Abstract
Atopic dermatitis is a chronic inflammatory skin disease associated with increasing prevalence, morbidity, and cost in developed Western countries. Frequently associated with respiratory allergy during adulthood, atopic dermatitis often represents the first phenotypic appearance of atopy in early childhood when the allergic ‘march’ starts and progressively moves toward food allergy, asthma, and rhinitis.
At present, a consistent body of evidence supports the view that atopic dermatitis may represent the skin compartmentalization of a systemic allergic inflammation. Lymphocytes infiltrating early lesional skin express a T helper (Th) 2 pattern of cytokine secretion (increased levels of interleukin [IL]-4 and/or IL-13 and decreased levels of interferon-γ) as well as the typical Th2-type chemokine receptor CCR4, specific to the thymus and activation-regulated chemokines. Keratinocytes from patients with atopic dermatitis produce thymic stromal lymphopoietin, a novel cytokine that supports the early lymphocyte development in mouse models, and activates dendritic cells involved in the pathogenesis of allergic diseases in humans. Increased levels of circulating hemopoietic precursor cells have been reported in atopic dermatitis, as in allergic asthma and rhinitis. Furthermore, the recognition of CD34+ hemopoietic precursor cells, and evidence for cellular differentiation/ maturational events occurring within atopic dermatitis skin lesion infiltrates, are consistent with the recent reinterpretation of the Th2/Th1 paradigm, where Th2 cells appear to belong to the early stages and Th1 to the ultimate stages of a linear, rather than divergent, pattern of lymphoid differentiation.
This more detailed understanding of the immunologic derangements contributing to the atopic dermatitis pathogenesis has led to growing interest in allergen-specific immunotherapy for the disease. Due to the complexity intrinsic to atopic dermatitis and the lack of consensus-based guidelines for standardized outcome measure, only eight studies are available in the literature for a qualitative evaluation of this treatment approach. Two of these studies were double blind and placebo controlled, and six were cohort studies. Immunotherapy was found to be effective in one controlled study and five observational reports. Uncertain results were provided by one low-powered, controlled study, and negative outcomes were raised by a unique study performed with oral immunotherapy, which is not an effective route of mucosal allergen administration.
Thus, more efficacy studies are required before immunotherapy could be recommended for the routine treatment of atopic dermatitis. Allergen-specific sublingual immunotherapy, given its excellent safety profile and ability to interfere with the systemic aspects of allergic inflammation, appears a good potential candidate for the pathogenetic treatment of the disease.
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References
Daniels J, Harper J. The epidemiology of atopic dermatitis. Hosp Med 2002; 63: 649–52
Oranje AP, de Waard-van der Spek FB. Atopic dermatitis: review 2000 to January 2001. Curr Opin Pediatr 2002; 14: 410–3
Bousquet J, Van Cauwenberge P, Khaltaev N, et al. Allergic rhinitis and its impact on asthma. J Allergy Clin Immunol 2001 Nov; 108 Suppl. 5: S147–334
Uchida T, Suto H, Ra C, et al. Preferential expression of T(h) 2-type chemokine and its receptor in atopic dermatitis. Int Immunol 2002; 14: 1431–8
Saurat JH. Eczema in primary immune-deficiencies: clues to the pathogenesis of atopic dermatitis with special reference to the Wiskott-Aldrich syndrome. Acta Derm Venereol 1985; 114: 125–8
