Annual Dermatology Conference
December 11, 2005
ALLERGIC DISEASES IN THE DOG AND CAT
NEW AND TRIED AND TRUE
Flea Allergy: The Battle Continues …
Carol S. Foil, MS, DVM (LSU SVM 1978), Dip ACVD
Professor Emeritus of Dermatology
Flea allergy dermatitis is the still amongst the most common skin diseases of dogs and cats. In the south, FAD is one of the most common non-routine reasons for seeking veterinary care. Recent advances in flea control methods have given veterinarians real tools for combating this miserable skin disease and have relieved many owners of flea allergic pet from the necessity of treating the home and garden with insecticides and other environmentally undesirable chemicals. Never-the-less, flea control challenges abound in our practices. The flea prevails ….
Review the Parasite
Ctenocephalides felis is an obligate ectoparasites of its animal hosts - cats and dogs- and adult fleas can survive only briefly off the host after taking a first blood meal. Factors that limit numbers of fleas and flea longevity on pets are self-grooming and owner-applied insecticides.
The cat flea is not host specific: It may be found on dogs, cats, raccoons, and opossums, but not on rabbits or rodents. The major portion of the flea life cycle occurs off the host in select sites within the host environment.
Eggs are laid in the hair coat but fall off the host; they are resistant to insecticides, but susceptible to Insect Growth Regulators (IGR) or Insect Development Inhibitors (IDI) for a period of time after they are laid and if the female flea ingests the chemicals before egg laying (Methoprene, Lufenuron, Pyriproxifen, Selamectin).
Larvae in the host’s environment feed on adult flea feces (blood). They are negatively phototactic and they can move horizontally over smooth surfaces quite rapidly to avoid light, heat, and dessication. Outdoors, larvae are easily killed or washed away by heavy rainfall, direct sunlight and any number of predators and even fungal infections. They require shaded, loose substrates with good drainage, and will not survive in lawns or on patios. Larvae are susceptible to traditional insecticides as well as environmental IGR’s, including those shed in flea feces from the pet’s coat (Lufenuron, Pyriproxifen, Methoprene; Fipronil - shed with pet hair, Permethrin). For larvae, optimum conditions are 65-80o F and high humidity. Dryness within the home (when heater or A/C is running) is fatal, meaning that flea ‘hot spot’ are confined to more humid areas in the dry home.
Pupae are encased within cocoons (often within carpet fibers). They are resistant to freezing, desiccation, insecticides and IDI’s / IGR’s. Pupa can lie dormant for many months and are stimulated to expupate by vibration, body temp., CO2. Once emerged, they are susceptible to insecticides, although they usually find a host within seconds of emerging so that exposure to environmental insecticides is limited. The life cycle can be completed in as little as 16 days.
The Allergy - Pathogenesis
Factors that determine development of allergy are not completely understood. Delayed Type (IV), Type I and cutaneous basophil hypersensitivity are all allergic mechanisms identified in patients and experimental models. The antigen(s) are polypeptides found in the flea saliva. Dogs and cats respond individually to a variety of these antigens, not all patients responding to the same specific chemicals. The major salivary allergen, termed Cte f 1, and a few of the others have been cloned and expressed by scientists at the Heska Corporation who have encorporated them into a specific in vitro ELISA test for flea allergy. These recombinant allergens do offer great potential for immunotherapy if they can be produced to be affordable.
In research it has been shown that either continuous or intermittent exposure to fleas can result in sensitization. However, in dogs, continual exposure has been shown to delay the onset and reduce the extent of the hypersensitivity response. Most animals, once allergic, remain so for life, although the degree of hypersensitivity may decline or disappear in some patients. There is some evidence that lack of exposure neonatally may contribute to the later development of flea allergy. Some time in the future it might be possible to “vaccinate” neonates. Atopic animals are predisposed to FAD.
Clinical signs of FAD in dogs
There is no breed or sex predilection. The most common age of onset is 10 months to 5 years, but FAD can be seen in puppies as young as 4 months, and older animals with new exposures can develop hypersensitivity (the ‘snow-bird’ phenomenon).
