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Management of
atopic dermatitis
exacerbations. Recurrent exacerbations affect
quality of life, necessitate more aggressive
therapy and are more likely to lead to chronic
dermatitis.
2. Mild, superficial infections can be managed
with anti-inflammatory therapy. Reduction
of inflammation is associated with reduced
microbial adherence and infection.
Tim Nuttall, BSc, BVSc, CertVD,
PhD, CBiol, MIBiol, MRCVS
Small Animal Teaching Hospital,
The University of Liverpool, Leahurst,
Cheshire, UK
Dr. Nuttall graduated from the University of
Bristol in 1992. After three years in general
practice he joined the University of Edinburgh,
where he gained the RCVS CertVD and a PhD in
canine atopic dermatitis. Dr. Nuttall joined the
University of Liverpool in 2001 and is currently
Senior Lecturer in Veterinary Dermatology.
The dermatology clinic at the University of
Liverpool has an active research program in
atopic dermatitis and microbial infections.
Diagnosis of atopic dermatitis
- History
–
a chronic, relapsing, usually steroid
responsive dermatitis. Most cases start between
six months and three years of age.
- Clinical signs
–
pruritus and diffuse erythema
affecting the ears, muzzle, eyes, flexor surfaces,
feet and ventral body. Recurrent
Malassezia
and bacterial infections are common. Chronic
lesions include alopecia, lichenification and
hyperpigmentation.
- Hair plucks, tape-strips, skin scrapes, trial
therapy and/or
Sarcoptes
serology to exclude
ectoparasites.
- No response to a six week food trial using a
commercial or home-cooked novel protein, or a
hydrolyzed hypoallergenic diet.
- Allergy tests are not required for a diagnosis.
10-20% of clinically atopic dogs will have
negative intradermal and serological tests. This
has recently been termed atopic-like dermatitis.
A
topic dermatitis (AD) is a multifactorial
disease involving allergies, cutaneous
barrier defects, microbial infections and
other flare factors. Best results are obtained
by using more than one therapeutic approach.
Treatment, however, should be tailored to
individual clinical problems, temperament,
finances etc. The owners must appreciate that
treatment is likely to be lifelong, and it is
therefore important to confirm the diagnosis
(see below). Two theories on long term therapy
have recently become accepted:
Flare factors
Ectoparasites
Fleas and
Neotrombicula
frequently complicate
AD. Atopic dogs can also contract
Sarcoptes
.
Demodicosis may be associated with immuno-
suppression particularly iatrogenic hyperadreno-
corticism.
Microbial infections
Secondary infections should be identified and
treated promptly. Topical therapy can reduce
1. Treatment should keep an animal in remission
and not be used intermittently to manage
32 / / Veterinary Focus / / Vol 18 No 1 / / 2008
microbial populations and recurrence of infections.
Immunosuppression may result in infections
but control of inflammation usually reduces
colonization and infection with
Malassezia
and staphylococci. Dogs that are very prone to
pyoderma, however, can benefit from long term
pulse antibiotic therapy.
Colloidal oatmeal may also have a direct anti-
pruritic action. Virbac’s Allermyl
®
range contains
linoleic acid (improves the skin lipid barrier),
vitamin E and mono-oligosaccharides (may reduce
TNF-
α
production and prevent microbial adherence)
and piroctone olamine (modulates the skin flora).
Chitosanides and microspherulites help prolong
retention and activity on the skin and coat. Other
topical products that may be helpful in individual
cases include ear cleaners and anti-microbial or
anti-scaling shampoos. The exact balance of
desired effects varies between individuals, so be
prepared to try different products and/or alternate
between antimicrobial and emollient shampoos.
Stress
Stress can exacerbate human inflammatory dermat-
oses, and this may be true in animals. There is
anecdotal evidence that behavioral therapy and
pheromones can help.
Environmental effects
Excesses of temperature and humidity, irritant
surfaces or cleaning solutions etc. can all worsen
skin diseases. Observant owners will often report
associations.
Essential fatty acids (EFA)
Numerous clinical trials and studies have evaluated
EFAs particularly the n-3 EFA eicosapentenoic acid
(EPA) and the n-6 EFA gamma-linolenic acid (GLA).
Supplementation can result in altered plasma levels
and incorporation into cell membranes, which may
lead to production of less inflammatory leucotrienes
and prostaglandins and improved cutaneous lipid
barrier. Recent studies, however, have not found
consistent changes in plasma, subcutaneous fat or
cutaneous EFAs following supplementation in atopic
and healthy dogs, and no correlation with the
clinical response (1-3).
Improving skin barrier function
Diet and the skin
Many atopic animals non-specifically improve
following food trials, probably because high quality,
essential fatty acid (EFA) enriched, single-protein
sensitivity control and hydrolyzed hypoallergenic
diets affect the skin barrier and/or skin immune
system. Nutrients believed to be important include:
•Zinc
–
decreases inflammation.