Hanifin JM, Butler JM, Chan SC. Immunopharmacology of the atopic diseases. J Invest Dermatol 1985; 85: 161–4
Mastrandrea F, Minardi A, Coradduzza G, et al. Atopic dermatitis: towards a plausible pathogenetic model. Ital J Allergy Clin Immunol 1998; 8: 503–17
Mastrandrea F, Cadario G, Bedello PG, et al. Expression of T-lineage early developmental markers by cells establishing atopic dermatitis skin infiltrates. J Investig Allergol Clin Immunol 1998; 8: 359–64
Mastrandrea F, Cadario G, Nicotra MR, et al. Hemopoietic progenitor cells in atopic dermatitis skin lesions. J Investig Allergol Clin Immunol 1999; 9: 386–91
Robert C, Kupper TS. Inflammatory skin diseases, T cell and immune surveillance. N Engl J Med 1999; 341: 1817–28
Picker LJ, Michie SA, Rott LS, et al. A unique phenotype of skin-associated lymphocytes in humans: preferential expression of the HECA-452 epitope by benign and malignant T cells at cutaneous sites. Am J Pathol 1990; 136: 1053–68
Butcher EC, Picker LJ. Lymphocyte homing and homeostasis. Science 1996; 272: 60–6
Galy AH, Cen D, Travis M, et al. Delineation of T-progenitor cell activity within the CD34+ compartment of adult bone marrow. Blood 1995; 85: 2770–8
Galy A, Morel F, Hill B, et al. Hematopoietic progenitors cells of lymphocytes and dendritic cells. J Immunother 1998; 21: 132–41
Cerasoli DM, Kelsoe G, Sarzotti M. CD4+Thy1- thymocytes with a Th-type 2 cytokine response. Int Immunol 2001; 13: 75–83
Kikkawa E, Yamashita M, Kimura M, et al. T(h)1/T(h)2 cell differentiation of developing CD4 single-positive thymocytes. Int Immunol 2002; 14: 943–51
Soumelis V, Reche PA, Kanzler H, et al. Human epithelial cells trigger dendritic cell-mediated allergic inflammation by producing TSLP. Nat Immunol 2002; 3: 637–80
De Vries IJ, Langeveld-Wildschut EG, Van Reijsen FC, et al. Nonspecific T-cell homing during inflammation in atopic dermatitis: expression of cutaneous lymphocyte-associated antigen and integrin αEβ7 on skin-infiltrating T-cells. J Allergy Clin Immunol 1997; 100: 694–701
Mastrandrea F, Coradduzza G, Serio G, et al. T-cell receptor Vβ repertoire in mite-allergic subjects after sub-lingual immunotherapy. Invest Allergol Clin Immunol 2000; 10: 142–8
Kelso A. Th1 and Th2 subsets: paradigms lost? Immunol Today 1995; 16: 374–9
Allen JE, Maizels RM. Th1-Th2: reliable paradigm or dangerous dogma? Immunol Today 1997; 18: 387–92
Borish L, Rosenwasser L. TH1/TH2 lymphocytes: doubt some more. J Allergy Clin Immunol 1997; 99: 161–4
Noble A, Kemeny DM. Do functional subsets of leukocytes arise by divergent or linear differentiation? Immunology 2002; 106: 443–6
Codlin S, Soh C, Lee T, et al. Characterization of a palindromic enhancer element in the promoters of IL4, IL5, and IL13 cytokine genes. J Allergy Clin Immunol 2003; 111: 826–32
Mastrandrea F. Immunotherapy in atopic dermatitis. Expert Opin Investig Drugs 2001; 10: 49–63
Trinchieri G. Interleukin 12: a proinflammatory cytokine with immunoregulatory functions that bridge innate resistance and antigen specific adaptive immunity. Annu Rev Immunol 1995; 13: 251–76
McDyer JF, Wu CY, Seder RA. The regulation of IL12: Its role in infectious, autoimmune and allergic diseases. J Allergy Clin Immunol 1998; 102: 11–5
Tang ML, Kemp AS, Thoburn J, et al. Reduced interferon-gamma secretion in neonates and subsequent atopy. Lancet 1994; 344: 983–5
Warner JA, Miles EA, Jones AC, et al. Is deficiency of interferon gamma production by allergen-triggered cord blood a predictor of atopic eczema? Clin Exp Allergy 1994; 24: 423–30
