---start---- derm 11/6/98 morris: fleas we were talking about Advantage (imidocloprid) this is a new adulticide but we have resistance developing already even though it's only been three years. A Bayer product. they now claim it is also a control for flea allergic dogs, on the label. However, there are no reliable therapies for flea allergy from an adulticide standpoint except 2% permethrin. Imidocloprid is the first adulticide that works by disrupting neurotransmission via nicotinyl ACH receptors. it's the original, safe, 30 day spot-on for dogs and cats, though probably works better used a little smaller interval than that. However, in a heavy flea environment, it won't control fleas for allergic animals. Fleas definitely still get a blood meal before they die with this and with Frontline. They do die within a few hours, but they do take that first bite, so FAD still occurs. doesn't kill ticks. Degreasing shampoos will remove this product - it is lipophilic. FrontLine (fipronil) - Rhone-Merieux's answer to Advantage. first, was just a spray - works well to keep fleas off pets. q 30 day spot on not against FAD interrupts NT via GABA chloride channel blockade also kills ticks "TopSpot" is the spot on product, FrontLine is the spray the mechanism this uses to get across the body is not as good as the Advantage mechanism - this product in TopSpot formulation should be used q 2 weeks. degreasing shampoos remove this. fleas do take a blood meal before dying. Insect Growth Regulators: IGRs - synthetic compounds mimicking flea growth hormone. keep levels elevated instead of dropping and allowing pupation or whatever. Methoprene (a trademarked product by the folks who make VetKem) and pyriproxifen (Nylar - owned by a company that licenses stuff out so many products contain Nylar while only VetKem contains methoprene) Insect Development inhibitors: interfere with chitin synthesis - Program (lufenuron) - interferes with exoskeleton, egg tooth. Lufenuron is available as Sentinel, which combines Interceptor with Program - hooks, whips, rounds, and fleas in one go. So this is a once a month per os therapy. but with lufenuron, cats do not like the taste. this is a good way to control flea infestations but does not kill adult fleas. if a dog is walked near squirrels, stray cats, other dogs - adults can get onto the dog and live there for 2 mos. then people complain lufenuron isn't working but it is. Alternative methods - -flea combing for puppies and kittens < 6 weeks of age - works fairly well if you do it a few times a day and treat environment with premise spray -Avon skin-so-soft: some people are convinced this works, fine. good for them. if pet is still showing signs of FAD then you have to use something else. -Citrus-based dips/sprays/shampoos - he hates these. they smell good, people think that is works b/c of PetSmart marketing. they have quick knockdown but short acting activity - reinfestation w/in hours. D-limonene is citrus based too, but has serious toxic potential esp in cats, can cause fulminant hepatotoxicity. you shouldn't use that. ineffective: yeast, garlic, electronic collars, these are all crap, people will testimonialize about them but it's not something that works at all. client education is key. Environmental control: indoor: -vacuum, launder pet bedding -apply premise spray (like Knockout): adulticide plus IGR - also Siphotrol by VetKem also good. concentrate on the hotspots in the house, where pets really hang out, b/c that is where eggs are usually. do not forget to go under furniture, near baseboards, etc. professional exterminators are fine, they use microencapsulated products which is good, but consumer must beware and make sure that they are using products specific for fleas, not just for roaches. -sodium polyborate powder - safest indoor tx for those afraid of chemicals. "Rx for Fleas," "Flea Busters" - nonchemical alternative. (I used FleaBusters once). kills by dessication of eggs/larva and intestinal blockage. doesn't kill pupas or adults. so any pupa will still grow up. helpful to also use premise spray, but will work after a month or so as adults die off. there is also do it yourself powder out there - FleaMarshall. Be careful with imitator products b/c some are not sodium polyborate - some are boric acid, which can be toxic to kids and pets. Outdoor control: in some areas, not workable (Houston) but here, it is. remove organic debris that might serve as a nidus -use yard sprays or granules (OPs like diazenone, dursban) - concentrate