Dermatol. 2010;162:661-8.

69. Akdis CA, Akdis M, Bieber T, Bindslev-Jensen C, Boguniewicz M, Eigenmann P, et al. Diagnosis and treatment of atopic dermatitis in children and adults: European Academy of Allergology and Clinical Immunology/ American Academy of Allergy, Asthma and Immunology/PRACTALL Consensus Report. J Allergy Clin Immunol. 2006;118:152-69.

70. Schmitt J, Schmitt N, Meurer M. Cyclosporin in the treatment of patients with atopic eczema – a systematic review and meta-analysis. J Eur Acad Dermatol Venereol. 2007;21:606-19.

71. El-Khalawany MA, Hassan H, Shaaban D,Ghonaim N, Eassa B. Methotrexate versus cyclosporine in the treatment of severe atopic dermatitis in children: a multicenter experience from Egypt. Eur J Pediatr. 2013;172:351-6.

72. Deo M, Yung A, Hill S, Rademaker M. Methotrexate for treatment of atopic dermatitis in children and adolescents. Int J Dermatol. 2014;53(8):1037‑41.

73. Murphy LA, Atherton DJ. Azathioprine as a treatment for severe atopic eczema in children with a partial thiopurine methyl transferase (TPMT) deficiency. Pediatr Dermatol. 2003;20:531‑4.

74. Meggitt SJ, Gray JC, Reynolds NJ. Azathioprine dosed by thiopurine methyltransferase activity for moderate-to-severe atopic eczema: a double-blind, randomised controlled trial. Lancet. 2006;367:839‑46.

75. Grundmann-Kollmann M, Podda M, Ochsendorf F, Boehncke W-H,Kaufmann R, Zollner T. Mycophenolate mofetil is effective in the treatment of atopic dermatitis. Arch Dermatol. 2001;137:870‑3.

76. Heller M, Shin HT, Orlow SJ, Schaffer JV. Mycophenolate mofetil for severe childhood atopic dermatitis: experience in 14 patients. Br J Dermatol. 2007;157:127‑32.

77. Schneider LC, Baz Z, Zarcone C, Zurakowski D. Long-term therapy with recombinant interferon-gamma (rIFN-gamma) for atopic dermatitis. Ann Allergy Asthma Immunol. 1998;80:263‑8.

77. Turner PJ, Kakakios A, Wong LC, Wong M, Campbell DE. Intravenous immunoglobulin to treat severe atopic dermatitis in children: a case series. Pediatr Dermatol. 2012;29:177-81.

78. Ozen A, Baris S, Karakoc Aydiner E, Yucelten D, Nadir Bahceciler N. Experience with intravenous immunoglobulin in severe childhood atopic dermatitis. Allergol Immunopathol (Madr). 2012;40:131‑3.

79. Werfel T, Allam J, Biedermann T, Eyerich K, Gilles S, Guttman-Yassky E, Hoetzenecker W, et al. Cellular and molecular immunologic mechanisms in patients with atopic dermatitis.J Allergy Clin Immunol. 2016;138:336-49.

80. Ondas do espectro eletromagnético. Disponível em www. brasilescola.uol.com.br/fisica/espectro-eletromagnetico.htm acessado em 20 de fevereiro de 2017.

81. Garritsen FM, Brouwer MW, Limpens J, Spuls PI. Photo(chemo) therapy in the management of atopic dermatitis: an update systematic review with implications for practice and research. Br J Dermatol. 2014;170:501‑13.

82. Gambichler T, Kreuter A, Tomi NS, Othlinghaus N, Altmeyer P, Skrygan M. Gene expression of cytokines in atopic eczema before and after ultraviolet al phototherapy. Br J Dermatol 2008;158:1117‑20.

83. Hong SP, Kim MJ, Jung MY, Jeon H, Goo J, Ahn SK, et al. Biopositive effects of low dose UVB on epidermis: coordinate up regulation of antimicrobial peptides and permeability barrier reinforcement. J Invest Dermatol. 2008;128:2880‑7.

84. Thaci D, Salgo R. Malignancies concerns of topical calcineurin inhibitors for atopic dermatitis: facts and controversies. Clin Dermatol. 2010;28:52‑6.

