New and Emerging Therapies for Pediatric Atopic Dermatitis

1.

Kim BE, Leung DYM. Significance of skin barrier dysfunction in atopic dermatitis. Allergy Asthma Immunol Res. 2018;10(3):207–15. https://doi.org/10.4168/aair.2018.10.3.207.CrossRefPubMedPubMedCentral

2.

Han H, Roan F, Ziegler SF. The atopic march: current insights into skin barrier dysfunction and epithelial cell-derived cytokines. Immunol Rev. 2017;278(1):116–30. https://doi.org/10.1111/imr.12546.CrossRefPubMedPubMedCentral

3.

David Boothe W, Tarbox JA, Tarbox MB. Atopic dermatitis: pathophysiology. Adv Exp Med Biol. 2017;1027:21–37. https://doi.org/10.1007/978-3-319-64804-0_3.CrossRefPubMed

4.

Malik K, Heitmiller KD, Czarnowicki T. An update on the pathophysiology of atopic dermatitis. Dermatol Clin. 2017;35(3):317–26. https://doi.org/10.1016/j.det.2017.02.006.CrossRefPubMed

5.

Leung DY, Guttman-Yassky E. Deciphering the complexities of atopic dermatitis: shifting paradigms in treatment approaches. J Allergy Clin Immunol. 2014;134(4):769–79. https://doi.org/10.1016/j.jaci.2014.08.008.CrossRefPubMedPubMedCentral

6.

Silverberg JI, Gelfand JM, Margolis DJ, Boguniewicz M, Fonacier L, Grayson MH, et al. Patient burden and quality of life in atopic dermatitis in US adults: a population-based cross-sectional study. Ann Allergy Asthma Immunol. 2018;121(3):340–7. https://doi.org/10.1016/j.anai.2018.07.006.CrossRefPubMed

7.

Drucker AM, Wang AR, Li WQ, Sevetson E, Block JK, Qureshi AA. The burden of atopic dermatitis: summary of a report for the National Eczema Association. J Invest Dermatol. 2017;137(1):26–30. https://doi.org/10.1016/j.jid.2016.07.012.CrossRefPubMed

8.

Whiteley J, Emir B, Seitzman R, Makinson G. The burden of atopic dermatitis in US adults: results from the 2013 National Health and Wellness Survey. Curr Med Res Opin. 2016;32(10):1645–51. https://doi.org/10.1080/03007995.2016.1195733.CrossRefPubMed

9.

Eckert L, Gupta S, Amand C, Gadkari A, Mahajan P, Gelfand JM. The burden of atopic dermatitis in US adults: Health care resource utilization data from the 2013 National Health and Wellness Survey. J Am Acad Dermatol. 2018;78(1):54–61e1. https://doi.org/10.1016/j.jaad.2017.08.002.CrossRefPubMed

10.

Eckert L, Gupta S, Amand C, Gadkari A, Mahajan P, Gelfand JM. Impact of atopic dermatitis on health-related quality of life and productivity in adults in the United States: an analysis using the National Health and Wellness Survey. J Am Acad Dermatol. 2017;77(2):274–279e3. https://doi.org/10.1016/j.jaad.2017.04.019.CrossRefPubMed

11.

Vivar KL, Kruse L. The impact of pediatric skin disease on self-esteem. Int J Womens Dermatol. 2018;4(1):27–31. https://doi.org/10.1016/j.ijwd.2017.11.002.CrossRefPubMed

12.

Abraham A, Roga G. Topical steroid-damaged skin. Indian J Dermatol. 2014;59(5):456–9. https://doi.org/10.4103/0019-5154.139872.CrossRefPubMedPubMedCentral

13.

Ashcroft DM, Dimmock P, Garside R, Stein K, Williams HC. Efficacy and tolerability of topical pimecrolimus and tacrolimus in the treatment of atopic dermatitis: meta-analysis of randomised controlled trials. BMJ. 2005;330(7490):516. https://doi.org/10.1136/bmj.38376.439653.D3.CrossRefPubMedPubMedCentral

14.

Siegfried EC, Jaworski JC, Hebert AA. Topical calcineurin inhibitors and lymphoma risk: evidence update with implications for daily practice. Am J Clin Dermatol. 2013;14(3):163–78. https://doi.org/10.1007/s40257-013-0020-1.CrossRefPubMedPubMedCentral

15.

Margolis DJ, Abuabara K, Hoffstad OJ, Wan J, Raimondo D, Bilker WB. Association between malignancy and topical use of pimecrolimus. JAMA Dermatol. 2015;151(6):594–9. https://doi.org/10.1001/jamadermatol.2014.4305.CrossRefPubMedPubMedCentral

16.

Legendre L, Barnetche T, Mazereeuw-Hautier J, Meyer N, Murrell D, Paul C. Risk of lymphoma in patients with atopic dermatitis and the role of topical treatment: a systematic review and meta-analysis. J Am Acad Dermatol. 2015;72(6):992–1002. https://doi.org/10.1016/j.jaad.2015.02.1116.CrossRefPubMed

17.

Cury Martins J, Martins C, Aoki V, Gois AF, Ishii HA, da Silva EM. Topical tacrolimus for atopic dermatitis. Cochrane Database Syst Rev. 2015. https://doi.org/10.1002/14651858.cd009864.pub2.CrossRef

18.

Castellsague J, Kuiper JG, Pottegard A, Anveden Berglind I, Dedman D, Gutierrez L, et al. A cohort study on the risk of lymphoma and skin cancer in users of topical tacrolimus, pimecrolimus, and corticosteroids (Joint European Longitudinal Lymphoma and Skin Cancer Evaluation-JOELLE study). Clin Epidemiol. 2018;10:299–310. https://doi.org/10.2147/CLEP.S146442.CrossRefPubMedPubMedCentral

19.

Cattaneo D, Perico N, Gaspari F, Remuzzi G. Nephrotoxic aspects of cyclosporine. Transplant Proc. 2004;36(2 Suppl):234S–9S. https://doi.org/10.1016/j.transproceed.2004.01.011.CrossRefPubMed

20.

Fuggle NR, Bragoli W, Mahto A, Glover M, Martinez AE, Kinsler VA. The adverse effect profile of oral azathioprine in pediatric atopic dermatitis, and recommendations for monitoring. J Am Acad Dermatol. 2015;72(1):108–14. https://doi.org/10.1016/j.jaad.2014.08.048.CrossRefPubMedPubMedCentral

21.

Dvorakova V, O’Regan GM, Irvine AD. Methotrexate for severe childhood atopic dermatitis: clinical experience in a tertiary center. Pediatr Dermatol. 2017;34(5):528–34. https://doi.org/10.1111/pde.13209.CrossRefPubMed

22.

Drucker AM, Eyerich K, de Bruin-Weller MS, Thyssen JP, Spuls PI, Irvine AD, et al. Use of systemic corticosteroids for atopic dermatitis: International Eczema Council consensus statement. Br J Dermatol. 2018;178(3):768–75. https://doi.org/10.1111/bjd.15928.CrossRefPubMedPubMedCentral

23.

