Unraveling the skin; a comprehensive review of atopic dermatitis, current understanding, and approaches
Language English Country Switzerland Media electronic-ecollection
Document type Journal Article, Review, Research Support, Non-U.S. Gov't
PubMed
38500882
PubMed Central
PMC10944924
DOI
10.3389/fimmu.2024.1361005
Knihovny.cz E-resources
- Keywords
- Th Lymphocytes, atopic dermatitis, epidermal barrier dysfunction, filaggrin gene mutations, immune dysregulation, nano-delivery systems, nano-dermatology, skin immunology,
- MeSH
- Dermatitis, Atopic * diagnosis etiology therapy MeSH
- Epidermis pathology MeSH
- Skin MeSH
- Humans MeSH
- Anxiety MeSH
- Treatment Outcome MeSH
- Check Tag
- Humans MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Review MeSH
Atopic dermatitis, also known as atopic eczema, is a chronic inflammatory skin disease characterized by red pruritic skin lesions, xerosis, ichthyosis, and skin pain. Among the social impacts of atopic dermatitis are difficulties and detachment in relationships and social stigmatization. Additionally, atopic dermatitis is known to cause sleep disturbance, anxiety, hyperactivity, and depression. Although the pathological process behind atopic dermatitis is not fully known, it appears to be a combination of epidermal barrier dysfunction and immune dysregulation. Skin is the largest organ of the human body which acts as a mechanical barrier to toxins and UV light and a natural barrier against water loss. Both functions face significant challenges due to atopic dermatitis. The list of factors that can potentially trigger or contribute to atopic dermatitis is extensive, ranging from genetic factors, family history, dietary choices, immune triggers, and environmental factors. Consequently, prevention, early clinical diagnosis, and effective treatment may be the only resolutions to combat this burdensome disease. Ensuring safe and targeted drug delivery to the skin layers, without reaching the systemic circulation is a promising option raised by nano-delivery systems in dermatology. In this review, we explored the current understanding and approaches of atopic dermatitis and outlined a range of the most recent therapeutics and dosage forms brought by nanotechnology. This review was conducted using PubMed, Google Scholar, and ScienceDirect databases.
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Kapur S, Watson W, Carr S. Atopic dermatitis. Allergy Asthma Clin Immunol. (2018) 14:52. doi: 10.1186/s13223-018-0281-6 PubMed DOI PMC
de Lusignan S, Alexander H, Broderick C, Dennis J, McGovern A, Feeney C, et al. . The epidemiology of eczema in children and adults in England: A population-based study using primary care data. Clin Exp Allergy. (2021) 51:471–82. doi: 10.1111/cea.13784 PubMed DOI PMC
Laughter MR, Maymone MBC, Mashayekhi S, Arents BWM, Karimkhani C, Langan SM, et al. . The global burden of atopic dermatitis: lessons from the Global Burden of Disease Study 1990-2017. Br J Dermatol. (2021) 184:304–9. doi: 10.1111/bjd.19580 PubMed DOI
Smith Begolka W, Chovatiya R, Thibau IJ, Silverberg JI. Financial burden of atopic dermatitis out-of-pocket health care expenses in the United States. Dermatitis. (2021) 32:S62–s70. doi: 10.1097/DER.0000000000000715 PubMed DOI PMC
Bantz SK, Zhu Z, Zheng T. The atopic march: progression from atopic dermatitis to allergic rhinitis and asthma. J Clin Cell Immunol. (2014) 5:2. doi: 10.4172/2155-9899.1000202 PubMed DOI PMC
Garmhausen D, Hagemann T, Bieber T, Dimitriou I, Fimmers R, Diepgen T, et al. . Characterization of different courses of atopic dermatitis in adolescent and adult patients. Allergy. (2013) 68:498–506. doi: 10.1111/all.12112 PubMed DOI PMC
Sidbury R, Kodama S. Atopic dermatitis guidelines: Diagnosis, systemic therapy, and adjunctive care. Clin Dermatol. (2018) 36:648–52. doi: 10.1016/j.clindermatol.2018.05.008 PubMed DOI
Williams HC, Burney PG, Pembroke AC, Hay RJ. The U.K. Working Party's Diagnostic Criteria for Atopic Dermatitis. III. Independent hospital validation. Br J Dermatol. (1994) 131:406–16. doi: 10.1111/j.1365-2133.1994.tb08532.x PubMed DOI
Lyons JJ, Milner JD, Stone KD. Atopic dermatitis in children: clinical features, pathophysiology, and treatment. Immunol Allergy Clin North Am. (2015) 35:161–83. doi: 10.1016/j.iac.2014.09.008 PubMed DOI PMC
Mollanazar NK, Smith PK, Yosipovitch G. Mediators of chronic pruritus in atopic dermatitis: getting the itch out? Clin Rev Allergy Immunol. (2016) 51:263–92. doi: 10.1007/s12016-015-8488-5 PubMed DOI
Urashima R, Mihara M. Cutaneous nerves in atopic dermatitis. A histological, immunohistochemical and electron microscopic study. Virchows Arch. (1998) 432:363–70. doi: 10.1007/s004280050179 PubMed DOI
Hanifin JM, Baghoomian W, Grinich E, Leshem YA, Jacobson M, Simpson EL. The eczema area and severity index-A practical guide. Dermatitis. (2022) 33:187–92. doi: 10.1097/DER.0000000000000895 PubMed DOI PMC
