S Y M P O S I U M

SYMPOSIUM
PEER-REVIEWED
Allergy testing and treatment
for canine atopic dermatitis
Now that you’ve diagnosed atopic dermatitis, how do you alleviate the patient’s
suffering? Allergen-specific immunotherapy, which requires allergy testing, holds
the best chances for relief, but symptomatic treatment can help as well.
ANDREW HILLIER, BVSc, MACVSc,
DACVD
Department of Veterinary Clinical Sciences
College of Veterinary Medicine
The Ohio State University
Columbus, OH 43210-1089
AS DISCUSSED in the first article in
this symposium, the diagnosis of
atopic dermatitis is based on a suggestive history, typical clinical signs,
and ruling out differential diagnoses.
Positive allergy test results are not a
prerequisite for diagnosis. Allergy
tests are most useful in selecting allergens for allergen-specific immunotherapy and in determining
allergen-avoidance measures.
The options for treating and controlling atopic dermatitis include allergen avoidance, allergen-specific
immunotherapy, symptomatic antiinflammatory therapy, and antimicrobial therapy. The treatment selected
and the response to it differ from animal to animal depending on the nature and intensity of clinical signs and
flare factors (e.g. pyoderma, yeast dermatitis, otitis); the patient’s tolerance
of repeated topical, oral, or injectable
treatment; and the owner’s willingness
to accept the time, effort, and expense
of treatment. Anti-inflammatory therapy alone may be adequate in dogs
with a short and confined allergy season, in dogs responsive to nonsteroidal symptomatic therapy, or in
dogs in which intermittent low-dose
alternate-day prednisone controls clinical signs without side effects. But
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most dogs with atopic dermatitis have
nonseasonal disease, are inadequately
controlled with symptomatic therapy
alone, or have unacceptable side effects from symptomatic therapy. In
these circumstances, allergen-specific
immunotherapy is the primary therapeutic option. As response to immunotherapy is allergen-specific,1,2 allergy testing is necessary to determine
which allergens are causing disease in
a patient. This is the true indication
for allergy testing.
Allergy testing
Two types of allergy tests are available: intradermal tests (skin tests), and
allergen-specific IgE serology (serum
tests). Although widely used, the term
allergy test is a misnomer. Neither intradermal tests nor allergen-specific
IgE serology definitively rule in or
rule out allergy (i.e. clinical disease).
Rather, they are useful in demonstrating IgE-mediated hypersensitivity to
allergens that may be causing skin
disease, such as atopic dermatitis
(true allergy), or that are not causing
disease (subclinical hypersensitivity),
as seen in normal dogs that can have
positive allergy tests.3,4 This is the
principal reason why allergy tests
cannot be used as a screening test at
the initial consultation.
There has been much debate concerning the usefulness of intradermal
testing and allergen-specific IgE serology and the advantages of one over
the other. Historically, intradermal
testing has been considered the gold
standard, and the accuracy of
allergen-specific IgE serology is often
evaluated by comparative analysis
with the results of intradermal
testing.5 This is perhaps unfair, because intradermal testing detects IgE
in the skin, and allergen-specific IgE
serology detects IgE in the serum. The
two are not necessarily equivalent.
Also, in veterinary medicine, allergen
extracts, testing methodologies, and
interpretation of results have not been
standardized for either intradermal
testing or allergen-specific IgE serology. Neither test has been demonstrated to be superior to the other.
Both intradermal testing and
allergen-specific IgE serology offer the
potential for useful information when
performed and interpreted according
to broadly defined accepted criteria.
Generally, there is a fairly good correlation between the results of the separate
tests in individual animals. But some
dogs with positive reactions on intradermal testing have negative results on
allergen-specific IgE serology, and vice
versa. I routinely perform both intradermal testing and allergen-specific IgE
serology when allergen-specific immunotherapy is anticipated. Since most
general practitioners do not perform intradermal testing, further discussion is
focused on allergen-specific IgE serology. The general principles of allergy
test result interpretation are similar for
both intradermal testing and allergenspecific IgE serology.
SYMPOSIUM
Treating canine atopic dermatitis (cont’d)
Choosing a serum-based allergy test
Numerous laboratories and companies offer allergen-specific I g E
serology. When choosing a laboratory, consider the scientific basis of
the assay, the published results of
studies using the assay, the laboratory’s involvement in allergy research,
the quality and efficiency of the service, the availability of qualified technical staff for consultation, and the
cost. There are marked differences
among the assays performed by each
of the laboratories, including the allergen source, the reacting phase (liquid
or solid), the IgE-specific detection
reagent (e.g. monoclonal antibody,
polyclonal antibody, α chain of IgE
receptor), and the methods of calculating, reporting, and interpreting results. The effect and importance of
differing assays have not been criti-
cally evaluated in controlled independent studies, and claims of superiority
of one assay over another need to be
interpreted with extreme caution.5
In general, most allergen-specific
IgE serology assays have good sensitivity (ability to identify true allergen hypersensitivity) but seem to have variable and lower specificity (ability to
correctly identify the absence of allergen hypersensitivity).5 Low specificity
is associated with false positive results,
possibly resulting in an incorrect diagnosis and incorrect formulation of
allergen-specific immunotherapy.
