diagnosis & management of the allergic cat, dr. michelle tranchina, 11/8/14
Post on 16-Jul-2015
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What is an allergy? An abnormal reaction to a normal
substance
Classic allergic reactions are Type I hypersensitivities or IgE mediated hypersensitivity
What is an allergen? Substance which upon exposure elicits an
immunologic reaction Almost always proteins Must be of sufficient size to stimulate the
immune system (>10kda) Hapten phenomenon- small proteins that
link to larger proteins and together induce an immune response
Hypersensitivity Reactions Type I IgE mediated Immediate type Crosslinking of allergen specific IgE on
mast cells following exposure and recognition to the allergen
Degranulation of mast cells results in release of pro-inflammatory mediators
Hypersensitivity Reactions Type II Antibody mediated Cytotoxic hypersensitivity Antibody attaches to cell membrane
resulting in cell lysis Usually endogenous though can be
exogenous e.g. pemphigus, IMHA
Hypersensitivity Reactions Type III Antigen-Antibody complexes Mostly IgG though can be IgM e.g. vasculitis
Hypersensitivity Reactions Type IV Delayed type hypersensitivity Also known as cell mediated
hypersensitivity T lymphoyctes, monocytes, macrophages
mediate cell damage
Stranger Danger! Classic view of immunology based on self vs
non-self Immune system triggered by ‘foreign-ness’ Does not well explain for tolerance of body
changes (e.g. puberty, pregnancy, lactation, metamorphosis, neoplasia)
Does not well explain the rarity of adverse reactions to vaccines
Does not well explain why most of us have auto reactive lymphocytes but so few of us have autoimmune disease
Danger Model Proposed by Polly Matzinger Represents a major paradigm shift Immune system is stimulated by damage Immune system responds to cellular signals
indicative of tissue health Cells dying of programmed cell death are
usually scavenged before they release their contents
Release of any intracellular substance can be a potential ‘danger’ signal
Danger Model and Atopic Dermatitis Exposure to allergens, bacteria, fungi,
proteases Mechanical damage from scratching May induce IL-33 which stimulate Th2 cells
and mast cells Th2 cells activate B cells which produce
IgE
Atopic Dermatitis Type I hypersensitivity Pruritic dermatosis Triggered by exposure to environmental
or aeroallergens In dogs and cats cutaneous absorption is
believed to be the primary source of exposure
Food allergy
Pruritic dermatosis Can be Type I, Type II, Type III or Type IV
hypersensitivity Exposure to a food item(s) induces an
immune response NOT the same as intolerance which is a
non-immunologic reaction May or may not be associated with
gastrointestinal signs
Diagnosis Food allergies and atopic dermatitis are
clinical diagnoses Based on compatible history and physical
exam Laboratory tests sometimes helpful
Presentation Atopic dermatitis Strong genetic predisposition Most common age of onset 1-3 years May be seasonal or year round
Atopic dermatitis Associated with elevated serum levels of
total and allergen specific IgE IgE synthesis is stimulated by T cell derived
cytokines Production of IgE is enhanced by IL-4 and
IL-13 High numbers of IL-4 producing Th2 (CD4+) cells are found in lesional skin
and peripheral blood mononuclear cells
Atopic dermatitis IgE mediated allergen presentation can
lead to enhanced activation of the immune system
Leads to expansion of Th2 population and increased IgE
Lesional skin shows increased numbers of T cells and high CD4+/CD8+ ratio
Atopic dermatitis Biopsy features No pathognomonic changes Epidermal hyperplasia Mixed perivascular inflammation including
mast cells, eosinophils, neutrophils, lymphocytes,
Presentation Food allergies May or may not have a genetic
predisposition No specific age Year round but may wax and wane
Flea allergy dermatitis Most common allergic skin disease in dogs
and cats Lack of recent publications re-evaluating
its prevalence Significance of FAD probably
underestimated in pampered pets Use of flea control does not rule out flea
exposure
Presentation Four commonly recognized reaction
patterns in the cat1) Non-lesional pruritus2) Symmetric alopecia3) Miliary dermatitis4) Eosinophilic granuloma complex
Non lesional pruritus Cats in a dog suit Primary complaint from owner will be
itching Exam will show hair loss, excoriations,
erythema, etc. May or may not be complicated by
secondary infection
Symmetric Alopecia ‘Fur mowers’ Presenting complaint may be excessive
