The season is upon us when approximately 10% of horses worldwide are faced with one of the most frustrating skin diseases in the equine industry, insect bite hypersensitivity (IBH), more commonly known as “sweet itch” or “summer eczema.” This an allergic, recurrent, seasonal dermatitis develops when the immune system overacts or becomes “hypersensitive” to allergens in the saliva primarily of biting midges (Culicoides) and other biting insects.

Although there is no cure for IBH, there is ongoing research to assess immunotherapies as future treatment options for horses suffering with IBH.

While IBH has a multifactorial cause, it is acknowledged that the immune system plays a role in its development. Hypersensitivity reactions are classified into four types, and IBH is a combination of Type I and Type IV. Type I hypersensitivity reactions develop when antigen specific allergens bind to IgE and cross-link receptors on mast cells, basophils, and eosinophils. These cells release vasoactive amines, such as histamine, that affect blood vessel size and leakage and produce inflammatory cytokines and other mediators, which result in inflammation and pruritus (itchiness). Type IV reactions, often referred to as delayed-type hypersensitivity reactions, involve cell-mediated responses particularly of activated Th-2 lymphocytes which produce IL-5 cytokine and large numbers of eosinophils, both contribute to clinical IBH manifestations.

Immunotherapy treatment is based on a century-old concept that the immune system can be desensitized to specific allergens that trigger hypersensitivity reactions. Allergen immunotherapy (AIT) involves inoculation with gradually increasing doses of an allergen to which the individual is allergic. The incremental increases in exposure to the allergen cause the immune system to become less sensitive to the substance, which reduces the allergy signs when the substance is encountered in the future.

Data are conflicting as to whether or not traditional AIT therapies are successful in treating IBH. Research is now exploring whether IBH can be prevented by vaccination with recombinant Culicoides antigens versus whole antigen preparations to more successfully modulate the immune response, in particular, IgE response. Another interesting area under current investigation is oral immunotherapy, whereby transgenic barely expressing allergens are administered orally to prevent hypersensitivity to Culicoides.

Finally, given the important role of eosinophils in IBH pathology and the fact that IL-5 drives eosinophil activity, a novel and allergen independent vaccine has been evaluated that targets IL-5 and limits eosinophil recruitment to the affected skin. This is one of the few equine studies to investigate whether a vaccine can induce autoantibodies to cytokine IL-5 and result in clinical efficacy for IBH. This immunotherapeutic approach could be the new generation for treating chronic immune diseases and could signal that new therapies are on the horizon for horses suffering from IBH.

CONTACT: Amanda A. Adams, PhD——859/218-1097—University of Kentucky Gluck Equine Research Center, Lexington

This is an excerpt from Equine Disease Quarterly, funded by underwriters at Lloyd’s, London.