The Unique Molecular Signatures of Contact Dermatitis and Implications for Treatment
Tóm tắt
Irritant contact dermatitis (ICD) and allergic contact dermatitis (ACD) are common skin disorders that are characterized by inflammation, oozing, crusting, and pruritus. Atopic dermatitis (AD) is an inflammatory skin disease characterized by immune and barrier abnormalities and is additionally a risk factor for acquiring ICD and ACD. New work on allergic sensitization to common allergens (e.g., nickel and fragrance) in human skin has shown that different allergens have distinct molecular fingerprinting. For example, nickel promotes strong Th1/Th17 polarization, whereas fragrance allergy causes Th2/Th22 skewing, which is similar to the phenotype of AD. While ACD has previously been considered to be constant across all allergens, largely based on mouse models involving strong sensitizers, these new data suggest that ACD differs mechanistically according to allergen. Further, ACD in the setting of concurrent AD shows a different and attenuated phenotype as compared to healthy individuals with ACD, which influences the way AD patients respond to vaccination and other treatment modalities. As in contact sensitization, skin challenged by food patch testing shows that common food allergens (e.g., peanut and barley) also cause distinct immune polarizations in the skin. Additionally, house dust mite reactions in human skin have been profiled to show unique Th2, Th9, and Th17/22 activation as compared to controls, which are similar to the phenotype of psoriasis and contact responses to nickel. Given this information, ACD patients should be treated based on their unique allergen polarity. Refined understanding of the molecular behavior of contact dermatitis and related diseases translates to improved methods of inducing tolerance in sensitized allergic patients, such as with targeted drug therapy and epicutaneous immunotherapy.
Tài liệu tham khảo
Saint-Mezard P, Rosieres A, Krasteva M, Berard F, Dubois B, Kaiserlian D, Nicolas JF (2004) Allergic contact dermatitis. Eur J Dermatol: EJD 14(5):284–295
Zack B, Arrandale VH, Holness DL (2017) Preventing occupational skin disease: a review of training programs. Dermat : Contact, Atopic, Occup, Drug 28(3):169–182
Thyssen JP, Johansen JD, Linneberg A, Menne T (2010) The epidemiology of hand eczema in the general population--prevalence and main findings. Contact Dermat 62(2):75–87
Eckert L, Gupta S, Amand C, Gadkari A, Mahajan P, Gelfand JM (2017) The burden of atopic dermatitis in US adults: health care resource utilization data from the 2013 National Health and Wellness Survey. J Am Acad Dermatol
Weidinger S, Novak N (2016) Atopic dermatitis. Lancet (London, England) 387(10023):1109–1122
Chew AL, Maibach HI (2003) Occupational issues of irritant contact dermatitis. Int Arch Occup Environ Health 76(5):339–346
Gittler JK, Krueger JG, Guttman-Yassky E (2013) Atopic dermatitis results in intrinsic barrier and immune abnormalities: implications for contact dermatitis. J Allergy Clin Immunol 131(2):300–313
Clark SC, Zirwas MJ (2009) Management of occupational dermatitis. Dermatol Clin 27(3):365–383 vii-viii
Nosbaum A, Vocanson M, Rozieres A, Hennino A, Nicolas JF (2009) Allergic and irritant contact dermatitis. Eur J Dermatol: EJD. 19(4):325–332
Bonneville M, Chavagnac C, Vocanson M, Rozieres A, Benetiere J, Pernet I, Denis A, Nicolas JF, Hennino A (2007) Skin contact irritation conditions the development and severity of allergic contact dermatitis. J Investig Dermatol 127(6):1430–1435
Vocanson M, Hennino A, Rozieres A, Poyet G, Nicolas JF (2009) Effector and regulatory mechanisms in allergic contact dermatitis. Allergy 64(12):1699–1714
DaSilva SC, Sahu RP, Konger RL, Perkins SM, Kaplan MH, Travers JB (2012) Increased skin barrier disruption by sodium lauryl sulfate in mice expressing a constitutively active STAT6 in T cells. Arch Dermatol Res 304(1):65–71