•Long chain omega (n-3) EFAs
–
alter eicosanoids
and decrease inflammation.
•Inositol, choline, histidine, pantothenate,
nicotinamide
–
improve epidermal lipid barrier
formation.
•Aloe vera and curcumin
–
up regulate fibroblasts,
proteoglycan synthesis and TGF-
Clinical results have been variable in controlled
trials, and no relationship between efficacy and
ratio of n-3/n-6 EFAs have been proven, although
high doses seem to be more effective. Recent
studies have shown that high quality, EFA enriched
diets are beneficial in canine AD although how
much of this is due to anti-inflammatory activity
or cutaneous barrier improvements is unclear (4).
β
production,
and decrease inflammation.
Allergen specific therapy
Allergen specific therapy will only be appropriate
in animals with identified sensitivities. The aim of
allergen testing is to identify allergens for avoidance
and immunotherapy, not to confirm the diagnosis.
In the author’s opinion, unpublished data from
randomized cross-over studies have shown that
Eukanuba Dermatosis FP and Royal Canin Skin
Support diets significantly ameliorated clinical
signs in atopic dogs.
Allergen avoidance
Allergen avoidance measures can result in a signific-
ant reduction in exposure to house dust mite (5).
Whether allergen avoidance results in clinically
significant improvement is controversial, although
one uncontrolled study demonstrated that allergen
avoidance was beneficial in canine AD (6).
Topical therapy
Topical therapy has a number of benefits although
it is time-consuming. Physical removal of allergens
is likely to be helpful. Hydration can be prolonged
by using moisturizing shampoos and conditioners.
These can also improve the skin lipid barrier.
Vol 18 No 1 / / 2008 / / Veterinary Focus / / 33
Allergen specific immunotherapy (ASIT)
ASIT involves the administration of gradually
increasing amounts of allergen by subcutaneous
injection. The mechanism of action is unknown
but it is thought that administering large doses
of allergen in an unusual route (
i.e.
subcutaneous
instead of epidermal) induces tolerance. Many
studies (albeit mostly open or retrospective)
have shown that 60-80% of dogs have a greater
than 50% improvement following ASIT. The
best results seem to occur with early treatment,
although a 9-12 month trial is necessary to assess
the response in each case. Animals on ASIT
require careful supervision to control microbial
No adverse effects were seen in either case
although the dogs were pre-medicated with
an anti-histamine.
Alum precipitated vaccines have a depot effect
and require less frequent administration. Alum
adjuvants potentiate IgE responses in experimental
animals but no differences in efficacy between
alum-precipitated and aqueous vaccines have been
demonstrated in dogs. There are anecdotal reports
of improved efficacy with low dose ASIT, but a
controlled study, however, found no difference in
efficacy between low dose and conventional
alum-precipitated ASIT (8).
If ASIT proves successful, the interval between
injections can be extended. Increased pruritus
before the next injection is due indicates that the
interval is too long. The interval may also vary
through the year, especially in pollen sensitive
animals. Some dogs can be weaned off treatment,
but most require maintenance injections every
1-2 months.
Re-testing may reveal new sensitivities in dogs
with initially negative tests, dogs <12 months
old at the time of the original test, if there has
been a poor response to ASIT or where a good
response is not maintained. Re-formulating ASIT
can be beneficial in these dogs.
Adverse effects are uncommon. Injection site
reactions and anaphylactic shock are very rare,
although many dermatologists advise giving the
first 5-6 doses in a veterinary clinic. Increased
pruritus after an injection indicates that the dose is
too high although mild reactions can sometimes be
managed with antihistamines.
Figure 1.
A rare case of angio-edema following allergen specific
immunotherapy in an atopic Boxer.
infections and other flare factors, to administer
anti-inflammatory treatment as required and to
adjust the dose and/or frequency according
to the clinical response
(Figure 1)
.
Anti-inflammatory therapy
Anti-inflammatory therapy is used as required
to control residual pruritus and inflammation.
Almost all atopics will require treatment in the
short to medium term, but the dose, frequency
and/or potency of drugs can be reduced if other
treatments are successful in the long term.
The exact protocol varies widely but usually
involves repeated injections a few days to 1-2
weeks apart. Once the full dose is reached, the
interval between injections can be extended.
A rush protocol, where the initial loading course
is given within a single day, was recently shown
to be as effective as conventional ASIT in a small
number of dogs (7). Recent reports also described
starting with a full dose (monodose therapy).
Cyclosporine
Cyclosporine suppresses T-cells, which have been
implicated in the pathogenesis of canine AD.
It also inhibits other key cells in allergic
34 / / Veterinary Focus / / Vol 18 No 1 / / 2008
MANAGEMENT OF ATOPIC DERMATITIS
Figure 2a and 2b.
