The CSI approach to pruritic pets: an overview and flowchart (Proceedings)

Once we have ruled out the possibility of parasites and treated a secondary microbial dermatitis, our history taking skills and physical examination will often point to an allergic etiology as the cause of the pruritus. In the non-seasonal dog, rule outs will include an adverse food reaction and environmental allergy. One must not be blinded to the possibility that there is more than one etiology at play. Indeed, in a study performed at our facility looking at feline self trauma, we found that 52% of our cases were multifactorial.

"Hypoallergenic"/ Elimination Diet

The possibility of an adverse food reaction has most often been considered by our clients before they present their pruritic pets. Most commonly, they believe that they have adequately ruled out this differential and our seeking alternative explanations. Unfortunately, there is a plethora of media misinformation on the subject. Clients have the impression is that food allergies are a common cause of allergic dermatitis in dogs when in fact, in one study, adverse food reactions account for at most 22% of allergies in dogs (Chesney 2002). There is also confusion between the use of diets to help environmental allergies and hypoallergenic diets. As a result, I spend a large part of my appointment time with the client discussing adverse food reactions and their diagnosis. I believe that the diagnosis of a possible food allergy can easily be missed due to poor "technique". The following is a summary of how I try to rule out food allergies in my patients.

The most important aspect of the diagnosis goes back to the first lecture of the day – interviewing the witness. A complete dietary history is essential (be sure to include treats in the discussion). Many clients are too embarrassed to admit what they feed their dog. The importance of an accurate evaluation must be emphasized. The next step is to find out if the pruritus is chronic or intermittent – without a change in diet or treatment. Age of onset can help a lot too. Environmental hypersensitivity most commonly starts between 6 months and 3 – 5 years of life. Adverse food reactions do not seem to have the same time constraints and are seen as well in the very young or the very old. A poor response to adequate doses of steroids in the absence of another explanation will increase the suspicion that food is playing a role. However, the converse is not true; adverse food reactions can be steroid responsive.

I will often tell clients that, regardless of what the person at the pet supply store tells you, there is only one perfect hypoallergenic diet – it's the diet that doesn't contain the ingredient to which the dog is allergic! People need to be aware at the onset that there are many studies looking at hypoallergenic diets and all diets have their deficiencies. For this reason, multiple dietary trials may need to be tried before one can rule out adverse food reactions. I will go as high as three different trials before completely ruling out food. One also needs to educate the client on how to properly perform a food trial (and how difficult it is to do one appropriately).

Serum IgE testing for food is commonly offered amongst allergy testing laboratories. They refer to how common this test is in the medical field. In fact, in people, it has been stated that "the high rate of false positives combined with the wide commercial availability of food-specific IgE testing (particularly the food allergy panels) has led to over diagnosis and unnecessarily restrictive diets. Food-specific IgE testing has a specificity of ~ 50%" (Stephanie 2010). This test is not recommended to diagnose a food allergy. It is also important to clarify to owners that intradermal testing does not assess for food allergies. A study presented at the 2011 NAVDF looked at patch testing and blood testing (Mueller, 2011). The conclusion was that, at best, negative tests can be considered to select appropriate proteins for a food trial. However, this test does not take into consideration the possibility of food intolerance (as opposed to a food allergy). Indeed, in people, an undetectable IgE level (< 0.35 kU/L) for peanut is still associated with a 20% chance of reactivity (Chapman 2006)

As in people, the ideal test is a food trial. But how to do a good scientific food trial? Here are a number of things to consider:

     1. The diet must be performed strictly

                    ⇒ The first step is to explain to the client how difficult it is to do a proper dietary trial. All members of the family need to be "on board". It is especially difficult when there are very young people in the home (or older people that won't listen to you). I will often give the example of how some children are so exquisitely sensitive to peanut butter that they can react with miniscule amounts.

     2. Decide on the appropriate diet

          A. Choice of protein

               • Selected protein diet. My favorite proteins are rabbit and kangaroo. Here's why:

                    ⇒ This is where dietary history is key. Whenever possible, I will take into considerations the potential for cross reactions. For example, in people,

                         o 50% of people allergic to one type of fish are allergic to another

                         o While avian meat allergy is uncommon, some people allergic to chicken are also allergic to eggs. In fact, when a concurrent egg allergy is not present, there may be an increased risk of allergy to other avian meats such as turkey, pheasant and quail

                         o 10% of patients allergic to milk are also allergic to beef

                         o There is a protein in venison that cross reacts with a protein in beef

                         o Clinical reactivity to multiple grains appears to be uncommon; however, cereal grains do share homology with certain grass pollens

                         o Are fruits and vegetables safe to give as a snack? 55% of people allergic to birch or ragweed pollen have a risk of being allergic to one of apples, peach or honey dew. Indeed celery can cross react with mugwort