FDA. Atopic dermatitis: timing of pediatric studies during development of systemic drugs guidance for industry; 2018. https://www.fda.gov/media/117570/download.

24.

FDA. E11(R1) addendum: clinical investigation of medicinal products in the pediatric population guidance for industry; 2018. https://www.fda.gov/media/101398/download.

25.

Siegfried EC, Jaworski JC, Eichenfield LF, Paller A, Hebert AA, Simpson EL, et al. Developing drugs for treatment of atopic dermatitis in children (≥3 months to <18 years of age): draft guidance for industry. Pediatr Dermatol. 2018;35(3):303–22. https://doi.org/10.1111/pde.13452.CrossRefPubMed

26.

Grewe SR, Chan SC, Hanifin JM. Elevated leukocyte cyclic AMP-phosphodiesterase in atopic disease: a possible mechanism for cyclic AMP-agonist hyporesponsiveness. J Allergy Clin Immunol. 1982;70(6):452–7.CrossRef

27.

Chan SC, Reifsnyder D, Beavo JA, Hanifin JM. Immunochemical characterization of the distinct monocyte cyclic AMP-phosphodiesterase from patients with atopic dermatitis. J Allergy Clin Immunol. 1993;91(6):1179–88.CrossRef

28.

Hanifin JM, Chan SC. Monocyte phosphodiesterase abnormalities and dysregulation of lymphocyte function in atopic dermatitis. J Investig Dermatol. 1995;105(1 Suppl):84S–8S.CrossRef

29.

Gantner F, Gotz C, Gekeler V, Schudt C, Wendel A, Hatzelmann A. Phosphodiesterase profile of human B lymphocytes from normal and atopic donors and the effects of PDE inhibition on B cell proliferation. Br J Pharmacol. 1998;123(6):1031–8. https://doi.org/10.1038/sj.bjp.0701688.CrossRefPubMedPubMedCentral

30.

Zebda R, Paller AS. Phosphodiesterase 4 inhibitors. J Am Acad Dermatol. 2018;78(3S1):S43–52. https://doi.org/10.1016/j.jaad.2017.11.056.CrossRefPubMed

31.

Hanifin JM, Chan SC, Cheng JB, Tofte SJ, Henderson WR Jr, Kirby DS, et al. Type 4 phosphodiesterase inhibitors have clinical and in vitro anti-inflammatory effects in atopic dermatitis. J Investig Dermatol. 1996;107(1):51–6.CrossRef

32.

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):494–503e6. https://doi.org/10.1016/j.jaad.2016.05.046.CrossRefPubMed

33.

Zane LT, Kircik L, Call R, Tschen E, Draelos ZD, Chanda S, et al. Crisaborole topical ointment, 2% in patients ages 2 to 17 years with atopic dermatitis: a phase 1b, open-label, maximal-use systemic exposure study. Pediatr Dermatol. 2016;33(4):380–7. https://doi.org/10.1111/pde.12872.CrossRefPubMedPubMedCentral

34.

Eichenfield LF, Call RS, Forsha DW, Fowler J Jr, Hebert AA, Spellman M, et al. Long-term safety of crisaborole ointment 2% in children and adults with mild to moderate atopic dermatitis. J Am Acad Dermatol. 2017;77(4):641–649e5. https://doi.org/10.1016/j.jaad.2017.06.010.CrossRefPubMed

35.

Zane LT, Hughes MH, Shakib S. Tolerability of crisaborole ointment for application on sensitive skin areas: a randomized, double-blind, vehicle-controlled study in healthy volunteers. Am J Clin Dermatol. 2016;17(5):519–26. https://doi.org/10.1007/s40257-016-0204-6.CrossRefPubMedPubMedCentral

36.

Murrell DF, Gebauer K, Spelman L, Zane LT. Crisaborole topical ointment, 2% in adults with atopic dermatitis: a phase 2a, vehicle-controlled, proof-of-concept study. J Drugs Dermatol. 2015;14(10):1108–12.PubMed

37.

Stein Gold LF, Spelman L, Spellman MC, Hughes MH, Zane LT. A phase 2, randomized, controlled, dose-ranging study evaluating crisaborole topical ointment, 0.5% and 2% in adolescents with mild to moderate atopic dermatitis. J Drugs Dermatol. 2015;14(12):1394–9.PubMed

38.

Nemoto O, Hayashi N, Kitahara Y, Furue M, Hojo S, Nomoto M, et al. Effect of topical phosphodiesterase 4 inhibitor E6005 on Japanese children with atopic dermatitis: results from a randomized, vehicle-controlled exploratory trial. J Dermatol. 2016;43(8):881–7. https://doi.org/10.1111/1346-8138.13231.CrossRefPubMed

39.

Ohba F, Matsuki S, Imayama S, Matsuguma K, Hojo S, Nomoto M, et al. Efficacy of a novel phosphodiesterase inhibitor, E6005, in patients with atopic dermatitis: an investigator-blinded, vehicle-controlled study. J Dermatol Treat. 2016;27(5):467–72. https://doi.org/10.3109/09546634.2016.1157257.CrossRef

40.

Furue M, Kitahara Y, Akama H, Hojo S, Hayashi N, Nakagawa H, et al. Safety and efficacy of topical E6005, a phosphodiesterase 4 inhibitor, in Japanese adult patients with atopic dermatitis: results of a randomized, vehicle-controlled, multicenter clinical trial. J Dermatol. 2014;41(7):577–85. https://doi.org/10.1111/1346-8138.12534.CrossRefPubMed

41.

Ohba F, Nomoto M, Hojo S, Akama H. Safety, tolerability and pharmacokinetics of a novel phosphodiesterase inhibitor, E6005 ointment, in healthy volunteers and in patients with atopic dermatitis. J Dermatol Treat. 2016;27(3):241–6. https://doi.org/10.3109/09546634.2015.1093587.CrossRef

42.

Kitahara Y, Hojo S, Nomoto M, Onozuka D, Furue M, Hagihara A. Pharmacokinetic disposition of topical phosphodiesterase-4 inhibitor E6005 in patients with atopic dermatitis. J Dermatol Treat. 2018. https://doi.org/10.1080/09546634.2018.1530439.CrossRef

43.

Seif F, Khoshmirsafa M, Aazami H, Mohsenzadegan M, Sedighi G, Bahar M. The role of JAK-STAT signaling pathway and its regulators in the fate of T helper cells. Cell Commun Signal. 2017;15(1):23. https://doi.org/10.1186/s12964-017-0177-y.CrossRefPubMedPubMedCentral

44.

Banerjee S, Biehl A, Gadina M, Hasni S, Schwartz DM. JAK-STAT signaling as a target for inflammatory and autoimmune diseases: current and future prospects. Drugs. 2017;77(5):521–46. https://doi.org/10.1007/s40265-017-0701-9.CrossRefPubMedPubMedCentral

45.