Koppes SA, Engebretsen KA, Agner T, Angelova-Fischer I, Berents T, Brandner J, Brans R, Clausen ML, Hummler E, Jakasa I, Jurakić-Tončic R, John SM, Khnykin D, Molin S, Holm JO, Suomela S, Thierse HJ, Kezic S, Martin SF, Thyssen JP (2017) Current knowledge on biomarkers for contact sensitization and allergic contact dermatitis. Contact Dermat 77(1):1–16
Landeck L, Visser M, Kezic S, John SM (2012) Impact of tumour necrosis factor-alpha polymorphisms on irritant contact dermatitis. Contact Dermat 66(4):221–227
Allen MH, Wakelin SH, Holloway D, Lisby S, Baadsgaard O, Barker JN et al (2000) Association of TNFA gene polymorphism at position -308 with susceptibility to irritant contact dermatitis. Immunogenetics 51(3):201–205
de Jongh CM, John SM, Bruynzeel DP, Calkoen F, van Dijk FJ, Khrenova L et al (2008) Cytokine gene polymorphisms and susceptibility to chronic irritant contact dermatitis. Contact Dermat 58(5):269–277
Dhingra N, Shemer A, Correa da Rosa J, Rozenblit M, Fuentes-Duculan J, Gittler JK, Finney R, Czarnowicki T, Zheng X, Xu H, Estrada YD, Cardinale I, Suárez-Fariñas M, Krueger JG, Guttman-Yassky E (2014) Molecular profiling of contact dermatitis skin identifies allergen-dependent differences in immune response. J Allergy Clin Immunol 134(2):362–372
Martin SF, Jakob T (2008) From innate to adaptive immune responses in contact hypersensitivity. Curr Opin Allergy Clin Immunol 8(4):289–293
Weltzien HU, Martin SF, Nicolas JF (2014) T cell responses to contact allergens. EXS 104:41–49
Weltzien HU, Moulon C, Martin S, Padovan E, Hartmann U, Kohler J (1996) T cell immune responses to haptens. Structural models for allergic and autoimmune reactions. Toxicology 107(2):141–151
Larson RP, Zimmerli SC, Comeau MR, Itano A, Omori M, Iseki M, Hauser C, Ziegler SF (2010) Dibutyl phthalate-induced thymic stromal lymphopoietin is required for Th2 contact hypersensitivity responses. J Immunol 184(6):2974–2984
Vocanson M, Hennino A, Cluzel-Tailhardat M, Saint-Mezard P, Benetiere J, Chavagnac C, Berard F, Kaiserlian D, Nicolas JF (2006) CD8+ T cells are effector cells of contact dermatitis to common skin allergens in mice. J Investig Dermatol. 126(4):815–820
Saint-Mezard P, Krasteva M, Chavagnac C, Bosset S, Akiba H, Kehren J, Nicolas JF, Berard F, Kanitakis J, Kaiserlian D (2003) Afferent and efferent phases of allergic contact dermatitis (ACD) can be induced after a single skin contact with haptens: evidence using a mouse model of primary ACD. J Investig Dermatol. 120(4):641–647
Malajian D, Belsito DV (2013) Cutaneous delayed-type hypersensitivity in patients with atopic dermatitis. J Am Acad Dermatol 69(2):232–237
Newell L, Polak ME, Perera J, Owen C, Boyd P, Pickard C, Howarth PH, Healy E, Holloway JW, Friedmann PS, Ardern-Jones MR (2013) Sensitization via healthy skin programs Th2 responses in individuals with atopic dermatitis. J Investig Dermatol. 133(10):2372–2380
Correa da Rosa J, Malajian D, Shemer A, Rozenblit M, Dhingra N, Czarnowicki T, Khattri S, Ungar B, Finney R, Xu H, Zheng X, Estrada YD, Peng X, Suárez-Fariñas M, Krueger JG, Guttman-Yassky E (2015) Patients with atopic dermatitis have attenuated and distinct contact hypersensitivity responses to common allergens in skin. J Allergy Clin Immunol 135(3):712–720
Ungar B, Correa da Rosa J, Shemer A, Czarnowicki T, Estrada YD, Fuentes-Duculan J, Xu H, Zheng X, Peng X, Suárez-Fariñas M, Nowak-Wegrzyn A, Sampson HA, Krueger JG, Guttman-Yassky E (2017) Patch testing of food allergens promotes Th17 and Th2 responses with increased IL-33: a pilot study. Exp Dermatol 26(3):272–275
Tordesillas L, Goswami R, Benede S, Grishina G, Dunkin D, Jarvinen KM et al (2014) Skin exposure promotes a Th2-dependent sensitization to peanut allergens. J Clin Invest 124(11):4965–4975
Malik K, Ungar B, Garcet S, Dutt R, Dickstein D, Zheng X, et al. 2017 Dust mite induces multiple polar T-cell axes in human skin. Clinical and experimental allergy: journal of the British Society for Allergy and Clin Immunol
Kaplan DH, Igyarto BZ, Gaspari AA (2012) Early immune events in the induction of allergic contact dermatitis. Nat Rev Immunol 12(2):114–124
