Introduction

Allergen immunotherapy (AIT) in human patients is a safe and effective treatment for allergic rhinitis, asthma and venom hypersensitivity. It has also been used for atopic dermatitis and food allergy. AIT may also be effective in preventing sensitisation to new allergens and halting the “atopic march”.

In dogs, AIT is an effective treatment for canine atopic dermatitis. It is the only current treatment that can modify the allergic disease and potentially improve the allergic clinical signs and reduce the amount of anti-pruritic medications required long term. Recently, food specific sublingual immunotherapy has been shown to be well tolerated and safe in healthy dogs and effective in a small number of dogs with adverse food reactions. AIT has also been used to manage feline atopic dermatitis and feline asthma.

Mechanisms of AIT

Briefly, allergy is characterised by a dominance of T-helper 2 cells and their cytokines resulting in production of allergen-specific IgE. A summary of the immunological changes in allergic disease and with AIT is provided by Mueller et al. 2018, and shown in Table 1.

The main aims for AIT are to induce tolerance to these allergens and stimulate T regulatory responses. A summary of the mechanisms of AIT in human patients is provided by Jutel et al., 2016 and shown in Figure 1. Generally, similar findings are found in dogs.

Table 1. Immunological data about allergy and allergen immunotherapy in humans and dogs (Mueller et al. 2018) (VIN editor: Table not included.)

Figure 1. Mechanisms of allergen immunotherapy (Jutel et al. 2016) (VIN editor: Figure not included.)

Subcutaneous Immunotherapy (SCIT)

AIT in humans and dogs has traditionally been administered subcutaneously. For dogs, different protocols using different adjuvants are used but generally they consist of an induction phase with increasing allergen doses followed by a maintenance phase. SCIT should be continued for at least 12 months before efficacy is determined. If effective, SCIT is recommended for at least 3–5 years. Adverse reactions can occur at any stage of SCIT but more commonly during induction phase. They range from localised (e.g., erythema, pruritus and swelling) to serious systemic anaphylaxis.

Sublingual Immunotherapy (SLIT)

In this route, allergen extract is administered (usually as a tablet or liquid formulation for human patients) under and around the tongue. The formulation contains ingredients to stabilise allergen and promote mucosal absorption. This route has the additional benefit of having the allergen taken up by dendritic cells (antigen presenting cells) in the oral mucosa and presented to T cells in draining lymph nodes. Neither food nor drink is allowed for at least 5 minutes. The optimal duration of SLIT is not standardised but at least 3 years is recommended.

Systemic adverse reactions to SLIT are much lower compared to SCIT due to lower number of mast cells within the oral and sublingual mucosa. Localised adverse reactions include oropharyngeal pruritus and/or swelling. Most importantly, the risk for systemic adverse reactions is significantly lower in SLIT compared to SCIT. For example, 0.1 to 3.5% of SCIT result in a systemic allergic reaction compared to 0.056% for SLIT.

Studies on SLIT in dogs for allergic disease are few. There are different suppliers providing different formulations, administration protocols, storage conditions with different reported efficacy and potential adverse reactions. SLIT is usually administered using a metered pump dispenser.

A small placebo controlled study of 13 house dust mite sensitive dogs where 7 of the 13 dogs received daily doses of house dust mite culture mixed with cream cheese applied to inside of cheeks and hard palate every day for 7 months did not show any clinical improvement nor changes in allergen specific IgE levels. Another small study in 18 atopic dogs sensitised to dust mites, timothy grass and ragweed that received one year of SLIT showed a slight improvement in clinical signs but significant increases in TGF-beta and IL 10. Another small study of 10 dust mite sensitive dogs showed clinical improvement with supportive serological changes (decreased mite specific IgE and increased IgG levels) after 6 months of SLIT. Another multicentre open trial where dogs received twice daily SLIT for at least 6 months, reported 55% (66/124) of dogs had a good to excellent response. Interestingly, 49% (23/47) of dogs that had a good to excellent response to SLIT had previously failed SCIT.

SCIT vs SLIT in Dogs (Table 2)

In dogs, until more studies are performed investigating the ideal dose, protocol and efficacy, SLIT is best suited for dogs where either owner or dog is needle-phobic, if the dog developed serious adverse reactions to SCIT or has failed SCIT.

Table 2. Pros and cons of SCIT and SLIT in dogs

References

1.  Maina E, Cox E, A double blind, randomized, placebo controlled trial on the efficacy, quality of life and safety of food allergen specific sublingual immunotherapy in client owned dogs with adverse food reactions: a small pilot study, Veterinary Dermatology, 2016: 27:5:361–e91.

2.  Jutel M et al., International Consensus on Allergen Immunotherapy II: Mechanisms, standardization, and pharmacoeconomics, Journal of Allergy and Clinical Immunology, 2016: 137: number 2.

3.  Mueller RS et al., Allergen immunotherapy in dogs, cats and horses—differences, similarities and research needs, Allergy, 2018, [Epub ahead of print].

4.  Loewenstein C, Mueller RS, A review of allergen specific immunotherapy in human and veterinary medicine, Veterinary Dermatology, 2009: 20: 84–98.

5.  Cox LS, Linnemann DL, Nolte H, Weldon D, Finegold I, Nelson HS. Sublingual immunotherapy: a comprehensive review. Journal of Allergy and Clinical Immunology 2006;117:1021–35.

6.  Marsella R, Tolerability and clinical efficacy of oral immunotherapy with house dust mites in a model of canine atopic dermatitis: a pilot study, Veterinary Dermatology, 21:566–571

7.  Marsella R, Ahrens K, Investigations on the effects of sublingual immunotherapy on clinical signs and immunological parameters using a canine model of atopic dermatitis: a double blinded, randomized, controlled study, Veterinary Dermatology 2012, 65.

8.  Deboer DJ, Verbrugge M, Morris M, Pilot trial of sublingual immunotherapy (SLIT) in mite-sensitive atopic dogs, Veterinary Dermatology, 21: 311–328.

9.  DeBoer DJ, Verbrugge M, Morris M, Clinical and immunological responses of dust mite sensitive, atopic dogs to treatment with sublingual immunotherapy (SLIT), Veterinary Dermatology, 2016, 27:82–e24.

10.  Deboer DJ, Morris M, Multicentre open trial demonstrate efficacy of sublingual immunotherapy in canine atopic dermatitis, 2012, Veterinary Dermatology, 23 (Suppl 1): 65.