A systematic review of allergen immunotherapy, a successful therapy for canine atopic dermatitis and feline atopic skin syndrome

Ralf S. Mueller Centre for Clinical Veterinary Medicine, Faculty of Veterinary Medicine, University of Munich, München, Germany

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Abstract

Canine atopic dermatitis and feline atopic skin syndrome are common presentations in small animal practice. Numerous drugs are used for symptomatic therapy. The only definitive treatment based on the cause of the disease is allergen immunotherapy. Classical allergen immunotherapy (AIT) consists of subcutaneous injections of an extract containing offending allergens, with increasing doses and allergen concentrations at short intervals during the induction phase of several weeks to months followed by a maintenance phase, where a fixed dose is typically given at longer intervals. Dose and interval are tailored to the individual patient. Newer types of AIT include rush immunotherapy, where the induction phase is abbreviated, intralymphatic immunotherapy, and oromucosal or sublingual immunotherapy. AIT aims at inducing a regulatory T-cell response and subsequently downregulating the exaggerated immune response to offending allergens leading to clinical signs. This article reviews the published knowledge about allergen immunotherapy in dogs and cats for small animal practitioners.

Abstract

Canine atopic dermatitis and feline atopic skin syndrome are common presentations in small animal practice. Numerous drugs are used for symptomatic therapy. The only definitive treatment based on the cause of the disease is allergen immunotherapy. Classical allergen immunotherapy (AIT) consists of subcutaneous injections of an extract containing offending allergens, with increasing doses and allergen concentrations at short intervals during the induction phase of several weeks to months followed by a maintenance phase, where a fixed dose is typically given at longer intervals. Dose and interval are tailored to the individual patient. Newer types of AIT include rush immunotherapy, where the induction phase is abbreviated, intralymphatic immunotherapy, and oromucosal or sublingual immunotherapy. AIT aims at inducing a regulatory T-cell response and subsequently downregulating the exaggerated immune response to offending allergens leading to clinical signs. This article reviews the published knowledge about allergen immunotherapy in dogs and cats for small animal practitioners.

  • 1.

    Bizikova P, Pucheu-Haston CM, Eisenschenk MN, Marsella R, Nuttall T, Santoro D. Review: role of genetics and the environment in the pathogenesis of canine atopic dermatitis. Vet Dermatol. 2015;26:95-e26. doi:10.1111/vde.12198

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 2.

    Marsella R. Advances in our understanding of canine atopic dermatitis. Vet Dermatol. 2021;32:547-e151. doi:10.1111/vde.12965

  • 3.

    Marsella R, Sousa CA, Gonzales AJ, Fadok VA. Current understanding of the pathophysiologic mechanisms of canine atopic dermatitis. J Am Vet Med Assoc. 2012;241:194207. doi:10.2460/javma.241.2.194

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 4.

    Pucheu-Haston CM, Bizikova P, Eisenschenk MN, Santoro D, Nuttall T, Marsella R. Review: the role of antibodies, autoantigens and food allergens in canine atopic dermatitis. Vet Dermatol. 2015;26:115-e130. doi:10.1111/vde.12201

    • Search Google Scholar
    • Export Citation
  • 5.

    Pucheu-Haston CM, Bizikova P, Marsella R, Santoro D, Nuttall T, Eisenschenk MN. Review: lymphocytes, cytokines, chemokines and the T-helper 1-T-helper 2 balance in canine atopic dermatitis. Vet Dermatol. 2015;26:124-e132. doi:10.1111/vde.12205

    • Search Google Scholar
    • Export Citation
  • 6.

    Pucheu-Haston CM, Santoro D, Bizikova P, Eisenschenk MN, Marsella R, Nuttall T. Review: innate immunity, lipid metabolism and nutrition in canine atopic dermatitis. Vet Dermatol. 2015;26:104-e128. doi:10.1111/vde.12199

    • Search Google Scholar
    • Export Citation
  • 7.

    Halliwell R, Banovic F, Mueller RS, Olivry T. Immunopathogenesis of the feline atopic syndrome. Vet Dermatol. 2021;32:13-e14. doi:10.1111/vde.12928

    • Search Google Scholar
    • Export Citation
  • 8.

    Santoro D, Marsella R, Pucheu-Haston CM, Eisenschenk MN, Nuttall T, Bizikova P. Review: pathogenesis of canine atopic dermatitis: skin barrier and host-micro-organism interaction. Vet Dermatol. 2015;26:84-e25. doi:10.1111/vde.12197

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 9.

    Favrot C, Steffan J, Seewald W, Picco F. A prospective study on the clinical features of chronic canine atopic dermatitis and its diagnosis. Vet Dermatol. 2010;21:2331. doi:10.1111/j.1365-3164.2009.00758.x

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 10.

    Jaeger K, Linek M, Power HT, et al. Breed and site predispositions of dogs with atopic dermatitis: a comparison of two continents. Vet Dermatol. 2010;21:118122.

    • Search Google Scholar
    • Export Citation
  • 11.

