Immunology of atopic dermatitis: Novel insights into mechanisms and immunomodulatory therapies

Seminars in Cutaneous Medicine and Surgery

Volumn 32, Issue 3, 2013, Pages 132-139

  Harskamp, Caitlin T ^a   Armstrong, April W ^a  

^a UNIVERSITY OF CALIFORNIA   (United States)

Author keywords

Atopic dermatitis; Biologics; Eczema; Immunology; Mechanism; Pathogenesis; Therapy

Indexed keywords

ALLERGEN; APREMILAST; CYTOKINE; DUPILUMAB; IMMUNOMODULATING AGENT; INFLIXIMAB; INTERLEUKIN 37; LEFLUNOMIDE; MEPOLIZUMAB; OMALIZUMAB; PLACEBO; RITUXIMAB; IMMUNOLOGIC FACTOR;

ARTICLE; ATOPIC DERMATITIS; CELLULAR IMMUNITY; DISEASE ASSOCIATION; DRUG RESEARCH; ENZYME INHIBITION; HUMAN; IMMUNE RESPONSE; IMMUNOLOGY; IMMUNOMODULATION; IMMUNOPATHOGENESIS; IMMUNOTHERAPY; MYCOBACTERIUM VACCAE; NONHUMAN; PHASE 1 CLINICAL TRIAL (TOPIC); PHASE 2 CLINICAL TRIAL (TOPIC); PHASE 3 CLINICAL TRIAL (TOPIC); RANDOMIZED CONTROLLED TRIAL (TOPIC); REMISSION; TH1 TH2 BALANCE; TREATMENT RESPONSE; DERMATITIS, ATOPIC; DESENSITIZATION; INNATE IMMUNITY; PROCEDURES;

DERMATITIS, ATOPIC; DESENSITIZATION, IMMUNOLOGIC; HUMANS; IMMUNITY, INNATE; IMMUNOLOGIC FACTORS;

EID: 84891539297     PISSN: 10855629     EISSN: 15580768     Source Type: Journal    
DOI: 10.12788/j.sder.0018     Document Type: Article

References (87)

