The first article in this series discussed the breeds of dogs in the Western Province, South Africa, that were tested at Newlands Veterinary Clinic using Allergen Specific Ig E Serology (ASIS) testing. The plant (tree, grass, weed) and fungal (mould) species that these dogs tested positive for were discussed. In this article, we discuss other allergens which may play a role. These allergens, mostly non-seasonal, include the dietary and household allergens, as well as infections (yeast and bacteria) and ectoparasites.

The first article in this series discussed the breeds of dogs in the Western Province, South Africa, that were tested at Newlands Veterinary Clinic using Allergen Specific Ig E Serology (ASIS) testing. The plant (tree, grass, weed) and fungal (mould) species that these dogs tested positive for were discussed. In this article, we discuss other allergens which may play a role. These allergens, mostly non-seasonal, include the dietary and household allergens, as well as infections (yeast and bacteria) and ectoparasites.

DIETARY ALLERGY

Dietary hypersensitivity was discussed at the World Congress of Veterinary Dermatology held recently in Vienna, and the following terminology proposed:

1. Adverse food reactions include any clinically abnormal response attributable to the ingestion of food or food additive.
2. Food intolerance is the term given to any abnormal physiological response to food or food additive with no immunological basis. Food intolerance includes food idiosyncrasies, food poisonings, and pharmacological reactions to food.
3. Food allergy is any immunologically mediated adverse food reaction with a proven immunological basis. It is important to note that not all reactions to food are allergic reactions. A reaction to a foodstuff at first exposure is obviously not an allergic reaction (the body needs time to become sensitized).
4. Cutaneous adverse food reaction (CAFR) is the preferred term where the lesions involve (but are not necessarily confined to) the skin.

It was emphasised that food allergy in children is often the first presentation of atopy and these are steps in the process of allergy development - the so-called "atopic march". Atopic dermatitis, in humans, is now considered to be virtually indistinguishable from food allergy. The predominant presenting symptom of CAFR in dogs is a non-seasonal pruritus. The pruritus may affect any part of the body, although involvement of the face and peri-anal area is more common. Recurrent otitis externa is another common complaint with secondary otic and cutaneous infections (bacteria or yeast). In cats, pruritus is often restricted to the face and neck, but other body areas can be affected. True food allergy is usually to glycoproteins present in the diet. However, food additives have also been shown to be allergenic and in humans these include the azo dyes, non-azo dyes and the anti-oxidants. Elimination dietary trials are the "gold standard" for the evaluation of CAFR in dogs. The most likely allergen in the diet is a low molecular weight glycoprotein. Dogs are therefore placed on either a novel ("home cook") diet, not previously encountered by the pet, or a commercial diet containing low molecular weight hydrolysed protein ingredients. This diet is fed for a minimum of 6 weeks, and usually for 8 to 12 weeks. Strict control over the feeding of the diet includes no tidbits, no flavoring, no additives, no vitamins, etc, other than the designated diet for the trial period.

The novel diet will usually consist of one protein and one carbohydrate ingredient - these are then boiled (no additives) to provide the "homecook" diet. In North America (a beef and wheat country), a lamb and rice diet is frequently advised to test for food allergies. Since pet diets in this country often have lamb and/or rice, we seek out alternative ingredients. In our study (see Table 1), the low numbers of dogs positive to lamb may be because these cases have been selected out by elimination dietary trials prior to serotesting. Ostrich meat is readily available in the Western Cape and the author uses this routinely as the protein ingredient in dietary trials, with potato as a carbohydrate source. This has resulted in the manufacturing of ostrich and potato dog foods in South Africa which may, but also may not, be as good for dietary elimination trials (colouring, flavouring, preservatives, etc are added). Rabbit has promise as a basic protein source in South Africa and is still a relatively novel foodstuff. A venison and boiled potato diet has also been used successfully as a novel elimination diet (personal communication, J van Heerden, Animal Allergy Management). Other possibilities include turkey, tofu as well as certain fish species not commonly included in pet foods. Homecook diets may be deficient for long term use, and in young dogs, it may be better to use a commercial diet with the hydrolysed ingredients. However, no adverse effects have been found by the author with homecook diets for 8 - 12 week trial periods.

Elimination dietary trials are easier in households where there is a single pet, no cats, no young children, and/or where the owner can feed the allergic dog separately. After the 8 - 12 week period, the pet is challenged with the previously fed diet ("provocative challenge") and changes in the level of pruritus noted. Should pruritus increase, return to the hypo-allergenic diet for 2 weeks and re-challenge sequentially with individual dietary ingredients. The ostrich and potato diet has worked well for the author. Potatoes are boiled with no additives and mashed. The ostrich meat is boiled separately and the juice used to flavour the mashed potato. No other ingredient, additive, flavouring, preservative, anti-oxidant, colouring dye, etc, is allowed to be added. This is fed in a ratio of 1/3 ostrich to 2/3 potato for 2 -3 months with no treats, tidbits, etc, whatsoever allowed. The supplementation of calcium is perhaps the only additive necessary in dogs under 10 months of age. However, non-flavoured, additive-free vitamin/mineral supplements which do not contain animal or vegetable protein are also unlikely to be a source of ingested allergen.