Villarino AV, Kanno Y, O’Shea JJ. Mechanisms and consequences of Jak-STAT signaling in the immune system. Nat Immunol. 2017;18(4):374–84. https://doi.org/10.1038/ni.3691.CrossRefPubMed

46.

Leonard WJ, O’Shea JJ. Jaks and STATs: biological implications. Annu Rev Immunol. 1998;16:293–322. https://doi.org/10.1146/annurev.immunol.16.1.293.CrossRefPubMed

47.

Damsky W, King BA. JAK inhibitors in dermatology: the promise of a new drug class. J Am Acad Dermatol. 2017;76(4):736–44. https://doi.org/10.1016/j.jaad.2016.12.005.CrossRefPubMedPubMedCentral

48.

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(3):395–9. https://doi.org/10.1016/j.jaad.2015.06.045.CrossRefPubMed

49.

Vu M, Heyes C, Robertson SJ, Varigos GA, Ross G. Oral tofacitinib: a promising treatment in atopic dermatitis, alopecia areata and vitiligo. Clin Exp Dermatol. 2017;42(8):942–4. https://doi.org/10.1111/ced.13290.CrossRefPubMed

50.

Bissonnette R, Papp KA, Poulin Y, Gooderham M, Raman M, Mallbris L, et al. Topical tofacitinib for atopic dermatitis: a phase IIa randomized trial. Br J Dermatol. 2016;175(5):902–11. https://doi.org/10.1111/bjd.14871.CrossRefPubMed

51.

Guttman-Yassky E, Silverberg JI, Nemoto O, Forman SB, Wilke A, Prescilla R, et al. Baricitinib in adult patients with moderate-to-severe atopic dermatitis: a phase 2 parallel, double-blinded, randomized placebo-controlled multiple-dose study. J Am Acad Dermatol. 2018. https://doi.org/10.1016/j.jaad.2018.01.018.CrossRefPubMed

52.

Guttman-Yassky E, Silverberg JI, Nemoto O, Forman SB, Wilke A, Prescilla R, et al. Efficacy and safety of upadacitinib treatment over 32 weeks for patients with atopic dermatitis from a phase 2b, randomized, placebo-controlled trial. In: 27th European Academy of Dermatology and Venerology (EADV) Congress, 12 September, Paris, France; 2018.

53.

Peeva E, Hodge MR, Kieras E, Vazquez ML, Goteti K, Tarabar SG, et al. Evaluation of a Janus kinase 1 inhibitor, PF-04965842, in healthy subjects: a phase 1, randomized, placebo-controlled, dose-escalation study. Br J Clin Pharmacol. 2018;84(8):1776–88. https://doi.org/10.1111/bcp.13612.CrossRefPubMedPubMedCentral

54.

Raedler LA. Jakafi (ruxolitinib): first FDA-approved medication for the treatment of patients with polycythemia vera. Am Health Drug Benefits. 2015;8(Spec Feature):75–9.PubMedPubMedCentral

55.

Mascarenhas J, Hoffman R. Ruxolitinib: the first FDA approved therapy for the treatment of myelofibrosis. Clin Cancer Res. 2012;18(11):3008–14. https://doi.org/10.1158/1078-0432.ccr-11-3145.CrossRefPubMed

56.

Kim BS, Nasir A, Papp K, Parish LC, Kuligowski M, Venturanza M, et al. A phase II randomized, dose-ranging, vehicle- and active-controlled study to evaluate the safety and efficacy of topical ruxolitinib in adult patients with atopic dermatitis. In: 27th European Academy of Dermatology and Venerology, 12 September, Paris, France; 2018.

57.

Kaur M, Singh M, Silakari O. Inhibitors of switch kinase ‘spleen tyrosine kinase’ in inflammation and immune-mediated disorders: a review. Eur J Med Chem. 2013;67:434–46. https://doi.org/10.1016/j.ejmech.2013.04.070.CrossRefPubMed

58.

Wu N-L, Huang D-Y, Wang L-F, Kannagi R, Fan Y-C, Lin W-W. Spleen tyrosine kinase mediates EGFR signaling to regulate keratinocyte terminal differentiation. J Investig Dermatol. 2016;136(1):192–201. https://doi.org/10.1038/JID.2015.381.CrossRefPubMed

59.

Wu NL, Huang DY, Tsou HN, Lin YC, Lin WW. Syk mediates IL-17-induced CCL20 expression by targeting Act1-dependent K63-linked ubiquitination of TRAF6. J Investig Dermatol. 2015;135(2):490–8. https://doi.org/10.1038/jid.2014.383.CrossRefPubMed

60.

Emma Guttman-Yassky ABP, Song T, Kim HJ, Denis L, Rao N, Zammit DJ. ASN002, a dual oral inhibitor of JAK/SYK signaling, improves the lesional skin phenotype towards non-involved skin in moderate-to-severe atopic dermatitis patients, correlating with clinical outcomes. In: European Academy of Dermatology and Venerology 2018, September 12, Paris, France; 2018.

61.

Emma Guttman-Yassky CM, Forman S, Bhatia N, Lee M, Fowler J, Tyring S, Pariser D, Sofen H, Dhawan S, Zook M, Pavel AB, Estrada Y, Zammit DJ, Toker S, Rao N, Bissonnette R. Efficacy, safety and pharmacology of oral ASN002, a novel JAK/SYK inhibitor, in patients with moderate-to-severe atopic dermatitis: results of a randomized, double-blind, placebo-controlled clinical study. In: International symposium on atopic dermatitis 2018, April 11–13, The Netherlands; 2018.

62.

Nakagawa H, Nemoto O, Yamada H, Nagata T, Ninomiya N. Phase 1 studies to assess the safety, tolerability and pharmacokinetics of JTE-052 (a novel Janus kinase inhibitor) ointment in Japanese healthy volunteers and patients with atopic dermatitis. J Dermatol. 2018;45(6):701–9. https://doi.org/10.1111/1346-8138.14322.CrossRefPubMedPubMedCentral

63.

Nakagawa H, Nemoto O, Igarashi A, Nagata T. Efficacy and safety of topical JTE-052, a Janus kinase inhibitor, in Japanese adult patients with moderate-to-severe atopic dermatitis: a phase II, multicentre, randomized, vehicle-controlled clinical study. Br J Dermatol. 2018;178(2):424–32. https://doi.org/10.1111/bjd.16014.CrossRefPubMed

64.

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(8):890–7. https://doi.org/10.1001/archdermatol.2012.812.CrossRefPubMedPubMedCentral

65.

Saporito RC, Cohen DJ. Apremilast use for moderate-to-severe atopic dermatitis in pediatric patients. Case Rep Dermatol. 2016;8(2):179–84. https://doi.org/10.1159/000446836.CrossRefPubMedPubMedCentral

66.

