2012 SA81 DERMATOLOGIC PEARLS IN VETERINARY MEDICINE.pdf

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					                            84th Annual Western Veterinary Conference



SA81
DERMATOLOGIC PEARLS IN VETERINARY MEDICINE
Anthony A. Yu, DVM, MS, Diplomate ACVD
Ontario Veterinary College,
Guelph, Ontario, Canada


The field of veterinary dermatology is evolving rapidly with improved diagnostic techniques,
specialized dermatopathologist, and development of new medications on both the human and
veterinary front. The following is a summary of the latest PEARLS in Dermatology that I use
on a regular basis in my referral practice.
CONCEPTUAL DERMATOLOGIC PEARLS
   a) The T Helper-1: T Helper-2 Cell Paradigm
       - CD4+ cells, balance between TH1: TH2 direct the immune system
       - T Helper 1 cells – local immune defense system (IFN)
       - T Helper 2 cells – humoral immune defense system (IL4, IL5)
       - Allergies result in TH2 stimulation and TH1 suppression
               - secondary bacterial, yeast, fungal, parasitic & viral infections
   b) The Allergic/Pruritic Threshold
       - Level above which a pet will start to exhibit clinical signs
       - Allergies are a spectrum of disease, not separate entities
       - Food, flea, contact and environmental allergies add up to push a patient
         above its allergic threshold (summation of effect)
   c) Yu-Ski Protocol to treating severe allergic patients - address summation of effect
       One allergy by itself (e.g. Food allergies) may not be enough of an allergic stimulus to
       push a patient over their allergic threshold. Rather, it is common to have two or more
       pruritogenic conditions acting together (e.g. Food allergies + Environmental allergies
       during the summer months) at the same time, whereby their summation of effect
       results in pushing a pet over the allergic threshold for clinical signs to be seen.
   “Cut through the onion approach” versus “peel the layers of the onion” approach
   1. Treat bacterial and yeast infections identified on skin cytology. Continue antimicrobials
       for 4-6 weeks until complete resolution. (e.g. Cephalexin, ketoconazole)
   2. Use anti-inflammatories that have a guaranteed response (e.g. steroids or Atopica®) for
       6-8 weeks to help alleviate signs of environmental allergy.
   3. Maintain a strict novel protein source (e.g. Kangaroo and oatmeal diet) for 8-12 weeks
   4. If high index of suspicion, treat ectoparasites every 2 weeks for 3 treatments, then one
       time monthly to treat and prevent recurrence of Sarcoptes and/or Fleas
Recheck exams: Reverse Sherlock Holmes approach to figure out the major role player
   4 weeks - Expect a significant response to therapy (decreased pruritus and improvement of
       clinical infection) and the antimicrobial treatment may be discontinued.
   - If there is a relapse of clinical signs then one needs to rule-out microbial
       hypersensitivities (if pruritus is noted before lesions recur) or a metabolic disease (if
       lesions relapse before pruritus is noted).
   6 weeks- Discontinue the anti-inflammatory treatment if pruritus is still controlled
   - If a relapse of clinical signs is noted, then suspect environmental allergies.
   -    Options would then either include intradermal and serological allergy testing to generate
        allergen-specific immunotherapy for the patient OR long-term symptomatic approach
   8 weeks - Pursue a dietary challenge if there has been no relapse of clinical signs with the
        withdrawal of both antimicrobials and anti-inflammatory medication
   - If no notable changes are noted with the dietary challenge, then consider either a
        seasonal allergic condition (look for possible relapse in peak pollen season) or that
        unrecognized Sarcoptes was the culprit.
   d) Vaccinating the allergic patient
   - Vaccines can cause sensitization to food antigens (1)
   - Vaccines can stimulate lymphocytic thyroiditis in dogs (2)
   - Vaccines can stimulate allergen specific reactions in predisposed dogs (3,4)
   - Based on the above findings, I am recommending the following in my allergic breeds:
   i) Vaccinate outside of the pet’s allergy season (e.g. winter time = lowest allergen load)
   ii) Move to a 3-year rotating vaccination protocol with labeled and licensed 3-year vaccines
   iii) If not able to move to 3-year rotation, split-up vaccine injections by 2-4 week intervals
   iv) Consider titers in dog with severe reactions to vaccine
   v) Consider pre-/post-vaccination use of anti-inflammatory medication to prevent reactions