Honda T, Egawa G, Grabbe S, Kabashima K (2013) Update of immune events in the murine contact hypersensitivity model: toward the understanding of allergic contact dermatitis. J Investig Dermatol. 133(2):303–315
Peiser M (2013) Role of Th17 cells in skin inflammation of allergic contact dermatitis. Clin Dev Immunol 2013:261037
Zug KA, Warshaw EM, Fowler JF, Jr., Maibach HI, Belsito DL, Pratt MD, et al. Patch-test results of the North American Contact Dermatitis Group 2005-2006. Dermat : Contact, Atopic, Occup, Drug. 2009;20(3):149–160
Suarez-Farinas M, Tintle SJ, Shemer A, Chiricozzi A, Nograles K, Cardinale I et al (2011) Nonlesional atopic dermatitis skin is characterized by broad terminal differentiation defects and variable immune abnormalities. J Allergy Clin Immunol 127(4):954–64.e1–4
Czarnowicki T, Krueger JG, Guttman-Yassky E (2014) Skin barrier and immune dysregulation in atopic dermatitis: an evolving story with important clinical implications. J Allergy Clin Immunol Pract 2(4):371–379 quiz 80-1
Brunner PM, Emerson RO, Tipton C, Garcet S, Khattri S, Coats I, Krueger JG, Guttman-Yassky E (2017) Nonlesional atopic dermatitis skin shares similar T-cell clones with lesional tissues. Allergy 72:2017–2025
Guttman-Yassky E, Krueger JG (2017) Atopic dermatitis and psoriasis: two different immune diseases or one spectrum? Curr Opin Immunol 48:68–73
Brunner PM, Silverberg JI, Guttman-Yassky E, Paller AS, Kabashima K, Amagai M, Luger TA, Deleuran M, Werfel T, Eyerich K, Stingl G, Bagot M, Hijnen DJ, Ardern-Jones M, Reynolds N, Spuls P, Taieb A (2017) Increasing comorbidities suggest that atopic dermatitis is a systemic disorder. J Investig Dermatol. 137(1):18–25
Candi E, Schmidt R, Melino G (2005) The cornified envelope: a model of cell death in the skin. Nat Rev Mol Cell Biol 6(4):328–340
Cabanillas B, Novak N (2016) Atopic dermatitis and filaggrin. Curr Opin Immunol 42:1–8
Bin L, Leung DY (2016) Genetic and epigenetic studies of atopic dermatitis. Allergy, Asthma, Clin Immunol : Off J Can Soc Allergy Clin Immunol 12:52
Howell MD, Kim BE, Gao P, Grant AV, Boguniewicz M, DeBenedetto A, Schneider L, Beck LA, Barnes KC, Leung DYM (2009) Cytokine modulation of atopic dermatitis filaggrin skin expression. J Allergy Clin Immunol 124(3 Suppl 2):R7–r12
Ewald DA, Malajian D, Krueger JG, Workman CT, Wang T, Tian S, Litman T, Guttman-Yassky E, Suárez-Fariñas M (2015) Meta-analysis derived atopic dermatitis (MADAD) transcriptome defines a robust AD signature highlighting the involvement of atherosclerosis and lipid metabolism pathways. BMC Med Genet 8:60
Danso M, Boiten W, van Drongelen V, Gmelig Meijling K, Gooris G, El Ghalbzouri A et al (2017) Altered expression of epidermal lipid bio-synthesis enzymes in atopic dermatitis skin is accompanied by changes in stratum corneum lipid composition. J Dermatol Sci 88(1):57–66
Dickel H, Bruckner TM, Schmidt A, Diepgen TL (2003) Impact of atopic skin diathesis on occupational skin disease incidence in a working population. J Investig Dermatol. 121(1):37–40
Dhingra N, Gulati N, Guttman-Yassky E (2013) Mechanisms of contact sensitization offer insights into the role of barrier defects vs. intrinsic immune abnormalities as drivers of atopic dermatitis. J Investig Dermatol. 133(10):2311–2314
Savage J, Johns CB (2015) Food allergy: epidemiology and natural history. Immunol Allergy Clin N Am 35(1):45–59
Seltmann J, Roesner LM, von Hesler FW, Wittmann M, Werfel T. IL-33 impacts on the skin barrier by downregulating the expression of filaggrin. The Journal of allergy and clinical immunology. 2015;135(6):1659–61.e4
AnaptysBio Initiates Multiple Ascending Dose Cohorts In ANB020 Phase 1 Clinical Trial. [press release]. July 6, 2016 2016
Jurakic Toncic R, Lipozencic J (2010) Role and significance of atopy patch test. Acta Dermatovenerol Croat : ADC 18(1):38–55
Reisacher WR, Davison W (2017) Immunotherapy for food allergy. Curr Opin Otolaryngol Head Neck Surg 25(3):235–241
Herve PL, Descamps D, Deloizy C, Dhelft V, Laubreton D, Bouguyon E et al (2016) Non-invasive epicutaneous vaccine against respiratory syncytial virus: preclinical proof of concept. J Control Release : Off J Control Release Soc 243:146–159