Abrouk M, Farahnik B, Zhu TH, Nakamura M, Singh R, Lee K, et al. Apremilast treatment of atopic dermatitis and other chronic eczematous dermatoses. J Am Acad Dermatol. 2017;77(1):177–80. https://doi.org/10.1016/j.jaad.2017.03.020.CrossRefPubMed

67.

Farahnik B, Beroukhim K, Nakamura M, Abrouk M, Zhu TH, Singh R et al. Use of an oral phosphodiesterase-4 inhibitor (apremilast) for the treatment of chronic, severe atopic dermatitis: a case report. Dermatol Online J. 2017;23(5):1–5.

68.

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(3):341–6.PubMed

69.

Simpson EL, Imafuku S, Poulin Y, Ungar B, Zhou L, Malik K, et al. A phase 2 randomized trial of apremilast in patients with atopic dermatitis. J Investig Dermatol. 2018. https://doi.org/10.1016/j.jid.2018.10.043.CrossRefPubMed

70.

Nagata K, Tanaka K, Ogawa K, Kemmotsu K, Imai T, Yoshie O, et al. Selective expression of a novel surface molecule by human Th2 cells in vivo. J Immunol. 1999;162(3):1278–86.PubMed

71.

Satoh T, Moroi R, Aritake K, Urade Y, Kanai Y, Sumi K, et al. Prostaglandin D2 plays an essential role in chronic allergic inflammation of the skin via CRTH2 receptor. J Immunol. 2006;177(4):2621–9.CrossRef

72.

Matsushima Y, Satoh T, Yamamoto Y, Nakamura M, Yokozeki H. Distinct roles of prostaglandin D2 receptors in chronic skin inflammation. Mol Immunol. 2011;49(1–2):304–10. https://doi.org/10.1016/j.molimm.2011.08.023.CrossRefPubMed

73.

He R, Oyoshi MK, Wang JY, Hodge MR, Jin H, Geha RS. The prostaglandin D(2) receptor CRTH2 is important for allergic skin inflammation after epicutaneous antigen challenge. J Allergy Clin Immunol. 2010;126(4):784–90. https://doi.org/10.1016/j.jaci.2010.07.006.CrossRefPubMedPubMedCentral

74.

Boehme SA, Chen EP, Franz-Bacon K, Sasik R, Sprague LJ, Ly TW, et al. Antagonism of CRTH2 ameliorates chronic epicutaneous sensitization-induced inflammation by multiple mechanisms. Int Immunol. 2009;21(1):1–17. https://doi.org/10.1093/intimm/dxn118.CrossRefPubMed

75.

Boehme SA, Franz-Bacon K, Chen EP, Sasik R, Sprague LJ, Ly TW, et al. A small molecule CRTH2 antagonist inhibits FITC-induced allergic cutaneous inflammation. Int Immunol. 2009;21(1):81–93. https://doi.org/10.1093/intimm/dxn127.CrossRefPubMed

76.

Yahara H, Satoh T, Miyagishi C, Yokozeki H. Increased expression of CRTH2 on eosinophils in allergic skin diseases. J Eur Acad Dermatol Venereol. 2010;24(1):75–6. https://doi.org/10.1111/j.1468-3083.2009.03267.x.CrossRefPubMed

77.

Jariwala SP, Abrams E, Benson A, Fodeman J, Zheng T. The role of thymic stromal lymphopoietin in the immunopathogenesis of atopic dermatitis. Clin Exp Allergy. 2011;41(11):1515–20. https://doi.org/10.1111/j.1365-2222.2011.03797.x.CrossRefPubMed

78.

Ito T, Wang YH, Duramad O, Hori T, Delespesse GJ, Watanabe N, et al. TSLP-activated dendritic cells induce an inflammatory T helper type 2 cell response through OX40 ligand. J Exp Med. 2005;202(9):1213–23. https://doi.org/10.1084/jem.20051135.CrossRefPubMedPubMedCentral

79.

Liu YJ. Thymic stromal lymphopoietin and OX40 ligand pathway in the initiation of dendritic cell-mediated allergic inflammation. J Allergy Clin Immunol. 2007;120(2):238–44. https://doi.org/10.1016/j.jaci.2007.06.004(quiz 45-6).CrossRefPubMed

80.

Sano Y, Masuda K, Tamagawa-Mineoka R, Matsunaka H, Murakami Y, Yamashita R, et al. Thymic stromal lymphopoietin expression is increased in the horny layer of patients with atopic dermatitis. Clin Exp Immunol. 2013;171(3):330–7. https://doi.org/10.1111/cei.12021.CrossRefPubMedPubMedCentral

81.

Glenmark Pharmaceuticals announces oral presentation of new data on GBR 830, an investigational, anti-OX40 monoclonal antibody, at the international investigative dermatology meeting; 2018. https://www.prnewswire.com/news-releases/glenmark-pharmaceuticals-announces-oral-presentation-of-new-data-on-gbr-830-an-investigational-anti-ox40-monoclonal-antibody-at-the-international-investigative-dermatology-meeting-682946661.html.

82.

Simpson EL, Parnes JR, She D, Crouch S, Rees W, Mo M, et al. Tezepelumab, an anti-thymic stromal lymphopoietin monoclonal antibody, in the treatment of moderate to severe atopic dermatitis: a randomized phase 2a clinical trial. J Am Acad Dermatol. 2019;80(4):1013–21. https://doi.org/10.1016/j.jaad.2018.11.059.CrossRefPubMed

83.

Quintana FJ, Basso AS, Iglesias AH, Korn T, Farez MF, Bettelli E, et al. Control of T(reg) and T(H)17 cell differentiation by the aryl hydrocarbon receptor. Nature. 2008;453(7191):65–71. https://doi.org/10.1038/nature06880.CrossRefPubMed

84.

Quintana FJ, Sherr DH. Aryl hydrocarbon receptor control of adaptive immunity. Pharmacol Rev. 2013;65(4):1148–61. https://doi.org/10.1124/pr.113.007823.CrossRefPubMedPubMedCentral

85.

Veldhoen M, Hirota K, Westendorf AM, Buer J, Dumoutier L, Renauld JC, et al. The aryl hydrocarbon receptor links TH17-cell-mediated autoimmunity to environmental toxins. Nature. 2008;453(7191):106–9. https://doi.org/10.1038/nature06881.CrossRefPubMed

86.

Furue M, Tsuji G, Mitoma C, Nakahara T, Chiba T, Morino-Koga S, et al. Gene regulation of filaggrin and other skin barrier proteins via aryl hydrocarbon receptor. J Dermatol Sci. 2015;80(2):83–8. https://doi.org/10.1016/j.jdermsci.2015.07.011.CrossRefPubMed

87.

Negishi T, Kato Y, Ooneda O, Mimura J, Takada T, Mochizuki H, et al. Effects of aryl hydrocarbon receptor signaling on the modulation of TH1/TH2 balance. J Immunol. 2005;175(11):7348–56.CrossRef

88.