A severely atopic
German Shepherd
Dog before (a) and
after (b) treatment
with cyclosporine.
a
b
inflammatory reactions such as mast cells and
eosinophils. This has profound effects on antigen
presentation, IgE production, mononuclear cell
activity and the development of inflammatory
lesions, although at the doses used in canine AD,
cyclosporine is immuno-modulating rather than
immunosuppressive
(Figure 2)
.
daily dosing, one third every other day and one
third twice weekly to maintain remission.
Using cyclosporine as part of an integrated
management program can be more cost-effective
than relying on it alone.
The effect on intradermal testing and serology is
thought to be minimal, although the data is sparse.
Anecdotal data suggests that cyclosporine does
not affect the response to ASIT any more than
glucocorticoids although controlled studies have
not yet been performed.
Cyclosporine is rapidly absorbed and distributed.
Bioavailability varies from 15-60% in individual
dogs and is not affected by food. There is little
correlation between trough levels and efficacy, and
dose adjustments are made according to the clinical
response rather than monitoring plasma levels.
Metabolism is via the cytochrome P450 system.
Numerous drugs can decrease metabolism, notably
itraconazole and ketoconazole, which increases
plasma concentrations, efficacy and the likelihood of
adverse effects
(Figure 3)
. Phenobarbital increases
metabolism and decreases plasma levels.
Cyclosporine is well tolerated by the majority of dogs.
Transient anorexia and vomiting are the most likely
problems. Persistent vomiting is uncommon but
may be eased by administering with food, and/or by
using the gastrointestinal protectant sucralfate
or H-2 blocking agents such as ranitidine. Other
uncommon adverse effects include hirsuitism,
increased shedding of hair and transient alopecia,
gingival hyperplasia, papillomatosis, diarrhea,
lameness and muscle tremors, and erythema
and edema of the ears. These are largely dose-
dependent and reversible. The nephropathy,
hepatopathy and hypertension seen in humans
have not been recognized in dogs except at doses
>20 mg/kg.
Cyclosporine is administered for canine AD at a
dose of 5 mg/kg once daily. Controlled studies
have shown that it is at least as effective as
prednisolone and methyl-prednisolone (9,10),
although this may take 2-3 weeks to become
apparent. Glucocorticoids can be initially co-
administered to achieve more rapid remission.
Approximately one third of treated dogs require
Figure 3a and 3b.
Adverse effects of
cyclosporine: hirsutism
(a) and gingival
hyperplasia (b).
a
b
Vol 18 No 1 / / 2008 / / Veterinary Focus / / 35
b
weeks either side of vaccination, although this
will lead to worsening of the skin condition. The
pros and cons for each individual case should
be discussed with the owner.
Tacrolimus
Tacrolimus has a similar mechanism of action to
cyclosporine. A 0.1% tacrolimus ointment lead
to a greater than 50% improvement in 70-75% of
atopic dogs with localized lesions in two trials
(12,13). Plasma levels remained low throughout
and no adverse effects apart from minor self
trauma immediately after application were seen.
Phytopica™
Phytopica™, a compound derived from
Rehmannia
glutinosa, Paeonia lactiflora
and
Glycyrrhiza
uralensis
improved canine AD in a preliminary
study (14). In a recent randomized, double-blind
and placebo-controlled trial of 120 dogs Phytopica™
(200 mg/kg/day) appeared to be an efficacious,
safe and palatable non-steroidal treatment for
canine AD, although the effect was modest with
most dogs achieving a 20-50% improvement in
clinical signs (15). Responses are typically evident
within four weeks
(Figure 4)
. Adverse effects are
self-limiting gastro-intestinal disturbances such as
diarrhea and vomiting. This is generally a better
safety profile than has been reported for other
anti-inflammatory therapies (16).
a
Figure 4a and 4b.
An atopic West Highland White Terrier
before (a) and after (b) treatment with Phytopica™.
Immunosuppression is a potential concern.
Inhibition of cell-mediated immunity in particular
could result in bacterial and protozoal infections,
dermatophytosis and demodicosis. In practice,
however, the risk appears to be very small and most
atopic dogs experience fewer secondary infections
following treatment. Feline and human patients on
long term treatment have a small risk of developing
lymphoma and cutaneous neoplasms. Lympho-
plasmatoid dermatitis has been seen following
doses >20 mg/kg and there is a single case report
of lymphoma in an older dog following treatment
for anal furunculosis. These have, however, not
been reported in atopic dogs (11). Inhibition of
T-helper cell function and
Glucocorticoids
Corticosteroids, synthesized in the adrenal cortex,
have glucocorticoid (anti-inflammatory and
gluconeogenic) and mineralocorticoid (salt
and water balance) activity. Glucocorticoids are
simultaneously the most used and abused drugs
-cell activation could
affect the response to vaccination. Some authors
advocate withdrawing treatment for up to two
β
36 / / Veterinary Focus / / Vol 18 No 1 / / 2008
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