An in-clinic screening test has recently been released that detects the
presence of allergen-specific I g E
(Allercept E-Screen—Heska). This
test is designed to be a guide in
determining whether further full
allergen-specific IgE serology is indicated. This test should only be used
once a clinical diagnosis of atopic
dermatitis has been made; do not use
it to screen for atopic dermatitis at
the initial visit. It may be useful as a
relatively inexpensive test to convince owners who are reluctant to
spend money on full allergen-specific
IgE serology that such testing is warranted. Further, this screening test
may be useful in determining whether it is an appropriate time for a full
test. Independent analysis of this test
has not been published to date, and
its sensitivity and specificity have yet
to be studied.
despite the fact that studies suggest
allergen-specific IgE serology is not
helpful in diagnosing cutaneous adverse food reactions.6,7 These tests
also do not appear to be of value in
determining which foods to avoid in
a food trial. Thus, they should not be
used in place of appropriate hypoallergenic elimination diet food trials.
Interpreting positive test results
You must determine which positive results of allergy testing (if any)
are of clinical relevance in each case
and, thus, which allergens should be
included in allergen-specific immunotherapy. Examine the medical
record to determine whether the pattern of the disease is seasonal or
nonseasonal, and ask the owner
about the exact nature of the dog’s
habitat and likely exposure to those
allergens within the dog’s environment. In general, allergens may be
categorized as8:
• Nonseasonal: house dust mites
(Dermatophagoides species), storage mites (e.g. Tyrophagus, Lepidoglyphus, and Acarus species),
cockroaches, moths, dander or
epidermals, and indoor molds
(Penicillium, Aspergillus, Rhizopus, and Mucor species)
• Spring: tree pollens
• Summer: grass pollens and outdoor molds (Alternaria and Cladosporium species)
• Fall: weed pollens and outdoor
molds.
Food allergen testing
The history and clinical signs of
cutaneous adverse food reactions are
often identical to those of atopic dermatitis, and a hypoallergenic food
trial is necessary to distinguish between the two diseases. In addition,
some dogs with atopic dermatitis
have concurrent cutaneous adverse
food reactions. Most laboratories offer
food allergen panels for serum testing
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Some nonseasonal allergens may
be more abundant at certain times of
the year, such as house dust mites in
the summer and fall and indoor
molds during more humid times of
the year. Information on pollen seasons in different regions can be obtained by visiting the National Allergy
Bureau’s Web site at www.aaaai
.org/nab/ or visiting www.pollen.com.
SYMPOSIUM
Treating canine atopic dermatitis (cont’d)
TABLE 1
Allergen Avoidance and Control Measures
House dust mites
Cover mattresses, pillows, dog beds, chairs, and sofas with impermeable covers (vinyl).
Remove clutter, such as stuffed animals, from the pet’s sleeping areas to prevent dust
accumulation and to facilitate thorough cleaning.
Do not allow the pet into areas in which dust typically accumulates, such as closets,
the laundry room, and under the beds.
Vacuum the house with a HEPA filter as frequently as possible—at least weekly.
Keep the pet outdoors during vacuuming and for one hour afterward.
Remove as many carpets and rugs as possible, especially from poorly ventilated rooms
such as the basement, garage, and laundry room.
Wash linen, bedding, and blankets every week in hot water (> 130 F [54.4 C]).
Keep the humidity in the home at 30% to 45% relative humidity by using
a dehumidifier, air conditioning, or a humidifier when needed.
Molds
Keep the dog away from freshly mowed grass, mulch, leaf piles, hay, and barns.
Keep the dog’s kennel dry and clean.
out the year, but inconclusive or
negative results may be seen
outside of the optimal times.
• Important allergens were not included in the allergy test. Storage
mites may be important allergens
in dogs in the United States,14 as
they are in Europe.15-18 But these
mites are not routinely included
in allergen-specific IgE serology
and intradermal tests in the
United States.
• A small percentage of dogs with
atopic dermatitis are thought to
have persistently negative allergy
test results. This is unproved in
dogs but a known fact in people
with atopic diseases.
Keep the humidity in the home at 30% to 45% relative humidity.
Keep the pet out of basements, closets, the laundry room, and bathrooms.
Keep the pet’s bedding clean and dry.
Allergen avoidance
Store food in a dry environment.
Clean moist areas where molds thrive with a fungicide or dilute sodium hypochlorite
solution (1 part bleach to 9 parts water).
Interpreting negative test results
If allergy test results are negative
or if positive results do not correlate
with a patient’s disease, consider
these possibilities:
• The dog does not have atopic
dermatitis. Make sure you’ve appropriately ruled out flea allergy
dermatitis, cutaneous adverse
food reactions, scabies, insect
bite hypersensitivity, and contact
dermatitis.
• Alternative allergy testing may
be indicated (i.e. intradermal
testing if only allergen-specific
IgE serology was performed, or
vice versa).
• Certain drugs can interfere with
allergy testing. Antihistamines
are known to affect intradermal
tests9 but not allergen-specific
IgE serology. Corticosteroids are
also known to affect intradermal
tests.10,11 Preliminary evidence
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Treatment
suggests that glucocorticoids do
not affect allergen-specific IgE
serology results.12,13 Since this is
purported as an advantage of
allergen-specific I g E serology
over intradermal testing, more
extensive studies are necessary
to confirm these initial findings.
