Read the German translation: Interpretation von Laboruntersuchungen bei Allergien beim Hund

Introduction

There is widespread use of serum allergy tests (SAT) designed for identification of serum antibodies against certain allergens in atopic dermatitis, scabies infestation and also food hypersensitivity in dogs. Around 20 years ago the first in vitro tests were developed to identify allergen-specific IgE in dogs with atopic dermatitis. Since then, technical developments have markedly improved the quality of antibodies as well as methods. The limitation of serum tests lies in the interpretation of test results as well as the diseases they are used for. This overview discusses their usefulness and limitations in different skin diseases.

Serum Allergy Test (SAT) in Atopic Dermatitis

The diagnosis of atopic dermatitis in dogs (cAD) is a clinical diagnosis which is based on history, typical clinical signs and exclusion of other relevant skin diseases. The demonstration of allergen-specific IgE serves only the purpose of choosing allergens for specific immunotherapy (SIT) and possible elimination, reduction or avoidance of the identified allergens. Moreover it should be realized that with the current definition of cAD also food allergens (food-induced allergic dermatitis; FIAD) can be associated with cAD and cAD also encompasses a group of dogs with atopy-like dermatitis (ALD). Dogs with ALD do not have demonstrable IgE against environmental allergens or food but have all clinical features of cAD.

The following factors may cause problems in the interpretation of SAT results:

Allergen-specific IgE can be demonstrated in healthy dogs without skin problems as well and SAT values can lie in the positive range. In addition there is no good correlation between the level of allergen-specific IgE and the severity of clinical symptoms. The clinical symptoms are the result of several factors including secondary bacterial and/ or yeast (Malassezia) infections. The local inflammatory skin reaction is the net result from interplay between microbial infections, skin barrier defects, immunological response and severity of pruritus.

Different laboratory techniques are used for determination of allergen-specific IgE in SAT. Polyclonal and monoclonal antibodies against canine IgE are used and also a recombinant human high-affinity IgE epsilon receptor fragment (rhFcεR1α) is frequently used to determine canine IgE. In an ideal world results of different SAT should be the same. However, studies report different findings. A small study investigated the repeatability of 4 commercial SAT which was between 77.1 and 99% for the different tests.¹ A recent study comparing 2 different test systems (a monoclonal antibody cocktail--ELISA (macELISA) and a rhFcεR1α- based test (FcεR1α-ELISA) showed that interlaboratory concordance of results comparing both test systems was 92% and the intra-assay variance for the macELISA was 9.7%.²

Most dogs with cAD react positive in SAT against Dermatophagoides farinae and possibly other house dust and storage mites. Extensive in vitro cross-reactivity between house dust mites (Dermatophagoides pteronyssinus and Dermatophagoides farinae), between D. farinae and storage mites (Acarus siro and Tyrophagus putrescentiae) and between A. siro and T. putrescentiae was demonstrated and plays a role besides possible natural exposure to the allergens.³

The occurrence of house dust- and storage mites in the environment varies per country and even per small geographic area within countries. A study in England showed that in only 22% of the households with a dog house dust mites (D. pteronyssinus) were found however no D. farinae mites. House dust mite allergens including Der p 1 and Der f 1 were more often detected than the mites and Der p 1 was much more prevalent compared to Der f 1.⁴

Storage mites are less often demonstrated in collected house dust samples and could not be demonstrated in opened bags containing dry dog food in Germany.⁵ Taken together these data support cross reactivity between these allergens.

In contrast, immunotherapy with only D. farinae did not lead to more improvement compared to the placebo in cAD dogs that had positive intradermal skin test reactions against D. farinae and other allergens including other house dust or storage mites.⁶ Unfortunately, the efficacy of immunotherapy containing all allergens the dogs were reactive to in IDT, could not be tested in the same study.

Further, currently it is unknown what the exact importance is of allergen- specific IgE for development cAD. Therefore the demonstration of allergen-specific IgE should not be over interpreted and a diagnosis of cAD can only be made after a thorough clinical work up and exclusion of other differential diagnoses including an elimination diet and provocative testing. In other words positive results in SAT do not automatically lead to the diagnosis of cAD.

Serum Test for Demonstration of Sarcoptes Antibodies

It is not easy to make the diagnosis of a scabies infestation in dogs by skin scrapings as mites are found only in 20-50% of the infected dogs.⁷

Clinical signs of sarcoptic mange may vary but can be very similar to clinical symptoms of dogs with cAD or a food adverse reaction. An ELISA is an easy and helpful test to identify antibodies (IgG) against Sarcoptes scabiei, especially since a diagnostic therapy cannot always be persecuted.

One study evaluating an ELISA for S. scabiei in dogs demonstrated a sensitivity of 84.2% and a specificity of 89.5%.⁷ Cross-reactivity between house dust mites and S. scabiei allergens was reported in in vitro and in vivo testing. Dogs with scabies infestation may show positive reactions in SAT and IDT for house dust mites. However dogs with cAD seem to have rarely positive results in the scabies ELISA.

False negative results can occur when insufficient antibodies are present which can occur in the early stage of infestation. Dogs show seroconversion 3-5 weeks post infection or around 1-3 weeks after the occurrence of clinical symptoms. High dosages of glucocorticoids may inhibit antibody formation and may lead to false negative results.

Scabies antibodies can be found up to 5 months after treatment and therefore may lead to false positive test results. Demonstration of antibodies against S. scabiei can therefore not be used to evaluate immediate therapy efficacy.

Serum Tests for Demonstration of Antibodies Against Food Substances

A serum test is a very attractive method for demonstrating a food adverse reaction and of course may circumvent the problems of an elimination diet. Unfortunately demonstration of antibodies (IgE and IgG) against food proteins is not a reliable method to identify a food adverse reaction. Up to now studies could not demonstrate a correlation between allergen-specific IgE and clinical symptoms. Moreover in a laboratory model of dogs with food sensitivity an increase in allergen-specific IgE could be demonstrated after provocation with the culprit food in individual dogs but the difference in IgE level before and after provocation was not significant. The increased levels of allergen-specific IgE did not allow a prediction of development of clinical signs.⁸

Another point is that some of the food adverse reactions may not be mediated by IgE or IgG and in those cases a serum test is not helpful. In other words at present the only reliable way to demonstrate a food adverse reaction remains an elimination diet followed by provocation with the previously fed food.

References

1.  Hnilica KA. Vet Dermatol 2006; 17:209.

2.  Lee KW, et al. Vet Dermatol 2009; 20:157.

3.  Saridomichelakis, et al. Vet Dermatol 2008; 19:67.

4.  Jackson A, et al. Vet Dermatol 2005; 16:32.

5.  Henneveld, et al. Vet Dermatol 2008; 19:209.

6.  Willemse, et al. Vet J 2009; 180:337.

7.  Lower K, et al. Vet Dermatol 2001; 12:315.

8.  Jackson H, et al. Vet Dermatol 2003; 14:181.