HISTORICAL DERMATOLOGIC PEARLS
   a) Calendar updates
   - Record events on a daily basis for easy review at recheck or via email/telecom
   - Able to visualize pattern of response
   - Minimizes “husband/wife” discrepancies
   - Makes efficient use of appointment time
   b) Diet history in suspected food allergic patients
   - A thorough history is crucial to the success of a dietary trial
   - Verbally reviewing food items with owners including examples such as rawhides, drive-
      thru treats, flavored medication (e.g. heartworm preventatives), fruits & vegetables (Oral
      Allergy Syndrome) and medications with binders and/or dyes (e.g blue dye) (5)
   c) OTC diets by owner NOT for dietary trial
   - Use VETERINARY diets for trial period, then consider challenging with OTC
   - Quality assurance before and after ingredients are combined. (6)
DERMATOLOGIC EXAMINATION PEARLS
  a) Diagnostic criteria for atopic dermatitis in dogs (7)
     - Exclusion of ectoparasites (appropriate test and/or treatment), bacterial/fungal
     diseases and diet to determine CAFR role in the development of the disease.
   Criteria Set 1 for NFIAD                    Criteria Set 2 for NFIAD
   1. Age at onset <3 years                    1. Age at onset<3 years
   2. Mostly indoor                            2. Mostly indoor
   3. Chronic or recurrent yeast infections    3. Pruritus sine material at onset
   4. Affected front feet                      4. Affected front feet
   5. Affected ear pinnae                      5. Affected ear pinnae
   6. Non-affected ear margins                 6. Non-affected ear margins
   7. Non-affected dorso-lumbar area           7. Non-affected dorso-lumbar area
   8. Corticosteroid-responsive pruritus
   5 criteria: Sens=0.854; Spec=0.791          5 criteria: Sens=0.772; Spec=0.83
   6 criteria: Sens= 0.582; Spec=0.885         6 criteria: Sens=0.42; Spec=0.937

   b) Food (FIAD) versus atopic dermatitis in cats (NFIAD) (8)
   - n = 417; 20 veterinary dermatologists Belgium, Estonia, France, Germany, Greece,
   Sweden, Switzerland, UK and the USA
   - Exclusion of ectoparasites, fungal and bacterial diseases, neoplastic & viral conditions.
   - Consider food especially if non-seasonal
   Criteria set for diagnosis of feline Non Flea Hypersensitivity Disease after
   exclusion of flea HD
   1. Presence of pruritus at onset
   2. Presence of at least two of the following classical clinical reaction patterns:
          a) Symmetrical alopecia
          b) Miliary dermatitis
          c) Eosinophilic dermatitis
          d) Head and neck erosions/ulcerations
   3. Presence of at least two sites affected
   4. Presence of miliary dermatitis as a dominant pattern
   5. Presence of eosinophilic dermatitis or symmetrical alopecia or erosions/ulcerations
      on the head, face, lips, ears or neck
   6. Presence of nonsymmetrical alopecia on the rump, tail or hindlimbs
   7. Presence of symmetrical alopecia on the abdomen
   8. Absence of erosions/ulcerations on the forelimbs
   9. Absence of lesions on the sternum or axilla
   10. Absence of nodules or tumours
   6/10 criteria: sensitivity of 90% and a specificity of 83% for NFHD.