Mondoulet L, Dioszeghy V, Ligouis M, Dhelft V, Dupont C, Benhamou PH (2010) Epicutaneous immunotherapy on intact skin using a new delivery system in a murine model of allergy. Clin Exp Allergy : J Br Soc Allergy Clin Immunol 40(4):659–667
Jones SM, Sicherer SH, Burks AW, Leung DY, Lindblad RW, Dawson P et al (2017) Epicutaneous immunotherapy for the treatment of peanut allergy in children and young adults. J Allergy Clin Immunol 139(4):1242–52.e9
Ewald DA, Noda S, Oliva M, Litman T, Nakajima S, Li X, Xu H, Workman CT, Scheipers P, Svitacheva N, Labuda T, Krueger JG, Suárez-Fariñas M, Kabashima K, Guttman-Yassky E (2017) Major differences between human atopic dermatitis and murine models, as determined by using global transcriptomic profiling. J Allergy Clin Immunol 139(2):562–571
Swindell WR, Johnston A, Carbajal S, Han G, Wohn C, Lu J, Xing X, Nair RP, Voorhees JJ, Elder JT, Wang XJ, Sano S, Prens EP, DiGiovanni J, Pittelkow MR, Ward NL, Gudjonsson JE (2011) Genome-wide expression profiling of five mouse models identifies similarities and differences with human psoriasis. PLoS One 6(4):e18266
Bromley SK, Larson RP, Ziegler SF, Luster AD (2013) IL-23 induces atopic dermatitis-like inflammation instead of psoriasis-like inflammation in CCR2-deficient mice. PLoS One 8(3):e58196
Neumann C, Gutgesell C, Fliegert F, Bonifer R, Herrmann F (1996) Comparative analysis of the frequency of house dust mite specific and nonspecific Th1 and Th2 cells in skin lesions and peripheral blood of patients with atopic dermatitis. J Mol Med(Berlin, Germany) 74(7):401–406
Gfesser M, Rakoski J, Ring J (1996) The disturbance of epidermal barrier function in atopy patch test reactions in atopic eczema. Br J Dermatol 135(4):560–565
Tanaka A, Amagai Y, Oida K, Matsuda H (2012) Recent findings in mouse models for human atopic dermatitis. Exp Anim 61(2):77–84
Noda S, Suarez-Farinas M, Ungar B, Kim SJ, de Guzman Strong C, Xu H et al (2015) The Asian atopic dermatitis phenotype combines features of atopic dermatitis and psoriasis with increased TH17 polarization. J Allergy Clin Immunol 136(5):1254–1264
Suarez-Farinas M, Dhingra N, Gittler J, Shemer A, Cardinale I, de Guzman Strong C et al (2013) Intrinsic atopic dermatitis shows similar TH2 and higher TH17 immune activation compared with extrinsic atopic dermatitis. J Allergy Clin Immunol 132(2):361–370
Esaki H, Brunner PM, Renert-Yuval Y, Czarnowicki T, Huynh T, Tran G, Lyon S, Rodriguez G, Immaneni S, Johnson DB, Bauer B, Fuentes-Duculan J, Zheng X, Peng X, Estrada YD, Xu H, de Guzman Strong C, Suárez-Fariñas M, Krueger JG, Paller AS, Guttman-Yassky E (2016) Early-onset pediatric atopic dermatitis is TH2 but also TH17 polarized in skin. J Allergy Clin Immunol 138(6):1639–1651
Czarnowicki T, Krueger JG, Guttman-Yassky E (2017) Novel concepts of prevention and treatment of atopic dermatitis through barrier and immune manipulations with implications for the atopic march. J Allergy Clin Immunol 139(6):1723–1734
Nakajima S, Igyarto BZ, Honda T, Egawa G, Otsuka A, Hara-Chikuma M et al (2012) Langerhans cells are critical in epicutaneous sensitization with protein antigen via thymic stromal lymphopoietin receptor signaling. JAllergy Clin Immunol 129(0):1048–55.e6
Steinbrink K, Mahnke K, Grabbe S, Enk AH, Jonuleit H (2009) Myeloid dendritic cell: from sentinel of immunity to key player of peripheral tolerance? Hum Immunol 70(5):289–293
Novak N, Gros E, Bieber T, Allam JP (2010) Human skin and oral mucosal dendritic cells as ‘good guys’ and ‘bad guys’ in allergic immune responses. Clin Exp Immunol 161(1):28–33
Our innovative EPIT® mechanism of action may have the potential to offer compelling clinical benefits to patients suffering from food allergies. 2014 [Available from: https://www.dbv-technologies.com/en/epit/moa]
Bissonnette R, Papp KA, Poulin Y, Gooderham M, Raman M, Mallbris L, Wang C, Purohit V, Mamolo C, Papacharalambous J, Ports WC (2016) Topical tofacitinib for atopic dermatitis: a phase IIa randomized trial. Br J Dermatol 175(5):902–911