85. Luger T, Boguniewicz M, Carr W, Cork M, Deleuran M, Eichenfield L, et al. Pimecrolimus in atopic dermatitis: consensus on safety and the need to allow use in infants. Pediatr Allergy Immune. 2015;26:306‑15.

86. Rodenbeck DL, Silverberg JI, Silverberg NB. Phototherapy for atopic dermatitis. Clin Dermatol. 2016;34(5):607-13.

87. Kaufman HS, Roth HL. Hyposensitization with alum precipitated extracts in atopic dermatitis: a placebo-controlled study. Ann Allergy. 1974;32:321-30.

88. Jutel M, Agache A, Bonini S, Burks W, Calderon M, Canonica W, et al. International consensus on allergy immunotherapy. J Allergy Clin Immunol. 2015;136:556‑8.

89. Cox L, Nelson H, Lockey R, Calabria C, Chacko T, Finegold I, et al. Allergen immunotherapy: A practice parameter third update. J Allergy Clin Immunol. 2011;127:s1-s55.

90. Darsow U, Forer I, Ring J. Allergen-specific immunotherapy in atopic eczema. Curr Allergy Asthma Rep. 2011;11:277‑83.

91. Ring J, Alomar A, Bieber T, Deleuran M, Fink-Wagner A, Gelmetti C, et al. Guidelines for treatment of atopic eczema (atopic dermatitis) part II. J Eur Acad Dermatol Venereol. 2012;26:7776‑7.

92. Cadario G, Galluccio AG, Pezza M, Appino A, Milani M, Pecora S, et al. Sublingual immunotherapy efficacy in patients with atopic dermatitis and house dust mites sensitivity: a prospective pilot study. Curr Med Res Opin. 2007;23:2503-6.

93. Pajno GB, Caminiti L, Vita D, Barberio G, Salzano G, Lombardo F, et al. Sublingual immunotherapy in mite-sensitized children with atopic dermatitis: a randomized, double-blind, placebo-controlled study. J Allergy Clin Immunol. 2007;120:164-70.

94. Novak N. Allergen specific immunotherapy for atopic dermatitis. Curr Opin Allergy Clin Immunol. 2007;7:542‑6.

95. Nahm DH, Lee ES, Park HJ, Kim HA, Choi GS, Jeon SY. Treatment of atopic dermatitis with a combination of allergen-specific immunotherapy and a histamine-immunoglobulin complex. Int Arch Allergy Immunol. 2008;146:235-40.

96. Bussmann C, Maintz L, Hart J, Allam JP, Vrtala S, Chen KW, et al. Clinical improvement and immunological changes in atopic dermatitis patients undergoing subcutaneous immunotherapy with a house dust mite allergoid: a pilot study. Clin Exp Allergy. 2007;37:1277‑85.

97. Werfel T, Breuer K, Rueff F, Przybilla B, Worm M, Grewe M, et al. Usefulness of specific immunotherapy in patients with atopic dermatitis and allergic sensitization to house dust mites: a multi-centre, randomized, dose-response study. Allergy. 2006;61:202‑5.

98. Novak N, Bieber T, Hoffmann M, Fölster-Holst R, Homey B, Werfel T, et al. Efficacy and safety of subcutaneous allergen-specific immunotherapy with depigmented polymerized mite extract in atopic dermatitis. J Allergy Clin Immunol. 2012;130:925‑31.

99. Bae JM, Choi YY, Park CO, Chung KY, Lee KH. Efficacy of allergenspecific immunotherapy for atopic dermatitis: a systematic review and meta-analysis of randomized controlled trials. J Allergy Clin Immunol. 2013;132:110-7.

100. Gendelman SR, Lang DM. Specific immunotherapy in the treatment of atopic dermatitis: a systematic review using the GRADE system. Ann Allergy Asthma Immunol. 2013;111:555-61.

101. Gendelman SR, Lang DM. Sublingual immunotherapy in the treatment of atopic dermatitis: a systematic review using the GRADE system. Curr Allergy Asthma Immunol. 2015;15:498‑505.

102. Tam H, Calderon MA, Manikam L, Nankervis H, García Núñez I, Williams HC, et al. Specific allergen immunotherapy for the treatment of atopic eczema. Cochrane Database of Systematic Reviews. 2016, Issue 2. Art. No.: CD008774. DOI:

0.1002/14651858.CD008774.

