The Pathogenesis of the Atopic Eczema/Dermatitis Syndrome

  • N. Novak
  • T. Bieber


Substantial progress has been made in elucidating the immunoallergic mechanisms underlying the cutaneous inflammatory reaction in atopic eczema/dermatitis syndrome (AEDS). AEDS is a chronic inflammatory skin disease clinically and histologically very similar to allergic contact dermatitis. Hence, immunoallergic events are assumed to be pivotal in this condition. However, the exact mechanisms remain elusive, even though, thanks to modern immunology and molecular biology, some progress has been made in unravelling the pathophysiology of this complex disease (Fig. 2.1). Based on clinical observations and concomitant allergological investigations, it has been proposed that AEDS can be subdivided into two distinct forms: the extrinsic form/allergic form, occurring in the context of elevated serum immunoglobulin E (IgE) and sensitisation towards environmental allergens; and the intrinsic form/non-allergic form, occurring in the absence of any typical sensitisation. While the pathophysiology of the intrinsic/non-allergic form remains a black box, more progress has been made in understanding the extrinsic/allergic form. Thus, since IgE plays a major role in other atopic diseases, such as asthma and allergic rhinitis, it is assumed that in the extrinsic/allergic form as well, IgE mediates the specificity of the inflammatory condition in the skin.


Atopic Dermatitis Atopic Dermatitis Patient Atopy Patch Test Mast Cell Chymase Skin Immune System 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    Abeck D, Mempel M (1998) Cutaneous Staphylococcus aureus colonisation of atopic eczema. Mechanisms, pathophysiological importance and therapeutic consequences. Hautarzt 49(12): 902–906CrossRefGoogle Scholar
  2. 2.
    Agosti JM, Sprenger JD, Lum LG, Witherspoon RP, Fisher LD, Storb R et al. (1988) Transfer of allergen-specific IgE-mediated hypersensitivity with allogeneic bone marrow transplantation. N Engl J Med 319(25): 1623–1628PubMedCrossRefGoogle Scholar
  3. 3.
    Akdis CA, Akdis M, Simon D, Dibbert B, Weber M, Gratzl S et al. (1999) Role of T cells and cytokines in the intrinsic form of atopic dermatitis. Curr Probl Dermatol 28: 37–44PubMedCrossRefGoogle Scholar
  4. 4.
    Akdis M, Simon HU, Weigl L, Kreyden O, Blaser K, Akdis CA (1999) 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 163(1): 466–475PubMedGoogle Scholar
  5. 5.
    Asahina A, Hosoi J, Murphy GF, Granstein RD (1995) Calcitonin gene-related peptide modulates Langerhans cell antigen-presenting function. Proc Assoc Am Physicians 107(2): 242–244PubMedGoogle Scholar
  6. 6.
    Austyn JM (1996) New insights into the mobilization and phagocytic activity of dendritic cells. J Exp Med 183(4): 1287–1292PubMedCrossRefGoogle Scholar
  7. 7.
    Bieber T (1997) Fc epsilon RI on human epidermal Langerhans cells: an old receptor with new structure and functions. Int Arch Allergy Immunol 113(1–3): 30–34PubMedCrossRefGoogle Scholar
  8. 8.
    Bieber T (1997) Fc epsilon RI-expressing antigen-presenting cells: new players in the atopic game. Immunol Today 18(7): 311–313PubMedCrossRefGoogle Scholar
  9. 9.
    Bieber T, de la Salle H, Wollenberg A, Hakimi J, Chizzonite R, Ring J et al. (1992) Human epidermal Langerhans cells express the high affinity receptor for immunoglobulin E (Fc epsilon RI). J Exp Med 175(5): 1285–1290PubMedCrossRefGoogle Scholar
  10. 10.
    Birbeck MS, Breathnach AS, Everall JD (1961) An electron microscope study of basal melanocytes and high-level clear cells (Langerhans cells) in vitiligo. J Invest Dermatol 37: 51–64Google Scholar
  11. 11.
    Bleck O, Abeck D, Ring J, Hoppe U, Vietzke JP, Wolber R et al. (1999) Two ceramide subfractions detectable in Cer(AS) position by HPTLC in skin surface lipids of non-lesional skin of atopic eczema. J Invest Dermatol 113(6): 894–900PubMedCrossRefGoogle Scholar
  12. 12.
    Boguniewicz M, Sampson H, Leung SB, Harbeck R, Leung DY (2001) Effects of cefuroxime axetil on Staphylo-coccus aureus colonization and superantigen production in atopic dermatitis. J Allergy Clin Immunol 108(4): 651–652PubMedCrossRefGoogle Scholar
  13. 13.
    Bos JD (1997) The skin as an organ of immunity. Clin Exp Immunol 107(Suppl 1): 3–5PubMedGoogle Scholar
  14. 14.
    Bos JD, Zonneveld I, Das PK, Krieg SR, van der Loos CM, Kapsenberg ML (1987) The skin immune system (SIS): distribution and immunophenotype of lymphocyte subpopulations in normal human skin. J Invest Dermatol 88(5): 569–573PubMedCrossRefGoogle Scholar
  15. 15.
    Bos JD, Van Leent EJ, Sillevis Smitt JH (1998) The millennium criteria for the diagnosis of atopic dermatitis. Exp Dermatol 7(4): 132–138PubMedCrossRefGoogle Scholar
  16. 16.
