Atopik dermatit patogenezi

Atopik dermatit (AD), klinikte sık karşılaşılan ve tekrarlayan kronik inflamatuvar bir cilt hastalığıdır. AD özellikle endüstriyelleşmiş ülkelerin sorunudur. Ancak son yıllarda ülkemizde de AD sıklığı artmaktadır. Atopik dermatit’in patogenezinde birçok faktörün üzerinde durulmaktadır. Ancak etyolojisi tam olarak bilinmemekle beraber genetik olarak eğilimli kişilerde bir grup tetikleyici faktörlerin etkisiyle T hücre fonksiyonlarındaki immünoljik sapma sonucu oluşmaktadır. Bu makalede atopik dermatitin etyopatogenezi ile ilgili güncel literatür bilgiler gözden geçirilmiştir.

The pathogenesis of atopic dermatitis

Atopic dermatitis (AD) is a very common and recurrent chronic an inflammatory skin diseases. Atopic dermatitis is a health problem for especially industrialized countries. However in recent years AD has been more common in our country. Multiple factors play role in the pathogenesis of AD. Although the etiology is not clear, it may be related to immunologically deviated T cell functions with precipitating factors in genetically predisposed people. In present article, we reviewed actual literature on the etiopathogenesis of AD.

PDF

___

1. Kristal L, Klein PA. Atopic dermatitis in infants and children. Pediatr Clin North Am 2000;47:877-95.
2. Wıllıam HC. Atopic Dermatitis. N Engl J Med 2005;352:231-5.
3. Horii KA, Simon SD, Liu DY, Sharma V. Atopic dermatitis in children in the United States, 1997-2004: visit trends, patient and provider characteristics, and prescribing patterns. Pediatrics 2007;120:527-34.
4. Arıkan Ç, Nerin N Bahçeçiler. Atopik dermatit. Allerji Astım Dergisi 2001;3:22-4.
5. Illi S, von Mutius E, Lau S, et al. The natural course of atopic dermatitis from birth to age 7 years and the association with asthma. J Allergy Clin Immunol 2004;113:925-31.
6. Zutavern A, Hirsch T, Leupold, et al. Atopic dermatitis, extrinsic atopic dermatitis and he hygiene hypothesis: results from a cross-sectional study. Clin Exp Allergy 2005;35:1301-8.
7. Harmanyeri Y. Atopik dermatit etyopatogenezi. 1.Ulusal Pediatrik Dermatoloji Günleri Program ve Metin Kitabı, İstanbul, Turgut Yayıncılık, 2004;178-81.
8. Leung DY, Tharp M, Boguniewicz M. Atopic dermatitis. In: Fitzpatrick TB, Eisen AZ, Wolf K, Freedberg IM, Austen KF. Fitzpatrick's Dermatology In General Medicine 5th ed Newyork, Mc Graw Hill, 1999;1464-80.
9. Bieber T. The pro- and anti-inflammatory properties of human antigen-presenting cells expressing the high affinity receptor for IgE (Fc epsilon RI). Immunobiology 2007;212:499-503.
10. Forrest S, Dunn K, Eliott K et al. Identifying genes predisposing to atopic eczema. J Allergy Clin Immunol 1999;104:1066-70.
11. Haagerup A, Bjerke T, Schiotz PO, et al. Atopic dermatitis: a total genome scan for susceptibility genes. Acta Derm Venereol 2004;84:346-52.
12. Palmer LJ, Cardon LR. Shaking the tree: mapping complex disease genes with linkage disequilibrium. Lancet 2005;366:1223-34.
13. Lange J, Heinzmann A, Zehle C, Kopp M. CT genotype of promotor polymorphism C159T in the CD14 gene is associated with lower prevalence of atopic dermatitis and lower IL-13 production. Pediatr Allergy Immunol 2005;16:456-7.
14. Van Leent E, Bos JD. Atopic dermatitis. In: Katsambas A, Lotti TM, eds. European Handbook of Dermatological Treatments. Berlin: Springer-Verlag, 2003: 54–62.
15. Larsen FS. Genetic epidemiology of atopic eczema. In: Williams HC, ed. Atopic Dermatitis. Cambridge: Cambridge University Pres, 2000:113-24.