103. Wyrzykowska N, Czarnecka-Operacz M, Adamski Z. Long-term efficacy of allergen specific immunotherapy in atopic dermatitis patients in relation to quality of life. Eur Ann Allergy Clin Immunol. 2015;47:5-9.

104. Lee J, Park CO, Lee KH. Specific immunotherapy in atopic dermatitis. Allergy Asthma Immunol Res. 2015;7:221‑9.

105. Simon D, Bieber T. Systemic therapy for atopic dermatitis. Allergy. 2014;69:46‑55.

106. Bussmann C, Bockenhoff A, Henke H, Werfel T, Novak N. Does allergen-specific immunotherapy represent a therapeutic option for patients with atopic dermatitis? J Allergy Clin Immunol. 2006;118:1292‑8.

107. Addor FAZ, Aoki V. Barreira cutânea na Dermatite Atópica. An Bras Dermatol. 2010;85(2):184-94.

108. Prety V, Bonamigo RR, Bessa GR, Poziomczyck CS, Oliveira CF, Weber MB, et al. Colonização bacteriana e infecções de pele em pacientes com Dermatite Atópica. An. Bras Dermatol. 2012;87(5):729-34.

109. Neto AP, Simão HML. Dermatite atópica. In: Lopez FA, Junior DC. Tratado de Pediatria – Sociedade Brasileira de Pediatria. 2ª ed. Barueri, SP: Manole; 2010. p. 577-89.

110. Neto PTL, Weber HB, Fortes SD, Cestari TF. A dermatite atópica na criança: Uma visão psicossomática. Rev Psiquiatr Rio Gd Sul. 2006;28(1):78-82.

111. Lifschitz C. The impact of atopic dermatitis on quality of life. Ann Nutr Metab. 2015;66(suppl 1):34-40.

112. Fontes Neto PTL, Weber MB, Fortes SD, Cestari TF, Escobar GF, Mazotti N, et al. Evaluation of emotional and behavioral symptoms in children and adolescents with atopic dermatitis. Rev Psiq Rio Gd Sul. 2005;27(3):279-91.

113. Manzoni APDS, Pereira RL, Townsend RZ, Weber MB, Nagatomi ARS, Cestari TF. Assessment of the quality of life of pediatric patients with the major chronic childhood skin diseases. An Bras Dermatol. 2012;87(3):361-8.

114. Alvarenga TMM, Caldeira AP. Quality of life in pediatric patients with atopic dermatitis. J Pediatr (Rio J). 2009;85(5):415-20.

115. Jiráková A, Vojácková N, Göpfertová D, Hercogová J. A comparative study of the impairment of quality of life in Czech children with atopic dermatitis of different age group and their families. Int J Dermatol. 2012;51:688-92.

116. Lewis-Jones MS., Finlay AY. The Children’s Dermatology Life Quality Index (CDLQI): Initial validation and practical use. Br J Dermatol. 1995;132:942-9.

117. Finlay AY, Khan GK. Dermatology Life Quality Index (DLQI): a simple practical measure for routine clinical use. Clin Exp Dermatol. 1994;19:210-6.

118. Weber MB, Fontes Neto PT, Soirefmann M, Mazzoti NG, Cestari T. Tradução e adequação cultural para o português de questionários sobre qualidade de vida para pacientes portadores de dermatite atópica [resumo]. An Bras Dermatol. 2005;80(Suppl 2):S127‑8.

119. Amaral CSF, March MFBP, Sant’Anna CC. Quality of life in children and teenagers with atopic dermatitis. An Bras Dermatol. 2012;87(5):717-23.

120. Pustisek N, Zivkovic MV, Situm M. Quality of life in families with children with atopic dermatitis. Pediatric Dermatol. 2016;33:28‑32.

121. Chernyshov PV, Jiráková A, Ho RCM, Moed H, Caldeira AP, Alvarenga TM, et al. An international multicenter study on quality of life and family quality of life in children with atopic dermatitis. Indian J Dermatol Venereol Leprol. 2013;79:52-8.

