Hypersensitivity Disorders I - Urticaria, Angioedema and FAD (1).pdf

Hypersensitivity Disorders I Urticaria and Angioedema VCS 80610 – Small Animal Medicine I PAULO GOMES, DVM, DACVD COLLEGE OF VETERINARY MEDICINE CLINICAL ASSISTANT PROFESSOR OF VETERINARY DERMATOLOGY DEPARTMENT OF VETERINARY CLINICAL SCIENCES Urticaria and Angioedema Ø Cutaneous hypersensitivi...

Hypersensitivity Disorders I Urticaria and Angioedema VCS 80610 – Small Animal Medicine I PAULO GOMES, DVM, DACVD COLLEGE OF VETERINARY MEDICINE CLINICAL ASSISTANT PROFESSOR OF VETERINARY DERMATOLOGY DEPARTMENT OF VETERINARY CLINICAL SCIENCES Urticaria and Angioedema Ø Cutaneous hypersensitivity reaction ü Immunologic and nonimmunologic mechanisms ü Triggering factors: drugs, vaccines, bacterins, food, food additives, and sitting or biting insects Ø Common in dogs and uncommon in cats Ø Atopic dogs may be at increased risk Urticaria and Angioedema Ø Pathogenesis ü Primarily Type I hypersensitivity • IgE against prviously encountered allergen ü Type III hypersensitivity • Formation of antigen-antibody complex (immune complexes) Ø Clinical manifestation ü Localized mast cell or basophilic degranulation leading to vascular dilation and recruitment of inflammatory cells Urticaria and Angioedema Ø Pathogenesis ü Repeated allergenic exposures is necessary for development of hypersensitivity reactions ü Once sensitization has occured, clinical signs develop within minutes or hours depending of the underlying mechanisms and the sensitivity of the patient ü Non immunologic factors that can lead to mast cell degranulation • Pressure, sunlight, heat, cold, exercise, stress, and chemicals Urticaria and Angioedema Ø Clinical Features ü Urticaria: acute onset of variably pruritic wheals • Urticarial lesions may resolve and appear elsewhere ü Angioedema: large, edematous swellings Usually localized to the head May generalize Affected skin is often erythematous Hair loss is not a feature Dyspnea from pharyngeal, nasal, or laryngeal angioedema may occur • Rarely: anaphylactic schock with hypotension, colapse, GI signs, or death • • • • • Urticaria: multifocal, raised erythematous wheals. Lesions may coalesce and form large edematous plaque. Angioedema: Edematous swelling of the face and erythematous skin. Urticaria and Angioedema Ø Top differential diagnoses ü Urticaria • Folliculitis (bacteria, dermtophyte, Demodex), vasculitis, erythema multiforme, cutaneous lymphoma, amyloidosis, and mast cell tumor ü Angioedema • Juvenile cellulitis, bacterial or fungal cellulitis, neoplasia, and snake bite Urticaria and Angioedema Ø Diagnosis ü Thorough history to identify the triggering factors ü Information regarding all allergenic stimulators that occured in the few weeks prior to the development of the clinical signs ü Timing between certain drug administration and development of problems ü Can be seasonal ü Response to previous treatment if attenpted ü The lack or reported problems with a certain drug or vaccine administration in the past does not rule out the possibility that they may be triggering factors Urticaria and Angioedema Ø Diagnosis ü Diascopy: a glass slide is pressed onto the erythematous lesion • Urticaria: the lesion blanches (turns white), indicating vasodilation • If the lesions remains red, the lesion is then a result of petechiae or echymosis indicating vasculitis or tick-borne disease • Pyoderma does not blanch on diacopy ü Dermatohistopathology • Skin biopsy only if necessary • Vascular dilation and edema in the superficial and mid dermis • Perivascular to intersticial dermatitis with mononuclear cless, neutrophils, mast cells and rarely eosinophils Diascopy: Blanching indicates urticaria (vasodilation). Hnilica, K. A., Patterson A. P. Small Animal Dermatology: A Color Atlas and Therapeutic Guide. Fourth edition, 2017. p239. Urticaria and Angioedema Ø Treatment ü Identification and elimination of triggering factors ü Urticaria and mild angioedema • Prednisone or prednisolone 2mg/kg [PO, IM, orIV] • Dexamethasone sodium phosphate 0.5-0.8 mg/kg IM • Diphenhydramine 2-4 mg/kg PO or IM, TID for a minumum of 3 days ü Angioedema • • • • If severe enough to interfere with breathing Dexamethasone sodium phosphate (1-2mg/kg IV) Prednisolone sodium succinate (100-500 mg/dog IV) Epinephrine (1:100 at 0.1-0.5 ml IV once for severe reactions, or 0.2-0.5 ml SC for mild to moderate reactions) Urticaria and Angioedema Ø Prognosis ü Good for animals that do not develop anaphylatic shock Ø Further recommendations ü For patients with concurent underlying allergic dermatitis it is recommended long term therapy for the allergic disease and hypoallergenic diet Hypersensitivity Disorders I Flea Bite Hypersensitivity (Flea Allergy Dermatitis) PAULO GOMES, DVM, DACVD COLLEGE OF VETERINARY MEDICINE