16. Proksch E, Jensen JM, Elias PM. Skin lipids and epidermal differentiation in atopic dermatitis. Clin Dermatol 2003;21:134-44.
17. Schmid-Wendtner MH, Korting HC. The pH of the skin surface and its impact on the barrier function. Skin Pharmacol Physiol 2006;19:296-302.
18. Hansson L, Bäckman A, Ny A, et al. Epidermal overexpression of stratum corneum chymotryptic enzyme in mice a model for chronic itchy dermatitis. J Invest Dermatol 2002;118:444-9.
19. Seguchi T, Cui CY, Kusuda S, et al. Decreased ex pression of filaggrin in atopic skin. Arch Dermatol Res 1996;288:442-6.
20. Scott IR, Harding CR. Filaggrin breakdown to water binding compounds during development of the rat stratum corneum is controlled by the water activity of the environment. Dev Biol 1986;115:84-92.
21. Cookson W. The immunogenetics of asthma and eczema: a new focus on the epithelium. Nat Rev Immunol 2004;4:978-88.
22. Braff MH, Gallo RL. Antimicrobial peptides: an essential component of the skin defensive barrier. Curr Top Microbiol immunol 2006;306:91-110.
23. Kerschenlohr K, Darsow U, Burgdorf WH, Ring J, Wollenberg A. Lessons from atopy patch testing in atopic dermatitis. curr Allergy Asthma Rep 2004;4:285-9.
24. Novak N, Bieber T. Allergic and non allergic forms of atopic diseases. J Allergy Clin Immunol 2003;112:252-62.
25. Leung DYM. Atopic dermatitis: The skin as a window into the pathogenesis of chronic allergic disease. J Allergy Clin İmmuol 1995;96:302-18.
26. Yuksel H, Can D, Reisli I, et al. Characteristics and prognosis of childhood atopic dermatitis: A multicenter study in Turkey Int Arch Allergy Immunol 2010;152:362-67.
27. Shreffler WG, Castro RR, Kucuk ZY, et al. The major glycoprotein allergen from arachis hypogaea, Ara h 1, is a ligand of dendritic cell-specific ICAM-grabbing nonintegrin and acts as a Th2 adjuvant in vitro. J İmmunol 2006;177:3677-85.
28. Kupper TS, Fuhlbrigge RC. Immune surveillance in the skin: mechanisms and clinical consequences. Nat Rev Immunol 2004;4:211-22.
29. Soumelis V, Reche PA, Kanzler H, et al. Human epithelial cells trigger dendritic cell mediated allergic inflammation by producing TSLP. Nat Immunol 2002;3:673-80.
30. Denburg JA, van Eeden SF. Bone marrow progenitors in inflammation and repair: new vistas in respiratory biology and pathophysiology. Eur Respir J 2006;27:441-5.
31. Hallstrand TS, Sprenger JD, Agosti JM, et al. Long-term acquisition of allergen-specific IgE and asthma following allogeneic bone marrow transplantation from allergic donors. Blood 2004;104:3086-90.
32. Novak N, Bieber T. The role of dendritic cell subtypes in the pathophysiology of atopic dermatitis. J Am Acad Dermatol 2005;53: 2:171-6.
33. Wollenberg A, Wagner M, Gunther S, et al. Plasmacytoid dendritic cells: a new cutaneous dendritic cell subset with distinct role in inflammatory skin diseases. J Invest Dermatol 2002;119:1096-102.
34. Wollenberg A, Kraft S, Hanau D, Bierber 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;106:446-53.
35. Novak N, Valenta R, Bohle B, et al. FcepsilonRI engagement of Langerhans cell-like dendritic cells and inflammatory dendritic epidermal cell-like dendritic cells induces chemotactic signals and different T-cell pHenotypes in vitro. J Allergy Clinical İmmunol 2004;113:949-57.