    Buelens C, Willems F, Delvaux A, Pierard G, Delville JP, Velu T et al. (1995) Interleukin-10 differentially regulates B7-1 (CD80) and B7-2 (CD86) expression on human peripheral blood dendritic cells. Eur J Immunol 25(9): 2668–2672PubMedCrossRefGoogle Scholar
  17. 17.
    Bunikowski R, Mielke M, Skarabis H, Herz U, Bergmann RL, Wahn U et al. (1999) Prevalence and role of serum IgE antibodies to the Staphylococcus aureus-derived superantigens SEA and SEB in children with atopic dermatitis. J Allergy Clin Immunol 103(1 Pt 1): 119–124PubMedCrossRefGoogle Scholar
  18. 18.
    Bunikowski R, Mielke ME, Skarabis H, Worm M, Anagnostopoulos I, Kolde G et al. (2000) Evidence for a dis-ease-promoting effect of Staphylococcus aureus-derived exotoxins in atopic dermatitis. J Allergy Clin Immunol 105(4): 814–819PubMedCrossRefGoogle Scholar
  19. 19.
    Capoluongo E, Giglio AA, Lavieri MM, Lesnoni-La Parola I, Ferraro C, Cristaudo A et al. (2001) Genotypic and phenotypic characterization of Staphylococcus aureus strains isolated in subjects with atopic dermatitis. Higher prevalence of exfoliative B toxin production in lesional strains and correlation between the markers of disease intensity and colonization density. J Dermatol Sci 26(2): 145–155Google Scholar
  20. 20.
    Caux C (1998) Pathways of development of human dendritic cells. Eur J Dermatol 8: 375–384PubMedGoogle Scholar
  21. 21.
    Caux C, Dezutter-Dambuyant C, Schmitt D, Banchereau J (1992) GM-CSF and TNF-alpha cooperate in the generation of dendritic Langerhans cells. Nature 360(6401): 258–261PubMedCrossRefGoogle Scholar
  22. 22.
    Cho SH, Strickland I, Boguniewicz M, Leung DY (2001) Fibronectin and fibrinogen contribute to the enhanced binding of Staphylococcus aureus to atopic skin. J Allergy Clin Immunol 108(2): 269–274PubMedCrossRefGoogle Scholar
  23. 23.
    Cho SH, Strickland I, Tomkinson A, Fehringer AP, Gelfand EW, Leung DY (2001) Preferential binding of Staphylococcus aureus to skin sites of Th2-mediated inflammation in a murine model. J Invest Dermatol 116(5): 658–663PubMedCrossRefGoogle Scholar
  24. 24.
    Cogswell JJ, Mitchell EB, Alexander J (1987) Parental smoking, breast feeding, and respiratory infection in development of allergic diseases. Arch Dis Child 62(4): 338–344PubMedCrossRefGoogle Scholar
  25. 25.
    Cookson W (1994) The genetics of atopy. J Allergy Clin Immunol 94(3 Pt 2): 643–644PubMedCrossRefGoogle Scholar
  26. 26.
    Cookson WO (1998) Genetic aspects of atopic allergy. Allergy 53 (45 Suppl): 9–14PubMedCrossRefGoogle Scholar
  27. 27.
    Cookson WO, Young RP, Sandford AJ, Moffatt MF, Shirakawa T, Sharp PA et al. (1992) Maternal inheritance of atopic IgE responsiveness on chromosome 11q. Lancet 340(8816): 381–384PubMedCrossRefGoogle Scholar
  28. 28.
    Darsow U, Vieluf D, Ring J (1999) Evaluating the relevance of aeroallergen sensitization in atopic eczema with the atopy patch test: a randomized, double-blind multicenter study. Atopy Patch Test Study Group. J Am Acad Dermatol 40(2 Pt 1): 187–193PubMedCrossRefGoogle Scholar
  29. 29.
    Davison S, Allen M, Vaughan R, Barker J (2000) Staphylococcal toxin-induced T cell proliferation in atopic ec-zema correlates with increased use of superantigen-reactive Vbeta-chains in cutaneous lymphocyte-associated antigen (CLA)-positive lymphocytes. Clin Exp Immunol 121(2): 181–186PubMedCrossRefGoogle Scholar
  30. 30.
    Deichmann KA, Heinzmann A, Forster J, Dischinger S, Mehl C, Brueggenolte E et al. (1998) Linkage and allelic association of atopy and markers flanking the IL4-receptor gene. Clin Exp Allergy 28(2): 151–155PubMedCrossRefGoogle Scholar
  31. 31.
    Di Nardo A, Wertz P, Giannetti A, Seidenari S (1998) Ceramide and cholesterol composition of the skin of patients with atopic dermatitis. Acta Derm Venereol 78(1): 27–30PubMedCrossRefGoogle Scholar
  32. 32.
    Dieu MC, Vanbervliet B, Vicari A, Bridon JM, Oldham E, Ait-Yahia S et al. (1998) Selective recruitment of immature and mature dendritic cells by distinct chemokines expressed in different anatomic sites. J Exp Med 188(2): 373–386PubMedCrossRefGoogle Scholar
  33. 33.
    Dieu-Nosjean MC, Massacrier C, Vanbervliet B, Fridman WH, Caux C (2001) IL-10 induces CCR6 expression during Langerhans cell development while IL-4 and IFN-gamma suppress it. J Immunol 167(10): 5594–5602PubMedGoogle Scholar
  34. 34.
    Fartasch M (1997) Epidermal barrier in disorders of the skin. Microsc Res Tech 38(4): 361–372PubMedCrossRefGoogle Scholar
  35. 35.