Saurat JH, Kaya G, Saxer-Sekulic N, Pardo B, Becker M, Fontao L, et al. The cutaneous lesions of dioxin exposure: lessons from the poisoning of Victor Yushchenko. Toxicol Sci. 2012;125(1):310–7. https://doi.org/10.1093/toxsci/kfr223.CrossRefPubMed

89.

Tan NS, Wahli W. The emerging role of Nrf2 in dermatotoxicology. EMBO Mol Med. 2014;6(4):431–3. https://doi.org/10.1002/emmm.201303797.CrossRefPubMedPubMedCentral

90.

Bissonnette R, Chen G, Bolduc C, Maari C, Lyle M, Tang L, et al. Efficacy and safety of topical WBI-1001 in the treatment of atopic dermatitis: results from a phase 2A, randomized, placebo-controlled clinical trial. Arch Dermatol. 2010;146(4):446–9. https://doi.org/10.1001/archdermatol.2010.34.CrossRefPubMed

91.

Bissonnette R, Poulin Y, Zhou Y, Tan J, Hong HC, Webster J, et al. Efficacy and safety of topical WBI-1001 in patients with mild to severe atopic dermatitis: results from a 12-week, multicentre, randomized, placebo-controlled double-blind trial. Br J Dermatol. 2012;166(4):853–60. https://doi.org/10.1111/j.1365-2133.2011.10775.x.CrossRefPubMed

92.

Peppers J, Paller AS, Maeda-Chubachi T, Wu S, Robbins K, Gallagher K, et al. A phase 2, randomized dose-finding study of tapinarof (GSK2894512 cream) for the treatment of atopic dermatitis. J Am Acad Dermatol. 2019;80(1):89–98e3. https://doi.org/10.1016/j.jaad.2018.06.047.CrossRefPubMed

93.

Howell MD, Kim BE, Gao P, Grant AV, Boguniewicz M, Debenedetto A, et al. Cytokine modulation of atopic dermatitis filaggrin skin expression. J Allergy Clin Immunol. 2007;120(1):150–5. https://doi.org/10.1016/j.jaci.2007.04.031.CrossRefPubMedPubMedCentral

94.

Kim BE, Leung DY, Boguniewicz M, Howell MD. Loricrin and involucrin expression is down-regulated by Th2 cytokines through STAT-6. Clin Immunol. 2008;126(3):332–7. https://doi.org/10.1016/j.clim.2007.11.006.CrossRefPubMed

95.

Honzke S, Wallmeyer L, Ostrowski A, Radbruch M, Mundhenk L, Schafer-Korting M, et al. Influence of Th2 cytokines on the cornified envelope, tight junction proteins, and ss-defensins in filaggrin-deficient skin equivalents. J Investig Dermatol. 2016;136(3):631–9. https://doi.org/10.1016/j.jid.2015.11.007.CrossRefPubMed

96.

Agrawal R, Woodfolk JA. Skin barrier defects in atopic dermatitis. Curr Allergy Asthma Rep. 2014;14(5):433. https://doi.org/10.1007/s11882-014-0433-9.CrossRefPubMedPubMedCentral

97.

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(2):130–9. https://doi.org/10.1056/NEJMoa1314768.CrossRefPubMed

98.

Thaci D, Simpson EL, Beck LA, Bieber T, Blauvelt A, Papp K, et al. Efficacy and safety of dupilumab in adults with moderate-to-severe atopic dermatitis inadequately controlled by topical treatments: a randomised, placebo-controlled, dose-ranging phase 2b trial. Lancet. 2016;387(10013):40–52. https://doi.org/10.1016/S0140-6736(15)00388-8.CrossRefPubMed

99.

Simpson EL, Bieber T, Guttman-Yassky E, Beck LA, Blauvelt A, Cork MJ, et al. Two phase 3 trials of dupilumab versus placebo in atopic dermatitis. N Engl J Med. 2016;375(24):2335–48. https://doi.org/10.1056/NEJMoa1610020.CrossRefPubMed

100.

Blauvelt A, de Bruin-Weller M, Gooderham M, Cather JC, Weisman J, Pariser D, et al. Long-term management of moderate-to-severe atopic dermatitis with dupilumab and concomitant topical corticosteroids (LIBERTY AD CHRONOS): a 1-year, randomised, double-blinded, placebo-controlled, phase 3 trial. Lancet. 2017;389(10086):2287–303. https://doi.org/10.1016/S0140-6736(17)31191-1.CrossRefPubMed

101.

Regeneron Pharmaceuticals I. FDA approves Dupixent® (dupilumab) for moderate-to-severe atopic dermatitis in adolescents; 2019. https://www.prnewswire.com/news-releases/fda-approves-dupixent-dupilumab-for-moderate-to-severe-atopic-dermatitis-in-adolescents-300810264.html. Accessed 15 Mar 2019.

102.

Antoniu SA. Pitrakinra, a dual IL-4/IL-13 antagonist for the potential treatment of asthma and eczema. Curr Opin Investig Drugs. 2010;11(11):1286–94.PubMed

103.

Corren J, Lemanske RF, Hanania NA, Korenblat PE, Parsey MV, Arron JR, et al. Lebrikizumab treatment in adults with asthma. N Engl J Med. 2011;365(12):1088–98. https://doi.org/10.1056/NEJMoa1106469.CrossRefPubMed

104.

May RD, Monk PD, Cohen ES, Manuel D, Dempsey F, Davis NH, et al. Preclinical development of CAT-354, an IL-13 neutralizing antibody, for the treatment of severe uncontrolled asthma. Br J Pharmacol. 2012;166(1):177–93. https://doi.org/10.1111/j.1476-5381.2011.01659.x.CrossRefPubMedPubMedCentral

105.

Ultsch M, Bevers J, Nakamura G, Vandlen R, Kelley RF, Wu LC, et al. Structural basis of signaling blockade by anti-IL-13 antibody Lebrikizumab. J Mol Biol. 2013;425(8):1330–9. https://doi.org/10.1016/j.jmb.2013.01.024.CrossRefPubMed

106.

Popovic B, Breed J, Rees DG, Gardener MJ, Vinall LM, Kemp B, et al. Structural characterisation reveals mechanism of IL-13-neutralising monoclonal antibody tralokinumab as inhibition of binding to IL-13Ralpha1 and IL-13Ralpha2. J Mol Biol. 2017;429(2):208–19. https://doi.org/10.1016/j.jmb.2016.12.005.CrossRefPubMed

107.

Wollenberg A, Howell MD, Guttman-Yassky E, Silverberg JI, Kell C, Ranade K, et al. Treatment of atopic dermatitis with tralokinumab, an anti-IL-13 mAb. J Allergy Clin Immunol. 2018. https://doi.org/10.1016/j.jaci.2018.05.029.CrossRefPubMedPubMedCentral

108.

