Tracking Our Progress...Atopic Dermatitis

Editor's note; This is part two of Dr. Olivry's article. Definition, epidemiology, clinical signs, and diagnosis of the disease were covered in the Summer issue.

Atopic Dermatitis, a Common Skin Disease of West Highland White Terriers
Dr. Thierry Olivry DrVet, PHD, DipACVD, DipECVD

Fall 2004, NEWS

TREATMENT

The treatment of canine AD usually involves the concurrent use of multiple interventions aimed at different targets.

Allergen Avoidance and Prevention of Allergen Contact

In dogs, aeroallergens (e.g. pollens, house dust mites) as well as food and arthropod antigens have been recognized as flare factors (i.e. exacerbation factors) for canine AD for decades. It is logical to recognize that one of the first steps in the management of canine AD should be the environmental elimination of these offending substances, or the avoidance from contact with these allergens.

For aeroallergens such as pollens and molds, this concept is almost impossible to set forth. Reducing outdoor exposure when offending pollens and molds are present in high amounts should reduce allergen contact, however. The use of internet-displayed weekly pollen counts could be useful to determine the peaks of aeroallergens in the various US regions http://www.aaaai.org/nab/index.cfm?p=pollen.

When dogs are allergic to Dermatophagoides house dust mite allergens, environmental measures, such as the use of mattress pillow cases made of fabric with low-diameter pores impermeable to house dust mites allergens, could be proposed to the owners. The impact of acaricides, arthropod growth regulators and desiccants on the reduction of symptoms of canine AD induced by house dust mites has not been studied adequately at this time. However, these measures should prove beneficial to reduce the population of Dermatophagoides mites from the animal's environment.

Whenever the elimination of allergens is impossible, avoidance of their prolonged contact to the dog's skin should be considered. Contact with grasses should be reduced when grass allergens have been identified to exacerbate AD lesions. Frequent bathing with emollient shampoos could be proposed, especially after the dog goes outside. Various topical formulations have been recently proposed as "skin barriers" to prevent symptoms of contact dermatitis in humans. These formulations could prove beneficial in preventing the contact of allergens with immune-competent cells in the epidermis of atopic patients. However, this theoretical therapeutic concept has not been tested in either humans or dogs with AD.

Because dogs with AD probably exhibit an abnormal epidermal lipid barrier, it is theoretically possible, yet unproven, that a diet rich in linoleic acid, one of the main component of epidermal ceramides, could restore the defective barrier. A similar concept could be proposed with topical formulations including fatty acids or ceramides. These hypothetical theories have not been verified at this time.

In some dogs with AD, clinical signs have been shown to abate, partially or completely, after an elimination diet. These observations suggest that concurrent food allergy could contribute to disease exacerbation in these patients. In these dogs, the removal of culprit dietary allergens therefore could decrease overall allergen burden. Prevention of the ingestion of offending dietary allergens can be made by switching to a diet containing novel protein and carbohydrate sources to which the dog has not been in regular contact in past times. Additionally, diets containing hydrolyzed proteins have been made available commercially. The hypothesis behind the generation of such diets is that low-molecular weight peptides would be too small to provoke IgE cross-linking on sensitized mast cells. These diets, unfortunately, could prove ineffective in case of immunologic mechanisms not involving IgE, or not involving peptide antigenic epitopes. Regrettably, there is little information documenting the efficacy of these low-molecular weight diets in reducing gastrointestinal or cutaneous clinical signs in dogs spontaneously allergic to the native "parent" non-hydrolyzed proteins. At this time, there is thus insufficient evidence to recommend for or against the use of such "hypoallergenic" diets until large blinded randomized controlled trials have been made available to the veterinary community.

Atopy appears to predispose dogs to develop an hypersensitivity to flea salivary allergens. Dogs with AD, therefore, seem prone to develop cutaneous reactions to the bites of arthropods such as fleas and clinical manifestations of concurrent flea allergy dermatitis. Consequently, a thorough flea eradication program should be proposed to all patients with this disease.

Allergen-Specific Immunotherapy

In most dogs with AD, both elimination of offending allergens and prevention of contact with allergens are difficult to achieve and response to pharmacotherapy often is unsatisfactory. In these cases, the possibility of modulating the immunological response that results from allergen exposure is appealing. This concept has led to the development of allergen-specific immunotherapy (ASIT), also known as hyposensitization, desensitization or allergy "vaccination." Such therapy results in a variety of immunological changes, none of which are perfectly correlated with efficacy. The precise mechanism is thus unknown.