Liao SY, Liao TN, Chiang BL, et al. Decreased production of IFN gamma and increased production of IL6 by cord blood mononuclear cells of newborns with a high risk of allergy. Clin Exp Allergy 1996; 26: 397–405
Loza MJ, Perussia B. Peripheral immature CD2-/low T cell development from type 2 to type 1 cytokine production. J Immunol 2002; 169: 3061–8
Smart JM, Tang ML, Kemp AS. Polyclonal and allergen-induced cytokine responses in children with elevated immunoglobulin E but no atopic diseases. Clin Exp Allergy 2002; 32: 1552–7
Loza MJ, Perussia B. Final steps of natural killer cell maturation: a model for type 1- type2 differentiation. Nat Immunol 2001; 2: 917–24
Loza MJ, Zamai L, Azzoni L, et al. Expression of type 1 (interferon gamma) and type 2 (interleukin-13, interleukin-5) cytokines at distinct stages of natural killer cell differentiation from progenitor cells. Blood 2002; 99: 1273–81
Gadue P, Stein PL. NK T cell precursors exhibit differential cytokine regulation and require Itk for efficient maturation. J Immunol 2002; 169: 2397–406
Klangsinsirikul P, Russell NH. Peripheral blood stem cell harvested from G-CSF-stimulated donors contain a skewed Th2 CD4 phenotype and a predominance of type 2 dendritic cells. Exp Hematol 2002; 30: 495–501
Mosca PJ, Hobeika AC, Colling K, et al. Multiple signals are required for maturation of human dendritic cells mobilized in vivo with Flt3 ligand. J Leukoc Biol 2002; 72: 546–53
Kaiser A, Bercovici N, Abastado JP, et al. Naive CD8+ T cell recruitment and proliferation are dependent on stage of dendritic cell maturation. Eur J Immunol 2003; 33: 162–71
Ujike A, Takeda K, Nakamura A, et al. Impaired dendritic cell maturation and increased T(H)2 responses in PIR-B(-/-)mice. Nat Immunol 2002; 3: 542–8
Aiba S, Manome H, Yoshino Y, et al. Alteration in the production of IL-10 and IL-12 and aberrant expression of CD23, CD83 and CD86 by monocytes or monocyte-derived dendritic cells from atopic dermatitis patients. Exp Dermatol 2003; 12: 86–95
Poussier PP, Julius M. Thymus independent T cell development and selection in the intestinal epithelium. Annu Rev Immunol 1994; 12: 521–53
Lundqvist C, Baranov V, Hammarstrom S, et al. Intra-epithelial lymphocytes: evidence for regional specialization and extrathymic T-cell maturation in the human gut epithelium. Int Immunol 1995 Sep; 7 (9): 1473–87
Page ST, Bogatzki LY, Hamerman JA, et al. Intestinal intraepithelial lymphocytes include precursors committed to the T cell receptor alpha beta lineage. Proc Natl Acad Sci U S A 1998; 95: 9459–64
Saito H, Kanamori Y, Takemori T, et al. Generation of intestinal T cells from progenitors residing in gut cryptopatches. Science 1998; 280: 275–8
Antica M, Scollay R. Development of T lymphocytes at extrathymic sites. J Immunol 1999; 163: 206–11
Oida T, Suzuki K, Nanno M, et al. Role of cryptopatches in early extrathymic maturation of intestinal intraepithelial T cells. J Immunol 2000; 164: 3616–26
Guy-Grand D, Vassalli P. Gut intraepithelial lymphocyte development. Curr Opin Immunol 2002; 14: 255–9
Guy-Grand D, Azogui O, Celli S, et al. Extrathymic T cell lymphopoiesis: ontogeny and contribution to gut intraepithelial lymphocytes in athymic and euthymic mice. J Exp Med 2003; 197: 333–41
Denburg JA, Telizyn S, Belda A, et al. Increased numbers of circulating basophil progenitors in atopic patients. J Allergy Clin Immunol 1985; 76: 446–72
Denburg JA, Dolovich J, Harnish D. Basophil mast cell and eosinophil growth and differentiation factors in human allergic disease. Clin Exp Allergy 1989; 19: 249–54
Denburg JA, Woolley M, Leber B, et al. Basophil and eosinophil differentiation in allergic reaction. J Allergy Clin Immunol 1994; 94: 1135–41
