Allergy Asthma Immunol Res.  2018 May;10(3):207-215. 10.4168/aair.2018.10.3.207.

Significance of Skin Barrier Dysfunction in Atopic Dermatitis

Affiliations
  • 1Department of Pediatrics, National Jewish Health, Denver, CO, USA. LeungD@NJHealth.org

Abstract

The epidermis contains epithelial cells, immune cells, and microbes which provides a physical and functional barrier to the protection of human skin. It plays critical roles in preventing environmental allergen penetration into the human body and responsing to microbial pathogens. Atopic dermatitis (AD) is the most common, complex chronic inflammatory skin disease. Skin barrier dysfunction is the initial step in the development of AD. Multiple factors, including immune dysregulation, filaggrin mutations, deficiency of antimicrobial peptides, and skin dysbiosis contribute to skin barrier defects. In the initial phase of AD, treatment with moisturizers improves skin barrier function and prevents the development of AD. With the progression of AD, effective topical and systemic therapies are needed to reduce immune pathway activation and general inflammation. Targeted microbiome therapy is also being developed to correct skin dysbiosis associated with AD. Improved identification and characterization of AD phenotypes and endotypes are required to optimize the precision medicine approach to AD.

Keyword

Atopic dermatitis; epidermal barrier; antimicrobial peptide; microbiome; moisturizer

MeSH Terms

Dermatitis, Atopic*
Dysbiosis
Epidermis
Epithelial Cells
Human Body
Humans
Inflammation
Microbiota
Peptides
Phenotype
Precision Medicine
Skin Diseases
Skin*
Peptides

Figure

  • Fig. 1 Impaired skin barrier enhances allergen penetration and activates the innate immune system. Multiple factors, including immune dysregulation, defects in terminal epithelial differentiation such as lack of filaggrin (FLG), deficiency of antimicrobial peptides (AMPs), altered composition of stratum corneum intercellular lipids, and altered skin microbiome cause skin barrier defects. Source: Czarnowicki et al. J Allergy Clin Immunol 2017;139:1723–34.

  • Fig. 2 Keratinocytes differentiated in the presence of IL-4 and IL-13 exhibit significantly reduced filaggrin. Primary human keratinocytes were cultured for 5 days in 0.06 or 1.3 mmol/L CaCl2 in the presence of IL-4 plus IL-13 or interferon (IFN)-gamma. *P<0.05; ***P<0.001 between the exposure groups. Source: Howell et al. J Allergy Clin Immunol 2007;120:150–5.


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Reference

1. Brunner PM, Guttman-Yassky E, Leung DY. The immunology of atopic dermatitis and its reversibility with broad-spectrum and targeted therapies. J Allergy Clin Immunol. 2017; 139:S65–S76. PMID: 28390479.
Article
2. Bieber T, D'Erme AM, Akdis CA, Traidl-Hoffmann C, Lauener R, Schäppi G, et al. Clinical phenotypes and endophenotypes of atopic dermatitis: where are we, and where should we go? J Allergy Clin Immunol. 2017; 139:S58–S64. PMID: 28390478.
Article
3. Leung DY, Guttman-Yassky E. Assessing the current treatment of atopic dermatitis: unmet needs. J Allergy Clin Immunol. 2017; 139:S47–S48. PMID: 28390476.
Article
4. Czarnowicki T, Krueger JG, Guttman-Yassky E. Novel concepts of prevention and treatment of atopic dermatitis through barrier and immune manipulations with implications for the atopic march. J Allergy Clin Immunol. 2017; 139:1723–1734. PMID: 28583445.
Article
5. Ahn K. The prevalence of atopic dermatitis in Korean children. Allergy Asthma Immunol Res. 2016; 8:1–2. PMID: 26540495.
Article
6. Beattie PE, Lewis-Jones MS. A comparative study of impairment of quality of life in children with skin disease and children with other chronic childhood diseases. Br J Dermatol. 2006; 155:145–151. PMID: 16792766.
Article
7. Rao DR, Sordillo JE, Kopel LS, Gaffin JM, Sheehan WJ, Hoffman E, et al. Association between allergic sensitization and exhaled nitric oxide in children in the School Inner-city Asthma Study. Ann Allergy Asthma Immunol. 2015; 114:256–257.e1. PMID: 25595887.
