The role of environmental allergen immunotherapy in current management of dogs with atopic dermatitis
Until the last decade of the previous century, canine atopic dermatitis (AD) was considered an IgE-mediated, type I hypersensitivity reaction to environmental allergens. In addition to flea prevention and treatment of bacterial and Malassezia “complications” with systemic and/or topical antimicrobials, the only highly effective medical treatment available was the lifelong administration of glucocorticoids at the minimum dose that could effectively control clinical signs. Due to the frequent appearance of glucocorticoid side-effects, every effort had to be made to reduce their dose (or even to discontinue their administration) with the addition of H1 antihistamines and/or n-3 and n-6 fatty acid supplements. Unfortunately, due to the low efficacy of these medications, this effort was condemned to failure in most of patients. In addition, avoidance of exposure to the “offending” environmental allergens was laborious and usually minimally helpful and the only vital alternative to glucocorticoids was allergen immunotherapy (AIT).
In principle, AIT is a highly effective therapeutic modality for classical type I hypersensitivity reactions, such as food allergen-induced anaphylaxis in laboratory animals and stinging insect venom allergies in humans. Also, it shows an acceptable efficacy in allergic diseases with a more complicated pathogenesis but still with a clear type I hypersensitivity component, such as human allergic rhi- nitis and allergic asthma. The efficacy of AIT in dogs with AD was documented in a single study published in 1984 (Willemse et al. 1984). That study was a breakthrough in veterinary medicine because it was designed as a randomized, double-blinded placebo-controlled clinical trial. A total of 51 dogs with AD were randomly assigned to be treated with either AIT using alum-precipitated allergens (27/51) or with placebo using the alum-containing diluent of the allergens (24/51), for a period of 6-54 months (median: 16 months for the AIT and 13 months for the placebo group) and without other interventions. Since, by that time, there were no validated instruments to measure the severity of AD, an arbitrary scoring system was applied to measure a “total clinical score” that was used to evaluate the response. At the end of the trial, “total clinical score” had been reduced by more than 50% in 59% (16/27) of the dogs treated with AIT and only in 21% (5/24) dogs in the placebo group, whereas 33% (9/27) and 17% (4/24) dogs, respectively, were in complete remission.
Although the response of the placebo group was surprisingly high and a self-cure of canine AD in 17% of the cases is not common in clinical practice, this study rendered AIT the first-line treatment of canine AD, since it was safe and able to help 3/5 of the patients and to complete control 1/5 of them. In the four decades since that publication, many controlled studies and systematic reviews have been done, comparing different routes of AIT administration (subcutaneous or intralymphatic), (Mueller et. al 2023) different types (aqueous, alum-precipitated, with tyrosine, recombinant, and allergoids) (Tham & Olivry 2022) and dosage regimens (classical, low or “rush”) (Colombo et al. 2005, Mueller et al. 2005, Park et al. 2017) of allergens but none comparing AIT to placebo.
Our current view of canine AD is completely different than some decades ago. The disease is not considered anymore to be a type I hypersensitivity reaction and the production of IgE against environmental allergens is probably an epiphenomenon secondarily to the defective epidermal barrier that allows allergen penetration and the abnormal immunological response that promotes IgE production. Furthermore, it is well known that many dogs with AD are not sensitized to environmental allergens and some of them are not sensitized to any type of allergens. Bacterial overgrowth/infection and Malassezia dermatitis are not considered “complications” but an integral part of the disease pathogenesis and the result of bacterial and fungal dysbiosis that occurs on the skin of these dogs. Topical products aiming to restore the defective epidermal barrier are available, and, most importantly, highly effective, and safe drugs with antipruritic (lokivetmab) or both antipruritic and anti-inflammatory activity (ciclosporin, oclacitinib) are available. This explosion of our understanding of the pathogenesis of canine AD and the resultant expansion of the therapeutic armamentarium, made AIT as second-line treatment that is mainly indicated when medical management fails or results in unacceptable side-effects. Unfortunately, there are no studies to prove that, under these conditions, AIT is effective because, for example, it permits better control of the disease with the same consumption of medication, or it permits the same control of the disease with a lower consumption of medication. Until such studies will become available, veterinarians are advised to inform dog guardians on the lack of scientific data supporting current use of AIT in dogs with AD but, due to the high safety margin, AIT may be tried in the hope that a better control of the disease may be achieved.
As a final remark, it has been more than two decades ago when investigations proved that canine and human AD are very similar to each other (if not identical). Yet, all current guidelines for the treatment of human AD, do not recommend AIT as a routine treatment of the disease (Sidbury et al. 2014).
Manolis N. Saridomichelakis, DVM, PhD
Diplomate of the European College of Veterinary
Dermatology (ECVD)
Professor of Companion Animal Medicine,
University of Thessaly, Greece
References
- Willemse A, Van den Brom WE, Rijnberk A (1984) Effect of hyposensitization on atopic dermatitis in dogs. J Am Vet Med Assoc184,1277-80.
- Mueller RS, Zablotski Y, Baumann K, Boehm T, Kasper B, Klinger C, Monke M, Udraite-Vovk L, Weitzer T, Gedon NKY (2023) A randomised, double-blinded comparison between subcutaneous rush and intralympathic allergen immunotherapy induction in atopic dogs. Vet Dermatol 34, 91-98.
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- Mueller RS, Fieseler KV, Zabel S, Rosychuk RAW (2005) Conventional and rush allergen-specific immunotherapy in the treatment of canine atopic dermatitis In: Hillier A, Foster AP, Kwochka KW, eds. Advances in Veteinary Dermatology. Volume 5 ed. Oxford, U.K., Blackwell Publishing, pp. 60-69.
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- Sidbury R, Tom WL, Bergman JN, Cooper KD, Silverman RA, Berger TG, Chamlin SL, Cohen DE, Cordoro KM, Davis DM, Feldman SR, Hanifin JM, Krol A, Margolis DJ, Paller AS, Schwarzenberger K, Simpson EL, Williams HC, Elmets CA, Block J, Harrod CG, Smith Begolka W, Eichenfield LF (2014) Guidelines of care for the management of atopic dermatitis: Section 4. Prevention of disease flares and use of adjunctive therapies and approaches. J Am Acad Dermatol 71, 1218-33.