1. Leung DY, Bieber T. Atopic dermatitis. Lancet. 2003;361(9352):151-160
2. Hill L, Sulzberger M. Yearbook of Dermatology and Syphilology. Chicago, IL: Year Book Medical Publishers; 1933:31-70
3. Johansson SG, Bieber T, Dahl R, et al. Revised nomenclature for allergy for global use: Report of the Nomenclature Review Committee of the World Allergy Organization, October 2003. J Allergy Clin Immunol. 2004;113(5): 832-836
4. Bieber T. Atopic dermatitis. N Engl J Med. 2008;358(14):1483-1494
5. Strachan DP: Hay fever, hygiene, and household size. BMJ. 1989; 299(6710): 1259-1260
6. Flohr C, Pascoe D, Williams HC. Atopic dermatitis and the 'hygiene hypothesis': too clean to be true? Br J Dermatol. 2005;152(2):202-216
7. O'Regan GM, Sandilands A, McLean WH, Irvine AD. Filaggrin in atopic dermatitis. Allergy Clin Immunol. 2008;122(4):689-693
8. Wolf R, Wolf D. Abnormal epidermal barrier in the pathogenesis of atopic dermatitis. Clin Dermatol. 2012;30(3):329-334
9. Leyden JJ, Marples RR, Kligman AM. Staphylococcus aureus in the lesions of atopic dermatitis. Br J Dermatol. 1974;90(5):525-530
10. Leyden JJ, Kligman AM. The case for steroid-antibiotic combinations. Br J Dermatol. 1977;96(2):179-187
11. Bauman R. Adaptive Immunity. In: Microbiology: with diseases by body system. 3rd ed. San Francisco, CA: Pearson Education, Inc.; 2012:471-497
12. Broere F, Apasov SG, Sitkovsky MV, van Eden W. T cell subsets and T cellmediated immunity. In: Nijkamp FP, Parnham MJ, eds. Principles of Immunopharmacology. 3rd ed. Springer; 2011:14-27. URL: http://link.springer. com/chapter/10.1007/978-3-0346-0136-8_2. Accessed February 5, 2013
13. Alberts B, Johnson A, Lewis J, Raff M, Roberts K, Walter P. The Adaptive Immune System. In: Molecular Biology of the Cell. 4th ed. New York: Garland Science; 2002:1363-1364. http://www.ncbi.nlm.nih.gov/books/NBK21070/. Accessed January 25, 2013
14. Akdis CA, Akdis M, Trautmann A, Blaser K. Immune regulation in atopic dermatitis. Curr Opin Immunol. 2000;12(6):641-646
15. Picker LJ, Michie SA, Rott LS, Butcher EC. A unique phenotype of skinassociated lymphocytes in humans. Preferential expression of the HECA-452 epitope by benign and malignant T cells at cutaneous sites. Am J Pathol. 1990;136(5):1053-1068
16. Akdis M, Trautmann A, Klunker S, Blaser K, Akdis CA. Cytokine network and dysregulated apoptosis in atopic dermatitis. Acta Odontol Scand. 2001; 59(3):178-182
17. Kapp A, Piskorski A, Schöpf E. Elevated levels of interleukin 2 receptor in sera of patients with atopic dermatitis and psoriasis. Br J Dermatol. 1988; 119(6):707-710
18. Allam JP, Bieber T, Novak N. Recent highlights in the pathophysiology of atopic eczema. Int Arch Allergy Immunol. 2005;136(2):191-197
19. Leung DY, Boguniewicz M, Howell MD, Nomura I, Hamid QA. New insights into atopic dermatitis. J Clin Invest. 2004;113:651-657
20. Ohmen JD, Hanifin JM, Nickoloff BJ, et al. Overexpression of IL-10 in atopic dermatitis. Contrasting cytokine patterns with delayed-type hypersensitivity reactions. J Immunol. 1995;154(4):1956-1963
21. Chan S, Henderson WR, Jr., Li SH, Hanifin JM. Prostaglandin E2 control of T cell cytokine production is functionally related to the reduced lymphocyte proliferation in atopic dermatitis. J Allergy Clin Immunol. 1996;97(1 Pt 1):85-94
22. Hanifin JM. Evolving concepts of pathogenesis in atopic dermatitis and other eczemas. J Invest Dermatol. 2009;129(2):320-322
23. Betz M, Fox BS. Prostaglandin E2 inhibits production of Th1 lymphokines but not of Th2 lymphokines. J Immunol. 1991;146(1):108-113
