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Basics

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BASICS

Definition!!navigator!!

AD is defined as a multifactorial disease in which a genetic predisposition leads to the development of a cutaneous IgE- and cell-mediated hypersensitivity, most commonly against environmental allergens, and, upon exposure to that allergen, to clinical signs in the patient.

Pathophysiology!!navigator!!

The pathophysiology of equine atopy is not well elucidated. In human and canine AD, deviations in T-cell development have been detected. Allergen-specific IgE has been identified in atopic horses and CD4+ CD25+ regulatory cells in horses with IH. Whether the exact pathomechanism is similar to dogs and humans, with an initial development of Th2 cells secreting IL-4, IL-5, and IL-13 leading to a switch to IgE production and cellular and humoral hyperreactivity against specific antigens, remains to be elucidated.

Systems Affected!!navigator!!

Skin/Respiratory

The skin is only one of the organs that can be affected. There is evidence that equine asthma (heaves, recurrent airway obstruction) may also be due to a type I hypersensitivity to airborne allergens in some patients.

Genetics!!navigator!!

The genetic basis of equine AD is largely unknown. Based on anecdotal reports and one study, Arabians seem to be predisposed, but the number of affected horses was small and no further genetic studies were reported.

Incidence/Prevalence!!navigator!!

After IH, AD it is the second most common hypersensitivity in the horse.

Geographic Distribution!!navigator!!

Worldwide

Signalment!!navigator!!

  • No age or gender predisposition has been identified
  • In most animals, the first clinical sign is pruritus, often affecting the head and legs
  • Initial pruritus may only be seasonal
  • With time, pruritus becomes more severe, more generalized, and year round

Signs!!navigator!!

  • AD may present as a pruritus with no primary lesions or perhaps mild erythema, or with pruritus leading to secondary lesions such as alopecia, excoriations, and crusting
  • It may also present as urticaria
  • Secondary surface infections may cause a bacterial folliculitis, which may be clinically mistaken for dermatophytosis

Causes!!navigator!!

  • The most common environmental allergens causing equine AD are storage mites, mold spores, and pollens
  • Depending on the geographic location and the exact type of allergen, mold spores and pollens may have a strict seasonal occurrence or may be perennial
  • Many horses have concurrent IH

Risk Factors!!navigator!!

Concurrent pruritic dermatosis, such as IH or ectoparasitic disease (summation effect).

Diagnosis

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DIAGNOSIS

Differential Diagnosis!!navigator!!

The list of differential diagnoses varies with the predominant site of pruritus (Table 1. As there is no reliable test differentiating AD from other hypersensitivities, ectoparasites, or other differential diagnoses, those diseases must be ruled out before AD can be confirmed.

CBC/Biochemistry/Urinalysis!!navigator!!

Hemogram may reveal an eosinophilia but this is nonspecific for AD as ecto- and endoparasite burdens or IH may show this change.

Other Laboratory Tests!!navigator!!

  • A number of tests are used to identify the offending allergens in AD
  • An ELISA that uses the Fc-epsilon receptor on the immunoglobulin IgE as the detection platform to identify serum IgE compared better in one study than a radioallergosorbent test and a polyclonal antibody-based ELISA
  • Histamine-releasing assays may be useful but are not commercially available
  • None of these tests reliably differentiates AD from other skin disease and, thus, cannot be used to establish a diagnosis
  • These tests serve as a guide to choosing offending allergens used in ASIT, together with the history of the patient including possible seasonality and/or specific locations

Imaging!!navigator!!

  • Skin—N/A
  • Respiratory signs—thoracic radiographs

Other Diagnostic Procedures!!navigator!!

  • Intradermal skin tests detect the level of allergen-specific IgE in the skin directed to a panel of allergens that are region specific and thought to be clinically relevant
  • Knowledge of predominant allergens and their seasonality in the area of one's practice is essential when interpreting results of allergy tests
  • False-positive reactions or results that indicate subclinical sensitization may occur with both serum and intradermal testing in the horse. Several studies with control groups of healthy nonallergic horses had immediate or late-phase IDT reactions, although horses with AD, urticaria, and severe asthma showed a higher number of positive reactions. As such, IDT results cannot differentiate a hypersensitivity from another pruritic skin disease, but rather act only as a guide to choose offending allergens for ASIT
  • Surface cytology from erosions or ulcers shows a neutrophilic exudate with intra- and/or extracellular cocci representative of a secondary bacterial folliculitis
  • Perform skin scrapings to rule out ectoparasites
  • Perform dermatophyte cultures to help rule out secondary dermatophytosis

Pathologic Findings!!navigator!!