122. Stalder JF, Bernier C, Ball A, De Raeve L, Gieler U, Deleuran M, et al. Therapeutic patient education in atopic dermatitis: worldwide experiences. Oriented patient-education Network in dermatology. Pediatr Dermatol. 2013;30(3):329-34.

123. Barbarot S, Bernier C, Deleuran M, De Raeve L, Eichenfield L, El Hachem M, et al. Oriented Patient-Education Network in Dermatology. Therapeutic patient education in children with atopic dermatitis: position paper on objectives and recommendations. Pediatr Dermatol. 2013; 30(2):199-206.

124. Shaw M, Morell DS, Goldsmith LA. A study of targeted enhanced patient care for pediatric atopic dermatitis (STEP PAD). Pediatr Dermatol. 2008;25(1):19-24.

125. Weber MB, Lorenzini D, Reinehr CPH, Lovato B. Assessment of the quality of life of pediatric patients at a center of excellence in dermatology in Southern Brazil. An Bras Dermatol. 2012;87(5):697‑702.

126. Ricci G, Bendandi B, Aiazzi R, Patrizi A, Mais M. Three years of Italian experience of an educational program for parents of young children affected by atopic dermatitis: improving knowledge produces lower anxiety levels in parents of children with atopic dermatitis. Pediatr Dermatol. 2009;26:1‑5.

127. Weber MB, Fontes Neto Pde T, Prati C, Soirefman M, Mazzotti NG, Barzenski B, et al. Improvement of pruritus and quality of life of children with atopic dermatitis and their families after joining support groups. J Eur Acad Dermatol Venereol. 2008;22:992‑7.

128. Futamura M, Masuko I, Hayashi K, Ohya Y, Ito K. Effects of a short-term parental education programo on atopic dermatites a randomized controlled trial. Pediatr Dermatol. 2013;30(4):438‑43.

129. AADA - Grupos de apoio. Disponível em http://www.aada.org.br/ grupos-de-apoio/ acessado em 20 de fevereiro de 2017.

130. Schlichte MJ, Vandersall A, Katta R. Diet and eczema: a review of dietary supplements for the treatment of atopic dermatitis. Dermatol Pract Concept. 2016;6(3):23-9.

131. Avershina E, Cabrera Rubio R, Lundgård K, Perez Martinez G, Collado MC, Storrø O, et al. Effect of probiotics in prevention of atopic dermatitis is dependent on the intrinsic microbiota at early infancy. J Allergy Clin Immunol. 2016 Dec 5. pii: S0091- 6749(16)31443-9.

132. Rautava S, Kalliomäki M, Isolauri E. Probiotics during pregnancy and breast-feeding might confer immunomodulatory protection against atopic disease in the infant. J Allergy Clin Immunol. 2002;109(1):119-21.

133. Isolauri E, Arvola T, Sütas Y, Moilanen E, Salminen S. Probiotics in the management of atopic eczema. Clin Exp Allergy. 2000;30(11):1604-10.

134. Islam SU. Clinical uses of probiotics. Medicine (Baltimore). 2016;95(5):e2658.

135. Chang YS, Trivedi MK, Jha A, Lin YF, Dimaano L, García-Romero MT. Symbiotics for Prevention and Treatment of Atopic Dermatitis: A Meta-analysis of Randomized Clinical Trials. JAMA Pediatr. 2016;170(3):236-42.

136. Simpson MR, Dotterud CK, Storrø O, Johnsen R, Øien T. Perinatal probiotic supplementation in the prevention of allergy related disease: 6 year follow up of a randomised controlled trial. BMC Dermatol. 2015;15:13.

137. Simpson EL, Berry TM, Brown PA, Hanifin JM. A pilot study of emollient therapy for the primary prevention of atopic dermatitis. J Am Acad Dermatol. 2010;63(4):587-93.

138. Simpson EL, Chalmers JR, Hanifin JM, Thomas SK, Cork MJ, Irwin McLean WH, et al. Emollient enhancement of the skin barrier from birth offers effective atopic dermatitis prevention. J Allergy Clin Immunol. 2014;134(4):818‑23.

139. Horimukai K, Morita K, Narita M, Kondo M, Kitazawa H, Nozaki M, et al. Application of moisturizer to neonates prevents development of atopic dermatitis. J Allergy Clin Immunol. 2014;134(4):824‑30.