    Firooz A, Davoudi SM, Farahmand AN, Majdzadeh R, Kashani N, Dowlati Y (1999) Validation of the diagnostic criteria for atopic dermatitis. Arch Dermatol 135(5): 514–516PubMedCrossRefGoogle Scholar
  36. 36.
    Floret D (2001) Clinical aspects of streptococcal and staphylococcal toxinic diseases. Arch Pediatr 8(Suppl 4): 762s–768sPubMedCrossRefGoogle Scholar
  37. 37.
    Forrest S, Dunn K, Elliott K, Fitzpatrick E, Fullerton J, McCarthy M et al. (1999) Identifying genes predisposing to atopic eczema. J Allergy Clin Immunol 104(5): 1066–1070PubMedCrossRefGoogle Scholar
  38. 38.
    Foster TJ, Hook M (1998) Surface protein adhesins of Staphylococcus aureus. Trends Microbiol 6(12): 484–488PubMedCrossRefGoogle Scholar
  39. 39.
    Gantner F, Gotz C, Gekeler V, Schudt C, Wendel A, Hatzelmann A (1998) Phosphodiesterase profile of human B lymphocytes from normal and atopic donors and the effects of PDE inhibition on B cell proliferation. Br J Pharmacol 123(6): 1031–1038PubMedCrossRefGoogle Scholar
  40. 40.
    Gfesser M, Rakoski J, Ring J (1996) The disturbance of epidermal barrier function in atopy patch test reactions in atopic eczema. Br J Dermatol 135(4): 560–565PubMedCrossRefGoogle Scholar
  41. 41.
    Gfesser M, Abeck D, Rugemer J, Schreiner V, Stab F, Disch R et al. (1997) The early phase of epidermal barrier regeneration is faster in patients with atopic eczema. Dermatology 195(4): 332–336PubMedCrossRefGoogle Scholar
  42. 42.
    Hanifin JM (1984) Atopic dermatitis. J Allergy Clin Immunol 73(2): 211–226PubMedCrossRefGoogle Scholar
  43. 43.
    Hanifin JM (1999) Diagnostic criteria for atopic dermatitis: consider the context. Arch Dermatol 135(12): 1551PubMedCrossRefGoogle Scholar
  44. 44.
    Hanifin JM, Chan SC (1995) Monocyte phosphodiesterase abnormalities and dysregulation of lymphocyte function in atopic dermatitis. J Invest Dermatol 105(1 Suppl): 84S–88SPubMedCrossRefGoogle Scholar
  45. 45.
    Hara J, Higuchi K, Okamoto R, Kawashima M, Imokawa G (2000) High-expression of sphingomyelin deacylase is an important determinant of ceramide deficiency leading to barrier disruption in atopic dermatitis. J Invest Dermatol 115(3): 406–413PubMedCrossRefGoogle Scholar
  46. 46.
    Hershey GK, Friedrich MF, Esswein LA, Thomas ML, Chatila TA (1997) The association of atopy with a gain-of-function mutation in the alpha subunit of the interleukin-4 receptor. N Engl J Med 337(24): 1720–1725PubMedCrossRefGoogle Scholar
  47. 47.
    Herz U, Schnoy N, Borelli S, Weigl L, Kasbohrer U, Daser A et al. (1998) A human-SCID mouse model for allergic immune response bacterial superantigen enhances skin inflammation and suppresses IgE production. J Invest Dermatol 110(3): 224–231PubMedCrossRefGoogle Scholar
  48. 48.
    Hill S, Griffiths S, Kimber I, Knight SC (1993) Migration of dendritic cells during contact sensitization. Adv Exp Med Biol 329: 315–320PubMedCrossRefGoogle Scholar
  49. 49.
    Hofer MF, Harbeck RJ, Schlievert PM, Leung DY (1999) Staphylococcal toxins augment specific IgE responses by atopic patients exposed to allergen. J Invest Dermatol 112(2): 171–176PubMedCrossRefGoogle Scholar
  50. 50.
    Holden CA, Chan SC, Hanifin JM (1986) Monocyte localization of elevated cAMP phosphodiesterase activity in atopic dermatitis. J Invest Dermatol 87(3): 372–376PubMedCrossRefGoogle Scholar
  51. 51.
    Hosoi J, Murphy GF, Egan CL, Lerner EA, Grabbe S, Asahina A et al. (1993) Regulation of Langerhans cell function by nerves containing calcitonin gene-related peptide. Nature 363(6425): 159–163PubMedCrossRefGoogle Scholar
  52. 52.
    Immervoll T, Wjst M (1999) Current status of the asthma and allergy database. Nucleic Acids Res 27(1): 213–214PubMedCrossRefGoogle Scholar
  53. 53.
    Isolauri E, Tahvanainen A, Peltola T, Arvola T (1999) Breast-feeding of allergic infants. J Pediatr 134(1): 27–32PubMedCrossRefGoogle Scholar
  54. 54.
    Jakob T, Ring J, Udey MC (2001) Multistep navigation of Langerhans/dendritic cells in and out of the skin. J Allergy Clin Immunol 108(5): 688–696PubMedCrossRefGoogle Scholar
  55. 55.
    Jamora MJ, Verallo-Rowell VM, Samson-Veneracion MT (2001) Patch testing with 20% dermatophagoides pteronyssinus/farinae (Chemotechnique) antigen. Am J Contact Dermat 12(2): 67–71PubMedCrossRefGoogle Scholar
  56. 56.
