Atopik Dermatit Güncel Patofizyolojisi

Abstract

Atopik dermatit (AD); en sık görülen kronik, kaşıntılı, inflamatuar deri hastalığıdır. Genetik ve çevresel faktörlerin etkisiyle deride meydana gelen hastalık, genellikle bebeklik döneminden itibaren bulgu vermeye başlar. Egzema , enfeksiyonlar, kaşıntı, kaşıntıya bağlı ortaya çıkan uyku bozuklukları hastaların hayat kalitesini doğrudan ve olumsuz etkilemektedir. AD tanı ve tedavisi eşlik eden/edebilecek komorbiditeler nedeniyle multidisipliner bir yaklaşımla ele alınmalıdır. Bu yazıda AD sini güncel çalışmalarla ve son verilerle ortaya koyarak tartışmayı amaçlıyoruz

Keywords

• atopik
• dermatit
• patofizyoloji

Current Pathophsiology of Atopic Dermatitis

Abstract

Atopic dermatitis (AD); is the most common chronic, itchy, inflammatory skin disease. The disease that occurs on the skin under the influence of genetic and environmental factors, usually begins to show symptoms from infancy. Eczema, itching, infections and sleep disorders caused by itching directly and negatively affect the quality of life of patients. Diagnosis and treatment of AD should be handled with a multidisciplinary approach. We aim to discuss the pathophysiology of AD by presenting current studies and latest data.

Keywords

• atopic
• dermatitis
• pathophysiology

References

1. Kim J, Kim BE, Leung DYM. Pathophysiology of atopic dermatitis: Clinical implications. Allergy Asthma Proc. 2019;40(2):84-92.
2. Langan SM, Irvine AD, Weidinger S. Atopic dermatitis. Lancet. 2020;396(10247):345-360.
3. Eichenfield LF, Stripling S, Fung S, Cha A, O’Brien A, Schachner LA. Recent developments and advances in atopic dermatitis: A focus on epidemiology, pathophysiology, and treatment in the pediatric setting. Paediatr Drugs. 2022;24(4):293-305.
4. Gerner T, Haugaard JH, Vestergaard C, Deleuran M, Jemec GB, Mortz CG, et al. Disease severity and trigger factors in Danish children with atopic dermatitis: a nationwide study. J Eur Acad Dermatol Venereol. 2021;35(4):948-957.
5. Tsakok T, Woolf R, Smith CH, Weidinger S, Flohr C. Atopic dermatitis: the skin barrier and beyond. Br J Dermatol. 2019;180(3):464-474.
6. Ständer S. Atopic dermatitis. N Engl J Med. 2021;384(12):1136-1143.
7. Irvine AD, McLean WH, Leung DY. Filaggrin mutations associated with skin and allergic diseases. N Engl J Med. 2011;365(14):1315-1327.
8. Eichenfield LF, Tom WL, Chamlin SL, Feldman SR, Hanifin JM, Simpson EL, et al. Guidelines of care for the management of atopic dermatitis: section 1. Diagnosis and assessment of atopic dermatitis. J Am Acad Dermatol. 2014;70(2):338-351.