Cameron L, Christodoulopoulos P, Lavigne F, et al. Evidence for local eosinophil differentiation within allergic nasal mucosa: inhibition with soluble IL-5 receptor. J Immunol 2000; 164: 1538–45
Stirling RG, van Resen EL, Barnes PJ, et al. Interleukin-5 induces CD34(+) eosinophil progenitor mobilization and eosinophil CCR3 expression in asthma. Am J Respir Crit Care Med 2001; 164: 1403–9
Mwamtemi HH, Koike K, Kinoshita T, et al. An increase in circulating mast cell colony-forming cells in asthma. J Immunol 2001; 166: 4672–7
Kim YK, Uno M, Hamilos DL, et al. Immunolocalization of CD34 in nasal polyposis. Am J Respir Cell Mol Biol 1999; 20: 388–97
Cyr MM, Denburg JA. Systemic aspect of allergic disease: the role of the bone marrow. Curr Opin Immunol 2001; 13: 727–32
Mastrandrea F, Minardi A, Coradduzza G, et al. Emopoiesi leucocitaria tissutale nelle malattie allergiche: rapporti con il modello patogenetico. In: Arsieni A, Tursi A, Ventura MT, editors. La terapia delle malattie allergiche. Atti dell’ VIII Congresso della Sezione A. L. della Società Italiana di Allergologia e Immunologia Clinica: Bari, 1999: 43–9
Denburg JA, Dolovich J, Ohtoshi T, et al. The microenvironmental differentiation hypothesis of airway inflammation. Am J Rhinol 1990; 4: 29–32
Mastrandrea F, Coradduzza G, De Vita L, et al. CD34+ cells in peripheral blood of healthy human beings and allergic subjects: clue to acute and minimal persistent inflammation. Allergol Immunopathol (Madr) 2002; 30: 209–17
Dhabhar FS. Acute stress enhances while chronic stress suppresses skin immunity: the role of stress hormones and leukocyte trafficking. Ann N Y Acad Sci 2000; 917: 876–93
Marshall Jr GD, Agarwal SK. Stress, immune regulation, and immunity: applications for asthma. Allergy Asthma Proc 2000; 21: 241–6
Glaser R, MacCallum RC, Kaskowski BF, et al. Evidence for a shift in the Th-1 to Th-2 cytokine response associated with chronic stress and aging. J Gerontol A Biol Sci Med Sci 2001; 56: 477–82
Elenkov IJ, Chrousos GP. Stress hormones, proinflammatory and antiinflammatory cytokines, and autoimmunity. Ann N Y Acad Sci 2002; 966: 290–303
Brewer JA, Kanagawa O, Sleckman BP, et al. Thymocyte apoptosis induced by T cell activation is mediated by glucocorticoids in vivo. J Immunol 2002; 169: 1837–43
Strauss G, Osen W, Debatin KM. Induction of apoptosis and modulation of activation and effector functions in T cells by immunosuppressive drugs. Clin Exp Immunol 2002; 128: 255–66
Lill-Elghanian D, Schwartz K, King L, et al. Glucocorticoid-induced apoptosis in early B cells from human bone marrow. Exp Biol Med 2002; 227: 763–70
Siena S, Bregni M, Brando B, et al. Circulation of CD34+ hematopoietic stem cells in the peripheral blood of high-dose cyclophosphamide-treated patients: enhancement by intravenous recombinant human granulocyte-macrophage colony-stimulating factor. Blood 1989; 74: 1905–14
Ciprandi G, Buscaglia S, Pesce G, et al. Minimal persistent inflammation is present at mucosal level in patients with asymptomatic rhinitis and mite allergy. J Allergy Clin Immunol 1995; 96: 971–9
Ricca V, Landi M, Ferrero P, et al. Minimal persistent inflammation is also present in patients with seasonal allergic rhinitis. J Allergy Clin Immunol 2000; 105: 54–7
Ingordo V, D’Andria G, D’Andria C, et al. Results of atopy patch test with dust mite in adults with ‘intrinsic’ and ‘extrinsic’ atopic dermatitis. J Eur Acad Dermatol Venereol 2002; 16: 450–4
Corbo GM, Ferrante E, Macciocci B, et al. Bronchial hyper-responsiveness in atopic dermatitis. Allergy 1989; 44: 595–8