Noda S, Suárez-Fariñas M, Ungar B, Kim SJ, de Guzman Strong C, Xu H, et al. . The Asian atopic dermatitis phenotype combines features of atopic dermatitis and psoriasis with increased TH17 polarization. J Allergy Clin Immunol. (2015) 136:1254–64. doi: 10.1016/j.jaci.2015.08.015 PubMed DOI
Thawer-Esmail F, Jakasa I, Todd G, Wen Y, Brown SJ, Kroboth K, et al. . South African amaXhosa patients with atopic dermatitis have decreased levels of filaggrin breakdown products but no loss-of-function mutations in filaggrin. J Allergy Clin Immunol. (2014) 133:280–2.e1-2. doi: 10.1016/j.jaci.2013.09.053 PubMed DOI PMC
Hu Y, Liu S, Liu P, Mu Z, Zhang J. Clinical relevance of eosinophils, basophils, serum total IgE level, allergen-specific IgE, and clinical features in atopic dermatitis. J Clin Lab Anal. (2020) 34:e23214. doi: 10.1002/jcla.23214 PubMed DOI PMC
Lopez-Ojeda W, Pandey A, Alhajj M, Oakley AM. Anatomy, Skin (Integument). Treasure Island (FL: StatPearls Publishing; (2022). PubMed
Fujii M. The Pathogenic and therapeutic implications of ceramide abnormalities in atopic dermatitis. Cells. (2021) 10. doi: 10.3390/cells10092386 PubMed DOI PMC
Hata TR, Gallo RL. Antimicrobial peptides, skin infections, and atopic dermatitis. Semin Cutan Med Surg. (2008) 27:144–50. doi: 10.1016/j.sder.2008.04.002 PubMed DOI PMC
Miller LS. Toll-like receptors in skin. Adv Dermatol. (2008) 24:71–87. doi: 10.1016/j.yadr.2008.09.004 PubMed DOI PMC
Viganò S, Perreau M, Pantaleo G, Harari A. Positive and negative regulation of cellular immune responses in physiologic conditions and diseases. Clin Dev Immunol. (2012) 2012:485781. doi: 10.1155/2012/485781 PubMed DOI PMC
Gomez de Agüero M, Vocanson M, Hacini-Rachinel F, Taillardet M, Sparwasser T, Kissenpfennig A, et al. . Langerhans cells protect from allergic contact dermatitis in mice by tolerizing CD8(+) T cells and activating Foxp3(+) regulatory T cells. J Clin Invest. (2012) 122:1700–11. doi: 10.1172/JCI59725 PubMed DOI PMC
Igyártó BZ, Kaplan DH. Antigen presentation by Langerhans cells. Curr Opin Immunol. (2013) 25:115–9. doi: 10.1016/j.coi.2012.11.007 PubMed DOI PMC
Hennino A, Vocanson M, Toussaint Y, Rodet K, Benetière J, Schmitt AM, et al. . Skin-infiltrating CD8+ T cells initiate atopic dermatitis lesions. J Immunol. (2007) 178:5571–7. doi: 10.4049/jimmunol.178.9.5571 PubMed DOI
Dubois B, Bridon JM, Fayette J, Barthélémy C, Banchereau J, Caux C, et al. . Dendritic cells directly modulate B cell growth and differentiation. J Leukoc Biol. (1999) 66:224–30. doi: 10.1002/jlb.66.2.224 PubMed DOI
Guttman-Yassky E, Lowes MA, Fuentes-Duculan J, Whynot J, Novitskaya I, Cardinale I, et al. . Major differences in inflammatory dendritic cells and their products distinguish atopic dermatitis from psoriasis. J Allergy Clin Immunol. (2007) 119:1210–7. doi: 10.1016/j.jaci.2007.03.006 PubMed DOI
Geissmann F, Manz MG, Jung S, Sieweke MH, Merad M, Ley K. Development of monocytes, macrophages, and dendritic cells. Science. (2010) 327:656–61. doi: 10.1126/science.1178331 PubMed DOI PMC
Hashimoto D, Chow A, Noizat C, Teo P, Beasley MB, Leboeuf M, et al. . Tissue-resident macrophages self-maintain locally throughout adult life with minimal contribution from circulating monocytes. Immunity. (2013) 38:792–804. doi: 10.1016/j.immuni.2013.04.004 PubMed DOI PMC
Lin A, Loré K. Granulocytes: new members of the antigen-presenting cell family. Front Immunol. (2017) 8:1781. doi: 10.3389/fimmu.2017.01781 PubMed DOI PMC
Galli SJ, Maurer M, Lantz CS. Mast cells as sentinels of innate immunity. Curr Opin Immunol. (1999) 11:53–9. doi: 10.1016/S0952-7915(99)80010-7 PubMed DOI
Caughey GH. Mast cell tryptases and chymases in inflammation and host defense. Immunol Rev. (2007) 217:141–54. doi: 10.1111/j.1600-065X.2007.00509.x PubMed DOI PMC
Chiricozzi A, Maurelli M, Peris K, Girolomoni G. Targeting IL-4 for the treatment of atopic dermatitis. Immunotargets Ther. (2020) 9:151–6. doi: 10.2147/ITT.S260370 PubMed DOI PMC
Mizutani Y, Takagi N, Nagata H, Inoue S. Interferon-γ downregulates tight junction function, which is rescued by interleukin-17A. Exp Dermatol. (2021) 30:1754–63. doi: 10.1111/exd.14425 PubMed DOI PMC
Gri G, Frossi B, D'Inca F, Danelli L, Betto E, Mion F, et al. . Mast cell: an emerging partner in immune interaction. Front Immunol. (2012) 3:120. doi: 10.3389/fimmu.2012.00120 PubMed DOI PMC
Weissler KA, Frischmeyer-Guerrerio PA. Genetic evidence for the role of transforming growth factor-β in atopic phenotypes. Curr Opin Immunol. (2019) 60:54–62. doi: 10.1016/j.coi.2019.05.002 PubMed DOI PMC
Brillantes M, Beaulieu AM. Memory and memory-like NK cell responses to microbial pathogens. Front Cell Infect Microbiol. (2020) 10:102. doi: 10.3389/fcimb.2020.00102 PubMed DOI PMC
Janeway CA, Jr, Travers P, Walport M, Shlomchik MJ. Immunobiology: The Immune System in Health and Disease. 5th edition. New York: Garland Science; (2001).
