Annual Dermatology Conference
December 11, 2005
Carol S Foil MS DVM Dip ACVD
Professor Emeritus of Dermatology
Arthropods that can be associated with hypersensitivity reactions in dogs include biting insects (mosquitoes and flies), stinging insects (bees, wasps, fire ants, assassin bugs), and insects and mites whose body parts and excreta become environmental antigens (dust mites, storage mites and cockroaches). For the most part, it has been difficult to develop good information about the prevalence of any of these allergies other than house dust mite allergy. HDM allergens are the most commonly identified allergens for atopic dogs in most geographic regions, and certainly are the most important allergens in our area in south Louisiana. The true prevalence or clinical relevance of other arthropod hypersensitivities is a big unknown.
Making an accurate diagnosis of arthropod allergies presents a problem in two clinical settings. The first is in the evaluation of the dog or cat with symptoms of allergy that is proving to be difficult to diagnose as having standard atopic dermatitis/food allergy or that is not responding well to standard management. In those patients, it may be worth investigating other arthropod allergies and some allergists advocate doing so.
The second problem arises in the evaluation of positive arthropod skin test or in vitro reactions when these are included in a standard evaluation panel. The allergist must then try to interpret these reactions knowing that there is little good information on the diagnostic accuracy of testing with these antigens. This type of problem can be illustrated by skin test data recently provided to me by Dr. Steve Lemarié from his south Louisiana dermatology referral practice.
Antigen % positive
HDM 1:5000 86
HDM 1:10,000 81
Black Ant 89
Fire Ant 95
Deer Fly 73
Horse Fly 78
House Fly 84
These represent the last 37 dogs tested at his practice; reactions at 3-4+; 17 dogs reacted to all antigens tested.
In this lecture I will try to review what is known and provide some guidelines for dealing rationally with these allergies.
Thirteen species of microscopic mites have been found in house dust samples. These mites are in 3 closely related families: Glycyphagidae (Blomia, Glycyphagus, Lepidoglyphus), Pyroglyphidae (Dermatophagoides, Euroglyphus) and Acaridae (Acarus, Tyrophagus). Sarcoptidae and Psoroptidae (includes Otodectes) are also related closely.
The most important allergenic mites are: Dermatophagoides pteronyssinus, D. farinae, Euroglyphus maynei, and in tropical areas, Blomia tropicalis. Dermatophagoides maynei and D. microceras are found in some areas. Other species of interest are: Glycyphagus domesticus, Tarsonemus spp (Glistening mites), Storage mites: Acarus, Tyrophagus, Lepidoglyphus.
Both fragments of mites’ bodies and fecal particle contents contain antigens; most fecal antigens are digestive enzymes. Antigens are divided according to chemical properties and allergen cross-reactivity into 13 groups. The antigens have cross-reacting and species specific epitopes. Antigens are named by mites species and group antigen designations. (Der p 1, Der f 6, etc.) Group 1 antigens: Der p 1, Der f 1 are most allergenic for humans; large amounts are present in mite feces and remain in the environment despite killing off the dust mites.
Unfortunately, most HDM + dogs’ sera show little reactivity with Group 1 and 2 antigens.
There are higher molecular weight antigens recognized by atopic dog sera that have
no homology with currently characterized human. One of the HMW antigens has been characterized
as Der f 15, a digestive chitinase.
Cross reactivity with other mites:
There is extensive cross-reactivity within traditional house dust mites species and genera, within the antigen groups. There can also be clinically important cross-reactivities with storage mites in house dust mite sensitive patients, which has made it more difficult to interpret the reactions to the commonly tested antigen from T putrescentiae.
Lack of cross-reactivity can be a problem in areas where tropical dust mites are more prevalent (Orleans Parish and south). Blomia tropicalis allergy may be missed by tests utilizing only antigens from Dermatophagoides spp. Several studies indicate ASIT is most efficient if specific antigens and species of mites are identified and used, where possible.
Sensitization, as demonstrated by skin testing and allergen-specific IgG measurement has been demonstrated in 15 of 20 dogs with sarcoptic mange, although none of the dogs developed signs of AD. ID testing went negative by 90 – 180 days after treatment. Looking at the opposite problem, of 83 AD dogs with reactivity to HDM antigens, 17 had scabies IgE. In skin testing, Otodectes infected dogs are 54% positive in skin testing to D far but become negative 20 days post tx.