Also, cyclosporine is likely to affect both intradermal testing and
allergen-specific IgE serology, although this has not yet been
studied in dogs.
• It may be the wrong time of
year for allergy testing in this patient. The peak of the allergy
season (highest I g E levels) is
best for allergen-specific I g E
serology. Toward the end or
shortly after the peak allergy
season is best for intradermal
testing. Both allergen-specific IgE
serology and intradermal testing
are usually performed through-
Table 1 provides guidelines you
can give owners that may help reduce the allergen load and exposure
in patients hypersensitive to house
dust mites and mold.19 These guidelines will help owners decide how
much time, effort, and expense they
want to invest in these avoidance
measures. The guidelines are based
on recommendations in people with
allergies. They have not been evaluated in controlled studies in dogs.
However, in several of my patients,
skin disease improved after their
owners implemented these measures.
Allergen-specific immunotherapy
Allergen-specific immunotherapy
(also known as hyposensitization or
desensitization) is the practice of administering gradually increasing
quantities of an allergen extract to an
allergic subject to ameliorate the
signs associated with subsequent exposure to the causative allergen.20 Allergens are given by subcutaneous injection in increasing doses up to a
maintenance dose or a patient-
SYMPOSIUM
Treating canine atopic dermatitis (cont’d)
determined maximum dose. The
mechanism of action of this treatment
has not been determined in dogs.
Some of the advantages of
allergen-specific immunotherapy
compared with conventional symptomatic therapy (see below) include a
lower frequency of administration, a
low risk of long-term side effects,
and the potential to permanently
alter the course of the disease. In addition, allergen-specific immunotherapy is often more cost-effective long
term. But some owners may be reluctant to give injections, and some
dogs will not accept repeated injections. In these cases, injections may
be given at the clinic by the veterinarian. There is also a very low risk
of anaphylaxis.
As no blinded randomized trials of
allergen-specific immunotherapy with
aqueous allergens have been reported, the true efficacy of allergenspecific immunotherapy in canine
atopic dermatitis is unknown. Numerous open uncontrolled studies imply
that between 50% and 100% of dogs
treated with allergen-specific immunotherapy will have at least a 50%
improvement in clinical signs.21-34 Further, open studies have reported that
factors such as the age at onset, age
at the time of allergen-specific immunotherapy initiation, duration of
disease, severity of clinical signs,
breed, strength of intradermal testing
or allergen-specific IgE serology reactions, number of intradermal testing
or allergen-specific IgE serology reactions, and type of allergen to which a
patient is hypersensitive may be predictive of the outcome of allergenspecific immunotherapy.23-25,29-31,34,35
These observations remain to be validated in controlled studies.
Allergen-specific immunotherapy
is indicated in any dog with nonseasonal atopic dermatitis or any dog
with seasonal atopic dermatitis in
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which symptomatic therapy is ineffective, is associated with unacceptable
side effects, or cannot be maintained
for extended periods. Since allergenspecific immunotherapy is administered most often at home, owners
need to be prepared to accept the
technical aspects of the treatment, observe the dog for side effects, maintain the protocol as prescribed, and
present the dog for regular rechecks.
Concurrent therapy
Glucocorticoids and cyclosporine,
sometimes given in dogs with atopic
dermatitis as symptomatic therapy,
have multiple effects on the immune
reaction. The consequences of these
effects on the response to allergenspecific immunotherapy have not
been specifically studied, but it may
be best to avoid their use, especially
during the initial phases of allergenspecific immunotherapy.
Protocols
As none of the variables (e.g. dose
of allergen, dosing interval) associated
with allergen-specific immunotherapy
have been studied in controlled experiments, it is impossible to make
definitive recommendations. There are
no data proving that one protocol is
better than another. Unlike in most
conventional drug therapies, the pharmacokinetic characteristics of allergenspecific immunotherapy have not
been rigorously studied. By convention or habit, most protocols follow
these guidelines:
• There can be 10 to 12 allergens
per vaccine.
• The initial loading phase starts
with a low dose of allergen (200
to 2,000 PNU/ml) given subcutaneously every two to seven days
with incremental increases in allergen dose.
• A maintenance dose of 10,000 to
20,000 PNU/ml is given every
one to three weeks.
Some dogs start to improve within
a few weeks, but most take many
months. Allergen-specific immunotherapy should be continued for at
least one year before the full effects
may be appreciated or a lack of response is assessed. If the immunotherapy is efficacious, continue
it for the life of the dog. If it fails to
improve clinical signs after one year,
reevaluate the patient (see below).
Safety and adverse reactions
Localized swelling, erythema, pain,
or pruritus may be seen at the injection site. Pretreatment with antihistamines may help control these reactions.20 The most common systemic
reaction is a worsening of clinical
signs, especially pruritus.20 Other reported systemic reactions include
weakness, depression, anxiety, vomiting, diarrhea, urticaria, and angioedema. Rarely, but importantly,
anaphylaxis may occur, with collapse
and possibly fatal consequences. Be
sure to inform owners of the clinical
signs of such reactions, and advise
them to observe their dogs for one
hour after each injection. If any clinical
signs appear, urgent care is necessary.
Recheck evaluations
Recheck examinations are one of
the most overlooked aspects of
allergen-specific immunotherapy.