FAD is one of the 3 most pruritic skin disease of dogs (along with scabies and food allergy). Primary lesions are papules which may be topped with small crusts. Most of the symptoms noticed by owners are self-inflicted, secondary lesions: excoriations, alopecia, lichenification, scaling and crusting. The signs are quite variable in severity, and tend to worsen from year to year. Affected sites include lower back, perineum, tail head, hind limbs and umbilical region. Lesions can become generalized and mimic atopy or scabies, but usually spare the head. The symptoms may be seasonal or constant, depending on exposure. Even with continued exposure, symptoms may wax and wane. FAD has been called ‘waist disease’ by John MacDonald (lesions all behind the ‘waist’).
Young pups with early-onset FAD may have unique clinical signs with a widespread papular,
very pruritic disease mimicking scabies.
Many dogs develop staphylococcal folliculitis secondary to FAD. Some (especially German Shepherd dogs) develop furunculosis (deep pyoderma). Malassezia dermatitis can be a complication, along with secondary ‘seborrhea.’ Another complication we can see is the development of tumor-like fibropruritic nodules, in areas of chronic lichenified FAD. Because this is such a difficult disease to manage, some patients present with signs of iatrogenic Cushing’s disease.
Clinical Signs of Flea Allergy in the Cat
Cats with flea allergy may show signs similar to the dog (papular dermatitis, racing stripe distribution) but most often present with miliary dermatitis or with one of the other cutaneous reaction patterns - alopecia with no dermatitis (feline symmetric alopecia), eosinophilic plaque or eosinophilic granuloma. Cats with flea allergy may have behavioral problems or neurodermatoses, including hyperesthesia syndrome. This and severe head and neck pruritus are amongst the most difficult of feline syndromes to manage. Cats with flea allergy are often found to be negative on flea-comb examinations!
Diagnosis of FAD
Use a flea comb to look for fleas and flea ‘dirt - comma-shaped feces which consist of dried blood. Put specks of flea dirt on a moistened white paper towel and it will turn red. However, in allergic animals, fleas may be found in surprisingly low numbers or even be absent because pruritic animals with their constant obsessive grooming will be removing most fleas. Remember that even very minimal exposure may be sufficient to perpetuate pruritus in the hypersensitive patient—one or 2 bites per week are enough. Other animals (especially cats) in the household may be “carriers”. The real situation is that these animals seed the environment with preadult fleas which then emerge continuously to affect the allergic pet. Inspect other household pets for fleas if possible or send home a flea comb for owners to do so. The animal may have been bathed or dipped just prior to examination, so examination at home is often informative. Finally, look for tapeworm segments or a search for flea exoskeletons in fecal flotation in cats.
On occasion, in vitro testing for IgE titers against flea salivary antigens (Heska test) may be useful as a method to inspire a good flea control program. This test measures only antigen-specific IgE and does not document a delayed hypersensitivity; may be negative in 15-30% of patients with FAD.. We rarely recommend specific intradermal skin testing with commercially available whole flea extracts, as the test lacks sensitivity and specificity.
When flea allergy is suspected, as it should be in most every dog or cat with pruritic dermatitis, the ultimate diagnostic test is the response to a complete ‘flea vacation’ achieved by intensification of modern flea control practices.
Therapy for FAD
Four options that may be used in combination: 1) Move to a flea free environment – up north or up high - Denver, for example); 2) Antipruritic therapy (prednisone orally at 1 mg/kg x 5-7 days then reduce slowly to 0.5 mg/kg QOD or every third day) Don’t make the treatment worse than the disease! FAD patients become predictably more resistant to corticosteroid relief with time. Many develop secondary problems where steroids are contraindicated. Many patients are made Cushingoid. Few patients with FAD can be safely controlled with corticosteroids for a lifetime. Antihistamines and pentoxifylline are worth a try but less effective than in atopy. Cyclosporine is, amazingly, untested in pure flea allergy. 3) Allergen-specific immunotherapy - No Joy, so far. Heska’s salivary antigens are being investigated for this, and look promising experimentally. 4) Control fleas! Every small animal veterinarian in the south should become an expert in this field!
Flea Control Principles
Flea control for the family owning a flea-allergic pet is a whole ‘nother world from what is needed for routine health maintenance. I like to divide the challenge into two phases: The Flea Vacation Phase (Induction of Control) and Maintenance Phase.
