5 Flea allergic dermatitis INITIAL PRESENTATION Pruritus with papules, erythema, scaling and hyperpigmentation in a Jack Russell terrier. 28 INTRODUCTION In some parts of the world, flea allergic dermatitis (FAD) is the most common allergic disease and a major cause of pruritus in dogs and cats. In other parts it is a significant problem only at certain times of the year. Although allergic dermatitis is the main condition associated with fleas, a distinction between pruritus resulting from severe flea infestation and a hypersensitivity response should be made. In very young puppies and kittens, severe flea infestations provoke varying degree of pruritus, but more often patients exhibit signs of weakness, lethargy and anaemia. Fleas are also vectors of infectious organisms such as Bartonella, Rickettsia felis and Haemoplasma spp. CASE PRESENTING SIGNS A 6-year-old female Jack Russell terrier was presented with severe erythema, pruritus, papules, alopecia and hyperpigmentation affecting the dorsum, feet, periocular skin, ears and muzzle. CASE HISTORY This varies between individuals but most pruritic dogs are presented with a history of pruritus and varying lesions affecting the lumbo-sacral region. As the flea life cycle is affected by environmental factors such as temperature and humidity, seasonal exacerbations may occur. Often flea control is only intermittently used and in-contact animals, especially cats, are inadequately treated. The history in this particular case was long and complex. The most relevant parts were: Long-standing history of non-seasonal pruritus involving face, feet and ventrum, and more recently the dorsal trunk had also become involved. The pruritus has been managed with intermittent methylprednisolone acetate injections, but these had become ineffective with severe deterioration in the dog s clinical condition. The dog was mainly fed on a commercial pet food and more recently an 8-week diet trial with a prescription hydrolysed hypoallergenic diet had failed to resolve the pruritus or the clinical lesions. The indoor environment was fully carpeted and the dog normally slept under the owner s bed. Outdoor access was to the garden only. Previous flea control had been intermittent, using fipronil and most recently selamectin. The three in-contact cats were unaffected and were intermittently treated for fleas with a pet shop product. The owner had seen fleas on one of the cats some weeks back and had treated it with proprietary flea product from the supermarket. CLINICAL EXAMINATION A whole range of clinical signs, from primary lesions such as papules and pustules, to severe secondary hyperpigmentation, lichenification and fibropruritic nodules are seen, depending on the chronicity of the disease. Selfinduced alopecia due to over-grooming and secondary bacterial infection is often seen in affected dogs. Atopic dogs are predisposed to flea bite hypersensitivity, even those that have been well managed. Some dogs will present with pyotraumatic dermatitis on the rump, or at other sites.
5 Flea allergic dermatitis 29 Figure 5.1 Erythema, papules and self-induced alopecia on the dorsum. Figure 5.4 Periocular dermatitis. Figure 5.2 Lateral aspect on the trunk. Figure 5.5 Erythema and self-induced alopecia extending to the distal aspect of the leg. Figure 5.3 Papular dermatitis in inguinal regions. The clinical findings in this case were: Severe generalized erythema with papules, follicular papules and crusted patches on the trunk (Figs 5.1 and 5.2). Erythema, alopecia and papular rash on the ventrum and inguinal region (Fig. 5.3). The periocular skin was hyperpigmented, lichenified and erythematous, with evidence of excoriations (Fig. 5.4). Both the pinnae and vertical ear canals were erythematous. Erythema, self-induced alopecia, crusting and hyperpigmentation involving all four feet (Fig. 5.5). The skin was malodorous and greasy to the touch.