Reevaluating dogs receiving allergenspecific immunotherapy after one,
three, six, and 12 months (ideally,
but at least after three and 12
months) will be helpful in realizing
optimal results. Patient monitoring is
essential, because perpetuating factors (e.g. staphylococcal pyoderma,
yeast dermatitis, otitis) are likely to
recur until there is marked response
to allergen-specific immunotherapy,
which may take months. Also, owners may neglect to control concurrent
SYMPOSIUM
Treating canine atopic dermatitis (cont’d)
diseases (e.g. flea allergy dermatitis,
cutaneous adverse food reactions, insect hypersensitivity) as they concentrate on allergen-specific immunotherapy. In addition, compliance by
owners in following the injection protocol is reportedly low.32,36 Regular
rechecks will improve compliance.
Troubleshooting
At each recheck, ask the owner to
describe any changes observed after
each injection as well as any overall
changes in pruritus. If the pruritus initially decreases after each injection but
then slowly increases again before the
next injection, the effects of the
allergen-specific immunotherapy are
lasting for only a short time after each
injection. In this case, the interval between injections should be decreased,
and subsequent injections should be
administered when the increase in pruritus is expected. If the pruritus initially
increases after each injection, followed by improvement before the
next injection, the allergen dose is too
high and is inducing pruritus. Decrease the dose of allergen by 25%. If
the spike in pruritus after the injection
is still present, decrease the dose by
25% again.
At the six- and 12-month recheck
examinations, review the maintenance protocol. If the pruritus has
decreased overall but is still marked,
the allergen dose may be too high or
too low. Start by decreasing the dose
of allergen by 25%. If there is a further reduction in pruritus, continue to
decrease the dose by 25% until pruritus is minimal or eliminated. If the
initial decrease of 25% increases the
pruritus, then increase the maintenance dose by 25%. If the pruritus
decreases, continue to increase the
dose by 10% to 25% each time until
the pruritus is minimal or eliminated.
Be especially observant for side effects when increasing the dose.
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If a dog is worse at either the sixor 12-month recheck examination,
do not increase the allergen dose.
Check for any perpetuating factors
(e.g. pyoderma, yeast dermatitis) or
concurrent diseases (e.g. flea allergy
dermatitis, cutaneous adverse food
reactions, scabies, insect hypersensitivity). Once these factors have been
controlled, decrease the allergen
dose by 50%. If there is a decrease in
pruritus, decrease the dose by 50% at
each subsequent injection until the
pruritus is minimal or eliminated.
Symptomatic therapy
Based on limited controlled studies
and a large body of anecdotal evidence, symptomatic therapy may be
divided into three broad categories.
The first category includes drugs with
weak evidence of efficacy in treating
atopic dermatitis, including antihistamines, antidepressants, essential fatty
acids, and topical anti-inflammatory
therapy. These drugs are widely recommended, may be highly efficacious
in a few patients, and are mostly relatively safe and inexpensive. The next
category includes drugs with fair evidence of efficacy in treating atopic
dermatitis, including phosphodiesterase inhibitors and misoprostol.
The evidence for the efficacy of these
drugs is currently limited to a few
small studies. The final category includes drugs with good evidence of
efficacy in treating atopic dermatitis,
including glucocorticoids and cyclosporine. The evidence for the efficacy of these drugs is limited to a few
small studies. These treatments often
carry a higher risk for side effects, and
they may be expensive.
For dogs with limited seasonal disease or mild clinical signs or for dogs
early in the course of the disease, try
first-category drugs initially and then
second-category drugs, if necessary.
For dogs starting allergen-specific im-
munotherapy (before it has had any effect), try first- and second-category
drugs initially, and only use glucocorticoids sparingly if absolutely necessary.
For dogs with moderate to severe
disease or nonseasonal disease in
which allergen-specific immunotherapy is not being pursued or for dogs
that have not responded to allergenspecific immunotherapy, try first- and
second-category drugs first; but the
third category of drugs are often necessary. For crisis situations in which
pruritus is severe, try glucocorticoids
in short, aggressive, “crisis-busting”
doses (possibly in combination with
drugs in the first and second categories); apply Elizabethan collars; or
use T-shirts or bodysuits as barriers.
These recommendations vary in
each case according to response to
treatment; owners’ expectations,
compliance, and ability to treat their
dogs; cost considerations; and side
effects or adverse reactions.
First-category drugs
Few well-controlled studies demonstrate the efficacy of antihistamines
in treating atopic dermatitis, despite
their widespread use.37 Table 2 lists
some of the more commonly used
antihistamines. The response varies
from dog to dog and antihistamine to
antihistamine. Some dogs do not respond to any antihistamine, while a
minority have an excellent response.
Each antihistamine should be tried
for at least seven to 14 days. Side effects of antihistamine treatment include sedation, trembling, hyperesthesia, salivation, excitation, and
panting. Synergistic effects with glucocorticoids have been suggested,
potentially allowing for a decrease in
glucocorticoid requirement in some
dogs. 38 For this reason, in some
glucocorticoid-dependent patients I
use trimeprazine tartrate and prednisolone (Temaril-P—Pfizer; trimep-
SYMPOSIUM
Treating canine atopic dermatitis (cont’d)
TABLE 2
Antihistamines Commonly Used to Treat Canine Atopic Dermatitis
Antihistamine
Trade Name
Dosage
Hydroxyzine hydrochloride
Atarax (Pfizer), generics
2.2 mg/kg orally t.i.d.