Recently, the World Health Organization (WHO) has specified guidelines for allergen-specific immunotherapy designed for human allergic patients. Now defined as "the practice of administering gradually increasing quantities of an allergen extract to an allergic subject to ameliorate the symptoms associated with subsequent exposure to the causative allergen," immunotherapy is not indicated for every patient with AD. Indeed, the WHO proposes that "immunotherapy is best indicated for patients who have demonstrable evidence of specific IgE antibodies to clinically relevant allergens and whose allergic symptoms warrant the time and risk of allergen immunotherapy." Moreover, "the necessity for initiating immunotherapy depends on the degree to which symptoms can be reduced by medication, the amount and type of medication required to control symptoms, and whether effective allergen avoidance is possible."

At this time, there are few guidelines on when and how to use immunotherapy in dogs with AD. Moreover, none of these recommendations have been tested with rigor in blinded randomized controlled experimental trials examining various treatment protocols. Because of the lack of evidence-based recommendations for immunotherapy usage in dogs with AD, the WHO guidelines for immunotherapy in humans could be extrapolated to provide general directions of use. For example, one could propose that immunotherapy be reserved for dogs: i) with demonstrable and clinically-relevant allergen-specific IgE antibodies, ii) in which allergen contact is unavoidable, iii) with symptoms that respond poorly to antipruritic drugs, or in which cost or side-effects of therapy are unacceptable and iv) whose owners are ready to afford the time, expense and technical aspects of this regimen. However, such guidelines should be validated in appropriate controlled experiments. Finally, one should not forget that immunotherapy is the only treatment option available that has the potential to result in partial or complete remission of canine AD without the further need of additional anti-inflammatory drugs.

Anti-Inflammatory Pharmacotherapy

Whenever allergen avoidance is not feasible or when it doesn't reduce the clinical signs of the disease, then the use of anti-inflammatory drugs is warranted. The goal of the veterinarian therefore is to seek the drug, or the combination of medications, with maximum efficacy and minimum cost and side effects.

A recent systematic review evaluated the efficacy of pharmacological interventions for treatment of canine AD. Among the medications with evidence of efficacy are oral and topical glucocorticoids (steroids), oral cyclosporin, topical tacrolimus, or oral pentoxifylline and misoprostol. Remarkably, there is insufficient evidence for recommending the use of antihistamines for treatment of AD in dogs. Of note is that glucocorticoids and the calcineurin inhibitors cyclosporine and tacrolimus are also the drugs providing highest benefit for treatment of AD in human beings.

Antimicrobial Therapy

Dogs with AD commonly exhibit surface colonization, or superficial or deep skin infections, with pathogens such as Staphylococcus intermedius and Malassezia pachydermatis. These microbes and/or their secreted toxins could serve as flare factors of AD lesions by being targeted by IgE, thus serving as allergens. Moreover, they could by contributing to the recruitment or activation of dermal inflammatory cells, hence exacerbating directly atopic skin lesions. For these reasons, antimicrobial therapy is one of the most important parts of the management of AD in dogs. In most atopic dogs, it is one of the first therapeutic steps that should be undertaken. Whenever clinical signs of active infection are present, specific antibacterial or antifungal therapy should be initiated, topically and/or systemically. An appropriate course of antibiotics could help determine whether or not Staphylococci are involved in the genesis of symptoms of AD. A similar approach could be extrapolated with drugs targeting Malassezia, keeping in mind that some of the antifungal drugs (e.g. imidazoles) exhibit anti- inflammatory effects on their own.

CONCLUSIONS

Atopic dermatitis (AD) is a very common chronic, progressive allergic skin disease that results in a profound impairment of quality of life in affected dogs because of persistent itching, spontaneous and self-induced skin lesions, secondary skin infections, and loss of sleep. Behavioral changes in their pets, oftentimes constant scratching at night, constant malodor, as well as despair seeing the ineluctable progression of the disease also result in lower wellbeing in owners of severely affected dogs.

The treatment of canine AD is multifaceted and does not involve a single drug or approach. By being familiar with the different arms of therapy and by selecting relevant drugs or regimens, veterinarians will be able to achieve acceptable results whilst reducing the severity of adverse side effects.

Future studies should look for the gene(s) whose mutations underlie AD in predisposed breeds. Only with the identification of mutation carriers and responsible breeding practices will the frequency of the trait be decreased in such breeds. Additionally, interventions could be designed to prevent or decrease the severity of the disease in pets carrying the mutation before lesions develop.