grooming or hair loss Owners may believe hair loss is
spontaneous Clinical exam shows regional hypotrichosis
to alopecia Skin may be visually normal or mildly
inflamed
Is my cat crazy? Or is it just me? Previously known as psychogenic
alopecia Believed that cats literally pulled their own
hair out from stress or anxiety Behavior modifying drugs were commonly
recommended but often ineffective Many psychotropic drugs such as SSRIs,
TCAs often are potent anti-histamines
It’s probably just you… 2006 JAVMA study (Waisglass et al) n=21 Adult cats with a previous diagnosis of
psychogenic alopecia Extensive work ups on all cats including:
cbc/chem/t4, cytology, fungal cultures, diet trial, skin biopsy
Response to Depo injections where symptoms were otherwise unexplained
It’s probably just you… 76% (16 cats) were found to have a
medical reason for their hair loss 10% (2 cats) were found to have true
psychogenic alopecia 14% (3 cats) were found to have a
combination of psychogenic and medical factors
>90% of cats had some medical reason for hair loss
Food allergies vs atopic dermatitis 57% (12 cats) were confirmed to have a
food allergy Food allergies suspected but not
confirmed in an additional 2 cats (10%)
Histopathology 70% of cats had evidence of
inflammation of their skin biopsies 6 cats had ‘normal’ skin biopsies 2/3 cats with normal skin biopsies were
diagnosed with an allergic skin condition based on clinical response to therapy
Miliary dermatitis So named because these lesions feel like
millet seeds Characteristic lesion is a papule
surmounted by crust May be felt more easily than they are
seen May or may not be pruritic
Miliary dermatitis Not pathognomonic for allergic dermatitis Most common differentials include FAD,
atopy, food allergy Consider infectious causes such as
dermatophytosis and bacterial folliculitis Consider parasitic causes such as
demodicosis, otodectes, trombiculosis, lice, cheyletiella intestinal parasite hypersensitivity
Eosinophilic Granuloma Complex Umbrella term including: Rodent ulcer (indolent or lip ulcer) Eosinophilic plaque Linear granuloma (Eosinophilic
granuloma)
Eosinophilic Granuloma Complex Multiple forms may co-exist at the same
time May change pattern from season to
season or year to year
Eosinophilic Granuloma Complex Often associated with allergic skin disease One study (n=88) found 31% of allergic
cats to have one or more lesions of EGC May be heritable in some cases EGC lesions have occurred in SPF cats These cats typically ‘outgrow’ the disease
by 2-3 years of age Oral lesions could result from imbedded,
swallowed insect parts
Rodent ulcer Well circumscribed red-brown, alopecic
lesions May have a raised border Most often unilateral Most often on the upper lip Pruritus and pain are rare Rarely may undergo malignant
transformation to squamous cell carcinoma
Rodent ulcer Differentials: Infectious (bacterial, fungal, viral) Trauma Neoplasia (SCC, MCT, lymphoma)
Eosinophilic plaque Most often occur on the abdomen or
medial thighs Well circumscribed, raised, round to oval,
oozing, often ulcerated Often severely pruritic
Eosinophilic Granuloma Most often occur on the caudal thighs, face,
and oral cavity (esp tongue and palate) When on the thigh lesions are usually well
defined, raised, firm, yellowish to pink plaques with a distinctive linear configuration
Lesions on the face and oral cavity have a papular to nodular configuration
Usually discovered incidentally
Eosinophilic Granuloma Most common cause of lower lip swelling
and nodules (pouting cats) Most common cause of asymptomatic
swollen chins May resolve spontaneously in cats
younger than 1 year
Eosinophilic Granuloma Differentials Infectious (bacterial or fungal) Insect bite reactions Neoplasia
Head/Neck Pruritus Controversial designation Itching is confined to the head and neck Food allergic cats may be over-
represented
To biopsy or not to biopsy? Rarely helpful Biopsy will identify a reaction pattern but
will not provide clues as to the underlying cause
Allergy testing Who? Patients who you have clinically
diagnosed with atopic dermatitis Other causes of skin lesions or pruritus
have been ruled out
Allergy testing What? Intradermal skin testing remains the gold
standard Results are more difficult to interpret Results may be enhanced with
intravenous fluorescein Serology is a reasonable alternative
Allergy testing What? Intradermal skin testing (IDST) involves the
injection of an allergen into the dermis A positive reaction involves the
development of a wheal Wheal is a result of mast cell