Article
8. Boguniewicz M, Abramovits W, Paller A, Whitaker-Worth DL, Prendergast M, Cheng JW, et al. A multiple-domain framework of clinical, economic, and patient-reported outcomes for evaluating benefits of intervention in atopic dermatitis. J Drugs Dermatol. 2007; 6:416–423. PMID: 17668539.
9. Mancini AJ, Kaulback K, Chamlin SL. The socioeconomic impact of atopic dermatitis in the United States: a systematic review. Pediatr Dermatol. 2008; 25:1–6.
Article
10. Leung DY, Guttman-Yassky E. Deciphering the complexities of atopic dermatitis: shifting paradigms in treatment approaches. J Allergy Clin Immunol. 2014; 134:769–779. PMID: 25282559.
Article
11. Mahdavinia M, Rasmussen HE, Engen P, Van den Berg JP, Davis E, Engen K, et al. Atopic dermatitis and food sensitization in South African toddlers: role of fiber and gut microbiota. Ann Allergy Asthma Immunol. 2017; 118:742–743.e3. PMID: 28583264.
12. Visitsunthorn N, Chatpornvorarux S, Pacharn P, Jirapongsananuruk O. Atopy patch test in children with atopic dermatitis. Ann Allergy Asthma Immunol. 2016; 117:668–673. PMID: 27979025.
Article
13. Roerdink EM, Flokstra-de Blok BM, Blok JL, Schuttelaar ML, Niggemann B, Werfel T, et al. Association of food allergy and atopic dermatitis exacerbations. Ann Allergy Asthma Immunol. 2016; 116:334–338. PMID: 26947239.
Article
14. Pyun BY. Natural history and risk factors of atopic dermatitis in children. Allergy Asthma Immunol Res. 2015; 7:101–105. PMID: 25729616.
Article
15. Zheng T, Yu J, Oh MH, Zhu Z. The atopic march: progression from atopic dermatitis to allergic rhinitis and asthma. Allergy Asthma Immunol Res. 2011; 3:67–73. PMID: 21461244.
Article
16. Nakatsuji T, Chen TH, Narala S, Chun KA, Two AM, Yun T, et al. Antimicrobials from human skin commensal bacteria protect against Staphylococcus aureus and are deficient in atopic dermatitis. Sci Transl Med. 2017; 9:eaah4680. PMID: 28228596.
Article
17. Smith AR, Knaysi G, Wilson JM, Wisniewski JA. The skin as a route of allergen exposure: part I. Immune components and mechanisms. Curr Allergy Asthma Rep. 2017; 17:6. PMID: 28185161.
Article
18. van Smeden J, Bouwstra JA. Stratum corneum lipids: their role for the skin barrier function in healthy subjects and atopic dermatitis patients. Curr Probl Dermatol. 2016; 49:8–26. PMID: 26844894.
Article
19. Busse D, Kudella P, Grüning NM, Gisselmann G, Ständer S, Luger T, et al. A synthetic sandalwood odorant induces wound-healing processes in human keratinocytes via the olfactory receptor OR2AT4. J Invest Dermatol. 2014; 134:2823–2832. PMID: 24999593.
Article
20. Erkoçoğlu M, Kocabaş CN. Role of IgA and IgM in severity of atopic dermatitis. Ann Allergy Asthma Immunol. 2015; 114:433.
Article
21. Kim BE, Leung DY. Epidermal barrier in atopic dermatitis. Allergy Asthma Immunol Res. 2012; 4:12–16. PMID: 22211165.
Article
22. Candi E, Schmidt R, Melino G. The cornified envelope: a model of cell death in the skin. Nat Rev Mol Cell Biol. 2005; 6:328–340. PMID: 15803139.
Article
23. Kalinin A, Marekov LN, Steinert PM. Assembly of the epidermal cornified cell envelope. J Cell Sci. 2001; 114:3069–3070. PMID: 11590230.
Article
24. Proksch E, Brandner JM, Jensen JM. The skin: an indispensable barrier. Exp Dermatol. 2008; 17:1063–1072. PMID: 19043850.
Article
25. Potten CS. Cell replacement in epidermis (keratopoiesis) via discrete units of proliferation. Int Rev Cytol. 1981; 69:271–318. PMID: 6163744.