Debes GF, McGettigan SE. Skin-associated B cells in health and inflammation. J Immunol. (2019) 202:1659–66. doi: 10.4049/jimmunol.1801211 PubMed DOI PMC
Streilein JW. Skin-associated lymphoid tissues (SALT): origins and functions. J Invest Dermatol. (1983) 80 Suppl:12s–6s. doi: 10.1111/1523-1747.ep12536743 PubMed DOI
Silverberg NB, Silverberg JI. Inside out or outside in: does atopic dermatitis disrupt barrier function or does disruption of barrier function trigger atopic dermatitis? Cutis. (2015) 96:359–61. PubMed
Wollenberg A, Räwer HC, Schauber J. Innate immunity in atopic dermatitis. Clin Rev Allergy Immunol. (2011) 41:272–81. doi: 10.1007/s12016-010-8227-x PubMed DOI
Wang V, Boguniewicz J, Boguniewicz M, Ong PY. The infectious complications of atopic dermatitis. Ann Allergy Asthma Immunol. (2021) 126:3–12. doi: 10.1016/j.anai.2020.08.002 PubMed DOI PMC
Kawai T, Akira S. The role of pattern-recognition receptors in innate immunity: update on Toll-like receptors. Nat Immunol. (2010) 11:373–84. doi: 10.1038/ni.1863 PubMed DOI
Manicassamy S, Pulendran B. Modulation of adaptive immunity with Toll-like receptors. Semin Immunol. (2009) 21:185–93. doi: 10.1016/j.smim.2009.05.005 PubMed DOI PMC
Lai Y, Gallo RL. Toll-like receptors in skin infections and inflammatory diseases. Infect Disord Drug Targets. (2008) 8:144–55. doi: 10.2174/1871526510808030144 PubMed DOI PMC
Danso MO, van Drongelen V, Mulder A, van Esch J, Scott H, van Smeden J, et al. . TNF-α and Th2 cytokines induce atopic dermatitis-like features on epidermal differentiation proteins and stratum corneum lipids in human skin equivalents. J Invest Dermatol. (2014) 134:1941–50. doi: 10.1038/jid.2014.83 PubMed DOI
Zhang LJ, Guerrero-Juarez CF, Hata T, Bapat SP, Ramos R, Plikus MV, et al. . Innate immunity. Dermal adipocytes protect against invasive Staphylococcus aureus skin infection. Science. (2015) 347:67–71. doi: 10.1126/science.1260972 PubMed DOI PMC
Amarbayasgalan T, Takahashi H, Dekio I, Morita E. Interleukin-8 content in the stratum corneum as an indicator of the severity of inflammation in the lesions of atopic dermatitis. Int Arch Allergy Immunol. (2013) 160:63–74. doi: 10.1159/000339666 PubMed DOI
Zedan K, Rasheed Z, Farouk Y, Alzolibani AA, Bin Saif G, Ismail HA, et al. . Immunoglobulin e, interleukin-18 and interleukin-12 in patients with atopic dermatitis: correlation with disease activity. J Clin Diagn Res. (2015) 9:Wc01–5. doi: 10.7860/JCDR/2015/12261.5742 PubMed DOI PMC
Flacher V, Bouschbacher M, Verronèse E, Massacrier C, Sisirak V, Berthier-Vergnes O, et al. . Human Langerhans cells express a specific TLR profile and differentially respond to viruses and Gram-positive bacteria. J Immunol. (2006) 177:7959–67. doi: 10.4049/jimmunol.177.11.7959 PubMed DOI
Niebuhr M, Lutat C, Sigel S, Werfel T. Impaired TLR-2 expression and TLR-2-mediated cytokine secretion in macrophages from patients with atopic dermatitis. Allergy. (2009) 64:1580–7. doi: 10.1111/j.1398-9995.2009.02050.x PubMed DOI
Yu Y, Zhang Y, Zhang J, Dou X, Yang H, Shao Y, et al. . Impaired Toll-like receptor 2-mediated Th1 and Th17/22 cytokines secretion in human peripheral blood mononuclear cells from patients with atopic dermatitis. J Transl Med. (2015) 13:384. doi: 10.1186/s12967-015-0744-1 PubMed DOI PMC
Panzer R, Blobel C, Fölster-Holst R, Proksch E. TLR2 and TLR4 expression in atopic dermatitis, contact dermatitis and psoriasis. Exp Dermatol. (2014) 23:364–6. doi: 10.1111/exd.12383 PubMed DOI
Kuo IH, Carpenter-Mendini A, Yoshida T, McGirt LY, Ivanov AI, Barnes KC, et al. . Activation of epidermal toll-like receptor 2 enhances tight junction function: implications for atopic dermatitis and skin barrier repair. J Invest Dermatol. (2013) 133:988–98. doi: 10.1038/jid.2012.437 PubMed DOI PMC
Tsilingiri K, Fornasa G, Rescigno M. Thymic stromal lymphopoietin: to cut a long story short. Cell Mol Gastroenterol Hepatol. (2017) 3:174–82. doi: 10.1016/j.jcmgh.2017.01.005 PubMed DOI PMC
Indra AK. Epidermal TSLP: a trigger factor for pathogenesis of atopic dermatitis. Expert Rev Proteomics. (2013) 10:309–11. doi: 10.1586/14789450.2013.814881 PubMed DOI PMC
Kashyap M, Rochman Y, Spolski R, Samsel L, Leonard WJ. Thymic stromal lymphopoietin is produced by dendritic cells. J Immunol. (2011) 187:1207–11. doi: 10.4049/jimmunol.1100355 PubMed DOI PMC
Bogiatzi SI, Fernandez I, Bichet JC, Marloie-Provost MA, Volpe E, Sastre X, et al. . Cutting Edge: Proinflammatory and Th2 cytokines synergize to induce thymic stromal lymphopoietin production by human skin keratinocytes. J Immunol. (2007) 178:3373–7. doi: 10.4049/jimmunol.178.6.3373 PubMed DOI