    Jenmalm MC, Van Snick J, Cormont F, Salman B (2001) Allergen-induced Th1 and Th2 cytokine secretion in relation to specific allergen sensitization and atopic symptoms in children. Clin Exp Allergy 31(10): 1528–1535PubMedCrossRefGoogle Scholar
  57. 57.
    Johansson SG, Hourihane JO, Bousquet J, Bruijnzeel-Koomen C, Dreborg S, Haahtela T et al. (2001) A revised nomenclature for allergy. An EAACI position statement from the EAACI nomenclature task force. Allergy 56(9): 813–824Google Scholar
  58. 58.
    Jurgens M, Wollenberg A, Hanau D, de la Salle H, Bieber T (1995) Activation of human epidermal Langerhans cells by engagement of the high affinity receptor for IgE Fc epsilon RI. J Immunol 155(11): 5184–5189PubMedGoogle Scholar
  59. 59.
    Kalinski P, Hilkens CM, Wierenga EA, Kapsenberg ML (1999) T-cell priming by type-1 and type-2 polarized dendritic cells: the concept of a third signal. Immunol Today 20(12): 561–567PubMedCrossRefGoogle Scholar
  60. 60.
    Kanda N, Watanabe S (2001) Intracellular 3′,5′-adenosine cyclic monophosphate level regulates house dust miteinduced interleukin-13 production by T cells from mite-sensitive patients with atopic dermatitis. J Invest Dermatol 116(1): 3–11PubMedCrossRefGoogle Scholar
  61. 61.
    Katz SI, Tamaki K, Sachs DH (1979) Epidermal Langerhans cells are derived from cells originating in bone marrow. Nature 282(5736): 324–326PubMedCrossRefGoogle Scholar
  62. 62.
    Kawashima T, Noguchi E, Arinami T, Kobayashi K, Otsuka F, Hamaguchi H (1998) No evidence for an association between a variant of the mast cell chymase gene and atopic dermatitis based on case-control and haplotype-relative-risk analyses. Hum Hered 48(5): 271–274PubMedCrossRefGoogle Scholar
  63. 63.
    Kennedy MK, Picha KS, Shanebeck KD, Anderson DM, Grabstein KH (1994) Interleukin-12 regulates the proliferation of Th1, but not Th2 or Th0, clones. Eur J Immunol 24(10): 2271–2278PubMedCrossRefGoogle Scholar
  64. 64.
    Kinet JP (1999) The high-affinity IgE receptor (Fc epsilon RI): from physiology to pathology. Annu Rev Immunol 17: 931–972PubMedCrossRefGoogle Scholar
  65. 65.
    Knight SC, Krejci J, Malkovsky M, Colizzi V, Gautam A, Asherson GL (1985) The role of dendritic cells in the initiation of immune responses to contact sensitizers. I. in vivo exposure to antigen. Cell Immunol 94(2): 427–434CrossRefGoogle Scholar
  66. 66.
    Kraft S, Wessendorf JH, Hanau D, Bieber T (1998) Regulation of the high affinity receptor for IgE on human epi-dermal Langerhans cells. J Immunol 161(2): 1000–1006PubMedGoogle Scholar
  67. 67.
    Kruse S, Japha T, Tedner M, Sparholt SH, Forster J, Kuehr J et al. (1999) The polymorphisms S503P and Q576R in the interleukin-4 receptor alpha gene are associated with atopy and influence the signal transduction. Immunology 96(3): 365–371PubMedCrossRefGoogle Scholar
  68. 68.
    Kuster H, Thompson H, Kinet JP (1990) Characterization and expression of the gene for the human Fc receptor gamma subunit. Definition of a new gene family. J Biol Chem 265(11): 6448–6452Google Scholar
  69. 69.
    Lambert RW, Granstein RD (1998) Neuropeptides and Langerhans cells. Exp Dermatol 7(2–3): 73–80PubMedCrossRefGoogle Scholar
  70. 70.
    Langeveld-Wildschut EG, Bruijnzeel PL, Mudde GC, Versluis C, Van Ieperen-Van Dijk AG, Bihari IC et al. (2000) Clinical and immunologic variables in skin of patients with atopic eczema and either positive or negative atopy patch test reactions. J Allergy Clin Immunol 105(5): 1008–1016PubMedCrossRefGoogle Scholar
  71. 71.
    Langeveld-Wildschut EG, Riedl H, Thepen T, Bihari IC, Bruijnzeel PL, Bruijnzeel-Koomen CA (2000) Modulation of the atopy patch test reaction by topical corticosteroids and tar. J Allergy Clin Immunol 106(4): 737–743PubMedCrossRefGoogle Scholar
  72. 72.
    Lee YA, Wahn U, Kehrt R, Tarani L, Businco L, Gustafsson D et al. (2000) A major susceptibility locus for atopic dermatitis maps to chromosome 3q21. Nat Genet 26(4): 470–473PubMedCrossRefGoogle Scholar
  73. 73.
    Leonhardt A, Krauss M, Gieler U, Schweer H, Happle R, Seyberth HW (1997) In vivo formation of prostaglandin El and prostaglandin E2 in atopic dermatitis. Br J Dermatol 136(3): 337–340PubMedCrossRefGoogle Scholar
  74. 74.
    Leung DY (2000) Atopic dermatitis: new insights and opportunities for therapeutic intervention. J Allergy Clin Immunol 105(5): 860–876PubMedCrossRefGoogle Scholar
  75. 75.