Article
26. Furuse M, Hata M, Furuse K, Yoshida Y, Haratake A, Sugitani Y, et al. Claudin-based tight junctions are crucial for the mammalian epidermal barrier: a lesson from claudin-1-deficient mice. J Cell Biol. 2002; 156:1099–1111. PMID: 11889141.
27. Wan H, Winton HL, Soeller C, Taylor GW, Gruenert DC, Thompson PJ, et al. The transmembrane protein occludin of epithelial tight junctions is a functional target for serine peptidases from faecal pellets of Dermatophagoides pteronyssinus. Clin Exp Allergy. 2001; 31:279–294. PMID: 11251630.
28. Schneeberger EE, Lynch RD. Structure, function, and regulation of cellular tight junctions. Am J Physiol. 1992; 262:L647–L661. PMID: 1616050.
Article
29. Jonca N, Guerrin M, Hadjiolova K, Caubet C, Gallinaro H, Simon M, et al. Corneodesmosin, a component of epidermal corneocyte desmosomes, displays homophilic adhesive properties. J Biol Chem. 2002; 277:5024–5029. PMID: 11739386.
Article
30. Lai Y, Gallo RL. AMPed up immunity: how antimicrobial peptides have multiple roles in immune defense. Trends Immunol. 2009; 30:131–141. PMID: 19217824.
Article
31. Nakatsuji T, Gallo RL. Antimicrobial peptides: old molecules with new ideas. J Invest Dermatol. 2012; 132:887–895. PMID: 22158560.
Article
32. Howell MD, Gallo RL, Boguniewicz M, Jones JF, Wong C, Streib JE, et al. Cytokine milieu of atopic dermatitis skin subverts the innate immune response to vaccinia virus. Immunity. 2006; 24:341–348. PMID: 16546102.
Article
33. Niyonsaba F, Nagaoka I, Ogawa H, Okumura K. Multifunctional antimicrobial proteins and peptides: natural activators of immune systems. Curr Pharm Des. 2009; 15:2393–2413. PMID: 19601839.
Article
34. Kiatsurayanon C, Niyonsaba F, Smithrithee R, Akiyama T, Ushio H, Hara M, et al. Host defense (Antimicrobial) peptide, human β-defensin-3, improves the function of the epithelial tight-junction barrier in human keratinocytes. J Invest Dermatol. 2014; 134:2163–2173. PMID: 24633129.
Article
35. Hirsch T, Spielmann M, Zuhaili B, Fossum M, Metzig M, Koehler T, et al. Human beta-defensin-3 promotes wound healing in infected diabetic wounds. J Gene Med. 2009; 11:220–228. PMID: 19115333.
Article
36. 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; 127:773–786.e1-7. PMID: 21163515.
Article
37. Niyonsaba F, Ushio H, Nagaoka I, Okumura K, Ogawa H. The human beta-defensins (-1, -2, -3, -4) and cathelicidin LL-37 induce IL-18 secretion through p38 and ERK MAPK activation in primary human keratinocytes. J Immunol. 2005; 175:1776–1784. PMID: 16034119.
38. Niyonsaba F, Ushio H, Nakano N, Ng W, Sayama K, Hashimoto K, et al. Antimicrobial peptides human beta-defensins stimulate epidermal keratinocyte migration, proliferation and production of proinflammatory cytokines and chemokines. J Invest Dermatol. 2007; 127:594–604. PMID: 17068477.
39. Golec M. Cathelicidin LL-37: LPS-neutralizing, pleiotropic peptide. Ann Agric Environ Med. 2007; 14:1–4. PMID: 17655171.
40. Elias PM, Schmuth M. Abnormal skin barrier in the etiopathogenesis of atopic dermatitis. Curr Allergy Asthma Rep. 2009; 9:265–272. PMID: 19656472.
Article
41. Elias PM, Hatano Y, Williams ML. Basis for the barrier abnormality in atopic dermatitis: outside-inside-outside pathogenic mechanisms. J Allergy Clin Immunol. 2008; 121:1337–1343. PMID: 18329087.
Article
42. Kezic S, Jakasa I. Filaggrin and skin barrier function. Curr Probl Dermatol. 2016; 49:1–7. PMID: 26844893.
Article
43. Chng KR, Tay AS, Li C, Ng AH, Wang J, Suri BK, et al. Whole metagenome profiling reveals skin microbiome-dependent susceptibility to atopic dermatitis flare. Nat Microbiol. 2016; 1:16106. PMID: 27562258.