Salob SP, Laverty A, Atherton DJ. Bronchial hyper-responsiveness in children with atopic dermatitis. Pediatrics 1993; 91: 13–6
Majamaa H, Isolauri E. Evaluation of gut mucosal barrier: evidence for increased antigen transfer in children with atopic dermatitis. J Allergy Clin Immunol 1996; 97: 985–90
Cantani A. The growing genetic links and the early onset of atopic diseases in children stress the unique role of the atopic march: a meta-analysis. J Invest Allergol Clin Immunol 1999; 9: 314–20
Gustafsson D, Sjoberg O, Foucard T. Development of allergies and asthma in infants and young children with atopic dermatitis: a prospective follow-up to 7 years of age. Allergy 2000; 55: 240–5
Ohshima Y, Yamada A, Hiraoka M, et al. Early sensitization to house dust mite is a major risk factor for subsequent development of bronchial asthma in Japanese infants with atopic dermatitis: results of 4-year follow up study. Ann Allergy Asthma Immunol 2002; 89: 265–70
Eichenfield LF, Hanifin JM, Beck LA, et al. Atopic dermatitis and asthma: parallels in the evolution of treatment. Pediatrics 2003; 111: 608–16
Ramirez F. Glucocorticoids induce a Th2 response in vitro. Dev Immunol 1998; 6: 233–43
Williams CM, Colemann JW. Induced expression of mRNA for IL-5, IL-6, TNF-alpha, MIP-2 and IFN-gamma in immunologically activated rat peritoneal mast cells: inhibition by dexamethasone and cyclosporin A. Immunology 1995; 86: 244–9
Wu CY, Wang K, McDyer JF, et al. Prostaglandin E2 and dexamethasone inhibit IL-12 receptor expression and IL-12 responsiveness. J Immunol 1998; 161: 2723–30
Visser J, van Boxel-Dezaire A, Methorst D, et al. Differential regulation of interleukin-10 (IL-10) and IL-12 by glucocorticoids in vitro. Blood 1998; 91: 4255–64
Jabara HH, Ahern DJ, Vercelli D, et al. Hydrocortisone and IL-4 induce IgE isotype switching in human B cells. J Immunol 1991; 147: 1557–60
Zieg G, Lack G, Harbeck RJ, et al. In vivo effects of glucocorticoids on IgE production. J Allergy Clin Immunol 1994; 94: 222–30
Akdis CA, Blesken T, Akdis M, et al. Glucocorticoids inhibit human antigen-specific and enhance total IgE and IgG4 production due to differential effects on T and B cells in vitro. Eur J Immunol 1997; 27: 2351–7
Jabara HH, Brodeur SR, Geha RS. Glucocorticoids upregulate CD40 ligand expression and induce CD40L-dependent immunoglobulin isotype switching. J Clin Invest 2001; 107: 371–8
Barnes PJ. Corticosteroids, IgE, and atopy. J Clin Invest 2001; 107: 265–6
Chen SS, Stanescu G, Magalski AE, et al. Cyclosporin A is an adjuvant in murine IgE antibody responses. J Immunol 1989; 142: 4225–32
Weeler DJ, Robins A, Pritchard DI, et al. Potentiation of in vitro synthesis of human IgE by cyclosporin A (CsA). Clin Exp Immunol 1995; 102: 85–90
Nagai H, Hiyama H, Matsuo A, et al. FK-506 and cyclosporin A potentiate the IgE antibody production by contact sensitization with hapten in mice. J Pharmacol Exp Ther 1997; 283: 321–7
Kawamura N, Furuta H, Tame A, et al. Extremely high serum level of IgE during immunosuppressive therapy: paradoxical effect of cyclosporin A and tacrolimus. Int Arch Allergy Immunol 1997; 112: 422–4
Hanifin JM, Schneider LC, Leung DYM, et al. Recombinant interferon gamma therapy for atopic dermatitis. J Am Acad Dermatol 1993; 28: 189–97
Ellis CN, Stevens SR, Blok BK, et al. Interferon-gamma therapy reduces blood leukocyte levels in patients with atopic dermatitis: correlation with clinical improvement. Clin Immunol 1999; 92: 49–55
Jang IG, Yang JK, Lee HJ, et al. Clinical improvement and immunohistochemical findings in severe atopic dermatitis treated with interferon gamma. J Am Acad Dermatol 2000; 42: 1033–40
