Canine atopic dermatitis: A review and update (Proceedings)

Etiology and Pathogenesis

Canine atopic dermatitis (atopy, allergic inhalant dermatitis) is a hereditary, pruritic (itchy) skin disease. The disease is caused by an allergic reaction to the inhalation of pollens, mold spores, dust, or epidermals (animal dander, feathers wool). Upon future challenge with that specific allergen, IgE molecules are bridged on the mast cell surface. This sends a signal for the mast cell to degranulate and release inflammatory mediators. This is a type I hypersensitivity reaction. Histamine is the most important mediator but proteolytic enzymes, kinins, ECF, etc. are also involved. The release of these mediators results in inflammation and pruritus. The development of this inflammatory reaction is the body's attempt to rid itself of the foreign substance.

More recently additional pathways are thought to be involved in atopic dermatitis. A specific subclass of IgG (IgGd) is thought to be involved in human and canine atopic dermatitis. In addition, specific IgE receptors have also been found on Langerhans cells of atopic patients. The presence of these IgE receptors suggests that percutaneous absorption may play a more important role than previously suspected. Concurrent abnormalities in cell mediated immunity (CMI) in atopic dermatitis patients can lead to decreased T-lymphocytes, neutrophils and macrophages.

History

Certain breed, age, and sex predispositions exist. Since canine atopic dermatitis is an inherited condition, certain breed dispositions have been noted. Terrier, retrievers, Dalmatians, Maltese, Lhasa Apso, English Bulldogs, and Shar Pei. Poodles tend to have the lowest incidence of atopic dermatitis. The typical age of onset for atopic dermatitis is between 1 to 3 years of age. However, dogs as young as 6 months and as old as 5 years have been reported. Female dogs appear to be more predisposed to develop atopic dermatitis than male dogs (2:5:1, female:male).

Atopic dermatitis is typically a seasonal pruritic problem. However, in warmer climates, atopic dermatitis can be nonseasonal. Therefore, canine atopic dermatitis may be seasonal or nonseasonal depending on the circumstances.

Clinical signs

Canine atopic dermatitis has been described as the itch that rashes. Therefore, erythema and pruritus are hallmark clinical signs associated with canine atopic dermatitis. The dog with atopic dermatitis must be exposed to the antigen for some time before clinical signs will appear. It is for this reason that the first symptoms are most often noticed at an age between 6 months and 5 years. The symptoms often start out "seasonal" and become worse each year. Duration and severity of the symptoms increase as the animal becomes allergic to more antigens.

The first signs that are likely to be noticed are scratching, chewing, rubbing, or licking at the face (especially muzzle and periorbital areas), proximal forelegs, feet, ears, axillae and inguinal areas. One or more of these body locations may be involved. Early on there may be no observable change in the skin in these areas. As the disease progresses the skin may become red and there may be hair loss due to the trauma. Types of skin lesions that are typically seen in cases of canine atopic dermatitis include: alopecia, excoriations, superficial moist dermatitis ("hot spots") and salivary staining. Symptoms usually start suddenly when the animal is exposed to the causative antigen. When the animal is kept away from the antigen the symptoms may subside within minutes to hours without other treatment.

Chronic or long-term disease can result in secondary changes such as thickening of the skin (lichenification), hyperpigmentation, otitis externa (ear infections), bacterial skin disease (pyoderma), and loss of hair and / or acute moist dermatitis (hot spots). Unusual presentations, approximately 10% of the cases, have hyperhidrosis or pseudosweating. Intact females may exhibit irregular heat cycles. Other possible clinical findings include: urticaria, conjunctivitis, rhinitis, asthma, diarrhea, and personality changes such as irritability. The disease can be complicated or made worse by other allergies such as food, flea, or contact allergies. When this occurs, it becomes a difficult diagnostic challenge and cooperation between owner and the veterinarian is of utmost importance if a solution to the problem is to be obtained.

Differential diagnoses

The list of differential diagnoses for canine atopic dermatitis is long. Differentials for canine atopic dermatitis include: food allergy, flea allergy, scabies, Malassezia dermatitis, allergic contact or irritant dermatitis, and parasitic dermatoses (ie pelodera or hookworm dermatitis). irritant dermatitis

Diagnosis

Historical and clinical signs are useful for determining whether atopic dermatitis is a reasonable differential for canine pruritus. Historical findings include age of onset, breed, sex, seasonality and the primary complaint of pruritus. Clinical signs (types of skin lesions and lesion distribution) are also helpful. However, it is important to remember that although the history and clinical signs may be highly suggestive of atopic dermatitis but it does not identify the offending antigen.

