Treatment implications of New Physiopathology Insights in Atopic Dermatitis

  • Ana Sofia Borges Interna Formação Específica de Dermatovenerologia/Resident of Dermatovenereology, Serviço de Dermatovenerologia, Hospital Santo António dos Capuchos, Centro Hospitalar Lisboa Central, Lisboa, Portugal
  • Rita Pinheiro Interna Formação Específica de Dermatovenerologia/Resident of Dermatovenereology, Serviço de Dermatovenerologia, Hospital Santo António dos Capuchos, Centro Hospitalar Lisboa Central, Lisboa, Portugal
  • Ana Brasileiro Assistente Hospitalar de Dermatovenerologia/Consultant of Dermatovenereology, Serviço de Dermatovenerologia, Hospital Santo António dos Capuchos, Centro Hospitalar Lisboa Central, Lisboa, Portugal
Keywords: Dermatitis, Atopic/drug therapy, Atopic/immunology, Atopic/physiopathology

Abstract

Atopic dermatitis is a chronic inflammatory skin disease that usually affects children, but can also start in adults. This disease has a strong impact on the quality of life, however treatment options for severe atopic dermatitis are scarce. New insights into the physiopathology, emphasizing the crucial role of epidermal barrier dysfunction and its relationship with immune dysregulation, contributed to the development of new treatments.

Downloads

Download data is not yet available.

References

Brito HS, Tavares E, Parente J, Aranha J, Silva MJ. Terapêutica biológica no eczema atópico. Rev Soc Port Dermatol Venereol. 2014; 72:86-9.

Murota H, Takeuchi S, Sugaya M, Tanioka M, Onozuka D, Hagihara A, et al. Characterization of socioeconomic

status of Japanese patients with atopic dermatitis showing poor medical adherence and reasons for drug discontinuation. J Dermatol Sci 2015; 79:279-87.

Totri CR, Eichenfield LF, Logan K, Proudfoot L, Schmitt J, Lara-Corrales I, et al. Prescribing practices for systemic agents in the treatment of severe pediatric atopic dermatitis in the US and Canada: The PeDRA TREAT survey. J Am Acad Dermatol. 2017; 76:281-5.

Jensen JM, Pfeiffer S, Witt M, Bräutigam M, Neumann C, Weichenthal M, et al. Different effects of pimecrolimus and betamethasone on the skin barrier in patients with atopic dermatitis. J Allergy Clin Immunol. 2009; 124 (3 Suppl 2):19-28.

Miller DW, Koch SB, Yentzer BA, Clark AR, O'Neill JR, Fountain J, et al. An over-the-counter moisturizer is as

clinically effective as, and more cost-effective than, prescription barrier creams in the treatment of children with

mild-to-moderate atopic dermatitis: a randomized, controlled trial. J Drugs Dermatol. 2011; 10:531-7.

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; 134:818-23.

Weidinger S, Novak N. Atopic dermatitis. Lancet. 2016; 387:1109-22.

Wollenberg A, Bieber T. Proactive therapy of atopic dermatitis: an emerging concept. Allergy. 2009; 64:276-8.

Berth-Jones J, Damstra RJ, Golsch S, Livden JK, Van Hooteghem O, Allegra F, et al. Twice weekly fluticasone propionate added to emollient maintenance treatment to reduce risk of relapse in atopic dermatitis: randomised, double blind, parallel group study. BMJ. 2003; 326:1367.

Wollenberg A, Reitamo S, Atzori F, Lahfa M, Ruzicka T, Healy E, et al. Proactive treatment of atopic dermatitis in adults with 0.1% tacrolimus ointment. Allergy. 2008; 63:742-50.

Elias PM, Steinhoff M. “Outside-to-inside” (and now back to “outside”) pathogenic mechanisms in atopic dermatitis. J Invest Dermatol. 2008; 128:1067-70.

Samuelov L, Sprecher E. Peeling off the genetics of atopic dermatitis-like congenital disorders. J Allergy Clin Immunol. 2014; 134:808-15.

Kim JE, Kim JS, Cho DH, Park HJ. Molecular mechanisms of cutaneous inflammatory disorder: atopic dermatitis. Int J Mol Sci. 2016; 17: E1234.