degranulation secondary to cross-linking of allergen specific IgE within the skin
Allergy testing What? Serologic allergy testing involves
screening the serum for allergen specific IgE
Based on the premise that tolerance induces production of IgG and hypersensitivity induces the production of IgE
Food allergy Consider in any case where symptoms
occur year round Consider in any case where symptoms do
not respond to steroids
Food allergy The only accurate test for food allergies
remains a strict elimination diet trial Minimum of 4-6 weeks No other food item crosses the pets lips
during this time
Food allergy ELISA and RAST tests are exceptionally
poor diagnostic tools for diagnosing food allergies
Patch testing shows promise but is logistically difficult and expensive
Cooking for cats Basic principles Feed a novel protein Eliminate all access to other food items
until the diet trial is complete All or nothing
Cooking for cats No protein is inherently hypoallergenic Look for a food your patient has not
eaten before
Cooking for cats Hydrolyzed diets Based on the principle that an enzymatically
degraded protein will be below the molecular threshold to be recognized as an allergen
There is a lack of research in veterinary medicine to know what this molecular threshold is
These are all commercial diets and therefore have preservatives, additives and ‘other’ ingredients
Approximately 20% of dogs who have an allergy to a food item cannot tolerate a hydrolyzed version of that food
Cooking for cats Approximately 15-20% of dogs cannot
tolerate any commercial diet No specific studies on this in cats A home cooked diet may be the only
means of diagnosis and managing a food allergic cat
Proceed cautiously given risks of nutritional HCM and hepatic lipidosis
Treatment Every pruritic cat needs strict flea control Many great options Topicals (Frontline, Advantage, etc) Comfortis Seresto collars Some cases may require off label use of
products for optimal results
Atopic Dermatitis Treatment Corticosteroids Antihistamines Atopica Immunotherapy Interferon Mast cell inhibitors Ovaban
Atopic dermatitis Steroids Highly effective Cats may be more tolerant to adverse
effects of glucocorticoids Still have risks of cutaneous atrophy,
hepatopathy, kidney disease, diabetes Oral and injectable forms available
Atopic dermatitis Glucocorticoids work by altering gene
transcription Bind to intracellular glucocorticoid
receptor Leads to increase of lipocortin-1 Reduces activity of phospholipase A2 on
cell membranes which inhibits arachidonic acid cascade
Atopic dermatitis Glucocorticoids Some cats may not be able to efficiently
convert prednisone (pro-drug) to prednisolone
For chronic oral use wean to alternate day administration
For injectable repositol steroids no more than 1 injection every 6-8 weeks
Administer injectable steroids IM or IV
Atopic dermatitis Atopica (Cyclosporine) Fat soluble cyclic polypeptide metabolite of
fungus Tolypocladium inflatum gams Used to treat a variety of different conditions Microemulsified or modified form is absorbed
better and produces more stable blood levels For skin disease blood levels do not appear to
correlate to clinical efficacy
Atopic dermatitis Atopica (cyclosporine) Blocks IL-2 transcription and T cell responsiveness
to IL-2 Diminishes amplification signals for macrophage
and monocyte activation Production of other cytokines such as IL-3, IL-4, IL-5,
TNF-alpha and IFN-gamma may also be impaired Inhibits mononuclear cell function, antigen
presentation, neutrophil adherence, natural killer cell activity, growth and differentiation of B cells
May inhibit mast cell degranulation by affecting the interaction between mast cells and nerves
Atopic dermatitis Atopica (Cyclosporine) Safety Humans experience high incidence of
nephrotoxicity and hepatoxicity Hepatic lipidosis and jaundice were reported
in less than 2% of cats Increased ALT reported in less than 2% of cats Increased BUN/Cre reported in less than 2% of
cats
Atopic dermatitis Atopica Most common adverse effect is vomiting
and/or decreased appetite Reported in approximately 30% of cases Palatibility and difficulty of administration
can be a problem for many owners May be able to reduce to alternate day
or twice weekly use in some cases
Atopic dermatitis
Atopica (Cyclosporine) Potential increased susceptibility to
infectious diseases Reports of fatal toxoplasmosis Recommend cats be kept indoors
Atopic dermatitis Interferon-omega Interferon-gamma Extensive use in Europe, Australia, Asia Not approved for use in U.S.