Isolauri E, Arvola T, Sutas Y, et al. Probiotics in the management of atopic eczema. Clin Exp Allergy 2000; 30: 1604–10
Pessi T, Sutas Y, Hurme M, et al. Interleukin-10 generation in atopic children following oral Lactobacillus rhamnosus GG. Clin Exp Allergy 2000; 30: 1804–8
Murch SH. Toll of allergy reduced by probiotics. Lancet 2001; 357: 1057–9
Kalliomaki M, Salminen S, Arvilommi H, et al. Probiotics in primary prevention of atopic disease: a randomised placebo-controlled trial. Lancet 2001; 357: 1076–9
Rosenfeldt V, Benfeldt E, Nielsen SD, et al. Effect of probiotic Lactobacillus strain in children with atopic dermatitis. J Allergy Clin Immunol 2003; 111: 389–95
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: 531–4
Wills-Karp M, Santeliz J, Karp CL. The germless theory of allergic diseases: revisiting the hygiene hypothesis. Nat Rev Immunol 2001; 1: 69–75
Yazdanbakhsh M, Kremsner PG, van Ree R. Allergy, parasites, and hygiene hypothesis. Science 2002; 296: 490–4
Braun-Fahrlander C. Does the ‘Hygiene Hypothesis’ provide an explanation for the relatively low prevalence of asthma in Bangladesh? Int J Epidemiol 2002; 31: 488–9
Weiss ST. Eat dirt: the hygiene hypothesis and allergic diseases. N Engl J Med 2002; 347: 930–1
Medzhitov R, Janeway Jr CA. Innate immunity: impact on the adaptive immune response. Curr Opin Immunol 1997; 9: 4–9
Anderson KV. Toll signals pathways in the innate immune response. Curr Opin Immunol 2000; 12: 13–9
Ghosh S, May MJ, Kopp EB. NF-kB and Rel proteins: evolutionarily conserved mediators of immune responses. Annu Rev Immunol 1998; 16: 225–60
May MJ, Ghosh S. Signal transduction through NF-kB. Immunol Today 1998; 19: 80–8
Brightbill HD, Libraty DH, Krutzik SR, et al. Host defense mechanisms triggered by microbial lipoproteins through toll-like receptors. Science 1999; 285: 732–6
Thoma-Uszynski S, Kiertscher SM, Ochoa MT, et al. Activation of toll-like receptor 2 on human dendritic cells triggers induction of IL-12 but not IL-10. J Immunol 2000; 165: 3804–10
Kubo S, Nakayama T, Matsuoka K, et al. Long term maintenance of IgE-mediated memory in mast cells in the absence of detectable serum IgE. J Immunol 2003; 170: 775–80
Mastrandrea F, Mottolese M, Maietta G, et al. The Dermatophagoides pteronyssinus native major antigen Der p II acts as polyclonal activator. Fund Clin Immunol 1995; 3: 131–8
Mastrandrea F, Serio G, Minelli M, et al. Specific sublingual immunotherapy in atopic dermatitis. Results of a 6-year follow-up of 35 consecutive patients. Allergol Immunopathol 2000; 28: 54–62
Noon L, Cantab BC. Prophylactic inoculation against hay fever. Lancet 1911; 1: 1572–3
Canonica GW, Passalacqua G. Noninjection routes for immunotherapy. J Allergy Clin Immunol 2003; 111: 437–48
Bousquet J, Lockey R, Malling H. Allergen immunotherapy: therapeutic vaccines for allergic diseases. A WHO position paper. Allergy 1998 Oct; 102: 558–62
Malling HJ, Abreu-Nogueira J, Alvarez-Cuesta E, et al. Local immunotherapy. Allergy 1998; 53: 933–44
Bousquet J, van Cauwenberge P, Khaltaev N, et al. Allergic rhinitis and its impact on asthma. J Allergy Clin Immunol 2001; 108 Suppl. 5: S147–334
Madonini E, Agostinis F, Barra R, et al. Long-term and preventive effects of sublingual allergen-specific immunotherapy: a retrospective, multicentric study. Int J Immunopathol Pharmacol 2003; 16: 73–9
Di Rienzo V, Marcucci F, Puccinelli P, et al. Long-lasting effect of sublingual immunotherapy in children with asthma due to house dust mite: a 10-year prospective study. Clin Exp Allergy 2003; 33: 206–10
