Allergic dermatitis remains the most common presenting complaint attended to by veterinary practitioners in North America with regard to diseases of the skin. Atopy, or sensitivity to inhaled or percutaneously absorbed environmental allergens is second only to flea bite hypersensitivity as the most common form of allergic dermatitis. Atopy displays a strong familial and breed predilection and appears to be polygenic in origin. Treatment of atopic dermatitis has evolved with our understanding of the disease and traditionally has been based upon immune modulation and anti-inflammatory therapies. Increased interest among veterinarians and pet owners in alternative treatment modalities has developed rapidly over the last decade and has resulted in a proliferation of natural-based products for treatment of skin diseases, namely antioxidants. The perceived ambiguity of just how natural products work on a biochemical and physiological level has made product recommendation difficult for many veterinarians attempting to meet the demand for rational alternative and complementary care. A review of the medical literature does prove rewarding for an investigator looking for scientific data, but the search can be time consuming. The purpose of this chapter is to summarize some of the more promising nutrient therapies for atopic dermatitis as well as review the disease itself, comparing and contrasting the mechanisms of traditional and complementary approaches. Although not an exhaustive summary, this chapter may aid the general practitioner in selecting adjunct approaches to the treatment of atopic dermatitis. For most patients alternative therapies will never supplant traditional care, but they can complement chronic disease management, improve client relations, build trust, and reduce the side effects and cost associated with standard therapies.

Hypersensitivity reactions occur as a result of very complex sequences of events that are beyond the scope of this chapter. Outlined here are the major cellular and biochemical interactions simplified for the purpose of review and highlighting where antioxidant and nutrient therapies can be of benefit both in a theoretical and practical sense. In healthy individuals, immune surveillance of benign environmental antigens results in the formation of either IgG or IgM, effectively binding and facilitating the removal of foreign material without a systemic response. In atopic individuals the immune system forms IgE antibodies against some antigens, initiating the cascade of events that cumulatively result in allergy, otherwise known as atopic dermatitis. IgE formation in healthy individuals is generally reserved for response to parasitic infestation. This response, referred to as a type-I hypersensitivity reaction, can be divided into two distinct phases: the immediate and delayed phase responses.

The immediate phase is seen just minutes following allergen exposure and is initiated as previously sensitized IgE-activated mast cells degranulate in response to intimate contact with the allergen. Mast cells release their granules of histamine as well as prostaglandin D₂ into the capillary beds of the skin causing capillaries to dilate, endothelium to contract, and tissue edema to form as a result of vascular leak. The late phase response in type-I hypersensitivity reactions begins 2–4 h postallergen exposure and involves the recruitment of inflammatory leukocytes, primarily eosinophils, helper T lymphocytes (T_H2s, CD4 T cells), and neutrophils, into affected areas of the skin. Tissue macrophages elaborate tumor necrosis factor alpha which in turn increases the expression of leukocyte adhesion molecules, allowing escape of leukocytes into the interstitium through previously dilated capillaries [1]. This response is perpetuated through continued allergen exposure and complicating sequelae such as pyoderma and secondary yeast proliferation.

Oxidative stress is a term assigned to a state in which an individual’s ability to reduce oxidants in situ has been diminished by disease or the production of oxidants has overwhelmed the normal defense mechanisms, disrupting homeostasis. Free radicals are defined as independent molecules with one or more unpaired electrons. As with most inflammatory diseases, the production of several species of radical oxygen and nitrogen are produced in above normal and locally toxic levels in patients suffering with atopy. It has been demonstrated that significant disruptions to homeostasis occur in human pediatric patients suffering with atopic dermatitis [21]. Both markers of oxidative stress (8-hydroxy-2′-deoxyguanosine, nitrite/nitrate) and antioxidant status (selenium) experienced significant derangements when compared to healthy controls [2].

Cellular respiration is the main source of oxygen radical formation but many enzymatic pathways are capable of producing various radical species. Superoxide radicals, hydroxyl radicals, hydrogen peroxide, hypochlorous acid, and nitric oxide all result from and have the potential to incite inflammation during a sensitivity reaction [3]. A quantitative assessment of the magnitude of oxidative stress as well as the antioxidant response of patients may eventually be within the reach of practitioners, but for now it remains the realm of the researcher. Interest in measuring oxidative stress and quantifying its effects has led to recent advancements in methods of testing for oxidized by-products of DNA, protein, and lipids. These assays may assume a commercial form available through veterinary diagnostic laboratories in the future allowing the practitioner to identify individuals under oxidative stress and assist in selecting therapeutic intervention [4]. Until that time, subjective assessment of clinical response remains our most practical tool for guiding therapy.

Treatment for allergic dermatitis, whether due to flea bite sensitivity or atopic dermatitis, has been directed toward intervening at crucial steps along the chain of events leading to disease manifestation. Glucocorticoids, long the mainstay therapy for allergic conditions, affect leukocyte kinetics, phagocytic defenses, cell-mediated immunity, humeral immunity, and production of inflammatory mediators [5]. Cyclosporine binds to specific intracellular receptors in T-lymphocytes. This action inhibits synthesis of cytokines interleukin 2 (IL-2), interleukin 3 (IL-3), and tumor necrosis factor (TNF) resulting in a suppression of the activated T-lymphocytes [22]. Subsequent generations of specific T-cell inhibitors, namely tacrolimus and pimecrolimus, act similarly and carry several advantages over cyclosporine; specifically a much smaller molecular size allowing penetration of the epidermis when given topically [6].

Topical therapies have also been deployed with varying amounts of success. These include antiseborrheic agents, topical glucocorticoids, and antimicrobial preparations. Antihistamines have limited use against allergic dermatitis in veterinary patients and this limitation is most likely due to our inability to recognize the immediate phase response during which antihistamine therapy is most likely to be effective. A positive response to antihistamine therapy in atopic canine patients is thought to occur in approximately 10–15% of cases.

Control of secondary conditions is also often necessary and these most often include systemic and topical antibiotics, antifungals, ceruminolytics, and antiseborrheals. Hyposensitization therapy has been a useful tool for decreasing the magnitude of allergic response in humans with environmental sensitivities. Repeated administration of antigen injected subcutaneously has been demonstrated to decrease IgE levels and increase IgG titers in allergic individuals. Specific T-cell tolerance of antigen is thought to be induced by changing the predominant phenotype of antigen-specific T-cells from T_H2 to T_H1 [1]. T_H1 cells evoke cell-mediated immunity and phagocyte-dependent inflammation whereas T_H2 mediated reactions evoke strong antibody responses and eosinophilic accumulation, with the latter carrying a much greater implication for allergic diseases. Similar results have been achieved in some veterinary patients but overall the response to hyposensitization is considered to be sporadic. The expense and inconvenience of allergen testing and follow-up injections is cost prohibitive for many clients. The low response rates are thought to be due to incomplete identification of allergens in individuals sensitive to numerous environmental components.