Prevalence of serum allergen-specific immunoglobulin E for canine atopic dermatitis in Korea

Introduction

The definition of canine atopic dermatitis (CAD) is genetically predisposed inflammation and pruritic skin disease with characteristic clinical features associated with immunoglobulin E (IgE) antibodies most commonly directed against environmental allergens [1]. Since there is currently no definitive diagnostic test for CAD, veterinary diagnosis is based on the evaluation of clinical symptoms and the exclusion of other potential causes [2, 3, 4].

Once a tentative diagnosis of CAD is made based on clinical criteria, testing for allergen-specific IgE can help to confirm the diagnosis. The most common methods of allergen-specific testing in veterinary medicine are the intradermal skin test (IDT) and the serum allergen-specific IgE test (SAT). IDT is widely accepted as the gold-standard technique for allergic skin diseases [5]. Nonetheless, IDT is limited by the requirement for anesthesia, shaving, and the withdrawal of medication that may influence allergic reactions [5]. Consequently, SAT is used more frequently than IDT because of its convenience: only a small volume of animal serum is required for testing and withdrawal of anti-allergy drugs is not necessary [6]. It is essential to identify the specific environmental allergens in domestic region and residential area for allergen-specific IgE tests. Unfortunately, there is no commercially available SAT based on specific geographical allergens for dogs in Korea. In this study, 120 common allergens in Korea were designed for use in a canine SAT and applied to eight dogs with CAD. Four of them were also tested by IDT to compare the results between SAT and IDT.

Materials and Methods

Results

Serum allergen-specific IgE test (SAT)

Based on the results obtained from panels 1 and 2 (common food allergens in Korea), banana was the most frequent positive allergen, stimulating a positive response in seven out of the eight dogs (87.5%; Fig. 1). On panels 3 and 4 (common inhalant allergens in Korea; Fig. 2), seven dogs (87.5%; Fig. 2) reacted positively to Botrytis cinerea (a fungal allergen) and six (75%; Fig. 2) reacted to Blomia tropicalis and Glycyphagus domesticus (mite allergens). Other allergens, such as Euroglyphus maynei, mite mixture 1 Korea, Alternaria alternate, mold fungi mixture 11, mold fungi mixture, and tree pollen mix 3 Korea produced a positive reaction in five of the eight dogs (62.5%; Fig. 2).

Fig. 1. The results of food allergen-specific IgE tests in this study.

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Fig. 2. The results of inhalant allergen-specific IgE tests in this study.

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Discussion

The atopic disease is defined as genetically predisposed tendency to develop IgE-mediated allergy to environmental allergen [1]. The environmental allergens vary significantly across countries and regions, thus it is essential to establish the geographic causative allergens in CAD. Here we present the first use of allergens prevalent in Korea for allergy testing in eight cases of CAD. This research may represent a valuable resource for Korean veterinary medicine.

There is currently no definitive diagnostic test for CAD and thus diagnosis of CAD is based on clinical manifestations, medical history and the exclusion of other potential causes of similar clinical symptoms [7]. In this study, we evaluated atopic dermatitis in eight dogs by applying Favrot’s criteria [2], considered the most sensitive and specific clinical criteria in veterinary medicine [7]. According to Farvot’s criteria, when the patient meets more than 5 of 8 criteria in set 1, the sensitivity is 0.854 and the specificity is 0.791 for CAD. In set 2, the sensitivity is 0.772 and the specificity is 0.83 for CAD if more than 5 of 7 criteria are presented [2].

Allergen-specific IgE tests, such as SAT or IDT, could represent the next step towards a diagnostic method for CAD. Allergen-specific IgE tests should not be used for sole diagnostic methods of CAD, but for identification of allergens to avoid causative substances and to inform the design of immunotherapy regimens [7]. Several investigators have demonstrated the diagnostic value of both allergen-specific IgE tests for CAD, when detected allergens are used for immunotherapy or avoidance strategies [8, 9].