Skin biopsies submitted for histopathology from horses with AD typically reveal edema with a superficial to deep, perivascular to interstitial, eosinophilic dermatitis and possible epidermitis pointing to hypersensitivities or ectoparasites and are not diagnostic for environmental allergy. Biopsies may be useful to rule out differential diagnoses.

Treatment

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TREATMENT

Appropriate Health Care!!navigator!!

  • Identification and avoidance of the offending allergen is the best strategy for horses with AD
  • In rare cases, changing the type of stabling, paddock, or feeding habits will lead to clinical remission
  • In the majority of cases, the etiologic allergens will either be ubiquitous or not identified and therefore unavoidable

Nursing Care!!navigator!!

N/A

Activity!!navigator!!

  • Horses with mild AD may be worked normally with appropriate symptomatic therapy. Severely pruritic horses may not be able to perform
  • Use of some antipruritic medications are illegal in competing horses

Diet!!navigator!!

A diet high in polyunsaturated fatty acids or supplementation of such fatty acids as cold-pressed linseed or flax seed oil has been recommended. One small randomized, placebo-controlled, double-blind cross-over trial showed a reduction in the intradermal skin test response to Culicoides in AD horses after 42 days of supplementation with flaxseed.

Client Education!!navigator!!

  • Clients rarely appreciate learning that their horse has a chronic skin disease that requires ongoing, long-term management. The need for a thorough workup to confirm a diagnosis of AD (by exclusion) is step 1. Client acceptance of long-term therapy is step 2
  • Owners need to decide if they will limit treatment to symptomatic therapy or if they will choose ASIT, which is the only specific treatment available and currently the only chance of “cure”
  • As they are active participants in the treatment regime, owners also need to understand how to assess response to therapy, be aware of signs of adverse effects, and when to consult the veterinarian for a needed change in treatment

Surgical Considerations!!navigator!!

N/A

Medications

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MEDICATIONS

Drug(s) of Choice!!navigator!!

  • Treatment of choice for horses with AD is ASIT. ASIT is an extract containing offending allergens that is given subcutaneously at regular intervals
  • Base the selection of allergens for inclusion in ASIT on test results, the history of the patient, and local exposure to regional allergens
  • Tailor the amount and the frequency of administration of ASIT to the patient's response. For example, pruritus directly after the injection prompts a decrease in the amount or strength of ASIT, whereas increased pruritus at the end of the treatment interval before the next injection is due suggests a need to increase ASIT frequency of administration

Contraindications!!navigator!!

None

Precautions!!navigator!!

One possible (albeit very rare) adverse effect of ASIT is anaphylaxis. This can have particularly dramatic consequences in horses with concurrent severe asthma. In such patients, injection of the allergen extract should be preceded by 2 h by administration of an antihistamine (see Alternative Drugs) and epinephrine should be available. Monitor the horse closely for the first hour after immunotherapy injection.

Possible Interactions!!navigator!!

None

Alternative Drugs!!navigator!!

  • There are a number of drugs used for symptomatic therapy, as an alternative or concurrent treatment to ASIT
  • The most frequently used drugs for allergic horses are glucocorticoids. They inhibit a wide array of inflammatory mediators and cells and thus have a high efficacy in the treatment of equine pruritus. Prednisolone is preferred. It is initially given at 0.5–1 mg/kg/day and tapered after 7–14 days to the lowest possible dose every 48 h. Recent well-conducted studies have not found an association between prednisolone administration and laminitis. An alternative to prednisolone is dexamethasone, which is given initially at 0.05–0.1 mg/kg/day for a few days and then tapered to 0.01 mg/kg every third day or less, if possible
  • Antihistamines are used for long- or short-term control of pruritus
  • Pharmacokinetic data for many antihistamines in the horse are unknown
  • Antihistamines used in the horse and their doses are listed in Table 2 Assess efficacy after 2 weeks of therapy
  • Polyunsaturated omega 3 and 6 fatty acids act most likely through their influence on the immune response as well as the epidermal barrier. Their effect on horses with AD is not as clear as the one seen on canine AD. Studies have shown variable results with commercial products, flax seed, or linseed oil. If fatty acid supplementation is beneficial, improvement may occur within 4–8 weeks after commencement

Follow-up

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FOLLOW-UP

Patient Monitoring!!navigator!!