Diphenhydramine
hydrochloride
Benadryl (Warner-Lambert),
generics
2.2 mg/kg orally t.i.d.
Clemastine fumarate
Tavist Allergy (Novartis
Consumer), generics
0.05–0.1 mg/kg
orally b.i.d.
Chlorpheniramine maleate
Chlortrimeton, generics
0.2–0.5 mg/kg
orally b.i.d. to t.i.d.
Cyproheptadine hydrochloride
Periactin (Merck), generics
0.3–2 mg/kg
orally b.i.d.
Promethazine hydrochloride
Phenergan (Wyeth-Ayerst),
generics
0.2–1 mg/kg orally
b.i.d. to t.i.d.
razine 5 mg, prednisolone 2 mg) at a
dosage of 1 tablet/10 kg (maximum
of three tablets) every 12 hours given
orally for seven days and then tapered to the lowest possible dose
every other day. Synergistic effects
with essential fatty acids have also
been suggested.39
Two antidepressants have been
used in dogs with atopic dermatitis.
Doxepin hydrochloride (0.5 to 2
mg/kg orally b.i.d.), a tricyclic antidepressant, may be helpful in some
dogs with atopic dermatitis because
of its potent antihistaminic effects, anticholinergic effects, and serotonin reuptake inhibition. Fluoxetine hydrochloride (1 mg/kg orally once a
day), a selective serotonin reuptake
inhibitor, has also been studied, with
contradictory results.40,41 Disadvantages of fluoxetine include side effects
(e.g. excitation, polydipsia, polyuria,
lethargy) and a three- to four-week
period until an effect is seen.
Two types of essential fatty acids
have been used to treat dogs with
atopic dermatitis. Omega-6 fatty acids
(most common in vegetable oils) are
potentially useful in correcting epidermal lipid barrier defects that are suspected to be present in dogs with
atopic dermatitis. Omega-3 fatty acids
(marine oils, flaxseed oils) are potentially useful in atopic dermatitis be220
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cause of their modulatory effects on
eicosanoid production and other immunomodulatory properties. Despite
more than 20 studies, the true efficacy
of essential fatty acids remains uncertain, as most studies are inadequately
designed and controlled.42 An omega3 fatty acid (eicosapentaenoic acid 40
mg/kg orally once a day)43 may be
best for anti-inflammatory effects.
Omega-6 fatty acids (60 to 138 mg/kg
orally once a day)42 may be best to
restore the epidermal lipid barrier if
dry skin is a prominent clinical sign.
Numerous topical anti-inflammatory
agents are available for use in dogs
with pruritic and inflammatory skin
disease, including corticosteroids
(e.g. hydrocortisone, fluocinolone
acetonide, triamcinolone acetonide,
dexamethasone, betamethasone), antihistamines (e.g. diphenhydramine
hydrochloride), local anesthetics (e.g.
pramoxine hydrochloride), colloidal
oatmeal, capsaicin, menthol, aloe vera,
moisturizing agents, and antimicrobial
agents (e.g. chlorhexidine, benzoyl
peroxide, ethyl lactate, miconazole,
ketoconazole). These are available in
various formulations, including shampoos, rinses, sprays, lotions, and leaveon conditioners. Their use is usually
limited to dogs with localized disease,
where owners can apply the product
on a regular (often daily) basis. These
products are usually used in conjunction with systemic treatment. I favor
leave-on conditioners with glucocorticoids or local anesthetics for localized
treatment of pruritic areas; antimicrobial shampoos in dogs with a history
of staphylococcal pyoderma or
Malassezia dermatitis; and, for routine
bathing, hypoallergenic moisturizing
shampoos to remove irritants and allergens. Long-term or excessive use of
topical corticosteroids may cause local
or systemic side effects of hypercortisolism, so carefully monitor their use.
Second-category drugs
Pentoxifylline (10 mg/kg orally
b.i.d.), a phosphodiesterase inhibitor
that inhibits proinflammatory cytokines (e.g. tumor necrosis factor-α,
interleukin-1, interleukin-6), was
found to significantly decrease pruritus and erythema in 10 dogs with
atopic dermatitis.44 No side effects
were reported. Arofylline, another
phosphodiesterase inhibitor, was
found to be as effective as prednisone in controlling pruritus in 40
dogs with atopic dermatitis,45 but
many dogs had gastrointestinal side
effects and were withdrawn from the
study. For this reason, arofylline is
currently not recommended.
Misoprostol is a synthetic prostaglandin E1 analogue with potent antiinflammatory properties. An initial
study with misoprostol (3 to 6 µg/kg
orally t.i.d.) on a small number of
dogs with atopic dermatitis reported
a decrease in pruritus of at least 50%
in 56% of the dogs and a similar decrease in skin lesions in 61% of the
dogs.46 A median decrease in pruritus
and lesions of 30% was reported in
another study.47
Third-category drugs
Despite widespread use (and misuse) of glucocorticoids, only a few
studies have evaluated their clinical
efficacy in treating canine atopic dermatitis. Prednisone given orally at 0.4
mg/kg once a day for seven days
gave a good to excellent response in
57% of dogs in one study,38 while
prednisolone given orally at a dose
of 0.5 mg/kg once a day for 30 days
produced a 69% reduction of lesion
scores and an 81% decrease in pruritus in another study of dogs with
atopic dermatitis.48 Long-acting injectable glucocorticoids are widely
used, but no studies have been conducted to critically assess their efficacy. Because of their high potency,
duration of effects, and propensity to
induce unacceptable side effects,
these long-acting injectable glucocorticoids are not recommended for
treating atopic dermatitis. Oral shortacting glucocorticoids, such as prednisone, are indicated for use as crisis
busters in cases of severe exacerbation and flare of pruritus (0.5 to 1
mg/kg once a day for three days) or
for longer-term control of chronic
atopic dermatitis that is not adequately controlled by alternative therapies (reducing doses to < 0.5 mg/kg
every other day).