30 SMALL ANIMAL DERMATOLOGY The peripheral lymph nodes were not enlarged and the other physical parameters were within normal limits. DIFFERENTIAL DIAGNOSES In this case, given the clinical signs and the distribution of the lesions, there was evidence for more than one type of hypersensitivity. The facial, pedal and ventral distribution suggested atopic dermatitis, and that affecting the dorsal aspect, flea allergy dermatitis. A concurrent adverse food reaction could also have been contributing to the pruritus. The other differentials included: Staphylococcal pyoderma Malasseziosis Sarcoptic mange Demodicosis Otodectes hypersensitivity Dermatophytosis Adverse drug reaction. CASE WORK-UP A number of the differential diagnoses were ruled out with simple in-house tests: Skin scrapes were performed to rule out demodicosis and to look for sarcoptic mange. Negative skin scrapes do not definitively rule out sarcoptic mange and therefore a Sarcoptes IgG ELISA test was performed, which was also negative. There was no fungal growth after 3 weeks of culturing of a sample obtained by the MacKenzie toothbrush technique. Tape-strip samples, obtained from crusted lesions, revealed clumps of coccoid bacteria, neutrophils and keratinocytes. Staphylococcus intermedius was isolated from a swab submitted for bacterial culture, which was sensitive to amoxicillin/clavulanate, cefalexin, enrofloxacin, marbofloxacin, clindamycin and trimethoprim/ sulphonamide. It was resistant to amoxicillin, penicillin and tetracycline. Coat brushings failed to demonstrate any fleas or flea faeces. In addition to atopic dermatitis, the history, clinical signs and distribution of lesions were suggestive of flea allergic dermatitis. The diagnosis of flea allergy dermatitis is supported with additional tests and with response to aggressive flea control. The simplest test is the demonstration of fleas or flea faeces using a flea comb; however, about a third of animals fail to show any evidence of fleas, for various reasons: Self-grooming removes the fleas and flea faeces Owners often groom or bath the animals before coming into the practice Intermittent flea control reduces the numbers, making it difficult to find them Exposure to the flea source may be intermittent. In these cases further diagnostic tests may be of value; however, it is important to remember their limitations and ultimately a positive response to aggressive flea control is needed to confirm the diagnosis. In vitro testing: In this case an in vitro Allercept IgE ELISA test using recombinant flea saliva revealed a markedly elevated flea allergen specific IgE concentration, which was consistent with flea allergy dermatitis and suggested current flea exposure. However, the specificity and the sensitivity of the testing are variable, and the test does not recognize those animals with cell-mediated hypersensitivity immune responses. It is useful as a diagnostic aid but a negative test should not necessarily rule out FAD. It is estimated that about 15 30% of individuals may show just cell-mediated immune responses. In addition, a serum IgE test for other allergens was performed (see Chapter 3) to assess the role of environmental allergens. This revealed high levels of IgE to house dust and storage mite allergens. Intradermal testing: Intradermal testing with wholebody flea antigen or flea saliva may also support the diagnosis. This test produces immediate reactions (15 30 minutes), or late-phase reactions (4 6 hours) or delayed reactions (24 48 hours) to specific antigens injected intradermally. The test site should be examined at the appropriate times. Late-phase and delayed-type reactions are recognized either by an erythematous ring at the site of injection and/or a raised wheal. In this case this test was not deemed to be suitable for either flea antigen or other environmental allergens, because the last injection of methylprednisolone acetate had been given only 2 months prior to the initial examination by the dermatologist. The duration of action of this drug is anything between 4 and 6 weeks, and varies between individuals. Ideally, intradermal testing should be carried
5 Flea allergic dermatitis 31 out not less than 12 weeks after the injection of a reposital glucocorticoid. flea bite and accounts for 15 30% of the flea allergic cases. DIAGNOSIS The diagnosis in this case was that of bacterial pyoderma, flea allergic dermatitis and atopic dermatitis. PROGNOSIS The long-term prognosis was good, provided the owner was able to maintain thorough long-term flea control on all the animals in the house and it was possible to effectively manage the concurrent atopic dermatitis. There may be flare-ups from time to time depending on the allergen load. AETIOPATHOGENESIS OF FLEA ALLERGIC DERMATITIS Although most cats and dogs have fleas at some point or other, not all develop clinical signs associated with hypersensitivity and it is probable that those that don t are not sensitized to the flea saliva. However, exposure, either intermittent or continuous, to flea bites is a predisposing factor in the development of the allergic response, as is atopic dermatitis. Sensitization can occur at any age and is usually lifelong. Several allergenic proteins identified in flea saliva can result in an individual becoming sensitized. The proteins range from 12 to 50 kda in molecular weight. Three types of allergic responses immediate, late-phase and delayed-type responses have been identified. Immediate-type hypersensitivity occurs within