Currently, IDT is considered the gold-standard method for identifying causative allergens, since there is little evidence of a correlation between circulating serum IgE levels and cutaneous IgE reactivity in SAT [7]. Many studies have evaluated the agreement between SAT and IDT results and most have reported similar hypersensitivity reactions to at least some allergens in CAD [10, 11, 12, 13]. SAT may therefore have similar diagnostic value to IDT, being significantly more convenient, and is often preferred by veterinary practitioners.

In SAT of the present study, four types of mite (Bloomia tropicalis, Glycophagus domesticus, Euroglyphus maynei, and mite mixture 1 Korea; house dust mites), four types of mold (Botrytis cinerea, Alternaria alternata, mold fungi mixture 11, mold fungi mixture) and one type of pollen (tree pollen mix 3 Korea) promoted a reaction in more than half of dogs tested. In IDT, all four dogs reacted positively to Dermatophagoides farina and three reacted positively to Dermatophagoides pteronyssinus and house dust. The mean agreement rate between SAT and IDT in this study was 76.3% (Table 7).

According to the results of current study, banana was the most frequent positive food allergen, stimulating a positive response in seven out of the eight dogs (87.5%). Other food allergens were not detected in over half of the patients. The link between food allergens and CAD remains controversial. Classifications of food allergy and CAD have until now been completely segregated, but recently the theory that food allergens may play an important pro-inflammatory role in CAD is gaining traction [7]. In human medicine, 33% of infants and 38.7% of young children with atopic dermatitis also have a food allergy [14, 15]. Previous veterinary studies have similarly found that 30% of dogs with CAD have concurrent adverse food reactions and 13~30% of CAD patients also exhibit cutaneous adverse food reactions [16, 17]. According to one previous report [18], however, SAT showed very low sensitivity (6.7%) and high specificity (91.4%) in canine adverse food reaction study. The positive and negative predictive values were 15.4% and 80.7%, respectively [18]. These results indicated that a positive result of canine SAT in food allergy could not be very helpful. The negative result of SAT of food allergens demonstrates that those antigens are tolerated well [18], thus we could utilize the negative result data in practice. In the present study, we evaluated SAT of food allergens in dogs and results were described in Fig. 1. Because of low sensitivity, we suggested that SAT results of food allergens in this study should apply only as reference data.

One previous study [19] demonstrated allergens associated with CAD in 35 dogs using IDT with 42 types of Korean allergen extracts. In 2011, Kim et al [20] also tested 39 common Korean allergens in 58 dogs with CAD using IDT. Recently, investigations of SAT for 101 CAD dogs were performed in Korea with 92 inhalant and food allergens [21]. However, there has not been the trial to choose allergens based on domestic environment and also not report comparing the results between IDT and SAT for the same dogs in Korea. Comparing these previous reports with the current study, we demonstrate that the positive ratio of specific allergens showed similar results (Table 8).

Total IgE ELISA test kits were used to support a diagnosis of CAD in this study; serological total IgE testing is usually used as a screening method in human allergic disease. Several studies have reported that total serum IgE levels may be predictive of positive reactions in SAT, clinical severity, and diagnosis of allergic diseases, although their value as diagnostic tools in humans is limited by variation in responses across different races [22, 23]. In veterinary medicine, conversely, total IgE serological tests have been widely reported as unreliable, detecting no significant difference in total serum IgE levels between normal and atopic dogs [10]. Further studies are needed to evaluate the diagnostic value of total IgE levels relative to positive results of SAT in CAD.

This study represents the first evaluation of Korean CAD allergens by SAT which composed of selected Korean type 120 allergens and the first comparison of SAT with IDT in Korean veterinary medicine. The limitations of this study include a small sample size and the omission of a standard for comparison between SAT and IDT. Further study using larger cohorts and immunotherapy trials based on causative allergens detected by SAT will be necessary in the future.