Riethmuller C, McAleer MA, Koppes SA, Abdayem R, Franz J, Haftek M, et al. Filaggrin breakdown products

determine corneocyte conformation in patients with atopic dermatitis. J Allergy Clin Immunol. 2015; 136:1573-

Ewald DA, Malajian D, Krueger JG, Workman CT, Wang T, Tian S, et al. Meta-analysis derived atopic dermatitis (MADAD) transcriptome defines a robust AD signature highlighting the involvement of atherosclerosis and lipid metabolism pathways. BMC Med Genomics 2015; 8:60.

Leung DY. Clinical implications of new mechanistic insights into atopic dermatitis. Curr Opin Pediatr. 2016;

:456-62.

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.

Paller AS, Tom WL, Lebwohl MG, Blumenthal RL, Boguniewicz M, Call RS, et al. Efficacy and safety of crisaborole ointment, a novel, nonsteroidal phosphodiesterase 4 (PDE4) inhibitor for the topical treatment of atopic dermatitis (AD) in children and adults. J Am Acad Dermatol. 2016; 75:494-503.

Volf EM, Au SC, Dumont N, Scheinman P, Gottlieb AB. A phase 2, open-label, investigator-initiated study to evaluate the safety and efficacy of apremilast in subjects with recalcitrant allergic contact or atopic dermatitis. J Drugs Dermatol. 2012; 11:341-6.

Samrao A, Berry TM, Goreshi R, Simpson EL. A pilot study of an oral phosphodiesterase inhibitor (apremilast) for atopic dermatitis in adults. Arch Dermatol. 2012; 148:890-7.

Hamilton JD, Suárez-Fariñas M, Dhingra N, Cardinale I, Li X, Kostic A. Dupilumab improves the molecular signature in skin of patients with moderate-to-severe atopic dermatitis. J Allergy Clin Immunol. 2014; 134:1293-300.

Noda S, Krueger JG, Guttman-Yassky E. The translational revolution and use of biologics in patients with inflammatory skin diseases. J Allergy Clin Immunol. 2015;135:324-36.

Kraft M, Worm M. Dupilumab in the treatment of moderate-to-severe atopic dermatitis. Expert Rev Clin Immunol. 2017; 13:301-10.

Jancin B. Lebrikizumab opens new door in atopic dermatitis therapy [consultado15 Dez 2016] Disponivel

em : http://www.mdedge.com/edermatologynews/article/115736/atopic-dermatitis/lebrikizumab-opens-new-

-door-atopic-dermatitis

Son ED, Kim HJ, Kim KH, Bin BH, Bae IH, Lim KM, et al. S100a7 (psoriasin) inhibits human epidermal differentiation by enhanced IL-6 secretion through IkB/NF-kB signaling. Exp Dermatol. 2016; 25:636-41.

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; 165:492-8.

Gittler JK, Shemer A, Suarez-Farinas M, Fuentes-Duculan J, Gulewicz KJ, Wang CQ, et al. Progressive activation of Th2/Th22 cytokines and selective epidermal proteins characterizes acute and chronic atopic dermatitis. J Allergy Clin Immunol. 2012; 130:1344-54.

Sonkoly E, Muller A, Lauerma AI, Pivarcsi A, Soto H, Kemeny L, et al. IL-31: A new link between t cells and pruritus in atopic skin inflammation. J. Allergy Clin Immunol. 2006; 117:411-7.

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; 1:1-28.

Zhang Q, Putheti P, Zhou Q, Liu Q, Gao W. Structures and biological functions of IL-31 and IL-31 receptors. Cytokine Growth Factor Rev. 2008; 19:347-56.

Kato A, Fujii E, Watanabe T, Takashima Y, Matsushita H, Furuhashi T, et al Distribution of IL-31 and its receptor expressing cells in skin of atopic dermatitis. J Dermatol Sci. 2014; 74:229-35.

Hawro T, Saluja R, Weller K, Altrichter S, Metz M, Maurer M. Interleukin-31 does not induce immediate itch in atopic dermatitis patients and healthy controls after skin challenge. Allergy. 2014; 69:113-17.

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; 2; 376:826-35.

