Harnessing equine atopy

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Flowering fields, dusty barns, fabrics and leathers, hays and bugs galore: these are just a few of the itch makers that fill the horse’s world with a swirl of pesky antigens. Initial exposure sensitizes the immune system to these compounds, which when reintroduced can cause a type I hypersensitivity reaction that triggers an inflammatory cascade.^1,2 The trademark wheals are part of life for horses with atopic dermatitis, perhaps the most vexing manifestation of the allergic hypersensitivity condition known as atopy.

“This is very common not only in horses but in almost any species, including humans,” said Jeremy Redmond, DVM, MS, DACVIM, assistant professor of equine medicine at Louisiana State University School of Veterinary Medicine, at the American Veterinary Medical Association Convention in Denver, Colorado.

While atopy is a well-trod path for the equine immune system, horses’ top immune flare-up is insect bite hypersensitivity (IBH),^1,2 typified by scabby or scarred pinnae. This, along with equine asthma, is another type I reaction.

In type II hypersensitivity, the antibodies IgG and IgM mobilize against one’s own tissues, resulting in cell lysis.^1,2 “I always picture the horse eating itself,” Redmond said.

Triggers include drug exposures, which can lead to immune-mediated hemolytic anemia (IMHA), thrombocytopenia, and other such conditions.^1,2

Type III hypersensitivities churn out immune complexes that get deposited in blood vessel walls, causing vasculitis. Unlike the other 3 varieties, which utilize antibodies, type IV hypersensitivities involve T cells. These are slow to manifest: Contact dermatitis, for instance, can take 24 hours to set in after exposure.¹

The atopic showdown

Upon presentation of an inhaled or skin-contacted allergen, antigen-presenting cells deliver the antigen to immature helper T cells. Once mature, these cells release several types of interleukin (IL). One of these, IL-4, presses B lymphocytes to transform into plasma cells that manufacture IgE antibodies against the offending antigen.^1,2

Once the horse is reexposed, the antigen binds to IgE, causing primed basophils and mast cells to degranulate: The “itch” compound, histamine, floods out.^1,2

Equine atopy, hereditary in some horses—as demonstrated in certain warmblood lines—results from an aberrant immune response to typical environmental allergens. They encompass everything from dust mites to meadow grasses to fungal spores and may be either seasonal or ever present. Signs include erythema, urticaria, and pruritus, and may progress to secondary bacterial infections and dependent edema.^1,2

This clinical picture can be complex. “If you have [a horse with] one of these conditions,” Redmond said, “dive a little deeper for signs of other hypersensitivity disorders, like asthma or IBH.”

He illustrated atopic dermatitis with the case of Juicy, a 10-year-old Quarter Horse gelding that developed hives after moving from Arizona to Oregon. Wheals gave way to exudative, infected, pruritic lesions, and edematous ventral plaques. Redmond diagnosed allergic urticaria. Following treatment with corticosteroids, the hives dissipated but later recurred and spread to the lower legs.

Diagnosing equine atopy

Basic elimination trials, which consist of wiping the environment clean of a certain substance and then reintroducing it later to gauge effect, pose challenges. It’s often impossible, Redmond said, to purge the “dust in the air,” things like pollens and fungal spores. Plus, more than one allergen can be at play. Elimination trials are best suited for skin-contact allergens, such as tack and topical products.

Antibody titers can be checked for elevated IgE levels to subsets of allergens linked to a horse’s lifestyle or geographic region.³ False positives can occur, as well as false negatives for particular seasonal allergens when their IgE levels have dipped off-season. If various seasonal allergies are suspected, testing might need to be repeated throughout the year, which can drive up the cost of this generally inexpensive testing.

Because of these accuracy issues, Redmond usually skips antibody titers and goes straight to intradermal skin testing (IDST), considered the gold standard for diagnosing atopic dermatitis. Here, allergens are injected into the epidermis, and each site is monitored for local reaction.⁴

Testing requires an antigen test kit and a chunk of time. The patient’s hair is clipped down to skin, and a grid of dots corresponding to allergens is created using permanent markers. The positive (histamine) and negative (saline) controls are injected first, to serve as guidelines for interpretation of the test spots. Allergens are then injected at marked sites, using numbered syringes.

Initial readings identify injection-site wheals, which are scored from 0 to 4. Delayed (type IV hypersensitivity) reactions are assessed up to 24 hours post-injection. Redmond suggested dimming lights and then using a flashlight to cast revealing shadows on the often-subtle swellings.

IDST is somewhat costly, and the injection process takes about an hour. There are risks for particularly reactive horses. “We are exposing a horse to a whole bunch of allergens, and if he happens to be really, really sensitive to one of them, there’s a chance of a systemic reaction, possible anaphylaxis,” Redmond warned. He advised attendees to keep diphenhydramine and epinephrine on hand for these rare occurrences.

Interpretation errors can lead to false positives, but false negatives can occur, particularly if immunosuppressive agents have been given recently. Redmond recommended discontinuing steroids and antihistamines 2 weeks and 1 week, respectively, prior to testing.