minutes of the flea bite and is associated with mast cell degranulation triggered by the chain of events following the binding of the allergen to the IgE. Late-phase reactions are associated with an influx of inflammatory cells in response to the release of preformed and newly synthesized inflammatory mediators including cytokines and chemokines. Infiltration of basophils, in particular, occurs in flea allergic dermatitis. Degranulation of basophils is associated with basophil hypersensitivity. This occurs at 4 6 hours after a flea bite. Delayed-type hypersensitivity is cell mediated; there is an influx of lymphocytes and macrophages associated with an interaction of several cytokines. This reaction shows clinical signs about 24 48 hours following a EPIDEMIOLOGY There is no sex predisposition and sensitization can occur at any age, but appears to be seen mainly in older animals. Intermittent exposure is associated with increased sensitization, whereas continuous exposure may result in some tolerance. The incidence of the disease is dependent on the presence of environmental conditions in which the fleas are likely to thrive and perpetuate. An ambient temperature of 18 30ºC and high relative humidity of between 70% and 80% favours flea reproduction and survival; however, the flea s biology is such that it ensures its own and/or its intermediate stages survival, even when the conditions are unfavourable. Although the flea itself is unable to survive cold temperatures, or high temperatures with low relative humidity, the pupal stage (Fig. 5.6) is able to endure them for up to 300 days. Then, when appropriate environmental conditions are encountered (see below), the adult flea emerges. The flea life cycle from egg to adulthood can therefore vary from 15 to 300 days depending on the environmental conditions. The cat flea, Ctenocephalides felis felis, is the main species implicated in flea allergic dogs and cats. Ctenocephalides canis is also reported in some countries. Less commonly, flea species that normally infest other mammals and birds may be involved (Table 5.1). The female adult flea is an obligate parasite and needs a blood meal in order to produce eggs and, if the conditions on the host are ideal, it can lay up to 30 50 eggs a day. Feeding fleas can live up to 100 days and lay as many as 2000 eggs in their lifetime. Fleas do not jump on and off animals, but tend to live on the host. The eggs fall into the animals environ- Table 5.1 Flea species and their main hosts Flea species Ctenocephalides felis felis Ctenocephalides canis Pulex spp. Echnidophaga galinacea Spilopsysllus cuniculi Archaeopyslla erinacei Xenopsylla spp. Natural host Cats and dogs Dogs and cats Humans Birds Rabbits Hedgehogs Small mammals
32 SMALL ANIMAL DERMATOLOGY Female fleas: Produce on average 30 50 eggs per day following a blood meal Pupae: Can remain dormant for over a year but may hatch after 5 9 days under ideal environmental conditions (i.e. temperature, humidity and presence of host) Eggs: May hatch into larvae on the animal, or can fall off anywhere in the environment Larvae: Undergo 3 moults (L1 L2 L3) before pupating Figure 5.6 The flea life cycle. ment during grooming or scratching, as they are nonadherent. The eggs hatch into the first larval stage, which burrow deep into crevices, carpet pile, etc., as they are photophobic and geotrophic. This stage feeds on flea faecal pellets and other organic debris in the environment. There are three larval stages and the third stage transforms into the pupa. This stage is a cocooned pre-emerged flea which is protected from environmental insults (including parasiticidal agents) and will only emerge if conditions ensure that its survival is more or less guaranteed by the presence of a host. These conditions include carbon dioxide, warmth and air movements, which indicate the presence of a host. TREATMENT OPTIONS Multiple therapies are usually required in the early stages of treatment of flea allergy dermatitis. They include those that limit pruritus, deal with any secondary infections and those that specifically kill the flea and its intermediate stages, both on the animal and in the environment. Flea control: Both the treatment of all animals in the house and that of the environment should go hand in hand, at least during the initial stages. The treatment should be tailored to suit each case, depending on the number of animals within the household, the ability of the owner to use the products as indicated and the cost. Fipronil: Fipronil belongs to the phenylpyrazole family and its mode of action is by blocking the pre- and postsynaptic transfer of chloride ions through the cell membrane, thus acting as an insect GABA antagonist. It has both insecticidal and acaricidal activity. It is available in spray and spot-on formulations and kills fleas within 24 hours, and tick and other insects within 48 hours. It is combined with s-methoprene, an insect growth regulator which inhibits the development of immature stages by mimicking the juvenile hormone. Nitenpyram: Nitenpyram is used as a fast-acting, orally administered insecticide, which kills fleas on the animal as soon as 15 minutes after administration and has an efficacy of up to 100% kill within 24 hours. It acts by inhibiting specific nicotinic acetylcholine receptors. It is a useful product to achieve quick kill in cases such as this one, but is not designed to be used on its own. It can, however, be combined with lufenuron to provide integrated flea control.
