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Sublingual Immunotherapy for Atopic Dermatitis

Douglas J. DeBoer, DVM, DACVD, University of Wisconsin–Madison

Dermatology

|June 2013|Peer Reviewed

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In addition to his university affiliation, Dr. DeBoer consults with Heska Corporation. Neither the University  of Wisconsin–Madison nor Dr. DeBoer has any financial  interest in any SLIT product.

Allergen-specific immunotherapy (ASIT) is a common atopic dermatitis (AD) treatment for dogs and cats. The newest variation of this treatment is sublingual immunotherapy (SLIT).

Related Article: Immunotherapy for Atopic Dermatitis

Although SLIT has been widely used in Europe for treating human allergies, it has only recently become available for treating animals in the United States. Mechanisms for injection ASIT differ slightly from SLIT. SLIT involves absorption of allergens through the oral mucosa with uptake and processing by specialized oromucosal dendritic cells.1 SLIT is formulated differently than the allergy injection mixture; commercial preparations of SLIT typically include proprietary ingredients to stabilize the allergen and promote mucosal absorption. Currently, several SLIT suppliers offer their own formulations with different administration protocols, storage conditions, efficacy, adverse events, and other use-associated factors; because the therapy is new, studies on these factors are still underway. SLIT is administered via a metered pump dispenser that delivers drops of solution onto the mucosa under and around the tongue (Figure 1).

Clinician's Brief
Figure 1. Typical metered-dose dispensing bottle (A); the end of the dispenser is hooked over the lower arcade of teeth and the dispenser is actuated (B).

Indications & Contraindications
SLIT is primarily indicated for treatment of AD in dogs; results in cats and horses have not been reported. Patient evaluation for allergies is performed in the same manner for injectable ASIT and SLIT (see Steps for Evaluation & SLIT Treatment, next page, for an outline of the typical workup). Following clinical diagnosis of AD and elimination of other possible causes of pruritic dermatitis (eg, food allergy, parasitism), allergy testing should be performed with an intradermal test or allergen-specific IgE serologic test panel to identify each patient’s sensitivities. Concentrated allergen extracts should then be mixed by the SLIT supplier according to each patient’s reactivity and administered, starting with small doses and gradually escalating to larger doses over several (typically 1–3) months. During the initial months of treatment, antiinflammatories may be given and slowly tapered as response occurs.

Related Article: Allergen-Specific Immunotherapy

SLIT does not have specific contraindications for AD patients. Currently, SLIT is limited to environmental allergens (eg, dust and storage mites, pollens, molds) and has not been evaluated for management of food or flea allergies. SLIT has been used successfully for treating human peanut allergy,4 possibly indicating that further study may prove its usefulness for veterinary food allergies.

Advantages
ASIT, including SLIT formulations, is the only therapy that modifies part of the underlying disease pathogenesis (ie, it is designed to reverse the allergy rather than mask signs with antiinflammatory drug treatment). SLIT has some benefits:

  • SLIT has a relatively easy, small volume, needle-free method of administration.
  • For mold allergy, some SLIT formulations allow mixing mold extracts in the same vial, which is often not recommended for allergy injections (depending on the supplier).
  • Some formulations can be stored at room temperature.
  • Anaphylactic reactions to SLIT are rare; with injection ASIT, anaphylactic reactions may occur in ~1% of patients and can be severe enough to necessitate stopping treatment.
    • Anecdotally, some SLIT formulations can be used safely even if there is a history of anaphylaxis from allergy injections.
  • SLIT reportedly works in some cases of failed allergy injection treatment, perhaps because of its different mechanism of action.
    • In one study, nearly 50% of dogs that failed allergy injection treatment showed response to SLIT.2
  • The cost is comparable with that of injection ASIT.

Disadvantages

  • Like injection ASIT, SLIT does not work immediately (typically taking 3–6 months) or in every dog.
  • Currently only one study has reported the effectiveness of a commercial SLIT product (Allercept Therapy Drops, heska.com).
    • The study reported ~60% response, which is comparable with injection ASIT.2
  • SLIT requires direct administration via a small pump dispenser and is typically administered q12h every day.    
    • Although sublingual administration may be easier than injections, clients may find q12h schedule cumbersome.
  • Mild adverse events are possible (eg, face rubbing, stomach upset postadministration, transient worsening of signs) but typically disappear within 1–2 weeks.
    • If signs persist, they can be managed by altering the dose schedule.

Both injection ASIT and SLIT are long-term treatments; owners must be willing to try treatment for 6 to 12 months. If response occurs, continued administration for several years may be necessary.