Simpson EL, Flohr C, Eichenfield LF, Bieber T, Sofen H, Taieb A, et al. Efficacy and safety of lebrikizumab (an anti-IL-13 monoclonal antibody) in adults with moderate-to-severe atopic dermatitis inadequately controlled by topical corticosteroids: a randomized, placebo-controlled phase II trial (TREBLE). J Am Acad Dermatol. 2018;78(5):863–871e11. https://doi.org/10.1016/j.jaad.2018.01.017.CrossRefPubMed

109.

Shahabuddin S, Ponath P, Schleimer RP. Migration of eosinophils across endothelial cell monolayers: interactions among IL-5, endothelial-activating cytokines, and C-C chemokines. J Immunol. 2000;164(7):3847–54.CrossRef

110.

Ochiai K, Kagami M, Matsumura R, Tomioka H. IL-5 but not interferon-gamma (IFN-gamma) inhibits eosinophil apoptosis by up-regulation of bcl-2 expression. Clin Exp Immunol. 1997;107(1):198–204.CrossRef

111.

Corren J. Inhibition of interleukin-5 for the treatment of eosinophilic diseases. Discov Med. 2012;13(71):305–12.PubMed

112.

Poulakos MN, Cargill SM, Waineo MF, Wolford AL Jr. Mepolizumab for the treatment of severe eosinophilic asthma. Am J Health Syst Pharm. 2017;74(13):963–9. https://doi.org/10.2146/ajhp160291.CrossRefPubMed

113.

Ortega HG, Yancey SW, Mayer B, Gunsoy NB, Keene ON, Bleecker ER, et al. Severe eosinophilic asthma treated with mepolizumab stratified by baseline eosinophil thresholds: a secondary analysis of the DREAM and MENSA studies. Lancet Respir Med. 2016;4(7):549–56. https://doi.org/10.1016/S2213-2600(16)30031-5.CrossRefPubMed

114.

Pavord ID, Korn S, Howarth P, Bleecker ER, Buhl R, Keene ON, et al. Mepolizumab for severe eosinophilic asthma (DREAM): a multicentre, double-blind, placebo-controlled trial. Lancet. 2012;380(9842):651–9. https://doi.org/10.1016/S0140-6736(12)60988-X.CrossRefPubMed

115.

Ortega HG, Liu MC, Pavord ID, Brusselle GG, FitzGerald JM, Chetta A, et al. Mepolizumab treatment in patients with severe eosinophilic asthma. N Engl J Med. 2014;371(13):1198–207. https://doi.org/10.1056/NEJMoa1403290.CrossRefPubMed

116.

Shimoda T, Odajima H, Okamasa A, Kawase M, Komatsubara M, Mayer B, et al. Efficacy and safety of mepolizumab in Japanese patients with severe eosinophilic asthma. Allergol Int. 2017;66(3):445–51. https://doi.org/10.1016/j.alit.2016.11.006.CrossRefPubMed

117.

Magnan A, Bourdin A, Prazma CM, Albers FC, Price RG, Yancey SW, et al. Treatment response with mepolizumab in severe eosinophilic asthma patients with previous omalizumab treatment. Allergy. 2016;71(9):1335–44. https://doi.org/10.1111/all.12914.CrossRefPubMedPubMedCentral

118.

Keating GM. Mepolizumab: first global approval. Drugs. 2015;75(18):2163–9. https://doi.org/10.1007/s40265-015-0513-8.CrossRefPubMed

119.

Oldhoff JM, Darsow U, Werfel T, Katzer K, Wulf A, Laifaoui J, et al. Anti-IL-5 recombinant humanized monoclonal antibody (mepolizumab) for the treatment of atopic dermatitis. Allergy. 2005;60(5):693–6. https://doi.org/10.1111/j.1398-9995.2005.00791.x.CrossRefPubMed

120.

Nograles KE, Zaba LC, Shemer A, Fuentes-Duculan J, Cardinale I, Kikuchi T, et al. IL-22-producing “T22” T cells account for upregulated IL-22 in atopic dermatitis despite reduced IL-17-producing TH17 T cells. J Allergy Clin Immunol. 2009;123(6):1244–1252e2. https://doi.org/10.1016/j.jaci.2009.03.041.CrossRefPubMedPubMedCentral

121.

Lou H, Lu J, Choi EB, Oh MH, Jeong M, Barmettler S, et al. Expression of IL-22 in the skin causes Th2-biased immunity, epidermal barrier dysfunction, and pruritus via stimulating epithelial Th2 cytokines and the GRP pathway. J Immunol. 2017;198(7):2543–55. https://doi.org/10.4049/jimmunol.1600126.CrossRefPubMedPubMedCentral

122.

Wolk K, Kunz S, Witte E, Friedrich M, Asadullah K, Sabat R. IL-22 increases the innate immunity of tissues. Immunity. 2004;21(2):241–54. https://doi.org/10.1016/j.immuni.2004.07.007.CrossRefPubMed

123.

Guttman-Yassky E, Brunner PM, Neumann AU, Khattri S, Pavel AB, Malik K, et al. Efficacy and safety of fezakinumab (an IL-22 monoclonal antibody) in adults with moderate-to-severe atopic dermatitis inadequately controlled by conventional treatments: a randomized, double-blind, phase 2a trial. J Am Acad Dermatol. 2018;78(5):872–881e6. https://doi.org/10.1016/j.jaad.2018.01.016.CrossRefPubMed

124.

Brunner PM, Pavel AB, Khattri S, Leonard A, Malik K, Rose S, et al. Baseline IL-22 expression in patients with atopic dermatitis stratifies tissue responses to fezakinumab. J Allergy Clin Immunol. 2018. https://doi.org/10.1016/j.jaci.2018.07.028.CrossRefPubMed

125.

Akdis M, Aab A, Altunbulakli C, Azkur K, Costa RA, Crameri R, et al. Interleukins (from IL-1 to IL-38), interferons, transforming growth factor beta, and TNF-alpha: Receptors, functions, and roles in diseases. J Allergy Clin Immunol. 2016;138(4):984–1010. https://doi.org/10.1016/j.jaci.2016.06.033.CrossRefPubMed

126.

Raap U, Gehring M, Kleiner S, Rudrich U, Eiz-Vesper B, Haas H, et al. Human basophils are a source of—and are differentially activated by—IL-31. Clin Exp Allergy. 2017;47(4):499–508. https://doi.org/10.1111/cea.12875.CrossRefPubMed

127.

Kunsleben N, Rudrich U, Gehring M, Novak N, Kapp A, Raap U. IL-31 induces chemotaxis, calcium mobilization, release of reactive oxygen species, and CCL26 in eosinophils, which are capable to release IL-31. J Investig Dermatol. 2015;135(7):1908–11. https://doi.org/10.1038/jid.2015.106.CrossRefPubMed

128.

Bagci IS, Ruzicka T. IL-31: a new key player in dermatology and beyond. J Allergy Clin Immunol. 2018;141(3):858–66. https://doi.org/10.1016/j.jaci.2017.10.045.CrossRefPubMed

129.

