Atopic Dermatitis

Description

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 occures via percutaneous absorption. This further exposure gives mast cell degranluation, releasing istamine, 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 thtat they are not noted, but usually progress to become clinically apparent¹. Atopy is heritable and so breed predispoitions occur. Susceptible breeds include the : Beaceron, Boston Terrier, Boxer, Cairn Terrier, Cocker Spaniel, Dalmation, English Bulldog, English Setter, Fox Terrier, Sealyham Terrier, Setters, Shar-Pei, West Highland White Terrier, Wire Hiared fox Terrier, and Yorkshire Terrier^beale. 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, athorough 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 than 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 seen^beale. With time, lichenification, and hyperpigmentation develops. Because the route of allergen contact is thought to be percutaneous absorption^beale, 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^{merck, beale, willemse}. 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^beale.

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 betweem atopic and normal animals^beale. IgE levels are also influence 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 histoty 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-sprecific IgE^beale. 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 Testing

Intradermal skin tests (IST) detect the ability of allergens injected intradermally to cause mast cell degranulation leading to a subsequent wheal and flare reaction. Aqueous allergens are used for testing. Allergens are selected based upon the region in which the patient lives. Tree, weed, and grass pollens as well as molds, house dust mites, insects and epidermals should be included in the test. In theory, testing should be performed utilizing the highest concentration of extract that does not cause an irritant reaction. Recommended test strengths for allergens are as follows: 1000 PNU/ml for pollens, 1:50,000 W/V for house dust mites, 250-500 PNU for epidermals and 1000 PNU/ml for insects.

Aqueous allergen extracts lose potency over time, particularly when in their more dilute form for testing. Diluted allergens should not be kept for longer than 2 weeks. They should be stored at 4C. Prior to testing, allergens should be allowed to reach room temperature. Once testing is completed, allergens should be returned to the refrigerator as soon as possible.

Test results can be affected or inhibited by numerous factors: medications, sedatives, stress, etc.

Antihistamines: Hydroxyzine has been shown to inhibit skin test reactivity, and it is presumed that other antihistamines will have the same effect. A withdrawal period of 10 days is recommended, and longer for antihistamines with longer half-lives (ceterizine, etc).

Tricyclic Antidepressants: Histamine reactivity is affected by doxepin in people for up to 11 days.

Glucocorticoids: Withdrawal of topical glucocorticoids for 3 weeks has been suggested, oral glucocorticoids a minimum of 3 weeks, and repositol steroids for a minimum of 8 weeks. However, the optimal times have not definitively been established. Patients that have been receiving glucocorticoid therapy for extended periods of time may require a longer withdrawal period, and some dogs may have positive results with a shorter withdrawal period.

Inflamed or infected skin makes IST difficult. Ideally, patients should be treated for their pyoderma or Malassezia dermatitis prior to testing.

Sedation is recommended for IST as testing is more easily performed. Sedatives that have been demonstrated to not affect test results include xylazine HCL, Medetomidine, and Tiletamine/zolazepam. Diazepam, oxymorphone, acepromazine and propofal may all adversely affect test results. The lateral thorax is routinely used for testing. The site is clipped with a #40 blade.

Intradermal injections are made with 26-27 g needles. Sharp needles ensure less bruising and easier injections. Positive (histamine phosphate 1:100,000) and negative (0.9% buffered saline) control injections are made to help ensure test accuracy. Injections are made utilizing approximately 0.05-1.0 ml solution. Injections are made based on "bleb" size. The injection blebs should be of approximately the same size at each injection site. Reactions are most commonly evaluated subjectively on a scale of 0-4 (compared to the positive and negative controls). Reactions are read at approximately 15 minutes. False positive reactions may occur with irritants, or allergens used at too high a concentration. False negatives may occur as well with drug interference, host factors, time of year, and improper technique.

Treatment

cyclosporin

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.