Article
44. Oh J, Conlan S, Polley EC, Segre JA, Kong HH. Shifts in human skin and nares microbiota of healthy children and adults. Genome Med. 2012; 4:77. PMID: 23050952.
Article
45. Oh J, Byrd AL, Deming C, Conlan S, Kong HH, NISC Comparative Sequencing Program, et al. Biogeography and individuality shape function in the human skin metagenome. Nature. 2014; 514:59–64. PMID: 25279917.
Article
46. Capone KA, Dowd SE, Stamatas GN, Nikolovski J. Diversity of the human skin microbiome early in life. J Invest Dermatol. 2011; 131:2026–2032. PMID: 21697884.
Article
47. Knaysi G, Smith AR, Wilson JM, Wisniewski JA. The skin as a route of allergen exposure: part II. Allergens and role of the microbiome and environmental exposures. Curr Allergy Asthma Rep. 2017; 17:7. PMID: 28210979.
Article
48. Nakamizo S, Egawa G, Honda T, Nakajima S, Belkaid Y, Kabashima K. Commensal bacteria and cutaneous immunity. Semin Immunopathol. 2015; 37:73–80. PMID: 25326105.
Article
49. Byrd AL, Deming C, Cassidy SK, Harrison OJ, Ng WI, Conlan S, et al. Staphylococcus aureus and Staphylococcus epidermidis strain diversity underlying pediatric atopic dermatitis. Sci Transl Med. 2017; 9:eaal4651. PMID: 28679656.
Article
50. Lee E, Lee SY, Kang MJ, Kim K, Won S, Kim BJ, et al. Clostridia in the gut and onset of atopic dermatitis via eosinophilic inflammation. Ann Allergy Asthma Immunol. 2016; 117:91–92.e1. PMID: 27179583.
Article
51. Tang KT, Ku KC, Chen DY, Lin CH, Tsuang BJ, Chen YH. Adult atopic dermatitis and exposure to air pollutants-a nationwide population-based study. Ann Allergy Asthma Immunol. 2017; 118:351–355. PMID: 28126434.
Article
52. Knox SM, Erwin EA, Mosser-Goldfarb JL, Scherzer R. Sensitization patterns among patients with atopic dermatitis evaluated in a large tertiary care pediatric center. Ann Allergy Asthma Immunol. 2017; 118:645–647. PMID: 28372896.
Article
53. Spergel JM, Mizoguchi E, Brewer JP, Martin TR, Bhan AK, Geha RS. Epicutaneous sensitization with protein antigen induces localized allergic dermatitis and hyperresponsiveness to methacholine after single exposure to aerosolized antigen in mice. J Clin Invest. 1998; 101:1614–1622. PMID: 9541491.
Article
54. Nikolovski J, Stamatas GN, Kollias N, Wiegand BC. Barrier function and water-holding and transport properties of infant stratum corneum are different from adult and continue to develop through the first year of life. J Invest Dermatol. 2008; 128:1728–1736. PMID: 18200056.
Article
55. Irvine AD, McLean WH, Leung DY. Filaggrin mutations associated with skin and allergic diseases. N Engl J Med. 2011; 365:1315–1327. PMID: 21991953.
Article
56. Flohr C, England K, Radulovic S, McLean WH, Campbel LE, Barker J, et al. Filaggrin loss-of-function mutations are associated with early-onset eczema, eczema severity and transepidermal water loss at 3 months of age. Br J Dermatol. 2010; 163:1333–1336. PMID: 21137118.
57. Kim BE, Bin L, Ye YM, Ramamoorthy P, Leung DY. IL-25 enhances HSV-1 replication by inhibiting filaggrin expression, and acts synergistically with Th2 cytokines to enhance HSV-1 replication. J Invest Dermatol. 2013; 133:2678–2685. PMID: 23657503.
Article
58. Hamid Q, Boguniewicz M, Leung DY. Differential in situ cytokine gene expression in acute versus chronic atopic dermatitis. J Clin Invest. 1994; 94:870–876. PMID: 8040343.
Article
59. Howell MD, Kim BE, Gao P, Grant AV, Boguniewicz M, Debenedetto A, et al. Cytokine modulation of atopic dermatitis filaggrin skin expression. J Allergy Clin Immunol. 2007; 120:150–155. PMID: 17512043.