In humid areas of the world, up to 30% of human population have positive skin test reactions to at least one dust mite species. The prevalence in south Louisiana is quite high. In general, prevalence of allergy corresponds to geographic distribution of humidity clines; the highest prevalence is seen where winter is humid.
The most prevalent mites are D. pteronyssinus and D farinae, which co-inhabit homes in many regions, with one or the other species predominating. Within a region, which species predominates varies from home to home.
In many studies more dogs show reactions on IDST and in in vitro testing to D farinae, despite D pteronyssinus being the most prevalent mite in the area and despite allergy to D pter being most common in people in the region.
Here is a summary of results reported for dogs, using a variety of protocols: Netherlands 3.4%, Norway 1.6%, France 15%, France – coastal 80; India Ocean coastal D far 89%, Blomia 76%, P. africanus 72%; Japan – 69%; Ohio D far 68%. The ACVD TASK FORCE summary of dogs with AD +: skin test - D far 19 – 70%, D pter 2 – 54%, mixture 44-100%; in vitro – mixture 32 – 90%; Lemarié’s data for Metairie was 81% as shown above. Of dogs with serum reactivity against any dust mite (n=48), 96% have IgE against D far; only 35% against D pter.
Dogs with atopic dermatitis frequently have IgE directed against mites other than Dermatophagoides. In one study of 84 dogs, 94% had such antibodies; of these: 95% were against A siro, 92% - B. tropicalis, 89% - T put.
Cats: Netherlands 4/10 positive to D far
Classical AD, non-seasonal (in most regions); antigens may persist after mites die
out; patients stay indoors more in winter; worse in bed, when house cleaning is going
on; better when outdoors. One paper has described allergic rhinitis (sneezing, rhinorrhea;
steroid / antihistamine-responsive) in dogs with positive ID and in vitro reactivity
to D far and D pter.
Skin Testing: Antigens:
Sensitivity (75%) and Specificity (96%) and Diagnostic Accuracy (83%) using 1:50,000 w/v. Dogs with positive reactions – 88% confirmed to have AD. In 6 healthy pet dogs tested with 1:1000 and 1:50,000 w/v D farinae, 3 of 6 and 2 of 6 had immediate reactons; dogs that reacted at 1000 also reacted at 50,000.
Antigen strength: Definitive answer to this basic problem awaits standardization of antigen content in commercial extracts. ACVD task force: test at 1:50,000 wv. Greer: test at 1:5000 and 1:10000 wv and if positive, test also at 1:20000, 1:40000 to help rule out false positives. Halliwell et al showed negative reactions in lab beagles at 1:10,000 wv.
In Vitro tests: RAST, ELISA, VARL-EIA; Little data available.
One of 10 normal cats tested with D far was positive. Using Heska ELISA there was no difference in mite IgE levels between normal (n=54) and cats with allergic skin disease (n=59).
Symptomatic therapy: as for other forms of atopic dermatitis; may be less successful due to continuous exposure. Management in human medicine largely focuses on environmental control and topical (local) medical treatment as well as prevention.
Well-controlled trials in human AD do not show much response to ASIT and it is not much used. However, recent study showed 58% reduction in symptom scores and 20% reduction in use of rescue medication after 12 months of conventional immunotherapy in HDM allergic patients with allergic rhinitis.
For dogs: ACVD task force: “As a result of the scarcity of evidence from controlled trials, the true efficacy of ASIT, and the optimal protocols for allergen dose and frequency of injection are currently unknown.” Limited information available for the dog specifically for HDM allergy is fairly discouraging. Anecdotal reports and uncontrolled studies suggest 50% response rate. In one study from Great Britain, where HDM allergy is the most prevalent cause of AD, a long-term follow-up of ASIT in 277 cases had 33% lost to follow-up or failed to comply! Of the remaining 186 cases, 21.5% had a good response, 40% a partial response, and 38% a poor response.