    Picco F, Zini E, Nett C, et al. A prospective study on canine atopic dermatitis and food-induced allergic dermatitis in Switzerland. Vet Dermatol. 2008;19:150155. doi:10.1111/j.1365-3164.2008.00669.x

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 12.

    Bajwa J. Feline atopic syndrome–an update. Can Vet J. 2021;62:12371240.

  • 13.

    Santoro D, Pucheu-Haston CM, Prost C, Mueller RS, Jackson H. Clinical signs and diagnosis of feline atopic syndrome: detailed guidelines for a correct diagnosis. Vet Dermatol. 2021;32:26-e26. doi:10.1111/vde.12935

    • Search Google Scholar
    • Export Citation
  • 14.

    Mueller RS, Nuttall T, Prost C, Schulz B, Bizikova P. Treatment of the feline atopic syndrome–a systematic review. Vet Dermatol. 2021;32:43-e8. doi:10.1111/vde.12933

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 15.

    Olivry T, DeBoer DJ, Favrot C, et al. Treatment of canine atopic dermatitis: 2010 clinical practice guidelines from the International Task Force on Canine Atopic Dermatitis. Vet Dermatol. 2010;21:233248. doi:10.1111/j.1365-3164.2010.00889.x

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 16.

    Olivry T, DeBoer DJ, Favrot C, et al. Treatment of canine atopic dermatitis: 2015 updated guidelines from the International Committee on Allergic Diseases of Animals (ICADA). BMC Vet Res. 2015;11:210. doi:10.1186/s12917-015-0514-6

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 17.

    Loewenstein C, Mueller RS. A review of allergen-specific immunotherapy in human and veterinary medicine. Vet Dermatol. 2009;20:8498. doi:10.1111/j.1365-3164.2008.00727.x

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 18.

    Mueller RS, Jensen-Jarolim E, Roth-Walter F, et al. Allergen immunotherapy in people, dogs, cats and horses–differences, similarities and research needs. Allergy. 2018;73:19891999. doi:10.1111/all.13464

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 19.

    Keppel KE, Campbell KL, Zuckermann FA, Greeley EA, Schaeffer DJ, Husmann RJ. Quantitation of canine regulatory T cell populations, serum interleukin-10 and allergen-specific IgE concentrations in healthy control dogs and canine atopic dermatitis patients receiving allergen-specific immunotherapy. Vet Immunol Immunopathol. 2008;123:337344. doi:10.1016/j.vetimm.2008.02.008

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 20.

    DeBoer DJ, Verbrugge M, Morris M. Clinical and immunological responses of dust mite sensitive, atopic dogs to treatment with sublingual immunotherapy (SLIT). Vet Dermatol. 2016;27:82-e23. doi:10.1111/vde.12284

    • Search Google Scholar
    • Export Citation
  • 21.

    Fischer NM, Rostaher A, Favrot C. A comparative study of subcutaneous, intralymphatic and sublingual immunotherapy for the long-term control of dogs with nonseasonal atopic dermatitis. Vet Dermatol. 2020;31:365-e396. doi:10.1111/vde.12860

    • Search Google Scholar
    • Export Citation
  • 22.

    Foj R, Carrasco I, Clemente F, et al. Clinical efficacy of sublingual allergen-specific immunotherapy in 22 cats with atopic dermatitis. Vet Dermatol. 2021;32:67-e12. doi:10.1111/vde.12926

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 23.

    Hylander T, Latif L, Petersson-Westin U, Cardell LO. Intralymphatic allergen-specific immunotherapy: an effective and safe alternative treatment route for pollen-induced allergic rhinitis. J Allergy Clin Immunol. 2013;131:412420. doi:10.1016/j.jaci.2012.10.056

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 24.

    Senti G, Crameri R, Kuster D, et al. Intralymphatic immunotherapy for cat allergy induces tolerance after only 3 injections. J Allergy Clin Immunol. 2012;129:12901296. doi:10.1016/j.jaci.2012.02.026

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 25.

    Senti G, Prinz Vavricka BM, Erdmann I, et al. Intralymphatic allergen administration renders specific immunotherapy faster and safer: a randomized controlled trial. Proc Natl Acad Sci U S A. 2008;105:1790817912. doi:10.1073/pnas.0803725105

    • Search Google Scholar
    • Export Citation
  • 26.

    Fischer N, Rostaher A, Favrot C. Intralymphatic immunotherapy: an effective and safe alternative route for canine atopic dermatitis. Schweiz Arch Tierheilkd. 2016;158:646652. doi:10.17236/sat00085

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 27.

    Hatzmann K, Mueller RS. Practicability and safety of intralymphatic allergen-specific immunotherapy in dogs with atopic dermatitis. Annual Congress of the European Society of Veterinary Dermatology. European Society of Veterinary Dermatology; 2011:463464.

  • 28.

    Timm K, Mueller RS, Nett-Mettler CS. Long term effects of intralymphatic immunotherapy (ILIT) in canine atopic dermatitis. Vet Dermatol. 2018;29:123-e49. doi:10.1111/vde.12517

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 29.