OTHER CANINE ALLERGIES

House dust is a heterogenous mix of house dust mites, fungi, bacteria, insect and plant fragments and other debris (e.g. mixed feathers and mouse epithelium) and may be individually tested. House dust mite hypersensitivity is as a result of allergens in the mite's faecal material. Dogs may also be allergic to the household cat (cat hair/dander/epithelium). Other less well-documented insect/acarid allergens include cockroach, forage mites, storage mites, and house flies. Materials in furniture include cotton, kapok, mixed feathers, as well as orlon/rayon/nylon. Other household allergens include pyrethrum, horse hair, jute/sisal, and orris root.

RESULTS

ELISA testing for food allergy was found to have a positive predictive value of only 40% and RAST testing for foods is considered unreliable. Nevertheless, the results of ELISA testing assist in the selection of hypo-allergenic diets. Professor Richard Halliwell, an undisputed authority on canine allergic disease, recently found that serology has value in identifying suitable candidates for hypoallergenic diet trials as well as in the selection of a suitable diet. Results of the serology testing for food allergens in dogs in the Western Province are given in Table 1. The number of dogs tested for each foodstuff as well as the percentage of dogs which were positive for raised Ig E levels are listed. On a worldwide basis, beef, dairy products and wheat are the three most common foods found to be positive in hypoallergenic diet trials. The results given in Table 1 are from serology testing and can provide us with guidelines. Table 2 lists the results of the serotesting for insects, Staphylococci, Malassezia, as well as indoor allergens (including house dust mite, and epidermals).

House dust mites are key allergens in man as well as in dogs and should be suspected in every case. In this survey house dust mite appeared relatively low in the table. This may be due to rigorous eradication that the author pursues well before testing pets for allergies. Flea allergic dogs also appear relatively low in the table and this may also be due to rigorous flea eradication programmes eliminating these as candidates. Utilizing the concepts of the allergic threshold and summation of effects is crucial to managing allergic patients. Removal of one or more of the inciting causes will often bring the patient below the allergic threshold and return it to the asymptomatic state. Removal of a single allergen such as in flea eradication ably demonstrates this concept. Fleas, feathers (pillows, birds, etc), dander (cats), house dust, dust mite, newsprint (newspaper) and tobacco smoke are all examples of allergens which can be removed from the immediate environment of the patient. Dietary allergens are managed by removal of the incriminated foodstuffs or additives from the diet.

AVOIDANCE

In flea allergic dermatitis (FAD), it is the flea saliva which contains the antigen and, in order for fleas to precipitate the allergic response, they have to bite the pet. A study conducted in Cape Town (M Briggs) and Pretoria (H Schroeder) on flea allergic dermatitis examined the benefits of a flea repellant. In this pilot study, the symptoms of FAD subsided rapidly with the anti-feeding effect of a repellant. In the control of severe FAD, therefore, it is advantageous to prevent the flea from obtaining its blood meal.House dust and dust mites can be reduced by mopping floors with a damp cloth, avoiding overstuffed bedding and covering bedding with impermeable material. Cleansing materials for carpets and furniture with mite- and fungi-cidal ingredients are available. Dust mites live deep in the carpet and resist vacuuming by attaching to carpet fibres. However, vacuuming does remove epithelial debris (human and pet dander) on which mites feed. Humidity is of prime importance to mite replication. In a study at a paediatric unit in the Western Province, 80% of children living at the coast were sensitive to house dust mite. In human patients, allergy to dust mites is reduced with the use of household insecticides and mural paints which have both anti-mite and anti-mould effects. Expecting couples (if allergic) are encouraged to perform household mite control during pregnancy even, to avoid development of the allergic state in their newborn infant. Household products containing insect growth regulators, tannic acid solution, as well as insecticides such as pyrethrum and benzoyl benzoate (e.g. Acarosan) are applied to the floor/carpets for dust mite control. Tannic acid is a denaturing agent and is effective against allergens in mite faeces as well as against fungal spores. Polyborates such as DOT(disodium octoborate tetrahydrate) are powders which are dusted into floors with long-term effects.

Detergents may assist if followed by thorough vacuuming. Vacuum filters with mesh sizes down to 0.06 microns have been advised for allergen entrapment. If pollens are incriminated, avoid fields, keep grass short and bring pets inside during the evening and early mornings when pollen counts are high. Flare factors contributing to the allergic state include anxiety, boredom, obesity, self-excoriation, and secondary fungal, bacterial and parasitic involvement. Regular examinations for fleas, pyoderma, yeasts, stress factors, as well as the introduction of a playmate/companion may assist. For most adverse food reactions, avoiding the offending foods or food additives is the most efficient therapy. Some dogs may have a higher tolerance and how meticulous the diet must be depends on the individual animals sensitivity. Poor client compliance is the most common reason for a relapse or a poor response to avoidance. It is most important that clients understand the aims and expectations at each stage. Since owners have to absorb large amounts of information, practice handouts can explain rule-out programmes, avoidance, dietary exclusion trials, flea control, immunotherapy, and anti-histamine trials. Breaking down the allergy rule-out programme into manageable units (e.g. ectoparasitic, atopic, dietary and contact) may simplify the work-up.