9. Paternoster L, Standl M, Waage J, Baurecht H, Hotze M, Strachan DP, et al. Multi-ancestry genome-wide association study of 21,000 cases and 95,000 controls identifies new risk loci for atopic dermatitis. Nat Genet. 2015;47(12):1449-1456.
10. Drislane C, Irvine AD. The role of filaggrin in atopic dermatitis and allergic disease. Ann Allergy Asthma Immunol. 2020;124(1):36-43.
11. Guttman-Yassky E, Suárez-Fariñas M, Chiricozzi A, Nograles KE, Shemer A, Fuentes-Duculan J, et al. Broad defects in epidermal cornification in atopic dermatitis identified through genomic analysis. J Allergy Clin Immunol. 2009;124(6):1235-1244.
12. O’Regan GM, Sandilands A, McLean WHI, Irvine AD. Filaggrin in atopic dermatitis. J Allergy Clin Immunol. 2008;122(4):689- 693.
13. Silverberg JI, Hanifin J, Simpson EL. Climatic factors are associated with childhood eczema prevalence in the United States. J Invest Dermatol. 2013;133(7):1752-1759.
14. Vinding GR, Zarchi K, Ibler KS, Miller IM, Ellervik C, Jemec GB. Is adult atopic eczema more common than we think? - A population-based study in Danish adults. Acta Derm Venereol. 2014;94(4):480-482.
15. Flohr C, Yeo L. Atopic dermatitis and the hygiene hypothesis revisited. Curr Probl Dermatol. 2011; 41:1-34.
16. Garcovich S, Maurelli M, Gisondi P, Peris K, Yosipovitch G, Girolomoni G. Pruritus as a distinctive feature of type 2 inflammation. Vaccines (Basel). 2021;9(3):303.
17. Weidinger S, Beck LA, Bieber T, Kabashima K, Irvine AD. Atopic dermatitis. Nat Rev Dis Primers. 2018;4(1):1.
18. Honda T, Kabashima K. Reconciling innate and acquired immunity in atopic dermatitis. J Allergy Clin Immunol. 2020;145(4):1136-1137.
19. Brandner JM, Zorn-Kruppa M, Yoshida T, Moll I, Beck LA, De Benedetto A. Epidermal tight junctions in health and disease. Tissue Barriers. 2015;3(1-2): e974451. doi: 10.4161/21688370.2014.974451.
20. De Benedetto A, Rafaels NM, McGirt LY, Ivanov AI, Georas SN, Cheadle C, et al. Tight junction defects in patients with atopic dermatitis. J Allergy Clin Immunol. 2011;127(3):773-786.e1-7.
21. Kong HH, Oh J, Deming C, Conlan S, Grice EA, Beatson MA, et al. Temporal shifts in the skin microbiome associated with disease flares and treatment in children with atopic dermatitis. Genome Res. 2012;22(5):850-859.
22. Watanabe S, Narisawa Y, Arase S, Okamatsu H, Ikenaga T, Tajiri Y, et al. Differences in fecal microflora between patients with atopic dermatitis and healthy control subjects. J Allergy Clin Immunol. 2003;111(3):587-591.
23. Geoghegan JA, Irvine AD, Foster TJ. Staphylococcus aureus and atopic dermatitis: A complex and evolving relationship. Trends Microbiol. 2018;26(6):484-497.
24. Leung DY, Guttman-Yassky E. Deciphering the complexities of atopic dermatitis: shifting paradigms in treatment approaches. J Allergy Clin Immunol. 2014;134(4):769-779.
25. Oetjen LK, Mack MR, Feng J, Whelan TM, Niu H, Guo CJ et al. Sensory neurons co-opt classical immune signaling pathways to mediate chronic Itch. Cell. 2017;171(1):217-228.e13.
26. Simpson EL, Bieber T, Guttman-Yassky E, Beck LA, Blauvelt A, Cork MJ, et al. SOLO 1 and SOLO 2 investigators. Two phase 3 trials of dupilumab versus placebo in atopic dermatitis. N Engl J Med. 2016;375(24):2335-2348.
27. Ruzicka T, Hanifin JM, Furue M, Pulka G, Mlynarczyk I, Wollenberg A, et al. Anti-Interleukin-31 Receptor a Antibody for Atopic Dermatitis. N Engl J Med. 2017;376(9):826-835.
28. Rabenhorst A, Hartmann K. Interleukin-31: A novel diagnostic marker of allergic diseases. Curr Allergy Asthma Rep. 2014;14(4):423.