140. Ng JP, Liew HM, Ang SB. Use of emollients in atopic dermatitis. J Eur Acad Dermatol Venereol. 2015;29(5):854-7.

141. Bieber TH. Atopic dermatitis 2.0: from the clinical phenotype to the molecular taxonomy and stratified medicine. Allergy. 2012;67:1475‑82.

142. Bieber T, Cork M, Reitamo S. Atopic dermatitis: a candidate for disease-modifying strategy. Allergy. 2012;67:969‑75.

143. Eyerich K, Novak N. Immunology of atopic eczema: overcoming the Th1/Th2 paradigm. Allergy. 2013; 68:974‑82.

144. Ramadani F, Upton N, Hobson P, Chan YC, Mzinza D, Bowen H, et al. Intrinsic properties of germinal center-derived B cells promote their enhanced class switching to IgE. Allergy. 2015;70:1269‑77.

145. Howell MD, Kim BE, Gao P, Grant AV, Boguniewicz M, De Benedetto A, et al. Cytokine modulation of atopic dermatitis filaggrin skin expression. J Allergy Clin Immunol. 2009;124:R7-R12.

146. Beck LA, Thaci D, Hamilton JD, Graham NM, Bieber T, Rocklin R, et al. Dupilumab treatment in adults with moderate-to-severe atopic dermatitis. N Engl J Med. 2014;371:130‑9.

147. Simpson EL, Gadkari A, Worm M, Soong W, Blauvelt A, Eckert L, et al. Dupilumab therapy provides clinically meaningful improvement in patient-reported outcomes (PROs): a phase IIb, randomized, placebo-controlled, clinical trial in adult patients with moderate to severe atopic dermatitis (AD). J Am Acad Dermatol. 2016;75:506‑15.

148. Thaci D, Simpson EL, Beck LA, Bieber T, Blauvelt A, Papp K, et al. Efficacy and safety of moderate-to-severe atopic dermatitis inadequately controlled by topical treatments: a randomised, placebo-controlled, dose-ranging phase 2b trial. Lancet. 2016;387:40‑52.

149. Simpson EL, Bieber T, Guttman-Yassky E, Beck LA, Blauvelt A, Cork MJ, et al. Two Phase 3 Trials of Dupilumabe versus Placebo in Atopic Dermatitis. N Engl J Med. 2016;375:2335‑48.

150. Deleuran M, Thac D, Beck LA. Long-Term Safety and Efficacy of Open-Label Dupilumab in Patients with Moderate-to-Severe Atopic Dermatitis. J Allergy Clin Immunol. 2017;139:AB381.

151. Lee E, Lee SH, Kwon JW, Kim YH, Cho HJ, Yang SI, et al. Atopic dermatitis phenotype with early onset and high serum IL-13 is linked to the new development of bronchial hyperresponsiveness in school children. Allergy. 2016;71:692‑700.

152. Koga C, Kabashima K, Shiraishi N, Kobayashi M, Tokura Y. Possible pathogenic role of Th17 cells for atopic dermatitis. J Invest Dermatol. 2008;128:2625‑30.

153. Czarnowicki T, Gonzalez J, Shemer A, Malajian D, Xu H, Zheng X, et al. Severe atopic dermatitis is characterized by selective expansion of circulating TH2/TC2 and TH22/TC22, but not TH17/ TC17, cells within the skin-homing T-cell population. J Allergy Clin Immunol. 2015;136:104‑15.

154. Sonkoly E, Muller A, Lauerma AI, Pivarcsi A, Soto H, Kemeny L, et al. IL-31: a new link between T cells and pruritus in atopic skin inflammation. J Allergy Clin Immunol. 2006;117:411‑7.

155. Raap U, Weissmantel S, Gehring M, Eisenberg AM, Kapp A, Folster-Holst R. IL-31 significantly correlates with disease activity and Th2 cytokine levels in children with atopic dermatitis. Pediatr Allergy Immunol. 2012;23:285‑8.

156. Raap U, Wichmann K, Bruder M, Stander S, Wedi B, Kapp A, et al. Correlation of IL-31 serum levels with severity of atopic dermatitis. J Allergy Clin Immunol. 2008;122:421‑3.