on hotspots of lawn where animal hangs out, no need to treat unshaded areas because flea eggs don't survive there that long anyway. -"Beneficial Nematodes" - living creatures - freeze dried - like those Sea Monkeys. they come in a jar, you spread them on the lawn with a hose and lawn fertilizer applicator. they rehydrate, spring to life. are positively geotrophic. they burrow into soil and parasitize flea larvae and pupa. they are susceptible to desiccation, so it is hard for them to work during dry, hot periods - unless you water the lawn daily. in gulf areas, with high humidity, works great. these things do work quite well. Maintenance tailor program to each client's needs -outdoor roaming animals need continued adulticides -indoor pets may be ok with Program -flea allergic animals need special consideration -consider cumulative toxicity for cats and kids - there is no toxicity concern in people with FrontLine; people have had allergic responses to Advantage (his friend did) -wildlife as a reservoir for fleas - squirrels, possums, raccoons, other woodland creatures. Allergic dermatoses and immunomodulation: mostly type I reactions - immediate hypersensitivity -mediated by IgE -IgE is a host mechanism to defend against parasites -allergy is a dysregulation of IgE genetically existing in a population of animals and people -in these people, a subclass of IgE binds to mast cells and basophils - not so in normal people. -if genetically predisposed, your IgE binds to mast cells and basophils -when two IgE molecules bind to the cell, they crosslink, signal degranulation -inflammatory mediators are released into surrounding tissue - skin, resp tract, GI tract -response is immediate - within minutes - abates within an hour -disease examples: urticaria, angioedema, anaphylaxis, atopy, food allergy, flea bite allergy, allergic respiratory disease (rhinoconjunctivities, bronchitis, asthma), some drug reactions -classic response is the skin wheal Late phase reactions - part of type I pathology, occur within 2-4 hrs of exposure, persist up to 24 hrs -mast cells release further chemical mediators, newly synthesized ones, and this calles in eosinophils which infiltrate the tissue and contribute to bystander tissue injury by releasing toxic inflammatory mediators MBP, ECP -disease examples: FAD, atopy so the eos are called in by the mast cell products, and lymphocytes, and they do bad stuff. Type II hypersensitivity: binding of Ab or complement to tissue antigen leads to cell death. antibody dependent cytotoxicity - several types one is binding of Ab to Ag that allows a WBC to then recognize the Ag and kill it. there is also opsonized phagocytosis, where Ab binds all over an organism and oposonizes it, then mphages eat it. also complement mediated cytolysis - formation of MAC which punches hole in cell membranes, as in IMHA, ITP, cutaneous lupus (ADCC), bulluous pehmphigoid type III: arthus reaction: lupus nephritis, arthritis, cutaneous LCCV, serum sickness, equine purpura hemorrhagica, some drug reactions, tick bite hypersensitivity, staph hypersensitivity these reactions occur when Ag in blood is recognized by Ab - but there is excess Ag so can't be all bound by Ab, so free Ag makes membranes more sticky, causing Ag/Ab complexes to lodge in vessel walls. then they get trapped in BM, stimulating complement system, calling in WBCs (mainly neutrophils, also eosinophils) which come in to attack the Ag/Ab complex and also do a lot of tissue damage via elastase, collagenase, etc - causing vessel wall necrosis, thrombosis, etc. Type IV delayed hypersensitivity: sensitization phase elicitation phase main one is contact allergy - less common in dog/cat than people b/c of fur and b/c they do not wear zinc posted earrings or work with chemicals or whatever. some insect reactions (fleas) reactions to mycobacteria (TB, leprosy) sensitization phase: haptens (particles too small to be recognized by immune system) gain access through skin, bind to APC of the skin (langerhans cell), then once bound they form a complete allergen, are taken to the LN where T cells are stimulated to clonally expand. nothing happens, though. elicitation: hapten comes in again and now those T cells are already there. they jump right on it and create the response. usually a 24-72 hr time frame. Type V hypersensitivity: this is new!! these are physiologic reactions Ab binds to a cell and physiologically stimulates it eg: immune mediated hyperthyroidism (Graves' dz) when Ab binds