36. Kerschenlohr K, Decard S, Przybilla B, Wollenberg A. Atopy patch test reactions show a rapid influx of inflammatory dendritic epidermal cells in patients with extrinsic atopic dermatitis and patients with intrinsic atopic dermatitis. J Allergy Clin Immunol 2003;111:869-74.
37. Grewe M, Walther S, Gyufko K, et al. Analysis of the cytokine pattern expressed in situ in inhalant allergen patch test reactions of atopic dermatitis patients. J Invest Dermatol 1995;105:407-10.
38. Mihm MC Jr, Soter NA, Dvorak HF, Austen KF. The structure of normal skin and the morpHology of atopic eczema. J Invest Dermatol 1976;67:305-12.
39. Homey B, Steinhoff M, Ruzicka T, Leung DY. Cytokines and chemokines orchestrate atopic skin inflammation. J Allergy Clin Immunol 2006;118:178-89.
40. Gombert M, Dieu-Nosjean MC, Winterberg F, et al. CCL1-CCR8 interactions: an axis mediating the recruitment of T cells and Langerhans-type dendritic cells to sites of atopic skin inflammation. J Immunol 2005;174:5082-91.
41. Gilliet M, Soumelis V, Watanabe N, et al. Human dendritic cells activated by TSLP and CD40L induce proallergic cytotoxic T cells. J Exp Med 2003;197:1059-63.
42. Trautmann A, Akdis M, Kleemann D. T cell-mediated Fas-induced keratinocyte apoptosis plays a key pathogenetic role in eczematous dermatitis. J Clin Invest 2000;106:25-35.
43. Ou LS, Goleva E, Hall C, Leung DY. T regulatory cells in atopic dermatitis and subversion of their activity by superantigens. J Allergy Clin Immunol 2004;113:756-63.
44. Verhagen J, Akdis M, Traidl-Hoffmann C, et al. Absence of T-regulatory cell expression and function in atopic der-matitis skin. J Allergy Clin Immunol 2006;117:176-83.
45. Till S, Durham S, Dickason R et al. IL-13 production by allergen-stimulated T cells is increased in allergic disease and associated with IL-5 but not IFN-gama expression. Immunology 1997;91:53-7.
46. Cardona ID, Cho SH, Leung DY. Role of bacterial superantigens in atopic dermatitis: implications for future therapeutic strategies. Am J Clin Dermatol 2006;7:273-9.
47. Bunikowski R, Mielke M, Skarabis H, et al. 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 1999;103:119-24.
48. Diepgen TL. Long-term treatment with cetirizine of infants with atopic dermatitis: a multi-country, double-blind, randomized, placebo-controlled trial (the ETAC trial) over 18 months. Pediatr Allergy Immunol 2002;13:278-86.
49. Sonkoly E, Muller A, Lauerma AI, et al. IL-31: a new link between T cells and pruritus in atopic skin inflammation. J Allergy Clin Immunol 2006;117:411-417.
50. Neis MM, Peters B, Dreuw A, et al. Enhanced expression levels of IL-31 correlate with IL-4 and IL-13 in atopic and allergic contact dermatitis. J Allergy Clin Immunol 2006;118:930-7.
51. Aichberger KJ, Mittermann I, Reininger R, et al. Hom s 4, an IgE-reactive autoantigen belonging to a new subfamily of calcium-binding proteins, can induce Th cell type 1-mediated autoreactivity. J Immunol 2005;175:1286-94.
52. Schmid-Grendelmeier P, Flückiger S, Disch R, et al. IgE-mediated and T cell-mediated autoimmunity against manganese superoxide dismutase in atopic dermatitis. J Allergy Clin Immunol 2005;115:1068-75.
53. Mothes N, Niggemann B, Jenneck C et al. The cradle of IgE autoreactivity in atopic eczema lies in early infancy. J Allergy Clin Immunol 2005;116:706-9.
54. Johansson C, Sandström MH, Bartosik J, et al. Atopy patch test reactions to Malassezia allergens differentiate subgroups of Atopik Dermatitis patients. British Journal of Dermatology 2003;148:479-88.