Epidermal dysfunctions in canine atopic dermatitis: Clinical impacts and therapies

Tiago Cunha Ferreira, Rodrigo Fonseca de Medeiros Guedes, Diana Célia Sousa Nunes-Pinheiro

Resumo


Canine atopic dermatitis (CAD) is an immune-mediated disease characterized by inflammatory and pruritic processes. Recent theories propose that epidermal barrier failures can facilitate the entry of potential allergens, microorganisms and irritants, increasing the interaction with cells of the immune system, causing its excessive stimulation. Therefore, the present review aims to describe the main epidermal changes that contribute to the pathogenesis of CAD, as well as to present therapies used to recover the skin barrier. The most frequent changes in the epidermis of atopic animals involve transepidermal water loss, lipid and protein dysfunctions. Ceramides are lipids with structural functions, but they are also involved in cell signaling. These molecules, although present, have reduced concentrations in the skin of dogs with CAD, which is considered both primary and secondary defects of inflammatory processes. Other epidermal components, such as filaggrin, an essential protein in development and maintenance of skin barrier integrity, and antimicrobial peptides responsible for defense against pathogens and modulation of immune response, have mutations in atopic animals, contributing to the appearance of recurrent infections. These defects in cutaneous barrier may contribute to the pathogenesis of CAD, and such information helps in the treatment of this pathology, improving animal welfare with skin-healing therapies.


Palavras-chave


Canine Atopy, Tegument disorders, Ceramides, Filaggrin, Antimicrobial Peptides

Referências


AGERBERTH, B.; CHARO, J.; WERR, J.; OLSSON, B.; IDALI, F.; LINDBOM, L.; KIESLLING, R.; JORNVALL, H.; WIGZELL, H.; GUDMUNDSSON, G.H. The human antimicrobial and chemotactic peptides LL-37 and a-defensins are expressed by specific lymphocyte and monocytes populations. Blood, v.96, p. 3086–93, 2000.

BANKS, W. J. Histologia veterinária aplicada. 2. ed. São Paulo: Manole, 1992. 629 p.

BERDYSHEV, E.; GOLEVA, E.; BRONOVA, I.; DYJACK, N.; RIOS, C.; JUNG, J.; TAYLOR, P.; JEONG, M.; HALL, C.F.; RICHERS, B.N.; NORQUEST, K.A.; ZHENG, T.; SEIBOLD, M.A.; LEUNG, D.Y.M. Lipid abnormalities in atopic skin are driven by type 2 cytokines. JCI Insight, v.3, e98006, 2018.

BLASKOVIC, M.; ROSENKRANTZ, W.; NEUBER, A.; SAUTER-LOUIS, C.; MUELLER, R.S. The effect of a spot-on formulation containing polyunsaturated fatty acids and essential oils on dogs with atopic dermatitis. The Veterinary Journal, v.199, p.39-43, 2014.

BOURDEAU, P.; BRUET, V.; GREMILLET, C. Evaluation of phytosphingosine-containing shampoo and microemulsion spray in the clinical control of allergic dermatoses in dogs: preliminary results of a multicentre study (abstract). Veterinary Dermatology, v.18, p.177–8. 2007

BRAFF, M.H.; ZAIOU, M.; FIERER, J.; NIZET, V.; GALLO, R.L. Keratinocyte production of cathelicidin provides direct activity against bacterial skin pathogens. Infection and Immunity, v.73, p. 6771–6781, 2005.

BREIDEN, B.; SANDHOFF, K.. The role of sphingolipid metabolism in cutaneous permeability barrier formation. Biochimic et Biophysic Acta., v.1841, p.441–452, 2014.

BRUET V.; BOURDEAU, P.J.; ROUSSEL, A.; IMPARATO, L.; DESFONTIS, J.C. Characterization of pruritus in canine atopic dermatitis, flea bite hypersensitivity and flea infestation and its role in diagnosis. Veterinary Dermatology, v.23, p.487– e493, 2012.

CERRATO, S.; RAMIÓ-LLUCH, L.; BRAZIS, P.; FONDEVILLA, D.; SEGARRA, S.; PUIGDEMONT, A. Effects of sphingolipd extracts on the morphological structure and lipid profile in an in vitro model of canine skin. The Veterinary Journal, v.212, p.58-64, 2016.

CHERVET, L.; GALICHET, A.; McLEAN, W.H.; CHEN, H.; SUTER, M.M.; ROOSJE, P.J.; MULLER, E.J. Missing C-terminal filaggrin expression, NFkappaB activation and hyperproliferation identify the dog as a putative model to study epidermal dysfunction in atopic dermatitis. Experimental Dermatology, v.19, p.e343–e346, 2010.