thyroid receptor, stimulating overproduction of hormone pemphigus foliaceous and P. vulgaris are also type V reactions. Cutaneous Basophil Hypersensitivity: tick bite rxn, FAD: characterized by tons of basophils infiltrating skin 12-24 hrs post antigen exposure. mediated by lymphocytes rather than IgE. mixed features of type I and IV rxns. Insect hypersensitivities: FAD is the most common dermatosis of dogs and cats in all areas of the country where fleas exist. atopic animals (those making IgE against nonsense things) are at increased risk of FAD. one interesting thing about FAD is we may be promoting it by being so psychotic about there getting fleas at young ages. people use great products against fleas but we don't prevent flea bites. the intermittent exposure to bites as opposed to chronic low grade exposure is what favors FAD, the chronic low grade exposure favors tolerance!!! FAD is seasonal in most climates except the Gulf coast and tropical areas. pathophysiology: FAD shows features of Type I, IV, and late phase, and cutaneous basophil hypersenitivities. mammals can be allergic to many flea salivary antigens, which are deposited into the wounded skin as the flea feeds. these proteins are anticoagulants.flea spits into the wound to keep blood flowing while it eats. hx and signs: dogs: no age, sex, or breed predilection but atopics are predisposed. classic pattern: flea triangle - wedge over caudal rump and thighs, often groin and inguinum. if dog has flea triangle, fleas are on board. you may not find a flea, though. pruritis, papular rash over caudal 1/3 of body. most signs are self induced - excoriation, lichenification, folliculitis, crusts, hyperpigmentation, nodules (white fibrotic nodules). the only direct flea lesion is the papule. if there is severe pruritus of feet/face/ears, look for concurrent hypersensitivities!! there is probably more than FAD. finding fleas and flea dirt are not required to dx flea allergy. this is really important. clients do not believe it but it is true. slide: flea triangle - dermatitis over caudal dorsal 1/3 with or w/o ventral involvement think FAD cats: no age, breed, sex predilection a bit more heterogenous presentation miliary dermatitis: caudal 1/3, dorsal neck - clients ask why those areas, and we do not know, but that is where fleas like to hang out. symmetrical alopecia: self induced eosinophilic granuloma complex: eosinophilic collagenolytic granulomas (skin, lips, oral cavity); eosinophilic plaques; indolent ulcers of lips slide: linear granuloma in cat, secondary to FAD - pink raised cordlike skin lesion on medial thigh. FAD isn't only cause of these in cats - demodex, atopy, also do. slide: excoriation of lateral neck. slide: indolent ulcer of lip - this whole upper lip is gone. they do return to normal when you get rid of the problem. since cats groom and pick fleas off their bodies..study took five flea allergic cats and five normal ones, and put fleas on them. the flea allergic ones ate all their fleas within 20 minutes, the nonallergic ones left them alone and still had 95% of them 8 hrs later. but these cats that eat the fleas, they get oral lesions. dx of FAD: history, PE, flea combing can be supportive physical distribution pattern of lesions no fleas is NOT a negative diagnosis intradermal allergy testing is useful to confirm or convince client -immediate wheal and flare; delayed papular or miliary rash - either or both is positive response. histopathology - nonspecific - "allergic dermatitis" - do not bx this treatment of FAD: -aggressive flea control: zero tolerance - address the environment and companion pets. any flea bite will cause a problem -hyposensitization: doesn't work well for insect allergies in dogs and cats. classic protocols are nontherapeutic. but at ohio state, they are using Rush immunotherapy with a purified flea salivary antigen, and are having some success. this isn't clinically available at this time. -tx secondary infections which are common esp staph -steroid therapy to break cycle of pathologic itch, when needed. this is such a pruritic reaction - like poison ivy. sometimes you really need to give a short course of steroids. 