Mite antigens are difficult to remove, eg by vacuuming, ‘steam cleaning, or dry cleaning. Laundering, under specific conditions can remove antigens, as they are water-soluble. Mites are not closely related to insects and many insecticides and growth regulators are ineffective for the control of environmental mites.
The most effective strategies are lack of carpeting and use of mattress and pillow encasements and reduction of home humidity.
Bedding can be controlled by encasing mattress and pillow covers in occlusive, vapor-permeable, non-woven synthetic or tight weave fabrics with certified pore size (5 – 9 micron – fecal pellets are 10 microns; smallest mite stages are 20 microns) – called allergen impermeable covers (see http://www.natlallergy.com/poresize.html) and washing bedding with benzyl benzoate (0.03%) acaracidal additives or in hot water (130 def F).
High ventilation rate is an important factor (> 1 air exchange/hour); Dehumidifiers and air-conditioning are useful. Goal is maintaining RH below 50%. It may not be possible to achieve this in warm humid climate, however. To completely prevent population growth of D far, RH must be maintained below 35% for at least 22 hours per day!
Washing bedding weekly in hot water (130 F) kills mites and removes most allergens. Washing in cooler water does not kill mites, but does remove allergens. Adding benzyl benzoate to a conc. of 0.03% also kills mites. These are available commercially as laundry additives. Tumble drying at 130 F for 10 minutes kills all mites, may denature some antigens. Dry cleaning kills mites, but does not remove all allergens.
These are ‘house dust mite hotels.’ Wooden, vinyl or leather covered furniture is preferred. Blinds rather than drapes. Hard surfaces, not carpet.
Vacuuming can stir up antigens and elicit clinical signs in sensitive individuals, who should leave the area when vacuums are in use. Use bags with 2 layers or high efficiency particulate air filters or those drafted to outside. Vacuuming weekly removes only surface mites and allergens. Steam cleaning does not usually get hot enough or penetrate deeply enough to work and in fact, by wetting carpet pads, may make matters worse!
For at least 24 hrs kills mites. Follow by washing to remove antigens. (In cold climates, put mattresses out for 24 hours.)
Air filtration, ozone generators, duct cleaning, chemical acaricides; benzyl benzoate denatures the fecal antigens; its efficacy is controversial with conflicting results in studies.
Dermatophagoides group 2 antigens were not found in an investigation of commercial dog food in the north central United States. Many reports of Dermatophagoides antigens in stored cereal grain products come from sub-tropical locations; this need further study as does the presence of forage and storage mite allergens in commercial pet foods. Currently my recommendations are to store newly purchased dog food in sealed containers, preferably in the freezer.
A study was conducted in the Netherlands utilizing benzyl benzoate acaricide in the homes of house dust mite allergic dogs, whose clinical signs were followed after home samples became negative by testing for quinine. Results were 48% cure, 36% moderate improvement, 15% no response. It is worth noting that dogs that were sensitive to storage mites responded equally well. Also worth noting that benzyl benzoate was used very aggressively in this protocol – all fabric and carpeted surfaces treated, powder left on 24 hours, retreatment monthly for 3 or more months, treatment until guanine test negative!
Fecal material: Semi-quantitative measurement of guanine (fecal product) is commercially available as a test kit (AcarexR); less than 0.6 mg guanine/gm dust threshold to provide an estimate of dust mite fecal antigens.
Antigens by ELISA: MITE-T-Fast (AVEHO Biosciences) is a wand Elisa test to identify’clinically relevant levels of dust mite allergen on a rug or bed. No data available from the company. Measures <2 ug/g, to > 10 ug/g.
As discussed above, it is not clear whether storage mite reactivity in serum or on a skin test represents cross-reactivity with classical house dust mite allergens or whether animals who may be clinically hypersensitive are exposed to environmental house dwelling species of mites or whether this may represent a clinically important allergy to storage mites or their antigens in dog food.
Storage mites can infest stored grain and stored dog food, although the studies of packages of dog food purchased in the United States and western Europe have generally found few live or whole mites. Mites could also, and likely often do, infest the raw cereal ingredients of processed pet foods. There is currently no commercially available method to test for the presence of storage mite antigens in stored or newly purchased pet foods. Consequently, the importance of storage mite allergy in atopic dogs and cats remains an area that needs investigation.