This can severely limit the options in choosing a diet. Furthermore, how do you know that the diet is a single source protein? Unfortunately studies are starting to identify proteins in the diets that are not listed on the label. In one recently published study (Raditic, 2010), Three of the four over the counter (OTC) venison canine dry foods with no soy products named in the ingredient list were ELISA positive for soy; additionally one OTC diet tested positive for beef protein with no beef products listed as an ingredient list. In fact, none of the four OTC venison diets could be considered suitable for a diagnostic elimination trial as they all contained common pet food proteins, some of which were readily identifiable on the label and some that were only detected by ELISA. The conclusion was that, if the four OTC venison products selected in this study are representative of OTC products in general, then the use of OTC venison dry dog foods should not be used during elimination trials in suspected food allergy patients. One abstract presented at the 2011 NAVDF found that 3 of 4 OTC diets with no soy claims on the package were positive for soy. Veterinary therapeutic diets can be a problem too (see the comment below on hydrolyzed diets).

Home cooking is certainly one way to get around the problem of multiple proteins "sneaking" into the diet. However, clients tend to find this tedious and the diets are unbalanced

Hydrolyzed diets

As most of you are aware, these are diets where the protein should be so small as to not cross link antibodies – the pet should not recognize it as the parent protein. In studies looking at hydrolyzed diets, these too are found to be imperfect. In one study (Ricci, 2010) hydrolyzed chicken was fed to 12 dogs with known allergies to chicken. The pruritus was significantly reduced in 11 of the 12 dogs when fed hydrolysed chicken were compared to those fed whole chicken. In 1/12 the pruritus persisted. One could conclude that it is not possible to totally hydrolyze any diet and some patients are so sensitive that the small amount of protein can lead to a reaction. In fact, a study presented to the NAVDF in 2011 revealed that Elisa testing for soy was positive in some veterinary soy hydrolyzed diets as well as one diet that only had soybean oil on the label. When I choose a hydrolyzed diet, I try to choose a source protein that is unusual for the pet based on the dietary history

          A. Change companies? (Top dressing?)

          B. Raw versus cooked?

     1. Control concurrent microbes – I will often have patients on concurrent antibiotic (and sometimes antifungal) medications

     2. Control for parasites – don't let a flea mess up your test

     3. Control for Environment

                    ⇒ Seasonally relapsing pets "need not apply"

                    ⇒ Up to 20% of patients will have a concurrent adverse food reaction and environmental hypersensitivity (NAVDF 2011). Whenever possible, it is best to perform the diet when there is minimal exposure to seasonal pollens (I try to do my dietary trials in the winter). Naturally, there are regions where this is not possible. If the patient gets better, of course, the time of the year that the test is performed doesn't matter. But if there is no response, it could be that a concurrent environmental hypersensitivity is interfering with the diagnosis

     4. Trial length - minimum of 4 weeks (if responds); 8 weeks in general, but can take as much as 12 weeks for assessment of resolution of clinical signs.

     5. Challenge

     6. Provoke (also called re-challenge trials)

Environmental allergy testing

Salient points

     • Be sure to advise the owner that this test does not test for food allergies

     • A positive allergy test, whether performed as an in vivo test or in-vitro test, means that the test was positive; it does NOT mean that allergies are the cause of the itchiness. These tests should never be performed to make a diagnosis.

     • Twenty percent of pets and humans tested with either in-vitro or intradermal tests will have negative tests. These patients are thought to have "atopic-like dermatitis" or "intrinsic allergies" (Schmid 2001). Therefore this test cannot eliminate the possibility of environmental allergies. I believe that, regardless of methodology, testing sites that never have negative results should be viewed with suspicion

     • Intradermal skin tests (IDT) are still considered by most dermatologists to be the gold standard in veterinary medicine

     • Many of the in vitro allergy tests (IVAT) available do not correlate with intradermal testing and those that correlate better seem to have more false negatives. However, many patients will respond well to immunotherapy based on IVAT, although the response rate, in general, is not quite as good as IDT- based formulations, in my experience

     • Some dermatologists perform both IDT and IVAT and formulate immunotherapy based on both test results.

     • Formulation of allergen specific immunotherapy is an "art". I believe that choice of allergen, volume and formulation is critical to the success rate

     • There are regions where allergy testing is best performed seasonally. Different allergens are more prevalent in different regions

     • Sublingual immunotherapy (SLIT) is gaining in popularity

Once you know the questions to ask, the tests to do (and how best to do them) all you need is a diagnosis and you are on your way to making them better. While it isn't cookbook medicine, here is a flow chart that I will commonly employ in my quest for the elusive diagnosis.

The Diagnostic Approach to Chronic Non-Seasonal Pruritus