2% permethrin - trade name Preventic LA - has Nylar in it. Now is called KnockOut. this is the only flea repellent available in this country. but it is labelled for q 30 day use, and it needs to be used weekly to really work. it's about 18 bucks a bottle and you could use a bottle every 2 weeks on a husky. but it's all we have. 2% permethrin toxic to cats. can't use it. but Advantage works well for flea allergic cats - pretty well. but not for dogs. ---break---- Mosquito bite hypersensitivity in cats - a fairly newly described disease -affects outdoor cats - exposure mainly in the evening hours -may affect nasal planum, ear tips, footpads, periareolar skin [some australian vets described this; they videoed the cats being bitten and then showing signs within 6 hrs] -papules/plaques form, that ulcerate and crust; alopecia, muzzle edema -leukoderma (loss of pigment of skin) and scarring alopecia in chronic cases not all cats have all areas affected - some have only nose, some only ears, some only footpads. the common lesion is the papules/plaques. [slide] pissed off looking white cat with scabs on nose and cheeks. [slide] foot pad lesions - scabs, crusts on feet; ear tip lesions - scabs and hair loss. looks sort of like ringworm or pemphigus foliaceous. most typically dx by biopsy. Dx of mosquito hypersensitivity: one diagnostic option: restrict to indoors and see if it resolves mainly dx on signalment and signs ddx: pemphigus, atopy, food allergy, demodicosis, dermatophytosis, neoplasia if nonpruritic, that r/o food allergy and atopy which are very itchy scrapings, fungal cultures r/o dermatophyte, demodex histopath strongly suggestive, r/o autoimmune dz intradermal testing with whole mosquito extract not always positive but if it is, is diagnostic tx: steroids to break inflammatory cycle in cats with severe lesions - topicals often not well tolerated: oral pred, parenteral methylpred -restrict to inside esp at dusk/night use a repellent (permethrin, skin-so-soft?) - permethrin at 0.1% might have enough repellent activity for mosquitoes. Avon skin-so-soft mixed with water and massaged on also does seem to work. cats do not like it that much b/c of the smell but it seems to work for some cats better than a spray. insect and arachnid hypersensitivity: -air borne rxn: due to feces, exoskeletons, or other body parts - pathophysiology similar to atopy, similar presentation -reactions to bites/stings: bees, wasps, biting flies, spiders, etc. urticaria, angioedema, type I anaphylactoid rxn. rxns are to salivary Ag or envenomations. urticaria/angioedema more likely with envenomation. severe rxn can result in systemic anaphylaxis and require emergency therapy. we don't give clients epi-pens, we give steroid packs and teach how to give IM steroids. hyposensitization isn't used in dogs and cats so much b/c humans are forced to sit in the office for an hour, but with dogs, people do not want to do that. canine eosinophilic furunculosis (follicular rupture) of the face: assumed to be localized rxn to bee or wasp stings, or spider bites. pathophysiology is kind of unknown. histologically not like type I rxn. tons of eosinphils all over. hx/signs: young dolichocephalic dogs, med or large breeds acute onset affecting muzzle, nasal planum (most often - b/c dog sticks nose into insect nest or something) rapid progression from swelling/papule to ulceration, hemorrhage, crusting and very very painful cytology is good way to dx CEF - direct impression smear or FNA - tons of eosinophils biopsy: eosinophilic folliculitis/furunculitis with mucinosis (GAGs) and ulceration tx: steroids - antiinflammatory dosage x 5-7 days; antibiotics are ineffective topical astringent (aluminum hydroxide aka Donburows solution (?sp?) is useful. dirofilariasis: very uncommon cause of skin dz skin lesions associated with mmf: nodules, crusting lesions, nonpruritic crusting lesions, generalized seborrhea, interdigital granulomas. most are assumed to be related to hypersensitivity rxn. not that important - just dx HW dz usually with occult HW test and treat it! dx ELISA, knott's, skin bx with mmf in tissue and eosinophils. ddx: r/o allergy, other parasitism skin lesions resolve when you control the HW disease. this isn't that important, you won't really see it but maybe in subtropical areas. intestinal parasite hypersensitivity: with interceptor and other products being used to control these parasites, we tend to forget about these parasites but they can in fact provoke hypersensitivity reactions. assumed to be type I hypersensitivity like food allergy lesions: papules, crusts, pruritus, recurrent urticaria, seborrheic dermatitis, non-itchy lesions also reported dx/tx: demonstration of a parasite along with response to tx ddx: scabies, atopy, food allergy, contact allergy, dirofilariasis skin bx: nonspecific - allergic