157. Buddenkotte J, Steinhoff M. Pathophysiology and therapy of pruritus in allergic and atopic diseases. Allergy. 2010;65:805‑21.

158. Kasraie S, Niebuhr M, Baumert K, Werfel T. Functional effects of interleukin 31 in human primary keratinocytes. Allergy. 2011;66:845‑52.

159. Kasraie S, Niebuhr M, Werfel T. Interleukin (IL)-31 induces proinflammatory cytokines in human monocytes and macrophages following stimulation with staphylococcal exotoxins. Allergy. 2010;65:712‑21.

160. Cornelissen C, Marquardt Y, Czaja K, Wenzel J, Frank J, Luscher-Firzlaff J et al. IL-31 regulates differentiation and filaggrin expression in human organotypic skin models. J Allergy Clin Immunol. 2012;129:426‑33.

161. Kanda N, Hau CS, Tada Y, Sato S, Watanabe S. Decreased serum LL-37 and vitamin D3 levels in atopic dermatitis: relationship between IL-31 and oncostatin M. Allergy. 2012;67:804‑12.

162. Nemoto O, Furue M, Nakagawa H, Shiramoto M, Hanada R, Matsuki S, et al. The first trial of CIM331, a humanized antihuman interleukin-31 receptor A antibody, in healthy volunteers and patients with atopic dermatitis to evaluate safety, tolerability and pharmacokinetics of a single dose in a randomized, double-blind, placebo-controlled study. Br J Dermatol. 2016;174:296‑304.

163. Kabashima K, Furue M, Hanifin J, Pulka G, Mlynarczyk I, Wollenberg A. Humanized anti-interleukin-31 receptor A antibody nemolizumab (CIM331) suppresses pruritus and improves eczema in patients with moderate-to-severe atopic dermatitis. J Invest Dermatol. 2016;136:S161.

164. Landheer J, Giovannone B, Mattson JD, Tjabringa S, BruijnzeelKoomen CA, McClanahan T, et al. Epicutaneous application of house dust mite induces thymic stromal lymphopoietin in nonlesional skin of patients with atopic dermatitis. J Allergy Clin Immunol. 2013;132:1252‑4.

165. Phase 2a Study to Evaluate the Efficacy and Safety of MEDI9929 in Adults With Atopic Dermatitis (ALLEVIAD). Disponível em https://clinicaltrials.gov/ct2/show/NCT02525094. Acessado em 20 de fevereiro de 2017.

166. Cameron L, Depner M, Kormann M, Klopp N, Illig T, von Mutius E, et al. Genetic variation in CRTh2 influences development of allergic phenotypes. Allergy. 2009;64:1478‑85.

167. Straumann A, Hoesli S, Bussmann C, Stuck M, Perkins M, Collins LP, et al. Anti-eosinophil activity and clinical efficacy of the CRTH2 antagonist OC000459 in eosinophilic esophagitis. Allergy. 2013;68:375‑85.

168. Krug N, Gupta A, Badorrek P, Koenen R, Mueller M, Pivovarova A, et al. Efficacy of the oral chemoattractant receptor homologous molecule on TH2 cells antagonist BI 671800 in patients with seasonal allergic rhinitis. J Allergy Clin Immunol. 2014;133:414‑9.

169. Hall IP, Fowler AV, Gupta A, Tetzlaff K, Nivens MC, Sarno M, et al. Efficacy of BI 671800, an oral CRTH2 antagonist, in poorly controlled asthma as sole controller and in the presence of inhaled corticosteroid treatment. Pulm Pharmacol Ther. 2015;32:37‑44.

170. Efficacy and Safety Study of QAW039 in the Treatment of Patients With Moderate to Severe Atopic Dermatitis. Disponível em https:// clinicaltrials.gov/ct2/show/NCT01785602. Acessado em 20 de fevereiro de 2017.

171. Erpenbeck VJ, Popov TA, Miller D, Weinstein SF, Spector S, Magnusson B, et al. The oral CRTh2 antagonist QAW039 (fevipiprant): a phase II study in uncontrolled allergic asthma. Pulm Pharmacol Ther. 2016;39:54-63.