Cyclosporine is a calcineurin inhibitor with potent antiallergic and
immunosuppressive properties.49 In
dogs with atopic dermatitis, improvements in clinical lesions and pruritus
similar to those achieved with oral
prednisolone have been achieved at
a dose of 5 mg/kg given orally once
a day.48 Treatment for a minimum of
30 days may be necessary before full
clinical effects are appreciated. Dogs
do not appear to be prone to the hepatotoxic and nephrotoxic side effects seen in people. Side effects that
may occur include vomiting, diarrhea, increased susceptibility to bacterial infections, increased incidence
of neoplasia, gingival hyperplasia,
and bone marrow suppression. Cyclosporine is metabolized by the PVeterinary Medicine
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450 enzyme system, so concurrent
use of drugs with effects on this enzyme system need to be considered
with caution. Currently, the cost of
cyclosporine is high.
Conclusion
Atopic dermatitis is a disease that is
controlled and rarely cured, so the
aim is to find a treatment that is efficacious and sustainable and that has
minimal side effects. Various trials and
combinations of treatments are usually
necessary before a combination of
treatments is found that is acceptable.
The clinical signs can be extremely
difficult to control in some dogs, and
referral to a dermatologist should be
presented to owners as an option.
Editors’ note: Dr. Hillier has participated and is now participating in collaborative research studies with Heska
Corporation.
REFERENCES
1. Norman, P.S.; Lichtenstein, L.M.: The clinical and immunologic specificity of immunotherapy. J. Allergy Clin. Immunol. 61
(6):370-377; 1978.
2. Anderson, R.K.; Sousa, C.A.: Workshop report 7: In vivo vs. in vitro testing for canine
atopy. Advances in Veterinary Dermatology,
Vol. II (P.J. Ihrke et al., eds.). Pergamon Press,
Tarrytown, N.Y., 1993; pp 425-427.
3. Codner, E.C.; Lessard, P.: Comparison of
intradermal allergy test and enzyme-linked immunosorbent assay in dogs with allergic skin
disease. JAVMA 202 (5):739-743; 1993.
4. Lian, T.M.; Halliwell, R.E.W.: Allergenspecific IgE and IgGd antibodies in atopic and
normal dogs. Vet. Immunol. Immunopathol.
66:203-223; 1998.
5. DeBoer, D.J.; Hillier, A.: The ACVD task
force on canine atopic dermatitis (XVI): Laboratory evaluation of dogs with atopic dermatitis
with serum-based “allergy” tests. Vet. Immunol. Immunopathol. 81:277-287; 2001.
6. Jeffers, J.G. et al.: Diagnostic testing of
dogs for food hypersensitivity. JAVMA 198
(2):245-250; 1991.
7. Mueller, R.; Tsohalis, J.: Evaluation of
serum allergen-specific IgE for the diagnosis of
food adverse reactions in dogs. Vet. Dermatol.
9:167-171; 1998.
8. Aeroallergens and aerobiology. Allergic
Skin Diseases of the Dog and Cat, 2nd Ed. (L.M.
Reedy et al., eds.). W.B. Saunders, Philadel222
MARCH 2002
Veterinary Medicine
phia, Pa., 1997; pp 50-82.
9. Barbet, J.L.; Halliwell, R.E.W.: Duration of
inhibition of immediate skin test reactivity by
hydroxyzine hydrochloride in dogs. JAVMA
194 (11):1565-1569; 1989.
10. Rivierre, C. et al.: Effects of a 1% hydrocortisone conditioner on the prevention of immediate and late-phase reactions in canine skin.
Vet. Rec. 147 (26):739-742; 2000.
11. Kunkle, G. et al.: Steroid effects on intradermal skin testing in sensitized dogs (abst.).
Proc. AAVD/ACVD, AAVD/ACVD, Charleston,
S.C., 1994; 54-55.
12. Macina, M.; Helton-Rhodes, K.: An investigation on the influence of corticosteroids on
antigen-specific IgE and total serum IgE in
dogs using ELISA allergy testing (abst.). Proc.
AAVD/ACVD, AAVD/ACVD, Santa Fe, N.M.,
1995; pp 32-33.
13. Miller, W.H. et al.: The influence of oral
corticosteroids or declining allergen exposure
on serologic allergy test results. Vet. Dermatol.
3:237-244; 1992.
14. Hillier, A.: IgE-mediated hypersensitivity to
Tyrophagus putrescentiae and Lepidoglyphus
destructor storage mites in dogs in the USA
(abst.). Vet. Dermatol. 12:239; 2001.