For getting a flea vacation, use your best and fastest products and INTENSIFY. (I call this the Emeril Lagasse approach.) This means intensive Advantage or intensive Capstar. I use Advantage weekly on dogs needing baths weekly; re-apply 24 hours after each bath. I use it every 2 weeks in other dogs in the household and on cats. Capstar I use every other day. Keep the intensification program going until flea comb at home is negative for 2 – 3 weeks in a row. In our area, in my experience, about 85% of the time this program suffices. For the cases where it doesn’t, see below.
For maintenance, I like to rely on a regime that utilizes IGR or IDI as well as regular insecticide. For dogs on heartworm preventive, use Sentinel or Revolution plus routine on-animal flea control. Otherwise use Frontline Plus or other IGR-containing product. If the household relapses on maintenance, drop back to Intensification. Have the family monitor with a flea comb, regularly.
This includes households that do not go negative on Intensification or that do not stay negative on Maintenance. What are the likely reasons? To date, a very very uncommon reason is flea resistance to Advantage. Most often, the reason is continued emergence of previously seeded flea pupae from a highly infested environment. Within a relatively closed and simple homestead, most of the available pupae will have been stimulated to emerge by the presence of the treated pets and will die as they find the treated hosts, which is why Intensification works most of the time. This can break down if there are untreated pets in the household. More problems are encountered when the household pets have a larger home environment to roam around in, and when they are sharing protected outdoor areas with neighborhood hosts, wild or free-roaming. The larger and more complex the home territory, the more likely this is to be a problem. The ultimate challenge is flea control on a free-roaming flea allergic patient.
The solution? Confine the flea allergic pet more closely to the area surrounding the home, and call in the professionals. After a month of intensification fails, I ask owners to contract with a pest control company. (Ideally one I have checked out myself.) The professional should be prepared to identify flea larval ‘hot spots’ around the home for treatment, and the owner should be prepared to help with this, to clean up those places for specific treatment and to pay more than for standard pest control as well. Some common flea hot spots in and around households include: closet floors, under-the-bed hiding spots, outdoor carpets or mats by the back door, under decks, under houses, out-side storage sheds, piles of ‘stuff’ in garage or car-port, and sand-boxes. At times, raised land-scaping beds, especially in shaded areas, can be a problem. As a general rule, I find that do-it-yourself flea control is seldom successful, and I have about given up trying to sell or provide information to owners on at-home flea control.
Summary of Flea Control Products – Pros & Cons
IGRs / IDIs
How does Lufenuron work? Lufenuron is a chitin synthesis inhibitor. It has virtually no acute mammalian toxicity and no chronic toxicity recorded. It is the only feed-through IDI available for use on dogs and cats in the U.S., at present. Program7 is sold as tablets for dogs, liquid and injectable for cats and in combination with milbemycin as Sentinal7.
Problems with Lufenuron? It is SLOW. As the product has no efficacy against adult fleas, pets remain fully susceptible to the emergence of any fleas from the environment. The larger and more complex the pet=s environment, the greater this problem is. It may FAIL because in order for there to be no on-going environmental contamination with viable eggs, every animal in the patient=s environment must be on this medication for it to be effective. If there are problems administering the drug to one household pet or if there are feral or stray animals visiting the home turf with any regularity, continued fleas production is to be expected. Lufenuron is POORLY ABSORBED unless it is administered along with a fat-containing meal and there is little window for any delay in monthly administration. Female fleas can resume viable egg production within hours of blood levels falling below recommended levels. CATS can be difficult to treat on a regular basis with food, as is necessary. This has been overcome by introduction of new injectable formulation.
Nylar is licensed for use to many veterinary & OTC marketers. It is available as a spray-on for dogs in combination with 2% permethrin (KnockOut7 by Virbac), as a spray in combination with synergized pyrethrins for dogs and cats (FastAct IGR7 by Mycodex) and as a drip-on with permethrin for dogs (BreakThru7 and BioFlea Halt7 by Farnum) and as environmental foggers and sprays (EctoKyl7 by DVM, KnockOut7 by Virbac, and Environmental Control from Mycodex). Most pest control operators utilize Nylar in their home treatment.
How does pyriproxifen work? It is a traditional juvenoid IGR that has extraordinary
stability and high efficacy. As an ovisterilant it remains 100% effective for 150
days after a single spray application and even for 3-4 months after pyriproxifen-containing
collars are removed from test animals!