Hermanns HM. Oncostatin M and interleukin-31: cytokines, receptors, signal transduction and physiology. Cytokine Growth Factor Rev. 2015;26(5):545–58. https://doi.org/10.1016/j.cytogfr.2015.07.006.CrossRefPubMed

130.

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(2):296–304. https://doi.org/10.1111/bjd.14207.CrossRefPubMed

131.

Ruzicka T, Hanifin JM, Furue M, Pulka G, Mlynarczyk I, Wollenberg A, et al. Anti-interleukin-31 receptor A antibody for atopic dermatitis. N Engl J Med. 2017;376(9):826–35. https://doi.org/10.1056/NEJMoa1606490.CrossRefPubMed

132.

Kabashima K, Furue M, Hanifin JM, Pulka G, Wollenberg A, Galus R, et al. Nemolizumab in patients with moderate-to-severe atopic dermatitis: randomized, phase II, long-term extension study. J Allergy Clin Immunol. 2018;142(4):1121–1130e7. https://doi.org/10.1016/j.jaci.2018.03.018.CrossRefPubMed

133.

Toyoda M, Nakamura M, Makino T, Hino T, Kagoura M, Morohashi M. Nerve growth factor and substance P are useful plasma markers of disease activity in atopic dermatitis. Br J Dermatol. 2002;147(1):71–9. https://doi.org/10.1046/j.1365-2133.2002.04803.x.CrossRefPubMed

134.

Zhang Z, Zheng W, Xie H, Chai R, Wang J, Zhang H, et al. Up-regulated expression of substance P in CD8(+) T cells and NK1R on monocytes of atopic dermatitis. J Transl Med. 2017;15(1):93. https://doi.org/10.1186/s12967-017-1196-6.CrossRefPubMedPubMedCentral

135.

Zhan M, Zheng W, Jiang Q, Zhao Z, Wang Z, Wang J, et al. Upregulated expression of substance P (SP) and NK1R in eczema and SP-induced mast cell accumulation. Cell Biol Toxicol. 2017;33(4):389–405. https://doi.org/10.1007/s10565-016-9379-0.CrossRefPubMed

136.

Hon KL, Lam MC, Wong KY, Leung TF, Ng PC. Pathophysiology of nocturnal scratching in childhood atopic dermatitis: the role of brain-derived neurotrophic factor and substance P. Br J Dermatol. 2007;157(5):922–5. https://doi.org/10.1111/j.1365-2133.2007.08149.x.CrossRefPubMed

137.

Spitsin S, Pappa V, Douglas SD. Truncation of neurokinin-1 receptor-Negative regulation of substance P signaling. J Leukoc Biol. 2018. https://doi.org/10.1002/jlb.3mir0817-348r.CrossRefPubMed

138.

Stander S, Siepmann D, Herrgott I, Sunderkotter C, Luger TA. Targeting the neurokinin receptor 1 with aprepitant: a novel antipruritic strategy. PLoS One. 2010;5(6):e10968. https://doi.org/10.1371/journal.pone.0010968.CrossRefPubMedPubMedCentral

139.

Duval A, Dubertret L. Aprepitant as an antipruritic agent? N Engl J Med. 2009;361(14):1415–6. https://doi.org/10.1056/NEJMc0906670.CrossRefPubMed

140.

Torres T, Fernandes I, Selores M, Alves R, Lima M. Aprepitant: evidence of its effectiveness in patients with refractory pruritus continues. J Am Acad Dermatol. 2012;66(1):e14–5. https://doi.org/10.1016/j.jaad.2011.01.016.CrossRefPubMed

141.

Booken N, Heck M, Nicolay JP, Klemke CD, Goerdt S, Utikal J. Oral aprepitant in the therapy of refractory pruritus in erythrodermic cutaneous T-cell lymphoma. Br J Dermatol. 2011;164(3):665–7. https://doi.org/10.1111/j.1365-2133.2010.10108.x.CrossRefPubMed

142.

Song JS, Tawa M, Chau NG, Kupper TS, LeBoeuf NR. Aprepitant for refractory cutaneous T-cell lymphoma-associated pruritus: 4 cases and a review of the literature. BMC Cancer. 2017;17(1):200. https://doi.org/10.1186/s12885-017-3194-8.CrossRefPubMedPubMedCentral

143.

Jimenez Gallo D, Albarran Planelles C, Linares Barrios M, Fernandez Anguita MJ, Marquez Enriquez J, Rodriguez Mateos ME. Treatment of pruritus in early-stage hypopigmented mycosis fungoides with aprepitant. Dermatol Ther. 2014;27(3):178–82. https://doi.org/10.1111/dth.12113.CrossRefPubMed

144.

Ally MS, Gamba CS, Peng DH, Tang JY. The use of aprepitant in brachioradial pruritus. JAMA Dermatol. 2013;149(5):627–8. https://doi.org/10.1001/jamadermatol.2013.170.CrossRefPubMed

145.

Yosipovitch G, Ständer S, Kerby MB, Larrick JW, Perlman AJ, Schnipper EF, et al. Serlopitant for the treatment of chronic pruritus: Results of a randomized, multicenter, placebo-controlled phase 2 clinical trial. J Am Acad Dermatol. 2018;78(5):882–891.e10. https://doi.org/10.1016/j.jaad.2018.02.030.CrossRefPubMed

146.

Menlo Therapeutics. Menlo Therapeutics announces results from a phase 2 trial of serlopitant for pruritus associated with atopic dermatitis; 2018. http://www.menlotherapeutics.com/newsroom/menlo-therapeutics-announces-results-from-a-phase-2-trial-of-serlopitant-for-pruritus-associated-with-atopic-dermatitis/. Accessed 1 Oct 2018.

147.

Heitman A, Xiao C, Cho Y, Polymeropoulos C, Birznieks G, Polymeropoulos M. Tradipitant improves worst itch and disease severity in patients with chronic pruritus related to atopic dermatitis. J Am Acad Dermatol. 2018;79(3):AB300. https://doi.org/10.1016/j.jaad.2018.05.1184.CrossRef

148.

Reich A, Szepietowski JC. Non-analgesic effects of opioids: peripheral opioid receptors as promising targets for future anti-pruritic therapies. Curr Pharm Des. 2012;18(37):6021–4.CrossRef

149.

Tey HL, Yosipovitch G. Targeted treatment of pruritus: a look into the future. Br J Dermatol. 2011;165(1):5–17. https://doi.org/10.1111/j.1365-2133.2011.10217.x.CrossRefPubMedPubMedCentral

150.

Wikstrom B, Gellert R, Ladefoged SD, Danda Y, Akai M, Ide K, et al. Kappa-opioid system in uremic pruritus: multicenter, randomized, double-blind, placebo-controlled clinical studies. J Am Soc Nephrol. 2005;16(12):3742–7. https://doi.org/10.1681/ASN.2005020152.CrossRefPubMed

151.