Clinical Impact
SLIT may be a convenient, affordable, safe, and drug-free option for owners who are not enthusiastic about giving their pets injections. For now, there is insufficient evidence to decipher whether SLIT or injection ASIT is more effective. Thus, recommendations should be based mostly on owner preference, keeping in mind, however, that SLIT can provide cutting-edge medicine to more patients.

AD = atopic dermatitis, ASIT = allergen-specific immunotherapy, SLIT = sublingual immunotherapy

Steps for Evaluation & SLIT Treatment
1. A tentative diagnosis of AD should be established by confirming that the dog fulfills appropriate historical and clinical criteria (see Diagnostic Criteria for Canine AD).3

2. A firm clinical diagnosis of AD should be established by eliminating all other pruritic diseases that may mimic AD. This will typically involve:

  • Identifying and treating secondary bacterial or yeast infections
  • Eliminating fleas and ruling out other parasitic causes of pruritus (eg, Sarcoptes spp)
  • Eliminating food allergens as a factor via dietary restriction provocation trials

3. A serologic test (eg, allergen-specific IgE panel) and/or intradermal testing should be performed to identify specific allergens to which the dog is sensitive.

4. Test results should be provided to the SLIT supplier to formulate a treatment individualized for the patient. The veterinarian can specify which allergens are to be included in the treatment set or base selection on the advice of the SLIT supplier.

5. SLIT administration should be demonstrated, the schedule explained, and the importance of compliance emphasized to the owner. The treatment set and any concurrent medication necessary for temporary relief should be dispensed.

6. Recheck examinations should be scheduled q3mo during the initial year of SLIT. At each recheck examination, concurrent medication should be tapered and the patient assessed for adverse events or development of secondary complications (eg, staphylococcal or yeast infection).

7. If an adverse event is suspected, a medical consultant at the SLIT supplier should be contacted; suppliers are often a good source of information for how to revise the formulation to address adverse events.

Diagnostic Criteria for Canine AD
AD is highly likely if ≥5 of these criteria are present and other differentials have been ruled out3:

  • Age of onset <3 years
  • Dog mostly indoors
  • Corticosteroid-responsive pruritus
  • Chronic or recurrent yeast infections
  • Affected front feet
  • Affected ear pinnae
  • Nonaffected ear margins
  • Nonaffected dorsal lumbosacral area

DOUGLAS J. DEBOER, DVM, DACVD, is professor of dermatology at University of Wisconsin–Madison. His research and clinical interests center on the immunology of recurrent and chronic skin diseases, focusing on canine allergic skin diseases and feline dermatophytosis. He frequently lectures postgraduate CE courses, including NAVC Conference courses. Dr. DeBoer has served on the editorial boards of the American Journal of Veterinary Research and Veterinary Dermatology and is currently chair of the International Committee on Atopic Diseases of Animals. He graduated from University of California, Davis, where he also completed postgraduate training.


SUBLINGUAL IMMUNOTHERAPY FOR ATOPIC DERMATITIS • Douglas J. DeBoer

References

1. Induction of tolerance via the sublingual route: Mechanisms and applications. Moingeon P, Mascarell L. Clin Dev Immunol doi:10.1155/2012/623474.
2. Multicentre open trial demonstrates efficacy of sublingual immunotherapy in canine atopic dermatitis [abstract]. DeBoer DJ, Morris M. Vet Dermatol 23:65- 66, 2012.
3. A prospective study on the clinical features of chronic canine atopic dermatitis and its diagnosis. Favrot C, Steffan J, Seewald W, Picco F. Vet Dermatol 21:23-31, 2010.
4. Sublingual immunotherapy for peanut allergy: A randomized, double-blind, placebo-controlled multicenter trial. Fleischer DM, Burks AW, Vickery BP, et al. J Allerg Clin Immunol 131:119-127, 2013.

Suggested Reading

Allergen-specific immunotherapy. DeBoer DJ. In Bonagura JD and Twedt DC (eds). Kirk’s Current Veterinary Therapy XV—Philadelphia: Saunders Elsevier, in press 2013.
Sublingual immunotherapy for pets: A guide for veterinary dermatologists. Morris M, DeBoer DJ. Downloadable file from heska.com/Documents/Allergy/White-Paper,-Sublingual-Immunotherapy-for-Pets.pdf; accessed May 2013.
Systematic reviews of sublingual immunotherapy (SLIT). Radulovic S, Wilson D, Calderon M, Durham S. Allergy 66:740-752, 2011.

For global readers, a calculator to convert laboratory values, dosages, and other measurements to SI units can be found here.

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