24. Akdis M, Simon HU, Weigl L, Kreyden O, Blaser K, Akdis CA. Skin homing (cutaneous lymphocyte-associated antigen-positive) CD8+ T cells respond to superantigen and contribute to eosinophilia and IgE production in atopic dermatitis. J Immunol. 1999;163(1):466-475
25. Akdis M, Akdis CA, Weigl L, Disch R, Blaser K. Skin-homing, CLA+memory T cells are activated in atopic dermatitis and regulate IgE by an IL-13-dominated cytokine pattern: IgG4 counter-regulation by CLA-memory T cells. J Immunol. 1997;159(9):4611-4619
26. Yawalkar N, Uguccioni M, Schärer J, et al. Enhanced expression of eotaxin and CCR3 in atopic dermatitis. J Invest Dermatol. 1999;113(1):43-48
27. Coffman RL, Carty J. A T cell activity that enhances polyclonal IgE production and its inhibition by interferon-gamma. J Immunol. 1986;136(3):949-954
28. Finkelman FD, Katona IM, Urban JF, Jr, et al. IL-4 is required to generate and sustain in vivo IgE responses. J Immunol. 1988;141(7):2335-2341
29. Kühn R, Rajewsky K, Müller W. Generation and analysis of interleukin-4 deficient mice. Science. 1991;254(5032):707-710
30. Snapper CM, Paul WE. Interferon-gamma and B cell stimulatory factor-1 reciprocally regulate Ig isotype production. Science. 1987;236(4808):944-947
31. Bieber T, de la Salle H, Wöllenberg A, et al. Human epidermal Langerhans cells express the high affinity receptor for immunoglobulin E (Fc epsilon RI). J Exp Med. 1992;175(5):1285-1290
32. Wollenberg A, Kraft S, Hanau D, Biebert T. Immunomorphological and ultrastructural characterization of Langerhans cells and a novel, inflammatory dendritic epidermal cell (IDEC) population in lesional skin of atopic eczema. J Invest Dermatol. 1996;106(3):446-453
33. Church JA, Kleban DG, Bellanti JA. Serum immunoglobulin E concentrations and radioallergosorbent tests in children with atopic dermatitis. Pediatr Res. 1976;10(2):97-99
34. Wahn U, Warner J, Simons FE, et al. IgE antibody responses in young children with atopic dermatitis. Pediatr Allergy Immunol 2008;19(4):332-336
35. Determinants of total and specific IgE in infants with atopic dermatitis. ETAC Study Group. Early Treatment of the Atopic Child. Pediatr Allergy Immunol. 1997;8(4):177-184
36. Wakim M, Alazard M, Yajima A, Speights D, Saxon A, Stiehm ER. High dose intravenous immunoglobulin in atopic dermatitis and hyper-IgE syndrome. Ann Allergy Asthma Immunol. 1998;81(2):153-158
37. Trautmann A, Akdis M, Kleemann D, et al. T cell-mediated Fas-induced keratinocyte apoptosis plays a key pathogenetic role in eczematous dermatitis. J Clin Invest. 2000;106(1):25-35
38. Wollenberg A, Wagner M, Günther S, et al. Plasmacytoid dendritic cells: a new cutaneous dendritic cell subset with distinct role in inflammatory skin diseases. J Invest Dermatol. 2002;119(5):1096-1102
39. Hamid Q, Boguniewicz M, Leung DY. Differential in situ cytokine gene expression in acute versus chronic atopic dermatitis. J Clin Invest. 1994; 94(2):870-876
40. Taha RA, Leung DY, Ghaffar O, Boguniewicz M, Hamid Q. In vivo expression of cytokine receptor mRNA in atopic dermatitis. J Allergy Clin Immunol. 1998;102(2):245-250
41. Laberge S, Ghaffar O, Boguniewicz M, Center DM, Leung DY, Hamid Q. Association of increased CD4+ T-cell infiltration with increased IL-16 gene expression in atopic dermatitis. J Allergy Clin Immunol. 1998;102 (4 Pt 1):645-650
42. Toda M, Leung DY, Molet S, et al. Polarized in vivo expression of IL-11 and IL-17 between acute and chronic skin lesions. J Allergy Clin Immunol. 2003; 111(4):875-888
43. Hamid Q, Naseer T, Minshall EM, Song YL, Boguniewicz M, Leung DY. In vivo expression of IL-12 and IL-13 in atopic dermatitis. J Allergy Clin Immunol. 1996;98(1):225-231
44. Grewe M, Gyufko K, Schöpf E, Krutmann J. Lesional expression of interferon-gamma in atopic eczema. Lancet. 1994;343(8888):25-26