Sehra S, Yao Y, Howell MD, Nguyen ET, Kansas GS, Leung DY, et al. . IL-4 regulates skin homeostasis and the predisposition toward allergic skin inflammation. J Immunol. (2010) 184:3186–90. doi: 10.4049/jimmunol.0901860 PubMed DOI PMC
Furue K, Ito T, Tsuji G, Ulzii D, Vu YH, Kido-Nakahara M, et al. . The IL-13-OVOL1-FLG axis in atopic dermatitis. Immunology. (2019) 158:281–6. doi: 10.1111/imm.13120 PubMed DOI PMC
Howell MD, Boguniewicz M, Pastore S, Novak N, Bieber T, Girolomoni G, et al. . Mechanism of HBD-3 deficiency in atopic dermatitis. Clin Immunol. (2006) 121:332–8. doi: 10.1016/j.clim.2006.08.008 PubMed DOI
Legat FJ. Itch in atopic dermatitis - what is new? Front Med (Lausanne). (2021) 8:644760. doi: 10.3389/fmed.2021.644760 PubMed DOI PMC
Kondo S, Yazawa H, Jimbow K. Reduction of serum interleukin-5 levels reflect clinical improvement in patients with atopic dermatitis. J Dermatol. (2001) 28:237–43. doi: 10.1111/j.1346-8138.2001.tb00124.x PubMed DOI
Roufosse F. Targeting the interleukin-5 pathway for treatment of eosinophilic conditions other than asthma. Front Med (Lausanne). (2018) 5:49. doi: 10.3389/fmed.2018.00049 PubMed DOI PMC
Saleem MD, Oussedik E, D'Amber V, Feldman SR. Interleukin-31 pathway and its role in atopic dermatitis: a systematic review. J Dermatolog Treat. (2017) 28:591–9. doi: 10.1080/09546634.2017.1290205 PubMed DOI
Takaoka A, Arai I, Sugimoto M, Yamaguchi A, Tanaka M, Nakaike S. Expression of IL-31 gene transcripts in NC/Nga mice with atopic dermatitis. Eur J Pharmacol. (2005) 516:180–1. doi: 10.1016/j.ejphar.2005.04.040 PubMed DOI
Koga C, Kabashima K, Shiraishi N, Kobayashi M, Tokura Y. Possible pathogenic role of Th17 cells for atopic dermatitis. J Invest Dermatol. (2008) 128:2625–30. doi: 10.1038/jid.2008.111 PubMed DOI
Czarnowicki T, Gonzalez J, Shemer A, Malajian D, Xu H, Zheng X, et al. . Severe atopic dermatitis is characterized by selective expansion of circulating TH2/TC2 and TH22/TC22, but not TH17/TC17, cells within the skin-homing T-cell population. J Allergy Clin Immunol. (2015) 136:104–15.e7. doi: 10.1016/j.jaci.2015.01.020 PubMed DOI
Liu T, Li S, Ying S, Tang S, Ding Y, Li Y, et al. . The IL-23/IL-17 pathway in inflammatory skin diseases: from bench to bedside. Front Immunol. (2020) 11:594735. doi: 10.3389/fimmu.2020.594735 PubMed DOI PMC
Ravn NH, Halling AS, Berkowitz AG, Rinnov MR, Silverberg JI, Egeberg A, et al. . How does parental history of atopic disease predict the risk of atopic dermatitis in a child? A systematic review and meta-analysis. J Allergy Clin Immunol. (2020) 145:1182–93. doi: 10.1016/j.jaci.2019.12.899 PubMed DOI
Barnes KC. An update on the genetics of atopic dermatitis: scratching the surface in 2009. J Allergy Clin Immunol. (2010) 125:16–29.e1-11. doi: 10.1016/j.jaci.2009.11.008 PubMed DOI PMC
Armengot-Carbo M, Hernández-Martín Á, Torrelo A. The role of filaggrin in the skin barrier and disease development. Actas Dermosifiliogr. (2015) 106:86–95. doi: 10.1016/j.ad.2013.10.019 PubMed DOI
Robinson M, Visscher M, Laruffa A, Wickett R. Natural moisturizing factors (NMF) in the stratum corneum (SC). I. Effects of lipid extraction and soaking. J Cosmet Sci. (2010) 61:13–22. PubMed
Palmer CN, Irvine AD, Terron-Kwiatkowski A, Zhao Y, Liao H, Lee SP, et al. . Common loss-of-function variants of the epidermal barrier protein filaggrin are a major predisposing factor for atopic dermatitis. Nat Genet. (2006) 38:441–6. doi: 10.1038/ng1767 PubMed DOI
Bikle DD, Xie Z, Tu CL. Calcium regulation of keratinocyte differentiation. Expert Rev Endocrinol Metab. (2012) 7:461–72. doi: 10.1586/eem.12.34 PubMed DOI PMC
Sandilands A, Sutherland C, Irvine AD, McLean WH. Filaggrin in the frontline: role in skin barrier function and disease. J Cell Sci. (2009) 122:1285–94. doi: 10.1242/jcs.033969 PubMed DOI PMC
Gruber R, Elias PM, Crumrine D, Lin TK, Brandner JM, Hachem JP, et al. . Filaggrin genotype in ichthyosis vulgaris predicts abnormalities in epidermal structure and function. Am J Pathol. (2011) 178:2252–63. doi: 10.1016/j.ajpath.2011.01.053 PubMed DOI PMC
Kezic S, O'Regan GM, Lutter R, Jakasa I, Koster ES, Saunders S, et al. . Filaggrin loss-of-function mutations are associated with enhanced expression of IL-1 cytokines in the stratum corneum of patients with atopic dermatitis and in a murine model of filaggrin deficiency. J Allergy Clin Immunol. (2012) 129:1031–9.e1. doi: 10.1016/j.jaci.2011.12.989 PubMed DOI PMC
Savinko T, Matikainen S, Saarialho-Kere U, Lehto M, Wang G, Lehtimäki S, et al. . IL-33 and ST2 in atopic dermatitis: expression profiles and modulation by triggering factors. J Invest Dermatol. (2012) 132:1392–400. doi: 10.1038/jid.2011.446 PubMed DOI