CLINICAL ASSISTANT PROFESSOR OF VETERINARY DERMATOLOGY DEPARTMENT OF VETERINARY CLINICAL SCIENCES Flea Allergy Dermatitis Ø One of the most common pruritic skin disease of dogs ü Hypersensitivity reaction to numerous allergens present in the flea saliva Cause Ø Fleas are small, wingless, bloodsucking insects ü ü ü ü ü Over 2200 species and subspecies Mammals: 95% Birds: 5% Worldwide distribution In dogs and cats: Ctenocephalides felis • aka: cat flea, or sand flea ü Note: C. felis, C. canis, and Echidnophaga gallinacea • May also parasitize humans under the right conditions • In the absence of dogs and cats Fleas: where do they come from? Ø Infested animals Ø Infested environment ü Environment infestation is more intense where affected animals spend most of their time Ø Outdoor ü Shaded protected areas ü Eggs-larvae-pupae-adult fleas ü Feral dogs, cats and urban wildlife ü Emerging fleas jump on pets ü Emerging fleas may jump on humans Fleas in the outdoor environment Fleas in the outdoor environment Ø Shaded protected microhabitats ü Under decks, porches, and crawling spaces ü Places where feral animals have access Fleas in the indoor environment Ø Pet bedding, carpets, area rugs, cracks and crevices on hardwood floor ü Environmental source points Fleas in the indoor environment Life Cycle Ø Stages ü Eggs – 3 larval stages – pupa – adult ü Length of life cycle depends on environmental conditions ü Optimum conditions • 65 to 80F, with high humidity Ø Adult fleas ü Represents 1%-5% of the total infestation Ø Biggest problem ü Massive environmental contamination Flea Population Pyramid Flea Life Cycle https://www.youtube.com/watch?v=fxL9MGvMS6Q Life Cycle Ø Adult fleas ü Spend most of their time on the pet ü Actively feeding flea • • • • C. felis start feeding almost immediately once they acquire a host Do not survive longer than 3 to 4 days off the host Egg production begin as early as 24h During peak reproduction may produce up to 50 eggs per day Life Cycle Ø Newly emerged fleas seeking hosts ü Must find a host within 1 to 2 weeks or they die ü Stimulus for the jump response • Response to decreased light intensity • Jump on passing hosts in response to a shadow • Positive phototaxis and negative geotaxis Host-Ectoparasite Relationship Ø Grooming habits have a significant negative correlation in flea longevity ü Cats ingest/groom off a large number of fleas in short periods of time Ø Inter-host movement of adult fleas ü Before start reproduction fleas are not permanent ectoparasites • up to 20% transfer of fleas from the infested to the previously non-infested cats within 15 minutes (Franc et al, 2013) Ø C. felis are permanent ectoparasites as reproducing adults Fleabite Allergy Dermatitis Ø Flea feeding habits ü Start feeding very rapidly after finding a host ü Consume significantly large amounts of blood relative to their body weight ü Flea feces are excreted within 2 to 5 minutes ü Within 24h of blood feeding they start laying eggs Ø Even with topical insecticides it is not possible to completely prevent flea from feeding Ø Fact: Several topical and oral insecticides have a positive clinical effect in treating patients with flea allergy dermatitis (FAD) Fleabite Flea Allergy Dermatitis Ø Development of FAD ü Related to the pruritic threshold - degree of hypersensitivity of the individual animal ü Number of fleas and amount of antigen injected ü Prolonged feeding Pathogenesis Ø Host Hypersensitivity Response to Fleas ü Involves several different types of immunity • Classical type I (immediate, IgE-mediated ) • Type IV (delayed type, cell-mediated) • Late onset IgE-mediated response • Cutaneous basophil hypersensitivity Pathogenesis Ø When fleas bite ü Mouthparts release saliva ü Saliva contains anticoagulants and pruritogenic enzymes ü Immediate itch associated with the bite Ø Some of the salivary components are antigenic ü Evoking hypersensitivity response in the host ü Responsible for the majority of clinical signs Pathogenesis Ø Factors which favor the development and severity of clinical signs of flea allergy dermatitis ü Intermittent exposure to fleas ü First exposure to fleas later in life ü Dogs with atopic dermatitis Ø Hypersensitivity state is maintained for years Ø Dogs and cats do not achieve natural desensitization Clinical Signs Ø Dogs ü Any age affected - most commonly starts at 3-5 years ü Very pruritic ü Typical distribution • • • • • Dorsal lumbar-sacral area Base of the tail Medial and caudal hind limbs Abdominal and inguinal areas May generalize Clinical Signs Ø Dogs ü Lesions • Primary papular eruption, self-trauma, crusting, excoriation, scaling alopecia, lichenification, hyperpigmentation, pyotraumatic dermatitis (‘hot-spots’), secondary pyoderma; secondary seborrhea, and worn incisors Clinical Signs Ø Cats ü