Di Rienzo V, Pagani A, Parmiani S, et al. Post-marketing surveillance study on the safety of sublingual immunotherapy in pediatric patients. Allergy 1999; 54: 1110–3
Andre C, Vatrinet C, Galvain S, et al. Safety of sublingual-swallow immunotherapy in children and adults. Int Arch Allergy Immunol 2000; 121: 229–34
Madonini E, Agostini F, Barra R, et al. Safety and efficacy evaluation of sublingual allergen-specific immunotherapy a retrospective, multicenter study. Int J Immunopathol Pharmacol 2000; 13: 77–81
Lombardi C, Gargioni S, Melchiorre A, et al. Safety of sublingual immunotherapy with monomeric allergoid in adults: multicenter post-marketing surveillance study. Allergy 2001; 56: 989–92
Grosclaude M, Bouillot P, Alt R, et al. Safety of various dosage regimens during induction of sublingual immunotherapy: a preliminary study. Int Arch Allergy Immunol 2002; 129: 248–53
Marcucci F, Sensi L, Frati F, et al. Sublingual tryptase and ECP in children treated with grass pollen sublingual immunotherapy (SLIT): safety and immunologic implications. Allergy 2001; 56: 1091–5
Longley BJ, Tyrrel L, Lu S, et al. Chronically KIT-stimulated clonally-derived human mast cells show heterogeneity in different tissue microenvironments. J Invest Dermatol 1997; 108: 792–6
Peng Q, McEuen AR, Benyon RC, et al. The heterogeneity of mast cell tryptase from human lung and skin. Eur J Biochem 2003; 270: 270–83
Bagnasco M, Mariani M, Passalacqua G, et al. Absorption and distribution kinetics of the major Parietaria judaica allergen (Par j 1) administered by noninjectable routes in healthy human beings. J Allergy Clin Immunol 1997; 100: 122–9
Bagnasco M, Passalacqua G, Villa G. Parmacokinetiks of an allergen and a monomeric allergoid for oromucosal immunotherapy in allergic volunteers. Clin Exp Allergy 2001; 31: 54–60
Ino Y, Ando T, Haida M, et al. Characterization of the proteases in the crude mite extract. Int Arch Allergy Appl Immunol 1989; 89: 321–6
Hakkaart GA, Aalberse RC, van Ree R. Lack of lysozyme activity of natural and yeast-derived recombinant Der p 2. Int Arch Allergy Immunol 1997; 114: 202–4
Chua KY, Stewart GA, Thomas WR, et al. Sequence analysis of cDNA coding for a major house dust mite allergen, Der p 1. Homology with cysteine proteases. J Exp Med 1988; 167: 175–82
Mastrandrea F, Nicotra MR, De Vita L, et al. Mite antigens enhance ICAM-1 and induce VCAM-1 expression on Human Umbilical Vein Endothelium. Allergol Immunopathol 2003 Sep-Oct; 31 (5): 259–64
Stacey MA, Sun G, Vassalli G, et al. The allergen Der p1 induces NF-kappaB activation through interference with IkappaB alpha function in asthmatic bronchial epithelial cells. Biochem Biophys Res Commun 1997; 236: 522–6
Mitsuta K, Matsuse H, Fukushima C, et al. Production of TNF-alpha by peripheral blood mononuclear cells through activation of nuclear factor Kappa B by specific allergen stimulation in patients with atopic dermatitis. Allergy Asthma Proc 2003; 24: 19–26
Chen CL, Lee CT, Liu YC, et al. House dust mite Dermatophagoides farinae augments proinflammatory mediator production and accessory function of alveolar macrophages: implications for allergic sensitization and inflammation. J Immunol 2003; 170: 528–36
Collins T, Read MA, Neish AS, et al. Transcriptional regulation of endothelial cell adhesion molecules: NF-kappa B and cytokine-inducible enhancers. FASEB J 1995; 9: 899–909
Chen CC, Manning AM. Transcriptional regulation of endothelial cell adhesion molecules: a dominant role for NF-Kappa B. Agents Actions Suppl 1995; 47: 135–41
Franco L, Benedetti R, Ferek GA, et al. Priming or tolerization of the B- and Th2-dependent immune response by the oral administration of OVA-DNP is determined by the antigen dosage. Cell Immunol 1998; 190: 1–11