Atopic dermatitis Interferon Family of regulatory proteins with anti-
viral, anti-tumor and immunmodulatory effects
Type I (alpha, beta, omega, delta, tau) Type II (gamma) Interferon gamma shown to be effective
in managing atopic dermatitis in humans
Atopic dermatitis Mechanism of action not well understood Humans with AD have low levels of IFN-
gamma and high levels of IL-4 Also shown to be true in dogs (not studied
in cats) May restore ‘normal’ Th1/Th2 balance Dogs who respond well to
immunotherapy show significant increase in IFN-gamma:IL-4 ratio
Atopic dermatitis Canine studies show similar success rates
to Atopica Well tolerated therapy Concern about immunologic reactions
when used parenterally Improvement may take months Not approved for use in U.S. VERY expensive
Atopic dermatitis Allergen specific immunotherapy Allergens selected based on serologic or
intradermal skin testing Mechanism of action is not well understood Old theory was induction of blocking
antibodies (IgG) Newer theory is that it may increase
concentration of Th1 vs Th2 cytokines Keppel et al. study (2008) showed responders
to immunotherapy had increased levels of IFN-gamma, IL-10, T-reg cells
Atopic dermatitis Kinavet (Masitinab) Palladia (Toceranib phosphate) “Mast cell stabilizers” Oral tyrosine kinase inhibitors Target key kinases involved in various cancers
(KIT, PDGFR, Lyn) Main target is the mast cell which release a
number of pro-inflammatory cytokines capable of initiating and sustaining an allergic response
Atopic dermatitis Palladia v Kinavet Major difference is in their degree of
selectivity Kinavet is more selective Theoretical benefit is lower toxicity Theoretical trade off is lower anti-cancer
potency
Atopic dermatitis Kinavet carries FDA approval for treatment of
atopic dermatitis in dogs 2011 study Cadot et al. 61% of treated dogs showed significant reduction
in CADESI scores vs 35% of control dogs 60% of dogs reported to be refractory to
cyclosporine or steroids showed significant reduction in CADESI scores
46% of dogs showed a significant reduction in pruritus
65% of owners reported good to excellent control with masitinab
Atopic dermatitis Monitoring CBC (leukopenia, neutropenia, anemia) Chemistry (hypoproteinemia, elevated
liver and kidney enzymes) Baseline At 14d of therapy At 30d of therapy
Atopic dermatitis Extremely expensive Pills can be difficult for many cat owners
to administer Can be compounded but little data
available and a large volume is recommended
Atopic dermatitis One pilot study assessing the safety of Kinavet
in cats N= 20 healthy spf research colony cats 10 received 50 mg po 24h and 10 received 50
mg po q48h x 4 weeks 2/10 developed proteinuria 3/10 developed proteinuria Increased creatinine was noted in some cats GI side effects noted in some cats
Atopic dermatitis Apoquel (oclacitinab) JAK-STAT inhibitor IL-31 antagonist Approved for treatment atopic dermatitis
in dogs >1 year of age
Atopic dermatitis Apoquel Studies show reduced pruritus in 79% of
dogs Response is usually within 2-3 days Does not interfere with allergy testing Unknown if it affects response to
immunotherapy Not recommended to be combined with
other immunosuppressive agents
Atopic dermatitis Apoquel No routine monitoring recommended Similar drugs in humans warn or
liver/kidney toxicity, and blood dyscrasias Label warnings of increased susceptibility
to infection, neoplasia, demodicosis
Atopic dermatitis No published data on use of Apoquel in
cats Limited data suggests a very short half life
which could make dosing difficult
Case Studies Alex P Kitten 1 year old male, neutered DSH Severe facial pruritus since adopted No seasonal variability
Case Studies Lord Tubbington 12 year old male, neutered DSH 3-4 year history of warm weather miliary
dermatitis
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