Article
60. Jang H, Matsuda A, Jung K, Karasawa K, Matsuda K, Oida K, et al. Skin pH is the master switch of kallikrein 5-mediated skin barrier destruction in a murine atopic dermatitis model. J Invest Dermatol. 2016; 136:127–135. PMID: 26763432.
Article
61. Nicotera P, Melino G. Caspase-14 and epidermis maturation. Nat Cell Biol. 2007; 9:621–622. PMID: 17541415.
Article
62. Denecker G, Hoste E, Gilbert B, Hochepied T, Ovaere P, Lippens S, et al. Caspase-14 protects against epidermal UVB photodamage and water loss. Nat Cell Biol. 2007; 9:666–674. PMID: 17515931.
Article
63. Oyoshi MK, Murphy GF, Geha RS. Filaggrin-deficient mice exhibit TH17-dominated skin inflammation and permissiveness to epicutaneous sensitization with protein antigen. J Allergy Clin Immunol. 2009; 124:485–493. 493.e1PMID: 19665780.
Article
64. Man MQ, Hatano Y, Lee SH, Man M, Chang S, Feingold KR, et al. Characterization of a hapten-induced, murine model with multiple features of atopic dermatitis: structural, immunologic, and biochemical changes following single versus multiple oxazolone challenges. J Invest Dermatol. 2008; 128:79–86. PMID: 17671515.
Article
65. 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. PMID: 3516761.
Article
66. Gutowska-Owsiak D, Schaupp AL, Salimi M, Taylor S, Ogg GS. Interleukin-22 downregulates filaggrin expression and affects expression of profilaggrin processing enzymes. Br J Dermatol. 2011; 165:492–498. PMID: 21564072.
Article
67. Gutowska-Owsiak D, Schaupp AL, Salimi M, Selvakumar TA, McPherson T, Taylor S, et al. IL-17 downregulates filaggrin and affects keratinocyte expression of genes associated with cellular adhesion. Exp Dermatol. 2012; 21:104–110. PMID: 22229441.
Article
68. Kim BE, Leung DY, Boguniewicz M, Howell MD. Loricrin and involucrin expression is down-regulated by Th2 cytokines through STAT-6. Clin Immunol. 2008; 126:332–337. PMID: 18166499.
Article
69. Rodríguez E, Baurecht H, Herberich E, Wagenpfeil S, Brown SJ, Cordell HJ, et al. Meta-analysis of filaggrin polymorphisms in eczema and asthma: robust risk factors in atopic disease. J Allergy Clin Immunol. 2009; 123:1361–1370.e7. PMID: 19501237.
Article
70. Stemmler S, Parwez Q, Petrasch-Parwez E, Epplen JT, Hoffjan S. Two common loss-of-function mutations within the filaggrin gene predispose for early onset of atopic dermatitis. J Invest Dermatol. 2007; 127:722–724. PMID: 17008875.
Article
71. Wan J, Mitra N, Hoffstad OJ, Margolis DJ. Influence of FLG mutations and TSLP polymorphisms on atopic dermatitis onset age. Ann Allergy Asthma Immunol. 2017; 118:737–738.e1. PMID: 28479194.
Article
72. Yu HS, Kang MJ, Jung YH, Kim HY, Seo JH, Kim YJ, et al. Mutations in the filaggrin are predisposing factor in Korean children with atopic dermatitis. Allergy Asthma Immunol Res. 2013; 5:211–215. PMID: 23814674.
Article
73. O'Regan GM, Sandilands A, McLean WH, Irvine AD. Filaggrin in atopic dermatitis. J Allergy Clin Immunol. 2008; 122:689–693. PMID: 18774165.
74. Henderson J, Northstone K, Lee SP, Liao H, Zhao Y, Pembrey M, et al. The burden of disease associated with filaggrin mutations: a population-based, longitudinal birth cohort study. J Allergy Clin Immunol. 2008; 121:872–877.e9. PMID: 18325573.
Article
75. Gruber R, Börnchen C, Rose K, Daubmann A, Volksdorf T, Wladykowski E, et al. Diverse regulation of claudin-1 and claudin-4 in atopic dermatitis. Am J Pathol. 2015; 185:2777–2789. PMID: 26319240.