SPECIFIC IMMUNOTHERAPY

Aeroallergens (air-borne allergens) are ubiquitous and avoidance is not always possible. Allergen-specific Immunotherapy (ASIT), or "hyposensitization" has evolved as the preferred therapy for moderate to severe atopic disease. Allergen-specific hyposensitization is the careful selection of allergens for inclusion into ASIT. Only relevant allergens contributing to the hypersensitivity state are included. Ideally these should be based on both in vivo and in vitro test results, as well as careful evaluation of the clinical signs, seasonal effects, household materials, pets habits, pollinating plants and so on. For instance, if no one smokes, do not include tobacco extract. Ingested allergens are not usually included in ASIT - allergen free diets are required. In ASIT, small doses of the relevant allergen extracts are injected over time in order to stimulate the production of "blocking" antibodies (although the effect is now known to be more complex). No more than 10 - 12 allergens per vaccine vial is recommended (another vial can be utilised for up to 10 more allergens). In the USA, only aqueous extracts are used, whereas alum-precipitated extracts dominate in Europe. Usually, a low initial loading dose is administered for 2 - 7 days increasing incrementally to a maintenance dose of 10000 - 20000 PNU/ml every 1 - 3 weeks. Anti-histamines can be safely administered during ASIT. In severe outbreaks of pruritus, short courses of "crisis busting" prednisone/prednisolone (0.5 - 1.0 mg/kg once daily for 3 days only) may be necessary. Side-effects of ASIT in dogs are rare and usually not life-threatening. Side-effects may include localised swelling and worsening clinical signs.

Anaphylactic reactions (life-threatening in human patients) are unlikely to occur during ASIT in dogs. No correlation exists between breed predisposition and the benefit of ASIT. Results are better if pollens and dust mites are included. Young animals show greater improvement on ASIT if desensitized at an early age. ASIT will fail if the wrong allergen extracts are used. Injection of non-involved allergen extracts is undesirable and blanket hyposensitization based on panel testing, or mixed allergens (for example, all "indoor" allergens) is not advised. In vitro testing of serum samples by overseas laboratories is available to us here and selection of allergen extracts should be based on trusted test results. Concurrent low dose alternate day prednisolone administration, which may be necessary in severely allergic pets, has not been shown to decrease the success rate, although the ³ day "crisis busting" regime is the current recommendation. Patient follow-up and owner compliance are critical to the successful outcome of hyposensitization. Trials worldwide indicate that in 60 to 70 percent of cases, there is good to excellent long-term response. However, the results are much poorer if contributing factors and secondary complications are not controlled. Certain atopic dogs may require lifelong administration of ASIT, and the older the pet, the less successful is the outcome.

CONCLUSION

Identification of allergens involves a strict diagnostic rule-out programme as well as serotesting for Immunoglobulin E levels. Research into effective remedies continues (anti-cancer therapy by comparison, has undergone a quantum-leap) and yet, in allergic disease, therapy remains a challenge. The family of essential fatty acids has been shown to at least assist some, but not all atopic dogs. Anti-histamines have minimal side-effects in pets (apart from some sedation) and as such are under-prescribed in the authors opinion. These can give some relief while investigating allergens involved - as a first step to avoid the cortisone trap. Cyclosporine and pentoxifylline show promise as alternative or adjunctive therapy to the corticosteroids. Appropriate use of glucocorticoids has its place, but only after exhausting all possible alternatives and performing all possible tests. In vitro serological testing serves three main purposes - to support the clinical diagnosis, to permit selection of allergens for immunotherapy as well as the foods to be excluded from the diet. Furthermore, by hyposensitizing with selected allergen extracts, the pet can be brought below its pruritic threshold. The subsequent relief to the pet as well as the owner makes this a worthwhile procedure in clinical practice.

REFERENCES

1. Briggs M. 2003 Atopy Part II Management. Vetmed. 16 (2) 4 - 5
2. Briggs M. 2004 Serotesting for allergies in dogs: I Allergies to plants and fungi. Vetmed. 17 (4) 5 - 7
3. Halliwell R E W, Gordon C, Horvath C, et al 2004 IgE and IgG antibodies to food antigens in sera from normal dogs, atopic dogs and dogs with adverse food reactions. Veterinary Dermatology 15 (Suppl. 1), 2 - 3
4. Jasmin P, Briggs M, Schroeder H, et al. 2004 Comparison of a permethrin-pyripoxifen spray and fipronil spot-on used alone in a therapeutic trial for the diagnosis of canine flea allergic dermatitis. Veterinary Dermatology 15 (Suppl. 1), 47
5. Proceedings, 5th World Congress of Veterinary Dermatology, Vienna, Austria, 25 - 28 August, 2004