dermatitis the only helpful thing is if there are tons of eosinophils, it does suggest parasitism. tick bite hypersensitivity: problem around here several mechanisms suspected. most of the work done is in sheep in australia and we know some cool stuff about that. they are using vaccines against ticks in sheep there. but the tick bites tend to cause an ulcer, that then necroses. focal area of ulcer/necrosis - probably type III response with thrombosis. also can cause nodular lesions which sometimes mimic a skin cancer. those dogs are usually biopsied. may find tick mouthparts on biopsy. some dogs have pruritic pododermatitis or otitis externa - with that usually there is a strong history of ticks on those areas of the dog. dx/tx: history of tick exposure sometimes. biopsy: leukocytoclastic vasculitis (type III rxn) with necrosis/ulceration; nodular to diffuse pyogranulomatous inflammation (type IV), eosinophilic dermatitis tx: tick removal, +/- steroids; surgical excision of indolent lesions urticaria and angioedema: nonspecific type I reactions. horses are the champions of urtication. people and horses are big urticators. cats sometimes do it. very rare in dogs. plasma leakage into interstitium through leaky vessels - welts or diffuse swellings occur - results from release of vasoactive mediators from mast cells. slides; horse hypersensitive to culicoides gnat. urticaria: wheal and flare - ddx folliculitis, vasculitis, mast cell tumor, erythema multiforme. biggest ddx is folliculitis. diascopy blanches flare, but not purpura, so if it blanches out, it is truly just inflammation. angioedema: diffuse regional swelling - dogs get it in face, horse at coronary band ddx: lymphatic dz, CHF etiology of urticaria - in humans, tons of stuff immunologic: atopy, food allergy, insects, drugs nonimmune mediated (human): pressure, vibration, cholinergic heat reflex (also horse) adrenergic (emotional stress), cold, exercise (very common in people - don't eat apples and celery prior to exercise), light, dermographism (also horse. this is where you can draw on the skin with a finger. it runs in families - it itches and hurts afterwards...) dx/tx: eliminate cause if you can; pretreat with antihistimines if you can; immunotherapy if possible; life threatening angioedema may require high dose IV soluble glucocorticoids or epinephrine. steroids better in pets than epi. Atopic dermatitis: type I rxn, we think related to a heritable predisposition to make IgE against nonsense antigens like trees, weeds, etc. although often referred to as "inhalant allergies" as per human hay fever, AD is the result of percutaneously absorbed allergens (pollens, molds, insect parts). one big allergen for people by the way is tire rubber - causing obstructive asthma, we THINK but are not sure. anyway, there are three syndromes: atopic respiratory disease (ARD) which can be "hay fever" or life threatening asthma, atopic dermatitis, and increased susceptibility to bacteria/yeast infections. immunology of atopic dermatitis is complex: percutaneous absorption of allergen trapping by langerhans cells in epidermis via membrane bound antigen specific IgE. allergen processing occurs, T cells specific for that are made, etc. with atopic dermatitis, the langerhans cells express an IgE receptor, the T cells come in and provide help to langerhans cells and mast cells, this is very similar to contact allergy with addition of the IgE langerhans thing. another thing seeming to be genetically regulated is type of T cell which responsds. folks with one gene have type 2 response and lots of pathology, folks who are non atopic have type 1 response and no signs. pruritus and inflammation are the results. itchy itchy. dogs with atopy: about 10% of canine population. atopy is the fastest growing disease in the world in humans, due to urbanization? dogs seem to be following suit. breed predispositions - many female dogs may be at increased risk. age of onset: majority b/w 1-3 yrs, range 6 mos to 7 years. it costs a lot to work up atopy, so it would be great if we could know for sure based on signalment but we do not really. in dogs >5 yrs, probably think of something else first. many cases are initially seasonal, depending on the climate. in miami, they will not be seasonal. even here, after a few years, seasonality goes away. if they sensitize to house dust, they are always nonseasonal, of course. and that isn't uncommon. signs: no primary lesion per se - if you catch it before they scratch themselves lesional, they