Atopic Dermatitis

Introduction

Chronic allergic otitis in the dog. Source: Wikimedia Commons; Author: Caroldermoid (2006)

Atopic dermatitis is a heritable disorder in which animals are hypersenstive to common environmental allergens. It is one of the most common skin diseases of dogs worldwide.

The most common allergens involved in atopic dermatitis are those of house dust mites (Dermatophagoides farinae) and grain mites. Human and animal danders, house dust, grass and tree pollen and moulds also frequently incite reactions. Susceptible animals produce allergen-specific IgE to these normally-innocuous allergens, which then binds to receptors on cutaneous mast cells. Atopic animals may have defects in the epidermis, leading to impaired barrier function, and it is thought that further allergen exposure occurs via percutaneous absorption. This further exposure gives mast cell degranluation, releasing histamine, cytokines, chemokines, leukotrienes, prostaglandins and other chemical mediators. This is a type 1 (immediate) hypersensitivity reaction¹, and leads to vasodilation, inflammatory cell infiltration and pruritus. It appears that the cytokines involved are abnormally biased towards a Th2 response. IL-4 in particular is produced; this cytokine is responsible for B-cell production of IgE. Bacterial superantigens and autoantigens released due to keratinocyte damage play a role in perpetuating inflammation.

Signalment

Atopic dermatitis is a disease of dogs, although it can occur sporadically in the cat¹. The typical age of onset of atopic dermatitis is between 6 months and 3 years of age and signs are hardly ever seen in animals under 6 months of age. Signs may be so mild at first that they are not noted, but usually progress to become clinically apparent¹. Atopy is heritable and so breed predispositions occur. Susceptible breeds include the : Beauceron, Boston Terrier, Boxer, Cairn Terrier, Cocker Spaniel, Dalmation, English Bulldog, English Setter, Fox Terrier, Sealyham Terrier, Setters, Shar-Pei, West Highland White Terrier, Wire Haired Fox Terrier, and Yorkshire Terrier². Certain breeds such as the Cocker Spaniel, Dachshund, Doberman Pinscher, German Shepherd, German Short-Haired Pointer and Poodle appear to have a decreased risk of atopy. There is no sex predilection.

Diagnosis

The diagnosis of atopic dermatitis is based on the signalment, a thorough history and appropriate physical examination findings. Other causes of pruritus must also be ruled out. The differential diagnoses are¹:

• Food allergy: ruled out by a dietary exclusion trial.
• Flea allergy dermatitis: ruled out observing response to ectoparasiticides.
• Contact dermatitis: ruled out by confining animal to one area covered in e.g. newspaper.
• Scabies:ruled out observing response to ectoparasiticides.

Intradermal and serologic allergy testing are available but are not used to make a diagnosis of atopy. Their purpose is to identify the specific offending allergens in an animal in order that immunotherapy may be pursued. The results of allergy testing are only significant if the history and clinical signs are also suggestive of atopic dermatitis.

Clinical Signs

Signs are often, but not always, seasonal. Pruritus is the hallmark of atopic dermatitis and may be the only complaint. This gives rise to self-trauma, causing lesions. Lesions commonly include alopecia, erythema, scaling, crusting, excoriations and salivary staining. Macular-papular eruptions are occasionally seen². With time, lichenification, and hyperpigmentation develops. Because the route of allergen contact is thought to be percutaneous absorption^{1, 2}, it follows that hairless regions are most frequently affected: the face, ears, axillae, feet and inguinal regions are predilection sites. Secondary infections such as superficial staphylococcal pyoderma and Malassezia are common, and otitis externa often occurs concurrently^{2, 3, 4}. A small number of cases exhibit only chronic or recurrent otitis externa. Another uncommon presentation is allergic rhinitis, manifesting as sneezing, nasal discharge or allergic conjunctivitis^{1, 2}.

Signs commonly seen in different species are:

Dogs - face rubbing and foot licking; secondary pyoderma or seborrhea

Cats - facial, ear or generalised pruritus, miliary dermatitis, eosinophilic granuloma complex, symmetric alopecia

Horses - pruritic hea, pinnae, ventrum, legs, tailhead or recurrent urticaria

Laboratory Tests

Routine haematology and biochemistry rarely show any abnormalities in dogs, but eosinophilia is often seen in cats¹. The measurement of total serum IgE levels is not useful in the diagnosis of atopic dermatitis as IgE levels do not significantly differ between atopic and normal animals². IgE levels are also influenced by the presence of parasites, vaccinations and breed, and so this test is not reliable.

Allergen-specific IgE tests are only useful when a diagnosis of atopic dermatitis has already been reached by consideration of history and clinical exam, and by ruling out other causes of pruritus. The test is used to identify allergens for immunotherapy by evaluating serum levels of IgE specific for a variety allergens. The exact technique varies between laboratories, but the principle is the same: serum is allowed to react with the allergen before excess serum and antibodies are rinsed away. An IgE-specific reagent linked to an indicator is added, and the amount that binds is proportional to the amount of allergen-specific IgE². This can then be quantified. Several factors can adversely influence the test results. These include age, season, use of corticosteroids and laboratory inaccuracies.