15. Vollset, I. et al.: Immediate type hypersensitivity in dogs induced by storage mites. Res.
Vet. Sci. 40 (1):123-127; 1986.
16. Sture, G.H. et al.: Canine atopic disease:
The prevalence of positive intradermal skin
tests at two sites in the north and south of
Great Britain. Vet. Immunol. Immunopathol.
44:293-308; 1995.
17. Saridomichelakis, M.N. et al.: Canine atopic
dermatitis in Greece: Clinical observations and
the prevalence of positive intradermal test reactions in 91 spontaneous cases. Vet. Immunol. Immunopathol. 69 (1):61-73; 1999.
18. Noli, C.; Hillier, A.: House dust mites and
allergy. Advances in Veterinary Dermatology,
Vol. IV (K. Thoday et al., eds.). Butterworth
Heinemann, Oxford, U.K. (in press).
19. Platts-Mills, T.A.E. et al.: The role of intervention in established allergy: Avoidance of indoor allergens in the treatment of chronic allergic disease. J. Allergy Clin. Immunol. 106
(5):787-804; 2000.
20. Griffin, C.E.; Hillier, A.: The ACVD task
force on canine atopic dermatitis (XXIV):
Allergen-specific immunotherapy. Vet. Immunol. Immunopathol. 81:363-383; 2001.
21. Halliwell, R.E.W.: Atopic disease in the
dog. Vet. Rec. 89 (8):209-214; 1971.
22. Halliwell, R.E.W.: Hyposensitization in the
treatment of atopic disease. Current Veterinary
Therapy VI Small Animal Practice (R.W. Kirk,
ed.). W.B. Saunders, Philadelphia, Pa., 1977;
pp 537-541.
23. Nesbitt, G.H.: Canine allergic inhalant dermatitis: A review of 230 cases. JAAHA 172:5560; 1978.
24. Reedy, L.M.: Canine atopy. Compend.
Cont. Ed. 1:550-556; 1979.
25. Scott, D.W.: Observations on canine atopy.
JAAHA 17:91-100; 1981.
26. Scott, K.V. et al.: A retrospective study of
hyposensitization in atopic dogs in a flea-scarce
environment. Advances in Veterinary Dermatology, Vol. II (P.J. Ihrke et al., eds.). Pergamon
Press, Tarrytown, N.Y., 1993; pp 79-87.
27. Sousa, C.A.; Norton, A.L.: Advances in
methodology for diagnosis of allergic skin disease. Vet. Clin. North Am. (Small Anim. Pract.)
20 (6):1419-1427; 1990.
28. Miller, W.H. et al.: Evaluation of the performance of a serologic allergy system in atopic
dogs. JAAHA 29:545-550; 1993.
29. Mueller, R.S.; Bettenay, S.V.: Long-term immunotherapy of 146 dogs with atopic dermatitis—A retrospective study. Aust. Vet. Pract.
26:128-132; 1996.
30. Schwartzman, R.M.; Mathis, L.: Immunotherapy for canine atopic dermatitis: Efficacy in 125
atopic dogs with vaccine formulation based on
ELISA allergy testing. J. Vet. Allergy Clin. Immunol. 5:144-152; 1997.
31. Nuttall, T.J. et al.: Retrospective survey of
allergen immunotherapy in canine atopy. Vet.
Rec. 143 (5):139-142; 1998.
32. Rosser, E.J.: Aqueous hyposensitization in
the treatment of canine atopic dermatitis: A retrospective study of 100 cases. Advances in Veterinary Dermatology, Vol. III (K.W. Kwochka
et al., eds.). Butterworth Heinemann, Boston,
Mass., 1998; pp 169-176.
33. Park, S. et al.: Comparison of response to
immunotherapy by intradermal skin test and
antigen-specific IgE in canine atopy. J. Vet.
Med. Sci. 62 (9):983-988; 2000.
34. Willemse, A. et al.: Effect of hyposensitization on atopic dermatitis in dogs. JAVMA 184
(10):1277-1280; 1984.
35. Griffin, C.E.: Hyposensitization. Calif. Vet.
52:18-21; 1998.
36. Power, H.T.: Why do owners discontinue
immunotherapy? (abst.) Vet. Dermatol. 11
(suppl. 1):14; 2000.
37. DeBoer, D.J.; Griffin, C.E.: The ACVD task
force on canine atopic dermatitis (XXI): Antihistamine pharmacotherapy. Vet. Immunol.
Immunopathol. 81:323-329; 2001.
38. Paradis, M. et al.: Further investigations on
the use of nonsteroidal and steroidal antiinflammatory agents in the management of canine pruritus. JAAHA 27:44-48; 1991.
39. Paradis, M. et al.: The efficacy of clemastine (Tavist), a fatty acid-containing product
(Derm Caps), and the combination of both
products in the management of canine pruritus. Vet. Dermatol. 2:17-20; 1991.
40. Shoulberg, N.: The efficacy of Prozac (fluoxetine) in the treatment of acral lick granulomas and allergic inhalant dermatitis in canines
(abst.). Proc. AAVD/ACVD, AAVD/ACVD, San
Francisco, Calif., 1990; pp 31-32.
41. Melman, S.A.: Prozac (fluoxetine), Zoloft
(sertraline) and Anafranil (clomipramine) use
in animals for selected dermatological and behavioral conditions (abst). Proc. AAVD/ACVD,
AAVD/ACVD, Santa Fe, N.M., 1995; p 82.
