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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-

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).

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.

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).

Vol 18 No 1 / / 2008 / / Veterinary Focus / / 35

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).

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

36 / / Veterinary Focus / / Vol 18 No 1 / / 2008

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