Other Tests

Intradermal skin tests determine the ability of allergens injected intradermally to cause mast cell degranulation leading to a subsequent wheal and flare reaction. It is therefore a close approximation of the pathogenesis of atopic dermatitis, and is a useful tests for revealing specific allergens for use in immunotherapy. Aqueous allergens are used for testing and include such things as house dust mites, pollens, moulds, insects and epidermal antigens. These should be stored in the fridge to maintain potency, and allowed to reach room temperature before testing². Test results can be affected or inhibited by numerous factors such as medications, sedatives and stress. Drugs shown to affect intradermal skin testing include antihistamines, tricyclic antidepressants and glucocorticoids. Withdrawal times of 2, 4 and 6 weeks have been suggested for topical, oral and long-acting injectable steroids respectively³, although this may be difficult in a very pruritic animal. Some animals require sedation for intradermal skin testing and xylazine and medetomidine have been shown not to affect results. Diazepam and acepromzine should not be used².

Fine needles are used to inject allergen intradermally. Histamine is used as a positive control, and isotonic saline as a negative. Approximately 0.05-1.0 ml solution is injected at each site, and after around 15 minues the test is read by scoring each allergen based on the size of the bleb.

Biopsy

Biopsies may help rule out other differential diagnoses, but do not show any pathognomic changes for atopic dermatitis¹.

Pathology

Gross findings reflect the lesions seen in life and lesions are generally due to self-trauma.

Histological changes are non-specific but include acanthosis, a mixed mononuclear perivascular dermatitis, sebaceous gland metaplasia and secondary superficial pyoderma¹.

Other microscopical findings include: hyperplastic superficial perivascular dermatitis, mast cells, eosinophils and nonmetachromatic mononuclear cells. Perivascular inflammation may be involved especially in horses.

Treatment

Several factors exist that in normal dogs may by insufficient to cause pruritus. However, when these occur at the same time as allergen exposure in atopic dogs, there can be an additive effect that breaks the threshold for pruritus. These "flare factors" include ectoparasites, microbial infections, stress and environmental effects. When treating for atopic dermatitis it is therefore critical to keep these factors to a minimum. Atopic dogs should be regularly treated with an ectoparasiticide against fleas and mites, and secondary bacterial or Malassezia infections should be identified and treated promptly. Stress should be avoided and products that may be irritant, such as cleaning materials, should not be used in the environment. This requires a certain amount of vigilance on the part of the owners.

Improving Cutaneous Barrier Function

In normal animals, the skin has an important barrier function. The integrity of the epithelium may be impaired in atopic animals, facilitating further exposure to allergens. Finding ways to help improve the barrier function of the epidermis can contribute towards the effective management of atopy. Food trials are often used during the course of a work-up for atopic dermatitis to eliminate food allergy as a cause of pruritus. Many atopic animals non-specifically improve during food trials on prescription hypoallergenic diets, which may be attributable to several of their components. The inclusion of zinc and long-chain omega essential fatty acids is thought to reduce inflammation, and substances such as inositol, choline, histidine, pantothenate and nicotinamide may help improve epidermal lipid barrier³. The use of topical shampoos and emollients can also be beneficial. As well as physically removing allergens from the skin and coat, moisturising shampoos can hydrate the skin and improve the lipid barrier. Colloidal oatmeal may also have a direct antipruritic action³. Anti-microbial or anti-scaling shampoos, and ear cleaners can prove useful in certain cases depending on presentation. The effects of essential fatty acids in atopic dermatitis have been subjected to numerous clinical trials. EFA supplementation alters incorporation into cell membranes, which may reduce production of pro-inflammatory leukotrienes and prostaglandins³. The cutaneous lipid barrier may also be improved. However, there is some conflicting informtation, and high levels of supplementation may be neccessary to give beneficial effects.

Allergen Specific Therapy

In animals with demonstrated sensitivities to specific allergens, allergen-specific therapy can form part of the treatment regimen for atopic dermatitis. It may be possible to limit exposure to certain allergens. For example, exposure to house dust mites can be limited by keeping animals out of the bedroom and using hypoallergenic mattresses and pillow covers. Filtered vacuum cleaners can be used, and animals should be kept out of rooms for two to three hours after vacuuming. Soft toys harbour many dust mites and so should be avoided, or frozen for 24 hours once a month to keep the burden low. The animal's bedding should be washed at a temperature of greater than 70°C and the bed wiped out regularly with a damp cloth. Environmental flea control products are effective at killing dust mites in the home. If the animal is allergic to pollens, walking routes can be altered to avoid contact with the specific source, be it grasses, trees or weeds. Dogs can be washed after walking through vegetation to remove allergens, and lawns can be mown short.