42. Olivry, T. et al.: The ACVD task force on
canine atopic dermatitis (XXIII): Are essential
SYMPOSIUM
Treating canine atopic dermatitis (cont’d)
fatty acids effective? Vet. Immunol. Immunopathol. 81:347-362; 2001.
43. Logas, D.; Kunkle, G.A.: Double-blinded
crossover study with marine oil supplementation containing high-dose eicosapentaenoic
acid for the treatment of canine pruritic skin
disease. Vet. Dermatol. 5:99-104; 1994.
44. Marsella, R.; Nicklin, C.F.: Double-blinded
placebo-controlled crossover study on the effects of pentoxifylline in canine atopy. Vet.
Dermatol. 11:255-260; 2000.
45. Ferrer, L. et al.: Clinical anti-inflammatory
efficacy of arofylline, a new selective
phosphodiesterase-4 inhibitor, in dogs with
atopic dermatitis. Vet. Rec. 145 (7):191-194;
1999.
46. Olivry, T. et al.: Treatment of atopic dermatitis with misoprostol, a prostaglandin E-1
analogue—An open study. J. Dermatol. Treat.
8:243-247; 1997.
47. Olivry, T. et al.: A placebo-controlled,
blinded trial of misoprostol therapy for canine
atopic dermatitis: Effects on dermal cellularity
and cutaneous tumor necrosis factor-alpha gene
transcription (abst.). Vet. Dermatol. 11:21; 2000.
48. Olivry, T. et al.: Cyclosporin-A decreases
skin lesions and pruritus in dogs with atopic
dermatitis: A prednisolone-controlled blinded
trial (abst.). Vet. Dermatol. 11:19; 2000.
49. Gregory, C.L.: Immunosuppressive agents.
Current Veterinary Therapy XIII Small Animal
Practice ( J.D. Bonagura, ed.). W.B. Saunders,
Philadelphia, Pa., 2000; pp 509-513.
has been proven superior to the other.
2. Which statement is true of positive allergy test results?
a. They are only seen in dogs with clinical
allergy.
b. They indicate clinical or subclinical
hypersensitivity.
c. They are never seen in dogs with nonallergic skin disease.
d. They are never seen in healthy, normal
dogs.
e. None of the above
3. Which of these statements is true?
a. Tree pollen hypersensitivity is associated with fall allergies.
b. Grass pollen hypersensitivity is associated with winter allergies.
c. Weed pollen hypersensitivity is associated with spring allergies.
d. Outdoor mold hypersensitivity is associated with spring allergies.
e. Cockroach hypersensitivity is associated with nonseasonal allergies.
Article #2
4. Which of the following may be the
cause of negative allergy test results in a
dog with atopic dermatitis?
a. Serum testing was done during the
peak of the allergy season.
b.Concurrent scabies suppressed intradermal test reactions.
c. Important allergens were absent from
the allergen test panel.
d. Antihistamine interference affected the
serum allergy test results.
e. Skin testing was performed shortly after
the peak of the allergy season.
1. Which statement regarding allergy tests
is true?
a. Intradermal tests are superior to serologic tests.
b. Serologic tests are superior to intradermal tests.
c. Correlation between serologic and intradermal test results is close to 100%.
d. Correlation between serologic and intradermal test results is very poor.
e. Neither intradermal nor serologic testing
5. Which statement is true of allergenspecific immunotherapy?
a. It is ineffective in dogs with disease of
more than five years’ duration.
b. Specific protocols have been studied
and defined.
c. Response to treatment is seen within
three months.
d. Efficacy has not been established in
randomized controlled studies.
CE Q UESTIONS 2 CE hours
You can earn two hours of Continuing Education credit from Kansas
State University by answering the following questions on treating canine
atopic dermatitis. Circle only the best
answer for each question, and transfer your answers to the form on page
241.
224
MARCH 2002
Veterinary Medicine
e. If effective, it can be discontinued after
one year.
6. The most common side effect(s) from
allergen-specific immunotherapy is (are):
a. Anaphylaxis and collapse
b. Severe local swelling, skin necrosis,
and ulceration
c. Increased incidence of secondary
infections
d. Generalized angioedema
e. Increased pruritus
7. Which of these drugs has the weakest
evidence for efficacy in treating atopic
dermatitis?
a. Doxepin
b. Prednisone
c. Cyclosporine
d. Misoprostol
e. Pentoxifylline
8. Which therapy is indicated for the initial
treatment of a dog with mild seasonal
atopic dermatitis of three months’ duration?
a. Essential fatty acids and antihistamines
b. Cyclosporine
c. Injectable depot glucocorticoids
d. Allergen-specific immunotherapy
e. Misoprostol and prednisone
9. Which drug combination is thought to
work synergistically in atopic dermatitis?
a. Antihistamines and prednisone
b. Pentoxifylline and misoprostol
c. Fatty acids and topical antipruritics
d. Cyclosporine and antihistamines
e. Fatty acids and pentoxifylline
10. Disadvantages of cyclosporine use in
dogs include:
a. Frequent nephrotoxicity
b. Expense
c. Multiple doses per day
d. Frequent hepatotoxicity
e. Availability only in tablet formulation