45. 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):341-346
46. 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):890-897
47. ClinicalTrials.gov. http://clinicaltrials.gov/ct2/show/NCT01259323?term= regeneron&cond=atopicdermatitis&rank=5. Accessed January, 2013
48. Sakai N, Van Sweringen HL, Belizaire RM, et al. Interleukin-37 reduces liver inflammatory injury via effects on hepatocytes and non-parenchymal cells. J Gastroenterol Hepatol. 2012;27(10):1609-1616
49. Nold MF, Nold-Petry CA, Zepp JA, Palmer BE, Bufler P, Dinarello CA. IL-37 is a fundamental inhibitor of innate immunity. Nat Immunol. 2010;11(11): 1014-1022
50. Lane JE, Cheyney JM, Lane TN, Kent DE, Cohen DJ. Treatment of recalcitrant atopic dermatitis with omalizumab. J Am Acad Dermatol. 2006;54(1):68-72
51. Belloni B, Ziai M, Lim A, et al. Low-dose anti-IgE therapy in patients with atopic eczema with high serum IgE levels. J Allergy Clin Immunol. 2007; 120(5):1223-1225
52. Vigo PG, Girgis KR, Pfuetze BL, Critchlow ME, Fisher J, Hussain I. Efficacy of anti-IgE therapy in patients with atopic dermatitis. J Am Acad Dermatol. 2006;55(1):168-170
53. Quist SR, Ambach A, Göppner D, et al. Long-term treatment of severe recalcitrant atopic dermatitis with omalizumab, an anti-immuno-globulin E. Acta Derm Venereol. 2013;93(2):206-208
54. Krathen RA, Hsu S. Failure of omalizumab for treatment of severe adult atopic dermatitis. J Am Acad Dermatol. 2005;53(2):338-340
55. Simon D, Hösli S, Kostylina G, Yawalkar N, Simon HU. Anti-CD20 (rituximab) treatment improves atopic eczema. J Allergy Clin Immunol. 2008; 121(1):122-128
56. Sedivá A, Kayserová J, Vernerová E, et al. Anti-CD20 (rituximab) treatment for atopic eczema. J Allergy Clin Immunol. 2008;121(6):1515-1516; author reply 1516-1517
57. Oldhoff JM, Darsow U, Werfel T. Anti-IL-5 recombinant humanized monoclonal antibody (mepolizumab) for the treatment of atopic dermatitis. Allergy. 2005;60(5):693-696
58. Jacobi A, Antoni C, Manger B, Schuler G, Hertl M. Infliximab in the treatment of moderate to severe atopic dermatitis. J Am Acad Dermatol. 2005;52(3 Pt 1):522-526
59. Cassano N, Loconsole F, Coviello C, Vena GA. Infliximab in recalcitrant severe atopic eczema associated with contact allergy. Int J Immunopathol Pharmacol. 2006;19(1):237-240
60. Novak N, Bieber T, Hoffmann M, et al. Efficacy and safety of subcutaneous allergen-specific immunotherapy with depigmented polymerized mite extract in atopic dermatitis. J Allergy Clin Immunol. 2012;130(4):925-931
61. Werfel T, Breuer K, Ruéff F, 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(2):202-205
62. Brothers S, Asher MI, Jaksic M, Stewart AW. Effect of a Mycobacterium vaccae derivative on paediatric atopic dermatitis: a randomized, controlled trial. Clin Exp Dermatol. 2009;34(7):770-775
63. Arkwright PD, David TJ. Intradermal administration of a killed Mycobacterium vaccae suspension (SRL 172) is associated with improvement in atopic dermatitis in children with moderate-to-severe disease. J Allergy Clin Immunol. 2001;107(3):531-534
64. Arkwright PD, David TJ. Effect of Mycobacterium vaccae on atopic dermatitis in children of different ages. Br J Dermatol. 2003;149(5):1029-1034
65. Schmitt J, Wozel G, Pfeiffer C. Leflunomide as a novel treatment option in severe atopic dermatitis. Br J Dermatol. 2004;150(6):1182-1185
66. Wozel G, Vitez L, Pfeiffer C. Severe atopic dermatitis and leflunomide: first clinical experience and highlights of pertinent experimental data. Dermatol Online J. 2006;12(3):6
67. Schett G, Sloan VS, Stevens RM, Schafer P. Apremilast: a novel PDE4 inhibitor in the treatment of autoimmune and inflammatory diseases. Ther Adv Musculoskelet Dis. 2010;2(5):271-278
