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PEER REVIEWED 50 CE: CANINE ATOPIC DERMATITIS eosinophils, mast cells, and basophils in the affected tissues. 21 Rationally, allergens likely to contribute to CAD can be identified by using an intradermal test or serum IgE serology. In vivo challenge by intradermal allergen injection is considered the gold standard; this assay provides functional evidence of hyperreactivity within atopic skin. Results of in vitro assessments of allergen-specific IgE (serum allergy testing) vary between laboratories, and no standardization exists for this test. 28 Although AIT is not effective in every atopic dog, within 12 months approximately 50% and 80% of dogs with CAD exhibit an improvement in clinical signs and/or a decrease in use of symptomatic medications, respectively. 1,3 Anti- inflammatory/anti-itch drugs should be given temporarily during AIT administration and individually tailored to maintain a good quality of life until AIT is judged to be effective. Management of Inflammation and Pruritus Many cell types contribute to the complex immune network underlying cutaneous inflammation in CAD. 1,2 After activation, these cells up- or downregulate various modulators, cytokines, and chemokines that promote pathology in food- and environment-induced CAD skin lesions. Several drugs are effective in modulating these cells and mediators in food- and environment-induced CAD ( TABLE 1 ). Symptomatic intervention in dogs with food-induced atopic disease should resolve clinical signs within 6 to 10 weeks of a diet trial, whereas patients with environment- induced CAD may experience recurrent flares throughout the year, requiring long-term control. The guidelines from the International Task Force on Canine Atopic Dermatitis 1,3 base therapeutic recommendations for pruritus and skin inflammation interventions on whether the patient is experiencing an acute flare or has chronic skin lesions. This distinction can be confusing because most atopic dogs present with a wide spectrum of clinical phenotypes involving chronic pruritus and/or skin lesions ranging from acute erythematous papules to chronic lichenified plaques. As a simple rule of thumb, the management of CAD should focus on: 1. Inducing remission ("get control") and 2. Initiating long-term management for prevention of flares ("keep control") An example of this approach is daily, intensive systemic and topical glucocorticoid administration for a few weeks until clinical signs are resolved ("get control"), followed by only intermittent topical glucocorticoids twice weekly to previously affected areas, with a goal of suppressing subclinical inflammation ("keep control"). Topical therapy aimed at improving epithelial barrier dysfunction may also be appropriate ( BOX 6 ). BOX 5 Subcutaneous versus Sublingual Allergen Immunotherapy Subcutaneous immunotherapy has been a mainstay of AIT in dogs with CAD for decades, mainly because systemic adverse effects (eg, life-threatening anaphylaxis) are very rare compared with occurrence in human patients. 1,21 However, subcutaneous AIT in dogs lacks protocol standardization (eg, amount of allergen extract, frequency of administration, administration of purified or recombinant allergen). Two recent trials using a high-dose recombinant house dust mite allergen prevented allergen-induced skin lesions in experimentally sensitized atopic dogs 22 and reduced clinical scores in dust mite–sensitized naturally atopic dogs. 23 These observations warrant further larger randomized controlled trials using highly purified or recombinant major allergens for AIT in atopic dogs. Recently, sublingual AIT, in which allergen extracts are administered in the oral cavity instead of by injection, has emerged as another immunotherapy treatment for allergic diseases in humans. 24 Sublingual AIT reduces the risk for severe systemic reactions observed in humans receiving subcutaneous AIT; in dogs, however, it requires long-term, q12h administration by the owners, which may influence client compliance. Despite the demand for high-quality research, no consistent evidence supports the effectiveness of subcutaneous or sublingual AIT for the treatment of human atopic dermatitis. 21 Only a few studies demonstrate the efficacy of sublingual AIT in experimentally dust mite–sensitized atopic dogs. 25,26 An uncontrolled open- label study using sublingual AIT treatment (q12h spray application) produced mild clinical improvement in 10 dogs with dust mite–associated natural CAD; a formulation and dosing schedule equivalent to a commercial product (Heska Allercept Therapy Drops, heska.com ) were applied. 27