172. Levy LL, Urban J, King BA. Treatment of recalcitrant atopic dermatitis with the oral Janus kinase inhibitor tofacitinib citrate. J Am Acad Dermatol. 2015;73:395‑9.

173. Bissonnette R, Papp KA, PoulinY, Gooderham M, Raman M, Mallbris L, et al. Topical tofacitinib for atopic dermatitis: a phase IIa randomized trial. Br J Dermatol. 2016 doi:10.111/bjd.14871.

174. Study to Evaluate Pf-04965842 in subjects with moderate to severe atopic dermatitis. Disponível em www.clinicaltrials.gov/ct2/show/ NCT02780167. Acessado em 20 de fevereiro de 2017.

175. Samrao A, Berry TM, Goreshi R, Simpson EL. A pilot study of an oral phosphodiesterase inhibitor (apremilast) for atopic dermatitis in adults. Arch Dermatol. 2012;148:890‑7.

176. Volf EM, Au SC, Dumont N, Scheinman P, Gottlieb AB. A phase 2, open-label, investigator-initiated study to evaluate the safety and efficacy of apremilast in subjects with recalcitrant allergic contact or atopic dermatitis. J Drugs Dermatol. 2012;11:341‑6.

177. Thurmond RL. The histamine H4 receptor: from orphan to the clinic. Front Pharmacol. 2015;6:65.

178. Rossbach K, Schaper K, Kloth C, Gutzmer R, Werfel T, Kietzmann M, et al. Histamine H4 receptor knockout mice display reduced inflammation in a chronic model of atopic dermatitis. Allergy. 2016;71:189‑97.

179. Murata Y, Song M, Kikuchi H, Hisamichi K, Xu XL, Greenspan A, et al. Phase 2a, randomized, double-blind, placebo-controlled, multicenter, parallel-group study of a H4 R-antagonist (JNJ39758979) in Japanese adults with moderate atopic dermatitis. J Dermatol. 2015; 42:129‑39.

180. Kopp, M.V. Omalizumab: anti-IgE therapy in allergy. Curr Allergy Asthma Rep. 2011;11:101‑6.

181. Lane JE, Cheyney JM, Lane TN, Kent DE, Cohen DJ. Treatment of recalcitrant atopic dermatitis with omalizumab. J Am Acad Dermatol. 2006;54:68‑72.

182. Vigo PG, Girgis KR, Pfuetze PL, Critchlow ME, Fisher J, Hussain I. Efficacy of anti-IgE therapy in patients with atopic dermatitis. J Am Acad Dermatol. 2006;55:168‑70.

183. Amrol D. Anti-Immunoglobulin E in the treatment of refractory dermatitis. South Med J. 2010;103:554‑8.

184. Belloni B, Ziai M, Lim A, Lemercier B, Sbornik M, Weidinger S, et al. Low-dose anti-IgE therapy in patients with atopic eczema with high serum IgE levels. J Allergy Clin Immunol. 2007;120:1223‑5.

185. Toledo F, Silvestre JF, Munoz C. Combined therapy with low-dose omalizumab and intravenous immunoglobulin for severe atopic dermatitis. Report of four cases. J Eur Acad Dermatol Venereol. 2012;26:1325‑7.

186. Sanchez-Ramon S, Eguiluz-Gracia I, Rodriguez-Mazariego ME, Paravisini A, Zubeldia-Ortuno JM, Gil-Herrera J, et al. Sequential combined therapy with omalizumab and rituximab: a new approach to severe atopic dermatitis. J Investig Allergol Clin Immunol. 2013;23:190‑6.

187. Heil PM, Maurer D, Klein B, Hultsch T, Stingl G. Omalizumab therapy in atopic dermatitis: depletion of IgE does not improve the clinical course - a randomized, placebo-controlled and double blind pilot study. J German Soc Dermatol. 2010;8:990‑8.

188. Hotze M, Baurecht H, Rodriguez E, Chapman-Rothe N, Ollert M, Folster-Holst R, et al. Increased efficacy of omalizumab in atopic dermatitis patients with wild-type filaggrin status and higher serum levels of phosphatidylcholines. Allergy. 2014;69:132‑5.

6a4eb18fa9539521a6582223 aaai Articles
Links & Downloads

Arq Asma Alerg Imunol

Share this page
Page Sections