68. Schafer PH, Parton A, Gandhi AK, et al. Apremilast, a cAMP phosphodiesterase-4 inhibitor, demonstrates anti-inflammatory activity in vitro and in a model of psoriasis. Br J Pharmacol. 2010;159(4):842-855
69. Fujita H, Inoue Y, Seto K, Komitsu N, Aihara M. Interleukin-37 is elevated in subjects with atopic dermatitis. J Dermatol Sci. 2013;69(2):173-175
70. Banchereau J, Pascual V, O'Garra A.From IL-2 to IL-37: the expanding spectrum of anti-inflammatory cytokines. Nat Immunol. 2012;13(10):925-931
71. Johansson SG, Haahtela T, O'Byrne PM. Omalizumab and the immune system: an overview of preclinical and clinical data. Ann Allergy Asthma Immunol. 2002;89(2):132-138
72. Busse W, Corren J, Lanier BQ, et al. Omalizumab, anti-IgE recombinant humanized monoclonal antibody, for the treatment of severe allergic asthma. J Allergy Clin Immunol. 2001;108(2):184-190
73. Anderson DR, Grillo-López A, Varns C, Chambers KS, Hanna N. Targeted anti-cancer therapy using rituximab, a chimaeric anti-CD20 antibody (IDECC2B8) in the treatment of non-Hodgkin's B-cell lymphoma. Biochem Soc Trans. 1997;25(2):705-708
74. Scott SD. Rituximab: a new therapeutic monoclonal antibody for non-Hodgkin's lymphoma. Cancer Pract. 1998;6(3):195-197
75. Mepolizumab: 240563, anti-IL-5 monoclonal antibody-GlaxoSmithKline, anti-interleukin-5 monoclonal antibody-GlaxoSmithKline, SB 240563. Drugs R D. 2008;9(2):125-130
76. Oldhoff JM, Darsow U, Werfel T, et al. No effect of anti-interleukin-5 therapy (mepolizumab) on the atopy patch test in atopic dermatitis patients. Int Arch Allergy Immunol. 2006;141(3):290-294
77. Knight DM, Trinh H, Le J, et al. Construction and initial characterization of a mouse-human chimeric anti-TNF antibody. Mol Immunol. 1993;30(16): 1443-1453
78. Keating GM, Perry CM. Infliximab: an updated review of its use in Crohn's disease and rheumatoid arthritis. BioDrugs. 2002;16(2):111-148
79. Wright RC. Atopic dermatitis-like eruption precipitated by infliximab. J Am Acad Dermatol. 2003;49(1):160-161
80. Chan JL, Davis-Reed L, Kimball AB. Counter-regulatory balance: atopic dermatitis in patients undergoing infliximab infusion therapy. J Drugs Dermatol. 2004;3(3):315-318
81. Vestergaard C, Deleuran M, Kragballe K. Two cases of atopic dermatitis-like conditions induced in psoriasis patients treated with infliximab. J Eur Acad Dermatol Venereol. 2007;21(9):1272-1274
82. Berth-Jones J, Arkwright PD, Marasovic D, et al. Killed Mycobacterium vaccae suspension in children with moderate-to-severe atopic dermatitis: a randomized, double-blind, placebo-controlled trial. Clin Exp Allergy. 2006; 36(9):1115-1121
83. Hadley EA, Smillie FI, Turner MA, Custovic A, Woodcock A, Arkwright PD. Effect of Mycobacterium vaccae on cytokine responses in children with atopic dermatitis. Clin Exp Immunol. 2005;140(1):101-108
84. New medicines on the market. Evaluated information for NHS managers, budget holders, and prescribers. Leflunomide. United Kingdom: UK Drug Institution Pharmacists Group. March 2000; Monograph Number: 4/00/03
85. Breedveld FC, Dayer JM. Leflunomide: mode of action in the treatment of rheumatoid arthritis. Ann Rheum Dis. 2000;59(11):841-849
86. Behrens F, Finkenwirth C, Pavelka K, et al. Leflunomide in psoriatic arthritis: results from a large European prospective observational study. Arthritis Care Res (Hoboken). 2013;65(3):464-470
87. Eurpoean Medicines Agency: Science Medicines Health. EPAR Summary for the Public. 2011; http://www.emea.europa.eu/docs/en_GB/document_library/EPAR_-_ Summary_for_the_public/human/000235/WC500026284.pdf. Accessed February 2013