Problems with Pyriproxifen. Clients prefer to kill adult fleas. As the great success of Program has shown us, clients want convenience as well as efficacy. Environmental treatment is what we are all striving to move beyond. Products that offer combination with permethrin are not safe for cats, but are VERY effective and sold over-the-counter as well as through vets. The availability has been more limited recently.
Advantage7 and Advantix7 (imidacloprid + permethrin) from Bayer. This is a topical drip-on product available only through veterinarians (theoretically).
How does Imidacloprid work? It is a post-synaptic nicotinic receptor binder that is safe for mammalian exposure because of the lack of such receptors in the peripheral nervous system and because of its lack of measurable systemic absorption after topical application. Advantage7 is marketed as a dorsal spot-on for both dogs and cats that seems to be well-tolerated by sensitive cats and is much preferable to spray-on products. It provides flea knock-down withinin 24 hours. For cats 100% killing can be maintained for 21 days; for dogs 90% for 28 days.
Problems with Imidacloprid? It is susceptible to wash off, therefore outdoor active dogs and dogs that swim or must be bathed because of dermatitis must be re-treated frequently. (Weekly re-treatment is allowed.) Also, imidacloprid has no efficacy against ticks. The cost, for large dogs, does not compare favorably with competing products. HOWEVER, THIS IS A GREAT PRODUCT. MY FAVORITE for intensification.
Frontline7, from Merial. Available as Frontline Spray7, Frontline TopSpo7 and the spot-on Frontline Plus7 with S-methoprene (an IGR).
How does fipronil work? This is a broad spectrum insecticide that is a GABA receptor antagonist that works via chloride channel blockade. It is safe for mammalian exposure because of the lack of such receptors in the peripheral nervous system and because of its lack of measurable systemic absorption after topical application. It is labeled for puppies and kittens of 8 weeks. Fipronil spray is an alcohol-based spray that must be administered at a rate of 3-6 ml/kg ... to wetness. It takes 30-60 ml to treat a 10 kg dog. The drip-on requires less volume, but convenience is balanced against lower perceived efficacy in large dogs. Fipronil binds chemically to the hair, stratum corneum and is absorbed through the follicle by the sebaceous glands. It kills at 95% for over 80 days after application on dogs and for 1 month with bi-weekly bathing. Monthly application to dogs is sufficient to break the life cycle in a closed environment with dogs.
Problems with Fipronil? With the spray, the high volume of alcohol-based product that must be applied when the spray product is used is objectionable; many owners will apply insufficient amounts of the product. The time to total kill is perceptibly slower than Advantage and this can lead to a perception of product failure in a highly infested household. Also, the product must be applied no more than once a month so it cannot be used in Intensification. Frontline Plus7 spot-on with s-methoprene as an IGR for integrated pest management makes it a great product for Maintenance. A good idea!
Revolution7 from Pfizer, is available as a drip-on - systemically absorbed - for dogs
cats, kittens and puppies. It is an adulticide and I.D.I. for fleas and also can be
effective against Sarcoptic mange and with repeated dosing somewhat effective against
ticks. It also kills intestinal nematodes (labeled only for cats for this so far),
and pre-adult stages of heartworms and is licensed as an effective heartworm preventive.
It has a wide margin of safety and is safe for ivermectin-sensitive collies.
How does selamectin work? Like all avermectins, selamectin induces neuromuscular paralysis in susceptible parasites by increasing chloride permeability in glutamate-gated neuronal chloride channels. This drip-on is systemically absorbed and fleas and other ectoparasites are exposed with blood ingestion. It is ovicidal for fleas by preventing egg hatching.
Problems with selamectin?
It is not as effective an adulticide, compared to fipronil and imidacloprid. It is expensive.
Capstar7 from Novartis is a new synthetic compound derived from the same family of insecticides as imidacloprid (called neonicotinoids). It is available to be administered as capsules to dogs, puppies, cats and kittens. It has a rapid-kill and lasts less than 24 hours as a systemic insecticide. Nitenpyram is not normally used alone for flea control, but is safe enough to give every other day, if you want to use it that way for Intensification. It also can be used effectively for pets entering and departing boarding kennels, veterinary facilities as well as other areas away from home.