    Leung DY (2001) Atopic dermatitis and the immune system: the role of superantigens and bacteria. J Am Acad Dermatol 45(1 Suppl): S13–S16PubMedCrossRefGoogle Scholar
  76. 76.
    Leung DY, Harbeck R, Bina P, Reiser RF, Yang E, Norris DA et al. (1993) Presence of IgE antibodies to staphylococcal exotoxins on the skin of patients with atopic dermatitis. Evidence for a new group of allergens. J Clin Invest 92(3): 1374–1380CrossRefGoogle Scholar
  77. 77.
    Leung DY, Gately M, Trumble A, Ferguson-Darnell B, Schlievert PM, Picker LJ (1995) Bacterial superantigens induce T cell expression of the skin-selective homing receptor, the cutaneous lymphocyte-associated antigen, via stimulation of interleukin 12 production. J Exp Med 181(2): 747–753PubMedCrossRefGoogle Scholar
  78. 78.
    Leyden JJ, Marples RR, Kligman AM (1974) Staphylococcus aureus in the lesions of atopic dermatitis. Br J Dermatol 90(5): 525–530PubMedCrossRefGoogle Scholar
  79. 79.
    Luger TA, Schauer E, Trautinger F, Krutmann J, Ansel J, Schwarz A et al. (1993) Production of immunosuppressing melanotropins by human keratinocytes. Ann N Y Acad Sci 680: 567–570PubMedCrossRefGoogle Scholar
  80. 80.
    Manku MS, Horrobin DF, Morse N, Kyte V, Jenkins K, Wright S et al. (1982) Reduced levels of prostaglandin pre-cursors in the blood of atopic patients: defective delta-6-desaturase function as a biochemical basis for atopy. Prostaglandins Leukot Med 9(6): 615–628PubMedCrossRefGoogle Scholar
  81. 81.
    Mao XQ, Shirakawa T, Kawai M, Enomoto T, Sasaki S, Dake Y et al. (1998) Association between asthma and an intragenic variant of CC16 on chromosome 11q13. Clin Genet 53(1): 54–56PubMedCrossRefGoogle Scholar
  82. 82.
    Marekov LN, Steinert PM (1998) Ceramides are bound to structural proteins of the human foreskin epidermal cornified cell envelope. J Biol Chem 273(28): 17763–17770PubMedCrossRefGoogle Scholar
  83. 83.
    Maurer D, Ebner C, Reininger B, Fiebiger E, Kraft D, Kinet JP et al. (1995) The high affinity IgE receptor (Fc epsilon RI) mediates IgE-dependent allergen presentation. J Immunol 154(12): 6285–6290PubMedGoogle Scholar
  84. 84.
    Maurer D, Fiebiger S, Ebner C, Reininger B, Fischer GF, Wichlas S et al. (1996) Peripheral blood dendritic cells express Fc epsilon RI as a complex composed of Fc epsilon RI alpha-and Fc epsilon RI gamma-chains and can use this receptor for IgE-mediated allergen presentation. J Immunol 157(2): 607–616PubMedGoogle Scholar
  85. 85.
    Maurer D, Fiebiger E, Reininger B, Ebner C, Petzelbauer P, Shi GP et al. (1998) Fc epsilon receptor I on dendritic cells delivers IgE-bound multivalent antigens into a cathepsin s-dependent pathway of MHC class II presentation. J Immunol 161(6): 2731–2739PubMedGoogle Scholar
  86. 86.
    Melnik BC (1990) A chance for the prevention of atopic diseases. Monatsschr Kinderheilkd 138(3): 162–166PubMedGoogle Scholar
  87. 87.
    Melnick B, Plewig G (1992) Modulation of omega-6-fatty acid and eicosanoid metabolism in atopic dermatitis. Hautarzt 43(12): 800–802PubMedGoogle Scholar
  88. 88.
    Melnik B, Plewig G (1992) Are disturbances of omega-6-fatty acid metabolism involved in the pathogenesis of atopic dermatitis? Acta Derm Venereol Suppl (Stockh) 176: 77–85Google Scholar
  89. 89.
    Melnik B, Plewig G, Tschung T (1991) Are deficiencies of prostaglandin-E-mediated immunoregulation involved in increased IgE synthesis of atopic mononudear cells in vitro? Allergy 46(7): 502–506PubMedCrossRefGoogle Scholar
  90. 90.
    Michie CA, Davis T (1996) Atopic dermatitis and staphylococcal superantigens. Lancet 347(8997): 324PubMedCrossRefGoogle Scholar
  91. 91.
    Mosmann TR, Sad S (1996) The expanding universe of T-cell subsets: Th1, Th2 and more. Immunol Today 17(3): 138–146PubMedCrossRefGoogle Scholar
  92. 92.
    Murata Y, Ogata J, Higaki Y, Kawashima M, Yada Y, Higuchi K et al. (1996) Abnormal expression of sphingomyelin acylase in atopic dermatitis: an etiologic factor for ceramide deficiency? J Invest Dermatol 106(6): 1242–1249PubMedCrossRefGoogle Scholar
  93. 93.
    Nakata K, Inoue Y, Harada J, Maeda N, Watanabe H, Tano Y et al. (2000) A high incidence of Staphylococcus aureus colonization in the external eyes of patients with atopic dermatitis. Ophthalmology 107(12): 2167–2171PubMedCrossRefGoogle Scholar
  94. 94.