Very pruritic ü Distribution similar to dogs ü Lesions • Crusted papules – “miliary dermatitis” • FAD is the most common cause of the clinical syndrome of “feline miliary dermatitis” • Self inflicted hair loss Diagnosis Ø Nearly pathognomonic ü History, clinical signs, distribution of lesions, and pruritus ü Fleas and/or flea feces Ø Use flea comb to examine animals for flea and flea feces ü Feces: small, dry, black, “comma-shaped” specks ü Feces release a reddish-brown color when placed on moistened white paper Ø Fleas or flea feces are not always evident on the animal ü THEIR ABSENCE DOES NOT RULE OUT FLEA ALLERGY Diagnosis Ø Intradermal testing ü Not necessary for clinical diagnosis ü Demonstrate hypersensitivity to flea saliva ü Not all sensitive animals will have a positive immediate reaction, because of the multiple types of hypersensitivity present ü Screening tests with in-office “quick kits” that detect IgE against flea allergen may also be a useful client aid (Heska – ELISA test) Management of Flea Allergy Dermatitis Ø General procedures that must be followed ü Eliminate all fleas in the environment ü Treat secondary problems: pyoderma, seborrhea, pyotraumatic dermatitis ü In some cases: brief course of corticosteroids to suppress the allergic response Ø The “modern” approach to eradicate a flea infestation ü Clean the indoor environment ü Treat the shaded protected areas outdoors ü Treat ALL pets in the household Management of Flea Allergy Dermatitis Ø Insecticides ü Adulticide chemical (to kill existing fleas) ü Insect growth regulator (to interrupt the life cycle) Ø Immunotherapy (hyposensitization)with flea extracts ü Have been unsuccessful to date Ø Corticosteroid use in FAD ü Temporary measure only, while flea control is underway ü Prednisolone 0.5mg/kg SID to BID for 4 to 7 days, then EOD for 10 days, then stop Understanding speed of kill of flea adulticides Ø Speed of kill ü Initial speed of kill • How fast fleas are killed at the beginning of the treatment period ü Residual speed of kill • How fast fleas are killed towards the end of the application period Ø Rapidly killing of new acquired fleas ü ü ü Prevent flea reproduction Significantly reduce the amount of flea saliva protein injected while feeding Reduce or eliminate flea allergy dermatitis Management of Flea Allergy Dermatitis Ø Role of insecticides in managing FAD is to kill fleas fast enough to keep allergic animals below their pruritic threshold Ø Successful management of FAD is direct related to the product’s residual speed of kill Ø Systemically active compounds can manage FAD as well as topical insecticides Flea Control Ø Immature stages are usually developing in the house for several weeks prior the flea infestation is noted by pet owners Ø Bio-mass of flea immature stages provides an enduring source of new adult fleas that will continually reinfest pets Flea Control Ø Break-the life cycle at the host level ü Prevent reproduction ü Kill the fleas before they lay eggs ü Using highly effective topical and systemic residual flea products to control infestation in the premises ü Some modern products also contain insect growth regulator that kill flea eggs – stop larvae from turning into an adult Biomass exhaustion: 3-8 weeks, usually longer Flea Control Ø Premises treatment - Biomass reduction ü Mechanical control – enough in the vast majority of cases • • • • • Wash bedding Regular vacuuming (daily) Steam clean Wash area rugs Flea traps ü Chemical control (sprays, aerosols, pest control services) • Adulticide (pyrethroids) • IGR ( methoprene, pyriproxifen) • Two treatments 7 to 10 days apart Flea Control Ø Outdoor treatment ü Treat shaded protected areas • under decks, under porches, under crawling spaces ü Every 7 to 10 days ü Advertised as insect killers – EPA approved • Imidacloprid-cyfluthrin • Esfenvalerate • Permethrin Common Reasons for Failure of Flea Control Ø Poor selection of products Ø Failure to break the life cycle Ø Failure to treat all animals in contact with the household Ø Failure to treat the environment Special Considerations for Cats Ø Very sensitive to organophosphate toxicity Ø Sensitive to products containing permethrin at concentrations higher than 0.1% Ø Cats salivate profusely when alcohol based products are used Ø Commonly recommended for cats ü Frontline®; Revolution®; Bravecto® topical solution; Advantage®; Capstar®; Program®; Assurity® Client Education Ø Largest numbers of eggs are found where the pet spends most of its time Ø Larva will migrate under furniture Ø Pupa stage is difficult to kill and results in continued emergence of fleas(‘pupa window effect’) – new adult fleas are seen 3 to 4 weeks after treating the environment Ø Preventive flea control is more successful than waiting until a flea population is established