The identification of the offending antigen that provokes an allergic response can be determined in many ways:

1. The rapid response to exposure and the fact that the animal often learns to associate distress with exposure allows the keen observer to identify possible offending agents. Once a substance is suspected, intentional exposure and observation of a reaction helps to prove the diagnosis. This situation rarely occurs.

2. Two forms of allergy testing are available in veterinary medicine (ie intradermal allergy testing and serum allergy testing). Allergy should be considered in the following circumstances:

a. The pruritic season lasts longer than 3 months out of the year.

b. The dog has a poor response to symptomatic therapy other than steroids.

c. Secondary dermatological problems such as pyoderma and otitis are recurrent.

d. The owner elects for a safer long term therapy.

3. Intradermal allergy testing (IDATing) is considered the gold standard diagnostic test for canine atopic dermatitis. Skin testing is the best method available to identify animals with allergic inhalant dermatitis and to identify the antigen they are allergic to. This type of test requires chemical restraint (sedation or anesthesia) and clipping of the hair. Suspected antigens are injected into the skin on the side of the body and the reaction is observed and measured. This test should be done by someone who has had experience with the test since it is necessary to correlate the reactions with the clinical history. Medications and the time of year influence the results. Oral steroids and possibly cyclosporine should be withdrawn a minimum of 1 month prior to skin testing. Injectable steroids should not be administered for a minimum of 3 months. Antihistamines and fatty acids should not be given for 1 to 2 weeks prior to skin testing. Acepromazine cannot be given since it causes vasodilation and inhibits mast cell release.

4. Serum allergy testing testing (RAST or ELISA) is available for dogs. These tests are done by submitting a blood sample to a laboratory and are then tested for circulating antigen-specific antibodies. This is a convenient test (a simple blood test) but currently does not test for specific allergens, only groups. There is also a tendency for them to produce false positive results. When used in conjunction with the history and other test these may be of help in some cases but can be very expensive. Interestingly, the only time that IDATing and serum allergy testing correlate is when both tests are positive. Some researchers and veterinary dermatologists question whether what occurs in the blood with serum allergy testing occurs in the skin. Antedoctal reports exist that some dogs benefit from hyposensitization based on serum allergy testing. Therefore, this method of testing should not be dismissed.

5. Histopathology is another diagnostic test that can be performed. Atopic dermatitis usually shows up on histopathology as a superficial perivascular dermatitis with or without secondary changes (ie pyoderma). However, these changes are not specific for atopic dermatitis. Other types of allergies can appear similar histologically.

Management of Inhalant allergies

1. Limit exposure or remove material that provokes an allergic response.

2. Treat contributing conditions such as bacterial skin disease, fleas, fungal infections, or other parasites.

3. Symptomatic therapy, by using cool baths, topical medications or other treatment recommended by your veterinarian, can reduce the intensity of the itching.

4. Fatty acid supplements may help in up to 20% of the animals with this disease. This treatment usually takes up to 8 weeks to see the full effect.

5. Antihistamines may help some of the atopy dogs. They work best when given before the exposure to antigen. There are many types and sometimes one type will work when another type has not. It is often helpful to use antihistamines to reduce the need or dose of corticosteroids.

6. Corticosteroids (cortisone, prednisone, and prednisolone) are usually very effective in relieving the symptoms of atopy but the effect is temporary. Unfortunately, continued use of these drugs, especially at high dosages, can result in serious side effects. These side effects include the following:

a. Increased appetite and weight gain.

b. Increased thirst and urination

c. Reduced activity

d. Lack of hair growth and thinning of the skin

e. Lowered resistance to infection

It is there for necessary to try to identify the causative allergens, reduce the exposure to them and use the lowest dose of corticosteroids that relieves the clinical signs.

Corticosteroids in all forms are potent medications and can cause serious diseases (Cushing's, hypothyroidism) if used for extended periods of time. These drugs should be monitored closely by your veterinarian. Keep records of all corticosteroids used, their dos and their clinical effects so your veterinarian can better evaluate how adjustments need to be made.

7. Cyclosporine or Atopica® is an oral form of cyclosporine that is derived from a metabolite of a fungus (Beauveria nivea). Cyclosporine is a potent immunosuppressive agent that has been shown to work via suppression of T-helper and T-suppressor cells and inhibition of an inflammatory mediator (interleukin-2). It does not impair the hematopoietic system (bone marrow). The indications for cyclosporine usage are for controlling canine atopic dermatitis in dogs weighing at least 4 pounds. The recommended dose for cyclosporine is weight dependent according to the label chart or about 5 mg//kg once a day for 30 days then taper to every other day or twice weekly. The minimum frequency that will maintain a particular dog's allergies will vary between dogs.