Tamagawa-Mineoka R, Okuzawa Y, Masuda K, Katoh N. Increased serum levels of interleukin 33 in patients with atopic dermatitis. J Am Acad Dermatol. (2014) 70:882–8. doi: 10.1016/j.jaad.2014.01.867 PubMed DOI
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) 120:150–5. doi: 10.1016/j.jaci.2007.04.031 PubMed DOI PMC
Kondo H, Ichikawa Y, Imokawa G. Percutaneous sensitization with allergens through barrier-disrupted skin elicits a Th2-dominant cytokine response. Eur J Immunol. (1998) 28:769–79. doi: 10.1002/(SICI)1521-4141(199803)28:03<769::AID-IMMU769>3.0.CO;2-H PubMed DOI
De Benedetto A, Kubo A, Beck LA. Skin barrier disruption: a requirement for allergen sensitization? J Invest Dermatol. (2012) 132:949–63. doi: 10.1038/jid.2011.435 PubMed DOI PMC
Carson CG, Rasmussen MA, Thyssen JP, Menné T, Bisgaard H. Clinical presentation of atopic dermatitis by filaggrin gene mutation status during the first 7 years of life in a prospective cohort study. PloS One. (2012) 7:e48678. doi: 10.1371/journal.pone.0048678 PubMed DOI PMC
Margolis DJ, Gupta J, Apter AJ, Ganguly T, Hoffstad O, Papadopoulos M, et al. . Filaggrin-2 variation is associated with more persistent atopic dermatitis in African American subjects. J Allergy Clin Immunol. (2014) 133:784–9. doi: 10.1016/j.jaci.2013.09.015 PubMed DOI PMC
Shaheen SO, Rutterford C, Zuccolo L, Ring SM, Davey Smith G, Holloway JW, et al. . Prenatal alcohol exposure and childhood atopic disease: a Mendelian randomization approach. J Allergy Clin Immunol. (2014) 133:225–32.e1-5. doi: 10.1016/j.jaci.2013.04.051 PubMed DOI PMC
Kantor R, Kim A, Thyssen JP, Silverberg JI. Association of atopic dermatitis with smoking: A systematic review and meta-analysis. J Am Acad Dermatol. (2016) 75:1119–25.e1. doi: 10.1016/j.jaad.2016.07.017 PubMed DOI PMC
Kim JH. Role of breast-feeding in the development of atopic dermatitis in early childhood. Allergy Asthma Immunol Res. (2017) 9:285–7. doi: 10.4168/aair.2017.9.4.285 PubMed DOI PMC
Vaughn AR, Foolad N, Maarouf M, Tran KA, Shi VY, Medicine C. Micronutrients in Atopic Dermatitis: A Systematic Review. (2019) 25:567–77. doi: 10.1089/acm.2018.0363 PubMed DOI
Øien T, Schjelvaag A, Storrø O, Johnsen R, Simpson MR. Fish Consumption at One Year of Age Reduces the Risk of Eczema, Asthma and Wheeze at Six Years of Age. Nutrients. (2019) 11:9. doi: 10.3390/nu11091969 PubMed DOI PMC
Flohr C, Pascoe D, Williams HC. Atopic dermatitis and the 'hygiene hypothesis': too clean to be true? Br J Dermatol. (2005) 152:202–16. doi: 10.1111/j.1365-2133.2004.06436.x PubMed DOI
Martorano LM, Grayson MH. Respiratory viral infections and atopic development: From possible mechanisms to advances in treatment. Eur J Immunol. (2018) 48:407–14. doi: 10.1002/eji.201747052 PubMed DOI PMC
Lee SY, Lee E, Park YM, Hong SJ. Microbiome in the gut-skin axis in atopic dermatitis. Allergy Asthma Immunol Res. (2018) 10:354–62. doi: 10.4168/aair.2018.10.4.354 PubMed DOI PMC
Harris-Tryon TA, Grice EA. Microbiota and maintenance of skin barrier function. Science. (2022) 376:940–5. doi: 10.1126/science.abo0693 PubMed DOI
Coelho GDP, Ayres LFA, Barreto DS, Henriques BD, Prado M, Passos CMD. Acquisition of microbiota according to the type of birth: an integrative review. Rev Lat Am Enfermagem. (2021) 29:e3446. doi: 10.1590/1518.8345.4466.3446 PubMed DOI PMC
Wanke I, Steffen H, Christ C, Krismer B, Götz F, Peschel A, et al. . Skin commensals amplify the innate immune response to pathogens by activation of distinct signaling pathways. J Invest Dermatol. (2011) 131:382–90. doi: 10.1038/jid.2010.328 PubMed DOI
Clausen ML, Agner T, Lilje B, Edslev SM, Johannesen TB, Andersen PS. Association of disease severity with skin microbiome and filaggrin gene mutations in adult atopic dermatitis. JAMA Dermatol. (2018) 154:293–300. doi: 10.1001/jamadermatol.2017.5440 PubMed DOI PMC
Abeck D, Mempel M. Staphylococcus aureus colonization in atopic dermatitis and its therapeutic implications. Br J Dermatol. (1998) 139 Suppl 53:13–6. doi: 10.1046/j.1365-2133.1998.1390s3013.x PubMed DOI
Hong SW, Kim MR, Lee EY, Kim JH, Kim YS, Jeon SG, et al. . Extracellular vesicles derived from Staphylococcus aureus induce atopic dermatitis-like skin inflammation. Allergy. (2011) 66:351–9. doi: 10.1111/j.1398-9995.2010.02483.x PubMed DOI PMC
Al Kindi A, Williams H, Matsuda K, Alkahtani AM, Saville C, Bennett H, et al. . Staphylococcus aureus second immunoglobulin-binding protein drives atopic dermatitis via IL-33. J Allergy Clin Immunol. (2021) 147:1354–68.e3. doi: 10.1016/j.jaci.2020.09.023 PubMed DOI