Article
76. Leclerc EA, Huchenq A, Mattiuzzo NR, Metzger D, Chambon P, Ghyselinck NB, et al. Corneodesmosin gene ablation induces lethal skin-barrier disruption and hair-follicle degeneration related to desmosome dysfunction. J Cell Sci. 2009; 122:2699–2709. PMID: 19596793.
Article
77. Lee UH, Kim BE, Kim DJ, Cho YG, Ye YM, Leung DY. Atopic dermatitis is associated with reduced corneodesmosin expression: role of cytokine modulation and effects on viral penetration. Br J Dermatol. 2017; 176:537–540.
Article
78. Nomura I, Goleva E, Howell MD, Hamid QA, Ong PY, Hall CF, et al. Cytokine milieu of atopic dermatitis, as compared to psoriasis, skin prevents induction of innate immune response genes. J Immunol. 2003; 171:3262–3269. PMID: 12960356.
Article
79. Ong PY, Ohtake T, Brandt C, Strickland I, Boguniewicz M, Ganz T, et al. Endogenous antimicrobial peptides and skin infections in atopic dermatitis. N Engl J Med. 2002; 347:1151–1160. PMID: 12374875.
Article
80. Hata TR, Kotol P, Boguniewicz M, Taylor P, Paik A, Jackson M, et al. History of eczema herpeticum is associated with the inability to induce human β-defensin (HBD)-2, HBD-3 and cathelicidin in the skin of patients with atopic dermatitis. Br J Dermatol. 2010; 163:659–661. PMID: 20545685.
Article
81. Brauweiler AM, Goleva E, Leung DY. Th2 cytokines increase Staphylococcus aureus alpha toxin-induced keratinocyte death through the signal transducer and activator of transcription 6 (STAT6). J Invest Dermatol. 2014; 134:2114–2121. PMID: 24468745.
Article
82. Son ED, Kim HJ, Park T, Shin K, Bae IH, Lim KM, et al. Staphylococcus aureus inhibits terminal differentiation of normal human keratinocytes by stimulating interleukin-6 secretion. J Dermatol Sci. 2014; 74:64–71. PMID: 24398033.
Article
83. Brauweiler AM, Hall CF, Goleva E, Leung DY. Staphylococcus aureus lipoteichoic acid inhibits keratinocyte differentiation through a p63-mediated pathway. J Invest Dermatol. 2017; 137:2030–2033. PMID: 28528912.
Article
84. Howell MD, Wollenberg A, Gallo RL, Flaig M, Streib JE, Wong C, et al. Cathelicidin deficiency predisposes to eczema herpeticum. J Allergy Clin Immunol. 2006; 117:836–841. PMID: 16630942.
Article
85. Leung DY. New insights into atopic dermatitis: role of skin barrier and immune dysregulation. Allergol Int. 2013; 62:151–161. PMID: 23712284.
Article
86. Danso M, Boiten W, van Drongelen V, Gmelig Meijling K, Gooris G, El Ghalbzouri A, et al. Altered expression of epidermal lipid biosynthesis enzymes in atopic dermatitis skin is accompanied by changes in stratum corneum lipid composition. J Dermatol Sci. 2017; 88:57–66. PMID: 28571749.
Article
87. Kim D, Lee NR, Park SY, Jun M, Lee K, Kim S, et al. As in atopic dermatitis, nonlesional skin in allergic contact dermatitis displays abnormalities in barrier function and ceramide content. J Invest Dermatol. 2017; 137:748–750. PMID: 27826010.
88. Ito S, Ishikawa J, Naoe A, Yoshida H, Hachiya A, Fujimura T, et al. Ceramide synthase 4 is highly expressed in involved skin of patients with atopic dermatitis. J Eur Acad Dermatol Venereol. 2017; 31:135–141. PMID: 27358008.
Article
89. Li S, Villarreal M, Stewart S, Choi J, Ganguli-Indra G, Babineau DC, et al. Altered composition of epidermal lipids correlates with Staphylococcus aureus colonization status in atopic dermatitis. Br J Dermatol. 2017; 177:e125–e127. PMID: 28244066.
Article
90. Oh MJ, Nam JJ, Lee EO, Kim JW, Park CS. A synthetic C16 omegahydroxyphytoceramide improves skin barrier functions from diversely perturbed epidermal conditions. Arch Dermatol Res. 2016; 308:563–574. PMID: 27402316.