    Nickel RG, Casolaro V, Wahn U, Beyer K, Barnes KC, Plunkett BS et al. (2000) Atopic dermatitis is associated with a functional mutation in the promoter of the C-C chemokine RANTES. J Immunol 164(3): 1612–1616PubMedGoogle Scholar
  95. 95.
    Niggemann B (2001) The role of the atopy patch test (APT) in diagnosis of food allergy in infants and children with atopic dermatitis. Pediatr Allergy Immunol 12 (Suppl) 14: 37–40CrossRefGoogle Scholar
  96. 96.
    Ninan TK, Russell G (1992) Respiratory symptoms and atopy in Aberdeen schoolchildren: evidence from two surveys 25 years apart. BMJ 304(6831): 873–875PubMedCrossRefGoogle Scholar
  97. 97.
    Novak N, Bieber T (2000) The skin as a target for allergic diseases. Allergy 55(2): 103–107PubMedCrossRefGoogle Scholar
  98. 98.
    Novak N, Bieber T, Katoh N (2001) Engagement of Fc epsilon RI on human monocytes induces the production of IL-10 and prevents their differentiation in dendritic cells. J Immunol 167(2): 797–804PubMedGoogle Scholar
  99. 99.
    Novak N, Kraft S, Bieber T (2001) IgE receptors. Curr Opin Immunol 13(6): 721–726PubMedCrossRefGoogle Scholar
  100. 100.
    Novembre E, Cianferoni A, Lombardi E, Bernardini R, Pucci N, Vierucci A (2001) Natural history of “intrinsic” atopic dermatitis. Allergy 56(5): 452–453PubMedCrossRefGoogle Scholar
  101. 101.
    Ochs RL, Muro Y, Si Y, Ge H, Chan EK, Tan EM (2000) Autoantibodies to DFS 70 kd/transcription coactivator p75 in atopic dermatitis and other conditions. J Allergy Clin Immunol 105(6 Pt 1): 1211–1220PubMedCrossRefGoogle Scholar
  102. 102.
    O’Doherty U, Peng M, Gezelter S, Swiggard WJ, Betjes M, Bhardwaj N et al. (1994) Human blood contains two subsets of dendritic cells, one immunologically mature and the other immature. Immunology 82(3): 487–493PubMedGoogle Scholar
  103. 103.
    Ohnishi Y, Okino N, Ito M, Imayama S (1999) Ceramidase activity in bacterial skin flora as a possible cause of ceramide deficiency in atopic dermatitis. Clin Diagn Lab Immunol 6(1): 101–104PubMedGoogle Scholar
  104. 104.
    Olesen AB, Ellingsen AR, Larsen FS, Larsen PO, Veien NK, Thestrup-Pedersen K (1996) Atopic dermatitis may be linked to whether a child is first-or second-born and/or the age of the mother. Acta Derm Venereol 76(6): 457–460PubMedGoogle Scholar
  105. 105.
    Olweus J, Bit Mansour A, Warnke R, Thompson PA, Carballido J, Picker LJ et al. (1997) Dendritic cell ontogeny: a human dendritic cell lineage of myeloid origin. Proc Natl Acad Sci USA 94(23): 12551–12556PubMedCrossRefGoogle Scholar
  106. 106.
    Oppel T, Schuller E, Gunther S, Moderer M, Haberstok J, Bieber T et al. (2000) Phenotyping of epidermal dendritic cells allows the differentiation between extrinsic and intrinsic forms of atopic dermatitis. Br J Dermatol 143(6): 1193–1198PubMedCrossRefGoogle Scholar
  107. 107.
    Ostlere LS, Mallett RB, Kaminski A, Kaminski ER, Pereira RS, Holden CA (1995) Gamma-interferon production in atopic dermatitis shows differential modification by phosphodiesterase and prostaglandin inhibition. Br J Dermatol 133(1): 1–5PubMedCrossRefGoogle Scholar
  108. 108.
    Pastore S, Mascia F, Giustizieri ML, Giannetti A, Girolomoni G (2000) Pathogenetic mechanisms of atopic der-matitis. Arch Immunol Ther Exp (Warsz) 48(6): 497–504Google Scholar
  109. 109.
    Reich K, Heine A, Hugo S, Blaschke V, Middel P, Kaser A et al. (2001) Engagement of the Fc epsilon RI stimulates the production of IL-16 in Langerhans cell-like dendritic cells. J Immunol 167(11): 6321–6329PubMedGoogle Scholar
  110. 110.
    Ring J, Darsow U, Behrendt H (2001) Role of aeroallergens in atopic eczema: proof of concept with the atopy patch test. J Am Acad Dermatol 45(Suppl 1): S49–S52PubMedCrossRefGoogle Scholar
  111. 111.
    Rosenwasser LJ, Klemm DJ, Dresback JK, Inamura H, Mascali JJ, Klinnert M et al. (1995) Promoter polymorphisms in the chromosome 5 gene cluster in asthma and atopy. Clin Exp Allergy 25(Suppl 2): 74–78; discussion 95-96PubMedCrossRefGoogle Scholar
  112. 112.
    Sallusto F, Lanzavecchia A (1994) Efficient presentation of soluble antigen by cultured human dendritic cells is maintained by granulocyte/macrophage colony-stimulating factor plus interleukin 4 and down-regulated by tumor necrosis factor alpha. J Exp Med 179(4): 1109–1118PubMedCrossRefGoogle Scholar
  113. 113.