Currently, I do make certain recommendations about feeding and food storage for my patients who do test positive to storage mite antigens. I recommend using ZD and I recommend repackaging newly purchased bags of food into sealable containers and storing the food in a freezer.
This is also called "ears, nose and toes syndrome". This is a distinctive dermatosis and most often noticed because of lesions on the nose. It can develop suddenly and severely or it can be chronic. Primary lesions are papules and plaques or poorly defined swelling of the nose. These changes are associated with alopecia, crusting, erosion, excoriation, ulceration and macular depigmentation. Affected areas include the poorly haired sites on the dorsal muzzle, the pinnae, in front of the ears, around the eyes and the bases of the foot pads. On the ears, lesions are crusted or scaly erythematous papules. On the pads, there is swelling, depigmentation, crusting and scaling.
Histopathologic evaluation helps rule out important differential diagnoses such as Cryptococcosis, squamous cell carcinoma and mast cell tumor. The finding of intense eosinophilic dermatitis in the affected areas is very suggestive of this diagnosis.
Lesions develop at the sites of mosquito bite and the disease will resolve when the patient is protected from mosquito exposure. It remains to be seen whether other biting flies will be implicated in some cases. If the animal cannot be protected from the insects, then the prognosis is guarded. Megestrol acetate or cyclosporine therapy could be tried.
It has long been speculated, owing to sudden onset, seasonality in some climates, and exposure to outdoor environments that these syndromes can be initiated, at least, as a response to biting or stinging insects. In one prospective study, 9 dogs were identified for study and the majority did have known exposure to bees. Against this being a hypersensitivity response, however, is that the syndromes are not recurrent or chronic.
Most affected are large breed young adult dogs with short hair on the muzzle. The onset is very acute. The lesions are edematous papules and nodules that quickly progress to hemorrhagic furuncles. Pruritus is often marked leading to ulceration. The animal may become painful. Lesions are generally on the dorsal muzzle, but may also involve perioral muzzle and periocular skin. Untreated and unprotected, the disease will resolve in 3 weeks, but scarring may be significant. Cytology of unruptured furuncles demonstrates neutrophilic and eosinophilic hemorrhagic exudate without organisms.
This syndrome responds rapidly (within 48 hours) to strong anti-inflammatory doses of corticosteroids. We prefer oral prednisone 1 -2 mg/k for 7-10 days, then tapering for a total of 2 – 3 weeks of treatment. E-collar protection may help prevent scarring damage.
In contrast to the incidence in human medicine, severe adverse reactions to insect stings appear to be very infrequent. Allergic reactions, furthermore, must be distinguished from toxic reactions when multiple stings are sustained. Insect allergy is frequently considered in the work-up of chronic or recurrent urticaria in dogs but very seldom proven and is likely not a important cause of that uncommon syndrome, either.
There are some dermatologists, mostly located in southern California, who do provide immunotherapy for presumed Hymenoptera sensitivity for animals with edematous or systemic reactions, but there is no literature published on the procedure.
The contribution of mosquitoes and other biting flies to atopic dermatitis syndromes remains an open question. There is much evidence to suggest cross-reacting reactivity in dogs with flea allergy. The evidence is mostly empirical from those who manage patients with positive reactions whose AD seems to flare after exposure to mosquito bites. Unfortunately, it has also been shown the using mosquito and other insect antigens does not decrease the number of dogs with puzzlingly negative skin tests nor does including insect antigens in treatment mixtures improve response rate. Given also that few animals with atopic dermatitis fail to have reactions to other well-known allergens, we have suspended our testing for these allergens in our atopic patients.
Another implication of cross-reactivity is that other insect bite exposures might flare up a flea allergic dog, even in the absence of fleas.
If treatment aside from ASIT were to be undertaken, it would have to involve protection from mosquito and other biting fly exposure. Dogs could not be housed outside in Louisiana and be sufficiently protected. For indoor dogs, outside exposure can be ameliorated with repellents. DEET is of questionable safety and should not be used in very small dogs. Pyrethrins and synthetic pyrethroids provide some repellency but it may not be adequate or practical. Citronella-based repellents are likely the safest and most practical approach, but are not approved for use on dogs and also may not be entirely safe on very small dogs.