Article
91. Lowe AJ, Su JC, Allen KJ, Abramson MJ, Cranswick N, Robertson CF, et al. A randomized trial of a barrier lipid replacement strategy for the prevention of atopic dermatitis and allergic sensitization: the PEBBLES pilot study. Br J Dermatol. 2017; Forthcoming.
92. Eyerich K, Eyerich S, Biedermann T. The multi-modal immune pathogenesis of atopic eczema. Trends Immunol. 2015; 36:788–801. PMID: 26602548.
Article
93. Kobayashi T, Glatz M, Horiuchi K, Kawasaki H, Akiyama H, Kaplan DH, et al. Dysbiosis and Staphylococcus aureus colonization drives inflammation in atopic dermatitis. Immunity. 2015; 42:756–766. PMID: 25902485.
Article
94. Naik S, Bouladoux N, Wilhelm C, Molloy MJ, Salcedo R, Kastenmuller W, et al. Compartmentalized control of skin immunity by resident commensals. Science. 2012; 337:1115–1119. PMID: 22837383.
Article
95. Zeeuwen PL, Boekhorst J, van den Bogaard EH, de Koning HD, van de Kerkhof PM, Saulnier DM, et al. Microbiome dynamics of human epidermis following skin barrier disruption. Genome Biol. 2012; 13:R101. PMID: 23153041.
Article
96. Wollina U. Microbiome in atopic dermatitis. Clin Cosmet Investig Dermatol. 2017; 10:51–56.
Article
97. Kennedy EA, Connolly J, Hourihane JO, Fallon PG, McLean WH, Murray D, et al. Skin microbiome before development of atopic dermatitis: early colonization with commensal staphylococci at 2 months is associated with a lower risk of atopic dermatitis at 1 year. J Allergy Clin Immunol. 2017; 139:166–172. PMID: 27609659.
98. Ali SM, Yosipovitch G. Skin pH: from basic science to basic skin care. Acta Derm Venereol. 2013; 93:261–267. PMID: 23322028.
Article
99. Rippke F, Schreiner V, Schwanitz HJ. The acidic milieu of the horny layer: new findings on the physiology and pathophysiology of skin pH. Am J Clin Dermatol. 2002; 3:261–272. PMID: 12010071.
100. Brauweiler AM, Goleva E, Leung DY. Interferon-γ protects from staphylococcal alpha toxin-induced keratinocyte death through apolipoprotein L1. J Invest Dermatol. 2016; 136:658–664. PMID: 27015454.
Article
101. Czarnowicki T, Malajian D, Khattri S, Correa da Rosa J, Dutt R, Finney R, et al. Petrolatum: barrier repair and antimicrobial responses underlying this “inert” moisturizer. J Allergy Clin Immunol. 2016; 137:1091–1102.e7. PMID: 26431582.
Article
102. Lee HJ, Lee SH. Epidermal permeability barrier defects and barrier repair therapy in atopic dermatitis. Allergy Asthma Immunol Res. 2014; 6:276–287. PMID: 24991450.
Article
103. Eichenfield LF, Ahluwalia J, Waldman A, Borok J, Udkoff J, Boguniewicz M. Current guidelines for the evaluation and management of atopic dermatitis: a comparison of the Joint Task Force Practice Parameter and American Academy of Dermatology guidelines. J Allergy Clin Immunol. 2017; 139:S49–S57. PMID: 28390477.
104. Simpson EL, Berry TM, Brown PA, Hanifin JM. A pilot study of emollient therapy for the primary prevention of atopic dermatitis. J Am Acad Dermatol. 2010; 63:587–593. PMID: 20692725.
Article
105. Simpson EL, Chalmers JR, Hanifin JM, Thomas KS, Cork MJ, McLean WH, et al. Emollient enhancement of the skin barrier from birth offers effective atopic dermatitis prevention. J Allergy Clin Immunol. 2014; 134:818–823. PMID: 25282563.
Article
106. Cardona ID, Stillman L, Jain N. Does bathing frequency matter in pediatric atopic dermatitis? Ann Allergy Asthma Immunol. 2016; 117:9–13. PMID: 27371966.