    Sallusto F, Cella M, Danieli C, Lanzavecchia A (1995) Dendritic cells use macropinocytosis and the mannose receptor to concentrate macromolecules in the major histocompatibility complex class II compartment: down-regulation by cytokines and bacterial products [see comments]. J Exp Med 182(2): 389–400PubMedCrossRefGoogle Scholar
  114. 114.
    Sallusto F, Lanzavecchia A, Mackay CR (1998) Chemokines and chemokine receptors in T-cell priming and Th1/Th2-mediated responses. Immunol Today 19(12): 568–574PubMedCrossRefGoogle Scholar
  115. 115.
    Schafer T, Kramer U, Vieluf D, Abeck D, Behrendt H, Ring J (2000) The excess of atopic eczema in East Germany is related to the intrinsic type. Br J Dermatol 143(5): 992–998PubMedCrossRefGoogle Scholar
  116. 116.
    Schauer E, Trautinger F, Kock A, Schwarz A, Bhardwaj R, Simon M et al. (1994) Proopiomelanocortin-derived peptides are synthesized and released by human keratinocytes. J Clin Invest 93(5): 2258–2262PubMedCrossRefGoogle Scholar
  117. 117.
    Schmid-Grendelmeier P, Simon D, Simon HU, Akdis CA, Wuthrich B (2001) Epidemiology, clinical features, and immunology of the “intrinsic” (non-IgE-mediated) type of atopic dermatitis (constitutional dermatitis). Allergy 56(9): 841–849PubMedCrossRefGoogle Scholar
  118. 118.
    Schuller E, Teichmann B, Haberstok J, Moderer M, Bieber T, Wollenberg A (2001) In situ expression of the costimulatory molecules CD80 and CD86 on Langerhans cells and inflammatory dendritic epidermal cells (IDEC) in atopic dermatitis. Arch Dermatol Res 293(9): 448–454PubMedCrossRefGoogle Scholar
  119. 119.
    Schultze JL, Michalak S, Lowne J, Wong A, Gilleece MH, Gribben JG et al. (1999) Human non-germinal center B cell interleukin (IL)-12 production is primarily regulated by T cell signals CD40 ligand, interferon gamma, and IL-10: role of B cells in the maintenance of T cell responses. J Exp Med 189(1): 1–12PubMedCrossRefGoogle Scholar
  120. 120.
    Seiberler S, Bugajska-Schretter A, Hufnagl P, Binder BR, Stockl J, Spitzauer S et al. (1999) Characterization of IgE-reactive autoantigens in atopic dermatitis. 1. Subcellular distribution and tissue-specific expression. Int Arch Allergy Immunol 120(2): 108–116CrossRefGoogle Scholar
  121. 121.
    Seiberler S, Natter S, Hufnagl P, Binder BR, Valenta R (1999) Characterization of IgE-reactive autoantigens in atopic dermatitis. 2. A pilot study on IgE versus IgG subclass response and seasonal variation of IgE auto-reactivity. Int Arch Allergy Immunol 120(2): 117–125CrossRefGoogle Scholar
  122. 122.
    Seidenari S, Giusti G (1995) Objective assessment of the skin of children affected by atopic dermatitis: a study of pH, capacitance and TEWL in eczematous and clinically uninvolved skin. Acta Derm Venereol 75(6): 429–433PubMedGoogle Scholar
  123. 123.
    Shirakawa T, Li A, Dubowitz M, Dekker JW, Shaw AE, Faux JA et al. (1994) Association between atopy and variants of the beta subunit of the high-affinity immunoglobulin E receptor. Nat Genet 7(2): 125–129PubMedCrossRefGoogle Scholar
  124. 124.
    Shohet L, Shahar E, Davidson S (1985) Breast feeding as prophylaxis for atopic eczema: a controlled study of 368 cases. Acta Paediatr Hung 26(1): 35–39PubMedGoogle Scholar
  125. 125.
    Signoret R, Mathias N, Sayag J (1993) Physical urticaria and angioedema in children. Allerg Immunol (Paris) 25(8): 330–331Google Scholar
  126. 126.
    Soyland E, Lea T, Sandstad B, Drevon A (1994) Dietary supplementation with very long-chain n-3 fatty acids in man decreases expression of the interleukin-2 receptor (CD25) on mitogen-stimulated lymphocytes from patients with inflammatory skin diseases. Eur J Clin Invest 24(4): 236–242PubMedCrossRefGoogle Scholar
  127. 127.
    Steinman RM, Cohn ZA (1973) Identification of a novel cell type in peripheral lymphoid organs of mice. i. morphology, quantitation, tissue distribution. J Exp Med 137(5): 1142–1162Google Scholar
  128. 128.
    Strickland I, Hauk PJ, Trumble AE, Picker LJ, Leung DY (1999) Evidence for superantigen involvement in skin homing of T cells in atopic dermatitis. J Invest Dermatol 112(2): 249–253PubMedCrossRefGoogle Scholar
  129. 129.
    Taieb A (2001) The natural history of atopic dermatitis. J Am Acad Dermatol 45(1 Suppl): S4–S5PubMedCrossRefGoogle Scholar
  130. 130.
    Tanaka K, Sugiura H, Uehara M, Sato H, Hashimoto-Tamaoki T, Furuyama J (1999) Association between mast cell chymase genotype and atopic eczema: comparison between patients with atopic eczema alone and those with atopic eczema and atopic respiratory disease. Clin Exp Allergy 29(6): 800–803PubMedCrossRefGoogle Scholar
  131. 131.