DIAGNOSTIC DERMATOLOGIC PEARLS
Allergy testing – intradermal or serologic or both?
Commercial serum allergen-specific IgE testing laboratories may report positive results from
non-allergic sample sources (negative samples) (9)
What are our best options for longterm treatment of allergies? (In order of success)
1. Immunotherapy based on serologic allergy testing by the referring veterinarian DURING the
   peak allergy season AND intradermal allergy test by a dermatologist 60-90 days AFTER
   peak allergy season.
2. Immunotherapy based on intradermal allergy test by a dermatologist 60-90 days AFTER
   peak allergy season only
3. Immunotherapy based on serologic allergy testing by the referring veterinarian DURING the
    peak allergy season only
4. Longterm symptomatic therapy using non-steroidal alternatives such as cyclosporine
All of the above may require adjunctive therapy such as antihistamines, pentoxifylline,
essential fatty acids, ectoparasite control, barrier repair products and shampoo therapy.
Also, dietary restriction may be used longterm or during peak allergy seasons to minimize
CAFR’s contribution to the allergen load.
DERMATOLOGIC THERAPEUTIC PEARLS
a) Tacrolimus (ProTopic® 0.1% & 0.03%) for Local Immunomodulation
- Macrolide lactone produced by fungus Streptomyces tsukubaensis
- Inhibits T-lymphocyte response to antigens; production of IL2         decreased T-cell
   proliferation; IL3, IL4, IFN-γ, and TNF-α important in allergies and inflammation
- Down-regulates cytokine expression in Langerhans, mast cells, basophils, eosinophils,
   keratinocytes
- Uses: Localized DLE, SLE, PF, PE, Allergic Dermatitis, Vasculitis
- SE: +/- Irritation at site of application, erythema
b) Cyclosporine use in cats
- Licensing in Europe and USA (November 2011)
- Peak plasma levels 1-2 hrs; T½: longer than dogs at 9hrs
- Bioavailability in cats is 24-29%; Steady state after 1 week of administration
- < 6 mo and < 1.5 kg BW no safety/efficacy assessment
- Dose: 7.5 mg/kg per os of liquid formulation (100mg/ml) ideally on empty stomach
- STOP ACCESS TO or FEEDING RAW FOODS; Caution in Toxoplasma naïve outdoor
- Uses in cats: feline atopic dermatitis (EGC (eosinophilic plaques, granulomas>> indolent
   ulcers); symmetric alopecia; military dermatitis; ulcerative/erosive dermatitis); Feline asthma;
   Pemphigus foliaceus; Sebaceous adenitis
- SE: Weight loss, hypersalivation, lethargy, and GI upset, susceptibility to Toxoplasmosis
   and other potential (latent or new) infections (papilloma and herpes virus)
c) Pentoxifylline’s Multiple Uses
- Synthetic xanthine derivative related to caffeine and theophylline
- Phosphodiesterase inhibitor in RBC and immune system
- Rheologic agent, immunomodulator, wound healing
- Uses: vasculopathies, ischemic folliculopathies, allergic dermatitis, autoimmune disorders
- Dose: 10-35 mg/kg PO BID to TID
- SE: Rare; nausea, vomiting, hyperexcitability; minimized using sustained-release tablets
- Interaction: Cimetidine and fluoroquinolones decreases clearance
- DO NOT USE with warfarin, anticoagulants, or in patients with hemorrhagic conditions
d) Cetirizine - my new favourite antihistamine (10, 11)
- second-generation member of the piperazine family
- active metabolite of hydroxyzine with mild sedative effects.
- Uses: Antihistaminic activity AND also decreases influx of eosinophils into skin, which is
   great for treatment of eosinophilic granuloma complex patients and allergies.
- Onset of action is 1-3 hours following oral administration
- Peak concentrations at 10 hours
- Duration of action ranging between 12-24 hours.
- Cetirizine is excreted largely unchanged in urine.
- A minimum of 2 weeks of continuous dosing is necessary to fully assess any antihistamine.
- Dose: 0.5-1.0 mg/kg Q12-24hrs.
- SE: same as other antihistamines
e) Multi-Modal Anti-Inflammatory Therapy – The “Forest Fire” Analogy
Even with the introduction of non-steroidal alternatives such as cyclosporine with long-lasting
effects equivalent to those of steroids, glucocorticoids remain the only treatment option that will
give the patient immediate relief or “put out a fire” within 24-48 hours. If the analogy of a forest
fire is used, the “fire retardant” dropped from airplanes is the steroid, while the other
therapeutic options such as Omega-3 fatty acids, antihistamines, dietary restriction, flea
control, epidermal barrier repair, cyclosporine and allergen specific immunotherapy are the
“trench diggers” controlling the fire from spreading. The incorporation of this multi-modal
approach to control the allergic reactions, prevents discomfort and damage to the epidermal
barrier, and calms the microenvironment minimizing recurrence of secondary infections, so
much so, that I typically have client error on the side of giving a little extra steroid to prevent a
secondary infection rather than to give too little steroid and have to return to 4 weeks worth of
antimicrobial therapy to treat a Malassezia or bacterial infection.
f) Preventative use of anti-inflammatory medications
Lastly, once a pattern of seasonal reactions has been established and appears quite
predictable, use of cyclosporine, steroids or other anti-inflammatory medications in advance of
the allergy season may allow the owner to start at maintenance control doses as opposed to
using high loading doses to put out the fire first before moving to maintenance therapy.
Ultimately this approach will help minimize cost and side effects associated with high daily
doses of allergy medications as well as prevent costly secondary infections such as
Staphylococcus and Malassezia dermatitis.


References
1. Tater et al. Effects of routine prophylactic vaccination or administration of aluminum
    adjuvant alone on allergen-specific serum IgE and IgG responses in allergic dogs. AJVR
    2005;66(90:1572-1577
2. Scott-Moncrieff et al. Evaluation of antithyroglobulin antibodies after routine vaccination in
    pet and research dogs. JAVMA 2002;221(4):515-521
3. HogenEsch et al. Effect of vaccination on serum concentrations of total and antigen-
    specific immunoglobulin E in dogs. AJVR 2002;63:611–616
4. Frick et al. Immunoglobulin E antibodies to pollens augmented in dogs by virus vaccines.
    AJVR 1983;44:440–445.
5. Petersen A. "Cutaneous adverse reaction to several oral thyroid supplements in a dog with
    hypothyroidism & confirmed cutaneous adverse reaction to food" NAVDF 2011
6. Willis-Mahn C, et al. "ELISA testing for soy antigens in dry dog foods used in dietary
    elimination trials" NAVDF 2011
7. Favrot et al. Canine criteria Vet Derm 2010
8. Favrot et al. Feine criteria Vet Derm 2011
9. DeBoer DJ, Verbrugge MJ. Results of canine serum allergen-specific IgE determinations
    performed by commercial laboratories on canine IgE-free samples and on samples from
    nonallergic dogs. NAVDF 2005.
10. Papich MG et al. Pharmacokinetics of cetirizine in healthy cats. AJVR 2008;69(5): 670-674
11. Bizikova P et al. Hydroxyzine and cetirizine pharmacokinetics and pharmacodynamics after
    oral and intravenous administration of hydroxyzine to healthy dogs. Vet Derm
    2008;19(6):348 – 357
12. Olivry T,et al.Treatment of canine atopic dermatitis: 2010 clinical practice guidelines from
    the International Task Force on Canine Atopic Dermatitis. Vet Derm 2010;1:1-16

				
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