Imai Y. Interleukin-33 in atopic dermatitis. J Dermatol Sci. (2019) 96:2–7. doi: 10.1016/j.jdermsci.2019.08.006 PubMed DOI
Fania L, Moretta G, Antonelli F, Scala E, Abeni D, Albanesi C, et al. . Multiple Roles for Cytokines in Atopic Dermatitis: From Pathogenic Mediators to Endotype-Specific Biomarkers to Therapeutic Targets. (2022) 23:2684. doi: 10.3390/ijms23052684 PubMed DOI PMC
Murai-Yamamura M, Garcet S, Yamamura K, Gonzalez J, Miura S, Li X, et al. . T(H) 2 cytokines and Staphylococcus aureus cooperatively induce atopic dermatitis-like transcriptomes. Allergy. (2021) 76:3534–7. doi: 10.1111/all.15035 PubMed DOI
Schmid-Grendelmeier P, Flückiger S, Disch R, Trautmann A, Wüthrich B, Blaser K, et al. . IgE-mediated and T cell–mediated autoimmunity against manganese superoxide dismutase in atopic dermatitis. (2005) 115:1068–75. doi: 10.1016 PubMed
Flückiger S, Scapozza L, Mayer C, Blaser K, Folkers G, Crameri R. Immunological and structural analysis of IgE-mediated cross-reactivity between manganese superoxide dismutases. Int Arch Allergy Immunol. (2002) 128:292–303. doi: 10.1159/000063862 PubMed DOI
Lambers H, Piessens S, Bloem A, Pronk H, Finkel P. Natural skin surface pH is on average below 5, which is beneficial for its resident flora. Int J Cosmet Sci. (2006) 28:359–70. doi: 10.1111/j.1467-2494.2006.00344.x PubMed DOI
Ali SM, Yosipovitch G. Skin pH: from basic science to basic skin care. Acta Derm Venereol. (2013) 93:261–7. doi: 10.2340/00015555-1531 PubMed DOI
Oranges T, Dini V, Romanelli M. Skin physiology of the neonate and infant: clinical implications. Adv Wound Care (New Rochelle). (2015) 4:587–95. doi: 10.1089/wound.2015.0642 PubMed DOI PMC
Cork MJ, Danby SG, Vasilopoulos Y, Hadgraft J, Lane ME, Moustafa M, et al. . Epidermal barrier dysfunction in atopic dermatitis. J Invest Dermatol. (2009) 129:1892–908. doi: 10.1038/jid.2009.133 PubMed DOI
Engebretsen KA, Johansen JD, Kezic S, Linneberg A, Thyssen JP. The effect of environmental humidity and temperature on skin barrier function and dermatitis. J Eur Acad Dermatol Venereol. (2016) 30:223–49. doi: 10.1111/jdv.13301 PubMed DOI
Sato K, Kang WH, Saga K, Sato KT. Biology of sweat glands and their disorders. I. Normal sweat gland function. J Am Acad Dermatol. (1989) 20:537–63. doi: 10.1016/S0190-9622(89)70063-3 PubMed DOI
Vocks E, Busch R, Fröhlich C, Borelli S, Mayer H, Ring J. Influence of weather and climate on subjective symptom intensity in atopic eczema. Int J Biometeorol. (2001) 45:27–33. doi: 10.1007/s004840000077 PubMed DOI
Sargen MR, Hoffstad O, Margolis DJ. Warm, humid, and high sun exposure climates are associated with poorly controlled eczema: PEER (Pediatric Eczema Elective Registry) cohort, 2004-2012. J Invest Dermatol. (2014) 134:51–7. doi: 10.1038/jid.2013.274 PubMed DOI PMC
Osborne NJ, Ukoumunne OC, Wake M, Allen KJ. Prevalence of eczema and food allergy is associated with latitude in Australia. J Allergy Clin Immunol. (2012) 129:865–7. doi: 10.1016/j.jaci.2012.01.037 PubMed DOI
Dijkhoff IM, Drasler B, Karakocak BB, Petri-Fink A, Valacchi G, Eeman M, et al. . Impact of airborne particulate matter on skin: a systematic review from epidemiology to in vitro studies. Part Fibre Toxicol. (2020) 17:35. doi: 10.1186/s12989-020-00366-y PubMed DOI PMC
Eberlein-König B, Przybilla B, Kühnl P, Pechak J, Gebefügi I, Kleinschmidt J, et al. . Influence of airborne nitrogen dioxide or formaldehyde on parameters of skin function and cellular activation in patients with atopic eczema and control subjects. J Allergy Clin Immunol. (1998) 101:141–3. doi: 10.1016/S0091-6749(98)70212-X PubMed DOI
Ma C, Wang J, Luo J. Activation of nuclear factor kappa B by diesel exhaust particles in mouse epidermal cells through phosphatidylinositol 3-kinase/Akt signaling pathway. Biochem Pharmacol. (2004) 67:1975–83. doi: 10.1016/j.bcp.2004.01.023 PubMed DOI
Ushio H, Nohara K, Fujimaki H. Effect of environmental pollutants on the production of pro-inflammatory cytokines by normal human dermal keratinocytes. Toxicol Lett. (1999) 105:17–24. doi: 10.1016/S0378-4274(98)00379-8 PubMed DOI
Navarini AA, French LE, Hofbauer GF. Interrupting IL-6-receptor signaling improves atopic dermatitis but associates with bacterial superinfection. J Allergy Clin Immunol. (2011) 128:1128–30. doi: 10.1016/j.jaci.2011.09.009 PubMed DOI
Papapostolou N, Xepapadaki P, Gregoriou S, Makris M. Atopic dermatitis and food allergy: A complex interplay what we know and what we would like to learn. J Clin Med. (2022) 11:3–4. doi: 10.3390/jcm11144232 PubMed DOI PMC
Ramírez-Marín HA, Singh AM, Ong PY, Silverberg JI. Food allergy testing in atopic dermatitis. JAAD Int. (2022) 9:50–6. doi: 10.1016/j.jdin.2022.08.004 PubMed DOI PMC