are just itchy, maybe a bit of erythema. visible lesions are all due to self-trauma. not like insect lesions. sebaceous gland hypertrophy occurs, increases secretion, these dogs get seborrhea oleosa and look greasy. oils are hydrolyzed by surface bacteria so they smell bad. smelly dog who itches. secondary infections in skin, ear are hallmark, but immunodeficiency is limited to skin - this is due to the type 2 response which isn't anti-infection. rhinitis/sinusitis, bronchitis, asthma are very rare. this is good b/c we can try to desensitize them at home then b/c any reaction to shots will just be more itching, not respiratory distress. distribution of lesions can be classic - periocular, perioral, armpits, interdigital, groin; or non classic. the classic areas are where hair is sparse, or skin stays moist, favoring allergen presentation. dogs may chew hair off carpal/tarsal areas slide: totally lichenified shar-pei. looks like it could be scabies. note ventrally dependent pattern. probably also this dog has flea allergy. actually this dog is atopic and food allergic. otitis externa is a huge huge part of atopy and a big reason why dogs are referred here. this cocker spaniel had lateral canal resection, but still had awful problems; ear cartilage all turned mineralized to bone. this causes a big inflammatory response. slide: classic pseudomonas otitis. the only option is to really physically surgically remove that tube of mineralized cartilage, close the dead space and skin. results in a totally deaf dog. these dogs do not hear that well before surgery, though. cockers are different from other breeds with respect to how they respond to otitis and rapidly mineralize ear canals. secondary infections are a big problem: these dogs get repeated staph/yeast infections, sometimes both together. staph pyoderma has many faces: papules, pustules, epidermal collarettes, folliculitis, motheaten alopecia, crusts, scales, post-inflammatory hyperpigmentation. malassezia dermatitis doesn't cause circular peeling lesions, usually more erythema, hyperpigmentation, cheesy yellow surface exudate. this can also be a presentation of superficial staph, so you have to do an impression smear and look for yeast. skin immunodeficiency is just that - totally limited to skin. dogs have no increased risk for systemic infections. slide: dog with generalized staph - lots of hair loss, erythema. looks bad. dx of atopic dermatitis: history, signalment, signs if seasonal has to be atopy or insects - rule out FAD note: some atopic dogs with FAD also will be well controlled for atopy and FAD if you just get rid of the fleas, due to the response threshold thing. non seasonal cases: rule out food allergy, scabies, other parasitism non seasonal atopy often has seasonal exacerbation in intensity clear infections with antimicrobial therapy prior to using antipruritics in new cases. allergy testing: used to identify specific allergens for avoidance or immunotherapy strengthens the clinician's faith in the clinical diagnosis of atopic dermatitis concurrent food allergy should still be ruled out in nonseasonal cases with dietary trialing since allergy testing isn't always a reliable method of diagnosis. some clients will not do dietary trials, though. skin testing dogs, unless you for some reason really really can not, is probably the best method of allergy testing. the blood tests are less reliable. intradermal allergy testing: uses airborne allergens, insect allergens, molds, pollens. inject 0.05 to 0.1 cc ID in each site gold standard of allergy testing administer test under sedation to prevent them from rushing around and getting stress response. wheal and flare graded on a scale of 0 to 4 compared to saline and histamine controls - the histamine response is a 4 automatically. we also allergy test horses. it is harder to grade their tests though. kind of like radiology - you make a mountain out of a molehill. serologic allergy tests: all measure serum concentration of allergen specific IgE (RAST, ELISA, VARL) but most of these animals have had intestinal parasites so they have high baseline levels of IgE. so you can see a lot of cross reactivity with nonspecific IgE and with IgG. make you get false positives - dog allergic to 4 things may show up positive for 20 things. there is a newer serology test that does require drug withdrawal - most older ones do not. there are false negatives in the off season since serum IgE levels drop off quickly than mast cell bound IgE ----end----