Mathur VS, Kumar J, Crawford PW, Hait H, Sciascia T. A multicenter, randomized, double-blind, placebo-controlled trial of nalbuphine ER tablets for uremic pruritus. Am J Nephrol. 2017;46(6):450–8. https://doi.org/10.1159/000484573.CrossRefPubMed

152.

Dawn AG, Yosipovitch G. Butorphanol for treatment of intractable pruritus. J Am Acad Dermatol. 2006;54(3):527–31. https://doi.org/10.1016/j.jaad.2005.12.010.CrossRefPubMed

153.

Lim GJ, Ishiuji Y, Dawn A, Harrison B, Kim DW, Atala A, et al. In vitro and in vivo characterization of a novel liposomal butorphanol formulation for treatment of pruritus. Acta Derm Venereol. 2008;88(4):327–30. https://doi.org/10.2340/00015555-0480.CrossRefPubMed

154.

Tioga Pharmaceuticals. Tioga Pharmaceuticals’ asimadoline reduces nighttime itching and improves disease-related quality of life in patients with atopic dermatitis; 2017. https://www.prnewswire.com/news-releases/tioga-pharmaceuticals-asimadoline-reduces-nighttime-itching-and-improves-disease-related-quality-of-life-in-patients-with-atopic-dermatitis-300566114.html. Accessed 1 Oct 2018.

155.

Ohsawa Y, Hirasawa N. The role of histamine H1 and H4 receptors in atopic dermatitis: from basic research to clinical study. Allergol Int. 2014;63(4):533–42. https://doi.org/10.2332/allergolint.13-RA-0675.CrossRefPubMed

156.

Apfelbacher CJ, van Zuuren EJ, Fedorowicz Z, Jupiter A, Matterne U, Weisshaar E. Oral H1 antihistamines as monotherapy for eczema. Cochrane Database Syst Rev. 2013;28(2):CD007770. https://doi.org/10.1002/14651858.cd007770.pub2.CrossRef

157.

Dunford PJ, Williams KN, Desai PJ, Karlsson L, McQueen D, Thurmond RL. Histamine H4 receptor antagonists are superior to traditional antihistamines in the attenuation of experimental pruritus. J Allergy Clin Immunol. 2007;119(1):176–83. https://doi.org/10.1016/j.jaci.2006.08.034.CrossRefPubMed

158.

Rossbach K, Wendorff S, Sander K, Stark H, Gutzmer R, Werfel T, et al. Histamine H4 receptor antagonism reduces hapten-induced scratching behaviour but not inflammation. Exp Dermatol. 2009;18(1):57–63. https://doi.org/10.1111/j.1600-0625.2008.00762.x.CrossRefPubMed

159.

Werfel T, Layton G, Yeadon M, Whitlock L, Osterloh I, Jimenez P, et al. Efficacy and safety of the histamine H4 receptor antagonist ZPL-3893787 in patients with atopic dermatitis. J Allergy Clin Immunol. 2018. https://doi.org/10.1016/j.jaci.2018.07.047.CrossRefPubMedPubMedCentral

160.

Campana R, Dzoro S, Mittermann I, Fedenko E, Elisyutina O, Khaitov M, et al. Molecular aspects of allergens in atopic dermatitis. Curr Opin Allergy Clin Immunol. 2017;17(4):269–77. https://doi.org/10.1097/ACI.0000000000000378.CrossRefPubMedPubMedCentral

161.

Heratizadeh A. Atopic dermatitis: new evidence on the role of allergic inflammation. Curr Opin Allergy Clin Immunol. 2016;16(5):458–64. https://doi.org/10.1097/ACI.0000000000000308.CrossRefPubMed

162.

Navarrete-Dechent C, Perez-Mateluna G, Silva-Valenzuela S, Vera-Kellet C, Borzutzky A. Humoral and cellular autoreactivity to epidermal proteins in atopic dermatitis. Arch Immunol Ther Exp (Warsz). 2016;64(6):435–42. https://doi.org/10.1007/s00005-016-0400-3.CrossRef

163.

Werfel T, Allam JP, Biedermann T, Eyerich K, Gilles S, Guttman-Yassky E, et al. Cellular and molecular immunologic mechanisms in patients with atopic dermatitis. J Allergy Clin Immunol. 2016;138(2):336–49. https://doi.org/10.1016/j.jaci.2016.06.010.CrossRefPubMed

164.

Leung DY. Role of IgE in atopic dermatitis. Curr Opin Immunol. 1993;5(6):956–62.CrossRef

165.

Suarez-Farinas M, Dhingra N, Gittler J, Shemer A, Cardinale I, de Guzman Strong C, et al. Intrinsic atopic dermatitis shows similar TH2 and higher TH17 immune activation compared with extrinsic atopic dermatitis. J Allergy Clin Immunol. 2013;132(2):361–70. https://doi.org/10.1016/j.jaci.2013.04.046.CrossRefPubMedPubMedCentral

166.

Schulman ES. Development of a monoclonal anti-immunoglobulin E antibody (omalizumab) for the treatment of allergic respiratory disorders. Am J Respir Crit Care Med. 2001;164(8 Pt 2):S6–11. https://doi.org/10.1164/ajrccm.164.supplement_1.2103025.CrossRefPubMed

167.

Kawakami T, Blank U. From IgE to omalizumab. J Immunol. 2016;197(11):4187–92. https://doi.org/10.4049/jimmunol.1601476.CrossRefPubMedPubMedCentral

168.

Iyengar SR, Hoyte EG, Loza A, Bonaccorso S, Chiang D, Umetsu DT, et al. Immunologic effects of omalizumab in children with severe refractory atopic dermatitis: a randomized, placebo-controlled clinical trial. Int Arch Allergy Immunol. 2013;162(1):89–93. https://doi.org/10.1159/000350486.CrossRefPubMedPubMedCentral

169.

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 Dtsch Dermatol Ges. 2010;8(12):990–8. https://doi.org/10.1111/j.1610-0387.2010.07497.x.CrossRefPubMed

170.

Wang H-H, Li Y-C, Huang Y-C. Efficacy of omalizumab in patients with atopic dermatitis: a systematic review and meta-analysis. J Allergy Clin Immunol. 2016;138(6):1719–1722.e1. https://doi.org/10.1016/j.jaci.2016.05.038.CrossRefPubMed

171.

Shiratori-Hayashi M, Koga K, Tozaki-Saitoh H, Kohro Y, Toyonaga H, Yamaguchi C, et al. STAT3-dependent reactive astrogliosis in the spinal dorsal horn underlies chronic itch. Nat Med. 2015;21(8):927–31. https://doi.org/10.1038/nm.3912.CrossRefPubMed

Keynote webinar | Spotlight on medication adherence

Springer Medicine

New and Emerging Therapies for Pediatric Atopic Dermatitis

Abstract

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

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