Severity of patient's disease will dictate the need for monitoring. Patients with severe uncontrolled pruritus should be assessed frequently to ensure secondary infections are managed and controlled.

Prevention/Avoidance!!navigator!!

  • Prevention may be possible if the horse is relocated to a different ecologically diverse geographic location
  • Avoidance of allergens is not always possible or practical, especially as many patients have multiple allergens contributing to their disease

Possible Complications!!navigator!!

  • Change in allergen exposure or load precipitating disease flare or recurrence of previously controlled AD
  • Secondary bacterial infections
  • Adverse effects to symptomatic medications

Expected Course and Prognosis!!navigator!!

AD is a chronic skin disease and spontaneous remission is rare. Therapies should be continued long term. Prognosis is good to fair with appropriate management.

Miscellaneous

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MISCELLANEOUS

Associated Conditions!!navigator!!

  • Severe equine asthma
  • Allergic conjunctivitis
  • IH

Age-Related Factors!!navigator!!

Severity worsens with age.

Zoonotic Potential!!navigator!!

N/A

Pregnancy/Fertility/Breeding!!navigator!!

Long-term use of corticosteroids is contraindicated during pregnancy.

Synonyms!!navigator!!

Equine atopy.

Abbreviations!!navigator!!

  • AD = atopic dermatitis
  • ASIT = allergen-specific immunotherapy
  • CAFR = cutaneous adverse food reaction
  • ELISA = enzyme-linked immunosorbent assay
  • IDT = intradermal dilutional test
  • Ig = immunoglobulin
  • IH = insect bite hypersensitivity
  • IL = interleukin
  • Th2 = T-helper cell 2

Suggested Reading

Fadok VA. Update on equine allergies. Vet Clin North Am Equine Pract 2013;29:541550.

Hallamaa R, Batchu K. Phospholipid analysis in sera of horses with allergic dermatitis and in matched healthy controls. Lipids Health Dis 2016;15:45.

Hamza E, Mirkovitch J, Steinbach F, Marti E. Regulatory T cells in early life: comparative study of CD4+CD25high T cells from foals and adult horses. PLoS One 2015;10:e0120661.

Loewenstein C, Mueller RS. A review of allergen-specific immunotherapy in human and veterinary medicine. Vet Dermatol 2009;20:8498.

Lorch G, Hillier A, Kwochka KW, et al. 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;218:13141322.

Lorch G, Hillier A, Kwochka KW, et al. Results of intradermal tests in horses without atopy and horses with atopic dermatitis or recurrent urticaria. Am J Vet Res 2001;62:10511059.

Marsella R. Equine allergy therapy: update on the treatment of environmental, insect bite hypersensitivity, and food allergies. Vet Clin North Am Equine Pract 2013;29:551557.

Morgan EE, Miller JrWH, Wagner B. A comparison of intradermal testing and detection of allergen-specific immunoglobulin E in serum by enzyme-linked immunosorbent assay in horses affected with skin hypersensitivity. Vet Immunol Immunopathol 2007;120:160167.

O'Neill W, McKee S, Clarke AF. Flaxseed (Linum usitatissimum) supplementation associated with reduced skin test lesional area in horses with Culicoides hypersensitivity. Can J Vet Res 2002;66:272277.

Petersen A, Schott 2ndHC. Effects of dexamethasone and hydroxyzine treatment on intradermal testing and allergen-specific IgE serum testing results in horses. Vet Dermatol 2009;20:615622.

Scott DW, Miller JrWH, eds. Equine Dermatology, 2e. Maryland Heights, MO: Elsevier Saunders, 2011.

Stepnik CT, Outerbridge CA, White SD, Kass PH. Equine atopic skin disease and response to allergen-specific immunotherapy: a retrospective study at the University of California-Davis (1991–2008). Vet Dermatol 2012;23:2935.

Author(s)

Author: Ralf Mueller

Consulting Editor: Gwendolen Lorch

Acknowledgment: The author acknowledges the prior contribution of Gwendolen Lorch.