29. Kato A, Fujii E, Watanabe T, Takashima Y, Matsushita H, Furuhashi T, Morita A. Distribution of IL-31 and its receptor expressing cells in skin of atopic dermatitis. J Dermatol Sci. 2014;74(3):229-235.
30. Dubin C, Del Duca E, Guttman-Yassky E. The IL-4, IL-13 and IL-31 pathways in atopic dermatitis. Expert Rev Clin Immunol. 2021;17(8):835-852.
31. Hashimoto T, Yokozeki H, Karasuyama H, Satoh T. IL-31- generating network in atopic dermatitis comprising macrophages, basophils, thymic stromal lymphopoietin, and periostin. J Allergy Clin Immunol. 2023;151(3):737-746.e6.
32. Guttman-Yassky E, Krueger JG. Atopic dermatitis and psoriasis: two different immune diseases or one spectrum? Curr Opin Immunol. 2017; 48:68-73.
33. Akdis CA, Arkwright PD, Bruggen MC, Busse W, Gadina M, Guttman-Yassky E, et al. Type 2 immunity in the skin and lungs. Allergy. 2020;75(7):1582-1605.
34. Zhu J. T helper 2 (Th2) cell differentiation, type 2 innate lymphoid cell (ILC2) development and regulation of interleukin-4 (IL-4) and IL-13 production. Cytokine. 2015;75(1):14-24.
35. Guttman-Yassky E, Brunner PM, Neumann AU, Khattri S, Pavel AB, Malik K, et al. Efficacy and safety of fezakinumab (an IL22 monoclonal antibody) in adults with moderate-to-severe atopic dermatitis inadequately controlled by conventional treatments: A randomized, double-blind, phase 2a trial. J Am Acad Dermatol. 2018;78(5):872-881.e6.
36. Serra-Baldrich E, Santamaría-Babí LF, Francisco Silvestre J. Nemolizumab: An innovative biologic treatment to control interleukin 31, a key mediator in atopic dermatitis and prurigo nodularis. Actas Dermosifiliogr. 2022;113(7):674-684.
37. Kabashima K, Matsumura T, Komazaki H, Kawashima M. Nemolizumab-JP01 study group. Trial of nemolizumab and topical agents for atopic dermatitis with pruritus. N Engl J Med. 2020;383(2):141-150.
38. Guttman-Yassky E, Simpson EL, Reich K, Kabashima K, Igawa K, Suzuki T, et al. An anti-OX40 antibody to treat moderate-to-severe atopic dermatitis: a multicentre, double-blind, placebo-controlled phase 2b study. Lancet. 2023;401(10372):204-214.
39. Weidinger S, Bieber T, Cork MJ, Reich A, Wilson R, Quaratino S, et al. Safety and efficacy of amlitelimab, a fully human nondepleting, noncytotoxic anti-OX40 ligand monoclonal antibody, in atopic dermatitis: results of a phase IIa randomized placebo-controlled trial. Br J Dermatol. 2023;189(5):531-539.
40. Zane LT, Kircik L, Call R, Tschen E, Draelos ZD, Chanda S, et al. Crisaborole topical ointment, 2% in patients ages 2 to 17 years with atopic dermatitis: A phase 1b, open-label, maximal-use systemic exposure study. Pediatr Dermatol. 2016;33(4):380-387.
41. Draelos ZD, Stein Gold LF, Murrell DF, Hughes MH, Zane LT. Post hoc analyses of the effect of crisaborole topical ointment, 2% on atopic dermatitis: Associated pruritus from phase 1 and 2 clinical studies. J Drugs Dermatol. 2016;15(2):172-176.
42. Gooderham M, Kircik L, Zirwas M, Lee M, Kempers S, Draelos Z, et al. The safety and efficacy of roflumilast cream 0.15% and 0.05% in patients with atopic dermatitis: Randomized, double-blind, phase 2 proof of concept study. J Drugs Dermatol. 2023;22(2):139-147.
43. Saeki H, Baba N, Ito K, Yokota D, Tsubouchi H. Difamilast, a selective phosphodiesterase 4 inhibitor, ointment in paediatric patients with atopic dermatitis: a phase III randomized doubleblind, vehicle-controlled trial. Br J Dermatol. 2022;186(1):40-49.