Article
107. Pabst RC, Starr KP, Qaiyumi S, Schwalbe RS, Gewolb IH. The effect of application of aquaphor on skin condition, fluid requirements, and bacterial colonization in very low birth weight infants. J Perinatol. 1999; 19:278–283. PMID: 10685239.
Article
108. Glatz M, Polley E, Simpson E, Kong H. Emollient therapy alters skin barrier and microbes in infants at risk for developing atopic dermatitis. J Invest Dermatol. 2015; 135:S31.
109. Huang JT, Abrams M, Tlougan B, Rademaker A, Paller AS. Treatment of Staphylococcus aureus colonization in atopic dermatitis decreases disease severity. Pediatrics. 2009; 123:e808–e814. PMID: 19403473.
Article
110. Eriksson S, van der Plas MJ, Mörgelin M, Sonesson A. Antibacterial and antibiofilm effects of sodium hypochlorite against Staphylococcus aureus isolates derived from patients with atopic dermatitis. Br J Dermatol. 2017; 177:513–521. PMID: 28238217.
111. Myles IA, Williams KW, Reckhow JD, Jammeh ML, Pincus NB, Sastalla I, et al. Transplantation of human skin microbiota in models of atopic dermatitis. JCI Insight. 2016; 1:e86955. PMID: 27478874.
Article
112. Hyung KE, Kim SJ, Jang YW, Lee DK, Hyun KH, Moon BS, et al. Therapeutic effects of orally administered CJLP55 for atopic dermatitis via the regulation of immune response. Korean J Physiol Pharmacol. 2017; 21:335–343. PMID: 28461776.
Article
113. Notay M, Foolad N, Vaughn AR, Sivamani RK. Probiotics, prebiotics, and synbiotics for the treatment and prevention of adult dermatological diseases. Am J Clin Dermatol. 2017; 18:721–732. PMID: 28681230.
Article
114. Simpson EL, Bieber T, Guttman-Yassky E, Beck LA, Blauvelt A, Cork MJ, et al. Two phase 3 trials of dupilumab versus placebo in atopic dermatitis. N Engl J Med. 2016; 375:2335–2348. PMID: 27690741.
Article
115. Thaçi D, Simpson EL, Beck LA, Bieber T, Blauvelt A, Papp K, et al. Efficacy and safety of dupilumab in adults with moderate-to-severe atopic dermatitis inadequately controlled by topical treatments: a randomised, placebo-controlled, dose-ranging phase 2b trial. Lancet. 2016; 387:40–52. PMID: 26454361.
Article
116. Beck LA, Thaçi D, Hamilton JD, Graham NM, Bieber T, Rocklin R, et al. Dupilumab treatment in adults with moderate-to-severe atopic dermatitis. N Engl J Med. 2014; 371:130–139. PMID: 25006719.
Article
117. Hamilton JD, Suárez-Fariñas M, Dhingra N, Cardinale I, Li X, Kostic A, et al. Dupilumab improves the molecular signature in skin of patients with moderate-to-severe atopic dermatitis. J Allergy Clin Immunol. 2014; 134:1293–1300. PMID: 25482871.
Article
118. Rø AD, Simpson MR, Rø TB, Storrø O, Johnsen R, Videm V, et al. Reduced Th22 cell proportion and prevention of atopic dermatitis in infants following maternal probiotic supplementation. Clin Exp Allergy. 2017; 47:1014–1021. PMID: 28346719.
Article
119. di Mauro G, Bernardini R, Barberi S, Capuano A, Correra A, De'Angelis GL, et al. Prevention of food and airway allergy: consensus of the Italian Society of Preventive and Social Paediatrics, the Italian Society of Paediatric Allergy and Immunology, and Italian Society of Pediatrics. World Allergy Organ J. 2016; 9:28. PMID: 27583103.
Article
120. Kelleher M, Dunn-Galvin A, Hourihane JO, Murray D, Campbell LE, McLean WH, et al. Skin barrier dysfunction measured by transepidermal water loss at 2 days and 2 months predates and predicts atopic dermatitis at 1 year. J Allergy Clin Immunol. 2015; 135:930–935.e1. PMID: 25618747.
121. Kim J, Kim BE, Lee J, Han Y, Jun HY, Kim H, et al. Epidermal thymic stromal lymphopoietin predicts the development of atopic dermatitis during infancy. J Allergy Clin Immunol. 2016; 137:1282–1285.e4. PMID: 26879860.
Article
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