CZAMOWICKI, T.; KRUEGER, J.G.; GUTTMANN-YASSKY, E. Skin barrier and immune dysregulation in atopic dermatitis: an evolving story with important clinical implications. Journal of Allergy and Clininical Immunology: In Practice, v.2(4), p.371-379, 2014.

DI NARDO, A.; VITIELLO, A.; GALLO, R.L. Cutting edge: mast cell antimicrobial activity is mediated by expression of cathelicidin antimicrobial peptide. Journal of Immunology, v.170, p.2274–2278, 2003.

ELIAS, P.M.; HATANO, Y.; WILLIAMS, M.L. Basis for the barrier abnormality in atopic dermatitis: outside-inside-outside pathogenic mechanisms. Journal of Allergy and Clinical Immunology, v.121, p.1337–1343, 2008.

FAVROT, C.; STEFFAN, J.; SEEWALD, W.; PICCO, F. A prospective study on the clinical features of chronic canine atopic dermatitis and its diagnosis. Veterinary Dermatology, v.21, p. 23–31, 2010.

FRANCO, J.; FERREIRA, C.; PASCHOAL-SOBREIRA, T.J.; SUNDBERG, J.P.; HOGENESCH, H. Profiling of epidermal lipids in a mouse model of dermatitis: Identification of potential biomarkers. PLoS ONE, v.13, e0196595, 2018.

GRIFFIN, C.E.; DeBOER, D.J. The ACVD task force on canine atopic dermatitis (XIV): clinical manifestations of canine atopic dermatitis. Veterinary Immunology and Immunopathology, v.81, p.255–269, 2001.

HALLIWELL, R.E.W. Revised nomenclature for veterinary allergy. Veterinary Immunology and Immunopathology, v.114, p. 207–208, 2006.

HARA, J.; HIGUCHI, K.; OKAMOTO, R.; KAWASHIMA, M.; IMOKAWA, G. High-expression of sphingomyelin deacylase is an important determinant of ceramide deficiency leading to barrier disruption in atopic dermatitis. Journal of Investigative Dermatology, v.115, p.406–413, 2000.

HILLIER, A.; LLOYD, D.H.; WEESE, J.S.; BLONDEAU, J.M.; BOOTHE, D.; BREITSCHWERDT, E.; GUARDABASSI, L.; PAPICH, M.G.; RANKIN, S.; TURNIDGE, J.D.; SYKES, J.E. Guidelines for the diagnosis and antimicrobial therapy of canine superficial bacterial folliculitis (Antimicrobial Guidelines Working Group of the International Society for Companion Animal Infectious Diseases). Veterinary Dermatology, v.25, p.163-e43, 2014.

IRVINE, A.D.; McLEAN, W.H.; LEUNG, D.Y. Filaggrin mutations associated with skin and allergic diseases. New England Journal of Medicine, v.365(14), p.1315‑1327, 2011.

JENSSEN, H.; HAMILL, P.; HANCOCK, R.E.W. Peptide antimicrobial agents. Clinical Microbiology Review, v.19, p. 491–511, 2006.

KEZIC, S.; KEMPERMAN, P.M.; KOSTER, E.; JONGH, C.M.; THIO, H.B.; CAMPBELL, L.E.; IRVINE, A.D.; McLEAN, W.H.; PUPPELS, G.J.; CASPERS, P.J. Loss-offunction mutations in the filaggrin gene lead to reduced level of natural moisturizing factor in the stratum corneum. Journal of Investigative Dermatology, v.128, p.2117-2119, 2008.

KIERSZENBAUM, A. L. Histology and cell biology: An introduction to pathology. 2nd. ed. St. Louis: Mosby Elsevier, 2006. 688 p.

LEE, D.Y.; YAMASAKI, K.; RUDSIL, J.; ZOUBOLIS, C.C.; PARK, G.T.; YANG, J.M.; GALLO, R.L. et al. Sebocytes express functional cathelicidin antimicrobial peptides and can act to kill Propionibacterium acnes. Journal of Investigative Dermatology, v.128, p.1863–1866, 2008.

McGRATH, J.A. Filaggrin and the great epidermal barrier grief. Australasian Journal of Dermatology, v.49, p.67-74, 2008.

MENENDEZ, A.; BRETT FINLEY, B. Defensins in the immunology of bacterial infections. Current Opinion in Immunology, v.19, p.385–391, 2007.

NOLI, C.; FOSTER, A.P.; ROSENKRANTZ, W. Veterinary Allergy. Wiley-Blackwell, 2014. 470p.