Allergen specific immunotherapy (ASIT) can also be implemented. This involves the subcutaneous injection of gradually increasing quantities of allergen. The mechanism of action is not fully understood but it seems that administering large doses of allergen in an unusual route results in tolerance³. This may be because IgG level increase during the first few months of hyposensitization and binds circulating allergens, thereby blocking them from causing mast cell degranulation⁴ The effects of ASIT are highly variable: around 25% of dogs can be controlled with immunotherapy alone, a further 50% show some improvement, and 25% are non-responsive. Effects can take some time to be appreciated, and so a 9 to 12 month trial of immunotherapy is recommended. Generally, injections are initially given 1-2 weeks apart, building up to the full dose. Animals are usually monitored for around 30mins after the first few treatments, because anaphylaxis is an uncommon side-effect. Once the full dose is reached, the interval between injections can be extended to roughly once monthly. Most animals require ongoing treatment at this interval to maintain the effects of ASIT, but a few animals can be gradually weaned off ASIT.

Anti-inflammatory therapy

In most cases, anti-inflammatory drugs are required in addition to topical treatments and allergen-specific therapy to control residual pruritus and inflammation. The dose and treatment regime should be adapted according to how successful other treatments are, the response to treatment and the presence of allergen in the environment (for example, pollen is present in the summer but not the winter). The aim should be to use the minimum dose that gives effective control of pruritus.

Glucocorticoids the most commonly used anti-inflammatory drugs in veterinary dermatology. Although they are cheap and efficacious, they are associated with many undesirable side effects. They should therefore be used with caution in atopic dermatitis. Drugs such as prednisolone or methyl-prednisolone can be used in the initial stages of treatment to break the itch-scratch cycle while animals begin to respond to other forms of control. They may also be used to manage seasonal atopy for a few months of the year. Short courses that gradually taper off can be implemented in flare-ups, or corticosteroids can be used as a very last resort in pets non-responsive to other forms of treatment. Topical steroids may be used where inflammation is localised to small areas of relatively hairless skin, or to control pyotraumatic dermatitis. In most cases, lesions are more widespread and so systemic administration is necessary. A dose should be established that induces remission, and this should be gradually tapered to the minimal effective dose, for example alternate day treatment. "Depot" injections of corticosteroids do not permit this flexibility in dosing, and should not be used. Glucocorticoids will suppress reactions to intradermal allergen tests and allergen-specific serology. However, the drugs are not thought to hamper the efficacy of vaccines.

Cyclosporine is an immunosuppressive drug that acts by suppressing T-cells, as well as mast cells and eosinophils. The doses used in atopy are immuno-modulating, and suppression of these cells impairs antigen presentation, IgE production and the development of inflammatory lesions³. Studies have suggested that cyclosporine is at least as effective as prednisolone for controlling atopic dermatitis³, but is better tolerated than the corticosteroid. The most likely side effects are transient anorexia and vomiting, but this can be avoided by administering cyclosporine with food. Uncommonly, hirsutism, alopecia, gingival hyperplasia, diarrhoea, tremors or erythema of the ears may be seen, but these effects are dose-dependent and reversible³. Immunosuppression is a potential concern, and so patients should be observed closely for opportunistic infections or infestations. Cyclosporine may also affect the efficacy of vaccination, and so some vets choose to treat with corticosteroids around this time instead. The drug minimally affects intradermal and serological allergy testing⁴.

Phytopica is a product containing a selection of Chinese herbs, which has been shown to be an efficacious, safe and palatable treatment for atopic dermatitis in dogs³. However, only a 20-50% improvement in signs is achieved, and so Phytopica is best used in combination with other control strategies and anti-inflammatory drugs.

Hydrocortisone aceponate is a topical glucocorticoid that relieves pruritus. The topical administration and the fact that hydrocotisone aceponate is metabolised in the dermis means that many of the traditional side-effects of glucocorticoid therapy are avoided^{1, 3, 4}. The product is potent, and rapidly exerts its effects following application. The formulation of the product makes it easy to apply, even to haired skin, and most animals only require every-other-day treatment. Adverse effects are rare, and only one dog has been reported to suffer a contact reaction.

Antihistamines have some efficacy in the face of atopic dermatitis, and may have synergistic activity with essential fatty acids and glucocorticoids^{3, 4}.

Prognosis

If left untreated, the degree of pruritus worsens, but atopic dermatitis is not life threatening unless intractable pruritus warrants euthanasia¹. Some cases may spontaneously resolve.

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Links

• The Merck Veterinary Manual - Canine Atopy

References

1. Tilley, L P and Smith, F W K (2004) The 5-minute Veterinary Consult (Fourth Edition),Blackwell.
2. Beale, K M (2006) Atopic Dermatitis: Clinical Signs and Diagnosis. Proceedings of the North American Veterinary Conference 2006.
3. Willemse, T (2007) The Newest on Canine Atopic Dermatitis. Proceedings of the Southern European Veterinary Conference & Congreso Nacional AVEPA.
4. Merck & Co (2008) The Merck Veterianry Manual (Eight Edition), Merial.

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