    Mueller RS, Zablotski Y, Baumann K, et al. A randomised, double-blinded comparison between subcutaneous rush and intralympathic allergen immunotherapy induction in atopic dogs. Vet Dermatol. 2023;34:(2)9198.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 30.

    Mueller RS. Update on allergen immunotherapy. Vet Clin North Am Small Anim Pract. 2019;49:17. doi:10.1016/j.cvsm.2018.08.001

  • 31.

    Scott KV, White SD, Rosychuk RAW. A retrospective study of hyposensitization in atopic dogs in a flea scarce environment In: Ihrke PJ, Mason IS, White SD, eds. Advances in Veterinary Dermatology. Pergamon Press; 1993:7987.

    • Search Google Scholar
    • Export Citation
  • 32.

    Lian TM, Halliwell RE. Allergen-specific IgE and IgGd antibodies in atopic and normal dogs. Vet Immunol Immunopathol. 1998;66:203223. doi:10.1016/S0165-2427(98)00199-8

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 33.

    Mueller RS. Intradermale reaktionen gegen die vorratsmilbe Lepidoglyphus destructor bei normalen unden und hunden mit atopischer dermatitis. Kleintierpraxis. 2011;56:510.

    • Search Google Scholar
    • Export Citation
  • 34.

    Mueller RS, Fieseler KV, Rosychuk RA, Greenwalt T. Intradermal testing with the storage mite Tyrophagus putrescentiae in normal dogs and dogs with atopic dermatitis in Colorado. Vet Dermatol. 2005;16:2731. doi:10.1111/j.1365-3164.2005.00415.x

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 35.

    Mallmann S, Klinger CJ, Classen J, et al. Clinical relevance of intradermal test results in atopic dogs. Tierarztl Prax Ausg K Kleintiere Heimtiere. 2021;49:349356. doi:10.1055/a-1584-4965

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 36.

    Hobi S, Mueller RS. Efficacy and safety of rush immunotherapy with alum-precipitated allergens in canine atopic dermatitis. Tierarztl Prax Ausg K Kleintiere Heimtiere. 2014;42:167173.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 37.

    Nuttall TJ, Thoday KL, van den Broek AH, Jackson HA, Sture GH, Halliwell RE. Retrospective survey of allergen immunotherapy in canine atopy. Vet Rec. 1998;143:139142. doi:10.1136/vr.143.5.139

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 38.

    Mueller RS, Bettenay SV. Long-term immunotherapy of 146 dogs with atopic dermatitis–a retrospective study. Austr Vet Pract. 1996;26:128.

    • Search Google Scholar
    • Export Citation
  • 39.

    Mueller RS, Fieseler KV, Zabel S, et al. Conventional and rush immunotherapy in canine atopic dermatitis. In: Hillier A, Foster AP, Kwochka KW, eds. Advances in Veterinary Dermatology. Vol 5. Blackwell Publishing; 2005:6069.

    • Search Google Scholar
    • Export Citation
  • 40.

    Zur G, White SD, Ihrke PJ, Kass PH, Toebe N. Canine atopic dermatitis: a retrospective study of 169 cases examined at the University of California, Davis, 1992–1998. Part II. Response to hyposensitization. Vet Dermatol. 2002;13:103111. doi:10.1046/j.1365-3164.2002.00286.x

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 41.

    Mueller RS, Bettenay SV. Evaluation of the safety of an abbreviated course of injections of allergen extracts (rush immunotherapy) for the treatment of dogs with atopic dermatitis. Am J Vet Res. 2001;62:307310. doi:10.2460/ajvr.2001.62.307

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 42.

    Herrmann I, Loft KE, Olivry T. Shortened immunotherapy dose-escalation saves time, but is it safe? A case-control study comparing the rates of adverse reactions between conventional and fast-escalation subcutaneous immunotherapy protocols during the induction phase. Vet Dermatol. 2020;31:454-e120. doi:10.1111/vde.12892

    • Search Google Scholar
    • Export Citation
  • 43.

    Fujimura M, Ishimaru H. Rush sublingual immunotherapy in canine atopic dermatitis: a prospective pilot study. Pol J Vet Sci. 2016;19:36. doi:10.1515/pjvs-2016-0001

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 44.

    Rosser EJ. Aqueous hyposensitization in the treatment of canine atopic dermatitis: a retrospective and prospective study of 100 cases In: Kwochka KW, Willemse T, von Tscharner C, eds. Advances in Veterinary Dermatology. Vol 3. Butterwoth Heinemann; 1998:169176.

    • Search Google Scholar
    • Export Citation
  • 45.

    Fennis EEM, van Damme CMM, Schlotter YM, et al. Efficacy of subcutaneous allergen immunotherapy in atopic dogs: a retrospective study of 664 cases. Vet Dermatol. 2022;33:321-e375. doi:10.1111/vde.13075

    • Search Google Scholar
    • Export Citation

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