For Juicy, Redmond performed antibody titers and skin biopsies, but eventually recruited a dermatologist to come to his clinic to perform an IDST. Withdrawing Juicy’s hydroxyzine beforehand presented a challenge because urticaria returned with a vengeance. The dermatologist and Redmond’s team were, however, able to pinpoint a hive-free strip of skin below the mane for testing.

Juicy started to react to several injection sites within minutes, but the main result revealed itself 24 hours later. It turned out Juicy was a number of allergens, including cotton which is remnant of his saddle pad.

Succor for sensitive steeds

Treatment for atopy aims to control clinical signs and blunt the underlying allergic surge.“ [Owners] just want their horse to not look so miserable,” Redmond explained.

The mainstay is corticosteroids such as prednisOLone and dexamethasone. These have proven themselves in atopic horses, with short courses used to quell acute uprisings, and continuous, low-dose therapy for stubborn cases.

Steroids can cause skin thinning and alopecia, as well as delayed wound healing and immunosuppression. They are contraindicated in horses with foot problems, as they can predispose them to laminitis. For those on long-term steroids, Redmond advocates twice-annual hoof radiographs to flag subclinical laminitic changes.

Antihistamines can be used to mute clinical signs of atopy. These histamine H1-receptor antagonists, which include hydroxyzine, pyrilamine, cyproheptadine, and diphenhydramine, decrease dermal vascular permeability, pruritus, and bronchial constriction. Long-term, daily administration of antihistamines is recommended during a horse’s known allergy seasons.

Diphenhydramine has been shown to have poor oral bioavailability, but its injectable formulations are useful in urgent situations; caution is warranted when injecting intravenously, as hyperexcitability can occur.⁵

Redmond has found hydroxyzine to be the best antihistamine for stabilizing equine atopy. Although prescription only, it’s affordable. Its active metabolite, the second-generation antihistamine cetirizine (Zyrtec), is available over the counter, but its higher cost hinders daily use for many owners.

Other immunosuppressant agents include oclacitinib (Apoquel), pentoxifylline, cyclosporine, and azathioprine. Neither steroid nor antihistamine, oclacitinib downregulates cytokines that fuel itching and inflammation, and has shown promise for horses.

Pentoxifylline is, among other things, an inflammatory modulator that reduces vasculitis. Though costly, it has shown some efficacy in controlling immune hypersensitivity when used with proper dose titrations over time. Cyclosporine and azathioprine have been used for inflammatory conditions in small animals, but their use in horses lacks both FDA approval and adequate research.

Immunotherapy alters the allergic response by desensitizing the patient to the offending antigen and has shown to provide relief in horses.^6,7 Microdoses of allergens administered either subcutaneously or sublingually provide constant low-grade prodding that converts the body’s reaction from the fiery IgE to the protective IgG.

Preliminary antibody titers or IDST single out the allergens that bedevil the patient. When possible, these should be eliminated from the horse’s environment, such as contact allergens like Juicy’s saddle-pad cotton. However, ubiquitous ones—grasses, insects, and such, which are harder to extinguish—might be incorporated into immunotherapy serum. Treatment is usually lifelong but often can slowly be tapered down over time.

References

1. Smith BP, Van Metre DC, Pusterla N, eds. Large Animal Internal Medicine. 6th ed. Mosby; 2019.
2. Marsella R, White S, Fadok VA, et al. Equine allergic skin diseases: clinical consensus guidelines of the World Association for Veterinary Dermatology. Vet Dermatol. 2023;34(3):175-208. doi:10.1111/vde.13168
3. White SD. Advances in equine atopic dermatitis, serologic and intradermal allergy testing. Clin Tech Equine Pr. 2005;4(4):311-313. doi:10.1053/j.ctep.2005.10.005
4. Lorch G, Hillier A, Kwochka KW, Saville WJ, Kohn CW, LeRoy BE. Comparison of immediate intradermal test reactivity with serum IgE quantitation by use of a radioallergosorbent test and two ELISA in horses with and without atopy. J Am Vet Med Assoc. 2001;218(8):1314-1322. doi:10.2460/javma.2001.218.1314
5. Redmond JS, Stang BV, Schlipf JW Jr, Christensen JM. Pharmacokinetics of diphenhydramine following single-dose intravenous and oral administration in non-fasted adult horses. J Vet Pharmacol Ther. 2022;45(2):188-195. doi:10.1111/jvp.13041
6. Rees CA. Response to immunotherapy in six related horses with urticaria secondary to atopy. J Am Vet Med Assoc. 2001;218(5):753-755. doi:10.2460/javma.2001.218.753
7. Radwanski NE, Morris DO, Boston RC, Cerundolo R, Lee KW. Longitudinal evaluation of immunological responses to allergen-specific immunotherapy in horses with IgE associated dermatological disease, a pilot study. Vet Dermatol. 2019;30(3):255-e78. doi:10.1111/vde.12732