Cyclosporine has special precautions with administration. Cyclosporine should be

NOT be given ONE HOUR before a meal or TWO HOURS after a meal since food will affect absorption of drug. If a dose is missed the next dose should be administered as soon as possible without doubling the dose. In addition, certain medications may interact with cyclosporine. Drugs that increase cyclosporine blood levels and increase cyclosporine toxicity are: allopurinol, amiodarone, azole antifungals (ie ketoconazole, fluconazole), bromocriptine, calcium channel blockers, cimetidine, cisapride, corticosteroids, danzol, digoxin, macrolide antibiotics (ie erythromycin, clarithromycin), metoclopramide, omeprazole, and sertraline. The following drugs may decrease the blood levels of the cyclosporine: nafcillin, rifampin, Phenobarbital, phenytoin, St. Johns Wort, digoxin, and azole antifungals, methotrexate, nephrotoxic drugs (ie acyclovir, amphotercin B, aminoglycosides, colchicines, vancomycin, and nonsteroidal anti-inflammatory drugs, potassium sparing diuretics, vaccines (avoid use of live attenuated vaccines). Cyclosporine is contraindicated with a history of malignant tumors. In addition, gastrointestinal and gingival hyperplasia may occur at the recommended dose. Cyclosporine is not safe for dogs under 6 months of age or less than 4 pounds.

Adverse reactions for cyclosporine include: vomiting, diarrhea which

spontaneously resolved with continued dosing. Other reactions that can occur but are not as common: ear infections, urinary tract infections, enlarged lymph nodes (lymphadenopathy), depressed appetite, abnormal proliferations of the gums (gingival hyperplasia), depression/lethargy, skin growths (sebaceous cysts), increased drinking and urination, seizures and reddened skin.

Atopica is a good alternative to antigen injections for small to medium breed dogs. This

treatment is generally well tolerated and improvement in the dog is typically within one

month. Like with any other treatment the dog should be observed for any change in

condition and reported to your veterinarian so changes in treatment can be made or

improvements can be documented.

8. Hyposensitization (immunotherapy) is the name given to a series of injections of the antigens given in increasing dose. These injections should not be confused with corticosteroid injections which are sometimes referred to as "allergy shots". They can be very effective in some animals (60 to 75% of dogs on immunotherapy respond) but can take up to a year for the full effect to be noticed. Reduced exposure and small amounts of steroids or antihistamines may be necessary especially in the early treatment. It is usually necessary to continue the injections throughout the animal's life.

Comments/Conclusions

Canine atopic dermatitis is an inherited skin condition that is manageable but not curable. Several different treatment options exist for trying to control the clinical signs associated with this medical problem. The owner needs to be made aware of this situation and be prepared to deal with this problem for the rest of the animal's life.

Suggested Readings

Daigle JC. More economical use of cyclosporine through combination drug therapy. J Am Anim Hosp Assoc. 2002;38:205-208.

DeBoer DJ. Canine atopic dermatitis: new targets, new therapies. J Nutr. 2004:134:2056X-2061S.

Marsella R. Managing dogs with chronic atopic dermatitis. Compend Cont Ed Pract Vet. 2001;23:454-461.

Oliver T, Stefan J, Frisch RD, et al, European Veterinary Cyclosporine Group. Randomized controlled trial of the efficacy of cyclosporine in the treatment of atopic dermatitis in dogs. J Am Vet Med Assoc. 2002;221:370-377.

Steffan J, Horn J, Gruet P, et al. Remission of the clinical signs of atopic dermatitis in dogs after cessation of treatment with cyclosporine or methylprednsiolone. Vet Rec. 2004;154:681-684.

Zur G, Ihrke PJ, White SD, Kass PH. Canine atopic dermatitis:a retrospective study of 266 cases examined at the University of California, Davis, 1992-1998. Part I. Clinical features and allergy testing results. Vet Dermatol. 2002;13:89-102.

Zure G, White SD, Ihrke PJ, Kass PH, Toebe N. Canine atopic dermatitis: a retrospective study of 169 cases examined at the University of California, Davis, 1992-1998. Part II. Response to hyposensitization. Vet Dermatol. 2002;13:103-111.