OLIVRY, T.; DeBOER, D.J.; FAVROT, C.; JACKSON, H.A.; MUELLER, R.S.; NUTTALL, T.; PRELAUD, P. Treatment of canine atopic dermatitis: 2015 updated guidelines from the International Committee on Allergic Diseases of Animals (ICADA). BMC Veterinary Research, v.11, p.1-15, 2015.

O'REGAN, G.M.; SANDILANDS, A.; McLEAN, I.; Irvine, A. D. Filaggrin in atopic dermatitis. Journal of Allergy and Clininical Immunology, v.122, p.689-693, 2008.

OSAWA, R.; AKIYAMA, M.; SHIMIZU, H. Filaggrin gene defects and the risk of developing allergic disorders. Allergology Intternational, v.60 p.1–9, 2011.

PALFFY, R.; GARDLIK, R.; BEHULIAK, M.; KADASI, L.; TURNA, J.; CELEC, P. On the physiology and pathophysiology of antimicrobial peptides. Molecular Medicine, v.15, p. 51–59, 2009.

POPA, I.; THUY, L.H.; COLSH, B.; PIN, D.; GATTO, H; HAFTEK, M.; PORTOUKALIAN, J. Analysis of free and proteinbound ceramides by tape stripping of stratum corneum from dogs. Archives of Dermatological Research, v.302, p.639–644, 2010.

POPA, I., PIN, D.; REMOUE, N.; OSTA, B.; CALLAJEON, S.; VIDEMONT, E.; GATTO, H.; PORTOUKALIAN, J.; HAFTEK, M. Analysis of epidermal lipids in normal and atopic dogs, before and after administration of an oral omega-6/omega-3 fatty acid feed supplement. A pilot study. Veterinary Research Communications. V.35, p.501–509, 2011a.

POPA, I.; REMOUE, N.; HOANG, L.T.; PORTOUKALIAN, J. Atopic dermatitis in dogs is associated with a high heterogeneity in the distribution of protein-bound lipids within the stratum corneum. Archives of Dermatological Research, v.303, p.433–440, 2011b.

POPA, I.; REMOUE, N.; OSTA, B.; PIN, D.; GATTO, H.; HAFTEK, M.; PORTOUKALIAN, J. The lipid alterations in the stratum corneum of dogs with atopic dermatitis are alleviated by topical application of a sphingolipid-containing emulsion. Clinical and Experimental Dermatology, v.37, p.665-671, 2012.

RODRIGUES-HOFFMANN, A.; PATTERSON, A.P.; DIESEL, A.; LAWHON, S.D.; LY, H.J.; STEPHESON, C.E.; MANSELL, J.; STEINER, J.M.; DOWD, S.E.; OLIVRY, T.; SUCHODOLSKI, J.S. The Skin Microbiome in Healthy and Allergic Dogs. PLoS ONE, v.9 (1), doi:10.1371/journal.pone.003197, p.e83197, 2014.

SANTORO, D.; BUNICK, D.; GRAVES, T. K.; SEGRE, M. Evaluation of canine antimicrobial peptides in infected and noninfected chronic atopic skin. Veterinary Dermatology, v.22, p.61-67, 2010.

SCHAUBER, J.; GALLO, R.L. Antimicrobial peptides and the skin immune defense system. Journal of Allergy and Clinical Immunology, v.122, p. 261–266, 2008.

SCHITTEK, B.; PAULMANN, M.; SENYUREK, I.; STEFFEN, H. The role of antimicrobialpeptides in human skin and in skin infectious diseases. Infectious Disorders Drug Targets, v.8, p.135–143, 2008.

SHIMADA, K.; YOON, J.S.; YOSHIHARA, T.; IWASAKI, T.; NISHIFUJI, K. Increased transepidermal water loss and decreased ceramide content in lesional and non-lesional skin of dogs with atopic dermatitis. Veterinary Dermatology, v.20, p.541-546, 2009.

TIMMERMAN, J.G.; HEEDERIK, D.; SPEE, T.; VAN ROOY, F.G.; KROP, E.J.M.; KOPPELMAN, G.H.; RUSTEMEYER, T.; SMIT, L.A.M. Contact dermatitis in the construction industry: the role of fillaggrin loss-of-function mutations. British Journal of Dermatology, v. 174, p.348-355, 2016.

UCHIDA, Y. Ceramide signaling in mammalian epidermis. Biochimica et Biophysica Acta, v.1841, p.453–462, 2014.

WILHEM, S.; KOVALIK, M,; FAVROT, C. Breed-associated phenotypes in canine atopic dermatitis. Veterinary Dermatology, v.22, p.143–149, 2011


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