Kim BE, Leung DYM. Significance of skin barrier dysfunction in atopic dermatitis. Allergy Asthma Immunol Res. (2018) 10:207–15. doi: 10.4168/aair.2018.10.3.207 PubMed DOI PMC
Lee SE, Jeong SK, Lee SH. Protease and protease-activated receptor-2 signaling in the pathogenesis of atopic dermatitis. Yonsei Med J. (2010) 51:808–22. doi: 10.3349/ymj.2010.51.6.808 PubMed DOI PMC
Deraison C, Bonnart C, Lopez F, Besson C, Robinson R, Jayakumar A, et al. . LEKTI fragments specifically inhibit KLK5, KLK7, and KLK14 and control desquamation through a pH-dependent interaction. Mol Biol Cell. (2007) 18:3607–19. doi: 10.1091/mbc.e07-02-0124 PubMed DOI PMC
Zhu Y, Underwood J, Macmillan D, Shariff L, O'Shaughnessy R, Harper JI, et al. . Persistent kallikrein 5 activation induces atopic dermatitis-like skin architecture independent of PAR2 activity. J Allergy Clin Immunol. (2017) 140:1310–22.e5. doi: 10.1016/j.jaci.2017.01.025 PubMed DOI
Voegeli R, Doppler S, Joller P, Breternitz M, Fluhr JW, Rawlings AV. Increased mass levels of certain serine proteases in the stratum corneum in acute eczematous atopic skin. Int J Cosmet Sci. (2011) 33:560–5. doi: 10.1111/j.1468-2494.2011.00671.x PubMed DOI
Fortugno P, Furio L, Teson M, Berretti M, El Hachem M, Zambruno G, et al. . The 420K LEKTI variant alters LEKTI proteolytic activation and results in protease deregulation: implications for atopic dermatitis. Hum Mol Genet. (2012) 21:4187–200. doi: 10.1093/hmg/dds243 PubMed DOI
Brattsand M, Stefansson K, Lundh C, Haasum Y, Egelrud T. A proteolytic cascade of kallikreins in the stratum corneum. J Invest Dermatol. (2005) 124:198–203. doi: 10.1111/j.0022-202X.2004.23547.x PubMed DOI
Li Y, Li Y, Li W, Guo X, Zhou S, Zheng H. Genetic polymorphisms in serine protease inhibitor Kazal-type 5 and risk of atopic dermatitis: A meta-analysis. Med (Baltimore). (2020) 99:e21256. doi: 10.1097/MD.0000000000021256 PubMed DOI PMC
Bandier J, Johansen JD, Petersen LJ, Carlsen BC. Skin pH, atopic dermatitis, and filaggrin mutations. Dermatitis. (2014) 25:127–9. doi: 10.1097/DER.0000000000000045 PubMed DOI
Karlsson A, Arvidson S. Variation in extracellular protease production among clinical isolates of Staphylococcus aureus due to different levels of expression of the protease repressor sarA. Infect Immun. (2002) 70:4239–46. doi: 10.1128/IAI.70.8.4239-4246.2002 PubMed DOI PMC
Janssens M, van Smeden J, Gooris GS, Bras W, Portale G, Caspers PJ, et al. . Increase in short-chain ceramides correlates with an altered lipid organization and decreased barrier function in atopic eczema patients. J Lipid Res. (2012) 53:2755–66. doi: 10.1194/jlr.P030338 PubMed DOI PMC
Kim BE, Leung DY, Boguniewicz M, Howell MD. Loricrin and involucrin expression is down-regulated by Th2 cytokines through STAT-6. Clin Immunol. (2008) 126:332–7. doi: 10.1016/j.clim.2007.11.006 PubMed DOI PMC
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) 127:773–86.e1-7. doi: 10.1016/j.jaci.2010.10.018 PubMed DOI PMC
Tokumasu R, Yamaga K, Yamazaki Y, Murota H, Suzuki K, Tamura A, et al. . Dose-dependent role of claudin-1 in vivo in orchestrating features of atopic dermatitis. Proc Natl Acad Sci U.S.A. (2016) 113:E4061–8. doi: 10.1073/pnas.1525474113 PubMed DOI PMC
Batista DI, Perez L, Orfali RL, Zaniboni MC, Samorano LP, Pereira NV, et al. . Profile of skin barrier proteins (filaggrin, claudins 1 and 4) and Th1/Th2/Th17 cytokines in adults with atopic dermatitis. J Eur Acad Dermatol Venereol. (2015) 29:1091–5. doi: 10.1111/jdv.12753 PubMed DOI
Bäsler K, Galliano MF, Bergmann S, Rohde H, Wladykowski E, Vidal YSS, et al. . Biphasic influence of Staphylococcus aureus on human epidermal tight junctions. Ann N Y Acad Sci. (2017) 1405:53–70. doi: 10.1111/nyas.13418 PubMed DOI
Girolomoni G, Busà VM. Flare management in atopic dermatitis: from definition to treatment. Ther Adv chronic Dis. (2022) 13:5. doi: 10.1177/20406223211066728 PubMed DOI PMC
Liddell. Choosing a dermatological hero for the millennium. Hippocrates of Cos (460-377 BC). (2000) 25:86–8. doi: 10.1046/j.1365-2230.2000.0580d.x PubMed DOI
Bhattacharya T, Strom MA, Lio PA. Historical Perspectives on Atopic Dermatitis: Eczema Through the Ages. (2016) 33(4):375–9. doi: 10.1111/pde.12853 PubMed DOI
Bhattacharya T, Strom MA, Lio PA. Historical perspectives on atopic dermatitis: eczema through the ages. (2016) 33:375–9. doi: 10.1111/pde.12853 PubMed DOI
Sulzberger MB, Witten VH. The effect of topically applied compound F in selected dermatoses. J Invest Dermatol. (1952) 19:101–2. doi: 10.1038/jid.1952.72 PubMed DOI