5 Flea allergic dermatitis 33 Imidacloprid: Imidacloprid belongs to the group of chloronicotinyl compounds. Its mode of action is to bind to the nicotinergic acetylcholine receptors on the postsynaptic region of the insect nervous system, thereby stopping the acetylcholine from binding to the receptors. This results in the paralysis and death of the insect. Imidacloprid is effective against adult fleas as well as larval flea stages. It is available as a spot-on formulation and the label permits weekly use of this product. Selamectin: Selamectin is a semi-synthetic avermectin with a broad spectrum of activity against endoparasites as well as ectoparasites. It is an adulticide with larvicidal and ovicidal properties. The product is absorbed percutaneously and then redistributed back to the cutaneous tissue via the circulation. Metaflumizone: Metaflumizone belongs to the semicarbozone group of compounds and is available as a spot-on treatment against fleas. It is a sodium channel blocker which prevents the flow of sodium ions across the nerve cell membrane. This disrupts the transmission of nerve impulses and the eventual result is death by paralysis. For use in dogs, it is combined with amitraz to provide action against fleas and ticks. On its own, it is available for use in cats. Pyriprole: Pyriprole belongs to the phenylpyrazole group of compounds. It is a spot-on formulation that has both insecticidal and acaricidal activity and its mode of action is similar to that of fipronil (see above). It is licensed for use against fleas and ticks in dogs only. Pyrethrins: Pyrethrins are naturally occurring flea repellents and pyrethroids synthetic ones. A combination of permethrin, a pyrethroid and imidacloprid has a veterinary licence for use in dogs (contraindicated in cats). Environmental control Insect growth regulators: Insect growth regulators such as fenoxycarb, methoprene and pyriproxyfen are analogues of the juvenile hormone, which allows pupation when its concentration falls. Excessive concentrations prevent metamorphosis and thereby break the life cycle. These products are available as environmental aerosol sprays combined with an adulticide for effective control and in the case of methoprene as a spot-on treatment for the animal combined with fipronil. Insect growth inhibitors such as lufenuron inhibit the synthesis of chitin, thus preventing successive larval moults. Summary of environmental treatment: Aerosol sprays, pump sprays and foggers are available, which generally contain permethrin plus an insect growth inhibitor or regulator. Treat all the areas where the pet might visit (the whole house, cars, baskets, under beds, etc.). Clear out organic debris from the outside environment, as this can be a source for re-infestation even in the winter months. In cases where there is a severe infestation two treatments 2 weeks apart are necessary to eliminate newly hatched fleas. Delivery methods for topical treatment of pets: Spot-on formulations Spray formulations Shampoos Dips Flea collars Systemic products. Treatment in this case In this case the long-term treatment also included allergen-specific immunotherapy for the management of the atopic dermatitis. NURSING ASPECTS Many clients will discuss their concerns with the nurse, or lay staff, rather than the vet. They should be able, tactfully, to reassure them and give them the correct advice. A good grasp of the flea life cycle, together with knowledge of the range of flea products on the veterinary market and their modes of action, is the key to giving correct advice to the client. Flea control within an individual household should be tailored to its needs. Many owners who are registered with the practice will call in to buy products during the summer months when the problem is most apparent. It is at this point, when they recognize the problem, that the client is most receptive to advice on supplementing topical therapy with environmental treatment.
34 SMALL ANIMAL DERMATOLOGY CLINICAL TIPS Never believe an owner when they say they use routine flea control, unless your records show that enough products have been bought from the practice to regularly treat all the cats, dogs, rabbits and ferrets in the house. Sometimes, because of the expense, clients will only treat obviously infested animals within the house, but not all of them. Never dictate to the client which product they should use. For best compliance, involve the client in the decision making, so that the owner accepts the time and the cost involved. When considering a diagnosis of FAD, failure to find evidence of fleas does not rule out flea allergic dermatitis. Suspect FAD as a flare factor in atopic dogs in whom the pruritus was previously well controlled. During history taking, always find out about incontact animals, including visiting animals, dog walkers, visits to grooming parlours, boarding kennels/catteries, etc. Veterinary surgeries can also be the source of infestation, for instance in cats that are normally kept indoors but occasionally visit the practice. The concentration of the product on the skin is reduced by swimming, shampooing and frequent wetting of the hair. The environment was treated twice 2 weeks apart with a spray containing permethrin and methoprene. The cats and the dog were treated with a spot-on solution containing fipronil and methoprene every 2 weeks for four occasions (extra-label use), then every 3 4 weeks. At the start of the treatment, all the animals (three in-contact cats and the dog) were given 3 days of nitenpyram orally to ensure quick kill and reduction in the flea population as soon as possible. Antibiotic treatment: In this case cefalexin (15 mg/kg b.i.d.) was prescribed for 3 weeks, without any antipruritic treatment. At the end of the course, clinical examination and tape-strip preparations did not reveal any bacteria and antipruritic treatment was started (see below). Antipruritic treatment: Given the severe pruritus and its effects on the animal s welfare, 1 mg/kg every 24 hours of prednisolone was prescribed for 7 days, after which it was reduced to alternate-day treatment. After 4 weeks it was reduced to 0.5 mg/kg on alternate days and stopped once the dog reached the maintenance phase of the allergen-specific immunotherapy. FOLLOW-UP Long-term flea control was maintained on all the animals in the household. The pedal pruritus persisted even after 1 year on allergen-specific immunotherapy and so 0.1 mg/kg of prednisolone was administered as a concurrent treatment. The dog has been successfully managed on this combination at the time of writing. It is possible that this dog has a concurrent adverse food reaction as well, but the owner was unwilling to repeat a diet trial.