Chung Y, Chang SY, Kang CY. Kinetic analysis of oral tolerance: memory lymphocytes are refractory to oral tolerance. J Immunol 1999; 163: 3692–8
Shi HN, Grusby MJ, Nagler-Anderson C. Orally induced peripheral nonresponsiveness is maintained in the absence of functional Th1 or Th2 cells. J Immunol 1999; 162: 5143–8
Fanta C, Bohle B, Hirt W, et al. Systemic immunological changes induced by administration of grass pollen allergens via the oral mucosa during sublingual immunotherapy. Int Arch Allergy Immunol 1999; 120: 218–24
Marth T, Ring S, Schulte D, et al. Antigen-induced mucosal T cell activation is followed by Th1 T cell suppression in continuously fed ovalbumin TCR-transgenic mice. Eur J Immunol 2000; 30: 3478–86
Sato MN, Fusaro AE, Victor JR, et al. Oral tolerance induction in Dermatophagoides pteronyssinus-sensitized mice induces inhibition of IgE response and upregulation of TGF-beta secretion. J Interferon Cytokine Res 2001; 21: 827–33
Boonstra A, Asselin-Paturel C, Gilliet M, et al. Flexibility of mouse classical and plasmacytoid-derived dendritic cells in directing T helper type 1 and 2 cell development: dependency on antigen dose and differential toll-like receptor ligation. J Exp Med 2003; 197: 101–9
Izon D, Rudd K, DeMuth W, et al. A common pathway for dendritic and early B cell development. J Immunol 2001; 167: 1387–92
Glover MT, Atherton DJ. A double-blind controlled trial of hyposensitisation to Dermatophagoides pteronyssinus in children with atopic eczema. Clin Exp Allergy 1992; 22: 440–6
Leroy BP, Boden G, Lachapelle JM, et al. A novel therapy for atopic dermatitis with allergen-antibody complexes: a double-blind, placebo-controlled study. J Am Acad Dermatol 1993; 28: 232–9
Pacor ML, Biasi D, Maleknia T. The efficacy of long-term specific immunotherapy for Dermatophagoides pteronyssinus in patients with atopic dermatitis. Recenti Prog Med 1994; 85: 273–7
Trofimowicz A, Rzepcka E, Hofman J. Clinical effect of specific immunotherapy in children with atopic dermatitis. Rocz Akad Med Bialymist 1995; 40: 414–22
Galli E, Chini L, Nardi S, et al. Use of oral hyposensitization therapy to Dermatophagoides pteronyssinus in children with atopic dermatitis. Allergol Immunopathol 1994; 22: 18–22
Mosca M, Albani-Ronchetti G, Vignini MA, et al. La vaccinoterapia sub-linguale nella dermatite atopica. G. Ital Dermatol Venereol 1993; 128: 79–83
Zwacka G, Glaser S, Rieger B. Therapeutische erfahrungen mit Pangramin-SLIT im verleich zu einer subkutanen immunotherapie und zur symptomatischen medikamentosen behandlung bei kindern mit asthma bronchiale, rhinokonjunctivitis und atopischer dermatitis. Allergologie 1996; 19: 580–92
Petrova SIu, Berzhets VM, Albanova VI, et al. Immunotherapy in the complex treatment of patients with atopic dermatitis with sensitization to house dust mites. Zh Mikrobiol Epidemiol Immunobiol 2001; 1: 33–6
Boquete M, Carballada F, Exposito F, et al. Preventive immunotherapy. Allergol Immunopathol 2000; 28: 89–93
Pajno GB, Barberio G, De Luca F, et al. Prevention of new sensitisations in asthmatic children monosensitized to house dust mite by specific immunotherapy: a six-year follow-up study. Clin Exp Allergy 2001; 31: 1392–7
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Mastrandrea, F. The Potential Role of Allergen-Specific Sublingual Immunotherapy in Atopic Dermatitis. Am J Clin Dermatol 5, 281–294 (2004). https://doi.org/10.2165/00128071-200405050-00001
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DOI: https://doi.org/10.2165/00128071-200405050-00001