Goddard AL, Lio PA. Alternative, complementary, and forgotten remedies for atopic dermatitis. Evidence-Based complementary Altern Med eCAM. (2015) 2015:676897. doi: 10.1155/2015/676897 PubMed DOI PMC
Calabrese G, Licata G, Gambardella A, De Rosa A, Alfano R, Argenziano G. Topical and conventional systemic treatments in atopic dermatitis: have they gone out of fashion? Dermatol Pract conceptual. (2022) 12:e2022155. doi: 10.5826/dpc.1201a155 PubMed DOI PMC
Singh S, Behl T, Sharma N, Zahoor I, Chigurupati S, Yadav S, et al. . Targeting therapeutic approaches and highlighting the potential role of nanotechnology in atopic dermatitis. Environ Sci pollut Res Int. (2022) 29:32605–30. doi: 10.1007/s11356-021-18429-8 PubMed DOI
Rosado C, Silva C, Reis CP. Hydrocortisone-loaded poly(ϵ-caprolactone) nanoparticles for atopic dermatitis treatment. Pharm Dev Technol. (2013) 18:710–8. doi: 10.3109/10837450.2012.712537 PubMed DOI
Jensen LB, Petersson K, Nielsen HM. In vitro penetration properties of solid lipid nanoparticles in intact and barrier-impaired skin. Eur J pharmaceutics biopharmaceutics. (2011) 79:68–75. doi: 10.1016/j.ejpb.2011.05.012 PubMed DOI
Alam MS, Ali MS, Alam N, Siddiqui MR, Shamim M, Safhi MM. In vivo study of clobetasol propionate loaded nanoemulsion for topical application in psoriasis and atopic dermatitis. Drug Invention Today. (2013) 5:8–12. doi: 10.1016/j.dit.2013.02.001 DOI
Eichenfield LF, Tom WL, Berger TG, Krol A, Paller AS, Schwarzenberger K, et al. . Guidelines of care for the management of atopic dermatitis: section 2. Management and treatment of atopic dermatitis with topical therapies. J Am Acad Dermatol. (2014) 71:116–32. doi: 10.1016/j.jaad.2014.03.023 PubMed DOI PMC
Yu K, Wang Y, Wan T, Zhai Y, Cao S, Ruan W, et al. . Tacrolimus nanoparticles based on chitosan combined with nicotinamide: enhancing percutaneous delivery and treatment efficacy for atopic dermatitis and reducing dose. Int J nanomedicine. (2018) 13:129–42. doi: 10.2147/IJN.S150319 PubMed DOI PMC
Zhuo F, Abourehab MAS, Hussain Z. Hyaluronic acid decorated tacrolimus-loaded nanoparticles: Efficient approach to maximize dermal targeting and anti-dermatitis efficacy. Carbohydr polymers. (2018) 197:478–89. doi: 10.1016/j.carbpol.2018.06.023 PubMed DOI
Kang JH, Chon J, Kim YI, Lee HJ, Oh DW, Lee HG, et al. . Preparation and evaluation of tacrolimus-loaded thermosensitive solid lipid nanoparticles for improved dermal distribution. Int J nanomedicine. (2019) 14:5381–96. doi: 10.2147/IJN.S215153 PubMed DOI PMC
Pal RR, Maurya AK, Parashar P, Saraf SA. A comparative study of levocetirizine loaded vesicular and matrix type system for topical application: appraisal of therapeutic potential against atopic dermatitis. J Pharm Innovation. (2021) 16:469–80. doi: 10.1007/s12247-020-09465-x DOI
Barbosa AI, Costa Lima SA, Reis S. Application of pH-responsive fucoidan/chitosan nanoparticles to improve oral quercetin delivery. Molecules (Basel Switzerland). (2019) 24. doi: 10.3390/molecules24020346 PubMed DOI PMC
Verma DD, Fahr A. Synergistic penetration enhancement effect of ethanol and phospholipids on the topical delivery of cyclosporin A. J Controlled release Off J Controlled Release Soc. (2004) 97:55–66. doi: 10.1016/j.jconrel.2004.02.028 PubMed DOI
Akhavan A, Rudikoff D. Atopic dermatitis: systemic immunosuppressive therapy. Semin cutaneous Med Surg. (2008) 27:151–5. doi: 10.1016/j.sder.2008.04.004 PubMed DOI
Seegräber M, Srour J, Walter A, Knop M, Wollenberg A. Dupilumab for treatment of atopic dermatitis. Expert Rev Clin Pharmacol. (2018) 11:467–74. doi: 10.1080/17512433.2018.1449642 PubMed DOI
Aszodi N, Thurau S, Seegräber M, de Bruin-Weller M, Wollenberg A. Management of dupilumab-associated conjunctivitis in atopic dermatitis. J der Deutschen Dermatologischen Gesellschaft. (2019) 17:488–91. doi: 10.1111/ddg.13809 PubMed DOI
Ahluwalia J, Udkoff J, Waldman A, Borok J, Eichenfield LF. Phosphodiesterase 4 inhibitor therapies for atopic dermatitis: progress and outlook. Drugs. (2017) 77:1389–97. doi: 10.1007/s40265-017-0784-3 PubMed DOI
Berbert Ferreira S, Berbert Ferreira R, Scheinberg MA. Atopic dermatitis: Tofacitinib, an option for refractory disease. Clin Case Rep. (2020) 8:3244–7. doi: 10.1002/ccr3.3325 PubMed DOI PMC
Silverberg JI, Bissonnette R, Kircik L, Murrell DF, Selfridge A, Liu K, et al. . Efficacy and safety of etrasimod, a sphingosine 1-phosphate receptor modulator, in adults with moderate-to-severe atopic dermatitis (ADVISE). J Eur Acad Dermatol Venereol. (2023) 37:1366–74. doi: 10.1111/jdv.18914 PubMed DOI
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) 401:204–14. doi: 10.1016/S0140-6736(22)02037-2 PubMed DOI