Nemoto O, Furue M, Nakagawa H, Shiramoto M, Hanada R, Matsuki S, et al. The first trial of CIM331, a humanized antihuman interleukin-31 receptor A antibody, in healthy volunteers and patients with atopic dermatitis to evaluate safety, tolerability and pharmacokinetics of a single dose in a randomized, double-blind, placebo-controlled study. Br J Dermatol. 2016; 174:296-304.

Czarnowicki T, Krueger JG, Guttman-Yassky E. Skin barrier and immune dysregulation in atopic dermatitis: an evolving story with important clinical implications. J Allergy Clin Immunol Pract. 2014; 2:371-9.

Wlodek C, Hewitt H, Kennedy CT. Use of ustekinumab for severe refractory atopic dermatitis in a young teenager. Clin Exp Dermatol. 2016; 41:625-7.

Shroff A, Guttman-Yassky E. Successful use of ustekinumab therapy in refractory severe atopic dermatitis. JAAD Case Rep. 2014 22;1:25-6

Puya R, Alvarez-López M, Velez A, Casas Asuncion E, Moreno JC. Treatment of severe refractory adult atopic

dermatitis with ustekinumab. Int J Dermatol. 2012; 51:115-6.

Khattri S, Brunner PM, Garcet S, Finney R, Cohen SR, Oliva M, et al. Eficacy and safety of ustekinumab treatment in adults with moderate-to-severe atopic dermatitis. Exp Dermatol. 2017; 26:28-35.

Noda S, Hashim PW, Khattri S, Shroff A, Guttman-Yassky E. Successful use of secukinumab in an Asian patient with severe refractory atopic dermatitis. J Invest Dermatol. 2016; 136(5 suppl. 1):S40.

A pilot study to evaluate the efficacy and safety of secukinumab in the treatment of moderate to severe atopic dermatitis [consultado15 Dez 2016] Disponível em: https://clinicaltrials.gov/ct2/show/NCT02594098?term=%22secukinumab%22+AND+%22atopic+dermatitis%22&rank=1

Gao PS, Rafaels NM, Mu D, Hand T, Murray T, Boguniewicz M, et al. Genetic variants in thymic stromal lymphopoietin are associated with atopic dermatitis and eczema herpeticum. J Allergy Clin Immunol. 2010; 125:1403-7.

Nakajima S, Igyártó BZ, Honda T, Egawa G, Otsuka A, Hara-Chikuma M, et al. Langerhans cells are critical in epicutaneous sensitization with protein antigen via thymic stromal lymphopoietin receptor signaling. J Allergy Clin Immunol. 2012; 129:1048-55.

Landheer J, Giovannone B, Mattson JD, Tjabringa S, Bruijnzeel-Koomen CA, McClanahan T, et al. Epicutaneous application of house dust mite induces thymic stromal lymphopoietin in non-lesional skin of patients with atopic dermatitis. J Allergy Clin Immunol. 2013; 132:1252-4.

Amano W, Nakajima S, Kunugi H, Numata Y, Kitoh, A, Egawa G, et al. The janus kinase inhibitor JTE-052 improves skin barrier function through suppressing signal transducer and activator of transcription 3 signaling. J. Allergy Clin Immunol. 2015; 136:667-77.

Shreberk-Hassidim R, Ramot Y, Zlotogorski. A Janus kinase inhibitors in dermatology: A systematic review. J Am Acad Dermatol.2017; 3:31187-2.

Bissonnette R, Papp KA, Poulin Y, Gooderham M, Raman M, Mallbris L, et al. Topical tofacitinib for atopic dermatitis: a phase IIa randomized trial. Br J Dermatol. 2016;175:902-11.

Levy LL, Urban J, King BA. Treatment of recalcitrant atopic dermatitis with the oral Janus kinase inhibitor tofacitinib citrate. J Am Acad Dermatol. 2015; 73:395-9.

Published
2017-07-20
How to Cite
Borges, A. S., Pinheiro, R., & Brasileiro, A. (2017). Treatment implications of New Physiopathology Insights in Atopic Dermatitis. Journal of the Portuguese Society of Dermatology and Venereology, 75(2), 123-127. https://doi.org/10.29021/spdv.75.2.766
Section
Review Articles