    Taylor B, Wadsworth J, Wadsworth M, Peckham C (1984) Changes in the reported prevalence of childhood eczema since the 1939–45 war. Lancet 2(8414): 1255–1257PubMedCrossRefGoogle Scholar
  132. 132.
    Taylor RS, Baadsgaard O, Hammerberg C, Cooper KD (1991) Hyperstimulatory CD1a+CDlb+CD36+ Langerhans cells are responsible for increased autologous T lymphocyte reactivity to lesional epidermal cells of patients with atopic dermatitis. J Immunol 147(11): 3794–3802PubMedGoogle Scholar
  133. 133.
    Tengvall LM, Johansson C, Scheynius A, Wahlgren C (2000) Positive atopy patch test reactions to Pityrosporum orbiculare in atopic dermatitis patients. Clin Exp Allergy 30(1): 122–131CrossRefGoogle Scholar
  134. 134.
    Tharp MD (1996) Chronic urticaria: pathophysiology and treatment approaches. J Allergy Clin Immunol 98 (6 Pt 3): S325–S330PubMedGoogle Scholar
  135. 135.
    Valenta R, Natter S, Seiberler S, Wichlas S, Maurer D, Hess M et al. (1998) Molecular characterization of an autoallergen, hom S 1, identified by serum IgE from atopic dermatitis patients. J Invest Dermatol 111(6): 1178–1183PubMedCrossRefGoogle Scholar
  136. 136.
    Valenta R, Natter S, Seiberler S, Roschanak M, Mothes N, Mahler V et al. (1999) Autoallergy: a pathogenetic factor in atopic dermatitis? Curr Probl Dermatol 28: 45–50PubMedCrossRefGoogle Scholar
  137. 137.
    Van Parijs L, Abbas AK (1998) Homeostasis and self-tolerance in the immune system: turning lymphocytes off. Science 280(5361): 243–248PubMedCrossRefGoogle Scholar
  138. 138.
    Wang B, Rieger A, Kilgus O, Ochiai K, Maurer D, Fodinger D et al. (1992) Epidermal Langerhans cells from nor-mal human skin bind monomeric IgE via Fc epsilon RI. J Exp Med 175(5): 1353–1365PubMedCrossRefGoogle Scholar
  139. 139.
    Wehner J, Neuber K (2001) Staphylococcus aureus enterotoxins induce histamine and leukotriene release in patients with atopic eczema. Br J Dermatol 145(2): 302–305PubMedCrossRefGoogle Scholar
  140. 140.
    Werfel T, Kapp A (1999) What do we know about the etiopathology of the intrinsic type of atopic dermatitis? Curr Probl Dermatol 28: 29–36PubMedCrossRefGoogle Scholar
  141. 141.
    Williams HC, Burney PG, Pembroke AC, Hay RJ (1996) Validation of the U.K. diagnostic criteria for atopic dermatitis in a population setting. U.K. Diagnostic Criteria for Atopic Dermatitis Working Party. Br J Dermatol 135(1): 12–17Google Scholar
  142. 142.
    Wistokat-Wulfing A, Schmidt P, Darsow U, Ring J, Kapp A, Werfel T (1999) Atopy patch test reactions are associated with T-lymphocyte-mediated allergen-specific immune responses in atopic dermatitis. Clin Exp Allergy 29(4): 513–521PubMedCrossRefGoogle Scholar
  143. 143.
    Wjst M (1999) Specific IgE — one gene fits all? German Asthma Genetics Group. Clin Exp Allergy 29(Suppl 4): 5–10PubMedGoogle Scholar
  144. 144.
    Wjst M, Fischer G, Immervoll T, Jung M, Saar K, Rueschendorf F et al. (1999) A genome-wide search for linkage to asthma. German Asthma Genetics Group. Genomics 58(1): 1–8Google Scholar
  145. 145.
    Wollenberg A, Bieber T (1998) Two populations of CDla+ epidermal dendritic cells expressing B7 molecules in human skin [letter; comment]. Br J Dermatol 138(2): 358–359PubMedCrossRefGoogle Scholar
  146. 146.
    Wollenberg A, Bieber T (2000) Atopic dermatitis: from the genes to skin lesions. Allergy 55(3): 205–213PubMedCrossRefGoogle Scholar
  147. 147.
    Wollenberg A, Wen S, Bieber T (1995) Langerhans cell phenotyping: a new tool for differential diagnosis of in-flammatory skin diseases [letter]. Lancet 346(8990): 1626–1627PubMedCrossRefGoogle Scholar
  148. 148.
    Wollenberg A, Kraft S, Hanau D, Bieber T (1996) 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 106(3): 446–453PubMedCrossRefGoogle Scholar
  149. 149.
    Wuthrich B (1999) What is atopy? Condition, disease or a syndrome? Curr Probl Dermatol 28: 1–8PubMedCrossRefGoogle Scholar
  150. 150.
    Yang D, Chertov O, Bykovskaia SN, Chen Q, Buffo MJ, Shogan J et al. (1999) Beta-defensins: linking innate and adaptive immunity through dendritic and T cell CCR6 [In Process Citation]. Science 286(5439): 525–528PubMedCrossRefGoogle Scholar
  151. 151.
    Yu G, Bjorksten B (1998) Polyunsaturated fatty acids in school children in relation to allergy and serum IgE levels. Pediatr Allergy Immunol 9(3): 133–138PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 2004

Authors and Affiliations

  • N. Novak
  • T. Bieber

There are no affiliations available

Personalised recommendations